Melatonin - Miracle Molecule

MELATONIN
Miracle Molecule

John Lieurance, ND, DC, DACNB (Board Eligible)

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 Medical Disclaimer

This book details the author’s personal experiences with and opinions
about Melatonin.

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 Melatonin - Miracle Molecule

ACKNOWLEDGEMENTS

First and foremost, I would like to dedicate this book to my mother

Pamela for always supporting and believing in me. I'm happy to say
that she has been benefiting greatly from high-dose melatonin as
well.

I'd also like to dedicate this book to Dr. Russell Reiter who has spent
most of his career working to understand and share the secrets of
melatonin and its functions, with the desire to showcase its potential
role in our healthcare system. Also, Dr. Frank Shallenberger
because without his suggestion that I personally start taking high
doses of melatonin this book may have never been born.

I would further like to acknowledge Dr. Shallenberger for his

tireless efforts over the years to highlight many powerful and
natural strategies such as ozone and high-dose melatonin, professor
Venkataramanujam Srinivasan for a lifelong dedication to
conducting research unveiling the secrets of melatonin, colleagues
such as Dr . Patrick Gentempo and his wife Laurie , Dr . Joe
Mercola & Dr. Daniel Pompa. Also, my staff including Sarah
Carnegie , Candace Johnson , Irene Melendez , Dr . Daniel
Kirschner, and all the other people that have been on my journey
to share melatonin's story.

Lastly, to all of the people that have trusted me and started their own
journey using melatonin to improve their lives.
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 Melatonin - Miracle Molecule

CONTENTS

Acknowledgments iv

1 Intro To The Miracle Molecule 7

2 Melatonin & Mental Emotional Stress 22

3 How Melatonin Supports The Mitochondria 41

4 Melatonin & Neurological Health 55

5 Melatonin & Immune System 70

6 Melatonin & Infections 107

7 Melatonin & Autoimmune Diseases 123

8 Melatonin & Cardiovascular 136

9 Melatonin & Sex Hormones 151

10 Melatonin & Degenerative Neurologic Disease 163

11 Melatonin & Gut Health 204

12 Melatonin For Jet Lag & Disrupted Sleep 223

13 Melatonin & Skin 244

14 Melatonin Toxic Factors 272

15 Melatonin For Children 300

16 Melatonin For Diabetes 315

17 Melatonin & The Pineal Gland 336

18 Supra-Physiological Dosing 347

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Chapter 1: Intro To The
Miracle Molecule
Melatonin, commonly called the sleep
hormone or the hormone of darkness,
holds enormous importance which the
public is in the dark about! Melatonin
works for sleep; however, in this book
you will find it works around the clock
protecting you. Many doctors poorly
understand melatonin and the public is
told false and misleading information
such as that it's dangerous to take too
much or that the body will become reliant on melatonin and you will
stop making your own. I have interviewed the top scientists in the
world, and I’ve read through almost all the research and have found
that not only is melatonin safe in much higher doses than what’s
typically recommended, but it can be lifesaving and work on your
health at a cellular level like no other substance can do. I have come
to understand that this hormone has many medicinal properties
outside of just assisting you in restorative sleep.
As the scientists are digging further and further, they are finding
newer uses of melatonin in the treatment and prevention of a large
number of diseases. This has got researchers and doctors to sit up
and take notice of melatonin.
It’s not surprising to me that this miracle molecule has been ignored
by modern medicine. Big Pharma has tried very hard to reproduce a
molecule that is structurally close to melatonin in an effort to have
a molecule they can patent; however they have not been successful.
When you change this molecule even slightly it doesn't offer up the
magic that natural melatonin does.

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 Melatonin - Miracle Molecule

We live in a world where cures are not what Big Pharma is putting
their research dollars into, nor are budgets allocated to “un paten-
able” molecules like melatonin. What they prefer is a long-term
dosing schedule that keeps the dollars rolling in, stock price up, and
the shareholders happy. If you're looking for miraculous compounds
that can heal, cure, and prevent disease you found it with melatonin.
Big Pharma owns the media now and COVID censorship is at its
worst in the USA. Even with recent research showing melatonin can
be lifesaving for those infected with COVID-19, it has been
silenced. I have even been silenced by the FDA and FTC. Having
shared a multitude of scientific data on my MitoZen.com site on
melatonin and its relationship to viral infection and COVID-19, with
subsequent explanations on the mechanisms and links to leading
hospitals who are administering doses in the hundreds of milligrams.
I was asked to take it all down. Denying the public of this
information so they can keep the attention on vaccines touted to be
the answer to this pandemic.
Please know, the vaccines can do nothing to keep you from
becoming ill with COVID only prevent the severe and critical stages
of the disease. This is fairly rare and typically is found in aged
demographics and individuals with poor health. Chapter 6 well
covers how melatonin can protect you from these effects and many
other very serious and lethal infections such as EBOLA and
COVID.
Melatonin may be a better answer than vaccines, with zero risks.
However, this would never see the light of day due to the current
medical system, which is sadly based on money and politics. It's up
to you to look outside of mainstream media and demand answers,
understand risks associated with vaccines as well as judge
alternative options, and the potential safety and efficacy based on
years of research. This book aims to unravel the hidden benefits of
melatonin and provide some color on its potential in being what I
call the “miracle molecule” versus a mere sleep hormone.
In this book, I will dig into all the research and provide my own
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insights surrounding the use of high-dose melatonin with my own

patients. But first, let me begin with what sparked my interest in
melatonin and its benefits.

My first encounter with high dose melatonin

I was first introduced to using

higher than normal doses of
melatonin when I attended a
large presentation in Fort
Lauderdale in 2017. A
presenter was discussing using
melatonin in extremely high
doses.
The doctor sitting next to me
said that this was one of the
most exciting clinical pearls he
had learned in recent times, and
he had begun using high doses of melatonin for his patients in his
own clinic. This got my attention!
Shortly after I was doing an internship with Dr. Frank Shallenburger
in Reno Nevada, I was shocked to see Dr. Shellenberger utilizing
hundreds of milligrams of melatonin for his cancer patients as well
as for many of his neurologic cases such as Alzheimer's,
Parkinson's, and TBI or traumatic brain injuries. [1] [2] [3]
I myself suffered a brain injury from chronic Lyme disease and mold
illness and had arranged to be a patient with Dr. Shallenberger while
I was there interning.
I was having problems with finding correct words in speech,
difficulty with memory, and concentration. Dr. Shellenberger
prescribed 200mg of melatonin taken orally at bedtime. He even
suggested if I could tolerate it, to take 200mg each day for my

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condition. Wow, wouldn’t I sleep all day? Maybe not, we will get
into this later.
This is where my journey began into the miraculous benefits of
melatonin!
The more I started to dig into melatonin research, the more excited
I got, not just for myself, but for my patients as well.
Because melatonin works at the deepest level of the cells, which
involves the cell’s ability to make “clean” and efficient energy.
Melatonin is almost like a quarterback of the cell. And we all know
what happens when someone has a great quarterback like with
Tampa Bay in 2021. Or what occurs when the quarterback gets
sacked, and play goes dead!
If you don't understand football, then understand that the game
begins and ends with this position.
But here we’re talking about the game of biology. The game that's
played inside our cells and who the individual players are with
melatonin's critical position as a quarterback! When we speak about
the chemistry that's occurring in every cell of your body, we need to
consider the burning of glucose as energy in the presence of oxygen.
This process is at the heart of the energy of life within your body
and each cell.
We're going to be taking a deep dive into this process and how
melatonin is vitally important to keep this process or “game”
organized and clean, just like a quarterback in football calling the
shots. [4]
When one starts to ponder and consider the amazing benefit shown
in the research that has been conducted over the last several decades,
it is difficult to wrap one's head around why melatonin is not used
more commonly for a multitude of conditions. Due to melatonin's
ability to regulate your body and cells at such a deep level, it is an
important molecule to consider with many different diseases that are
rooted in chronic inflammation. Most diseases are rooted in

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inflammation which is itself rooted in dirty and inefficient energy

production at a cellular level. In this book you will discover that
poor cellular energy leads to a build-up of toxins, thus allowing
infections to run wild.
When researchers first
started to study this miracle
molecule, I had a difficult
time determining the
benefits that melatonin
provides to all animals
including humans. In fact,
when scientists first started
studying melatonin, they
didn’t find any health benefits. Not surprising seeing melatonin is
primarily involved with stress protection and when giving melatonin
to animal models in a normal environment (stress-free) they saw no
benefit. In other words, they gave melatonin to mice that were living
at the Ritz Carlton (stress-free) and they did not see a significant
difference in the melatonin group versus the placebo group. Again,
this is mainly due to melatonin's ability to protect the body at a
cellular level from stress.
It was not until they started to stress the animals in the study that
melatonin's miracle healing abilities began to shine. What they did
is place them in tiny tubes with just little pin holes for several hours
a day to simulate a stressful situation for these animals. Then when
they looked at the melatonin group, they saw significant
improvements. The melatonin group had less weight loss, lived
significantly longer, and avoided diseases when compared to the
animals that had no melatonin.
If you're looking to slow aging, improve brain function, or maybe
you're suffering from a disease that's rooted in a lack of efficient
energy production at a cellular level which is resulting in excess
inflammation then this book is for you, as we’ll take a close look at
how melatonin can quench this inflammation or “cytokine storm”.

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I was first introduced to the work of Otto Warburg back in the late
90s. I was working with a therapy called exercise with oxygen therapy
or EWOT. The concept of exercise with oxygen was pioneered by
Warburg’s protégé Dr. Van Arden. I created the Ultimate guide to
EWOT and was promoting the use of this therapy as early as 1999.
Furthermore, Otto Warburg won the Nobel prize for discovering that
oxygen, and cancer can't coexist, and in the process was able to
understand cancer at a much deeper level than anyone prior to him
had. We will speak more on Dr. Otto in later chapters.

The lack of adequate secretion of melatonin can affect these cellular

processes and increase the risk of several disorders including
infections like Lyme, influenza, and COVID-19, as well as cancer,
and autoimmune diseases. [5] [6] [7] [8]
Later, we will discuss melatonin supplements and how you can use
them to restore optimum health by protecting your body against
oxidation and inflammation at the cellular level.

What is melatonin?

Generally, melatonin is referred

to as the “hormone of darkness”
and is naturally produced in our
body. This hormone is stored in
our pineal gland during the
daytime and then released by
the gland as the night
approaches or when the body is
exposed to darkness. [9] [10]
[11]

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Besides the pineal gland, melatonin is also secreted by our

mitochondria in all cells throughout the body. Furthermore,
melatonin is also produced in your gut for protection purposes, and
to help stimulate microbiome health. Some amount of melatonin is
also produced within eye fluids, called intraocular fluid.
Melatonin is basically a methoxyindole compound, which, under
normal environmental conditions, follows an endogenous rhythm of
secretion. This means the secretion of melatonin is regulated by the
endogenous or internal rhythm
set by your body’s own biological
clock or the circadian rhythm.
The endogenous rhythm of
melatonin secretion is entrained
in the cycle of bright light during
daytime and darkness in the
evening and night. The intensity
of light your body is exposed to is able to synchronize or suppress
melatonin production.
That’s not all.
There are various factors at play when it comes to the amount and
timing of melatonin secretion.
The suprachiasmatic nuclei in the brain play a vital role in
determining the amount of melatonin secreted in your body at
different times of the day. Moreover, the production of melatonin
also adjusts to the length of the night or darkness in order to be more
in phase with the seasons.

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Melatonin is synthesized from tryptophan into

serotonin then to melatonin.

Here is the chemical schematic.

What is considered the primary function of

melatonin?
The primary physiological
function of melatonin for
sleep-wake is to convey
information about your
cyclical exposure to light
and darkness to all organs,
especially the brain. The
information conveyed by
melatonin can then be
used by the organs for the
organization of different

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functions that respond to the change in the photoperiod, such as

seasonal rhythms.
In addition, melatonin secretion occurring on a daily basis serves as
a robust biochemical mechanism signaling night. This mechanism
can be used by the tissues and organs for the organization and
regulation of the circadian rhythm.
Melatonin can further stabilize and strengthen the coupling of
circadian rhythms with the sleep-wake rhythms and the body’s core
temperature. The circadian organization controls such things as
antioxidant and immune defenses, glucose regulation, and
hemostasis also depends on the biochemical signals carried by
melatonin.
Melatonin has generated a great deal of interest as a therapeutic
modality for various diseases particularly diseases related to poor
sleep. You would be shocked to find out how many diseases are
correlated with poor sleep. This miracle molecule possesses
antioxidant, anti-inflammatory, endothelial-protective, and
anticoagulant properties.
This is just a glimpse of what melatonin can do. We will learn a lot
more about the functions and benefits of melatonin as we move
through the next chapters of this book.
The pineal gland is the primary seat of the production of melatonin.
We discuss the pineal gland in the chapter on pineal in great depth.

History of pineal science?

The first evidence that the Pineal gland produced a biologically

active hormone, now famously known as melatonin, was revealed
by the medicinal potential of the pineal tissue extracts obtained from
bovine sources. It was found that this extract of the pineal gland
could modify melatonin pigmentation in frogs by regulating melanin

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aggregation.
Melatonin got its name due to its particular property to regulate
melanin aggregation, thus prompting the researchers to name it
melatonin. These findings later led to the attempts to use melatonin
for treating vitiligo, which proved to be effective. We will dive deep
into this in chapter 13. This research also led to the incidental
discovery of the sleep-promoting effects of melatonin. [19] [20] [21]
[22]

The secretion, release, and storage of

melatonin

Melatonin is the primary hormone secreted in the pineal gland. It is

synthesized in response to darkness giving it the name, “the
hormone of darkness”. [23]
Melatonin is produced from a hormone called serotonin. Serotonin
is a neurotransmitter derived from the amino acid called tryptophan
through a chain of enzymatic reactions. Serotonin is acetylated in
the pineal gland and later, methylated to produce melatonin.
The last two steps in this pathway involve the conversion of
serotonin to NAS (N-acetylserotonin) catalyzed by another enzyme
called AANAT (arylalkylamine N acetyltransferase). This is
followed by the conversion of NAS to melatonin. This process is
further catalyzed by the enzyme HIOMT (hydroxyl-indole-O-
methyltransferase). [24] [25]
You might be wondering how the whole process begins? It so
happens that the pineal gland receives signals from some fibers
called the postganglionic fibers, thus leading to the production and
release of serotonin. The same process also results in an increased
production of cyclic AMP, thereby activating AANAT, which is
critical to the secretion of melatonin.

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Melatonin is secreted by the pineal gland and released into the

bloodstream through which it can penetrate all tissues. The pineal
gland is stimulated to secrete melatonin primarily in the presence of
darkness, whereas exposure to bright light can inhibit these
mechanisms thereby reducing melatonin production. [26] [27]
The mechanisms behind the unique pattern of melatonin secretion
during the darkness cycle can be attributed to the activities of NAT,
a rate-limiting enzyme that is lower during daylight and tends to
peak during the dark phase. So, when the NAT levels are higher,
which is when you are exposed to darkness, the melatonin levels
would peak and vice versa.
However, the activities of another enzyme called methyltransferase
involved in the conversion of serotonin to melatonin do not show
this form of regulation linked to the pattern of light exposure.
Darkness is the primary criterion needed for melatonin secretion,
there are also a few other factors linked to methyltransferase that
could determine the amount of melatonin secreted in your body.

Understanding the role of the blood-brain

barrier in melatonin production

Interestingly, the pineal gland, in spite of being part of the brain

during its embryological stage (while it is still being formed in the
fetus), is situated outside the blood-brain barrier. As a result, it loses
its direct connection with the brain or the central nervous system.
This explains why the pineal gland has to rely on the stimulation by
sympathetic nerves and serotonin for regulating melatonin
production.
The ability of the pineal gland to escape the restrictions imposed by
the blood-brain barrier also accounts for its capacity to have a larger
uptake of tryptophan that allows for an increased melatonin

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 Melatonin - Miracle Molecule

production in response to darkness.

The freedom to escape the blood-brain barrier also offers relative
protection to melatonin against premature enzymatic degradation
leading to a 10 to 20-fold rise in melatonin levels.
We will discuss the exact role of the blood-brain barrier as we move
to future chapters.
But, right now, as we are discussing the various processes involved
in melatonin secretion, it is essential to understand that the
production of this hormone is somewhat independent of the blood-
brain barrier, thanks to its unique location. [28]

How is melatonin secretion regulated?

The daily rhythmic production of melatonin in the pineal gland is

driven by the circadian clock. This 'clock', in turn, is regulated by a
region in the brain called the suprachiasmatic nuclei that express a
series of clock genes, which have a tendency to oscillate
continuously throughout the day.
This oscillation is synchronized with the solar day and night through
light rays falling onto the retina. The suprachiasmatic nuclei are
linked to the pineal gland via a complex pathway. The pathway
passes through different areas in the brain into the spinal cord,
finally reaching the pineal gland.
During the daytime, the suprachiasmatic nuclei block melatonin
secretion by sending inhibitory signals to the pineal gland.
However, at night, the suprachiasmatic nuclei are not as active as
they are during the daytime. So obviously, the inhibition induced
during the daytime is withdrawn, following which the melatonin
production is resumed with a greater force by the pineal gland.
From this, it is clear that light is the most important regulator for

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melatonin production. Firstly, it has the ability to reset a specific part

of the brain - the suprachiasmatic nuclei - and control the timing of
melatonin secretion. Secondly, exposure of the body to light, or to
be precise the LACK of light during the biological night-time
reduces melatonin secretion. [29]

Safety profile and administration of melatonin

for sleep

If you google Melatonin multiple sites including WebMD state

reported side effects including dizziness, headache, nausea, or
agitation can occur. However, these were based on a study where
these side effects happened just as much in the placebo group. This
creates confusion for the
public and does not properly
reflect the real potential side
effects of melatonin. Could
this be our beloved Big
Pharma putting out false
information to discourage
melatonin use? [30]
With regards to the administration of melatonin in the form of a
supplement for sleep aid, the time of administration might be as
important as the actual dosage in determining its effectiveness to
support sleep. For example, research studies have found that when
melatonin is administered at bedtime, it may not be effective unless
high doses are used. On the other hand, when smaller doses of
melatonin are administered about 2 to 4 hours before bedtime, it
tends to be more effective in reducing sleep latency.
But what is sleep latency? It is the period that we usually spend
waiting to fall asleep after going to bed. Higher sleep latency is
common in patients who suffer from severe mental stress,
depression, or pain disorders like arthritis.

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 Melatonin - Miracle Molecule

The use of melatonin during

early evening hours, even in
low doses, could help
reduce the latency period
and allow you to fall asleep
shortly after your head hits
the pillow. That’s the
beauty of melatonin! It all
depends on when you use it,
and how well you integrate
it with your body’s internal circadian rhythm. [31] [32] [33]
Obviously, if you were using a product like Sandman with 200mg
of melatonin this would be considered a high dose, and the
application time would not be a factor. Yet, if you're using smaller
dosing for sleep you might consider taking your melatonin earlier.
The safety profile of melatonin therapy is quite reassuring and much
superior to the commonly used sleep-inducing agents, including
sedatives. For example, unlike benzodiazepines and Zolpidem,
melatonin therapy is not known to cause dependence and
withdrawal symptoms.
There have been studies done where dosages reaching the equivalent
of 150,000mg in a 150 lb. human had no toxic effect. [34] [35] [36]
[37]

What is the difference between the

pharmacological and physiological effects of
melatonin?

The difference between the physiological effects produced by

melatonin secreted in your own body vs the pharmacological effects
created by exogenous melatonin needs to be understood clearly.

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 Melatonin - Miracle Molecule

A “physiological” dose refers

to the plasma level of the same
magnitude as that produced
during the nocturnal peak. A
pharmacological dose, on the
other hand, usually provides
supra-physiological or higher
than the normal physiological
levels of melatonin. When a lower dose of melatonin is used, a
narrow hormonal signal is created that may not mimic the expected
effects of endogenous secretion.
And this is the reason why most experts recommend using supra-
physiological doses of melatonin, to create signals that could bring
about the expected improvements in sleep and other health-related
parameters. [38] [39]

Conclusion

Melatonin is such an important hormone, perhaps the most

important one we make. Its therapeutic value reaches into almost
every disease known to us and we will be diving into many of them
in this book we will get into the substantial body of research done
over the years which has expanded our understanding of this
amazing molecule and demystified the potential benefits of this
hormone.
Melatonin is indeed the miracle molecule and is made in every cell
of your body and also in the miracle gland, the pineal. It is time we
dig deeper into all aspects of this hormone and learn how it can help
us be more resilient to stress, stay healthier, live longer, and with
more vitality.

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Chapter 2: Melatonin &

Mental Emotional Stress

When I was very sick with Lyme EBV and mold illness. Yes, I had
all those at one time, I had severe anxiety and depression. Because
I didn't find a doctor that properly worked me up with the right lab
work, I was just told my problem was in my head and that it was
emotionally based. I spent years meditating for hours a day to try to
work through this and it had limited effects. It wasn't until I began
to clear these stressors when I really found relief to my mental
emotional afflictions. If only I knew about melatonin back, then.
Melatonin would have supported the toxic and infection stress my
body and brain was suffering from.
Stress presents itself in many ways within our bodies. There are
various different forms of stress such as physical stress, chemical
stress, infections, mental and emotional stress, psychosocial stress,
and electromagnetic stress (EMF). Yet a common downstream
effect from all of these varying stressors is how it affects us on a
cellular level. [1] [2] [3] [4]

All of these stressors oftentimes lead to increased inflammation,

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 Melatonin - Miracle Molecule

oxidation and cytokines (as described in another chapter), and they

can further lead to a negative cycle of mental and emotional
problems. Nevertheless, this is where melatonin comes in! The
beneficial actions melatonin offers by easing anxiety directly on top
of how it can help to act as a buffer for almost all the stressors in our
world. In my case the support to the immune system, the
detoxification and buffering of the effect from exposure to toxins.
Read my history as a child in chapter 15 and learn how I was
exposed to toxins early on in life. We live in a very toxic world today
and EVERY one of us needs to consider that they are polluted and
need to have a regular plan to detox. Melatonin can play a role here,
but binder and cell membrane support are also important. We get
more into this in Chapter 3,4 & 10.
In our modern, technologically advanced, and industrialized world
besides toxins, stress has become synonymous with our life. For
instance, humans now endure a constant bombardment of
information and media. And while there’s no denying that our
capacity to be ever-connected via our cell phones brings with it
many advantages such as social media, online banking, easy access
to emails, and communication with loved ones at the click of a
button- the 24/7 endless supply of stimuli can be extremely stressful.
Moreover, as humans, we often try to shift blame, and a hectic
lifestyle is the most popular excuse. However, the uncertainties and
stressors surrounding life are unavoidable, and instead of trying to
fight this fact, learning how to better cope would serve as a more
proactive solution.

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As I sit here today

penning this book,
COVID-19 seems to have
highlighted just how
detrimental stress can be
for people all around the
world. And while
COVID-19 is a transient
global event it’s
important to note that there are also routine stressors like job
pressure, finance-based anxiety, relationship hardships, and many
other things which we tend to worry about on a daily basis.
Nowadays, it’s becoming painfully clear that nobody is able to
completely escape stress. Not even those who are aware of all the
health implications that can ensue after prolonged periods of fight
or flight such as our healthcare providers, psychiatrists, yoga
instructors, and even meditation teachers. Moreover, with our
current fast-paced and busy societies, there appears to be little
escape from the potentially devastating and life-taking impacts of
stress. [5] [6]
All this makes it painstakingly clear that the solution no longer lies
in striving to avoid stress. In fact, I’m about to suggest quite the
opposite! The real key lies in providing adaptive support, so not only
can we tolerate more stress, but we can actually benefit more from
stress.
Hormesis is a term used to describe the beneficial reaction your body
can respond with from a stressful event. Hormetic stress can be
described as a form of stress that given in the right dosage, not too
much and not too little, can give you a net gain in health. Hormetic
stressors can be fasting, cold and heat stress, physical stress like
exercise, and even infections are a few examples.

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Melatonin is like the

electromagnetic field of
the earth. Just like the
electromagnetic field is
produced by an internal
force due to the metals
putting off the energy that
extends beyond the surface
and protects life on our
planet from the harmful
UV rays from our sun, melatonin also is made within each cell of
your body and works to protect your cells from stress. Throughout
this book you will find out how melatonin can protect you from
things like cancer, metabolic diseases like diabetes, all infections
including COVID and Ebola, heart disease, digestive disease, sexual
dysfunction, mood disorders, neurological diseases like
Parkinson’s, Alzheimer’s, and cognitive decline. It can even extend
life too!

If you look at the graph on

hormesis you can see there is
a certain level of stress that
you can receive, and as long
as you don’t accede to this
your body responds to this
stress with an action that
actually strengthens rather
than weakens the body.
For example, if you do too much exercise you will exceed the stress
your body can deal with, and therefore you might get sick or feel
worn out for a few days until the body can recover from the stressful
injury incurred by overtraining. In our clinic, we do ozone therapy,
and ozone is the most oxidative substance on the planet. Meaning it

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 Melatonin - Miracle Molecule

is a huge stressor to our body. Why then would I want to run this as
an IV to a sick individual? It's all about hormesis. Ozone is a
stressor, however, in the right dose, it can be a way to activate the
endogenous antioxidant systems in the body. In other words, the
high levels of oxidation delivered from brief periods of time, when
exposed to your blood cells can activate enzymes and oxidizes the
lipids in your blood, then those oxidized lipids become signaling
factors that tell the body to do some work in order to be better
prepared for oxidation. Even telling the most core part of your cells
called the mitochondria to recycle the poor functioning
mitochondria, and build new strong ones called mitochondrial
biogenesis.
I use ozone as an example of hormetic stress as it’s the best medical
hermetic therapy I know of and use it very often in my practice.
What’s important to know with IV
ozone is that you need to be able to
tolerate the dosage of ozone. This
depends on your antioxidant capacity.
Melatonin is the primary antioxidant
for all of your cells and is involved in
the beneficial effects received by IV
ozone. Supplementing with melatonin
can allow you to better adapt to stress
and enable you to receive further
amounts and stay within the hermetic
curve so you may stand a better chance
to benefit from stressors versus it
wearing you down, thus causing disease and aging.
It makes good sense to minimize the negative impacts stress can
have on your health by leveraging the use of “stress protecting”
supplements, such as melatonin. I’m also a proponent of many other
stress-reducing activities such as exercise, breathing, and meditation
for stress reduction. However, sleep is at the top of my list which is

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 Melatonin - Miracle Molecule

another factor that melatonin can help with. Yet the numerous
advantages of melatonin go far beyond sleep, as you will discover
in this book.
Stress has indeed become synonymous with our life. The irony that
medical professionals including psychiatrists who emphasize
avoiding stress are not able to escape its impact speaks volumes. In
this chapter, we will be considering stress as the accumulation of all
the activities over the day such as overworking both physical and
mentally, exercise, toxic exposures such as pesticides and mold,
poor nutrition, lack of sleep, infections both acute and chronic, and
electromagnetic stress from cell phones and Wi-Fi.

Mental-emotional stress and

anxiety disorders have become
the most common of mental
illnesses, affecting nearly 40
million adults per year in the US
alone. [7]
While the list of factors that can
contribute to your mental and
emotional stress is endless, the anxiety-driven feeling is not. Stress
can be buffered, consequently diminishing the impact on your
mental and physical health.
It's amazing that a molecule that is not only produced in the brain
but like I've mentioned before, produced in every cell in your body,
can be so intrinsic to our mental, emotional and overall well-being.
Throughout this chapter we’re going to dive a little deeper into
various aspects of melatonin, and how it works similarly to the
electromagnetic field protecting the earth. It protects and lessens the
effects of stress and allows the body to handle different stressors in
a more optimized manner. Plus, by using melatonin we can further
benefit from greater forms of hormesis.

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 Melatonin - Miracle Molecule

Melatonin for mental-emotional stress

Besides improved sleep which has a balancing effect on the brain

the autonomics play a large role in supporting proper mental
emotional stress responses. Sympathetic dominance is common
where we get stuck in a fight or flight it can also cause confusion
and depression. Consider how powerfully melatonin supports the
parasympathetic side keeping the sympathetics calmed down. In a
minute we will dive into heart rate variability (HRV) and how it can
be a measure into your sympathetics and how melatonin can support
this.
First let's look at the sleep side on this equation and then dive into
HRT. Sleep disorders like insomnia are closely linked to stress,
anxiety, and depression. The more nights you spend feeling restless
without any sleep, the more stressed you’re going to be during the
daytime. [8] [9]
In fact, it works both ways.
I like to use the analogy of a revolving door. For instance, most of
us are more than familiar with the consequences of a bad night’s
sleep. We end up in a bad mood the following day, tired, with low
energy, and most likely running into further problems. Funnily
enough, it's these same anxieties that are capable of leaving you
without being able to sleep the following night. As you can see, it
becomes somewhat of a perpetual cycle. Part of this is related to a
stress hormone called cortisol which we will talk about in this
chapter. [10]
It’s comparable to a case of what came first - the chicken or the egg?
I guess it really doesn't matter because using melatonin could offer
a way to tackle both sides of that revolving door; And by this I mean,
the stress on one end and the sleeplessness on the other.
Moreover, research studies have suggested that sleep aids like

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 Melatonin - Miracle Molecule

melatonin could reduce stress while also improving your cognitive

function and boosting overall mood. [11] [12]
Melatonin is effective for managing mild day-to-day stress that we
all experience as well as severe mental stress that can lead to
complications like depression and generalized anxiety. This is
primarily due to the mechanism of action melatonin provides
towards regulating your circadian rhythm, promoting sleep quality,
and easing negative emotions. [13]
Melatonin actually works to support your autonomic nervous system
and particularly the parasympathetic. In other words, melatonin
works to improve something called heart rate variability or HRV.

HRV is a sign of health and the body's adaptation to stress. It’s a

great metric to track if you're trying to figure out if you are working
out too hard for example. It goes up when you're healthy and it's
lowered due to less variability when you're poorly adapting, or the
stress is too high.

Consider that the HRV is controlled through 2 opposite sides of your

autonomic nervous system, the sympathetic or fight or flight, and
your parasympathetic or resting and digesting side. One side is
telling your heart when to contract and the other when to relax, thus
when one side is overactive you get lower variability.
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 Melatonin - Miracle Molecule

Can you guess which side is overactive typically? If you guessed the
sympathetic you are correct. It’s the “stress” side of your nervous
system, so it's an obvious part of our nervous system that gets lots
of activation, therefore it's stronger. This is why we need to work on
things that support the parasympathetic system, like deep breathing,
my personal favorite, meditation, laughing, and doing things you
love. [39]

“Melatonin is protective in CNS on several different levels: It reduces

free radical burden, improves endothelial dysfunction, reduces
inflammation and shifts the balance between the sympathetic and
parasympathetic system in favor of the parasympathetic system.”

Moreover, there are actually receptors in the brain called G-protein

melatonin receptors, and the ones called MT1 and MT2 work with
the brain. Melatonin affects the brain through the activation of these
receptors. Let's circle back to HRV and consider the graph of how
this becomes more problematic as we get older.
The graph highlights a direct relationship of reduced stress enduring
capacity as we age. But what’s interesting is that this graph when
compared to the melatonin levels chart bears many similarities.
Is it the relationship melatonin has with HRV that reflects this? With
the science pointing toward that being true, supplementing with
melatonin when one is under stress makes more sense now than ever
before.
The aforementioned is exactly what we're going to dive deeper into
throughout the next section.

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 Melatonin - Miracle Molecule

How does melatonin work to reduce mental

stress?

Stress and getting the correct amount of sleep are two opposite states
of mind.
REM Sleep is the primary phase of sleep that allows our
subconscious mind to work out all of the challenges that it met
throughout the day. I think of it as a computer that has to go through
a defrag in order for it to function optimally. Think about how
conflicted we get throughout the day due to the multitude of
situations and experiences that arise, such as someone cutting us off
on the road or the way your siblings and parents interacted with you.
We all know that over time, things tend to calm down from an
emotional standpoint and this is what primarily happens during our
REM sleep.
Incidentally, alcohol and high THC (Tetrahydrocannabinol) levels
can further inhibit REM sleep thereby creating a devastating effect
on our emotional well-being. THC is nothing more than a compound
secreted by the cannabis plant. Cannabis has been shown to be
hugely beneficial when administered in the right dosages. The right
type of full-spectrum hemp product with a small amount of THC can
work wonders for sleep cycle health. We recommend the brand
NeuroDiol found at Mitozen.com as it has been shown clinically to
improve sleep dramatically.
Furthermore, there is something called a C1 receptor that a small
amount of THC activates, which is the brake system that many of us
need, especially after the age of 40. Most of the research has shown
that very high levels of CBD are necessary to induce quality REM
sleep. Personally, I've found success with suppositories in the
hundred and 125 to 300mg range to be quite effective, as well as
oral tinctures using higher milligram dosages.

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 Melatonin - Miracle Molecule

Taking melatonin in conjunction with the right type of full-spectrum

CBD health product can be a great way to improve sleep. Another
compound to look at is glutathione as it is one of the more successful
sleep-promoting substances, along with uridine. [14]
Another curious thing to note when it comes to melatonin and sleep
is that while your REM sleep can be adversely affected by alcohol
or narcotics, melatonin has shown to buffer the negative effects,
therefore, allowing for a more peaceful night’s sleep. [15] [16]

Sleep, melatonin and the mechanism of actions

The effect of melatonin on your mental health is not limited to how

it promotes sleep quality. It can also take care of the after-effects of
insufficient sleep and allow you to avoid additional stressors that
could worsen your emotional well-being.
Melatonin, being a sleep hormone, helps to maintain your body’s
circadian rhythm and enables you to get a sound sleep every night,
thereby protecting you against the consequences of insomnia.
The indirect benefits of sleep improvement brought about by
melatonin can go a long way in preventing stress, as well as the
factors that cause it.
This brings us to understanding the first mechanism of action which
melatonin contributes that can help you avoid stress and anxiety. It
basically works by improving your sleep pattern. [20]
Yet, that’s not all.
The stress-relieving action of melatonin is not limited to the
improvement of sleep. It also helps to regulate the production and
release of stress hormones like cortisol, and feel-good hormones like
dopamine and serotonin, to help you better absorb the impact of
unpleasant stress on your mental health.

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The complex interplay between melatonin and

mood-regulating hormones

Your mood, whether happy, sad, or anxious, depends on the

complex interplay between the levels of different hormones in the
body. Other than melatonin, hormones like dopamine, serotonin,
and cortisol are also responsible for mood regulation.
Among these, cortisol is largely responsible for increasing mental
stress and anxiety. Moreover, the production and release of
melatonin and cortisol in the nervous system are interdependent.
Since melatonin secretion is light-sensitive, it reacts to morning
light, which is how the brain is signaled to slow down or pull back
on melatonin secretion and release.
At the same time, the morning light also signals your brain to
produce more cortisol, which is your “awake” hormone. The
increased production of cortisol in the early morning hours is what
nudges us to wake up. During the daytime, the release of cortisol
continues to increase and reaches its peak, thus allowing us to feel
more alert. [21]
This is how melatonin and cortisol work in opposite ways, yet at the
same time symbiotically, to manage our sleep-wake cycle. When
melatonin secretion is high, the cortisol levels reduce and vice versa.
When the secretion of either of these hormones is out of balance,
your ability to sleep at night or stay awake throughout the day
becomes affected.

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 Melatonin - Miracle Molecule

Increased cortisol production

reduces melatonin secretion, and
this is the reason why your
stressful day can subsequently
lead to a poor night's sleep.
On top of this possible
dysregulation, you throw in the
constant text messages,
Instagram posting, returning
emails, TV watching, and any
other form of screen staring, which are known to emit tons of blue
and green light, and the mystery behind the suppression of
melatonin starts to become more apparent. When you are in a
distressed state you’re not in the best mindset to make positive
changes in your life, which then leads to further mental-emotional
stress thus, preventing you from falling asleep thereby, once again,
contributing to your stress and anxiety. This is one reason why it’s
important to ensure your body has a higher level of melatonin to
counter these fast-paced changes and adapt to the new age that we
live in now. [22] [23]
Nevertheless, the effects of cortisol are not limited to improving
your wakefulness and poor sleep. Chronically high cortisol levels
are also directly linked to a higher risk of cardiovascular disease,
psychological disorders, anxiety disorders, depression, postpartum
depression, post-traumatic stress syndrome (PTSD), OCD, and
many other psychological disorders. [24] [25]
Any form of stressor including toxic, chemical, emotional, and
psychological stressors can cause your cortisol levels to rise.
Furthermore, all of these stressors can lead to both inflammation in
the body, as well as an activation of the sympathetic nervous system.
This ultimately triggers higher cortisol levels, insufficient sleep, and
depressed melatonin production and release. Diseases such as
diabetes, sleep apnea, chronic infections, cancers, allergies, and
autoimmune disorders are all linked to elevated levels of cortisol.

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 Melatonin - Miracle Molecule

This is why regulating cortisol production is important when trying

to minimize the impact of stressors on your physical and mental
health. Besides getting a deeply restorative night's sleep, melatonin
can buffer the negative effects of chronic inflammation, cancer,
immune dysregulation such as autoimmune disease and allergies, as
well as acute and chronic infections. Again, this is why we refer to
melatonin as being the “quarterback”. Meaning that there's one
player that can have a widespread effect on the game.
The increased secretion of cortisol could be addressed by
supplementation of melatonin. The interdependency between the
secretion of melatonin and cortisol allows for the regulation of the
levels of cortisol in the nervous system. An increased melatonin
level would subsequently signal the brain to reduce cortisol
production. [26] [27]

Dopamine, serotonin, and melatonin

Now, let’s take a quick look at the other two hormones that play a
role in determining your moods and mental health.
These are dopamine and serotonin.
While cortisol is largely considered a stress hormone, dopamine and
serotonin are commonly referred to as the feel-good hormones,
which ultimately means these hormones play an important role in
mood regulation. Just like cortisol, the secretion of dopamine and
serotonin is also linked to the levels of melatonin in the nervous
system. The higher secretion of melatonin at night is essential for
inducing deep sleep, which, in turn, can improve the production of
serotonin and dopamine. The increased levels of these two feel-good
hormones induce a sense of relaxation, thereby reducing your
anxiety.

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 Melatonin - Miracle Molecule

But how do melatonin levels affect the balance of feel-good

hormones in the brain?
Serotonin is a neurotransmitter,
the deficiency of which is
associated with a higher risk of
depression. A research study
revealed that mice exhibited
more fears when serotonin
receptors were deleted.
Another experiment compared
the levels of serotonin of healthy individuals with those in patients
with panic disorders using a PET scan. This study showed that
patients who experienced panic attacks had about two-thirds of the
regular serotonin level of 1A receptors in certain parts of the brain
including midbrain raphe, anterior cingulate, and posterior
cingulate. [28]
This indicates how depleted serotonin levels are closely linked to
negative emotions like fear and anxiety.
Similarly, dopamine is another neurotransmitter commonly
associated with social anxiety and reward-motivated behavior. A
research study found that patients with generalized social phobia
have a lower dopamine level compared to healthy subjects. [29]
While on the other hand, higher dopamine levels are linked to
improved mental health, higher self-confidence, and reduced risk of
depression and anxiety.
This suggests that a higher secretion of dopamine and serotonin
could help to improve mood and avoid anxiety.
There is evidence to prove that melatonin, when injected in rats, can
help to control anxiety allowing them to spend a longer time in the
plus-size maze. It’s also believed to work by improving the quality
and duration of sleep, thereby allowing you to feel more refreshed
and energetic during the daytime. Getting adequate amounts of sleep
at night ultimately improves brain functions and enables higher
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 Melatonin - Miracle Molecule

secretion of dopamine and serotonin, thus relieving anxiety. [30]

This is how the anxiety-relieving effect of melatonin is linked to its
capacity to improve the secretion of dopamine and serotonin.
The complex interplay between melatonin and stress hormones, like
cortisol and feel-good hormones such as dopamine and serotonin,
could help you avoid anxiety. It might also improve your self-
confidence and enhance your cognitive and creative skills. [31]

The discovery of the anxiolytic properties of

melatonin

One of the primary and the beneficial effect of melatonin is its

potential to help protect us from the impact of poor mental health.
[32]
When scientists first started researching this miracle molecule, they
had a difficult time determining the benefits that melatonin could
provide to all animals, including humans. They did not notice a
significant difference when melatonin was given in a conventional
environment.
Initially, they gave
melatonin to mice that
were not under stress
to assess if it could
improve their health
status. However, they
didn't notice any significant improvement in the mice that were
administered melatonin.
The lack of noticeable improvement was mainly due to the
protective effect of melatonin on the body at a cellular level, which
is particularly notable during stress.
It wasn't until the researchers started to stress the animals in the
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 Melatonin - Miracle Molecule

study by placing them in tiny tubes with little holes for several hours
a day, that the protective effects of melatonin became obvious. The
simulation of a stressful situation induced these animals to activate
the protective effects of melatonin, from which a subsequent
improvement was observed in their health status. [33] [34]

What does the research say about the

anxiolytic properties of melatonin?

Several research studies have confirmed the anxiety-relieving

properties of melatonin, which have further shown to be effective
for improving mental health.
Let’s take a brief look at what the research has to say about the
anxiolytic action of melatonin.

Animal studies
One animal study conducted in 2017 revealed that melatonin can
increase the levels of GABA (gamma-aminobutyric acid) in specific
parts of the brain. A higher GABA level may induce a calming effect
on the mind and body, ultimately relieving symptoms of anxiety.
In fact, some medications commonly recommended for treating
anxiety, including benzodiazepines, also function by increasing
GABA levels. [35]

Human studies
Studies have linked the use of melatonin supplementation to relief
from presurgical anxiety. It’s common for patients to feel anxious
before a planned surgical procedure. Moreover, the clinical trials
conducted to assess the effect of melatonin administration in
surgical patients revealed that it can positively reduce the anxiety
that patients usually experience before surgery.
The anxiety-relieving effect was significantly higher compared to

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 Melatonin - Miracle Molecule

the patients who were given a placebo. These studies have indicated
the wider application of the anxiolytic properties of melatonin
across different use cases.
Also, medications such as benzodiazepines are commonly used to
reduce anxiety in presurgical patients. In an analysis of clinical
studies conducted in 2015, it was found that the anxiolytic effect of
melatonin was comparable to benzodiazepines such as midazolam
when given before a surgical procedure.
Most of the research studies conducted have revealed that melatonin
works better than placebo, and as effectively as midazolam for
lessening anxiety when given to pre-surgical patients. [36]
In another study, the use of melatonin was evaluated in patients who
had undergone a major procedure to open up blood vessels within
the heart. This study showed that the anxiolytic effect of melatonin
was superior to that of oxazepam. [37] [38]

Conclusion

Besides supporting our brain and brain chemistry through quality

sleep melatonin supports our cells and energy supply. It’s becoming
ever clearer that melatonin, the quarterback, has the potential to be
of great assistance in the management of mental and emotional
stress, both directly and indirectly. With melatonin’s ability to
improve sleep and regulate the secretion of cortisol, dopamine, and
serotonin it can be highly effective in reducing these afflictions and
improving your mental-emotional wellbeing.
Other important avenues to consider:
● Meditation.
● Breathing Exercises- Look into WimHof breathing or other
techniques.

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 Melatonin - Miracle Molecule

● The use of glutathione as an additional antioxidant to buffer

stress, as well as improve sleep quality.
● Get tested for toxins such as heavy metals and or pesticides.
● Get tested for chronic infections such as viral bacterial,
fungal and intestinal parasites.
● Test food allergies such as gluten, dairy, night shades.
● Try a ketogenic diet to improve brain power which supports
stress resilience.
● Try Mito Fast or other fasting programs to support your
mitochondria.
● Try NAD+ supplementation. (precursors such as NR and
NMN are also good).
● Full-spectrum CBD can also be leveraged for sleep and
stress management.
● Magnolia bark extract can help anxiety and sleep.
● Ketamine assisted psychotherapy.
● Sometimes, chronic infections in the sinuses can cause a lot
of s stress symptoms as well. If you feel like this might
possibly be affecting your stress levels, consider a 30-day
nasal cleanse, and if you're able to test the microbial health
of your sinuses it’s highly recommended. Systemic
infections with viruses such as Lyme disease and mold
illness can cause a lot of chronic mental-emotional stress as
well. Although melatonin could be very helpful in most of
these cases if this is the underlying root cause one needs to
make sure they get the appropriate testing and diagnosis so
that they could better understand the correct treatment.
I would suggest melatonin would be a great adjunct to any plan to
support becoming healthier and feeling better mentally and
emotionally. Consider some testing to see if there are stressors that
have gone undiagnosed such as toxicity, infections, sinus health,
food sensitivities and gut health.

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 Melatonin - Miracle Molecule

Chapter 3: How Melatonin

Supports The Mitochondria

Mitochondria are the important cellular organelles that makeup 1/3

of your body weight. Your mitochondria play a critical role in
determining how efficiently your body’s organs can work by simply
producing the energy needed for their everyday function. This
energy is critical for your body to deal with stressful events, which
include all types of stressful factors. Do you recall them? They are
mental/emotional, chemical/toxic, infection, physical & EMFs.
Mitochondrial function has been linked to many diseases and it’s
thought that the aging process is closely related to the dysfunction
that occurs over our lifetime. Meaning that, our bodies accumulate
more and more stress in the form of toxins, chronic infections,
nutrient depletion, poor antioxidant status, NAD+ levels, senescent
cells, and physical stress.
Mitochondria play a key role in energy production. This gives them
the common name of the ‘powerhouses of the cell/body’.

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 Melatonin - Miracle Molecule

The mitochondria ultimately make energy by converting glucose

from within the cells to form energy in the form of ATP, which is in
the presence of oxygen of
course. This process is
known and commonly
referred to in health and
biology circles. It’s basically
biology 101. This process of
energy production is called
the tricarboxylic acid cycle
(TAC) or the Krebs cycle.
[1] [2] [3]
Besides the pineal gland and endothelial tissues, the mitochondria
in each of your cells produce melatonin.
Let's dive into why melatonin is produced by your cells:
Although the pineal gland releases melatonin into the bloodstream
to be used by other organs and tissues, when your mitochondria in
your cells produce the melatonin, it is not secreted into the
bloodstream. This precious melatonin within the cell is utilized and
is extremely important. In other words, the cells selfishly hold onto
this melatonin, and we'll learn later that this action is critical to
protect and buffer stress where we need it most. Imagine that you
had a boat that had one motor. You were out at sea and your engine
stopped. If you have no backup propulsion, you’re dead in the water.
At a cellular level, it is much the same. Except instead of that motor
on the back of the boat you have thousands of little mitochondria
floating around each cell working hard to make energy. Just like any
engine, there needs to be a cooling system and an exhaust. These
systems are critical to the mitochondria as well. The stress involved
in producing energy needs to be buffered so that there is not a build-
up of stress around the energy-producing entity, whether it's a boat
engine or your little mitochondria’s.
You may be asking; how does melatonin play this role and buffer
stress at the energy-producing level of the mitochondria?
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 Melatonin - Miracle Molecule

The type of stresses the mitochondria experience universally result

in inflammation, thus cytokines are mental/emotional, chemical,
infection, physical & EMFs. Think about a log you place on a fire,
one burns for 10 hours (the one with no stress or lots of melatonin),
and the other only burns for 1 hour. This is efficiency at its finest
when it comes to making energy, but there is another factor which
is the pollution that log puts out. The second log not only creates
solely one burning hour of energy, but it puts out much more
pollution or smoke. This is a similar action to what occurs in the
form of oxidative stress. Since melatonin shields oxidation when
you don’t have enough you can’t buffer it, and build-up can occur
causing a further choking off of your mitochondrial and cellular
functions. [4]
In a perfect scenario, when things are functioning normally this
process leads to the release of 36 ATP molecules as a byproduct
from the breakdown of each molecule of glucose. Remember this
number, it's going to be important later.
Again, just to emphasize how important this energy is. It’s used by
the organs and tissues including your brain, heart, and lungs to
perform critical functions. The muscles in your body also use the
energy that’s generated to support bodily movements.
Routine stressors affect the optimal function of the mitochondria
and reduce the energy available for the cells to use, as well as
increase oxidative stress in the cells. This can have a critical and
devastating cascading negative effect on the functions of the cells
and in turn, affect the activities of the organs, tissues, and body as a
whole.
I hope you're starting to see just how important it is to address issues
that encompass the energy production of mitochondria. Before we
discuss how melatonin plays a role in protecting mitochondria, let
us have an idea of the factors that affect energy production in
mitochondria.

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 Melatonin - Miracle Molecule

Factors that affect energy production in

mitochondria

The process of energy production is severely affected in the

presence of stressors because they lead to both inflammation and
oxidation. These stressors often lead to excess free radicals within
cells which causes oxidation. This action is also referred to as a
reactive oxygen species or abbreviated as ROS. When this oxidation
exceeds a certain threshold, it forces the cell to continue to make
energy another way. It’s still producing energy in the presence of
oxygen; however, it is no longer going through the Krebs cycle.

This part of the

melatonin story is
fascinating, so hang
on because we're
going to get a little
technical, but it will
be well worth it for
your overall
understanding of this
miracle molecule.

So, there’s an enzyme produced in each of your mitochondria called

pyruvate dehydrogenase kinase (PDK). PDK has the ability to hold
phosphates derived from the energy released in the formation of
ATP. It can attach a phosphate to the pyruvate dehydrogenase
complex (PDC), thus disabling it. If you look at the above diagram,
you’ll be able to see how energy goes from glucose to pyruvate
which enters into the cell and then converts it into Acetyl-CoA. This
can then enter the crab cycle to make those 36 ATP. Even though
we're using the image demonstrating the inflammatory storm in an

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 Melatonin - Miracle Molecule

infection from COVID-19 as an example, this process is affected the

same way through most of the other stresses we've been discussing.
So again, we go from glucose to pyruvate to Acetyl-CoA then into
the Krebs cycle. This process is taken out in the face of inflammation
through the PDK enzyme, where pyruvate will no longer get
converted to Acetyl-CoA. This would be like the engine in your boat
still running, but barely. What's also very important to understand is
that that same Acetyl-CoA also goes on to produce melatonin within
the mitochondria. So, when the PDK enzyme gets taken out so does
your cell’s ability to make melatonin. Melatonin is produced in the
mitochondria to protect the cell from overheating through this
mechanism of energy production and trust me when I say that it’s
not a good situation when it gets cut off. It's like both the cooling
system and the exhaust system going out on the boat engine causing
it to completely choke.
What happens here is a devastating blow to the energy potential of
the mitochondria. There is a complete shift in the way that the
mitochondria produce energy at this point. The Acetyl-CoA isn't
being created so the pyruvate has to do all the work. Pyruvate is then
shuffled out of the mitochondria into the part of the cell called the
cytosol, and it's there that it will be converted into ATP through a
process called aerobic glycolysis. This energy system is much less
efficient than Krebs cycle, hence we only get 4 ATP versus 36.
That's approximately a 90% loss of the cells capacity to make
energy!
I hope it’s becoming more obvious now why it is important to keep
cytokines from shutting down pyruvate being moved to Acetyl-CoA
and to keep Pyruvate Dehydrogenase Kinase or PDK from being
activated by cytokines. Melatonin can calm this down and help to
restore normal cellular energy production even when taken in
supplement form. In fact, studies have shown that taking
supplemental melatonin can switch the production of the melatonin
within mitochondria back on.

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 Melatonin - Miracle Molecule

What is it that exactly regulates this PDK?

PDK is activated in the presence of pro-inflammatory substances

called cytokines in cells, which ensue as a result of various forms of
stress. Much of this is seen within the immune system at the level of
the macrophage, which is one of your body's immune cells.
Macrophages are released to fight infectious pathogens and they
produce these pro-inflammatory cytokines, such as interleukins and
human necrosis factors.
Moreover, one of the most amazing aspects of melatonin is that it
will suppress PDK. Melatonin can suppress some of the production
of PDK when the cell and mitochondria are under stress. This can
break the cycle created by PDK allowing the production of ATPs by
mitochondria to resume through Krebs cycle again back to 36 ATP
versus 4.
There’s another way by which melatonin helps mitochondria, and
that action is linked to its anti-inflammatory potential. Let me reveal
more about this as we go ahead.

How does the anti-inflammatory property of

melatonin protect mitochondria?

Chronic stress oftentimes includes infections that can trigger

inflammation and oxidation, leading to the immunological
involvement of macrophages and neutrophils on a chronic level.
This action makes your immune system weaker. The defense
mechanisms stimulated by the immune cells in the event of
infections may also lead to the destruction of cells, along with the
mitochondria, which will result in the creation of debris from dead
cells and cellular parts. These particles simply float around and lead

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 Melatonin - Miracle Molecule

to immunological activation.

This can stimulate the innate immune system leading to

macrophages eating up the cellular debris along with their damaged
mitochondria. This happens because macrophages consider the
debris as antigens due to which the cycle of inflammation is
triggered, releasing even more inflammatory cytokines which then
activate the PDK pathway even further. It's a bit of that cycle that
potentiates itself. Moreover, the inflammation caused due to
macrophages can worsen the damage to healthy tissues and cells,
leading to an increased risk of life-threatening consequences such as
many autoimmune conditions, cancer, degenerative neurologic
diseases, heart disease, etc.

The most sensitive organs toward mitochondrial function are the

brain and the heart because they're the most metabolically active.
It’s no surprise that we see problems in those two areas in any
mitochondrial challenged situation. Yet on the flip side, improving
mitochondrial function can also create great improvements for those
organ systems.

Melatonin can help in these endless cycles of inflammation by

regulating the immune system and inhibiting excessive
inflammation through the quenching of the oxidation within the
mitochondria, as well as the restoration of the PDC pathway and the
blocking of the PDK pathway.

Furthermore, melatonin in cells can support energy production and

reduce the activities of interleukins and other inflammatory
cytokines. This can help to calm the cytokine storm from most all
infections, as well as minimize tissue damage which is sometimes
related to autoimmune diseases such as multiple sclerosis,
rheumatoid arthritis, ankylosing spondylitis, and ALS. It's my
opinion that many of these autoimmune conditions have their root
causes in chronic infections that are typically associated with

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 Melatonin - Miracle Molecule

toxicity. It's these pathways that are at the core of many of these
diseases. [5]

Could melatonin really be that beneficial to this many diseases?

Let's take a look at how it relates to cancer as an example.

How does melatonin influence the Warburg

effect and regulate energy production in cancer
cells?

To start, let's circle back to our inefficient

form of producing energy called aerobic
glycolysis. This energy pathway, called the
Warburg effect, has a major role in cancer
cells. For this one reason melatonin has been
demonstrated in
literature to
inhibit cancer Dr. Manfred von Ardenne
growth. I was
first introduced to the work of Otto
Warburg back in the late 90s. I was
working with a therapy called exercise
with oxygen therapy or EWOT. The
concept of exercising with oxygen was
pioneered by Warburg’s protégé, Dr.
Van Arden.

I created the Ultimate Guide to EWOT and was promoting the use
of this therapy as early as 1999.

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 Melatonin - Miracle Molecule

Who was Otto Warburg?

Otto Warburg was a German
scientist in the early 1990s who won
the Nobel prize for discovering that
oxygen and cancer can't coexist, and
in the process was able to
understand cancer at a much deeper
level than anyone prior to him had.
He was the first to observe aerobic
glycolysis. This is the primary
means that the mitochondria in
OTTO WARBURG, MD
cancer cells make energy, and as
mentioned prior, is referred to as the
“Warburg Effect”. [6]

Warburg effect refers to a phenomenon that is observed

predominantly in cancer cells. This phenomenon occurs when the
cells ferment glucose to produce lactic acid during glycolysis in the
presence of oxygen. It was Otto Warburg, in 1926, who postulated
it as the fundamental cause of cancer.

This dysfunctional, energy-

producing process that leads to
the production of 4 ATP is
called glycolysis. During
glycolysis, 1 glucose is broken
down into 2 molecules of
pyruvate along with a small
amount of ATP. [7] [8]

As mentioned before, in a One of the hallmarks of cancer is

a change in cellular metabolism
normal situation your healthy which skips the mitochondria.
mitochondria will break down
the glucose into pyruvate and

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 Melatonin - Miracle Molecule

then Acetyl-CoA which subsequently goes into the Krebs cycle. At

this point, the mitochondria “burn” the pyruvate molecules released
from glycolysis to form much more ATP, up to 90% more!

Nevertheless, in the
absence of oxygen, the cells
can complete only the first
step, which is glycolysis,
releasing only 2 molecules
of ATP from each molecule
of glucose. This is where in
addition to that inhibition of
the PDK you also have a
depletion of oxygen.

CELLULAR FERMENTATION OR
Otto Warburg observed
AEROBIC GLYCOLYSIS DIAGRAM how the process of
oxidative phosphorylation
is altered in cancer cells. He also described how cancer cells
function differently, even in the presence of oxygen. He postulated
that while healthy cells can entirely "burn" the molecules of sugar,
cancer cells do so only partially. They tend to overindulge in the step
of glycolysis during respiration without completing the second step
of oxidative phosphorylation.

Now that we've described the science of this you now know what's
really happening at a cellular level to understand the difference
between these two cells. [9] [10] [11]

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 Melatonin - Miracle Molecule

What's the downstream effect of this?

As a result, only 2 molecules of ATP are released from each glucose

molecule. This reduced amount of energy is not adequate for cancer
cells to survive. Without these massive amounts of glucose, cancer
cells can't receive the energy needed for their survival. This is one
of the reasons that avoidance of sugars in the diet and even a strict
ketogenic diet can be so helpful. By starving cancer cells of glucose,
you can give your cells and body the advantage, because cancerous
cells rely heavily on sugars and thrive in high-sugar environments.

Furthermore, various fasting strategies are used by many alternative

cancer doctors to rob cancer cells of glucose. An interesting
alternative medical technique called Insulin Potentiation Therapy
(IPT) has been becoming more popular. IPT is where a practitioner
will give insulin to a fasting patient to put them into a severe
hypoglycemic state. Then they will intravenously introduce
substances that would be toxic to the cancer cells (chemo agents)
along with glucose. Because the cancer cells are so hungry for this
glucose, they will pull in the material from the IV very rapidly and
more robustly than your normal cells. It's like the trojan horse!

A surprising increase in science was

discovered back in these early days
in Germany. Otto Warburg is one of
my most admired scientists of that
era. He was the first to observe this
unusual behavior of energy-
deprived cancer cells. He described
how cancer cells utilize only
glycolysis and oxidative
phosphorylation even when oxygen
supply is adequate.

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 Melatonin - Miracle Molecule

I often wonder if we were to put Russell Reiter, MD together with

Otto Warburg, MD today what would transpire?

I'm sure Dr. Otto Warburg would've been a huge fan of melatonin
supplementation, especially when considering the interplay between
how the mitochondria become dysfunctional and how super-
antioxidants like melatonin can quench some of the negative effects
of this condition. Several research studies have revealed that
melatonin can reverse the 'Warburg effect". [12] [13] [14]

In cancer cells, glucose is metabolized to form pyruvate, and later to

lactate. Melatonin can support the conversion of pyruvate into
acetyl-CoA in mitochondria. Moreover, in studies, this mechanism
has shown to have the potential to reprogram the metabolism of
glucose in cancer cells to that of normal cells. [15]

This means melatonin has the potential to inhibit the Warburg-

dependent cancer cells by redirecting glucose oxidation to the
mitochondria. It works as a glycolytic agent and inhibits cancer
growth. Melatonin can compel the cancer cells to abandon partial
breakdown of glucose and switch to the conventional oxidative
phosphorylation or the Krebs cycle. [16] [17] [18] [19]

While doing so, melatonin also stops and slows down the
proliferative activities of cancer cells, and reduces their metastatic
potential, thus forcing them to undergo apoptosis more readily. This
explains how the use of melatonin has the potential to restore
cellular functions and support the recovery of cancer patients.

Finally, the same effects of melatonin on cancer cells can also

explain why tumors that have become resistant to chemotherapy are
re-sensitized to the treatment when melatonin is administered in the
form of supplements. [20] [21] [22] [23] [24] [25]

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Conclusion

This is probably the chapter I was most excited about writing and
one of the core reasons I wanted to bring forth this book. The idea
that melatonin is so intrinsically involved at the cellular level and in
the most important area of the cell, the mitochondria, is not
something most people or even healthcare providers are familiar
with.

I mentioned the above from experience, as it is now 2021 and I’ve

become somewhat of an advocate of melatonin, consequently
teaching other doctors as well as working closely with many chronic
patients. It is rare that any of them have been exposed to this
information previously, and this is usually new material for them. I
believe this chapter provides an argument for the supplementation
of melatonin in almost all cases of the disease.

We promote MitoFast which is

an anti-aging technique utilizing
a 3 phase fasting strategy to
improve mitochondria function
along with melatonin. The
MitoFast is a 3 phase fasting
program where we preload with
NAD+ prior to the fast then use
plant polyphenols during the
fasting period to support
autophagy, mitophagy, and cleanup zombie-like cells called
senescent cells which are extremely inflammatory.

We didn't have time to really dive into this subject, however, if this
is something you’re interested in you can find more information at
ultimatecellularreset.com. Moreover, fasting techniques can be

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hugely beneficial to calm chronic inflammation and there are

various ways these protocols can be executed safely. See my article
on MitoFast here.

I think in today's toxic and stressful world we need to rely on more

strategies than just melatonin.

Nevertheless, if you're looking to have more energy, less

inflammation, less oxidative stress, better immune function, and
stronger detoxification pathways, melatonin supplementation could
certainly be very helpful.

We will be getting more into dosage, super physiologic melatonin

dosing, routes of delivery like suppositories and liposomal in the
chapters to come.

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Chapter 4: Melatonin &
Neurological Health
Blood Brain-Barrier, Glymphatics & mTOR

More important than nutrition is your sleep! Sleep and melatonin do

more than just allow you to have good sleep, but this process as well
as the miracle molecule itself does more for your brain than you
could ever imagine.

Over the last 26 years, being a Naturopath and Functional

Neurologist, I have taken a lot of time to research this topic to help
my patients have a better brain. It is a common theme for most
patients that don’t get proper sleep to also have poor neurology and
brain health. Besides not feeling fresh in the morning, inadequate
sleep and poor melatonin levels can be detrimental to your brain,
therefore enjoyment of life.

If you don’t sleep, the repair activities do not happen the way they
should. This can accelerate the process of aging. This is also one of
the reasons why neurological diseases have become so rampant.
Lack of sleep and lack of proper healing! These factors are at the
root of most age-related diseases.

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 Melatonin - Miracle Molecule

In this chapter, I will be getting into some ideas on how poor sleep
can lead to toxic build-up in the brain, ultimately causing a poor
environment for optimal brain function. You’ll also learn how you
can use sleep and melatonin to detox the brain of many of the toxic
proteins associated with degenerative neurological diseases as well
as heavy metals.

To understand this better, allow me to explain by using an example

of what happens in patients with Alzheimer’s disease and the
glymphatic system.

Our body has a glymphatic system that acts as a deep cleansing

system for the brain. Like the lymphatic system throughout your
body, the glymphatics removes waste from the brain. The
glymphatic system is mostly only active during sleep.

Meaning that the glymphatic system works and is active primarily

during sleep and is deactivated while we are awake. The biological
need of all species to get adequate sleep reflects this. It indicates that
during sleep, the brain may enter the state of glymphatic activity,
thus enabling the removal of potentially neurotoxic products like
beta-amyloid, tau proteins, alpha-synuclein, and neurofibrillary
tangles.

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 Melatonin - Miracle Molecule

A good analogy to use

would be to imagine your
body and brain, either
being a swamp or a river.
Glymphatics move you
more towards the river
aspect keeping things
clean and clear, bringing
in the nutrients, and
taking out the waste.
Besides creating a toxic
environment, the buildup
of toxins makes for a
better breeding ground for infections such as EBV, HHV-6, Lyme,
and CMV to name just a few.

Melatonin, which is our sleep hormone, can actually powerfully

activate your glymphatic system and allow the brain to enter the
state of efficient cleansing and detoxifying activities. This is perhaps
one of the more important mechanisms by which melatonin can
support brain function and delay degenerative changes such as
memory loss and cognitive decline.

Detoxification of your nervous system by your glymphatics would

also slow down aging. And this seemingly indirect mechanism of
melatonin, in reality, can be remarkably effective for preventing
age-related neurological diseases such as Alzheimer's, dementia,
Parkinson's, and many more.

Circling back to Alzheimer's disease, by activating and supporting

the activity of glymphatics at night, melatonin can also prevent the
formation of amyloid plaques and neurofibrillary tangles that cause
the degeneration of neurons. Melatonin actually clears these
plaques, thus making way for healthy neurons to function more
efficiently.

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 Melatonin - Miracle Molecule

These amyloid plaques and AMYLOID BETA PLAQUE

neurofibrillary tangles can
cause degeneration of the
neurons and trigger the
development of Alzheimer's
disease.

Additionally, proteins released

by the immune system in
response to inflammation and
infection can also cause
immense damage to the brain. The immune protein and pro-
inflammatory agents can encapsulate the toxins in the nervous
system. As a result, these toxins accumulate in the brain and cause
long-term damage.

All these changes occur faster and in an uninhibited manner when

your glymphatic system is not functioning optimally due to poor
sleep. The detoxification of beta-amyloid plaques can occur only
when you’re sleeping. If you don’t get enough sleep, these toxins
would stay accumulated in your nervous system and keep causing
damage to more and more brain cells making you more likely to
develop neurodegenerative diseases like Alzheimer's and
Parkinson's at a much earlier age. Nevertheless, all of this could be
avoided by taking melatonin.

Melatonin can restore

brain functions including
memory, attention span,
focus, learning, and
logical thinking abilities.
That’s not all. As
discussed earlier, it would
further help you sleep
better so that your

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glymphatic system can eliminate toxins, free radicals, and pro-

inflammatory molecules from the brain.

To get a clear idea of the concept of glymphatic, beta-amyloid

plaques, and melatonin, think of the trash at your home that is
collected every day by a garbage collector.

These garbage collectors are doing the work of what glymphatics do

for your body. Garbage collectors remove the trash from your home
to be disposed of in a proper manner, leaving your house clean and
neat so that you can stay safe from diseases and infections caused
by the lack of hygiene.

The trash we are talking

about in this chapter is,
of course, all the toxins
released into the body
during various metabolic
activities. The trash also
includes free radicals
that cause oxidative
stress and even the pro-inflammatory substances released by your
immune cells. Your glymphatics can remove these toxins leaving
your body clean.

Now, imagine that the garbage collectors go on strike! With no one

to collect the garbage, all this trash remains accumulated in your
home, in a similar way to how the toxins stay in the brain when the
glymphatics aren’t working properly. If the strike continues, you’re
going to have heaps of trash stashed in your home which is going to
make your life miserable by making your environment prone to
infections and many other diseases.

At the same time, the trash will also provide a perfect setting for rats
to thrive. So, now you have a house with trash, plus rats.

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This is similar to the beta-amyloid plaques that form in your brain

when there is an accumulation of toxins. These plaques can increase
your risk of Alzheimer's disease and affect the ability of your brain
to function efficiently.

At this juncture, a good idea would be to have the garbage collected

so that the rats eventually go away.

Yet, this is not what most modern medicines do. Most drugs
prescribed to patients with Alzheimer’s disease work by removing
amyloid plaques. These medicines are only clearing away the rats,
leaving behind the garbage that is the root cause of all the problems.
We need to understand that just targeting amyloid plaques with a
single chemical compound is not going to address multifactorial
diseases like Alzheimer's.

The right way to treat this condition would be to check why amyloid
plaques developed in the first place. And of course, it’s because your
glymphatics haven’t been doing their work properly to remove all
toxins from the brain. They have been on strike because you don't
give them a chance to work peacefully, which, in turn, is because
you’re not getting enough quality sleep.

If you want to avoid this chain of events, you must make sure you
get sound sleep by using melatonin.

In short, good sleep, which is a function of melatonin, can protect

you against Alzheimer’s and other neurodegenerative diseases,
while bad sleep or lack of sleep can bring you closer to getting these
diseases.

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Is it good to eat while in bed?

Is it true that your body is

eating while you're sleeping?
Well, in all honesty, it's more
of a cleaning and recycling
process that the body goes
through in different cycles.
This process is called
autophagy. I was first made
aware of this process 15 years
ago at a neurology conference, and the subject was regarding
degenerative neurologic disease and how the application of fasting
can help clear up protein tangles which. It was a very new and novel
approach as a therapeutic, and 15 years later it’s starting to gain a
lot of popularity. I'm in the alternative scene and this is the type of
strategy I've used since I first learned about it, however, I'm starting
to see neurologists locally that are beginning to embrace this
methodology as well. So, let's take a bit of a dive into what this is
and how you could benefit from it. Yes, you can help your body
actually clean and recycle or “EAT” the unwanted harmful plaques
through this process we call autophagy.

Auto here means self, and autophagy refers to eating. So, in

short, autophagy means eating the self.

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Why is autophagy so important

here? Because this process can
help your body clean up and
recycle any old, weak, dead, or
dying cellular material. This
includes dysfunctional
mitochondria, cancer cells,
dysfunctional immune cells, all
dysfunctional cells, as well as
all of the protein plaques
associated with many of the
diseases of aging in the brain. These protein plaques include tau,
neurofibrillary tangles, beta-amyloid, and alpha's synuclein plaques!

It so happens that all tissues in our body are basically undergoing 2

processes continually which include the growth of new cells and
tissues, and on the other side of this, the breakdown and recycling
of old, dead, or dying, and weak tissues. This is mediated through a
process called mTOR. This acronym stands for mammalian target
of Rapimyosin. mTOR is either turned on or turned off through
various stimuli. When mTOR is turned on your body is growing,
and cellular growth is activated. But, when mTOR is turned off or
inhibited we switch to the breakdown cleaning and recycling phase.

Growth is good, right? Or is it? It helps you build muscles; it helps

you grow bigger, stronger bones; it helps us when we have an injury
to repair. The growth phase can help you grow new hair, new skin
cells, and all of this helps you look younger and stay healthier.

Nevertheless, let’s take a look at where growth might be bad.

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One of the big problems in civilized cultures is that we have way too
much activation of mTOR, thus too much growth in the body. One
of the key reasons for this problem is that we have very easy access
to food. When we are feeding it makes sense that our body wants to
be in a growth phase. However, when we are fasting the growth
switches to the cleaning and recycling phase, and mTOR is
inhibited. Some of the more obvious problems associated with too
much growth include cardiovascular and circulatory-related issues,
where the muscular layer inside of our blood vessels thickens, choking
off the flow of blood through the vessel. This is particularly a
problem for the perfusion of the brain in many people as they get
older. Enlargement of various organs can occur, for instance, polyps
in the digestive tract as well as growths or cyst formation throughout
the body. Then there's the most obvious of them all which is cancer.

The excessive multiplication of cells in the organs can initiate

cancerous changes in healthy tissues. Generally, when this gets out
of control the body will use a process called apoptosis, which is a
formula for autophagy.

When this growth gets out of hand, the body needs to turn off mTOR
and shift to the autophagy cleaning phase.

Now, there are two major influences to activate or inhibit these

important cycles. Nutrient deprivation or fasting, and sleep will dial
down mTOR. Ultimately, autophagy works like a recycling system in
which the body eats away what is in excess but keeps what’s in good
condition, such as healthy cells, tissues, and even cell organelles like
mitochondria. The proteins and nutrients from these cleanup cycles can
then be reused to build new mitochondria, senescent cells, and
dysfunctional tissues.

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Senescent cells are a

huge problem that are
key drivers of aging
inflammation and many
other diseases. It's
through the inhibition of
mTOR and autophagy
that we clear out these
incredibly problematic
and dangerous cells. Moreover, senescent cells have also been
referred to as “zombie cells”, this is because in actuality they are old
dysfunctional cells that produce toxins that can be extremely
inflammatory. Moreover, they also hog a lot of energy in exchange for
nothing, because the cells are working. Ultimately meaning that they
get fed yet you get no work out of them, only their waste product.
Furthermore, it is thought that the accumulation of senescent cells is
the leading cause of aging and could be a major factor in many
diseases as well.

Melatonin can play an important role in limiting the number of

senescent cells, decreasing the negative impact they have on your
body, as well as improving the cleanup and recycling of the cells
through stimulating deep sleep.

Though fasting is effective, today’s generation seems to be more

into overeating than into starving. Americans eat an average of
14.75 hours a day, we have mid-meal junk food, pre-meal snacks,
and then, even late-night desserts.

Like I stated earlier, this is what is driving a lot of diseases in our

modern society. It's an over-expression of mTOR. With the habits as
explained above, we have very little time where we are in a fasting
state where our body goes into recycling and cleaning mode, thus
enabling mTOR to be inhibited.

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Besides us accumulating dysfunctional mitochondria, cells, and

tissues we also don't readily have the building blocks needed to
produce more healthy ones.

Valter Longo is a scientist who has brought much light to how this
plays into cancer and many other diseases. He demonstrated that
through decreasing our feeding window every 24 hours there can be
a dramatic improvement in the body’s function as well as enhanced
longevity. Doing extended fasting turns on this process even more
robustly when an individual would do a 3-to-5-day water fast. Longo
has done experiments with consumption of fewer than 1500 calories
per day for 3-to-5-day protocol where he’s demonstrated that there is
much benefit to gain. [1]

How does melatonin and sleep play into this process?

This is a book about melatonin, so the miracle molecule

demonstrates yet another benefit with regard to sleep. Deep sleep
can be a strong proponent to inhibit mTOR.

Here is research showing what a powerful regulator melatonin is for

autophagy ‘Therapeutic potential of melatonin related to its role as an
autophagy regulator: A review’ [2]

Besides the body going into a cleaning and recycling phase during
sleep we also have the glymphatic system mopping up and shuffling
off all of the toxins and waste products from the central nervous
system. Preventing this from happening can be catastrophic to the
central nervous system.

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 Melatonin - Miracle Molecule

Melatonin is the primary driver for this to work properly. When

melatonin levels decline as we age this problem can become much
worse. We ultimately produce a buildup of dysfunctional
mitochondria which then creates an energy deficiency. This then
allows for a buildup of toxins that subsequently creates an
environment that favors microbial overgrowth such as viruses and
bacteria. Remember that the terrain is what drives microbial growth.

When you have a lack of cleanup you produce the situation that we
discussed earlier, where the trash builds up and then comes the rats.
What if we only focused on killing all the rats and not cleaning up
all trash or if we only focused on bailing the boat and not plugging
the leak? You're going to waste a lot of energy and you're not
actually addressing the core of what's driving the problem.

Anybody looking to live longer and have a more robust and vital life
needs to pay very close attention to these mTOR cycles!

This is what I would suggest: Try starting

with a 6 to 10 hour feeding window. I
personally only have one or two meals per
day, and generally, skip breakfast. This did
not come easy for me at first and I had
trouble with my blood sugar and energy
when originally embarking on this process.
What you're really asking the body to do is
to switch into a different form of energy
production using ketones as its primary fuel
source. When you're sleeping and fasting
you are in ketosis and your body is using these ketones as energy.
Ketones are a much more efficient form of energy for the brain and
body. This developed for humans over many thousands of years as
when we were hunting, we were hungry, and we needed to have an
edge where we functioned at a higher peak state. The problem is that
because we're constantly feeding ourselves with lots of

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carbohydrates our body is efficient using sugars as energy and you

haven't given the body an opportunity to become efficient with
breaking down fats and proteins for energy, which is where you get
ketones from. So, the trick is to start increasing your fat and protein
intake and decreasing your carbohydrate consumption. There is, of
course, a lot more to this topic and I would recommend the book
from my friend Dr. Dan Pompa called Beyond Fasting.

In the next section, I want to tell you one more aspect of melatonin
that's linked to the blood-brain barrier.

Understanding the role of the blood-brain

barrier in melatonin production

Melatonin can stabilize and

strengthen the coupling of
circadian rhythms with the
sleep-wake rhythms and the
body’s core temperature. The
circadian organization such as
antioxidant and immune
defenses, glucose regulation,
Blood Brain Barrier made of
and hemostasis also depends on
Astrocytes.
the biochemical signals carried
by melatonin. These functions of melatonin need to be understood
from the point of view of the blood-brain barrier. This is important
because how the blood-brain barrier affects melatonin secretion in
contrast to other hormones makes it unique and more powerful.

Interestingly, the pineal gland, in spite of being a part of the brain

during its embryological stage (while it is still being formed in the
fetus), is situated outside the blood-brain barrier. As a result, it loses
its direct connection with the brain.
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While discussing the various processes involved in the role of

melatonin secretion and deep sleep, it is essential to know that the
production of this hormone is somewhat independent of the blood-
brain barrier, thanks to its unique location.

Why is the special ability of melatonin to escape the blood-brain

barrier so important?

● It allows for a larger uptake of tryptophan, which, in turn,

supports an increased melatonin production in response to
darkness.
● The freedom to escape the blood-brain barrier offers relative
protection to melatonin against premature enzymatic
degradation leading to a 10 to 20-fold rise in melatonin
levels.
● It explains why the pineal gland has to rely on stimulation
by sympathetic nerves and serotonin for regulating
melatonin production. [3]

These properties of melatonin make it a unique and powerful

molecule that can be utilized in our fight against diseases linked to
poor sleep.

Another antioxidant called glutathione should also be something to

be considered. This is another nutrient that declines in many
diseases as well as in age. It has been shown that low glutathione
levels can contribute to a breakdown in the BBB. Moreover, it has
also been shown that by supplementing with a 600 mg glutathione
suppository such as GlutaMax or through intravenous
administration, you can support the repair and protection of your
BBB. In our clinic, we utilize supplements that enhance circulation.
Which ultimately produces or allows further nutrients to support the
BBB in combination with a melatonin and glutathione suppository
called Sandman.

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Conclusion

As I have compared before, melatonin is like the electromagnetic

field of the earth. It protects our body the same way the
electromagnetic field protects the earth from solar radiation. The
flow of liquid metals in the outer core of our planets generates an
electric current. The rotation of Earth causes these electric currents
to create a magnetic field extending around the planet. This
magnetic field helps to sustain life on Earth. Without it, the living
species would be exposed to a high amount of radiation from the sun
and cause our atmosphere to leak into space.

Besides supporting the BBB, melatonin creates an inner protective

rhythm of the sleep-wake cycle that is synchronized with the
activities of the glymphatics and the body’s repair mechanisms. This
can provide protection to healthy tissues against toxins, free
radicals, beta-amyloid plaques, and much more. Consequently,
allowing us to live a healthy life.

Fasting can clear up senescent cells and trigger the cleaning and
recycling of cells and cellular components like mitochondria. Using
the MitoFast as a technique to aid in autophagy and increase the
influence of the fasting protocol might be interesting to look at if
you're wanting to boost brain power and prolong brain health.

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Chapter 5. Melatonin &
Immune System
Immune Health & Autoimmune Disease

A strong immune system to fight infections has never been more

important than it is today. As I write this book, we are in a global
lockdown due to the COVID-19 virus and this global pandemic has
created the most interest in protecting ourselves from infections I
have seen in my 26 years of practice.

If only I could afford to run ads on

TV for melatonin, I would educate
the world on how it can be of great
benefit without any risky side
effects. My friend Dr. Russel Reiter
has been quietly putting out the
science on melatonin for COVID-
19. Yet, funnily enough, I was asked
to take down ALL virus-related
information from my website by the FTC and FDA. It was a special
operation by our government to limit the information that went
against the agenda they are promoting, which is vaccines.
Therapeutic options have been ignored for the most part during the

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COVID-19 warp speed rush for a cure. Therapeutics like melatonin

without any big pharma entity pushing it into the faces of the
government will surely not see its potential as useful support for
COVID-19 or anything in the foreseeable future.

There are a few things more important than a properly functioning

immune system. Your immune system is built on your white blood
cells which circulate throughout your blood and your tissues to
defend your body from foreign invaders, such as infections. But
there is much more to the immune system, and we will dive into that
later in this chapter.

It is important that your immune system is strong enough to be able

to deal with the challenges presented to it. It’s also important that
your immune system, not over-respond or continue to respond, even
after the challenge has been met and resolved.

Your immune system uses very toxic substances to destroy these

foreign invaders. In addition to these toxic substances, the immune
system also uses something called cytokines which are defined as “a
number of substances, such as interferon, interleukin, and growth
factors, which are secreted by certain cells of the immune system
and have an effect on other cells.”

You could almost think about the immune system as a combination

of a janitor, the trash collector, the recycling crew, and the maid all
in one. Similarly, to how cleaning solutions can be very toxic for
us, they also help to keep a sanitary and clean environment in our
home and work. And just like it’s important to use just enough and
not too many of these services, your cleaning would be similar to
the situation inside of your body with your immune system.

It's a very delicate balance between not too much not too little!

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Generally, a poorly functioning immune

system is due to low energy reserves as a
result of bad mitochondria, which we will
speak of at length in another chapter. Also,
an under-functioning immune system can
also be the result of not recognizing what
it needs to clean up. Moreover, when the
immune system is weak, it allows
infections to run rampant. For instance, in
cancer, the immune system recognizes the cancerous cells and
cleans them up through apoptosis. Furthermore, an over-exuberant
immune system lends itself to autoimmune diseases and causes out-
of-control inflammation in the body with an example being severe
allergies, and of course, the cytokine storm that COVID-19 has now
made so infamous.

A good example that comes to mind is Goldilocks and the three

bears in which the
bear’s porridge was
either too cold or too
hot, and mama’s
porridge was just right.
Our immune system
needs to be like mama’s
porridge.

At first glance, one would think melatonin would have no

involvement in the immune system. And as mentioned in previous
chapters, melatonin did not seem to have an impact when there was
no stress present in the body. Remember the example we gave you
where researchers were first looking at melatonin use in mice and
found that the mice had no benefit with melatonin supplementation.
But later, they started to subject the mice to stress which was
achieved by putting them in a tube with little holes drilled in it for a

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few hours each day. Again, this is a common way by which they
would induce stress on these laboratory animals. This is where
melatonin really seemed to shine where the animals that were
subjected to stress had little health consequences versus the ones that
were not.

It's been more than a decade since the unique ability of melatonin to
regulate and strengthen the immune system functions was
discovered. Moreover, there are multiple studies that now share
similar results, for example, this new study published in Behavioral
Pharmacology, ‘The effects of melatonin on the behavioral
disturbances induced by chronic mild stress in C3H/He mice’
showed that regular treatment of stressed mice using melatonin
could prevent CMS-induced disturbances. This study supported the
idea that melatonin might be implicated in a homeostatic system that
protects us from disruptions induced by stress. [1]

Another study, “Effects of

melatonin on stress-induced
and diurnal variations of
nociception in Wistar and
spontaneously hypertensive
rats”, conducted by
researchers at the Bulgarian
Academy of Sciences
reiterated that there is
substantial evidence proving the antinociceptive effects of
melatonin. This study proved the impact of melatonin in the
modulation of nociception when the subjects were examined under
acute immobilization stress as well as on diurnal variations of
spontaneously hypertensive rats and normotensive. [2]

Yet a blockbuster finding with regards to melatonin was when

scientists found that the white blood cells, which, as I mentioned,
are considered the main players in the defense functions performed

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by our immunity, have melatonin receptors. What this means, is that

melatonin has a lot of involvement within the immune system and
is a very important substance for it to function optimally,
particularly in states of stress where your immune system needs to
react in an appropriate manner.

Melatonin appears to help the immune system function in a strong

yet controlled manner.

Interesting facts about melatonin and the

immune system

It’s intriguing to understand how melatonin produces an ultra-

specific action on the immune cells. On one hand, it stimulates the
secretion of cytokines to help your body attack the invading viruses,
bacteria, or other pathogens. This action helps to indicate that
melatonin can STIMULATE immunity and thus, contribute to the
release of proinflammatory cytokines.

But there's a twist to it. Though Melatonin can activate the immune
system, it does just the opposite when there’s a need to reverse or
prevent the damage that has occurred due to excessive
inflammation. It can also STOP the immune system from producing
more pro-inflammatory cytokines when they are not needed, or
when they are likely to cause damage to the tissues.

It is this dual action of melatonin on the immune system that has

been particularly of great interest to scientists.

Now after this quick overview of melatonin, let's move deeper and
get a closer look at the action of this miracle molecule on the
function of your immune system.

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Role of melatonin in supporting immune system

functions

If the immune system had a gas

and brake pedal, then melatonin
would have a foot on each. The
immune system needs to be able
to accelerate and slow down in
order to protect your body, thus
not becoming more of a problem
than an answer to your health.

When this system isn't working,

it will wind up causing diseases
such as chronic infections, cancer, and autoimmune diseases.

If your immune system is functioning normally, and by normal, I

mean like mama’s porridge at the perfect temperature, neither too
weak nor too overstimulated…Then, you can fight infections, avoid
autoimmune diseases, overcome inflammatory damage, and even
protect your vital organs against inflammation.

If it's a situation where you contract an infection such as COVID-19

or Ebola, where the inflammatory storm is so severe that it might
kill you, then melatonin may actually protect you from the fatalities
involved with these infections.

Again, is it important to look at the studies that have been conducted

with melatonin as it relates to its protective action from infections
and the cytokine storm.

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 Melatonin - Miracle Molecule

There's a study published in the Journal of Pineal Research,

“Melatonin and viral infections'' in which they gave each 2 groups
of mice a lethal injection of EMCV (Encephalomyocarditis V.).
With the melatonin on board, the survival rate went from only 6%
to 82%. [3]

Now, if you are looking for a good driver for your immune system
sitting behind the steering wheel that responsibly applies the brakes
and gas pedal, supplementing with melatonin might be something
important to consider.

Another study published in the Current Topics in Medicinal

Chemistry has demonstrated that melatonin can regulate the
production of cytokines and thus, inhibit inflammation.

“There is overwhelming information demonstrating the immune-

enhancing properties of melatonin.”

Moreover, a 2002 study published in the Current Topics in

Medicinal Chemistry, “Melatonin-Immune System Relationships'',
highlighted the existence of the relationship between melatonin and
the immune system and revealed the rhythmic production of
melatonin that works in a synchronized manner with the activities
of the immune system. It also showed the effects of pinealectomy
and the administration of melatonin on the variety of immune
parameters, such as specific as well as non-specific immunity. The
data suggested the existence of membrane and nuclear receptors for
melatonin in the immune system. This study, in particular, provided
overwhelming findings demonstrating the immune-enhancing
effects of melatonin. [4]

But that’s not all! A 2005 study published in the journal “Endocrine”
talked about the effects of melatonin on cellular and humoral
immune responses as well as immune mediator production and
cellular proliferation. It, again, showed how this hormone can

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produce a direct immunomodulatory effect on cytokine production.

This effect is almost always going to be a positive calming down of
an activated immune system. Nevertheless, it's very important to be
able to apply brakes after a fast immune acceleration.

This review further highlighted melatonin’s actions in immune

pathologies including autoimmunity, infections, and inflammation,
and emphasized its role as an immunity regulator. “One of the main
features that distinguishes melatonin from the classical hormones is
its synthesis by a number of nonendocrine extrapineal organs,
including the immune system.” [5]

We've mentioned this before, but it's worth repeating here that
melatonin is not just released by your pineal gland, but it is also
released by your immune cells. In fact, it's utilized by your
mitochondria throughout all of your cells.

How does melatonin help to inhibit autoimmune

disorders?

Besides controlling the brake and gas pedal, melatonin is a highly

reliable and powerful immunopotentiating agent. In my view, it does
not act directly but produces a synchronizing effect on your entire
neuroendocrine system, which is how it controls and regulates the
immune system.

What exactly does an autoimmune disorder mean?

An autoimmune disorder is when your body sees itself as an enemy,
and consequently attacks your own cells and tissues. It so happens
that sometimes, your immune cells just fail to recognize the body’s
healthy cells and tissues as their own.

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It considers them as foreign bodies that must be killed and removed.

So, the immune system activates a chain of reactions that leads to
the destruction of healthy tissues:

● In your central nervous system such as in MS & ALS.

● In the thyroid gland such as in the case of Hashimoto's
thyroiditis.
● In joints as in rheumatoid arthritis and ankylosing
spondylitis.
● In skin such as psoriasis, lupus, and eczema.
● In the gut such as in Crohn's disease.
● In blood cells such as in autoimmune hemolytic anemia, and
so on.

As a result of an immune system with a poor driver behind the

wheel, you may develop rheumatoid arthritis, thyroiditis, psoriasis,
eczema, lupus, and many other diseases that are categorized under
the umbrella term, “autoimmune diseases”. Whether you were
looking to prevent or reverse these diseases, your only hope is by
regulating your immune system.

Several research studies have confirmed that melatonin might be

helpful in this regard. Among these, there was one research study
published in the International Journal of Molecular Sciences that
demonstrated the ability of melatonin to inhibit abnormal immune
responses by controlling the production of cytokines and T helper
cells.

It highlighted the modulatory effect of melatonin in the development

of inflammatory autoimmune diseases including diabetes mellitus,
systemic lupus erythematosus, multiple sclerosis, rheumatoid
arthritis, and inflammatory bowel diseases. “The effect of melatonin
on the suppression of proinflammatory cytokine production has
been proven in many studies.”

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Moreover, according to another research study, “Modulation by

Melatonin of the Pathogenesis of Inflammatory Autoimmune
Diseases” published in the International Journal Of Molecular
Science, in 2013, this modulatory effect of melatonin could be
effective in several inflammatory autoimmune diseases. [6]

Melatonin suppresses the production of tumor necrosis factor

(TNF)-α & IL-1β. Nitric oxide has been found to be an important
mediator in an inflammatory response. Melatonin also plays a role
in the regulation of nitric oxide synthesis. Interestingly enough,
previous studies have shown that melatonin inhibits the over-
expression of inducible nitric oxide synthase (iNOS) in the liver and
lungs of lipopolysaccharide (LPS)-treated rats.

There are several forms of nitric oxide and as a substance can be

taken to promote a better immune system and cardiovascular
function. For example, induced nitric oxide is the type you really
don't want much of. It's the nasty NOS that destroys tissue and cells
and you want it when you need it, but when it continues or occurs in
too large amounts it is linked to many destructive diseases.
Melatonin can act to modulate this so that iNOS doesn’t cause
damage to your body. The mechanism of melatonin in the reduction
of pro-inflammatory cytokine as well as iNOS production has been
suggested via the inhibition of either expression or activation of
nuclear factor-κB (NF-κB).

Let’s discuss how Nuclear Factor kappa for Activated B cells or NF-
κB is. NF-κB plays a key role in regulating the immune response to
infections. Incorrect regulation of NF-κB has been linked to cancer,
inflammatory and autoimmune diseases, septic shock, viral
infection, and improper immune development. NF-κB has also been
implicated in processes of synaptic plasticity and memory. NF-κB is
important for regulating cellular responses because it belongs to the
category of "rapid-acting" immune proteins present in cells in an
inactive state. This allows NF-κB to be a first responder to harmful

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cellular stimuli such as in a bacterial infection. It is not the bacteria

itself that activates this. But it's the chemicals that are released
during an infection such as pro-inflammatory cytokines, iNOS,
adhesion molecules, COX-2, and matrix metalloproteinases
(MMPs).

Moreover, NF-κB is widely used by eukaryotic cells as a regulator

of genes that control cell proliferation and cell survival. NF-κB is a
critical promoter of tumorigenesis, which creates a compelling
argument for the use of antitumor therapy that is based upon
suppression of NF-κB. There have been many studies showing
melatonin's ability to calm down this inappropriate expression of
NF-κB. For example, Gilad et al. showed that melatonin can
suppress the expression of iNOS in white blood cells via suppression
of NF-κB. Furthermore, the expression of damaging adhesion
molecules by NF-κB is also suppressed by melatonin, resulting in a
reduced recruitment of neutrophils to inflamed sites.

Many of the dangerous drugs being studied indiscriminately shut

NF-κB down. There are very important functions of NF-κB as you
can see in this chapter. Modulating NF-κB is one of many reasons
Big Pharma would love to patent Melatonin as it would be the
biggest blockbuster drug ever. The research has shown time and
time again that NF-κB activity enhances tumor cell sensitivity to
apoptosis and senescence.

Remember in an earlier chapter, we talked about senescent cells that

are zombie cells, which accumulate when we don't have the ability
to recognize, kill, and recycle these cells. Senescent cells are cells
that utilize lots of energy, produce a lot of metabolic waste, and are
extremely pro-inflammatory. Also, recall that many researchers see
the accumulation of senescent cells as a primary cause of aging and
disease formation.

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It's super important to be able to

recognize tumors and produce
apoptosis that essentially eats these
cancer cells up like a Pac-Man. I
guess the point is, you really need
NF-κB as well as all of your pro-
inflammatory cytokines, but you
also require them at the proper
amounts, and you need them to turn
on and turn off on a dime! Basically,
what you really want is a responsible person behind the immune
wheel, controlling both the brakes and the gas pedal. That's where
melatonin comes in once again.

Melatonin may also help by profoundly affecting the glands and

organs involved in the immune system, such as the thymus. It can
also control cell-mediated immunity thereby reducing your risk of
autoimmune disorders.

One study, “Melatonin rejuvenates degenerated thymus and

redresses peripheral immune functions in aged mice” published in
2003 in the Immunology Letters, assessed whether melatonin
rejuvenates degenerated thymus and restores immune functions in
aged mice. It showed the positive effect of melatonin on age-
associated thymic degeneration and immune system dysfunctions.
Exogenous melatonin administered through the drinking water to
mice for 60 consecutive days reversed the age-associated thymic
degeneration by the significant increase of thymus weight, the
percentage of thymocyte cells at G2+S phases, and the total number
of thymocytes. Spleen weight, number of splenocytes, and
peripheral immune capacity including NK cell activity and mitogen
responsiveness also recovered significantly by melatonin
application in aged mice. These findings demonstrated that
melatonin supplementation, even in late life may reverse thymic
degeneration and improve peripheral immune functions. This is

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HUGE! [7]
This benefit of melatonin may be specifically useful for those who
have a family history of autoimmune diseases. Because ultimately
melatonin might protect them against their genetic tendency to
develop these conditions.

One study “Cytokine & Growth Factor Reviews” assessed the

potential role of melatonin in autoimmune diseases linked to
genetics. It showed that melatonin can regulate the cellular and
humoral immune responses, and control immune mediators and cell
proliferation by correcting the underlying genetic abnormalities.

Treatment with melatonin may also promote the differentiation of

type 1 regulatory T cells through the extracellular signal-regulated
kinase 1/2 and ROR-α (retinoic acid-related orphan receptor-α). It
would suppress the differentiation of Th17 cells through the
inhibition of ROR-α and ROR-γt expressions through NFIL3.
Moreover, melatonin can also inhibit NF-κB signaling pathways and
reduce IL-1β and TNF-α expression while promoting Nrf2 genes.
Nrf2 gene activation is a big deal! Nrf2 can protect cells and tissues
from a variety of toxicants and carcinogens by increasing the
expression of a number of cytoprotective genes.
NRF2 regulates the expression of antioxidant proteins that protect
against oxidative damage triggered by injury and inflammation.
NRF2 also plays a vital role in the regulation of metabolism,
inflammation, autophagy, proteostasis, mitochondrial physiology,
and immune responses. Furthermore, Nrf2 also increases
intracellular glutathione, one of the more powerful antioxidants to
calm down autoimmunity.

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If you consider the diagram here you can see Nrf2 works closely
with your antioxidant systems: Catalase, SOD, Glutathione and
Heme Oxygenase. Basically, Nrf2 controls the inflammatory and
oxidative states in the body responsible for worsening the symptoms
of cancers and also autoimmune disorders. This suggests that
melatonin could serve as a potential therapeutic target, and create
opportunities for more efficient management of autoimmune
diseases by regulating the novel signaling pathways involved in
certain genetic expressions, such as with Nrf2 and NF-κB. [8]

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Commentary:
Dr. John’s Advice on Autoimmune
Besides melatonin, broccoli sprout extract supplementation
should be considered to further enhance the Nrf2 gene
activation.

In an article in Trends Food Sci Technol. 2017 Nov titled

“KEAP1 and done? Targeting the NRF2 pathway with
sulforaphane” they were able to demonstrate that
supplementing with sulforaphane was a powerful activator of
the Nrf2 genes.

“Broccoli, especially as young sprouts, is a rich source of

sulforaphane and broccoli-based preparations are now used
in clinical studies probing efficacy in health preservation and
disease mitigation. Many putative cellular targets are
affected by sulforaphane although only one, KEAP1-NRF2
signaling, can be considered a validated target at this time.
The transcription factor NRF2 is a master regulator of cell
survival responses to endogenous and exogenous stressors.”

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There could be an argument for using high doses of

melatonin sulforaphane and broccoli-based preparations in
autoimmune conditions. At our clinic we like to dig as deep
as we can to discover reasons the immune might be under
stress. Things like mold exposure, chronic viral infections
like with EBV, CMV, HHV-6, Lyme Disease are all common
core issues with autoimmune disease. The gut is a very
important system to look at and will be involved in almost
ALL autoimmune cases. Poor sinus and oral hygiene can also
chronically activate the immune system.

Things like oil pulling for and a solid 30 day sinus protocol
like with the GlutaStat line of products could be beneficial.
Leaky gut due to chronic gut stress which is typically a poor
microbiome, sympathetic nervous system taking blood and
nutrients away from your gut, microbial infection of the gut
such as candida, H.Pylori, SIBO, Clostridium P., and
multiple parasitic infections.

Fasting is an important consideration to allow autophagy to

clean up all the dysfunctional immune cells. Moreover, the
re-feeding phase (after the fast) will trigger new health
functioning immune cells to be made in your thymus gland
and bone marrow.

See MitoFast here for my fasting protocol. My best advice

would be to check all these factors as many cases do best
when multiple aspects of these suggestions are followed at
the same time to clear the system. For more on these natural
approaches to health see www.UltimateCellularReset.com.

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Melatonin in organ transplantation

The effects of melatonin have been shown to support proper immune

system functions post transplantation procedures.

We all know that organ transplantation and skin grafting have an

inherent risk of rejection resulting in the failure of the procedure.
This obviously occurs because the immune system considers the
organ or graft as a foreign body and tries to destroy it by producing
inflammatory cytokines. This is why; patients are administered
immunosuppressive drugs before, during, and after the treatment to
minimize the risk of rejection.

Yet in cases like these, melatonin can be of some use, thanks to its
natural immunosuppressive action. Isn’t it amazing how melatonin
can once again be a brake pedal for the immune system when
function goes the wrong way?

There was clinical research published in June 2020 in Scielo that

affirmed the above, showing that melatonin administration may
decrease rejection and improve transplant success. [9]

Furthermore, a research study published in the Journal of

Endocrinology provided experimental evidence that melatonin can
be useful in reducing graft failure, particularly in cardiac,
otolaryngology, bone, ovarian, lung, pancreas, testicular, liver, and
kidney transplantation. This study affirmed that melatonin can be
effective in patients undergoing transplantation for end-stage organ
failure. It can reduce the chances of organ rejection, and also
improve bodily functions during the post-transplantation period.
[10]

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“We may never see the light of day within these diseases in our
modern health care model though! Ahh if only melatonin was able
to gain a patent. Yet another pipeline for a Pharma company like
Glaxo-Smith Kline. They would spend the money for larger studies
proving its effectiveness and dosages for specific diseases, and
market the heck out of it on TV! That is what they do even if the
drug doesn’t work well or has terrible side effects. Melatonin has
neither of these problems!”

These immunomodulatory effects of melatonin are truly dramatic

and could provide newer and more innovative ways to support the
recovery of patients with end-stage organ failure.

How does melatonin affect the immunity

to help you fight infections?

Let's take a look at Influenza which is the most common viral

infection we face.

Influenza is one of the most common viral infections that affects

nearly everyone once or several times in life. If you have weak
immunity, you’re likely to get influenza during every flu season.

● The protective effect of melatonin against the influenza virus has

been revealed during a research study published in the Journal
of Functional Foods in 2019. Melatonin was found to be
effective for the pre-treatment and treatment procedures in
PR8(H1N1)/Influenza A virus in infected mice.

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● The severity of pneumonia was also found to be lower in mice

pre-treated and treated with melatonin. This study affirmed the
role of melatonin as a protective molecule against the flu. [12]

Melatonin & Sepsis

The positive effect of melatonin on the immune system has been

observed in the management of viral infections in both the very
young and old. Melatonin showed to help with adults as well as in
newborn babies with sepsis (when an infection goes systemic).

Melatonin showed to help in preterm infants suffering from

respiratory distress syndrome (ARDS), which is the common route
of death from an infection that goes septic during a study
“Melatonin: its possible role in the management of viral infections-
a brief review” published in the Italian Journal of Pediatrics. [13]

Another study “Efficacy of Melatonin in the Prophylaxis of

Coronavirus Disease 2019 (COVID-19) Among Healthcare
Workers” supported by the Instituto de Investigación Hospital
Universitario has shown that melatonin can be used as a
prophylactic treatment. It can be specifically beneficial for patients
with weak immunity and healthcare workers who are regularly
exposed to infectious pathogens. Again, it works best when there is
stress. [14]

Melatonin can minimize the damage to healthy tissues thus

providing relief from the symptoms. It also reduces the levels of
lipid peroxidation products in your blood, promoting your chances
of survival in the event of sepsis or septicemia. Again, sepsis or
septicemia is where an infection goes systemic throughout your
body and can often lead to death.

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This is the definition of Sepsis: “A potentially life-threatening

condition caused by the body's response to an infection. The body
normally releases chemicals into the bloodstream to fight an
infection. Sepsis occurs when the body's response to these chemicals
is out of balance, triggering changes that can damage multiple organ
systems.”

As mentioned before, sepsis is where an infection goes systemic

and can be life-threatening.

In a large number of scientific experiments related to septic shock

and septic disease, melatonin has reportedly exerted beneficial
effects to arrest multiorgan failure and cellular damage.

Melatonin works by preventing nitric oxide synthesis and the

consequent reduction in peroxynitrite formation. These are some of
the most potent reactive oxygen species or ROS. In fact,
peroxynitrites are linked as the most dangerous oxidants to
cardiovascular disease. It’s extremely corrosive to your heart and
blood vessels as well as all tissues in your body, so we need
something to neutralize this enemy to health.

Here is another study “Melatonin for the treatment of sepsis: the

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scientific rationale” published in the Journal of Thoracic Disease,

demonstrating how melatonin, being one of the most premier
antioxidants in your body, provides strong antioxidant defense
mechanisms in order to protect your mitochondria, as well as
promote mitochondrial functions. [15]

Melatonin may reverse septic shock symptoms by:

● Preventing oxidative damage induced by

lipopolysaccharide, endotoxemia, and metabolic
alterations.
● Suppressing gene expression linked to the inducible nitric
oxide synthase.
● Preventing apoptosis or cell death.
● Reducing the synthesis of proinflammatory cytokines.

The antiseptic effects of Melatonin could protect the body against

polymicrobial sepsis caused by more than one microorganism.
Melatonin offers natural protection by producing an antibacterial
effect on white blood cells, especially neutrophils. The research
study “Protective Effect of Melatonin Against Polymicrobial Sepsis
Is Mediated by the Anti-bacterial Effect of Neutrophils” published
in 2019 in the Frontiers in Immunology, has further revealed that
macrophages and neutrophils express melatonin receptors. The
depletion of neutrophils during sepsis can be countered by
melatonin. Ultimately meaning that melatonin treatment could also
reduce the mortality resulting from sepsis due to multiple pathogens,
where the immune system is depleted. I would suggest that this
would be a large percentage of those with more than one infection.

This study suggested that melatonin could promote neutrophil

formation during the middle of a major battle within your body
called polymicrobial sepsis. It has an anti-bacterial effect combined
with an anti-inflammatory one. Furthermore, I can tell you years ago

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when I was very sick with Lyme disease, I was finally diagnosed
with this myself. Both mold toxins, as well as infections such as
Lyme, can deplete your immune system creating a situation where a
variety of what they call coinfections begin to take hold.

This is actually more common than many physicians appreciate, and

anybody struggling with a chronic condition should be tested for
this. Moreover, a large percentage will probably find this is the root
cause of their disease. [16]

Melatonin & Parasitic infections

Let’s look at parasites and how melatonin can support your body
while one of these nasty invaders takes hold inside.

In patients with parasitic infections such as toxoplasmosis, Chagas’

disease, and African trypanosomiasis, melatonin can enhance the
host's immune response against the parasite by regulating the release
of inflammatory mediators. These findings were proven during a
study “The potential use of melatonin to treat protozoan parasitic
infections: A review” published in the Biomedicine &
Pharmacotherapy in 2018. [17]

Moreover, according to the study “The role of melatonin in

modulating parasite infections”, published in the Clinical
Microbiology and Infectious Diseases, Melatonin may also reduce
the amoebic lesions and induce leuco phagocytosis, thus increasing
the number of dead amoebae in patients with amoebiasis. [18]

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Melatonin & Hepatitis

Hepatitis is a condition where the liver is inflamed, and oftentimes this can
be due to a viral infection.
In patients with viral-
induced hepatitis, melatonin
can restore the normal
cellular processes in the
damaged hepatic tissues.

According to a research
study published in The
Nutrients in 2018, “Dietary
Melatonin Supplementation
Could Be a Promising Preventing/Therapeutic Approach for a Variety of
Liver Diseases”, melatonin supplementation should be considered
important for preventing disease settings, particularly in the liver. [19]
When melatonin improves the ability of the immune cells to fight viruses
and bacteria and control the damage during acute and chronic infective
stages, it has the potential to safeguard organs like the liver in cases of
hepatitis. When melatonin is supplemented in viral hepatitis researchers
see reduced fatigue, body aches, and weakness, as well as normalizing
blood levels of liver enzymes. In the study, “Effects of Melatonin on Liver
Injuries and Diseases” published in 2017 in the International Journal of
Molecular Sciences, patients suffering from hepatitis can benefit from
melatonin use. The scientist postulated that the support melatonin
provided was through the energy production in the mitochondria of cells.
[20]

This allows the liver to do its filtering and neutralizing of the toxins in the
blood. The filtration takes a lot of energy and when the mitochondria
become overloaded through fighting an infection, they need the
antioxidant support melatonin provides, as well as a brake system to not
overheat in the battle. It's a similar story in many of these cases where
melatonin does this extremely important job. [21]
We've already taken a deep dive into how melatonin regulates the over-
production of oxidation through its powerful antioxidant effects. And also,

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how melatonin calms down the cytokine activation in order to protect the
mitochondria. This prevents the mitochondria from having to shuffle out
pyruvate into the cytoplasm (outside of the mitochondria, yet still within
the cell) resulting in the utilization of aerobic glycolysis for energy. But,
remember that this energy production only gets a little over 10% of the
energy (4 ATP) that you would otherwise gain through the Krebs cycle
(36 ATP). This is also what happens with cancer cells. Recall the Warburg
effect where the Nobel prize winner, Dr. Otto Warburg, discovered the
difference between cancer cells and healthy cells and how they make
energy. This is why there have been many studies showings how
melatonin suppresses the growth of cancers, which we will dive into in
another chapter. Let's not get sidetracked and continue to understand how
melatonin protects us during infections.

EMCV and Ebola virus infections

Studies showed how amazing
our miracle molecule was at
protecting our body during
these extremely dangerous
microbial invasions. There was
confirmation of the protective
role of melatonin in both

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EMCV (Encephalomyocarditis V.) and the Ebola virus infection as

was revealed in “Melatonin, the Hormone of Darkness: From Sleep
Promotion to Ebola Treatment”. [22]

Ebola causes severe symptoms by activating the coagulation system

and thus, brings about considerable disruption in the vascular
endothelium. This is becoming evident with COVID-19 as well. Yet
scientific research has shown that melatonin can protect your
vascular endothelium by calming down the extreme inflammation
triggered by the Ebola virus.

In another study “Beneficial actions of melatonin in the

management of viral infections: a new use for this molecular
handyman?” published in 2012 in the Reviews in Medical
Virology, showed that melatonin produces a protective effect
against EMCV (Encephalomyocarditis V.) and Semliki Forest virus
(SFV).
Melatonin also appears to prevent the increase in the permeability
of capillaries induced by the re-perfusion or ischemia, ultimately
keeping the blood vessels intact and the capillary perfusion
preserved. Likewise, with COVID-19 the lung tissue is where a lot
of this endothelial damage occurs, which results in ARDS or acute
respiratory distress syndrome. This is the leading cause of death, due
to most infections when they go septic.

Can you imagine if Pfizer was able to get a patent on melatonin? If

it could do even 10% of what melatonin can do with sepsis, with the
current COVID-19 pandemic, melatonin would be the biggest
blockbuster drug we've ever seen.

When the pandemic first started, I began promoting melatonin very

aggressively online and was quickly shut down by the FDA. Their
reasoning was that melatonin has not gone through phase 1 to 3
placebo double-blind studies and shown advocacy for COVID-19.
Of course, at the time, I wasn't promoting it as a cure. However, I

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was pointing to all of the studies I have within this chapter, from
which one can only conclude that melatonin could not be harmful
but could help.

Thankfully, it seems that melatonin is starting to become more

recognized and is being adopted in high doses in some of the more
progressive hospitals.

Nevertheless, let’s head back to the research, which brings me to

one more study titled “Melatonin prevents ischemia-reperfusion
injury in hamster cheek pouch microcirculation” published in 1996
revealed the beneficial effect of melatonin related to its antioxidant
properties. This study highlighted that melatonin may protect the
endothelial barrier integrity while further preserving the
microvascular blood perfusion by dysfunctions following ischemia-
reperfusion. [23]

And lastly, in the study “Ebola virus disease: potential use of

melatonin as a treatment” published in the Journal of Pineal
Research, it was demonstrated that the application of melatonin
might prolong the patients’ survival by providing adequate time for
the immune system to recover and eradicate the viruses, including
Ebola. Why didn't we hear about melatonin during the Ebola
outbreak? Economics, pure and simple! [24]

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Use of melatonin in the light of COVID-19

pandemic

It is well known that melatonin levels are quite high in our younger
years and then subsequently drop significantly after 30/40 years of
age. Why does SARS-CoV-2 seem to spare younger children? The
reason behind this could be that the peak melatonin levels are higher
in children compared to that in adults.

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Dr. John Commentary:

Melatonin and COVID-19 are an important subject right

now and when you read this you may be looking back at
the catastrophic results of an expedited vaccine when
therapeutics were basically ignored and not funded by our
government, all the while billions were thrown at vaccine
development.

Although this is not a book on vaccines, it is my opinion

based on a review of the literature that there has actually
been little gained by the use of vaccines over the years and
much tragedy to human health has occurred. If melatonin
was able to have a patent, we would be watching
commercials on how great it is for COVID-19. Yet this is
not the world we live in due to the economics, government
cover-ups, and corruption with our CDC & FDA.

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We've touched on COVID in other chapters, however, let's take a deep and
hard look at melatonin and how it may be an applicable treatment for
COVID-19.

In this article published 6/15/2020, titled “Melatonin and COVID-19”

stated the following:

“In this special issue, we have reviewed as many aspects of

melatonin and COVID-19 as possible. Included in this series are
reports of how the CNS, heart, lungs, gut, and erythrocytes are
affected by COVID-19 and what is the potential of melatonin on
them. For the molecular mechanisms and signal transduction
pathways, these involve effects of melatonin on CD147 binding
with SARS-CoV-2 spike protein, the switch of aerobic glycolysis
to mitochondrial oxidative phosphorylation in immune cells, ER
stress-UPR-autophagy alterations and kynurenine and the alpha
7 nicotinic receptor activation. In addition, the melatonin doses
that can be used in COVID-19 treatment have also been
estimated based on the published reports. Most importantly, in
this special issue, we have collected the first clinical report using
melatonin to treat COVID-19 patients. Castillo et al. have
successfully treated 10 patients with high doses of melatonin.
Eight of these 10 patients were over 60 years old and 7 of them
had the comorbidities of hypertension, diabetes and/or COPD.
Advanced age and predisposed medical conditions are huge risk
factors for mortality in COVID-19 patients. Fortunately, under
melatonin treatment, all of the patients survived.”

In other words, all 10 patients survived and 70% of this patient base was
very sick and statistically vulnerable to developing lethal ARDS. [25]

Moreover, the investigators of the previous study have also hypothesized

that the peak melatonin levels achieved by using supplements may also
help adults prevent COVID-19.

Another recent study published in 2020 in Melatonin Research, “Potential

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utility of melatonin in deadly infectious diseases related to the

overreaction of innate immune response and destructive inflammation:
focus on COVID-19” focused on assessing the effect of melatonin has
revealed interesting results. It has shown:

“The high mortality of deadly virus

infectious diseases including SARS,
MERS, COVID-19, and avian flu is
often caused by the uncontrolled
innate immune response and
destructive inflammation. The
majority of viral diseases are self-
limiting under the help of the
activated adaptive immune system.
This activity is cell proliferation
dependent and thus, it requires
several weeks to develop. Patients
are vulnerable and mortality usually occurs during this window period.
To control the innate immune response and reduce the inflammation
during this period will increase the tolerance of patients and lower the
mortality in the deadly virus infection. Melatonin is a molecule that
displays respective properties, since it downregulates the overreaction of
the innate immune response and overshooting inflammation, but also
promotes the adaptive immune activity. Many studies have reported the
beneficial effects of melatonin on deadly virus infections in different
animal models and its therapeutic efficacy in septic shock patients.
Furthermore, melatonin has a great safety margin without serious adverse
effects. We suggest the use of melatonin as an adjunctive or even regular
therapy for deadly viral diseases, especially if no efficient direct antiviral
treatment is available.” [26]

Ultimately, this study evaluated the possible benefits of using melatonin

supplements for regulating the uncontrolled response of the innate system
that causes destructive inflammation in patients with COVID-19. It further
showed that melatonin may down-regulate the exaggerated response of the
immune cells, control inflammation, and promote the activities of the
adaptive immune system.

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Can Melatonin help with allergies?

Allergies are another common problem linked with the immune system.
Just like autoimmune disorders, allergies occur due to the abnormal
response of the immune cells. An allergic reaction can transpire on the skin
(atopic dermatitis or contact dermatitis), lungs (asthma), or upper
respiratory tract (allergic rhinitis).

Does Melatonin have a use-case when it comes to

allergies?
Detailed analysis and assessment of melatonin use in a study “Melatonin
modulates allergic lung inflammation” which was published in the Journal
of Pineal Research in 2001showed the following:

“Asthma is an inflammatory lung disease characterized by cell

migration, bronchoconstriction and hyperresponsiveness, and
can be induced, as an experimental model, by ovalbumin
sensitization followed by a challenge. In addition to the well-
known immunostimulatory effects of melatonin, research has
identified some of its anti-inflammatory properties. In this study,
we evaluated the influence of pinealectomy and melatonin
administration on cell migration in an experimental model of
allergic airway inflammation. We evaluated, in pinealectomized
rats treated or not with melatonin, cell migration into the
bronchoalveolar fluid, the number of cells and their proliferative
activity in the bone marrow, and plasma corticosterone levels.
Pinealectomy reduces, 24 hr. after the challenge, the total cell
number count in the lung and bone marrow cell proliferation,
without changing the number of cells in the bone marrow or in
the peripheral blood. This fact suggests that melatonin is
important in the control of cell recruitment from the bone marrow
and the migration of those cells to the lung. Melatonin
administration to pinealectomized rats seems to restore the
ability of cells to migrate from the bone marrow to the
bronchoalveolar fluid. So, the development of specific inhibitors
of melatonin would benefit patients with asthma.” [27] [28]

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These findings were reiterated by another research study “Melatonin

reduces airway inflammation in ovalbumin-induced asthma” published in
Immunobiology in 2014. This study ultimately confirmed the
immunomodulatory effects of melatonin that could be beneficial in the
management of asthma. It proved:

“The administration of melatonin significantly decreased the

number of inflammatory cells, airway hyperresponsiveness,
and immunoglobulin (Ig) E with reductions in interleukin (IL)-4,
IL-5, and IL-13. Melatonin attenuated the airway inflammation and
the mucus production in lung tissue and significantly suppressed
elevated MMP-9 expression and activity induced by an OVA
challenge. In TNF-α-stimulated BEAS-2B cells, treatment with
melatonin significantly reduced the levels of proinflammatory
cytokines and lowered the expression and activity of MMP-9. These
results indicate that melatonin effectively suppressed allergic
asthma induced by an OVA challenge. The results suggest a
potential role for melatonin in treating asthma.”

Several research studies have further indicated that melatonin may

minimize damage to the skin, lungs, and upper respiratory passages in
patients who have had repeated attacks of allergies by regulating the
response of the immune cells. It may also control the frequency and
intensity of allergic reactions such as asthma, rhinitis, or dermatitis by
inhibiting the exaggerated response of the immune cells to allergens.

How can Melatonin inhibit age-associated

immunosenescence?

Cellular senescence is something we work on with our MitoFast Protocol.

Moreover, fasting in general works to clear up senescent cells which are
“zombie-like” cells that divert energy, thus sending out lots of pollution
into your system, causing major inflammation and aging. Activating
autophagy through inhibition of mTOR through fasting and use of

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senolytics such as with Lucitol can be helpful, however, melatonin can

also aid in this fight.
When immune cells become senescent it's called immunosenescence. It’s
similar to the degenerative changes occurring in your immune system due
to aging. Just like your joints become worn out, and your skin becomes
loose due to aging, your immune system also wears out in a similar way.
This age-associated decline in our immune functions can have a cascading
effect on how all organs and
tissues in your body, including
the brain and heart work.
Immunosenescence is
characterized by a reduction in
the functional activities of NK
cells, macrophages, and
granulocytes, all of which are
immune cells that protect us
against diseases and infections.
Immunosenescence can also
bring about a significant reduction in the production of IL-1 and a decline
in the functions of monocytes. Additionally, researchers have also
revealed that immunosenescence can lead to a slow rise in IL-6 production
and a decrease in the activities of CD3 and CD4 cells.
But there’s more! As age increases, the immune cells lose their ability to
differentiate between the body’s own cells from those of harmful germs,
due to which any existing autoimmune diseases may become worse.
Macrophages and T cells also begin to act slower than ever, allowing the
symptoms of infections to become more serious, before pathogens can be
detected by the immune cells. Additionally, our antibodies further become
less effective, putting you at a very high risk of severe infections.
This is why; when aged people contract infections, such as influenza and
pneumonia, they develop more serious symptoms compared to younger
people with the same infections.
All these changes linked to immunosenescence can do a lot of harm to
your health. Research studies have shown that melatonin might play a
significant role due to its immunomodulatory properties.

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Melatonin would enhance the cellular and innate immunity, and stimulate
the synthesis of progenitor cells of macrophages, granulocytes, and NK
cells.

What are progenitor cells?

Progenitor cells are actually the descendants of stem cells that have the
ability to differentiate and form specialized cell types. There are several
types of progenitor cells throughout our body, a progenitor cell is capable
of differentiating into specific cells belonging to the specific organ or
tissue.
Melatonin, by activating and stimulating the secretion of these progenitor
cells, may put the body into reverse mode, and slow down aging. Just like
stem cells, progenitor cells can later be differentiated to form new healthy
cells that can replace the old, dead, and damaged cells, thus restoring
optimum health. Moreover, progenitor cells also help to slow down the
effect on immunosenescence.
There's more to melatonin and immunosenescence:

• Melatonin can also stimulate the production of IL-2, -6, and -12
and support T-helper cell production, particularly of the CD4+
cells.

• At the same time, melatonin may reduce CD8+ cells by acting

through the immuno-opioid network. All these changes melatonin
can bring about in your immune system would have a positive
effect on your health by slowing down immunosenescence.

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These findings were revealed during a research study “Melatonin, immune

function and aging” published in Immunity & Ageing in 2005. This study
confirmed the following findings:

“Aging is associated with a decline in immune function

(immunosenescence), a situation known to correlate with
increased incidence of cancer, infectious and degenerative
diseases. Innate, cellular and humoral immunity all exhibit
increased deterioration with age. A decrease in functional
competence of individual natural killer (NK) cells is found with
advancing age. Macrophages and granulocytes show functional
decline in aging as evidenced by their diminished phagocytic
activity and impairment of superoxide generation. There is also
a marked shift in cytokine profile as age advances, e.g., CD3+
and CD4+ cells decline in number whereas CD8+ cells
increase in elderly individuals. A decline in organ specific
antibodies occurs causing reduced humoral responsiveness.
Circulating melatonin decreases with age and in recent years
much interest has been focused on its immunomodulatory effect.
Melatonin stimulates the production of progenitor cells for
granulocytes-macrophages. It also stimulates the production of
NK cells and CD4+ cells and inhibits CD8+ cells. The
production and release of various cytokines from NK cells and
T-helper lymphocytes also are enhanced by melatonin.
Melatonin presumably regulates immune function by acting on
the immune-opioid network, by affecting G protein-cAMP signal
pathway and by regulating intracellular glutathione levels.
Melatonin has the potential therapeutic value to enhance
immune function in aged individuals and in patients in an
immunocompromised state.” [29]

I personally know many people that fly to Mexico to get their NK cells
expanded and the cost is approximately $40-50,000. Could it be that taking
high doses of melatonin could do that same thing for a fraction of the cost?

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Melatonin can offer special help for lung

injuries

Lungs are highly vulnerable to damage caused by inflammation and

infections. Breathing in environmental pollutants, smoking – both active
and passive – and inhaling chemical fumes and gases, can do a lot of
damage to your lung tissues putting you at the risk of emphysema,
bronchitis, and bronchiectasis. In case the damage is severe, patients may
develop chronic
obstructive lung disease
and lung cancer.
Recent clinical research
has shown that
melatonin could provide
potential benefits for
preventing lung damage.
It can bind to the
receptors on the lungs
called the NLRP3
inflammasomes that are associated with several infections, including
COVID-19.
Melatonin, by getting to these receptors first, would help in blunting the
injuries from infectious pathogens and other harmful toxins.
The research published in the journal, Life Sciences, in 2020 has also
explored this in detail. Moreover, others have shown that melatonin may
limit virus-related damage and could be beneficial for minimizing lung
injuries. [30]

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Conclusion

The immune system is the real backbone of your health. It can determine
how efficiently all the organs of your body function, and how well you are
able to fight and even avoid diseases. Melatonin offers a safe and effective
way to allow your immune system to function more efficiently. It would
not just strengthen the immunity but also regulate the activities of the
immune cells. The immune-boosting and immunoregulatory properties of
melatonin could provide a huge breakthrough in the management of
autoimmune diseases, infections, allergies, and immunosenescence.
Furthermore, in addition to using melatonin, I suggest a regular fasting
routine, such as with MitoFast where you do a 24hr fast weekly and a 3-5
day fast several times a year. Ozone therapy can also help strengthen the
immune system, as it activates autophagy or cleaning and recycling of
dysfunctional immune cells. For viral immunity, I further suggest
supplementing with glutathione, zinc, quercetin, and selenium.
Moreover, it is also my opinion that poor sinus health can be a major drain
on many people's immune systems, so a 30-day sinus cleanse is good to
do at least once a year.
Dosing melatonin is supra-physiologic dosing, in a manner that absorbs
better than the traditional oral route is a good idea. Using suppository or
liposomal in the 100’s of milligrams is my suggestion to many of my
patients, and even the most knowledgeable scientist on melatonin, Russel
Reiter, MD, PH.D., takes 100-200 per night himself.

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Chapter 6: Melatonin &
Infections
Cytokine Storm, ARDS & COVID-19

We already discussed various mechanisms through which melatonin

can help to manage infections. Now, let's take a deeper look into
how melatonin can help you avoid injury and death from infection
by inhibiting the cytokine storm.

A cytokine storm is when there is a poor brake system in place, and

the defense mechanisms run out of control. Without brakes, these
defense mechanisms turn against our own bodies by bringing about
a severe inflammatory process known as the cytokine storm.

To know why this happens and what melatonin can do in this regard,
let’s first take a closer look at what the cytokine storm is and means
to your body.

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What exactly is a cytokine storm?

Cytokine storm is actually an

immune reaction that has gone
wild. It seems to be linked with
some of the most severe
infections humans have ever
faced such as EBOLA, ZIKA
virus, MERS (Middle East
Respiratory Syndrome), SARS
(Severe Acute Respiratory
Syndrome) and, of course, the recent and ongoing pandemic
COVID-19.

Here’s what happens.

During an inflammatory episode such as with an infection, cytokines

are released in response to the infection, some of which are IL1B,
IL6 seen in the image below. These cytokines affect our immune
cells in a way that disables the ability of these cells to both produce
energy efficiently, as well as make their own melatonin. The
mitochondria within these immune cells, as in any other cell in our
body, are the way in which we make the APT from glucose, we need
this energy during infections more so than in normal situations.

The cytokines will have a direct impact on an enzyme called

pyruvate dehydrogenase kinase (PDK) which will inactivate the
pyruvate dehydrogenase complex (PDC) which is necessary to
convert pyruvate into acetyl Co-A. Acetyl Co-A subsequently then
allows the mitochondria to normally make energy through the TCA
or the Krebs cycle (producing 36 ATP) as well as create melatonin.

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As a side note, this melatonin is made through the conversion of

Acetyl Co-A to N-Acetylserotonin (NAS) then to melatonin from
the NAS. When the PDK is upregulated by too many cytokines, it
causes energy to be made through aerobic glycolysis which is where
pyruvate is shuffled outside of the mitochondria into the cytosol and
used to make ATP.

Remember, aerobic glycolysis makes only 4 ATP. So, now we are

really running low on gas in the time of need. It’s like running out
of gas while driving through an alligator alley in Florida. Not a good
day to be stranded on this dangerous stretch of road. On top of this,
we now cannot produce melatonin to calm this storm; so, things run
wild and out of control.

Those who suffer from recurrent infections due to a weak immune

system and individuals who are more likely to develop serious
complications due to COVID-19 and other infections are people
whose immune systems tend to react in a rather catastrophic way.
Moreover, “weak immune system” situations are simply weak
mitochondria within our immune cells, allowing for poor melatonin
and inefficient ATP due to chronic inflammation resulting in too
much chronic cytokines upregulation of PDK.

What happens in patients with COVID-19 once the body is exposed

to the viruses, is that the immune cells flood the respiratory system.
They attack the lungs, which they should actually be protecting.
Even the blood vessels begin to leak and the blood itself starts
forming clots within the vessels.

The lungs are particularly vulnerable due to the fact this is where
we have a large volume of oxygen which is very reactive and
oxidative.

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Slowly, the blood pressure

plummets, and this is
when the organs begin to
fail, resulting in the life-
threatening complications
responsible for the risk of
morbidity. Scientists and
doctors increasingly
believe that these changes
occur due to the immune
system losing the brakes, so much so that it harms instead of
providing protection.

Melatonin when present allows more production from your

macrophages to fight infections, interleukins IL6, IL1, IL8 & TNF
alpha from the macrophage. It’s signaling and telling the
macrophage “Hey, calm down and apply a little brake before you
have a car accident”. So, one aspect is that melatonin calms down
the interleukins and secondly it acts as an antioxidant for the
macrophages, monocytes, and neutrophils.

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Why does your immune system need an

antioxidant during an infection?

When your immune cells are active, they

are “eating” the pathogens, further
bringing these into the cells and placing
them into vesicles within the cells. Let’s call
these “Hot Tubs”.

These pathogens within the Hot Tubs are

killed through the cell, basically by injecting
bleach into this vesicle. This process produces
a lot of reactive oxygen species or ROS. This
requires a massive amount of oxidation from
the miracle molecule to quench this process as
your premier antioxidant.

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What is the difference between Interleukin

and Cytokine?

Cytokines are proteins that are made in response to

pathogens and other antigens that regulate inflammatory
and immune responses. Interleukin production is a self-
limited process. The messenger RNA encoding in most
interleukins is unstable and causes a transient synthesis.

What goes wrong while fighting infections to

cause a cytokine storm?
Normally, when the body
encounters a pathogen, your
immune system is entrusted with
the responsibility of attacking the
invader, followed by which it is
expected to stand down. But this
doesn’t happen all the time.
Sometimes, the orderly army of
immune cells wielding their
molecular weapons goes out of
control, just like the obedient

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soldiers morphing into an unruly mob.

While there are several tests and treatments, which may help to
identify and tame this form of self-destruction by immune cells, it
can also be too early to be sure of the best course of treatment for
those who are already too weak and suffering from COVID-19.

Common variants of such a hyperactive immune reaction may occur

in an array of other infections, as well as other conditions that are
triggered by faulty genes and autoimmune disorders. In patients with
these conditions, the body considers its own tissues as invaders,
attacks them, and then, destroys these healthy tissues by producing
a cytokine storm.

This is why; all of these diseases are categorized under one umbrella
term “cytokine storm”. It is named after the proinflammatory
cytokines that rampage through your bloodstream. Yet cytokines are
nothing but small proteinaceous compounds — there are dozens of
them — which serve as the messengers for the immune system,
transiting between different cells and tissues, producing a variety of
effects, with some asking for more severe immune activity and some
requesting less. [1]

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Which conditions can trigger a cytokine

storm?

A cytokine storm can occur in a variety of conditions such as:

● Viral infections like COVID-19, influenza, Epstein-Barr

virus, herpes viruses, and cytomegalovirus, can all trigger a
cytokine storm. It is, sometimes, referred to as the reactive
MAS or HLH. [2]
● Cytokine release syndrome may develop in people who
suffer from leukemia and are receiving immunotherapy or
treatment with infused immune cells or antibodies. [3]
● Hemophagocytic lymphohistiocytosis is a genetic disorder
that may cause excessive stimulation of immune cells. While
this condition can be deadly, especially in infants, it can be
treated by taming cytokine storms with a bone marrow
transplant that replaces the improperly functioning immune
cells with healthy ones. [4]
● Macrophage activation syndrome may occur in patients with
autoimmune disorders such as juvenile arthritis, lupus, or
Still’s disease.
● Blood infections such as sepsis can also trigger a cytokine
storm and bring about widespread destruction of healthy
tissues. [5]
● Lymphoma and leukemia are types of blood cancers that
may create a cytokine storm. [6]

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● Graft-versus-host disease can occur when transplanted stem

cells produce immune cells, which attack the healthy tissues
in the recipient’s body. Scientists suspect a cytokine storm
to underlie this condition. [7]

“The regulation of the melatonergic pathways, both pineal

and systemic, may be an important aspect in how viruses
drive the cellular changes that underpin their control of
cellular functions. The role of the melatonergic pathways in
viral infections, especially influenza and COVID‐19, needs to
be emphasized to control the outbreaks. Viral or preexistent
suppression of pineal melatonin disinhibits neutrophil
attraction, thereby contributing to an initial cytokine storm.
Virus ‐ and cytokine‐storm‐driven control of the pineal and
mitochondrial melatonergic pathway can regulate immune
responses against infectious pathogens.” [8]

How can melatonin help?

According to a research study, “Melatonin: Roles in influenza,

Covid‐19, and other viral infections” published in the Reviews In
Medical Virology, melatonergic pathways can play a role in calming
the cytokine storm. This study has postulated:

The study confirms the role of melatonin in taming the cytokine

storm with its ability to regulate the functions of the immune system.

In another recent research study, “Melatonin Inhibits COVID-19-

induced Cytokine Storm by Reversing Aerobic Glycolysis in
Immune Cells: A Mechanistic Analysis” published in the Medicine
in Drug Discovery in June 2020, it was proved that exogenously

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administered melatonin could inhibit cytokine storm induced during

viral infections. It further showed how melatonin could help to
reverse aerobic glycolysis by repressing HIF-1α and mTOR, thus
disinhibiting PDC activity and promoting acetyl-coenzyme. The
reinstated, mitochondria-generated melatonin in combination with
the parenteral melatonin may provide a formidable weapon to
reduce the cytokine storm, as well as its damaging consequences,
thereby relieving the signs of a COVID-19 infection. [9]

These studies suggest that melatonin can calm the cytokine storm
and can help to minimize the damage caused due to infections.

Damage caused by the rising cytokine storm

The damage caused by the rising cytokine storm is not limited to

how it affects you during infections. When the cytokines that
stimulate immune activities become abundant, the immune system
may lose its ability to stop it by itself. And this is a highly grave
situation iit simply means even the patient’s own immune system
would be rendered helpless when the cytokine storm gets out of
hand. The immune cells will then continue to spread beyond the
infected body part, and start attacking even the healthy tissues.

For example, the cytokines would gobble up white and red blood
cells, thus damaging the liver. It will cause the blood vessel walls to
open up to allow immune cells to enter the surrounding tissues. And
in severe cases, the blood vessels may get so leaky that the air
passages and lungs might fill with fluids, causing serious difficulty
in breathing.

The loss of fluids from the bloodstream into the tissue spaces will
cause blood pressure to drop, putting more strain on the heart that
will find it more and more difficult to pump blood. At the same time,

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the blood will begin to form abnormal clots throughout the body,
thus choking the blood flow further.

When the vital organs

don't get enough blood,
the person can go into a
state of shock, thereby
risking multiple organ
failures or in worst
cases, even death.

According to the expert

immunologist and
rheumatologist at the
University of Alabama in Birmingham, “Most patients with
infections only have a fever initially, and about half of them develop
some sorts of nervous system symptoms like headaches, seizures,
and even coma.” The findings of this research study have shown that
the development of symptoms from a simple fever to seizures or
coma can occur rather
rapidly if the patient’s
immunity is poor or
when the body’s own
defense mechanisms fail
to function optimally, as
it occurs due to low
melatonin production
due to the lack of sleep. [10]

It is only recently that doctors are coming to understand why and

how the cytokine storm develops. While there are no fail-safe tests
to detect the cytokine storm brewing, there are some signs that might
indicate it could be underway.

For example, the levels of the protein ferritin in the blood may rise

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in patients with severe infections who are at risk of cytokine storm

and multiple organ failure. This may occur as the concentrations of
the inflammation indicators, like C-reactive protein secreted by the
liver increase in the blood.

So, one of the ways to make sure your immune system is working
efficiently to fight the virus without going out of control to cause a
cytokine storm is to keep a check on the protein ferritin and C-
reactive protein levels in the blood.

What melatonin can do to tame the cytokine

storm?

It is possible to stay safe and avoid the serious consequences linked

to cytokine storms when your body has enough melatonin. Several
research studies have already been conducted to assess the effects of
different medications, supplements, and hormones on the cytokine
storm specifically in patients with COVID-19 and influenza. Among
the many supplements assessed, it is melatonin that has shown
promise.

One research study “Melatonin is a potential adjuvant to improve

clinical outcomes in individuals with obesity and diabetes with the
coexistence of Covid-19” published in the European Journal of
Pharmacology in 2020 showed how melatonin could be effective for
calming the cytokine storm. The researchers confirmed that the
increased accumulation of fats in body organs and tissues can cause
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several metabolic disorders. Due to its antioxidant properties,

melatonin treatment can improve inflammatory mechanisms and
energy metabolism. Moreover, melatonin efficiently decreases the
production of blood inflammatory cytokines such as leptin and
resistin.

It has been demonstrated that melatonin has a remarkable

therapeutic action in decreasing the inflammatory storm. The
authors anticipated that melatonin can be used as a low-cost
therapeutic agent to improve the disorders associated with cytokine
storm and obesity.

It was further reported that melatonin has immunomodulatory roles

with dual proinflammatory and anti-inflammatory actions. The
proinflammatory effect is exhibited while fighting pathogens,
whereas the anti-inflammatory action is manifested in high-grade
inflammation. In cases such as sepsis, oxidative stress, organ injury,
and also in low-grade inflammation associated with aging and
neurodegenerative diseases.

This double-edge blade of melatonin is attributed to several

mechanisms. Besides its ability to downregulate proinflammatory
cytokine production and upregulate anti-inflammatory cytokine
production, melatonin exhibits high antioxidant capacity. It can
downregulate inducible nitric oxide synthases (the bad one) and
cyclooxygenase-2, and prevent the activation of the inflammasomes
NLRP3, and NF-κB. [11]

The overall effect of these activities of melatonin would be reduced

inflammation.

Based on this information, sustaining normal levels of melatonin in

elderly individuals and people with weak immunity, like diabetic
and obese patients, is suggested to be an important strategy to
strengthen the body’s defense systems.”

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Lastly, another research study “Melatonin Inhibits COVID-19-

induced Cytokine Storm by Reversing Aerobic Glycolysis in
Immune Cells: A Mechanistic Analysis” published in the Medicine
in Drug Discovery in 20202 which has shown that: “Because of
melatonin's potent antioxidant and anti-inflammatory activities, it
would normally reduce the highly pro-inflammatory cytokine storm and
neutralize the generated free radicals thereby preserving cellular integrity
and preventing lung damage.” [12]

Melatonin & Vaccines

Considering the COVID 19 vaccine?

Because melatonin enhances
the immune response to
vaccines by increasing
peripheral blood CD4+ T
cells and IgG-expressing B
cells, scientists feel it's smart
to dose 2 weeks prior and 4 weeks post-vaccine. Based on the prior
knowledge from the influenza vaccine, up to 50% in lack of
effectiveness would be found among healthy adults receiving
vaccines against SARS-CoV-2. Evidence that insufficient sleep may
be a causal factor accounting for this variability. Thus, individuals
experiencing total or partial sleep loss exhibit markedly reduced
antigen-specific antibodies as compared to healthy sleepers.

This article suggests using melatonin pre and post to gain a healthier
effect from the vaccine:

“Exogenous melatonin as a potential adjuvant in anti-SarsCov2

vaccines”. Administration of exogenous melatonin might boost the
potency of the immune response, and duration of the vaccine-
induced immunity. Moreover, melatonin administration might be

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especially useful in elderly males, but the existing evidence point to

a general capacity of melatonin to enhance both cell-mediated and
humoral immune responses irrespective of sex and age. The author
suggests a very low dose of 2 mg of a long-acting form of melatonin
and references (Maestroni et al. 1987) regarding the administration
of supra-pharmacological doses, stating it might be wisely avoided
surrounding a vaccine as such doses may decrease the immune
response (Maestroni et al. 1987). [13] Yet, there’s no denying this
is a little controversial, and more research should be done in this
area. Here, another researcher who penned the paper “An urgent
proposal for the immediate use of melatonin as an adjuvant to anti-
SARS-CoV-2 vaccination”, references the use of 10-20 mg daily as
a dose to follow.

“Melatonin enhances the immune response to vaccines by

increasing peripheral blood CD4+ T cells and IgG-expressing B
cells. Administration of exogenous melatonin could increase the
potency of the immune response and the duration of the immunity
induced by the vaccine. Besides, melatonin could also prevent
adverse effects of the vaccination due to its antioxidant and
immunomodulatory properties.” [14]

Conclusion

These studies have provided enough evidence for doctors and

physicians to be sure of the powerful anti-inflammatory, and
immunomodulatory activities of melatonin that could be effective
for calming the cytokine storm. By now, you must be wondering
why melatonin isn’t more well known for its ability to save lives
with infections from the worst pathogens known to mankind, based
on a large body of research.

And the answer to that boils down to just one word… Patent.

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There is no economic upside for a large pharma company to promote

nor take it through placebo double-blind studies for an indication.
The way our FDA works is that one drug (one molecule usually) is
taken through 3 levels of study and it has various endpoints that the
company and the FDA see as reasonable. This allows the drug to be
used for a narrow and specific application.

Of course, drugs can then be used off-label after that. However,

many times they will need to do another phase 3 study for new
indications for insurances to pay. It generally costs many tens of
millions to do this. If there is no patent to protect the company from
competition selling the same drug, they have a much more difficult
time recouping their money. This is a huge problem for many natural
remedies that would be far safer and effective than most drugs on
the market.

This is why melatonin will, most likely, never be widely spoken

about for cytokine storm usage, or any other indication it works for.
And it's up to you to share this with your doctor and use this
information for yourself. If you’re a healthcare practitioner, it's time
to recognize the shortcomings of our “Big Parma” health system and
start looking at melatonin as well as other natural nutrients as safe
and efficient therapies for your patients. These alternatives options
and information sources are all around you these days on podcasts,
YouTube, Google, PubMed, and seminars.

Anybody at a high risk of a cytokine storm needs to consider

supplementing with melatonin.

Sometimes supraphysiologic doses are needed and we will be

discussing this a little later.

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Chapter 7: Melatonin &
Autoimmune Diseases
Autoimmune diseases are
conditions in which the body’s
immune system mistakenly attacks
healthy cells, tissues, or organs.
This results in different disease
conditions such as type 1 diabetes
mellitus, ALS (Amyotrophic
lateral sclerosis), SLE (systemic
lupus erythematosus), multiple
sclerosis, inflammatory bowel
disease, and rheumatoid arthritis.

Biological effects of melatonin

Melatonin is considered a pleiotropic molecule with both pro-

inflammatory and anti-inflammatory properties. It is
immunomodulatory, meaning that it reduces excessive immune
functions in inflammatory conditions while improving immune
response in immunocompromised individuals. So, you could say
melatonin is truly adaptogenic, meaning that it is ready to meet
whatever needs it is called for.
Melatonin receptors are seen in a wide variety of immune cells. That
means melatonin has an influence on almost your entire immune
system including the cells like CD4+ T cells, CD8+ T cells, and B
cells.[4] These cells are used to kill invading pathogens and help you

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to produce antibodies to protect you from future infections. I am

going to get a little bit deep here with studies; so, if this isn't your
interest, skip to the next section.
Here is a study showing that treatment with melatonin enhances the
production of natural killer cells and monocytes in the bone marrow
of mice. Other studies also show that mice treated with melatonin
have decreased expression of interleukin (IL)-2 and interferon (IFN)
gamma. At the same time, there is an increase in the production of
T helper cell cytokines like IL-4 and IL-10.
Melatonin is also essential in the development of T helper cells. The
balance of T helper cells is crucial in regulating cellular immune
responses.
T helper 1 (Th1) is important for inflammatory responses by
producing pro-inflammatory cytokines such as IFN-y and IL-2.
However, T helper 2 (Th2) is anti-inflammatory and produces
cytokines such as IL-4, IL-5, IL-10, and IL-13.
Studies show that low doses of melatonin increase Th1 cytokines,
thereby increasing inflammation, while high doses of melatonin
reduce pro-inflammation, thereby reducing inflammation.

Melatonin & Autoimmune Diseases

Autoimmune diseases could be classified as either organ-specific,

as is found in type 1 diabetes mellitus, or systemic as in systemic
lupus erythematosus. In the United States, autoimmune diseases are
said to affect about 5% of the population.] This results from the
activation of immune cells, T and B cells, discussed earlier, by
antigens on the body tissues, which the body mistakenly sees as a
threat.

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The activation of these immune cells by this antigen results in

damage to target tissues by the activated cells. This is where I need
to interject my personal opinions:
Autoimmune conditions don't just happen for no reason. Some of
the factors at the root of this include chronic toxicity, chronic
infections, and imbalances in the digestive tract leading to either
dysbiosis or leaky gut syndrome. All of these cause inflammations
which regulates cytokines which then break down your cells ability
to make energy and this results in the ability to have a properly
regulated immune system.
Besides having an improperly regulated immune system, there are
also specific triggers to the immune system whereby the immune
system gets confused, and the information is encoded in order to
attack a specific tissue in the body.
Although we are diving into melatonin in this article, these
considerations need to be addressed along with melatonin
supplementation, in my opinion. Without addressing the root cause,
it will be like bailing a leaking boat or painting over rust. You can
reference ultimatecellularreset.com for more up-to-date information
about melatonin as well as other strategies for autoimmune
conditions. So, as it indicates that melatonin is an
immunomodulatory hormone. Melatonin has been shown to have a
regulatory impact on the pathophysiology of these disease
conditions. Understanding this mechanism can help in the use of
melatonin supplements in alleviating symptoms and slowing the
progress of the disease.
We're going to take a look at a variety of different autoimmune
conditions and consider the latest research using melatonin and how
it might affect the specific conditions. Conditions such as Type 1
Diabetes mellitus, Multiple sclerosis, Systemic lupus

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erythematosus, inflammatory bowel diseases, and Rheumatoid

arthritis.

Pathophysiology of Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1D) is also known as insulin-dependent

diabetes mellitus. This autoimmune disease results from the
destruction of beta cells in the pancreatic islets, which are
responsible for producing insulin. It is also called childhood or
juvenile-onset diabetes because it usually starts during childhood
with symptoms of
polydipsia (increased
thirst), polyphagia
(increased eating), and
polyuria (increased
urination) with associated
weight loss.
This autoimmune disease
is T cell-mediated. There
is hyperglycemia, ketosis, insulitis, and the presence of anti-islet
antibodies, including anti-glutamic acid decarboxylase (GAD)
antibodies, anti-insulin antibodies (AIA), and IA-2 autoantibodies.

Melatonin Modulation of Type 1 Diabetes

Mellitus

On your pancreas, you have MT1 & MT2 receptors for melatonin.
They are called “G-coded melatonin receptors''. That means this is
a direct link to diabetes and melatonin. When you go to sleep these
receptors are activated by melatonin and insulin is lowered and

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glucose is increased via these MT1&2 receptors. These receptors

have a direct link through cAMP and cGMP which is a massive
signal to your metabolism. This is so you can have more glucose to
make repairs needed within the body. Although eating late might
increase serotonin which helps to increase building blocks for
melatonin it might not be best for your health long term. Especially
if you're leaning towards Type 2 diabetes. In this section, we will
discuss how melatonin assists in the autoimmune form of diabetes
which is type 1. In type 1 Diabetes mellitus, the destruction of
insulin-producing beta cells results from the activation of pro-
inflammatory cytokines such as TNF-alpha and IFN-gamma, which
are mediated by Th1 cells.

Studies carried out on non-obese diabetic mice, an animal model of

T1D, show that prolonged administration of melatonin resulted in
increased survival and delayed onset of diabetes. Melatonin helps
shift the immune response from Th1 cells to Th2 cells, thereby
reducing TNF alpha and IFN gamma production, which protects
against beta-cell destruction.
Studies also show that pancreatic islet grafts done for diabetic mice
increased survival rate from 7 days to 17 days when melatonin was
administered. This pancreatic islet graft is a potential surgical
therapy for T1D by administering melatonin to prevent the graft
from attack by the immune cells or rejection.
In chapter 16 we’ll be learning more about how melatonin can be
useful in cases of diabetes, both type 1 and 2.

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Pathophysiology of Multiple Sclerosis

Multiple sclerosis is a
chronic inflammatory
demyelinating disease of
the central nervous
system. It results from
the loss of the neuronal
myelin sheath due to an
attack by autoantigen-
specific immune cells. This leads to pain, fatigue, body weakness,
and even vision loss at times. The onset of the disease is usually
between the age of 20 and 40 years.
The pathogenesis of multiple sclerosis involves both the adaptive
and innate immune cells. Experimental autoimmune
encephalomyelitis (EAE) is the commonly used animal model for
multiple sclerosis due to its close similarities.
Findings show that animals with EAE have T cells and macrophages
infiltrating the CNS lesions. This autoimmune process is initiated by
the adaptive immune CD4 T cells, which results in the production
of inflammatory cytokines by the innate immune cells like
macrophages. These pro-inflammatory cytokines result in severe
inflammation and damage to the myelin sheath and neurons seen in
EAE.[11] The production of reactive oxygen species in the affected
areas as markers of oxidative stress is increased in the neurons of
Multiple sclerosis patients.

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Melatonin Modulation of Multiple Sclerosis

Findings show that there

is dysregulation of
melatonin production in
patients with multiple
sclerosis. There is an
excretion of a high
amount of melatonin
metabolites in such individuals’ urine at night.[9] This means that
such patients have a reduced level of melatonin. This is correlated
to the fluctuation of multiple sclerosis symptoms.
In multiple sclerosis, there is the activation of Th17 cells, which
worsens the inflammation. Melatonin suppresses the Th17 cells,
which helps slow down or stop the progression of the disease.

Pathophysiology of Systemic Lupus

Erythematosus

Systemic lupus erythematosus

(SLE) is an autoimmune disease
characterized by malar (butterfly)
rash, photosensitivity, nephritis,
and arthritis.[14] It results from
damage to tissues by immune cells.
SLE affects more women than men
and can manifest at any age.
In SLE, there is an activation of autoreactive T cells, resulting in B
cell hyperactivity. This leads to the production of Th1 cytokines

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such as IL-2 and IFN-gamma as well as TH2 cytokines IL-4. SLE

also shows increased levels of inflammatory cytokines TNF-alpha
and IL-6.

Melatonin Modulation of Systemic Lupus

Erythematosus

Research shows that melatonin administration can be helpful in the

treatment of SLE. The mice model of SLE shows improvement in the
symptoms after the administration of melatonin. However, the
effects of melatonin administration are time-dependent as well as
gender-sensitive.

When melatonin is administered to female mice in the morning,

there is an increase in survival rate, and symptoms improve.
However, when administered in the evening, there is no noticeable
improvement.
For male mice, however, the effect of melatonin is different.
Melatonin treatment of SLE in male mice worsens the symptoms by
increasing inflammatory cytokines and autoantibodies. This effect
in males may be due to testosterone in males, which increases
proinflammatory cytokines when combined with melatonin.
Therefore, for patients with SLE, melatonin supplements will
benefit female patients and should be used in the morning.

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ALS and Melatonin

In ALS oxidative stress is a common molecular denominator of the disease

progression. Melatonin shows a unique spectrum of antioxidative
effects not conveyed by classical antioxidants. Due to this unique
antioxidant property, it shows
effectiveness against ALS in
super-physiological doses.

A study performed in 2006

called “Reduced oxidative
damage in ALS by high-dose
enteral melatonin treatment”
used 300 mg melatonin
suppositories dust once a day for ALS. This is a section reported in
the study.

“In a clinical safety study, chronic high-dose (300 mg/day)

rectal melatonin was well tolerated during an observation
period of up to 2 yr. Importantly, circulating serum protein
carbonyls, which provide a surrogate marker for oxidative
stress, were elevated in ALS patients, but were normalized to
control values by melatonin treatment. This combination of
preclinical effectiveness and proven safety in humans suggests
that high-dose melatonin is suitable for clinical trials aimed at
neuroprotection through antioxidation in ALS.” [18]

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Safety of melatonin in the management of

autoimmune disorders

Another concern related to the use of melatonin for autoimmune

disorders is the higher doses used in several experiments. However,
melatonin has exhibited a high level of safety even in clinical trials
when used in higher doses.
According to a clinical trial ‘Modulation by Melatonin of the
Pathogenesis of Inflammatory Autoimmune Diseases’ published in
the International Journal of Molecular Sciences in 2013, participants
with amyotrophic lateral sclerosis, who were administered a daily
dose of 30 to 60 mg of melatonin orally tolerated it without any side
effects.
It has also shown that patients who received daily melatonin
treatment in the form of rectal suppositories at a higher dose of 300
mg per day also showed no complications while exhibiting
significant improvement in the symptoms.
Other than the oral doses and the suppositories, the safety and
efficacy of intravenous melatonin have also been proven.
The report has also demonstrated that the treatment of patients
undergoing aortic surgery can be combined with intravenous
melatonin administration in a dose of 60 mg to improve the
outcomes.
Therefore, the application of higher pharmacological doses of
melatonin in the management of autoimmune disorders can be
considered acceptable. [1]

In another research study, ‘Reduced oxidative damage in ALS by

high-dose enteral melatonin treatment’ published in the Journal of

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Pineal Research has suggested combining the conventional

treatment in patients with amyotrophic lateral sclerosis (ALS) with
melatonin to support faster recovery.
This study was focused on assessing the effectiveness of melatonin
in the management of ALS, which is a collective term used for the
fatal motor neuron diseases of different etiologies, having oxidative
stress or free radical damage as a common molecular precursor to
disease progression.
This study showed that the antioxidant effect of melatonin remains
active even when it is administered in the form of rectal
suppositories.
The potential role of melatonin as a neuroprotective compound was
also established in this study. It showed that melatonin could
attenuate glutamate-induced cell death in the cultured motoneurons.
Additionally, the higher doses of oral melatonin also worked
significantly by delaying disease progression and extending the
survival of the participants.
The clinical safety of melatonin was also demonstrated in this study.
It shows that the long-term use of high doses (300 mg) of rectal
melatonin in the form of suppositories could be well tolerated. It also
helped produce the desired results. The research study was
conducted over a period of 2 years during which no adverse effects
were noticed in participants.
Importantly, the melatonin uses also helped to reduce the circulating
levels of serum protein carbonyls, which is a marker for oxidative
stress in ALS patients. The serum protein carbonyls levels returned
to control values following melatonin treatment. The combination
of proven safety and preclinical effectiveness of melatonin
suppositories reiterate the usefulness of high doses of melatonin for
neuroprotection and antioxidation in patients with autoimmune
disorders such as ALS. [2]

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I suspect there would be considerably better results in many of the

studies where the dosing was performed poorly, if the original study
had been performed similarly to this one using a suppository.
Studies show that oral absorption of melatonin is only 2.5% whereas
a suppository bypassing the gut and digestive enzymes, as well as,
passing through the liver would have a much higher absorption.

Conclusion

In conclusion, anyone with an autoimmune condition should

seriously consider supplementing with quality melatonin. The
question is how much melatonin should one use? Will it shut down
my normal production of melatonin and if I take high doses of
melatonin is that dangerous? Anyone that is looking to deal with
sleep issues, as long as they're not trying to reset their circadian
rhythm in a separate time zone, will be fine with doses of melatonin
from 3 to 20 mg.
There's something called super-physiological dosing of melatonin
where doses up above 40 mg all the way up to 200-300 mg are taken.
These doses are both safe as studies show that even up to 150,000
mg, melatonin would not cause any toxicity. In addition to that,
unlike most hormones, melatonin does not create negative feedback
on your brain’s production of melatonin. Anyone suffering from an
autoimmune condition may consider taking higher doses of
melatonin. Due to melatonin only being 2 1/2% absorbed orally,
some may consider the use of suppositories or even a liposomal
delivery such as with Sandman.
In addition to melatonin supplementation, it is advised to seek the
care of a functional and or naturopathic practitioner that can run the
right laboratory tests to determine what's at the root cause of the
autoimmune condition. Once they have this knowledge, they can
work on correcting the underlying problem, wherein you start and

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continue your melatonin protocol. This commentary in the

conclusion of chapter 5 is worth repeating here:

The immune system is the real backbone of your health. It can

determine how efficiently all the organs of your body function, and
how well you are able to fight and even avoid diseases. Melatonin
offers a safe and effective way to allow your immune system to
function more efficiently. It would not just strengthen the immunity
but also regulate the activities of the immune cells. The immune-
boosting and immunoregulatory properties of melatonin could
provide a huge breakthrough in the management of autoimmune
diseases, infections, allergies, and immunosenescence.
Furthermore, in addition to using melatonin, I suggest a regular
fasting routine, such as with MitoFast where you do a 24hr fast
weekly and a 3-5 day fast several times a year. Ozone therapy can
also help strengthen the immune system, as it activates autophagy
or cleaning and recycling of dysfunctional immune cells. For viral
immunity, I further suggest supplementing with glutathione, zinc,
quercetin, and selenium.
Moreover, it is also my opinion that poor sinus health can be a major
drain on many people's immune systems, so a 30-day sinus cleanse
is good to do at least once a year.
Dosing melatonin is supra-physiologic dosing, in a manner that
absorbs better than the traditional oral route is a good idea. Using
suppository or liposomal in the 100’s of milligrams is my suggestion
to many of my patients, and even the most knowledgeable scientist
on melatonin, Russel Reiter, MD, PH.D., takes 100-200 per night
himself.

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Chapter 8: Melatonin &
Cardiovascular:
Heart Health, Cholesterol & Blood Pressure.

Much of your health depends on how efficiently your heart

functions. A poorly functioning heart is the beginning of most
diseases, as it would simply mean a lack of efficient supply of blood,
oxygen, red cells, white cells, and vital nutrients to all organs of the
body.

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We need to take special care of our hearts as we only get one for our
entire lifetime. Besides, the brain and the heart are among the top
two most metabolically sensitive organs in the body, meaning that,
any disruption in energy production from the cell will manifest in
both these organs first. Of course, the mitochondria are at the core
of this energy production, and we've already discussed in subsequent
chapters how melatonin is very important during stressful situations
to protect the mitochondria and our vital energy production.
There are a variety of different actions where melatonin improves
the functions of the heart and the entire cardiovascular system. In
fact, melatonin produces many favorable effects for your heart,
blood vessels, and even helps to lower blood pressure and
cholesterol.
In this chapter, we will learn how melatonin helps to improve heart
functions and protects you from the disorders linked to high blood
pressure, poor cardiac output, and irregular heart rhythm.

Melatonin and cardiovascular diseases

Atherosclerosis is one of the most common chronic vascular

diseases in which oxidative stress and inflammation are implicated
to be the major causative factors. The early stages of the
development and deposition of cholesterol plaques involve
endothelial activation, which is induced by the oxidized low-density
lipoproteins, inflammatory cytokines, and the modifications in
endothelial shear stress.
The research study “Melatonin and Cardiovascular Disease: Myth
or Reality?” published in the Cardiologia in March 2012 has shown
that melatonin can help to reduce the risk of atherosclerosis by
decreasing the levels of LDL or bad cholesterol and increasing the
levels of HDL, the good cholesterol.
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The study suggested that the antioxidant effects of melatonin on

low-density lipoprotein oxidation may depress the plasma level of
total cholesterol and VLDL (very low-density lipoprotein)
cholesterol. This action of melatonin is linked to improved heart
health. It indicates that this hormone would protect the heart against
atherosclerosis that basically occurs due to the deposition of
cholesterol plaques along the walls of the arteries.
Basically, these plaques are formed when your diet comprises foods
rich in unhealthy, pro-inflammatory fats, like trans fats and saturated
fats, but lacks healthy fats like monounsaturated fats (MUFA) and
polyunsaturated fats (PUFA). Heated up vegetable oils are the main
culprit that needs to be avoided. These are the primary oils used in
restaurants to cook food, therefore it's almost impossible to eat out
regularly and avoid them. Plaque buildup can also be indirectly
related to when your liver is not efficient enough to metabolize fats.
These unhealthy fats oxidize very easily then tend to remain
circulating in the bloodstream without being utilized to supply
energy to the body. The high level of oxidation and inflammation
will erode the protective layer within the blood vessels making it
easier for this plaque to accumulate. These circulating fats, over a
period of time, form thick plaques that get deposited at various
places along the inner walls of the blood vessels, thus clogging
them. In younger individuals, these plaques are generally softer and
can dislodge, creating a higher risk of stroke. As we get older, they
harden and become more calcified, with less risk of a stroke but lead
to poor circulation. These plaques can lodge themselves in the
arteries that supply blood to the heart or your brain. The result would
be a heart attack or stroke, respectively.
These dangerous consequences of high cholesterol levels could be
avoided if your body has sufficient melatonin. Melatonin may
reverse the hypercholesterolemic states by increasing an
endogenous cholesterol clearance effect.

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This means melatonin would stimulate the rate at which cholesterol

in the bloodstream and tissues is cleared from the body through
various mechanisms, like
being burnt up for energy or
broken down to be eliminated.
Due to its lipophilic nature,
melatonin can also enter the
lipid phase of low-density
lipoprotein particles readily
and prevent lipid peroxidation.
To confirm this hypothesis further, this study even showed the
association between nocturnal raised levels of oxidized LDL (low-
density lipoprotein) and the reduced melatonin levels in patients
with atherosclerosis-induced myocardial infarction.
These findings support the theory that melatonin has the potential to
lower total cholesterol levels and stimulate the levels of good or
high-density lipoprotein cholesterol levels. And these changes
would be protective against the development of cardiovascular
diseases.
The study showed that the administration of melatonin in
pharmacological doses would also reduce blood pressure as a
consequence of different mechanisms, including the direct
hypothalamic effect it can produce.

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For example, melatonin would act on

the hypothalamus and regulate its
activities to ensure your blood
pressure stays within normal limits.
Similarly, it may also help to lower
catecholamine levels, cause
relaxation of the smooth muscles in
the walls of blood vessels, and most
importantly, produce antioxidant
effects. So, here's the dichotomy, as
we get older, we have lower melatonin levels, and our blood
pressure goes up. Doctors then give us blood pressure-lowering
medications that have a negative effect on our melatonin levels. If
more doctors were aware of how melatonin works with blood
pressure, there would be fewer prescriptions for blood pressure
medications and many more for melatonin supplementation.
Catecholamines are hormones secreted by your adrenal glands,
located at the top of your kidneys. Some examples of
catecholamines include norepinephrine, dopamine, and epinephrine
(which was earlier called adrenalin). Your adrenal glands secrete
and release catecholamines into the blood when you are emotionally
or physically stressed. Some of the typical effects of catecholamines
include increased heart rate, blood pressure, and blood glucose
levels.
Melatonin, with its ability to downregulate catecholamines, could
bring your blood pressure within normal limits and prevent the
serious consequences related to hypertension, such as stroke and
heart attacks. If you are currently taking blood pressure medication
it might be a good subject to bring up to your doctor, regarding
starting melatonin and having him monitor your blood pressure in
order to taper off if you have less of a need for the medication. Please
keep in mind, none of the suggestions in this book are meant as
medical advice and you should always get the approval of your

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healthcare provider before you make any changes to your medicines

or supplement regime.

How do Mitochondrial dysfunctions affect your

heart?

We've discussed the mitochondria in detail and how it's the

powerhouse of the cell. Without healthy mitochondria, the cells in
your body would no longer be able to produce the energy they need
to survive or function.
So, what happens to your heart when stress from inflammation
cripples these mitochondria?
You may want to go back and review the section on how
inflammation regulates cytokines which then has a negative effect
on how the cell produces energy. How almost all stressful conditions
have a commonality where this inflammation and cytokines are
upregulated and thus have a negative impact on the mitochondria.
How we start to produce only 4 ATPs versus 36, which is less than
10% of the energy efficiency we would otherwise have. The heart
and brain are the 2 most metabolically active organs of your body.
So, they also need a continuous source of energy. The functions of
these 2 vital organs are highly vulnerable to low energy supply.
And this is why; when your body is struggling with inflammation,
the damage it brings to the mitochondria at the cellular level would
have a very bad impact on how efficiently your heart works? Let me
explain why.
Mitochondria play a crucial role in the normal functioning of your
heart and in the pathogenesis of various types of heart diseases.
Specific mitochondrial dysfunctions may trigger the development of
cardiomyopathies simply by affecting the energy supply to heart
muscles. [1]
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According to a research study published in the Texas Heart Institute

Journal in 2013, the heart depends highly on the generation of
oxidative energy in mitochondria to receive the large amount of
ATPs it requires for its continuous, contractile pumping activities.
Additionally, cardiac mitochondria also perform other cellular
functions like generating reactive oxygen species (ROS) and
regulating cellular apoptosis. [2]
The mitochondria also play a role in the regulation and growth of
cardiac bioenergetic arrangement.
Disruptions in energy production due to the impairment of
mitochondrial functions have been implicated in a wide range of
metabolic, degenerative, neoplastic, and age-related diseases
affecting the heart and other organs.
Mitochondrial cardiomyopathies are characterized by impaired
heart-muscle functions, structure, or both. It may present in various
forms such as hypertension, coronary artery disease, and valvular
diseases. The presentation of mitochondrial cardiomyopathies may
also include dilated hypertrophic left ventricular non-compaction,
ventricular tachyarrhythmia, and heart failure.
This just goes to show the severity or the extent to which
mitochondrial dysfunctions can affect the heart.
Is it possible to restore healthy functions of the heart by eliminating
the root cause of inflammation-causing mitochondrial dysfunctions?
If you can ensure your heart muscles are not deprived of energy
during stressful chemistry in the body, much of these complications
could be avoided.

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Doctor John’s Advice: Many people live in this stressful

chemistry their entire life or for many many years. This
stressful chemistry could be a consequence of your diet, the
exercise you're not getting, too much exercise, stressful
mental-emotional states, toxic exposure from pesticides and
herbicide, work-related toxic exposure, mold and biotoxin
exposure or accumulation, microwave stress from 4G and
5G, acute or chronic unresolved infections in the body to
include cavitation’s in the jaw and poor oral and sinus
hygiene, and heavy-metal exposure in accumulation. Many
of these things can be dealt with once we understand what
they are and how detrimental they are to our health and
well-being. This is where a solid functional doctor uses
natural and practical methods to isolate these things and to
begin to make positive changes in your life. Of course,
measuring the results along the way is important.

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The potential use of melatonin as an

antioxidant during myocardial infarction

There is evidence suggesting the cardioprotective benefits of

melatonin in patients with myocardial infarction. The extent of the
ischemic reperfusion injury to the heart could be decreased to some
extent when exogenous melatonin is included in the treatment
protocol.
Melatonin would reduce the infarct size and the risk area, plus
minimize the incidences of reperfusion arrhythmias.
Also, ischemia is associated with the formation of reactive oxygen
species from residual molecular oxygen molecules. So, it is
suggested that the cardioprotective effect of melatonin is probably
associated with its ability to scavenge and destroy free radicals and
stimulate the expression of antioxidant enzymes.
The scavenging action of
melatonin occurs in both
physiological and larger
pharmacological doses. Not
just melatonin but several of
its metabolites have the
ability to detoxify free
radicals and restore healthy heart functions. Yet melatonin is
believed to work by stimulating essential enzymatic intracellular
antioxidant enzymes such as superoxide dismutases (SOD) within
both mitochondrial and the cytosol of the cell. It may also induce
the activities of another powerful intracellular antioxidant called
glutathione.
Moreover, it might also protect mitochondria against oxidative
stress and thus, ensure the heart muscles receive a good supply of

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energy needed to perform pumping action and other functions. This

indicates the role of melatonin as a bioenergetic agent and its ability
to improve mitochondrial functions. Research data suggests that
patients with a history of myocardial infarction and angiographic
no-reflow tend to have a low level of intra-platelet melatonin and
higher systemic oxidative stress than people without this
phenomenon.
This data suggest that melatonin may act as a potent antioxidant
agent, thus reducing myocardial damage induced by ischemia or
reduced oxygen supply to the heart muscles.

Intravenous melatonin in myocardial

infarction patients

Interestingly, there have also been attempts to demonstrate the

inhibition of ischemic damage to the heart muscles after the
administration of melatonin intravenously, especially in patients
who have undergone treatments like a percutaneous coronary
intervention.
These studies have shown that intravenous, as well as intracoronary
injections of melatonin, might limit myocardial damage and help
patients recover faster after having suffered a heart attack.
Let's make a quick note here about what makes melatonin
particularly beneficial in acute cases of cardiac emergencies.
The molecules of melatonin can be distributed quickly throughout
the body; whether it is administered orally, through a suppository,
or oral liposomal as with Sandman. It can cross all physiological
barriers and enter the cardiac cells with ease and produce the desired
effect to repair the damaged muscles. [3]
Taking care of your heart and cardiovascular system through disease

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prevention and treatment is where melatonin can really help. The

heart has to work harder, and the pressure puts more stress on the
blood vessels potentially leading to thickening of these blood
vessels, therefore, causing more restriction of blood flow.
As stated, before melatonin keeps blood pressure low and melatonin
declines as we get older. So, could it be that it's the lack of melatonin
that is in part causing blood pressure to be elevated? It's also been
documented that blood pressure medication has a negative effect on
our production of melatonin, as well as the quality and duration of
our sleep. Most patients with cardiac diseases have to fight the
various side effects of blood pressure medications. Balancing the
blood pressure first with melatonin and then second with
antihypertensive medications makes the most sense to me.
Combined therapy using antihypertensive drugs with melatonin may
help to relieve these side effects to a great extent as well. Maybe in
a large number of cases simply just adding in melatonin may do the
trick. It's certainly worth trying but it's important that you do this
with the guidance of your healthcare provider and not try to do it by
yourself.
How does melatonin help to relieve the side effects of
blood pressure medications?

Patients with high blood pressure often suffer from poor sleep
quality as a result of the negative effects of medications called beta-
blockers.
According to a research study, patients treated for hypertension,
who also use melatonin, have an improved quality of sleep
compared to those who use only anti-hypertensive drugs. The
improvement in sleep quality is in the forms of a shorter sleep onset
period, reduced awakening during sleep, and more restful sleep.
This is an important finding considering beta-blockers are widely

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prescribed to patients with hypertension. These drugs are also used

for the treatment of several other cardiovascular diseases, as well as
anxiety disorders, migraine, and post-traumatic stress disorder.
It’s known that the lack of sleep can worsen hypertension, by
contributing to mental stress and impairing the natural healing
mechanisms of the body. Sleep deprivation has also been linked to
a higher risk of mortality in patients with heart diseases. And with
insomnia being the most common side effect of these drugs, it
becomes vital to include melatonin in the treatment protocol when
one fully considers all of the research presented in this chapter.
According to another study “Night-time exogenous melatonin
administration may be a beneficial treatment for sleeping disorders
in beta-blocker patients” published in the Journal of Cardiovascular
Disease Research in 2011, a clear improvement in sleep quality can
be achieved along with better control over blood pressure by
combining the use of beta-blockers and exogenous melatonin.
Also, unlike sedatives that are commonly prescribed to patients with
sleep problems, melatonin didn't produce a "rebound" effect. This
means, even after patients stop using melatonin, the improvement in
their sleep pattern persists. It does not deteriorate even after going
off the supplement, as it happens with several sedatives or sleep
drugs. [4]
Remember as stated in previous chapters, there's no negative
feedback loop where or when you take melatonin, no matter how
much you take, it does not shut down your own production of
melatonin. In fact, it may actually do the opposite and provide a
carry-over benefit. So, even after you stop taking melatonin, you
may continue to enjoy the benefits of improved sleep. Additionally,
the use of melatonin did not show any sign of rising tolerance that
would otherwise necessitate the use of higher doses. This shows that
melatonin could provide multifactorial benefits by reducing the
sleep problems caused due to the side effects of beta-blockers.

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Melatonin as a heavy metal chelating

agent for heart

According to a research study “Protection of Metal Toxicity by

Melatonin -Recent Advances “published in the Research Gate,
melatonin has a widespread subcellular distribution that enables it
to interact with several toxic metals and molecules, thereby reducing
the damage to the organs at the cellular level.
This property of melatonin makes it a powerful chelating agent,
moreover, these qualities have been related to the reduced toxicity
in the heart and other vital organs by heavy metals. It contributes to
the prevention of toxicity induced by heavy metals such as mercury
and lead. Melatonin may also alleviate cadmium-induced
endoplasmic reticulum and cellular stress, regulate unfolded protein
response, influence germ cell apoptosis, and prevent neurotoxic
effects.
The protective effects of melatonin against mercurial toxicity may
help in the prevention of myocardial toxicity, neurotoxicity, renal
toxicity, thyrotoxicity as well as reproductive toxicity. It may also
act as a chelating agent against arsenic toxicity as is manifested
through its natural anti-oxidative mechanisms. Furthermore, it
might also induce mitochondrial biogenesis and autophagy to
eliminate these toxins from the heart muscles and valves, thereby
restoring the healthy functions and higher efficiency of this organ to
pump blood.
This is a huge reason to take melatonin in and of itself.
Mitochondrial biogenesis to create new fresh healthy energy-
producing cellular components and clearing out all of the weak,
damaged and dysfunctional mitochondria which are just spewing
inflammatory and oxidative substances.

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Melatonin has also been found to protect the heart against copper,
chromium, and aluminum by exhibiting anti-inflammatory,
pleiotropic, anti-lipidic, antioxidative, and other therapeutic effects.
Moreover, melatonin may also mediate both intrinsic and extrinsic
pathways for apoptotic cell death and exhibit anti-metastatic effects
through the regulation of NFkB. These pleiotropic functions of
melatonin make it a powerful cardioprotective molecule especially
for men and women at risk of metal toxicity. [5]
Emerging further studies indicate the possibility that the cholesterol
plaques blamed to be the major precursor to most cardiovascular
diseases may actually contain microbes. The cholesterol plaques
having microbes can create a biofilm on the endocardium (the inner
walls of the heart), as well as the heart valves that regulate the flow
of blood through different chambers like the atrium and ventricles.
And this new emerging idea makes melatonin more important
considering its ability to boost your immune system’s response
against infections. The antioxidant property of melatonin would also
destroy reactive oxygen species and down-regulate inflammation
that would cause damage to cardiac muscles. This in combination
with the chelating effect of heavy metals, improved restorative
sleep, lowering of the blood pressure, and an improved cholesterol
profile, would protect and can even restore heart health to a great
extent.
How do you know if you are at a higher risk due to metal toxicity?
You can do testing to determine what type of heavy metal load you
have in your body, and it's important to take into consideration risk
factors such as mercury amalgam fillings. Especially if you have
mercury amalgam fillings and you drink a lot of hot coffee or tea
which will leach the mercury out of the amalgam more rapidly.
Other heavy metal risk factors include eating a lot of fish, especially
larger predatory fish, vaccinations, and environmental exposure.
For this reason, I think it's a good idea to take binders when one first

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starts to embark on melatonin supplementation. You can reference

ultimatecellularreset.com for more information about what type of
binders, when to take them etc.

Conclusion

Cardiovascular health is incredibly important and the simple fact

that melatonin can improve gut function and microbiome health, as
well as blood sugar and metabolic disorders makes it unsurprising
to see how beneficial melatonin can be in this arena. However,
melatonin goes a step further and improves your energy through the
mitochondria.

Remember the brain and the heart are the two most metabolically
sensitive organs and any challenges with energy are going to show
up in both of these places early. Improving sleep will improve stress
management, as well as down regulate the sympathetic nervous
system which drives blood pressure.

Time and time again, I have seen in the clinic how melatonin
improves blood pressure and lipid profiles with my patients. Anyone
interested in improving cardiovascular function should seriously
consider melatonin supplementation.

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Chapter 9: Melatonin & Sex
Hormones

Who doesn’t want to improve their sex life? I’m sure the answer is
pretty obvious! Your overall vitality is ultimately a reflection of
your sexual vitality. When you're stressed, you're not typically
aroused. I’m sure anyone reading this has experienced being pushed
too far in some way, whether physically, mentally, or emotionally,
where they have found
themselves lacking sex drive.
Since melatonin works on
stress it should be no surprise
that there is also a body of
research on melatonin in this
specific area of health as well.
Think about how sexy YOU
feel after a great night’s sleep,
well guess what? That’s melatonin doing its work on your sex
hormones.

Your body relies on cycles and rhythms. The sleep-wake cycle is the
most obvious, and this cycle is wired into steroid hormones released
by both the testes and ovaries.
Through puberty, these steroid hormones help you grow and
develop. After puberty and in our later years the female hormones,
estrogen and progesterone, and the male hormone, testosterone

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influence metabolism, healing, proper weight and muscle mass,

reproduction, sexual functions, appetite control, urine secretion,
motivation, proper cardiovascular function, and overall physical
conditioning.
The imbalances in the levels of these hormones can trigger the
development of diseases. Melatonin has been found to be effective
in the management of disorders linked to imbalances in sex
hormones.

The discovery of hormone-balancing effects of

melatonin

The possible role of melatonin in maintaining the balance of sex

hormones was postulated when several studies showed abnormal
melatonin secretion in patients with sexual dysfunctions and
infertility. The research study “Melatonin and sex hormone
interrelationships-a review” published in the Journal of Pediatric
Endocrinology and Metabolism in 1999 revealed that there is
evidence supporting the relationship between melatonin and
reproductive hormones.
The evidence relies on the findings of abnormal levels of melatonin
in patients with reproductive disorders and the pathologies of the
pineal gland that were also associated with clinical manifestations
of abnormal levels of reproductive hormones.
What these studies have suggested is the change in the levels of
melatonin and the dysfunctions related to the pineal gland are more
common in patients with hormonal disturbances linked to sexual and
reproductive disorders. This raises the possibility that correcting
melatonin levels could be an effective strategy for restoring normal
levels of sex hormones in men and women.

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Also, this study pointed out that the normal rhythmic secretion of
melatonin is closely related to the rhythmic secretion of
reproductive hormones in infants. The same has been found to be
reciprocally related to hormonal levels during puberty. This
indicates that the secretion of melatonin and sex hormones are
closely interlinked. They can influence each other, both positively
and negatively.
So, maintaining optimum levels of melatonin could prove to be
effective for maintaining normal levels of sex hormones through
these interlinked mechanisms.
Moreover, the demonstration of melatonin receptors in reproductive
organs as well as in the brain, coupled with the localization of the
receptors for sex
hormones in the pineal
gland have further
strengthened these
relationships. It
indicated that the
presence of receptors for
sex hormones and
melatonin in common
organs and tissues could
be one of the factors for why and how they influence each other.
The findings of these studies have formed a basis on which the link
between melatonin and sex hormones can be further established. [1]
So how does the secretion of melatonin affect the levels of male and
female sex hormones and how can the use of exogenous melatonin
provide relief from the symptoms of sexual and reproductive
dysfunctions?

Melatonin can help in the management of ED

When the moment arises, yet other “male parts” don't, this is called
ED or erectile dysfunction and is actually pretty common. Sexual

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problems like erectile dysfunctions (ED) can be highly frustrating

for men. According to the National Institutes of Health (NIH), ED
has been found to affect nearly 30 million men in the United States.
It has also been estimated that about 4% of men in their 50s and 17%
of men in their 60s develop a complete lack of ability to get an
erection. [2]
While there are several different causes that can lead to sexual
dysfunctions, melatonin is considered by some as one of the most
effective ways to manage it.

How does melatonin affect ED?

Before diving into this section, you should understand that both men
and women rely on testosterone levels for sex drive. There is also an
erection that takes place in the clitoris which is linked to
testosterone. Porn or nerve function is one of the common causes of
ED. Research studies have shown that correcting nerve functions
and improving nerve health could help to restore sexual functions in
men.
According to a research study, “Melatonin and tadalafil treatment
improves erectile dysfunction after spinal cord injury in rats”
published in the Clinical and Experimental Pharmacology and
Physiology, using large doses of melatonin might help to heal the
damaged nerves and relieve the sexual dysfunctions linked to nerve
injuries.
This study involved the use of melatonin in a dose of 10 mg per kg
body weight. This would be 700mg to an average-sized male
human. The results of this study indicated that the antioxidant
capabilities of melatonin might help to restore and prevent tissue
damage. [3]
This study goes on the report the use of melatonin is also linked to
an improved balance of hormones in the body. Since the production
of all hormones in the body is interlinked and based on a cycle,

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“Circadian Rhythm”. Maintaining healthy levels of melatonin and

the natural rhythm of hormone production is considered one of the
ways to improve levels of testosterone.
They concluded that melatonin supplementation might help to slow
the age-related decline in the production of testosterone in men and
thus, help them avoid ED linked to hormonal imbalances.
In a separate study ‘melatonin improves erectile dysfunction with
lower body ischemia’ it is discovered that melatonin has a positive
impact on circulation and can improve erectile dysfunction when it’s
linked to vascularity. [4]
The fight or flight side of your nervous system or sympathetic is
anti-erectile. However, the resting and digesting side or the
parasympathetic pathways are pro-erectile. [5]

As we discussed in other chapters melatonin has a positive effect on

the parasympathetic nervous system. Put plainly, melatonin
supports the parasympathetic nervous system that is an opposing
force to the stress-induced sympathetic nervous system. Without
this opposition, there would be a tremendous amount of stress as the
body would be in a constant state of fight, flight, or hide. This
chronic state is a common cause of many diseases as we’ve
discussed in this book. Because melatonin works to balance this, it
improves the ability to have an erection.

When we say that erectile dysfunction could be neurological, we

mean that it could be both neurological: through the autonomic
nervous system and the parasympathetic nervous system, as well as
neurologic meaning that the nerves in and around the penis are weak
and not functioning properly.
It appears that melatonin addresses erectile dysfunction from both
of the most common causes, neurogenic and vascular. I feel it's
more probable that most cases of ED have both neurogenic and
vascular causes involved, as the circulation will affect fuel delivery

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to the nerves and subsequently, poor nerve function will affect the
autonomics in the blood vessels which can disrupt blood flow.

Melatonin has a supportive effect on the female

reproductive system

Sex hormones are stimulated through a primary hormone from the

brain which then creates a cascade leading to the sex glands
producing the sex hormones. Melatonin affects the functions of the
female reproductive system by acting on the ovaries both directly
and indirectly. By indirect support, melatonin acts on the primary
signaling hormone GnRH. Thereby stimulating the release of
gonadotropins.
It should be noted that GnRH is responsible for the release of LH
(Luteinizing hormone) and FSH (Follicle Stimulating Hormone)
from the anterior pituitary gland in women. It is common for
treatment plans using hormone replacement therapy to cycle using
luteinizing hormones in order to maintain and preserve the sex
glands. Moreover, when you're given exogenous hormones,
meaning from outside, it tends to shut down your endogenous
production.
Remember, melatonin
doesn’t have a negative
feedback loop like many
other hormones do.
Nevertheless, your sex
hormones have a very
strong negative
feedback loop and this
needs to be considered
when giving hormone replacement therapy.
By pulsing luteinizing hormones you’ll stimulate your own
hormones to produce, therefore keeping them working when they
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would otherwise be inhibited by continuing to take the exogenous

hormones. Since melatonin works to invigorate all of your sexual
organs through this pathway, it seems to be a logical adjunct to any
hormone replacement therapy protocol.
Melatonin can also act on the ovaries directly through its anti-
apoptotic and antioxidant properties, as well as through its
regulation of LH and signaling molecules in the ovaries.
Since FSH and LH both play a vital role in the reproduction and
menstrual cycles in women, melatonin is believed to influence these
functions as well, thanks to its ability to regulate FSH and LH
through GnRH. Furthermore, MT-1 and MT-2 receptors for
melatonin have been detected on both the ovaries and testes.
Increasing evidence shows that melatonin acts at the level of the
ovary to modify ovarian functions via a receptor-mediated process
on the ovarian melatonin receptors. [6] [7]
Ultimately, there is a complex interplay between melatonin, GnRH,
LH, and FSH on the other sex hormones in women, their
reproductive functions, and menstrual cycles. [8]

Melatonin in the management of infertility

Melatonin supplementation may be a great therapy in the

management of infertility in women with endometrial dysfunctions.
This study demonstrates just that. “Melatonin Promotes Uterine and
Placental Health: Potential Molecular Mechanisms” published in the
International Journal of Molecular Sciences in 2019.
Researchers wanted to determine the effect of melatonin on
endometrial morphology and embryo implantation. They found that
melatonin can produce a positive effect on the endometrium. It can
allow for better implantation of the embryos on the endometrial

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lining of the uterus possibly by raising progesterone levels.

The results of this study suggested that the use of melatonin could
improve the chances of conception in women struggling with
fertility issues. It may also be used during ART (Assisted
Reproductive Techniques) like IVF (In-vitro fertilization) to
improve the chances of successful outcomes of infertility treatment.
During IVF, an embryo fertilized in a laboratory is implanted into
the uterus through artificial means. The successful implantation of
the embryo on the endometrial wall of the uterus is crucial for
conception. Melatonin might support the implantation of the embryo
to the endometrial lining, thereby improving the chances of
pregnancy in this case. [9]
To improve implantation,
melatonin also modifies the
epithelial and endometrial
thickness by lowering
estradiol levels while
improving its glandular
density. This, in turn, would
result in the attenuation of
reactive oxygen species with
increased production of TAS (total antioxidant substances).
This means the antioxidant capacity of melatonin would be further
enhanced allowing it to protect the endometrial tissues, making it
more efficient to perform the function of implantation essential for
successful conception.
Another research study ‘Melatonin and female reproduction’
published in the Journal of Obstetrics and Gynecology Research in
2014 showed that Melatonin can be successfully used to improve
ovulation and promote embryo implantation. Moreover, it might be
helpful in overcoming the deficiencies in fertilization, implantation,
and conception during in vitro fertilization. [10]
These studies have affirmed the role of melatonin in the
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management of infertility, even in women who need to undergo

advanced ART treatments.

Melatonin effects on breast cancer

Melatonin appears to have a protective effect on the development of

breast cancer. Some research studies have shown that women with
a lower level of melatonin hormone such as those who sleep fewer
hours or work in shifts have a higher risk of breast cancer.
The use of melatonin in such cases appears to slow down the growth
of cancer. It might improve the chances of survival of women with
breast cancer by minimizing the multiplication and spread of cancer
cells. This effect could be attributed to its ability to regulate the
production of female reproductive hormones like estrogen.
It may also modify the functions and activities of estrogens receptors
on the breast cells, thereby influencing the development of breast
cancer. Therefore, the use of melatonin is believed to be potentially
useful in the management of estrogen-dependent breast cancer.
The anticarcinogenic effect produced by melatonin could also be
linked to its antioxidant properties. It can protect the tissues against
free radical damage and thus, prevent cancerous changes. Moreover,
this antioxidant activity of melatonin could be considered effective
not just for the management of breast cancer but even ovarian,
prostate, uterine, and endometrial cancers that are triggered due to
oxidative stress and the imbalances in the levels of sex hormones.
[11]
Researchers believe melatonin can also be used to improve the
quality of life in women who have been diagnosed with cancer. It
may be used alone or in combination with other conventional
treatments.

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Stress is the killer of sex

It’s well documented that there is a process called “pregnenolone

steal” where we lose many of our sex hormones due to excessive
stress. When our bodies shift to this fight or flight mode, or
sympathetic dominant state, to deal with stress our endocrine system
prioritizes dealing with this emergency over the support to your
endocrine system.
Pregnenolone steal is when DHEA after having converted into
pregnenolone and when it would normally then convert into sex
hormones, is shifted into making cortisol to deal with stress. Due to
melatonin’s ability to shift from sympathetic to parasympathetic, it
can have a positive impact on preventing this pregnenolone steal.
Melatonin’s ability to buffer stress seems to be the common theme
throughout this book if you’re not already noticing. Stress is nothing
to hide from, it is a positive in the sense that our body can become
stronger if it’s able to deal with and be resilient to stress. Melatonin
allows for this to happen which is why it has such a wide reach as
far as health benefits.

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Comment Box
Some of the other methodologies in natural medicine to address
ED is the use of shockwave technology, which is a device that
creates sound and light energy into areas in and around the penis.
The device can stimulate nerves and blood vessel growth. Also,
platelet-rich plasma and stem cell injections into the penis can be
very helpful. Besides melatonin, these are some additional
therapeutics that can be done with great effectiveness that we
have utilized at Advanced Rejuvenation for many years.

Conclusion:
There is a major difference
between sex hormones and
melatonin, in the sense that
melatonin does not have a
negative feedback loop
where sex hormones have
a very strong negative
feedback loop. This
negative feedback loop
needs to be considered when giving hormone replacement therapy.
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In this chapter, we looked at studies showing the positive impact

melatonin has on gonadotropin-releasing hormone and luteinizing
hormone. It is common for treatment plans using hormone
replacement therapy to cycle using a luteinizing hormone to
maintain and preserve the sex glands. Moreover, when you’re given
exogenous hormones meaning from outside, meaning from outside
it tends to shut down your endogenous production. Yet, by pulsing
luteinizing hormones you’ll stimulate your own hormones to
produce, therefore, keeping them working when they would
otherwise be inhibited by continuing to take the exogenous
hormones. Since melatonin works to invigorate all of your sexual
organs through this pathway, it seems to be a logical adjunct to any
hormone replacement therapy protocol.
In summary, melatonin seems to be a safe and effective treatment
for the management of sexual problems linked to hormonal
imbalances which translates into so many health benefits related to
low hormone statuses such as poor injury healing, low energy, poor
quality of skin and hair, low motivation and sex drive, poor muscle
volume and strength, and poor cardiovascular function, are just a
few common problems associated with low testosterone.
When I think of vitality I think of strong male and female hormone
status. In our clinic, we test for these and strive to balance them
through various strategies including hormone replacement therapy
but also by improving sleep usually with super physiological
melatonin dosing. Isn’t the wide net melatonin casts in order to
improve our health span and lifespan impressive?

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Chapter 10: Melatonin &
Degenerative Neurologic
Disease
Stroke, Mental Illness & Mood

“Neurological Paradise”
Art by John Lieurance

Poor brain function can show up as minor forgetfulness or brain fog

all the way to severe end-stage degenerative neurological disorders
where our memories are lost or movement disorders where there's
an inability to control one's movements.

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These diseases are some of the most devastating as well as

challenging to treat. I started specializing in these types of
treatments through functional chiropractic neurology very early on
in my career, then one day I was on the other side of the equation as
a patient with neurological complaints myself.
It started in 2007 with depression and debilitating arthritis in my left
shoulder, then with the economic turndown in 2008 I had to close
my practice and try to heal myself. It was a perfect storm that had
great consequences on my health, spiraling me into a worse situation
over the following 10 years that resulted in several symptoms that
would come and go such as vertigo, POTS, cognitive issues like
word finding and memory challenges, emotional instability, blurry
vision, sensitivity to light and sound (photophobia, hyperacusis),
hearing loss and my inflammatory arthritis began to get much worse.
I was eventually diagnosed with ankylosing spondylitis or AS by a
rheumatologist and prescribed lots of drugs to cope with my
condition. I really had no diagnosis I believed to be accurate as I felt
like I had an infection, however, I was relying on the standard
medical establishment and even though I was very much into
alternative medicine myself, I could not figure out my own illness.
You can only imagine how difficult this was as I was the doctor who
folks came to see, even flying in from far away to seek my expertise
but fixing myself or even figuring out what was wrong with me
remained elusive for many years.
I lost my practice and the prestigious building I once owned was
foreclosed on and I went from being a robustly healthy multi-
millionaire to being in debt and looking like I was homeless due to
the toll the illness was taking my physical body. See more about my
story here.

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As painful as this
was, it was my “Pain
to Purpose” story
ultimately and led
me to find out what
was wrong, and even
writing this book
may never have
happened. I finally
tested myself for
Lyme disease and viral infections and the markers were literally off
the chart. Some of my EBV titers were among the highest a viral
expert had ever even seen! Why did numerous other doctors both
medical and alternative miss this? I was loaded with infection!
On top of this later I found mold in my home and then found I tested
positive for many mold illness markers. What happened to me is that
my immune system was depleted with the entourage of these
infections and all of the toxins they were releasing. It's not just about
the infections, but also these same infections release these fat-
soluble toxins that can have a devastating effect on health.
I bring the story up in this chapter because many neurological
diseases can have biotoxin illness and CIRS as part of the clinical
picture. Melatonin works on multiple aspects of both of these
complications. I didn’t know of the benefits of melatonin early on,
however, I found glutathione suppositories helped me more than any
other supplement and this was the beginning of my interest in
suppositories.
With my case and many others, we see in our clinic we have found
that there are very few mono strategies that can have a significant
improvement in brain function. There must be a combination of
several therapeutics in order to get a measurable response.
Dr. Dale Bredesen in his book The End to Alzheimer’s brought
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chronic infections and toxicity as a primary culprit. This has caught

the attention of the vast majority of the medical community. He
broke down the causes of Alzheimer's disease into three main
categories; infection and toxicity are 2 of them. After discovering
the stressor that was the cause leading to the inflammation in the
brain that resulted in Alzheimer's he then had various strategies and
combinations to address one or more of them.
I personally feel like these are the most prevalent, non-vascular or
traumatic, causes of most neurologic conditions. All causes of any
degenerative neurological disorder have inflammation as part of its
consequence. Dr. Bredesen also talks about the importance of deep
sleep and how that keeps the brain healthy and clear of toxins that
can build up. Because melatonin works on the glymphatics to
detoxify the brain, neutralizes toxins, protects the brain during
infections, and works to repair the brain. Melatonin hits all sides to
act as a powerful medicine for brain support and it has the brightest
application in this area of medicine.
Melatonin is one of
those therapeutics
that if I had only
one, I would use
this on all of my
neurologic cases.
Because melatonin
affects so many
different aspects of metabolism, mitochondrial health,
inflammation, regeneration, sleep, and immune functions, it is no
surprise that there's been loads of research demonstrating that
melatonin can help in a wide range of neurologic conditions.
I was at a conference in Fort Lauderdale called “Brain
Regeneration” where I sat next to some of the lead alternative
doctors in the country such as Dr. Joe Mercola. At the conference,

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we were presented data regarding super physiological melatonin

dosing. During the presentation, the doctor sitting next to me leaned
over and said, “We started doing this a couple of months ago and
this is one of the most significant treatments I've discovered”. Well,
that got my attention! And that was the beginning of my journey to
understand melatonin.
In regard to having a healthy brain and slowing or reversing some
of the devastating damage from many degenerative neurological
disorders, melatonin is one important molecule that needs to be
taken seriously. Leading researchers have discovered that melatonin
can guard against brain degeneration brought about by aging, toxic
exposure, and environmental factors. New studies have also
uncovered the ability of melatonin to protect against the common
age-related neurological diseases affecting the brain, including
Parkinson’s and Alzheimer’s.
Melatonin is so beneficial at protecting the brain that scientists have
found an age-related decline in the production of melatonin could
be one of the factors for the concomitant increase in the development
of neurodegenerative diseases. In fact, obvious signs of melatonin
deficiency can be seen in patients with Alzheimer’s, like disruptions
in the day/night pattern, delirium, and mood changes.
Supplementing with high doses of melatonin starting from middle
age and continuing through older age has been shown to protect
people against Alzheimer’s, as well as Parkinson’s disease.
One research study ‘Practical Evaluation and Management of
Insomnia in Parkinson's Disease: A Review Published in the
Movement Disorders’ has revealed that the dysfunctions of the
circadian system in patients with Parkinson's could be a
consequence of neurodegeneration. In advanced cases of
Parkinson's disease, behavioral factors like limited sunlight
exposure can weaken circadian rhythm and promote faster
degeneration of the brain tissues. The use of melatonin might be
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beneficial in such cases to reset the circadian rhythm and thus, slow
down the degeneration. [1]
This finding was proven during a research study ‘Usefulness of
Early Treatment With Melatonin to Reduce Infarct Size in Patients
With ST-Segment Elevation Myocardial Infarction Receiving
Percutaneous Coronary Intervention’ that was published in the
American Journal of Cardiology in 2017. It showed that melatonin
might limit the extent of the ischemia-reperfusion injury and
increase the efficacy of the mechanical reperfusion in patients with
myocardial infarction or stroke. The study also found that the infarct
size reduced in size when melatonin was administered early
following the onset of symptoms. [2]
Discoveries have validated melatonin’s potential to protect the brain
from oxidative stress. Remember that oxidative stress is like the
smoke coming out of the coal-burning train. Well, the brain being
one of the most metabolically active organs in the body is going to
produce a lot of smoke a.k.a. oxidation. With this fact, it is no
surprise that melatonin allows the brain to function at a much more
efficient level. Besides, the powerful antioxidant melatonin is also
responsible for deeper stages of sleep which stimulate the
detoxification of the brain. With these findings, it seems melatonin
deserves a new title: “The brain hormone.”
Melatonin has been proven to protect you against Alzheimer's,
Parkinson's, Stroke, Traumatic Brain Injuries, and much more.

The role of melatonin in neurodegenerative

diseases

The following study titled ‘Melatonin Antioxidative Defense:

Therapeutical Implications for Aging and Neurodegenerative

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Processes’ published in Neurotoxicity Research in 2013 revealed

that the decline in melatonin production in aged men and women is
a major factor contributing to the development of age-associated
neurodegenerative diseases. [3]
The application of melatonin in preventing oxidative stress in
neuronal cells or the brain of animals treated with neurotoxic agents
has revealed its use as a neuroprotective agent. The results of this
study suggested that melatonin could play a valuable therapeutic
role in the prevention and treatment of Parkinson's disease,
Alzheimer's disease, amyotrophic lateral sclerosis, stroke,
Huntington's disease, and brain trauma.
Melatonin's efficacy in reducing free radical damage in the brain
shows that it could also reduce swelling in the brain or cerebral
edema that occurs following brain injuries and stroke. [4]
Another study ‘Retardation of brain aging by chronic treatment with
melatonin’ published in the Annals of The New York Academy of
Sciences has reiterated similar findings. This study has shown that
slowing of the functional decline in the aging brain is highly relevant
for non-pathological senescence as well as a broad range of
neurodegenerative diseases. Aging of the brain associated with

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cumulative oxidative stress in macromolecules and the abnormal

levels of inflammatory activities in brain cells could be ameliorated
by using melatonin.
Maybe you remember us discussing cellular senescence where the
old dysfunctional cells which are normally cleaned up and recycled
continue to operate and create a lot of inflammation and oxidation.
Well, supplementation with melatonin would elucidate the key
intracellular targets associated with age-related inflammatory events
and thus, protect the brain against degenerative changes linked to
Alzheimer's and Parkinson's disease. [5]
Another study ‘Early melatonin supplementation alleviates
oxidative stress in a transgenic mouse model of Alzheimer's disease’
published in the Free Radical Biology and Medicine in 2006
demonstrated the increased brain oxidative stress can be reduced
through the use of melatonin.
The potent antioxidant and free radical scavenging effect of
melatonin were applied in a mouse model for Alzheimer's disease to
mimic the neuronal loss, accumulation of senile plaques, and
memory impairment. The mice were treated with melatonin in a
dose of 10 mg per kg body weight (comparable to 700 mg for an
average male human adult) for 4 months and the long-term influence
of melatonin was assessed before amyloid plaques were deposited.
The results of this study have shown that patients with Alzheimer's
disease have an increase in the level of TBARS (thiobarbituric acid-
reactive substances) in the brain and a decrease in GSH (glutathione)
content.
Let me explain what TBARS means to the health and functions of
the brain.
Thiobarbituric acid reactive substances (TBARS) are formed in the
body as a by-product of lipid peroxidation or degradation products
of fats. TBARS are generated as a result of damage to the brain
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tissues in patients with Alzheimer's or due to heart attacks or stroke.

Glutathione also plays a paramount role in improving the
antioxidant defenses in the brain and maintaining redox
homeostasis. The reduction in glutathione levels in the brain has also
been observed as a result of aging and neurological disorders such
as Alzheimer's and Parkinson's disease. In fact, reduced levels of
Glutathione can worsen the neurodegenerative changes in the brain
and contribute to the faster development of Alzheimer's disease and
Parkinson's.
When melatonin was administered to Alzheimer's and Parkinson's
patients, it was found that it helped reduce TBARS levels and
improved glutathione levels in the brain. This indicates the efficacy
of melatonin for reversing the abnormal changes in the nervous
system and slowing down the pathogenesis of Alzheimer's.
In addition, mice administered melatonin also showed a significant
decline in some factors that indicated inhibition of neuronal
apoptosis, which is basically neuronal self-destruction. These results
have supported the hypothesis that oxidative damage is an early
event in the pathogenesis of neurodegenerative brain disorders and
that antioxidant therapy using melatonin might be beneficial.
This study has recommended the use of melatonin as a potential
therapeutic candidate in the treatment of Alzheimer’s disease. It may
also be used as a preventive measure to inhibit the development of
this condition. [6]
.

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Dr. John’s Clinical Note:

We have been using glutathione in our clinic for neurologic
conditions for over 20 years with great responses.
Glutathione acts on improving the immune system,
decreasing oxidation as an antioxidant, it improves sleep
and lastly, it also detoxifies chemicals and heavy metals out
of the body and brain. Like melatonin, glutathione is one of
those substances that is poorly absorbed when taken orally
therefore we have traditionally been giving glutathione as
an IV or as a suppository. I have found better results with
suppository because I can provide this to our patients to do
at home and to do them regularly, whereas the intravenous
approach is more expensive and is usually more sporadic. I
think ultimately both glutathione and melatonin and a
suppository would provide better support than either of
them individually.

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What happens to the brain when there is

melatonin deficiency?

What's interesting, is if
you look at the decline of
melatonin as we age in
this graph it makes sense
that as we get older, we
are more vulnerable to
problems occurring with
our brain and nervous
system. It would therefore make sense how melatonin deficiency is
playing a role in the aging of the brain.
Profound reduction in melatonin levels has been found in patients
with Alzheimer’s. Melatonin, which is usually maintained at a high
level in the brain and spinal fluid during young and middle age starts
to decline sharply as age increases in a fashion that parallels closely
to the risk of Alzheimer’s incidence.
Research study ‘Role of melatonin in Alzheimer-like
neurodegeneration’ published in the Acta Pharmacologica Sinica in
2006 has revealed that Melatonin secretion decreases with aging.
Patients with Alzheimer's disease or other neurodegenerative
disorders like dementia and Parkinson’s may have a more profound
reduction in the secretion of this hormone.
Data from clinical trials have indicated that melatonin
supplementation in such cases could ameliorate sundowning and
slow down the progress of cognitive impairment. Melatonin has
been found to efficiently protect the neuronal cells from Abeta-

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mediated toxicity with its antioxidant, anti-inflammatory, and anti-

amyloid properties. Moreover, melatonin would not just inhibit
Abeta generation, but also arrest the formation and deposition of
amyloid fibrils by the structure-dependent interactions with Abeta.
Recent studies have further suggested that abnormal
hyperphosphorylation of tau protein in the brain plays a vital role in the
molecular pathogenesis of AD and in neurodegeneration. [7]

Tau is a necessary protein that helps nerve cells communicate through

microtubules. Tau is modified pathologically through abnormal
phosphorylation, glycosylation, ubiquitination, glycation, polyamination,
nitration, truncation, and aggregation. We need tau, but when it
misbehaves it creates major problems! Researchers have found that the
major component where tau misbehaves is hyperphosphorylation.

Recent studies have demonstrated that melatonin can attenuate

hyperphosphorylation of tau! A direct regulatory effect of
melatonin on the activities of the key chemistry in the brain that
protects us from this hyperphosphorylation of tau through
antioxidant pathways using protein phosphatases and protein
kinases. [8]

Basically, tau does rancid just like many vegetable oils

do when heated which also create lots of problems for
our body and nervous system. As a side note this is why I
never eat vegetable oils especially when used for
cooking. Vegetable oils are cheap so most all restaurants
use them to cook with so ask next time you dine out and
see if you can find a restaurant that doesn’t use vegetable
oil for cooking!

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Cholinergic nerves are the key nerves responsible for memory and
work with the neurotransmitter acetylcholine. Most of the AZ drugs
work on acetylcholine receptors. Things like phosphatidylcholine
can be beneficial supplements to boost brain function and is helpful
for brain fog all the way to later stage degenerative neurological
disorders.
I have found Alpha-GPC to work very well for both AZ and just
boosting cognition with many of my clients as well. The benefit of
using high and regular dosing of phosphatidylcholine is the cell
membrane flushing effect. Since many toxins find themselves
settling there a constant flush of PTC or phosphatidylcholine can be
of great benefit for many people with neurological challenges, as
well as chronic infections with Lyme, EBV, and CIRS in general,
which is related to biotin illness. In our clinic, besides melatonin, we
use a “Membrane Resolution” protocol which involves using good
fats, PTC, butyrate, and dietary changes.
If melatonin can do this for Alzheimer’s, then what do you think
melatonin would do for someone with brain fog? Do things need to
get that bad before we start considering melatonin? [9]

Moreover, another study was

focused on evaluating sleep
disruptions, sundowning,
nightly restlessness, and
other disturbances in the
circadian rhythm seen
frequently in patients with
Alzheimer's disease. The
changes in the pineal gland and suprachiasmatic nucleus were
thought to be the biological precursors for these behavioral

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disturbances. Melatonin is the primary endocrine messenger for

circadian rhythmicity therefore the major factor influencing the
pathogenesis of Alzheimer's.

This study compared the melatonin levels in healthy people, both

younger and older. It also compared melatonin levels in old people:
with and without Alzheimer's disease.

The results were as follows:

The first comparison showed that the melatonin levels in the spinal
fluid of HEALTHY older people above 80 years of age were just
half of that in younger people. This showed that as age increases,
the melatonin levels can reduce EVEN IN HEALTHY PEOPLE.

The second comparison showed that the age-related decline in

melatonin can become much worse once neurodegenerative changes
start to occur due to Alzheimer's disease. It was found that the
melatonin levels in the CSF of older patients WITH Alzheimer's
disease were just one-fifth of that in the people of the same age
WITHOUT Alzheimer's disease.

This means the age-related decline in the CSF levels of melatonin

can become more severe in patients with Alzheimer's. This study
suggests that melatonin supplementation might be an effective
strategy to restore healthy melatonin levels in the brain and CSF.
They state that melatonin supplementation should reduce and slow
down the degenerative changes in the brain and even reduce the risk
of developing Alzheimer's disease. [10]

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How does melatonin work in the management

of Parkinson's diseases?

It is common for patients with Parkinson's disease to develop sleep-

related symptoms. Several studies have already confirmed the
efficacy of melatonin in improving sleep quality, decreasing night-
time activity, and shortening the sleep latency period.

Researchers believe that

melatonin could be
beneficial for patients who
suffer from reduced sleep
due to Parkinson's.
A study ‘Melatonin for
sleep disturbances in
Parkinson's disease’ published in Sleep Medicine in 2005 revealed
the therapeutic role of melatonin in the management of Parkinson's
disease. It showed that supplementing with melatonin in a dose of
50 mg per day produced a significant improvement in the total night-
time sleep. There was also a significant decline in the sleep
disturbances experienced after they started using melatonin. They
also reported having better sleep which further helped to improve
their daytime alertness. Being able to sleep well at night allowed the
participants to feel fresh during the daytime and reduced sleepiness
and drowsiness during morning hours. This means melatonin
supplements given to Parkinson's sufferers could improve the
duration of sleep. [11]

The role of melatonin in the management of Parkinson’s is not

limited to improving sleep quality.

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Considering melatonin’s effects on the brain's detox mechanisms,

the glymphatics, might be playing an important role in the outcome
of these Parkinson's disease cases. Also, the disease is characterized
by the degeneration of neurons in a part of the brain called substantia
nigra. Melatonin is believed to inhibit these abnormal changes in the
brain by acting as a powerful antioxidant and neuroprotective agent.
Animal studies have demonstrated that melatonin supplementation
may prevent or even reverse the change in behaviors and motor
functions induced by Parkinson’s disease. This finding was proven
during a study ‘Melatonin attenuates tyrosine hydroxylase loss and
hypo-locomotion in MPTP-lesioned rats’ published in the European
Journal of Pharmacology in 2008.
The study was aimed at assessing the effects of melatonin on the
loss of tyrosine hydroxylase and hypo-locomotion. Before we learn
how melatonin helps in this case, let me first explain what the loss
of tyrosine hydroxylase and hypo-locomotion mean in terms of the
development of Parkinson's disease.

Hypo-locomotion or Bradykinesia, as seen in Parkinson’s disease,

refers to the reduced ability of patients to perform physical
movements due to the
degeneration or damage to
the nerves that produce
dopamine. It often slows
them down, making their
walk slow and erratic,
causing them to lose
balance, slow speech, or
lose normal facial
expressions. This explains
what hypo-locomotion means.

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The loss of tyrosine hydroxylase is a consistent neurochemical

abnormality related to Parkinson's disease. Tyrosine hydroxylase
plays a role in converting tyrosine to dopamine, which, in turn, is
needed for communication between nerves and muscles. Patients
with Parkinson's have a low level of dopamine due to the loss of
tyrosine hydroxylase. As a result, the nerve functions involved in
muscle movements are affected. This is one of the reasons why
patients with Parkinson's experience tremors, inability to maintain
balance, and unsteady gait.
The loss of tyrosine hydroxylase can also accelerate the
degeneration of some neurons called the dopaminergic neurons in
the part of the brain located within the substantia nigra. This
explains why it is important to improve or protect levels of tyrosine
hydroxylase in order to prevent the development of these movement
disorders.

Coming back to the study we were discussing, it showed that the

administration of melatonin in a dose of 50 mg per kg bodyweight
could inhibit hypo-locomotion and neuronal damage. It further
showed that melatonin could also reduce the risk of cognitive deficit
linked to Parkinson's disease.

Ultimately, the results of this study revealed that the use of

melatonin could be highly effective in the management of
Parkinson's. It would not just slow down but also reverse and
inhibit the brain damage caused due to this disease. [12]

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The similarities between Parkinson's and

Alzheimer’s where melatonin can strike

Parkinson’s has multiple

similarities to Alzheimer’s.
Both of these diseases can
lead to dementia and both
are linked to out-of-control
oxidative damage.

In the case of Parkinson’s,

oxidative stress is focused more on those regions of the brain that
control movements and balance (substantia nigra). And in both these
diseases, brain dysfunctions and cell death are brought about by the
accumulation of abnormal, inflammatory, and oxidizing proteins. In
Alzheimer’s, it's beta-amyloid whereas in Parkinson’s it's called the
alpha-synuclein.
Researchers have demonstrated how melatonin can attack the
development of Parkinson’s disease at each of its vital junctures. Let
me explain some of these mechanisms that involve the action of
melatonin in inhibiting the activities of alpha-synuclein.

A study, “Effect of melatonin on α-synuclein self-assembly and

cytotoxicity”, published in the Neurobiology of Aging in 2012,
implicated the accumulation of alpha-Synuclein (αS) in the brain
tissues as a critical step in the development of Parkinson's disease.
This study revealed that melatonin can reduce the build-up of alpha-
Synuclein by producing antioxidant and neuroprotection activities.
This anti-assembly effect on α-synuclein by melatonin is evident in
the form of reduced cytotoxicity in the brain cells as was assessed

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following the use of melatonin supplements. It showed that

melatonin would act as a neuroprotective agent and further enhance
the brain functions thereby protecting a person against the age-
related memory decline. It is believed to work by preventing the
production of alpha-synuclein in brain cells, while at the same time
attacking the existing molecules of this toxic protein making them
available for faster cellular cleanup. [13]
In another study published in the Journal of Pineal Research in 2011,
melatonin was shown to reduce the expression of alpha-synuclein in
the dopamine-containing neuronal regions of amphetamine-treated
postnatal rats. This study showed that melatonin can restore the
normal activities of key enzymes involved in the production of
dopamine specifically by reducing cytotoxicity induced by
Amphetamine (AMPH).
AMPH is a psychostimulant drug that has been abused very
commonly in recent years. It is known to induce severe
neurotoxicity in the central dopaminergic pathways associated with
increased oxidative stress in the brain. Recently, AMPH has also
been shown to increase the level of alpha-synuclein in dopaminergic
neuroblastoma cell cultures significantly.

This study has revealed that the neuroprotective and antioxidant

properties of melatonin could help to attenuate the adverse effects
of AMPH on the accumulation of alpha-synuclein in the
dopaminergic pathways. Melatonin supplementation before the use
of AMPH decreased the accumulation of alpha-synuclein to 70 to
90% of the base values.
Moreover, they saw an increased immunological hyper-reactivity in
the brain linked to the accumulation of alpha-synuclein following
the use of AMPH. This was restored to normal following melatonin
supplementation. Just like another study demonstrated that
melatonin can protect our brain against heavy metals. It seems it’s

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like melatonin is like the ozone layer protecting life on the earth.
This showed that melatonin has direct or indirect effects in
controlling the expressions of alpha-synuclein and prevents
neurotoxicity linked to the abuse of Amphetamine.

Melatonin is also believed to slow down, prevent, or reverse the

changes in behaviors and motor functions by enhancing the survival
of the dopamine-producing cells which were destroyed or damaged
in Parkinson’s disease. [14]

Does melatonin reduce stroke risk?

As you age, lower and

lower melatonin levels
make your brain more
vulnerable to damage!

Your brain without

adequate melatonin
levels to protect your
precious neurons
places you at higher
risk for short as well as
long-term neurological stresses. Decreased melatonin levels have
even been associated with a higher risk of stroke, with the odds
appearing to increase more than 2 percent for each 1 pg./mL
reduction in the melatonin production as was revealed by this study:
‘Impaired Nocturnal Melatonin in the Acute Phase of Ischemic
Stroke: A cross-sectional matched case-control analysis’ Published
in the Journal of Neuroendocrinology in 2009. [15]

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One study, ‘Pineal calcification is associated with symptomatic

cerebral infarction’ published in the Journal of Stroke and
Cerebrovascular Diseases in 2014 showed that people whose pineal
gland had become non-functional and calcified had their risk of
stroke increased by nearly 35%! [16]

Plenty of evidence is available to support and explain this increased

risk. The damage is done due to both types of stroke – ischemic
(insufficient blood supply) and hemorrhagic (bleeding inside the
brain tissues) – which is basically considered to be the result of
excessive free radical production. From the endothelial lining of
your blood vessels to the oxidizing of the lipids floating in your
blood it doesn’t take much imagination to realize that buffering this
oxidation can lower these risks.

In animal models of ischemic stroke, melatonin has been shown to

improve repair of the brain resulting in the return of cognition.
Again, scientists consider the antioxidant effect of our miracle
molecule, neutralizing and scavenging free radical oxidation. They
proved this during the research ‘Direct Measurement of Free
Radical Levels in the Brain After Cortical Ischemia Induced by
Photothrombosis’ Published in the Physiological Research in 2016.
[17]

Moreover, according to the study 'Melatonin and the cardiovascular

system’ published in the Neuroendocrinology Letters in 2002,
melatonin may also inhibit the indirect risk factors for stroke,
including elevated cholesterol, and high blood pressure. It has been
shown to reduce cholesterol plaque formation by 38%, reduce LDL
cholesterol by 42%, and decrease blood pressure to the normal
range. Again, most experts on cholesterol will agree that cholesterol
is not the bad guy. Fat is not the enemy; it is oxidized fat that is bad.
Rancid fat due to too much oxidation and not enough antioxidant
buffering capacity is generally the recipe for disaster - Setting you
up for cardiovascular damage such as stroke and heart disease. [18]

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Furthermore, these studies

have shown that once a stroke
begins to develop, melatonin
might minimize the damage
by inhibiting the death of
neurons in the affected part of
the brain, thereby, limiting the
damage. The neuroprotective
effects of melatonin along with the vascular protection make
melatonin the best defense against a stroke along with a healthy diet
and exercise.

I started looking at MMP-9 years ago with my patients and it is a

great marker for inflammation and can be elevated due to biotin
illness such as from CIRS due to mold or chronic infections like
EBV or Lyme. Stroke has also been shown to elevate MMP-9. In
fact, a study looking at MMP-9 ‘Melatonin decreases matrix
metalloproteinase-9 activation and expression and attenuates
reperfusion-induced hemorrhage following transient focal cerebral
ischemia in rats’ was published in the Journal of Pineal Research in
2008. It showed that the melatonin-mediated reduction in the
ischemic brain damage and reperfusion-induced hemorrhage could
be partly attributed to the ability of this hormone to reduce post-
ischemic activation of MMP-9.

MMP-9 (Matrix metallopeptidase 9) is a type of matrixin that

belongs to a class of enzymes involved in the degradation of the
extracellular matrix. The activation of MMP-9 following an
ischemic stroke can promote injury of the blood-brain barrier,
worsen edema in the brain tissues, and increase infarct size. The
reduced MMP-9 levels by melatonin would minimize degradation
of the extracellular matrix, thereby protecting the brain against
further damage.

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It’s my opinion that stroke may often be an effect of things like a

chronic infection or toxic exposure such as biotin illness. Melatonin
has been shown to support detoxification of the brain, support the
immune system during infections, support glymphatic detox, and
even neuroprotection. It's no wonder we see things like MMP-9
decreasing with our miracle molecule as it works on so many routes!

One of the important determinants of recovery from a stroke is the

extent of “plasticity” in the healthy and surviving neurons. Plasticity
indicates how well the
surviving neurons would be
able to shift their functions
and take on some of the
activities of destroyed and
damaged brain cells.
Plasticity is key to learning
as well as the brain's ability
to re-route pathways that
have been damaged.

This is the main reason why Chiropractic Neurologists are able to

correct so many neurological conditions. We use targeted therapies
to activate the brain and promote new connections to be made in
order to allow the brain to rewire itself. One of my favorite therapies
for post-stroke is mirror exercises, where the good side is used and
viewed by the patient. This tricks the brain into activating the nerves
to rewire in order to gain function for the nerves going to the
damaged side of the body.

This study ‘Melatonin improves presynaptic protein, SNAP‐25,

expression, and dendritic spine density and enhances functional
recovery following transient focal cerebral ischemia in rats’
published in the Journal of Pineal Research in 2009 has shown that
Melatonin might increase the plasticity of the neurons on both the
sides of the brain, including the affected side and the unaffected

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opposite side. And this effect is likely to speed the recovery. The
dendrites are the outgrowing arms that form when neurons make
these nerve connections related to plasticity. The connection point
that the dendrites make when they fuse is called the synapse. Our
miracle molecule works on this which is a major part of the healing
post-stroke or even after any type of neurologic damage. [19]

Another way melatonin might help to reduce the damage caused due
to a stroke is by preventing the activation of harmful “protein-
melting” enzymes. An ischemic stroke can trigger a rise in the levels
of “protein-melting” enzymes that can further impair the integrity of
the blood-brain barrier, resulting in brain swelling, increased
intracranial pressure, occasionally transforming the ischemic stroke
into a hemorrhagic stroke.

What do these enzymes damage?

These melting enzymes have a negative effect on the protection

layer that keeps things from the outside from getting into the brain,
the BBB, or blood-brain barrier.

This study ‘When melatonin gets on your nerves: its beneficial

actions in experimental models of stroke’ published in the
Experimental Biology and Medicine in 2005 showed that melatonin
administration during and after ischemia would reduce the
activation of these destructive enzymes and thus, tightened the
blood-brain barrier, reduced tissue swelling, and prevented
hemorrhagic transformation.

Moreover, a breakthrough in melatonin research has revealed the

unique potential of this molecule to protect the brain against
ischemia/reperfusion injury by controlling endoplasmic reticulum
stress. This study, “Melatonin protects the brain against
ischemia/reperfusion injury by attenuating endoplasmic reticulum

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stress” was published in the Internal Journal of Molecular Medicine

in 2018 showing how melatonin could be effective in the
management of neurodegenerative diseases of the brain by its ability
to attenuate endoplasmic reticulum stress.

Endoplasmic reticulum (ER) stress is known to play a key role in

mediating ischemic-reperfusion damage to the brain. This study was
aimed at evaluating whether melatonin could inhibit ER stress in
neurons that were exposed to glucose and oxygen deprivation and
in patients exposed to transient focal cerebral ischemia.

The participants were treated with melatonin in a dose of 5 mg per

kg body weight (30-40mg) at the onset of reperfusion after transient
occlusion (obstruction to induce loss of blood supply) of one artery
in the brain for about 90 minutes. This mechanism is similar to what
happens when a patient suffers a cerebrovascular stroke due to the
loss of blood supply to a part of the brain. The loss of blood supply
leads to brain infarction just the way myocardial infarction or heart
attack occurs when the blood supply to cardiac muscles is
interrupted.

The results of this study have demonstrated that treatment with

melatonin could significantly reduce the extent of infarction and
reduce the size of the lesion while increasing the number of
surviving neurons. This suggests that prior supplementation with
melatonin could play a key role in protecting the brain against
stroke, and ER stress. It may also reduce the extent of damage
caused to the brain due to the loss of blood supply as a result of
which the severity of symptoms of stroke would be reduced
considerably. The increased number of surviving neurons following
melatonin supplementation could enable patients to recover faster
by ensuring the infarcted part of the brain is able to heal in a shorter
period. I think we have provided enough evidence showing all the
way melatonin helps prevent or support faster and more robust
recovery after ischemic and hemorrhagic stroke.

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If you have a family history of stroke or you have risk factors like
high cholesterol, especially the LDL and you have high oxidation
which can be seen with a variety of inflammatory markers such as
TGF-Beta, MMP-9, CRP (cardiac high sensitivity best), diabetes
with dis-regulated insulin resistivity usually with a Hemoglobin
A1C over 5, Ferritin and high iron are some of the lab markers I like.
There are even urine tests you can do at home to test oxidation, one
of which is called the oxidata.

Besides melatonin supplementation, one should look for causes that

can drive up excessive oxidation. Also, keep in mind, oxidation is
not all bad, it's a cycle and it needs to be balanced. Oxidation in the
right amounts can be beneficial and actually work to kill infections
and stimulate your antioxidant system to become more efficient.

Another consideration is carbohydrates and sugars. Eating higher

carb meals with fats is much more dangerous than keeping your
meals to a slow-burning carb (like brussel sprouts) due to the
oxidation the sugar and insulin bring, which then oxidizes the fats
in your bloodstream. See it's not fats that are the enemy, it's actually
the type of fats and the foods eaten with them, such as fast-burning
carbs that place you more at risk for stroke. I will often suggest to
my patients to fast until lunch and use a ketogenic diet 4-5 days a
week. Keeping fast-burning carbs to a minimum most days.

You should find a doctor who understands these concepts and won’t
just place you on a statin that’s toxic to your mitochondria when it’s
a much more complicated issue and can be treated much more
eloquently with some basic dietary changes and supplementing with
melatonin. [20]

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Is ISRIB and melatonin related?

ISRIB or (integrated stress response inhibitor) is another molecule

that could work wonders just like melatonin.

The discovery of this molecule by the scientist Peter Walter has

created a scientific whirlwind. It has been looked up to as a highly
effective neuroprotective agent that could blunt the effect of
neurodegenerative diseases including Alzheimer’s or Parkinson’s,
and reverse injuries caused due to brain trauma. ISRIB is believed
to hold the power to regenerate, heal, and rejuvenate the damaged
or aging brain.

The discovery of ISRIB has been rather interesting. It is known that

the cells in our body are continually streaming out proteins to
perform different functions, including fighting off bacteria and
making new memories. Proteins are able to perform these functions
due to their highly specific shapes. If a cell begins to stream out
misshapen proteins, these unfolded proteins could trigger an
abnormal response that would lead to the slowing down of the
production of new proteins while destroying the abnormal or sloppy
ones.

If such errant proteins keep forming, the cell is unable to survive,

and this is what happens when the brain begins to age leading to
neuronal death and brain atrophy. In simple words, when the cell is
unable to fix the problem of protein synthesis, it dies.

If this response is overactive, it may lead to the death of too many

cells leading to the faster development of diseases like Alzheimer’s,
and Parkinson’s. If the process goes awry in other ways, it may lead
to the proliferation of cancer cells.

Peter Walter was interested in modifying the unfolded protein

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response so that the ability of the cell to survive could improve.

But this mechanism of altering unfolded protein response was too

complex as it involved multiple cellular pathways. So, Walter
needed a molecule that had the potential to stimulate or regulate
these mechanisms. After screening a vast number of compounds, he
was able to find that one molecule he was looking for, and that
molecule was ISRIB.

It was Walter who named this molecule as ISRIB (integrated stress

response inhibitor) for its potential to inhibit the integrated stress
response. He found out that ISRIB not only modified the unfolded
protein response, but also affected other critical chemical pathways
when cells were exposed to major stressors like UV light, iron
deficiencies, and viruses. In all these situations that are triggered by
the excessive creation of sloppy proteins at the cellular level, the
cells tend to respond by switching off the activities of a protein
called elF2 alpha. This protein is also linked to memory functions.

These links between ISRIB, elF2 alpha, and memory functions were
intriguing enough to set off more research on the neuroprotective
effect of ISRIB.

Research has shown that partial restoration of the protein synthesis

rate could be regulated by the small molecule ISRIB that prevents
neurodegeneration without causing pancreatic toxicity. This is a
major advancement that the medical field has witnessed in recent
times. The discovery of the unique effects of ISRIB molecules could
provide answers to reversing neurodegenerative disorders and
protecting the aging population against the decline in cognitive
functions due to Alzheimer's and Parkinson's.

This study, ‘Partial restoration of protein synthesis rates by the small

molecule ISRIB prevents neurodegeneration without pancreatic
toxicity’ was published in the Cell Death & Disease in 2015. It

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suggested that endoplasmic reticulum (ER) stress might result in the

transient repression of protein synthesis. This form of dysregulation
has been increasingly associated with a broad range of diseases,
especially neurodegenerative disorders. This study further found
that the treatment with the small molecule ISRIB could restore
protein synthesis without creating any adverse effect on the
pancreatic functions. ISRIB treatment could lead to the partial
restoration of protein synthesis. It is also likely to provide a
sufficient boost to protein synthesis adequate to support neuronal
survival, allowing some protective functions of the unfolded protein
response to persist in the secretory tissues.

Similar mechanisms might also be observed following melatonin

supplementation, which has got researchers excited about the
possibility of using small molecule ISRIB or melatonin against
Endoplasmic reticulum (ER) stress as an answer to brain
degeneration.

These studies on ISRIB have provided great insights into the

pathways that could be modified for inhibiting the development of
Parkinson's and Alzheimer's. Activating the functions of elF2 alpha
could also be mediated by melatonin which is why melatonin too is
considered a vital molecule that could protect the older population
against the development of neurodegenerative diseases just like
ISRIB does. [21]

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Other considerations besides melatonin for

neurological health
NAD+ An Important Nutrient Related to Brain Health,
Aging & Circadian Rhythm Adaptations

NAD+ is a good nutrient to replenish when you age, as its loss is

linked to aging and poor brain function as well as degenerative
neurological conditions.
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine
nucleotide that plays a critical role in many cellular processes
associated with energy production, development, mitochondria
function, and cellular protection against stress, and longevity.
Studies show that cellular levels of NAD+ reduce with aging at a
rate of 50% every 20 years. Modulation of NAD+ usage or
production can help prolong both healthspan and lifespan. NAD+ is
found in abundance in the mitochondria, nucleus, and cytoplasm. It
is important for key cellular energy-producing or metabolic
pathways such as glycolysis, tricarboxylic acid cycle, and fatty acid
beta-oxidation.
First, let’s discuss why you might want to supplement with NAD+.
NAD+ is a sister to Niacin, which is a vital vitamin that you cannot
live without. NAD+ is a critical coenzyme found in every cell in
your body, and it’s involved in hundreds of metabolic processes.
Maintenance of an optimal NAD+/NADH ratio is essential for
mitochondrial function. In fact, the maintenance of the
mitochondrial NAD+ pool is of crucial importance. From plants to
metazoans, an increase in intracellular levels of NAD+ directs cells
to make adjustments to ensure survival, including increasing energy
production and utilization, boosting cellular repair, and coordinating
circadian rhythms.

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By the time we are middle-aged, levels of NAD+ will have fallen to

half of the youthful levels. In recent years, several studies have
shown that the treatment of old mice with precursors to NAD+ can
greatly improve health. Observed effects include increased insulin
sensitivity, a reversal of mitochondrial dysfunction, reduced stem
cell senescence, and lifespan extension.

Euler-Chelpin, in his 1930 Nobel Prize speech said, “NAD+

is one of the most widespread and biologically most important
activators within the plant and animal world.”

Doctors in the know and scientists in the field all conclude

that molecules that maintain NAD+ levels, will allow people to
celebrate many more anniversaries. Inflammation is not just linked
to aging but is present and involved in almost all disease processes.

NAD+ levels naturally decline with age, and various stressors can
deplete your NAD+ at a more rapid rate. Poor restorative sleep and
alcohol use are the top two stressors that deplete NAD+; however,
any stressor will drain away NAD+ as well. Anytime you have a
higher energy demand, immune activation due to infections stress,
mental stress, emotional stress, physical stress, structural stress,
electromagnetic (EMF’s) stress, and chemical stress are the main
“Stress” categories. We cannot avoid these completely, and so,
inevitably, our NAD+ levels will be taxed, creating a need to replace
NAD+.

NAD+ supports your cells and supports senescent cells.

Researchers show that increased NAD+ will likely make the

inflammatory signaling of senescent cells worse. Senescence
typically occurs in response to damaging stimuli and stress.
Senescent cells increase with age and disease states, resulting in
inflammation and age-related diseases such as cancer,
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cardiovascular and metabolic diseases, and neurodegenerative

diseases. NAD+ and senescent cells are good reasons to pulse
NAD+ and not take this nutrient daily. This is why in our Mito Fast
protocol we include a couple of days in Phase 1 of NAD+ loading prior
to fasting in phase 2.
Moreover, one study suggests that chromatin structures change in a
circadian manner and that NAD+ is the key metabolite for circadian
chromatin remodeling. ‘The Circadian NAD+ Metabolism: Impact
on Chromatin Remodeling and Aging.’
Basically, this means,
during time changes and
seasonal changes, or even
sleep-wake changes your
NAD+ levels might be
important to consider for
you to adapt to the changes more efficiently!
Here is a more detailed article I wrote on NAD+.

How to take NAD+?

NAD+ can be taken using intravenous injections, IM injections,

patches, nasal spray (like NeuroNAD+), liposomal, or suppository
(like NAD+Max). Both NAD+, as well as the precursors (NR &
NMN), can be taken in the aforementioned forms.
Some products like NAD+Max have all three, yet there is much
controversy about absorption of NAD+ or its two precursors.
Suppositories make the most sense, and an IV is the next best choice
but usually a 5–8-hour drip and can cost $500-$1,500 USD. Versus
placing a suppository with the same amount of NAD+ that slowly
releases over 5-7 hours for $15-$20 with no inconvenience of time.

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Senolytic plant extracts inhibit mTOR,

activating autophagy & mitophagy

There are a few extracts worth mentioning that have been reported
to inhibit mTOR signaling.

● Apigenin, a family member of flavonoids, is abundant in

fruits (oranges, apples, cherries, grapes), vegetables (onions,
parsley, broccoli, sweet green pepper, celery, barley,
tomatoes), and beverages (tea, wine) [22].
● Cryptotanshinone is one of the major tanshinones isolated
from the roots of the plant Salvia miltiorrhiza Bunge
(Danshen. [23].
● Curcumin (diferuloylmethane), a natural polyphenol
product of the plant Curcuma longa [24].
● Fisetin might be the more powerful of all polyphenols, a
family member of flavonoids, that occurs in fruits and
vegetables, such as strawberries, apples, persimmons, and
onions [25].

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● Indoles are natural compounds in cruciferous vegetables

such as broccoli, cauliflower, cabbage, and brussels sprouts
[26].
● Isoflavones, a class of flavonoid phenolic compounds, are
rich in soybean [27].
● Quercetin, a polyphenolic compound, is mainly from tea
consumption, onions, red grapes, and apples [28].
● Pterostilbene from blueberries. [29]
● Resveratrol, a natural polyphenol-rich in red grapes and red
wine [30] suppresses mTOR signaling.
● Tocotrienols, members of vitamin E superfamily [31].
● Finally, it is worth mentioning that many other natural
products, such as caffeine, epigallocatechin gallate (EGCG,
in green tea), celastrol, butein, capsaicin, and β-elemene a
class of terpenes such as Beta Pinene from the pine tree
family can all inhibit mTOR and upregulate autophagy.

You can't possibly get all this or even a fraction of the dosage of
each of these plant extracts in a standard diet or even eating lots of
the plants high in them.

Research shows that for example, curcumin can't absorb well. You
need to take piperine to aid in its absorption, and even then, it's very
little that you absorb compared to what you ingest. This is why
delivery methods other than oral might be considered to get the most
robust autophagy and mitophagy.

Taking these polyphenols during fasting may have an even better

effect than during feeding times. This is why we suggest Lucitol
during phase 2 of the Mito Fast.

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Nicotine benefits for brain enhancement

Nicotine therapy might
also be an interesting
nutrient to look at for the
aging brain. The first
clue that nicotine might
have positive effects on
the brain was the
discovery that smoking reduces the risk of Parkinson’s disease
(PD), a progressive neurological disorder that affects movement.
[32]

Current smokers have almost half the risk of developing PD than

non-smokers. [33]

This disease is caused by the loss of brain cells that produce the
neurotransmitter dopamine, which is responsible for movement.
According to world-renowned nicotine expert Neil L. Benowitz,
MD, isolated nicotine exhibits few documented health risks. [34]

In his book Nicotine Safety and Toxicity (Oxford University Press),

he points out that nicotine, in fact, is undergoing evaluation as a
possible treatment for numerous medical and neurological disorders
including Alzheimer’s, Parkinson’s, attention deficit disorder,
ulcerative colitis, and sleep apnea.

Investigative journalist Dan Hurley extensively studied the effects

of nicotine on the brain while researching his book Smarter: The
New Science of Building Brain Power.

Using nicotine in a nasal spray like with Zen avoids all the damaging
effects of smoking. See Zen here for more on Zen Meditation Mist

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CIRS, melatonin & neurological health

CIRS was first described by Dr. Richie Shoemaker, who has
pioneered many aspects of diagnosing and treating CIRS due to
mold illness. Lyme disease, Breast Implant Illness, and Mold Illness
share similar phenomena, where toxins are not adequately cleared
from the cell. This is due to the exposure and or build-up of these
primary fat-soluble toxins, such as biotoxins from viruses, bacteria,
and mold.
Biotoxins are substances that are both toxic and have a biological
origin. They come in many forms and can be produced by nearly
every type of living organism. There are mycotoxins (made by
fungi), zootoxins (made by animals), and phytotoxins (made by
plants). What I have found clinically, is that there are genes some
individuals do not have, such as the immune response genes (HLA-
DR genes) that are required to eventually form an antibody to a
given foreign antigen. In these cases the biotoxins are not 'tagged'
and remain in the body indefinitely, free to circulate and wreak
havoc. This applies to a subset of the population (about 22%), which
prevents them from clearing these biotoxins from the cells.

The accumulation of these biotoxins occurs particularly within the

cell membranes, which is a fat-soluble area of the cell and has a slow
turnover of about 18 months to allow these toxins to remain for long
periods of time. The accumulation of these toxins within the cell is
the primary cause of CIRS. This is the primary way the cells
communicate with the environment, where it strives to balance itself
based on what it's exposed to.

When the messages through the cell membrane become altered, or

they are not able to properly make these communications, the cell
will begin to relate to its environment with inflammation, and nerve
cells won’t be able to transmit impulses properly.

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Clearing the cell membrane within your brain from biotoxin is not
an easy task and cannot occur quickly due to the turnover rate.
Therefore, it is important for any CIRS sufferer to focus on a long-
term care program to deal with this specific issue. (4-6 months at
least). I have outlined a protocol for what I call "Membrane
Resolution", where specific oils and Phosphatidylcholine (PTC) are
given IV and or orally to help flush the cell membranes.

Another important compartment is the hepato-biliary-enteric system

where these fat-soluble toxins circulate through the liver-
gallbladder-gut over and over again triggering inflammation. Using
specific binders, to pull these toxins out of circulation in the gut and
liver is as important as addressing the cell membranes. I prefer
natural toxin binders as well as cholestyramine —to lessen the toxic
load.

These binders are taken both first thing in the morning with fresh
organic lemon juice, stimulating the liver and gallbladder to release
the toxic build-up into the gut, as well as before bed as the
gallbladder secretes bile the first 2 hours of sleep.

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Your sinuses are a filter, and that filter needs to

be checked and serviced.
Sinuses are another place
infection can outgas biotoxins
and in fact, MARCoNS
infection is very common with
neurological cases as part of
the clinical picture. This
connection is not surprising
considering how close this
toxic reservoir is to your brain.

MARCoNS nasal infection is a Multiple Antibiotic Resistant

Coagulase Negative Staphylococcus infection, which produces a
very sticky substance called a biofilm. The bacteria use this to
protect and hide itself from your immune system. This infection is
particularly prevalent in Lyme and Mold Illness.

MARCoNS reside deep in the nasal passage of those suffering from

Biotoxin Illness and other chronic inflammatory illnesses, such as
CIRS (Chronic Inflammatory Response Syndrome) and CFIDS
(Chronic Fatigue and Immune Dysfunction Syndrome). This
percentage increases when the person has also been treated with
antibiotics for a month or more.

Once they have taken up residence, MARCoNS will lower your

Melanocyte-Stimulating Hormone, increase cytokines, and lower T-
reg cells. This results in chronic fatigue symptoms of body aches
and debilitating exhaustion.

Interestingly, MARCoNS is not an infection, but a commensal

colonization that can become an infection. These bacteria send
chemicals into the blood (exotoxins A and B), that increase

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inflammation. By cleaving MSH, it causes a further decrease in

MSH levels, which in turn creates more inflammation. Considering
what you’ve read in this chapter it should be evident that CIRS can
be a core complication in many neurological cases. The benefits of
melatonin are obvious, and it makes perfect sense that it would
support someone suffering from CIRS (Chronic Viral/Chronic
Lyme/ Mold Illness).

Conclusion

Your brain is fairly important and protecting it should be a priority.

Based on the information in this chapter you might consider
melatonin supplements to improve your chances of living longer and
keeping your brain sharper!
Melatonin improves detox through the lymphatics keeping your
brain clean of heavy metals and other chemicals, as well as proteins
that can build up. It further offers antioxidant protection during high
energy demand and helps to keep your brain free of infection.
Although doses in 1-20 mg can help, supra-physiological dosing of
melatonin make more sense.
Melatonin should be used as a complementary therapy along with
other strategies based on complicating factors leading to the
inflammatory process in each person. This can be unique and as Dr.
Dale Bredesen in his book The End to Alzheimer’s brought attention
to is that there are usually several factors that cause early aging of
the brain as well as degenerative neurological diseases. Bredesen
describes three subtypes of Alzheimer’s disease: (1) Inflammatory
(hot) (2) Atrophic (cold), and (3) Toxic (exposure to chemicals and
infections). Using labs, as we do at Advanced Rejuvenation, doctors
can now figure out the underlying cause of neurological challenges
and work towards answers to correct those problems.

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Besides melatonin for a healthy brain, you might consider activating

autophagy and mitophagy to break down and recycle weak and
dysfunctional cells and mitochondria through fasting and time-
restricted feeding. mTOR is a gene you want to inhibit to gain better
autophagy and mitophagy. Refeeding is also important as this is
where you repair and grow new cells.
For further information on mTOR see Mito Fast and read my article
on using fasting to improve brain function and mitochondrial health.
Senescent cells as mentioned above can be harmful, and strategies
to activate clearing of them are a good idea in any brain-based
protocol. Using fasting as well as senolytics to help clear senescent
cells can help greatly in neurological conditions.

Poor sleep can make all the following worse or

even cause them:

● CIRS & Biotoxin illness due to chronic infections and mold.

● Gut Imbalances: Dysbiosis, Leaky Gut & inflammatory bowel
disease. Read in chapter 11.
● Toxic accumulation of chemicals & heavy metals or fluoride
causing calcification of the pineal.
● Poor Glymphatics: Toxic accumulation of immune-mediated
proteins like beta-amyloid, alpha-synuclein, and tau.
● Immune Dysregulation: Poor NK cell production and healthy
strong immune cells.
● Mitochondrial Function: Energy levels become critically low
worsening brain function.

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● Poor Autophagy & Mitophagy leading to a build-up of

dysfunctional mitochondria and senescent cells.
● Poor Immune function causing chronic sinus infections or vise
versa. (MARCoNs)

These above complications lead to the development and worsening of

many neurological conditions. Testing and then addressing them as they
are needed is the multifactorial and comprehensive approach that is
needed!

What came first, the chicken or the egg? This saying rings true for
most of the above-listed complications. Did one or more of the
above cause the cascade of inflammation that lead to the diagnosis
of a neurological disease? Maybe the complication developed after
the disease process was well on its way due to the weakened state of
the central system and immune system keeping things in order?
Regardless of this answer, addressing sleep has the most “bang for
the buck” out of all considerations. Moreover, addressing it with
melatonin covers more bases than any other!

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Chapter 11: Melatonin & Gut
Support, digestion & microbiome

"There is nearly 400x more melatonin in our digestive

system than in the nervous system."

A robust, functional digestive tract is one

of our most vital bodily functions. It’s
well-known that when one's gut is unwell,
it affects the entire body's wellbeing. Yet,
I find that very few traditionally trained
medical practitioners have a proper
understanding of normal gut function.

Digestion starts during chewing when

enzymes are released in your mouth. The
contents then travel down into your
stomach, where a strong acid further
breaks down the food and converts pepsin
into pepsinogen, which you need to break down your proteins. In the
absence of strong stomach acid, there will be an inadequate breakdown of
food, and your pancreas will fail to release a buffer once the food comes
out of the stomach.

This buffer is critical to neutralize the acid contents moving into the small
intestines and ultimately helps your small intestines from the irritation
caused by acid. Without the strong acid from the stomach, this buffer will
not be released, leading to lower-gut problems.

Without getting too deep in the woods about digestion, it is easy to see that
there is much work going on along the digestive tract. Work from tissues

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and cells comes with a price: oxidative stress. Our miracle molecule is the
premier antioxidant that neutralizes oxidative stress, thus keeping your gut
healthy and working properly. Keep in mind that your gut has a massive
turnover of cells, where new cells and tissues are constantly being formed
along the entire digestive tract. In fact, the lining of your stomach turns
over every 5 minutes!

Here as much or more than anywhere, there is a need to protect this process
so that it works smoothly and the new cells have antioxidant protection,
quality DNA, and strong mitochondria to keep up with this incredible
demand. Melatonin can help keep your gut healthy and can even reverse
the damage. Melatonin is an antioxidant molecule that can help with
various digestive diseases caused by inflammation, poor flora, lack of
circadian rhythm influence leading to poor sleep, and excessive oxidative
stress.

Furthermore, melatonin can also help relieve symptoms of SIBO, leaky

gut syndrome, and poor digestion. By reducing inflammation and
improving the gut flora, melatonin comes to the rescue, particularly when
used in higher doses. Of course, this comes as no surprise by now, as I
have been suggesting much higher dosing than what many healthcare
providers typically recommend for sleep. I advocate super-physiologic
dosing with melatonin, especially when there are health considerations,
other than improving sleep. Research clearly shows that melatonin
combats stress, is anti-aging, and also protects against runaway cytokine
storms from infections through inflammasomes. Moreover, it can also
repair cells in the body, including those in the brain, heart, and yes, even
your GUT!

The role of endogenous circadian rhythmicity

in gut health

One research study, 'Human Gut Bacteria Are Sensitive to Melatonin and
Express Endogenous Circadian Rhythmicity', published in the PLoS One
in 2016, stated that "melatonin specifically increases the magnitude of

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swarming in cultures of E.
aerogenes, but not in
Escherichia coli or Klebsiella
pneumoniae."

This study focused on

assessing the impact of the
body's circadian rhythms on
gut health. Circadian rhythm
is the fundamental property of
most eukaryotes, including
humans, animals, plants, and
even fungi. However, the evidence that biological clocks can drive these
rhythms in prokaryotes like blue-green algae, E. coli, and mycoplasma has
been limited to Cyanobacteria. [1]

In invertebrates such as humans, the digestive system expresses a strong

circadian pattern dependent on gene expression, which means it could be
genetically linked. The motility of the bowels and secretion of different
digesting enzymes and juices also depend on the circadian rhythm.

Recent studies suggest that the gut flora, which is composed of trillions of
healthy bacteria, is regulated primarily by the circadian clock of the body.
The circadian rhythm, in turn, is regulated by the amount and frequency
of melatonin secretion in the body.

Healthy gut flora is an

indication of a good and
efficient digestive system, and
it’s also what your body needs
in order to digest foods, absorb,
and assimilate nutrients. By
regulating the circadian
rhythm, melatonin could play a
critical role in improving gut
flora and avoiding major
digestive issues linked to the
intestine's weak microbiota.

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This study specifically demonstrated that at least one species of bacterium

from the gastrointestinal system is sensitive to the effect of the
neurohormone melatonin. This species is Enterobacter aerogenes. The
findings of this study have revealed that, by expressing the circadian
pattern of motility and swarming, the activities of Enterobacter aerogenes
would be modified by melatonin secreted into the intestinal lumen.

Melatonin has been shown to specifically increase the magnitude of

swarming in the cultures of E. aerogenes, though not in other species such
as in Klebsiella pneumoniae and Escherichia coli. The swarming appeared
to occur on a daily basis and caused the transformation of E. aerogenes
found to be temperature-compensated by the body's circadian rhythm
synchronized perfectly in the presence of melatonin. Moreover, this data
demonstrated the circadian clock in the non-cyanobacterial prokaryote and
suggested that the human circadian system might regulate its microbiome
by bringing about the entrainment of the bacterial clocks with the help of
its own melatonin molecules.

In short, what this study demonstrates is that using melatonin to maintain

your body's circadian rhythm is what your digestive system needs to
function optimally. A regular circadian rhythm would create a favorable
internal environment within the stomach and intestine, meaning that both
digestion and gut flora are improved.

A separate study, 'Human Gut Bacteria Are Sensitive to Melatonin and

Express Endogenous Circadian Rhythmicity', published in PLoS One in
2016, hypothesized that one human signal potentially affecting gut
microbiota could be the secretion of melatonin into the lumen of the
intestine. [2]

Although melatonin is regarded primarily as the pineal and retinal

neuromodulator for the circadian rhythm and photoperiodic functions, it’s
present throughout the digestive system. While a part of this comes from
the pineal secretion, there is evidence showing the presence of melatonin
biosynthetic enzymes in the biliary cholangiocytes (liver and gallbladder),
intestinal mucosa (gut lining), and enterochromaffin cells (also gut lining).

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It’s complicated but the evidence is clear that the gut is hard wired to your
melatonin!

What is a biosynthetic enzyme?

Biosynthesis is an enzyme-catalyzed process where substrates are

converted into more complex products in living organisms. This means
melatonin is used for many critical chemical processes that occur inside
your gut.

The study, 'Extrapineal melatonin: sources, regulation, and potential

functions', published in Cellular and Molecular Life Sciences in 2014,
revealed that melatonin is found
in essentially all of the biological
fluids, including bile,
cerebrospinal fluid, synovial
fluid, saliva, amniotic fluid, and
even breast milk.

In some of these fluids, the

melatonin concentration exceeds
that of the blood. The continued
availability of melatonin in these tissues and fluids at the cellular level is
considered critical for all organs and systems' physiological regulation and
maintaining optimum homeostasis. This explains why the presence of
melatonin in bile and other digestive juices is essential for maintaining
optimum gut health. All this information makes a good argument to use a
much higher dosing of melatonin to achieve positive changes in a diseased
or stressed gut. I have found this to be the case in virtually all of my cases,
and I’ll share my gut protocol with you later. [3]

According to a research study, 'Gastrointestinal melatonin: localization,

function, and clinical relevance' published in the Digestive Diseases and
Sciences in 2002, the gastrointestinal tract of humans is a rich source of
pineal and extrapineal melatonin. The concentrations of melatonin in the
gastrointestinal organs and tissues would surpass the blood levels by

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nearly 10 to 100 times, and there is nearly 400x more melatonin in our
digestive system than in the pineal gland. [4]

Moreover, the gastrointestinal tract can contribute significantly to the

circulating concentration of melatonin, especially during the daytime
when melatonin might serve as an endocrine, pancreatic, and autocrine
hormone to influence the regeneration of the epithelial lining of the
stomach and intestine.

This paper discusses the importance of your microbiome, immune

health, and inflammation ‘Role of the Microbiota in Immunity and
inflammation’ published in 2014. In this paper, the author states
“The states of health or disease are the expressions of the success or
failure experienced by the organism in its efforts to respond
adaptively to environmental challenges”.

Your gut has an estimated composition of 100 trillion cells! That

outnumbers your entire body's cells by a factor of 10. Besides
outnumbering your own cells, they also express genes 10 times more so
than your own cells. [5]

These complex communities of microbes that include bacteria, fungi,

viruses, and other microbial and eukaryotic species, provide a tremendous
enzymatic capability and play a fundamental role in controlling most
aspects of host physiology. [6]

All of this means that ultimately you are your microbiome! Your health
is intrinsically linked to how strong your microbiome is. Your microbiome
creates messenger molecules, and t messenger molecules are produced
based on your diet, activity levels, toxic exposures, mental and emotional
signaling. The microbiome takes in this signaling to dictate your emotions,
thoughts, and behaviors as well as the vitality of your immune system.

Through this endocrine influence, melatonin can also reduce unnecessary

spasms or contractions of the gastrointestinal muscles.

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This study has also stated that a portion of the melatonin found in the
digestive tract could be of pineal origin. The production of melatonin in
the pineal gland is regulated in a photo-periodical manner, based on the
exposure through your eyes to the bright blue and green light or darkness.
The release of gastrointestinal melatonin, on the other hand, seems to be
linked more to our food intake. Food intake, and paradoxically, even long-
term food deprivation or fasting, might increase the blood plasma and
tissue concentrations of melatonin in the stomach and intestine.

Melatonin release can have a direct effect on several

gastrointestinal tissues and the digestive functions such as we have
discussed: Support through circadian rhythm effect for the
microbiome, bile & liver function and other gut functions,
protection from oxidation, support gut regeneration through
autocrine and endocrine influence, downregulate inflammation in
the gut, balancing effect through the central nervous system via
sympathetic and parasympathetic nerves.

This study has further stated that melatonin might prevent ulceration in the
gastrointestinal mucosa by acting as an antioxidant, reducing the secretion
of hydrochloric acid in the stomach (makes sense as there is no need for
hydrochloric acid while we sleep), and stimulating the immune system.

We have already covered how it can support epithelial regeneration, which

can be of great importance considering the massive damaging processes
in the gut such as gastric ulcers or ulcerative colitis.

Yet, a critical point in the study was melatonin's ability to increase

microcirculation in the gut. And lastly, a third crucial aspect of healing and
repair is the ability to "bring in the groceries and take out the garbage" or
blood supply. These unique properties make melatonin a must in the
treatment of a wide range of digestive issues, including gastritis, colorectal
cancer, gastric ulcers, ulcerative colitis, irritable bowel syndrome, and
colic.

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Why isn't this on the news like Tums and Prilosec? One word:
"Patent". Without a patent, there is zero economic motivation for
any company to pay for educating the public. You are being
brainwashed through commercials to think of pharmaceuticals as
the solution to your healthcare because this makes money for the
machine called Big Pharma.

The most common cause of heartburn is an infection and not

due to too much acid! In fact, heartburn is usually due to too
little acid being produced by your stomach. If not enough acid
is produced, insufficient buffers will be released to neutralize it
before it flows down the small intestines. The stomach contents
become rancid ("sour stomach"), and they come back up. I use
hydrochloric acid for my heartburn patients, and I address the
chronic H. Pylori infection most have, plus put them on high
doses of melatonin. This is called treating the cause and not
chasing symptoms. Since you need the effect that acid gives
you, which is killing harmful microbes in the food we eat,
breaking down food, converting enzymes, and activating the
buffer to protect the small intestines, we would not want to take
a long-term acid blocker. Even the instructions on all the acid-
blocking drugs say short-term use, but doctors commonly place
patients on them for years or even lifetimes, as if the acid in the
stomach is harmful.

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When we sleep our gut heals

Melatonin inhibits the activities of

unhealthy or harmful bacteria, thus
allowing the healthy bacteria to
survive and even thrive within the
digestive system. This effect is hard
linked to the circadian rhythm
activating a robust microbiome
growth phase called "swarming".
Your microbiome is a complex and
dynamic ecosystem of your gut and
entire body.

There are some fascinating connections as well as shared influences

between your sleep and gut flora. Scientists who have been investigating
the relationship between sleep and gut flora have found that this ecosystem
can affect sleep and sleep-related functions in many ways, possibly by
shifting the circadian rhythms, modifying the body's sleep-wake cycle, and
altering the hormones that control sleep and wakefulness such as
melatonin. Sleep, in turn, may affect the diversity and health of the human
microbiome.

The microbial life in our body is in perpetual flux, which means the
microbes are being generated and dying constantly. Some of this
form of decay or renewal occurs naturally during sleep. This brings
us to an important question,

“What role does sleep play in maintaining the health of the

gut microbiome, and how it contributes to our health so
significantly?”

There are some critical signs of this significant connection: We have

already seen that there are several studies demonstrating that
circadian rhythm disruptions could have a negative effect on the gut

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microbiome. But what about sleep’s connection? Well, there’s an

interesting study to note. [7]
This study highlights the important role of sleep is, 'Circadian
Disorganization Alters Intestinal Microbiota' published in the Plos One in
2014. Researchers found that intestinal dysbiosis and disruptions in the
circadian rhythm are associated with the risk of similar diseases such as
obesity, inflammatory bowel disease, and metabolic syndrome. The
overlap between the risks associated with dysbiosis and circadian
disorganization is a strong indication of how your sleep is determined by
your melatonin levels and linked to gut health, and how these influence
each other.

Melatonin to the gut microbiome is like honey

to the bee

The gut microbiome plays a

key role in supporting the
process of digestion and
absorption of nutrients we
consume. As mentioned
previously, the microbiome
helps in the breakdown,
absorption, and assimilation
of foods. Healthy gut flora is
vital for ensuring all the nutrients from foods are efficiently absorbed into
the blood. Meaning that a lack of healthy and diverse gut flora can affect
digestive processes, leaving some people with deficiencies in B vitamins,
folic acid, calcium, iron, vitamin C, and other micronutrients.

Furthermore, healthy gut flora is also essential for supporting the activities
of the immune cells. Patients with poor gut microbiota are more likely to
develop symptoms of allergies, autoimmune disorders, and repeated
infections due to the lack of efficient defense processes.

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Studies have shown that melatonin might have the potential to improve
the microbiota, especially in colitis. This study, 'Melatonin controls
microbiota in colitis by goblet cell differentiation and antimicrobial
peptide production through Toll-like receptor 4 signaling', was published
in Scientific Reports in 2020. The results of this study are based on the
concept that microbial dysbiosis could be associated with the pathogenesis
of IBD (inflammatory bowel disease). The study proposed that the anti-
colitic effect of melatonin could be related to this sleep hormone's ability
to improve gut flora. It showed that melatonin supplementation helped
improve the symptoms of colitis induced by DSS (dextran sulfate sodium)
by reversing microbial dysbiosis.

The improvement in the gut flora was also followed by the induction of
healthy goblet cells. Goblet cells are types of mucosal epithelial cells
lining the intestinal walls. These cells serve as the primary site for the
digestion of nutrients and their absorption through the mucosal lining.
Goblet cells also secrete mucus to protect the intestinal lining against
damage by the food traveling through the GI tract, which often holds
enzymes, abrasive surfaces, and various harmful agents such as toxins and
pro-inflammatory substances.

Melatonin treatment of the intestinal epithelial cells also improved mucous

production and stimulated wound healing while inhibiting the growth of
Escherichia coli. This means melatonin may also help protect the gut flora
by encouraging the healing of the mucosal lining and preventing damage
by infection-causing bacteria.

Earlier, we discussed the swarming effects melatonin activates with the

good bacteria in the gut, causing them to increase in number. Yet these
studies ultimately conclude that melatonin also holds significance in the
management of IBD through its ability to improve gut microbiota.

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Melatonin and Leaky Gut Syndrome

"Leaky gut" is a condition associated with an unhealthy gut lining, where

the gut becomes permeable to larger food items due to stressors. This is
what leads to many food sensitivities, such as IgG food sensitivities. We
regularly test for these in my practice, and it is not a matter of "if"; it’s a
matter of how many foods you are sensitive to. These sensitivities can be
delayed up to 4 days, and therefore, it can be notoriously difficult to gauge
this reaction directly without lab testing. Due to the constant activation of
the immune system, this problem fuels many situations, including chronic
inflammation. The activation of chronic inflammation is one of the leading
causes of most diseases in the body, and autoimmune conditions are an
excellent example of a condition created by a leaky gut. For example,
studies have shown a direct relationship to leaky gut in autoimmune
conditions such as Hashimoto's disease, and multiple sclerosis. [14]

This is why I typically test for these intolerances as soon as possible and
remove these foods to reduce the inflammatory burden. See more on this
at Ultimatecellularreset.com

The next study, 'The gut-brain axis: The role of melatonin in linking
psychiatric, inflammatory and neurodegenerative conditions' published in
the Advances in Integrative Medicine in 2015, has further explored the
link between lower melatonin secretion and the increased risk of leaky gut
syndrome. It showed that melatonin has the potential to restore the lining
of the intestine. This study further highlighted the importance of using
melatonin to manage various disorders by regulating immune-
inflammatory processes, neuroregulatory stressor tryptophan catabolites
(TRYCATs), and oxidative and nitric oxide stressors called nitrosative
stress (O&NS).

It identifies impaired gut permeability and lack of diversity in the gut

microbiome as the etiology and course of several diseases, including
mental health issues such as depression. Increased gut permeability would
be evident in several medical conditions. Moreover, it can contribute to
the higher immune-inflammatory cytokines, TRYCATs, and O&NS. By

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regulating the pathways that control the secretion of immune-

inflammatory cytokines, TRYCATs, and O&NS. Meaning, that melatonin
could provide a solution to the disorders that have leaky gut syndrome as
a root cause.

This study has also assessed the role of reduced melatonin in gut
permeability, primarily through the regulation of inflammasomes.
Inflammasomes have been found to have serious consequences across a
range of medical conditions,
including fatty liver disease,
Alzheimer's disease, fibromyalgia,
obesity, and alcoholism. Simply
put, by regulating the activities of
inflammasomes, melatonin might
restore normal gut permeability
and minimize the implications of
leaky gut syndrome, thereby
reducing the risk of these diseases.
[8]

How often do medications provide both symptomatic relief and cure? Not
often, but melatonin can do just this!

Does melatonin work for colitis?

Ulcerative colitis is a common inflammatory bowel disease characterized

by recurrent bouts of loose stools, constipation, abdominal pain, and blood
in stools. If not appropriately managed, ulceration in the colon may
become deeper, eroding the intestinal lining. In some cases, the ulcerated
tissues may turn cancerous, thus increasing the risk of colorectal cancer.

Studies aimed at assessing the role of melatonin in the management of

ulcerative colitis have shown encouraging results. Let’s take a look!

According to one study, 'Melatonin improves experimental colitis with

sleep deprivation', published in the International Journal of Molecular
Medicine in 2015, melatonin supplementation might help control the signs

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of colitis. This study has recognized sleep deprivation as an epidemic

phenomenon and an aggravating factor responsible for triggering the
development of inflammatory bowel disease.

Melatonin could help to control the symptoms of this disease by acting as

an antioxidant and anti-inflammatory agent. It would reduce oxidative
stress on the intestine's delicate mucosal lining and protect these tissues
against damage by free radicals, thereby reducing the risk of ulceration.
This is another excellent example of how melatonin comes to the rescue
when we are under stress.

The study further focused on the measurable effect of sleep deprivation on

experimental colitis and whether melatonin's protective effect could be
effective in minimizing these changes. The participants were divided into
four experimental groups as follows: the first group included participants
with colitis; the second was composed of those with colitis and sleep
deprivation; the third group had participants with colitis and sleep
deprivation and treated with melatonin, while the fourth was the control
group.

Colitis in the first three groups was induced artificially by the

administration of 5% DSS (dextran sulfate sodium) in their drinking water
for about six days. The participants were later sleep-deprived for three
days, and subsequently, the changes in the histological analysis of colon
tissues, body weight, and the levels of genes and pro-inflammatory
cytokines were evaluated.

The results of this study showed that

sleep deprivation causes worsening of
the inflammation in the colon, as was
evident in the histopathological
analysis of the tissues. It was also
found that the group of participants
that were treated with melatonin had
favorable results. The inflammatory
changes in the tissues caused due to
sleep deprivation were reversed by
melatonin. Additionally, even the weight loss caused due to colitis was

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reduced significantly by melatonin treatment, and it also led to an

improvement in the survival rates.

There was a rise in the levels of proinflammatory cytokines, including

interleukins, interferon-γ, and tumor necrosis factor-α in the serum of the
sleep-deprived group. However, the levels of these proinflammatory
substances were reduced remarkably following the treatment with
melatonin. Furthermore, gene analysis showed that the expression of some
inflammatory markers was initially increased due to sleep deprivation and
later reduced following treatment with melatonin.

The results of this study have provided a remarkable breakthrough in the

management of colitis. It has shown that melatonin holds great potential
as an anti-inflammatory agent and could reverse the effect of sleep
deprivation risk of ulceration and inflammation in the colon.

I suggest that anyone under stress would benefit from melatonin

supplementation - and who isn't these days? Lack of sleep is one of the
worst stressors there is, perhaps worse than poor nutrition and lack of
exercise. [9]

Melatonin in the management of colorectal

cancer

Melatonin has been found to play a role in inhibiting the abnormal

proliferation of cells responsible for triggering the development of many
cancers, including colorectal cancer.

Colorectal cancer is the third most commonly detected cancer. It’s also a
significant cause of cancer-related deaths around the world. Multiple
factors are associated with the development of colorectal cancer, including
poor sleep, poor gut function, general aging, dietary habits, inadequate
physical activities, and smoking.

At their root, all cancers are related to the poor function of your
mitochondria. Melatonin might help reduce the chances of developing this
cancer by supporting mitochondria as a primary antioxidant. Through this

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mechanism of supporting and protecting your mitochondria, melatonin

also protects against colorectal cancer as an anti-inflammatory agent,
creating immune modulation and activating anti-oncogenic and oncostatin
actions. All these work to inhibit the progress of many cancers, including
colorectal cancer.

Given that melatonin is produced in the gastrointestinal tract, it produces

a direct local effect on the cancer-causing agents the colon and rectum are
exposed to, thereby preventing the growth and spread of abnormal cells.

Moreover, the secretion of melatonin in the digestive tract holds particular

importance here as the total levels of melatonin are nearly 400 times more
than that produced in the pineal gland. This has been proven in a study,
'Thirty-four years since the discovery of gastrointestinal melatonin',
published in the Journal of Physiology and Pharmacology in 2008. [10]

Another study, 'Therapeutic Opportunities in Colorectal Cancer: Focus on

Melatonin Antioncogenic Action' published in the Biomed Research
International in 2019, showed that
the antitumor functions of
melatonin, coupled with the ability
of this hormone to regulate the
body's circadian rhythm, would
help people avoid the risk of
colorectal cancer. [11]

Problems in the circadian rhythm

were observed in patients with
colorectal cancer and reduced melatonin production, indicating the
possible involvement of melatonin deficiency as a possible cause for this
condition.

Another study confirms that melatonin has the potential to block colon
carcinogenesis. 'Melatonin suppresses AOM/DSS-induced large bowel
oncogenesis in rats' published in the chemical-biological Interactions in
2009 has supported these findings.

The study assessed the inhibitory effect of exogenous melatonin on the

cancerous changes occurring in the colon. It showed that the

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administration of melatonin helped to inhibit the development of colonic

adenocarcinoma. Moreover, exposure of the colon to exogenous melatonin
also modified the process of mitosis (a form of cell division) and apoptosis
(programmed cell death in cancer tissues), thereby indicating the efficacy
of melatonin as an anticarcinogenic agent. By regulating mitosis,
melatonin might inhibit the abnormal proliferation of cancer cells, limiting
the growth and spread of cancer. This means melatonin might also help
support the division or regeneration of new and healthy cells in the tissues
affected due to cancer, thereby supporting faster repair and healing. The
improvement in apoptosis brought about by melatonin would encourage
programmed cell death, enabling the body to selectively attack and destroy
cancer cells, ultimately limiting the extent of cancer mass.

Also noted in the study, was the possibility that melatonin might control
the secretion of inflammatory substances in patients with colonic
adenocarcinomas, minimizing damage to the tissues. These results
indicate the beneficial effects of exogenous melatonin on colon
carcinogenesis, particularly related to the inflammation in the colon,
suggesting the potential application of this hormone for inhibiting the
development of colorectal cancer. [12]

Altogether, these results suggest that melatonin might inhibit the

development and progression of colorectal cancer in humans. Which are
extremely interesting findings, that could make waves in the prevention
and treatment of specific types of cancer.

There is a cross-link between melatonin deficiency and the higher

occurrence of colorectal cancer. The lack of adequate levels of this
hormone might prevent the body from fighting cancer naturally. Several
potential mechanisms, including autophagy, suppression of cancer cell
proliferation, angiogenesis, and the activation of apoptosis and cancer-
related immunity, are believed to be stimulated by melatonin while
limiting the development and progression of the colorectal colon.

Moreover, there is experimental evidence showing that melatonin might

act through the membrane and nuclear receptors. One research study,
'Possible involvement of the nuclear RZR/ROR-alpha receptor in the
antitumor action of melatonin on murine Colon 38 cancer' published in the

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Tumour Biology in 2002 proposed that the nuclear melatonin receptors are
identical to the nuclear orphan receptors, suggesting that the antitumor
effect of melatonin also depends on nuclear signaling. This means
melatonin may produce an oncostatin effect on colon cancer cells by
regulating nuclear signaling mechanisms and reducing the excessive
proliferation of tumor cell nuclei. Once the proliferation of tumor cell
nuclei is prevented, it would automatically cause inhibition of cellular
proliferation. This demonstrates one of melatonin's roles in the body: to
stop the growth of colorectal cancer by creating an inhibitory effect on the
division of the nuclei of cells. [13]

The main takeaway from this chapter is that melatonin is a gut-protective

agent that helps enhance the immune functions of the gut flora, reduce
peristalsis, alter the intestinal microbiome diversity, and restore healthy
functions of the stomach and intestine.

Conclusion

The high concentration of melatonin within the gut (400x's) compared to

the melatonin produced by the pineal gland demonstrates how important
it is in gut health. The protective effect of melatonin on the gastrointestinal
tract has been proven with a variety of studies. Melatonin further supports
the beneficial bacteria through a robust circadian rhythm signaling which
causes the good bacteria to "swarm", and has a negative effect on the bad
bacteria, thereby improving the microbiome in your gut.

The microbiome should primarily live in your large intestines and not so
much in the small intestines. Using a suppository or enema implant with
probiotics and butyrate can be helpful. Especially when a post-fast
protocol to improve the health of your microbiome is desired. A 24 hour
or even 3-5 day fast followed with a supra-physiologic melatonin dose to
support a strong microbiome swarming effect is effective. Fasting is a
positive stress to the microbiome, and refeeding after the fast is how the
microbiome comes back with stronger health.

You can support your gut by restoring melatonin levels through

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supplementation. Once melatonin levels increase, the circadian rhythm

would be restored, and the gut functions would be regulated, thereby
preventing mechanisms responsible for poor gut health.

When deciding how much melatonin to supplement for gut support,

consider that the level of melatonin in your gut is four hundred times
higher than the levels associated with the pineal gland. I believe that the
typical 3-20mg prescribed by most doctors falls short of the optimal
dosage, where one can receive the most benefit from the miracle molecule.

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Chapter 12: Melatonin For Jet
Lag & Disrupted Sleep-Wake
Cycle In Shift Workers

What's more important than nutrition and exercise? Sleep is the

answer! Sleep is so important that it is now illegal to run research
on sleep deprivation due to the extreme harm it can do to us.

I recently traveled for a weekend spiritual retreat and my flight was

so early I had to set my alarm at 3:30am. I was so concerned I
wouldn’t wake up that I didn’t trust going to sleep at a deep level
and played in bed half asleep until 3:30am when I pulled myself out
of bed and dragged myself to the airport feeling horrible. This was
a rare occasion, but the after-effect was my hands were shaking and
I was unsteady on my feet all day. I was unable to recall many simple
words, and ideas were difficult to express in conversation. All due
to a poor night’s sleep. It hit me like a brick wall and what’s amazing
to me is that there are so many individuals out there that deal with
this night after night. It has become completely normal.

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Sleep is actually an active process. It takes a very specific release of

chemicals, and of course melatonin.
Many people experience difficulties falling asleep due to anxiety
like I did a few nights back. Sleep deprivation or the lack of adequate
sleep could work as a dangerous precursor to the decline in brain
and physical function, plus life and work productivity, and
performance.
Sleep does things for us that reach into every aspect of our health
and we will be diving into this subject a little further in this chapter,
as well as how we can leverage the use of melatonin to improve this.
I will also be covering ways to maximize sleep besides melatonin,
so for those that have sleep difficulties, this chapter is perfect for
you!
We will also be taking a look at how traveling through time zones
causes jet lag and whether this hormone could be used to avoid the
symptoms of jet lag for frequent travelers or the adverse effect of
changing sleep-wake patterns in people working shifts, such as in
the ER or security guards.

What does melatonin do?

Melatonin plays a vital role in improving the duration and quality of your
sleep. The secretion of this hormone in the pineal gland varies at different
times throughout the day. Melatonin production depends on the amount of
light or brightness your body is exposed to. Some other factors including

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your daily schedule, seasons, and emotional health can also influence the
secretion of melatonin in the
pineal gland, thereby creating a
positive or negative effect on
your sleep-wake cycle.
For example, during evening
hours, as darkness approaches,
the body begins to prepare itself
for sleep by releasing the
secretion of melatonin. On the
other hand, as daytime
approaches, the body is exposed
to bright sunlight. So, during
the early morning hours, the
secretion of melatonin begins to
reduce to prepare your body for
wakefulness. Cortisol is an opposing hormone to melatonin and when
melatonin decreases in the morning hours cortisol increases, and vice versa
in the evening.
These changes in melatonin production are regulated by exposure to bright
light and governed primarily by the suprachiasmatic nucleus which is hard
wired to your eyes. It's a part of the brain that is responsible for sending
signals to the pineal gland to produce and release melatonin at night and
then, suppress its production and release it during the daytime.
The increased level of melatonin during night hours is meant to help you
sleep, meanwhile the reduced level of melatonin along with elevated
cortisol during the daytime keeps you alert and awake.
Melatonin could be beneficial for those who are producing less due to
sleep stress factors. These include lack of sunlight exposure to eyes, poor
bedroom hygiene such as too hot or lack of total darkness, too much
exposure to green and blue light after sunset, meals too late in the evening,
and high physical, mental or emotional stress. Melatonin may also be
useful for managing the symptoms of jet lag which frequent travelers often
experience.
Melatonin supplementation taken at specific times based on the difference
in the time zones of your origin and destination would reduce the impact
of jet lag symptoms. Trust me, I grew up in Hawaii and currently live in

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Florida, so I fly back often to visit friends and family which is a 5–6-hour
time difference and I know jet lag well. I have figured out how to beat this
with something I call the “Travel Hacker Kit” which includes a very high-
dose melatonin product called Sandman. This protocol has been a
complete game changer and I am able to get right into the fun when I arrive
at my destination the first day. Incidentally, I’m actually writing this
chapter while on a flight to Hawaii at this very moment. I’m flying over
the Pacific Ocean right now headed to Hawaii for x-mas!
These strategies can be used by frequent travelers to feel fresh and reset
their body's circadian rhythm according to the day and night times of the
destination. This will happen naturally over time, but we want to get right
into the swing of things when we arrive so speeding this up is desirable.
Achieving a shorter acclimation duration using melatonin and even more
impactful the Travel Hacker Kit method is a big advantage. This is why;
it is important to explore the right ways melatonin supplementation can be
used in your travel plans to be able to avoid the impact of jet lag. Luckily,
we will outline my special hack later in this chapter.
The dual role of melatonin during the night and daytime also holds
importance for people who work in shifts. The lack of regular working
schedules and changing sleep-wake cycles prevents the body from creating
its own biological clock. This lack of regular routine ultimately disrupts
the body’s circadian rhythm. The dysregulation of the circadian rhythm,
in these cases, would not just affect the ability of the person to sleep well,
but also cause a decline in productivity during working hours.
Above all, the disruptions in the rhythmic activities of the body would
create an adverse effect on all functions that are regulated by the sleep-
wake cycle including repair and healing mechanisms, inflammation, and
the defense activities of the immune system. The overall impact of these
changes could be severely harmful.
Melatonin supplementation might provide a solution to the health issues
linked to shift working and enable people to have healthy sleep-wake
cycles while avoiding acute and chronic diseases linked to the distorted
circadian rhythm.
We have already discussed what melatonin means and how it affects sleep
in earlier chapters. But, in this chapter, we will specifically look at the role
of melatonin supplementation for reducing jet lag and the effect it can have
for those working in shifts.

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What is it about the sunlight and melatonin

secretion?

One of the best ways to stimulate the pineal gland and cells to
produce melatonin is to get some sun every day. Exposure to sun
rays for at least 10 to 15 minutes every day could support optimum
secretion of this hormone in the body. During the daytime, when the
sun rays fall onto the retina, they stimulate the optic nerve, which,
in turn, sends a message to the brain about the presence of bright
sunlight outside. Once the brain knows it is daytime, it sends a
message to the pineal gland to stop releasing melatonin in order to
prevent sleepiness and promote mental and physical alertness which
is essential for us to perform our daytime activities.

Exposure to the sun in the morning hours would also regulate the
production of melatonin in the pineal gland such that when you go
to sleep, the melatonin levels are at the peak allowing you to have
quality sleep. [1]

Melatonin is also secreted in the fluid in your eyes. So, it makes

sense to set aside your sunglasses in the morning hours, in particular,
while traveling. Not wearing sunglasses will allow the sun rays to
enter your eyes and promote the synthesis of melatonin in the
intraocular fluid. If you're a shift worker you might consider
investing in one of the hats or sunglasses products that puts out green
and blue light, or if you're traveling you should get out in the sun in
the morning and ditch those sunglasses. [2] [3] [4]

Whether you're traveling or not you might consider removing your

sunglasses before 11 am and after 3-4 pm. This would be an
effective way to ensure adequate signaling of the circadian rhythm
and production of melatonin in the pineal gland. [5]

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Support your pineal gland

Pineal calcification is calcium

deposition in the pineal gland,
which has long been reported in
humans. The occurrence of pineal
calcification depends on
environmental factors, such as
sunlight exposure, toxins like
fluoride, and increased metabolic
activity. This calcification is seen
in many chronic conditions.

Studies have found that the more metabolically active the pineal
gland is, the more likely it is to form calcium deposits. Furthermore,
researchers have conducted animal studies where gerbils who were
exposed to less light than others had higher amounts of pineal gland
calcifications. darkness strongly influences the pineal to release
melatonin. If the pineal gland has to produce larger amounts of
melatonin due to less sunlight exposure, calcification can occur. Do
certain chronic medical conditions increase the likelihood of pineal
gland calcifications or is pineal calcification lowering melatonin,
therefore, these conditions appear? Examples of these medical
conditions include Alzheimer's disease, migraine headaches, kidney
disease, and schizophrenia.

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Fluoride & your pineal gland?

Researchers have studied a

potential connection between
increased fluoride exposure
and pineal gland
calcifications. Fluoride is a
naturally occurring mineral
that some areas add to their
water supply to reduce tooth
decay. The mineral is present
in most toothpaste because it helps to strengthen tooth enamel. Yet,
fluoride is naturally attracted to calcium, and some researchers
believe increased fluoridation leads to increased pineal gland
calcification.

A study in 2019 in rats found those who were placed on a fluoride-

free diet for 4 to 8 weeks experienced a greater increase in the
number of pineal gland cells compared with those who consumed
fluoridated food and drinking water. See the chapter on pineal for
more details on this subject.

Can you decalcify your

pineal gland?

It’s pretty simple really, stop

consuming fluoridated water. If
you’re on a public water system,
you can request support from your
water supplier, which will contain

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information about fluoride and chlorine, which is another mineral

that may contribute to calcifications. As an alternative, some people
will either filter their water or drink bottled water. Avoid using
toothpaste that contains fluoride. Fluoride is also used in pesticides
and some chemicals used to create non-stick compounds for pots
and pans. Eat organic foods and avoid processed foods to reduce
fluoride consumption. Calcium supplementation consumed in
excess could be problematic. Especially if you're low in vitamin D
and K-2. Or you may be taking too much vitamin D and not enough
vitamin K-2, as the K-2 is needed to prevent the calcium from
depositing into your tissues.

Either way, to answer the question: Yes, it is possible to decalcify

the pineal gland.

The importance of using melatonin

supplements for sleep

Besides melatonin being a sleep-inducing hormone, it plays a major

role in regulating the body’s internal biological clock. It basically
works by regulating the sleep-wake pattern and helps to improve the
quality and duration of sleep. But let’s not forget that it also works
on your body and brain in so many other ways as you have read
throughout this book. Dialing in the circadian rhythm can be as
important as an exercise or nutrition program. This becomes even
more important when traveling and in shift workers due to the stress
both these situations place on your body.
Even though melatonin is produced in the body naturally, people
who work in shifts or those who have to travel across different time
zones frequently, are unable to derive the potential benefits of this
hormone, simply because the specific conditions needed for the
time-dependent or light-dependent secretion of melatonin by the
pineal glands are not adequate under these stressful situations.
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Neither the shift workers nor frequent travelers get an opportunity

to set their body’s rhythm so that it gets a similar amount of exposure
to sunlight at fixed times of the day or night. And this is the reason
they need to depend on melatonin in the form of supplements to be
able to enjoy the therapeutic benefits of the miracle molecule.

How to use melatonin supplements for sleep?

Since melatonin is a sleep-wake cycle regulating hormone, it’s

important that you use it at the right time to suit your routine,
keeping in mind the time you need to sleep against the time you need
to be awake and productive.
If you struggle to fall asleep
often due to jet lag or working
in shifts, you should take
melatonin supplements about
30 minutes before bedtime. The
other option is spending several
hours trying to fall asleep. I
know which one I prefer!
Moreover, some research suggests when taking smaller doses of
melatonin such as 3-20mg may be better for sleep latency, but these
doses should be taken 3-4 hours before bed, such as after dinner.
This principle does not seem to be true for the supra-physiological
dosing of melatonin, such as 100-200mg.
You need to consider your sleeping habits when you start using
melatonin for improving your sleep quality. This is true irrespective
of whether you’re an early bird or a night owl. These are the basic
chronotypes that determine the rhythmic activities your body
follows in order to allow you to perform and maintain various
functions.
Night owls are basically the people who tend to stay awake until the

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late hours of the night. So, they also have a tendency to get up later.
Early birds, on the other hand, are those who get to sleep early like
by 9 or 10 pm and are early to rise.
Therefore, depending on whether you are an early bird or a night
owl, you need to time the doses of your melatonin supplements so
that it matches your current sleep-wake cycle. You also need to take
into account your expected sleep-wake schedule. This means if you
plan to change your bedtime routine or the time you wake up, you’ll
also need to change the time you take melatonin supplements to
derive optimum benefits.
If you are an early bird, it’s advisable to take melatonin in a slow-
release delivery format so that the melatonin is provided throughout
the evening. Oral routes generally have a short half-life and fast
absorption, versus a suppository which can release slowly over 5-7
hours. Liposomal versions can also be time-released, nevertheless, I
have found the suppository to be the most effective. Also, keep in
mind studies show oral melatonin is only 2.5% absorbable, so a
Liposomal or suppository might be best all around.
In the case of early birds who often wake up too early in the
morning, say at 3 or 4 am, using a melatonin supplement might be
helpful for you to signal a stronger sleep cycle through your
circadian rhythm. Melatonin will extend the sleep duration allowing
you to sleep for the extra 2 hours, meaning that you would wake up
at 5 or 6 am. Tracking your sleep is a great way to know for certain
the quality and exact duration of rest you’re getting each night. Oura
rings are what I use as they have been studied to be one of the best
products on the market, but there are also several options to choose
from.

Most people believe that going to bed early and waking up early is
a good habit. However, while it’s true that sleeping and getting up
early is good for health, the total duration of sleep should still be 8
hours. If you sleep early but wake up too early, you may not get
adequate sleep. Your total sleep time would be shortened by a few
hours. This might deprive your body of the multiple benefits of

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having a sound sleep, and it may also hamper the biological

processes like memory storage, and healing that occur more
efficiently while sleeping.
This is the reason why even early birds may need to take melatonin
supplements in order to extend their sleep duration. Proper dosing
of melatonin taken at the right time could help early birds get the
correct amount of sleep and prevent their risk of diseases linked to
poor immunity, inflammation, oxidative stress, and degeneration all
of which are connected to sleep insufficiency.

Should night owls try and return to the

natural rhythms of the earth?

The need to use melatonin

supplements is more important
in night owls than it is for the
early birds. This is because the
night owls are more likely to
already be suffering from health
issues linked to poor sleep
habits. They are out of sync
with the earth's natural rhythms!
Staying awake until late hours and then subsequently waking up late
in the morning can disrupt the body’s circadian rhythm, which is
regulated by the amount of exposure to sunlight. If your actual sleep-
wake cycle is not in sync with the night-time and daytime, your brain
would fail to be in sync with various mechanisms that depend on the
circadian rhythm to function efficiently.
Your brain will be left confused about whether to follow the signals
received through exposure to darkness and sunlight based on
external conditions or whether to follow the signals provided by you
with your out-of-sync sleep-wake schedule.

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This might create huge disturbances in the overall functioning of all

organs and systems putting you at risk of several diseases. For
instance, it could cause disruptions in your immune system, your
heart rate, body's healing mechanisms, natural antioxidant defenses,
and much more. So, the only way to restore health here is to reset
your sleep-wake cycle so that it is attuned to the actual day and night
cycles of the earth.
Melatonin supplements along with some lifestyle factors can be
effective tools to rebalance your sleep-wake cycles. Night owls can
start taking melatonin supplements approximately 2 hours prior to
their normal bedtime in order to fall asleep early and bring your
body’s circadian rhythm closer to that of the sun's rhythm. This
would advance your sleep-wake schedule and sync your body's
circadian rhythm.
How much melatonin should one take for these situations? I feel 10-
20mg can be a good place to start. Although we’ve discussed
supplementing with much higher doses, where sleep is concerned
these are unnecessary. Lower doses can be tried and if they work
well then higher doses could be used occasionally for a “Melatonin
Reset”, which is something we will discuss a little later on in this
chapter.

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Jet lag & time zone acclimation

What is jet lag?

Jet lag refers to a physiological state

that is characterized by the disruption
in the sleep-wake cycles of a person
due to the rapid traveling across
multiple time zones leading to
imbalances in the circadian rhythm.
The circadian rhythm, as we already
know, is the internal biological clock
your body is accustomed to following
in order to determine the time to sleep and stay awake, eat meals, bowel
movements, and so on.
When you travel through more than two time zones in a very short period,
say in 5 to 6 hours, it does not provide adequate time for your body to
adjust to the new day-night cycle of the destination.
As a result, you may experience an inability to sleep during the night and
stay awake during the day once at your new destination, resulting in what
we call jet lag. In simple words, it means your body is lagging behind in
terms of the time zone you jet traveled from causing you to be out of tune
with the time zone you are currently in.
What about people who have to put up with frequent changes in their
sleep-wake cycles due to the need to travel across multiple time zones?
Working professionals and businessmen often have to travel from one
country to another to attend meetings, give presentations, and so on. They
often have to jet set from one location to another across time zones
throwing a monkey wrench in their circadian rhythm.
In cases like these, if the difference in the time zone of their place of origin
and the destination is approximately a 5/6-hour difference, as is the case
from Florida to Hawaii, then the body's sleep cycle gets disrupted.

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What are the common signs of jet lag?

It’s surprising to note that in spite

of using the words, jet lag,
repeatedly, most travelers are not
aware of the specific symptoms
they may develop. Most of the
time people say they have jet lag
just to describe the fatigue caused
due to the lack of proper sleep after having traveled to a different
time zone.
However, unbeknown to most, jet lag does not only involve loss of
sleep or fatigue.
It’s important to be aware of the specific symptoms of jet lag so that
you know the long-term implications this problem may cause if you
choose to ignore it. Jet lag is characterized by several symptoms that
can disturb your routine schedule significantly.

Here are the top 3 common signs and

symptoms that frequent travelers often develop
due to jet lag:

1. Disturbed sleep and daytime fatigue

A research study ‘Jet Lag: Current and Potential Therapies’

published in the Pharmacy and Therapeutics in 2011 has shown that
patients may develop extreme daytime fatigue for the first few days
after arriving at the destination. This may occur due to the inability
to sleep well at night. [6]

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It has been found that the loss of sleep after travel is linked to the
disturbances in the production of melatonin, the primary function of
which is to regulate your sleep-wake cycle.
Most people find it too difficult to get enough sleep because the new
time zone they have arrived at has a different schedule than what
their body’s circadian rhythm is used to.
As a result, when nightfall arrives at the new destination, they cannot
sleep, or experience fragmented or disturbed sleep. This might affect
their daytime productivity and make them feel tired and drowsy
while performing tasks.
This indicates why it’s important for frequent travelers to not ignore
jet lag and use melatonin to be able to avoid these symptoms. This
is especially important if they need to attend meetings or events that
hold high importance in their life or career. Feeling tired with low
motivation while performing such tasks might negate the very
purpose of traveling to the destination and lead to unpleasant
consequences.

2. Lowers cognitive skills

Frequent jet lag may affect your cognitive skills by reducing your
sleep duration and quality.
A research study, 'How To Travel the World Without Jet lag’
published in the Sleep Medicine Clinic in 2010 showed that jet lag
may also reduce your concentration and prevent you from focusing
on tasks. [7]
As a result, your ability to make quick decisions and your sense of
judgment can be negatively affected.

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3. Irritability

Lastly, one of the more

notable symptoms of jet lag
is irritability. might
experience severe
irritability and anger
issues during the period
in which your body is
trying to adjust to the
day-night cycle of the
new time zone.
A research study, 'Associations Between Jet Lag and Cortisol
Diurnal Rhythms After Domestic Travel’ published in Health
Psychology in 2011 showed that jet lag could disrupt the production
of cortisol in the brain. As a result, you may develop irritability and
poor mood. [8]
Most of these symptoms of jet lag are related to the changes in the
production of melatonin within the pineal gland. Ultimately,
travelers should leverage the use of melatonin supplements in order
to restore their body’s circadian rhythm and avoid jet lag caused by
hopping across different time zones. Moreover, melatonin taken
even before the trip can be helpful, for instance dosing a day or two
before your trip around the approximate bedtime of the destination
you're traveling to. I usually suggest a dose of 20-60mg in this case.
It is advisable that you understand how a daytime melatonin dose
affects you prior to doing this so you don’t have any disruption in
your travel plans.
I find this advice difficult going to time zones where it is earlier
where you would be dosing the melatonin in the middle of the night.
I feel getting good rest according to the cycle you're in at this point
is more important. However, heading to later time zones as with a
Hawaii to Florida trip is a different story.

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When it comes to folks that travel frequently, say more than once
every month or so, their bodies ultimately never get adequate time
to adjust to any time zone. As a result, their circadian rhythm
remains disrupted month after month and they are largely deprived
of the benefits of having a well-regulated body clock. This happens
because, by the time they get adjusted to the day-night cycle of one
time zone, it's the time to pack their bags and head off on another
trip.
But fear not! If you’re a frequent traveler and have to hop across
different time zones several times in a year, I’m sure you’ll want to
know how you can avoid the effect of jet lag and hack your body
clock as quickly and efficiently as possible. In this next section,
“Melatonin Reset” I’ll highlight exactly how to effectively reset the
body's circadian rhythm.

Melatonin Reset
If you're wanting to really reset your circadian
rhythm this method is for you. It’s what I will do
tonight on my first evening in Hawaii.

First of all, I’ll take advantage of as much

sunlight as I can this afternoon to make the
most of as much natural signaling as I can. I
won’t wear sunglasses, which I rarely do these
days for the same reason anyway.
Secondly, I will try and get some physical
exercise as well by going for a short hike to
build up sleep stress.
Thirdly, I’ll use caffeine this afternoon to keep me alert as it can be
quite difficult to stay awake till 9 or 10pm the first night without
some form of energy beverage.
Ok so here is the real magic…

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For the melatonin reset ill dose 200mg of melatonin in the form of a
suppository at 9/10pm this evening. And if you've been reading
through other chapters in this book, you're probably already more
than familiar with the safety and efficacy of using melatonin in these
high doses. It's nontoxic at very high levels, does not shut down your
natural production with any negative feedback loop, and it works
quite well for this utility. However, if you're an executive or travel
for business, let me forewarn you that the first time or two you take
this much melatonin you could be a little groggy the next morning.
Melatonin also detoxifies heavy metals from the brain so you won’t
want to be detoxing while on vacation, and while 90% of people will
do just fine doing 200mg of melatonin right out of the gate, however
there is a small percentage of individuals who might need a few days
to acclimate themselves to that dosage.

Eating late & melatonin

This information is from chapter 7 yet it's worth mentioning here
again, as traveling can oftentimes throw our mealtimes out of
whack.

In your pancreas, you have MT1 & MT2 receptors for melatonin.
These are called “G-coded melatonin receptors''. This means that
there is a direct link between your pancreas, insulin, and melatonin.
When you go to sleep, these receptors are activated by melatonin.
And subsequently, insulin is lowered, and glucose is increased, via
these MT1&2 receptors.

These receptors have a direct action through cAMP and cGMP

which is an important signal to your metabolism. This activation and
signaling enables you to have more glucose which ultimately helps
make repairs needed within the body while you sleep.

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The point I’m trying to make is although eating late might increase
serotonin, which helps to increase building blocks for melatonin, it
might not be best for your health long term. Especially if you're
leaning towards Type 2 diabetes. Therefore, this is something to be
extremely mindful of if you’re a frequent traveler.

Travel hacker kit

I find traveling daily stressful
and before I discovered the
protocol I’m going to share
with you now I always needed
a few days to feel “normal”
after any trip.
My personal challenges were
partly due to time zone
changes, yet there are other
factors that I struggled with,
especially when using air
travel. Nevertheless, I suspect that air travel might be better now that
the airlines have been somewhat forced to use better air filtration
systems due to the COVID pandemic.
I say this because I was diagnosed with severe mold illness,
therefore my tolerance for poor air quality is low.
Another reason many of us feel
quite tired after a long flight is the
EMF exposure from the engines,
plane, and altitude. I find a very
high CBD dose to be very helpful to
combat the EMF exposure, which I
prefer in a suppository form. I take a
product called NeuroDiol 300mg
which offers a neuroprotective and
inflammatory effect while flying.

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I also enjoy using a nice natural antimicrobial nasal spray a few

times while on the plane to keep my sinus clear and prevent picking
up any unwanted nasties on the flight as well.
I’ve been using the travel hack kit for a while now and it’s never let
me down. It’s well worth it, especially if you’re someone who’s
either sensitive to EMFs, air quality, and environmental changes
such as time zones.

Travel Hacker Kit in a nutshell:

• 300mg CBD suppository upon take-off and redose 5 hours
into the flight if it’s a long-haul flight.
• Antimicrobial nasal spray each hour or so while flying, I like
GlutaStat Nasal Spray.
• Take 100-200mg melatonin in suppository or liposomal form
the night of and for several nights into my trip.

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Conclusion

In this chapter we’ve seen how melatonin can be used when travelers
wish to reset their circadian rhythm, and how it can further be
leveraged by night owls in order to create healthier sleep-wake
cycles that are more in tune with nature.

We also highlighted the use of melatonin for shift workers. And

although melatonin can be applied successfully in these cases, it’s
also super important to sleep in complete darkness during the night
and get out in the sunshine when possible. Shift workers could also
use blue or green lights at night to mimic the sun's neurologic
influence on the circadian rhythm. Moreover, nowadays there are
even hats and glasses that are designed to shine these daylight
mimicking colors into your eyes.

We further discussed the Travel Hacker Kit which you can also find
at MitoZen.com.
In the various strategies covered in this chapter the melatonin
dosages can vary from 10-200, yet it’s definitely worth testing as
there are numerous health challenges poor sleep leads to in the body,
and correcting sleep-wake cycles can be an important factor in
reaching optimal and balanced health.

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Skin Disease & Anti-aging strategy for skin

I started working with a woman who was dealing with cancer a

while back and she asked me to connect with her holistic doctor to
discuss using high-dose melatonin. Her doctor was super-open to
adding melatonin to her program as she already had a good
experience with using melatonin in the past. She was mainly
applying it for her female patients for skin in a melatonin cream. She
asked if we made any melatonin skin products and at that time, it
was the first I had heard of melatonin used this way.

She stated that she was seeing dramatic skin results with a cream she
was having made through a compound pharmacy. It made sense to
me as the science behind this approach would work just like it does
with many of the other conditions we have discussed in this book.
As antioxidant and mitochondrial support, it could help your skin be
healthier and more youthful.

So, I began making a facial serum and a body lotion with melatonin
and, of course, I had to boost this with my own additions of

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resveratrol, apocynin, GHK peptide, methylene blue, and hyaluronic

acid.

I found this to be an amazing combination for skincare. Besides the

direct application of melatonin to the skin, there is also the quality
of your sleep as “beauty sleep”. Beauty or the health of your skin is
dependent on the quality of your sleep. If you get consistent quality
sleep every night, you will look fresh, and your complexion will
glow with radiance.

But can melatonin, orally or in the forms of gels or creams, bring

back the glow on your face? We will dive into this subject in this
chapter.

Using melatonin for improving skin health

When we think of melatonin, the odds are that you will think of
sleep. Yet, as we have discussed in prior chapters, melatonin is not
just a sleep hormone that regulates our circadian rhythm and
improves our sleep-wake cycle. Melatonin is also one of the most
effective natural remedies to improve our skin health, as it’s
considered a natural anti-aging hormone. These “skin benefits” of
melatonin are directly related to the ability of this hormone to
improve your sleep pattern, protect your skin against oxidative
damage through its antioxidant qualities, and the cellular energy it
provides to your skin through the support of your mitochondria in
cells.

How is this possible? It turns out that besides being produced in the
brain by the pineal gland, melatonin is also produced in your skin
cells. This makes your skin a site of local production and activity of
melatonin. Melatonin has a somewhat wider range of action when it
comes to the skin. For example, melatonin suppresses the UV-

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induced damage to the skin cells and works as the skin’s own natural
antioxidant, protecting cellular DNA against free-radical damage,
delaying the aging signs like wrinkles, improving the thickness of
the skin, and maintaining its tone.

Let's take a closer look at each of these melatonin benefits for your
skin, and what has been revealed through research about the effect
the miracle molecule can have on your skin and overall external
beauty.

The anti-aging benefits of melatonin for skin

Do you know why those

signs of aging appear on
your skin? Those
wrinkles and fine lines
on your face give away
your actual age. These
signs are nothing but the
effect of loss of collagen
in your skin.

As you age, your skin begins to lose both collagen and elastin. These
two are the most important components of the skin and primary
contributors to its appearance. Collagen and elastin together form a
strong matrix of skin tissues and provide a firm structure that
supports your skin. Unless you do something to prevent the loss of
your collagen and elastin, your youthful appearance can only last as
long as you are young. Therefore, slowly, it begins to lose its
elasticity like a rubber band that has lost its stretchable nature.

Now that we know why these wrinkles and fine lines appear, it’s
time to learn how we can influence the skin to produce more elastin

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and collagen. The best way to do this is to ensure your skin is

supplied with a rich amount of melatonin.

According to a study, ‘Protective Effects of Melatonin on the Skin:

Future Perspectives’ published in the International Journal of
Molecular Sciences in 2019, melatonin has the potential to stimulate
the production of collagen and elastin in the skin. It might strengthen
the skin matrix and prevent or slow down the degradation of the skin
structure due to aging.

Melatonin may also be used to protect the skin against sun damage
that is known to accelerate the signs of aging. Exposure of the skin
to harsh ultraviolet rays in the sunlight can cause wrinkles and fine
lines to appear at a younger age. The skin may look dry and dull and
loses its natural glow due to excessive exposure to sunlight.

The damage to the superficial and deeper layers of the skin due to
UV radiation can also lead to the appearance of age spots and dark
patches, that can make you look older than your actual age. The
effects of sun damage to your skin could be avoided by using
melatonin. Moreover, this study shows the natural antioxidant
potential of melatonin can minimize free radical damage in the skin
and slow down the effect of sun exposure.

Melatonin may also stimulate mitochondrial functions locally

within the layers of the skin, reduce inflammation, and modify the
expression of some genes, thereby improving your skin tone and
complexion. Consequently, melatonin has been shown to have an
excellent anti-aging effect on the skin.

When used regularly, you will notice your skin looking firmer and
more elastic. This would occur not just due to the increased collagen
and elastin produced in the skin following melatonin
supplementation, but also due to how this sleep hormone stimulates
the healing processes throughout your body. Moreover, melatonin

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would accelerate the repair of the dead and damaged skin cells and
stimulate the regeneration of new cells so that they can replace the
old cells.

Exploring the Gut – Sleep – Skin axis

There is another mechanism through which melatonin can create a

favorable response on
your skin, and that
mechanism works
through the gut-sleep-
skin axis.

Your gut and skin are

closely related. And
the gut flora, in turn, is
linked to your sleep.
As we discussed in
Chapter 11, your gut bacteria or the microbiome goes through a
daily regenerative phase called swarming, which is primarily
signaled through the circadian rhythm and the release of melatonin.
This is different from the melatonin release in the brain and is called
gut melatonin which is 400 times more elevated than the brain
levels.

Melatonin for gut flora and swarming

Melatonin plays a key role in supporting the development of healthy

gut flora. Moreover, healthy gut flora is essential not just for
improving the functions of the digestive system but also for
strengthening your immunity.

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Healthy gut functions and a strong immune system, in turn, can have
a remarkable and positive influence on your skin's health.

Let's dive deeper into how your skin is linked to your gut flora,
sleep, and your immune system.

What forms the gut-sleep-skin axis?

The health of your skin at any given time can be the result of a
number of factors. From hormones and genetics to your diet and
nutrition, your skin is the reflection of what is happening inside your
body.

There is no larger influence on your skin health-driven through

internal conditions than the state of your gut. Besides improving
skin health, there are a few common skin diseases driven through an
unhealthy gut such as d, eczema, rosacea, psoriasis, severe skin
redness, severe itching, severe rashes, and even acne eruptions are
all reflections of a sick and inflamed gut with a poor microbiome.
The gut-sleep-skin axis is so important that it can oftentimes lead to
some of the worst skin conditions doctors see in their clinics.

According to the Human Microbiome Project by the National

Institutes of Health (NIH), our body consists of trillions of
microorganisms, including bacteria that outnumber human cells by
a huge margin of 10 to 1. That gives you an idea of the number of
microorganisms residing in your body. The largest number of these
microbes are found in your gut flora located within your large
intestines. [1]

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As reported by the researchers at the Harvard School of Public

Health, microorganisms in the gut flora support digestion, stimulate
the immune functions, break down toxic compounds, and synthesize
amino acids and vitamins like all your B vitamins which are critical
to bodily functions. [2]

In the intestine, bacterial imbalances are associated with

inflammatory conditions such as irritable bowel syndrome (IBS),
and leaky gut syndrome. These gut issues can manifest in several
other organs of the body, among which skin is the commonest. For
example, the overgrowth of bacteria in your gut, due to a condition
called small intestinal bacterial overgrowth (SIBO), is linked to the
two most common skin conditions, namely acne, and rosacea.

Bottom line is that if you take good care of your gut, it will
eventually have a positive impact on your skin’s health and
appearance. Moreover, in Chinese medicine, they call the skin the
reflection of what is going on inside your gut. On the other hand, if
you experience any gut issues, like inflammation, or leaky gut, your
skin would likely be the first place where you'd notice problems.

Scientists have proven the direct as well as the indirect connection

between gut flora and skin issues like eczema, psoriasis, dermatitis,
rosacea, and acne. For example, one study, ‘Allergic Disease Linked
To Irritable Bowel Syndrome’ sourced from the Rush University
Medical Center has shown that inflammation in the gut may spread
to the skin.

This might happen due to the involvement of the immune system in

gut flora. The increased secretion of inflammatory substances by the
immune system would cause damage to the gut tissues due to which.

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may develop into digestive diseases like ulcerative colitis,

colorectal cancer, leaky gut syndrome, or inflammatory bowel
disease. The inflammatory substances would be carried to the skin
through the blood due and thus you may notice redness, itching,
rashes, acne eruptions, rosacea, and sunburns all of which are
characterized by skin inflammation.

Now, this direct impact of gut diseases in your skin can be easily
avoided if you take good care of your gut flora. Maintaining a
healthy and diverse gut flora would improve the functions of your
immune system so much so that it can calm down the excessive
secretion of proinflammatory substances by the immune cells. The
immediate effect of this would be evident first in your gut and then
with your skin.

Ultimately, by healing your gut you’d further start to notice how you
no longer develop skin rashes, itching, and redness. There may also
be a reduced chance of frequent flare-ups of dermatitis, eczema,
rosacea, psoriasis, and so on.

This is how strengthening your gut-sleep-skin axis would have a

healthy influence on your skin and protect you against a number of
skin diseases. If you don’t have a skin condition you may find
supporting your microbiome with melatonin orally and/or topically
might greatly improve your skin's youthful appearance as well.

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Skin Microbiome: how does it relate to your

melatonin levels and immune health?

The skin microbiome is a vital parameter for assessing the ability of

your skin to protect itself against infections and other disease-
causing agents like inflammation, sun exposure, and oxidative
stress. Interestingly enough, melatonin can get into the skin
microbiome and help restore a diverse skin microbiota just like it
does for the gut flora.

The skin microbiota is made of a number of microorganisms. Most

cutaneous organisms are able to produce molecules that can inhibit
the colonization or growth of other microorganisms and even alter
their behaviors. Moreover, the skin microbiota in healthy adults
remains stable and keeps them protected against the development of
skin diseases like eczema, psoriasis, and sunburns. What is more
interesting is these skin microorganisms also play an important role
in training the adaptive and innate arms of the cutaneous immune
system. This means having a healthy skin microbiota is vital for
ensuring the immune cells in the skin are able to work efficiently.

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The role of the skin microbiome in maintaining

skin health
The interaction of the surface of the body with the external
environment occurs through the skin that acts as a physical barrier
and prevents the invasion of foreign bodies, including pathogens.
The harsh physical landscape of the human skin, particularly in the
nutrient-poor, desiccated, acidic environment, may contribute to the
adversities that pathogens face while colonizing the human skin. In
spite of this, the skin is often colonized by diverse strains of
microorganisms. [3]

The term skin flora, commonly called the skin microbiota, refers to
the microorganisms residing on the skin. Furthermore, the skin's
microbiota may also be composed of different strains of fungi that
reside on the skin and cause diseases or symptoms like itching,
rashes, and redness. These fungi are mainly found in different parts
of the skin including the chest, forearm, ear canal, the back of the
head, between the eyebrows, the heel, behind the ear, toenails,
between the toes, back, groin, nostrils, and palms.

Skin flora is often non-pathogenic in nature. It is either commensal,

which means not harmful to the host, or mutualistic, which means it
might offer a benefit. The benefits that bacteria can offer to the skin
and human body include the prevention of the colonization of the
skin surface by the transient pathogenic organisms competing for
vital nutrients, stimulating the immune system of the skin, and
secreting chemicals against them. But resident microbes may also
cause skin diseases or enter the bloodstream, creating life-
threatening consequences, particularly in people with
immunosuppressed states. So, it is considered important to adopt
measures to restore a healthy skin microbiota so that it can provide
benefits to your skin, or at least, not be harmful to the body.

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I found some studies aimed at assessing the impact of melatonin on

the skin microbiome and whether the effect of melatonin could help
modify the risk of skin problems.

One study, ‘Gut microbiota and nutrient interactions with skin in

psoriasis: A comprehensive review of animal and human studies’
published in the World Journal of Clinical Cases has revealed that
the risk of psoriasis, a chronic systemic inflammatory disease,
closely associated with the interactions between genetic
susceptibility, environmental triggers, and immune response could
be modified by using melatonin.

Allergies and gut issues

The link between your gut is

clearly visible in the research!
If you suffer from skin issues,
it’s likely your gut is not in the
best health. This leads to the
development of allergies and
inflammation throughout the
body. Here is a study that
showed people with rosacea and acne are 10 times more likely to
have chronic gut issues. This study, ‘Allergic Disease Linked To
Irritable Bowel Syndrome’ was conducted by researchers at the
Rush University Medical Center and published in 2008.

Moreover, adults with allergy symptoms have a higher incidence of

Irritable Bowel Syndrome (IBS), suggesting another link between
allergic disorders and gut health. It showed that 34 percent of
patients with irritable bowel syndrome have skin manifestations
reiterating why you must consider the health of your gut health,
especially when you are having skin problems. [4]

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The Gut-Skin Axis is today a widely researched concept by

researchers. It has been clinically proven that when the digestive
balance is thrown off guard, -whether due to stress, poor sleep,
issues with the microbiome, or lack of nutrients in your diet - the gut
is likely to become overrun with harmful bacteria called dysbiosis.
This also leads directly to skin-aggravating manifestations
especially allergies and inflammation.

Getting enough sleep, having higher levels of melatonin, eating

healthy fermented foods, and managing stress are some ways that
could restore healthy and diverse gut flora and reverse these skin
manifestations.

Here is what I recommended for

supporting the microbiome:

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CONTINUED:

• Take a spore-based probiotic.

• Rotate probiotics as the diversity is as important as the quantity.
• Eat plenty of fermented foods.
• Cut down on simple carbohydrates as it supports the “bad”
bacteria in your gut.
• Consider a carnivore diet and or a lectin-free diet to cut down on gut
inflammation.
• Consider a fast such as “Mito Fast” see MitoFast Fasting is “good” stress
to the microbiome and supports healing of the gut lining. Taking high
doses of melatonin post fast will greatly improve a strong bounce-back of
the microbiome through swarming.
• Do a food allergy panel like Doctors Data or Cyrex Labs and avoid IgG
allergies for a month while doing a cleanse to support the gut lining to
heal and strengthen.
• Take a quality protein such as Collagen, Perfect Aminos, or Kion Amino’s
for building blocks to build healthy gut lining.
• Do a parasite and candida cleanse by using broad-spectrum antimicrobial
herbs for a month.
• Do a sinus cleanse such as the one discussed on
UltimatecellularReset.com/sinuscleanse/ as the nasal passage (a filter)
needs to be cleaned and serviced to prevent “bad” things from growing
there. The bacteria that can colonize there can seed into your gut
continuously and act as a primary source of gut issues.
• Practice meditation and deep breathing to support vagal tone and your
autonomics for improved nerve flow to your gut. Also, see Zen meditation
mist at MitoZen.com for vagus nerve strengthening.
• Do an extended fast such as with MitoFast for 3-5 days to stress the
microbiome and activate a hermetic positive effect on your flora strains.
Always follow this fast with a re-feeding strategy with melatonin,
probiotics, and fermented foods.
Practice good sleep hygiene and supplement with melatonin to support
swarming.

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Melatonin and sun burns

We learned that melatonin

supplementation, especially
in the form of a liposomal or
suppository could be just
what you need to improve
gut health. The benefits of
melatonin to your skin have
both a direct and indirect
effect on your skin.

The direct effect of melatonin is attributed to its anti-inflammatory

and antioxidant effects. And the indirect effects could come from an
improved microbiome, a stronger immune system, and better sleep,
thus leading to more efficient repair processes.

Speaking of repair processes, let's consider for a moment how

prolonged sun exposure can play havoc with your skin and create
oxidative stress that the body then subsequently needs to deal with.

Prolonged skin exposure to the harsh

sun rays causing sunburns can lead to
redness, blisters, long-term dark or
white patches, and wrinkles. In some
cases, sun damage can be serious
enough to trigger cancerous changes.
This is one of the most common causes
of a form of skin cancer called melanoma. You need to be careful
but not too careful as you need UV exposure, we will discuss this
later.

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The Melatoninergic System

A study revealed that the
melatoninergic system discovered
in the epidermis could be a possible
modulator for inflammation a\nd
healing. The cyclic nature of
sunlight influences the activities of
an area of the brain called the
suprachiasmatic nucleus (central
clock) which regulates melatonin
production. Moreover, the
peripheral tissues, such as the skin
(peripheral clock), also contain this melatoninergic system.

The shift in circadian rhythm caused due to the changes in the levels of
melatonin during night and daytime is particularly evident in psoriatic
patients. Interestingly, this study has also found that night-shift workers
exhibit an increase in severity of the psoriatic flares, suggesting that the
shift in the circadian rhythm linked to the lower levels of melatonin could
be a risk factor for psoriasis. In such cases, sunlight, in the form of a
narrow band UVB (Red Light Therapy) activating the melatoninergic
system, might also be curative for the psoriatic skin! The melatoninergic
system allows for the reprogramming of the body’s central circadian clock
through light exposure to the skin. [5]

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The efficacy of Melatonin in the management

of skin issues linked to sun exposure

One study ‘Protective Effects of Melatonin on the Skin: Future

Perspectives’ published in the International Journal of Molecular
Sciences in 2019 revealed that melatonin possesses the efficacy of
fighting the damage to the delicate skin due to ultraviolet A and B
rays in sunlight. This study showed that melatonin might suppress
the production of reactive oxygen species in the skin and protect it
against oxidative stress and inflammation. Let me explain how this
action works and helps:

The photoaging
processes are
initiated in the
skin following
excessive sun
exposure by an
increase in the
production of
reactive oxygen species (ROS). These reactive oxygen species, in
turn, can lead to an activation of some pathways that trigger
inflammation and induce the activation of pro-inflammatory factors.
This would worsen the inflammatory skin processes and cause
activation of proteases like MMPs (matrix metalloproteinases),
which can weaken the structure of your skin. Moreover, a gradual
rise in the MMP expression is also proposed to be one of the
mechanisms responsible for altering the elastic fiber network in the
skin. Repetitive UV exposure can contribute to the activities of
MMP due to which the elastic fiber network in your skin would be
further hampered.

Melatonin could be highly effective in such cases for reversing these

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changes. This study showed that melatonin could suppress the

production of ROS and consequently, reduce MMP-1 expression. It
may also stimulate the repair processes in the skin allowing the skin
to heal and regenerate faster.

This is how melatonin could play a key role in protecting your skin
against sun damage, by reversing oxidative stress and inflammation.
This would also protect the
skin against cancerous
changes reducing your risk
of melanoma.

But that’s not all! The

regenerative potential of
the skin tissue also declines
with aging due to the
changes in the proliferation and differentiation of cells. So, when
your age increases, your skin may no longer have the ability to repair
and regenerate itself after sun exposure. This marks the importance
of providing additional protection to your skin by using melatonin
to support the natural repair processes.

Melatonin has also been shown to reduce water loss after UVB
treatment. This just goes to show that melatonin might play a
multitude of roles in protecting your skin against a wide range of
effects of sun exposure including faster aging, cancer, and water
loss. It could restore hydration of your skin keeping it soft and
supple. [6]

Yes, we have to take precautions to protect our skin against the sun
by wearing long-sleeved clothes, using a wide-brimmed hat, and
applying healthy sun protection, and at the same time get some
exposure to our whole body and into our eyes, to be our healthiest!
It’s a catch 22, but similar to most things in life, balance is key.

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Our skin makes vitamin D through sun exposure; therefore, total

avoidance isn’t a good idea. As long as you don’t burn, you’re ok to
get sun without protection. In fact, 20-30 minutes of sun per day
without any protection or sunglasses is a good idea. The best time to
sunbathe would be before 11:00 am or after 3-4:00 pm so that you're
avoiding the most intense sun’s rays.

Ditch the shades and get out in the sun!

Believe it or not, when you wear your sunglasses, you’re more likely to
get burnt. This is because you trick your brain into not creating melanin,
and melanin is what offers a protective action against the sun UV rays.

This concept has been proven during one study, ‘The Protective
Role of Melanin Against UV Damage in Human Skin’ published in
the Photochemistry and Photobiology in 2009. This study revealed
that skin pigmentation brought about by melanin is the most
important photoprotective factor. Melanin, besides acting as a
broadband UV absorbent, also functions as an antioxidant and free
radical scavenging agent. [7]

Melanin is primarily stimulated by the

light that enters the eyes. This light is
measured by the brain and tells your
skin how much melanin to make based
on the amount of light detected. It’s a
genius built-in sensor (supra the
suprachiasmatic nucleus aka central
clock) yet we make the mistake of
always wearing sunglasses.
Try to avoid your sunglasses in the
morning on your drive to work. Instead, allow the light to enter your

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eyes. If it feels too bright that’s ok! It was like that for me when I
first started doing this and it gets better once you retrain your eyes
to deal with REAL light. I honestly never wear sunglasses while
driving unless it’s a long trip and try to not wear them most of the
time. Not just for the melanin, but for more melatonin to get
produced through the influences to the suprachiasmatic nucleus
(central clock) regulates the melatonin production and light
exposure to the peripheral tissues or skin (peripheral clock), in
numerous ways.
Moreover, light exposure to the eyes strengthens the circadian
rhythm, and it's made stronger when you're telling the brain its day
and when it's night. It's about the natural rhythm that the light
activates and making sure that it's supporting your healthy sleep and
wake states. If you want to be more rested after a night’s sleep, and
more energetic, alert and sharp during the day then you need to
consider following these suggestions.

Melatonin might help kids with eczema to

avoid sleep issues

Nowadays, we have kids on smartphones, tablets, and TVs for hours

after the sun goes down. This paired with poor nutrition, EMF, and
toxins in our environment is a headwind to the release of melatonin
with our children. This is why, coincidentally, children with a skin
condition called eczema often experience trouble sleeping.

A new study has suggested that melatonin might be helpful in such

cases to boost their sleep. The study, ‘Melatonin for Children with
Eczema’ was published in the online edition of the journal JAMA
Pediatrics in 2016. [8]

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Eczema, also referred to as atopic dermatitis, is characterized by

recurring episodes of itching, redness of the skin, and rashes. It
affects as many as 30% of children, more than half of whom develop
sleep difficulties. These sleep problems could be more difficult to
treat in children as compared to adults with similar problems
because sleeping pills and anxiolytics are not safe in children.

Having said that, it doesn’t mean that the use of sedatives is a great
idea for adults either. Yet with children, the risks of serious side
effects and dependency are much higher than in adults, and in fact,
most sedatives have contradictions for use in children.

What are better options for kids to help them sleep

well?

Researchers have revealed that supplementation with melatonin

could be a safer and more effective alternative for helping children
with eczema to fall asleep faster and avoid other issues related to
poor sleep hygiene such as academic performance and behavioral
changes like irritability, impulsiveness, aggressiveness, and anger.
Melatonin, being a natural human hormone without the risk of
severe adverse effects, seemed like a good choice for children with
eczema, which is what prompted researchers to study its effects in
detail.

This study was conducted to assess the safety and efficacy of

melatonin supplementation in 48 children between the ages of 22
months to 18 years. The children received melatonin treatment at
bedtime for 4 weeks. The results showed that the children who took
melatonin not only slept better but also experienced reduced severity
of eczema symptoms. Moreover, it was also observed that the kids
who were treated with melatonin fell asleep nearly 21 minutes

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earlier than the kids who were given a placebo. In fact, the total
nightly sleep in the melatonin group increased by an average of 10
minutes, while it reduced by 20 minutes in kids who were treated
with a placebo. This study ultimately provided greater insights into
the safety and efficacy of melatonin not just for the management of
sleep issues but also for chronic skin conditions like eczema.

While the study was primarily focused on checking whether

melatonin supplementation could be advisable for kids with sleep
issues, as an added benefit, it also opened the doors for assessing its
use for relieving the signs of eczema. The research results indicated
that melatonin could be useful for kids, as well as adults, who suffer
from atopic dermatitis not just for improving their sleep but also for
reducing annoying symptoms like itching, redness, and rashes. [9]
[10]

For patients with eczema, sleep disturbances are commonly known

to affect the quality of life, and m has demonstrated powerful anti-
inflammatory effects. To evaluate its efficacy in reducing the
severity of eczema (and, the resulting sleep disturbances),
researchers conducted one randomized study in patients who had at
least 5 percent of their body surface affected by this condition, with
subsequent documented sleep problems.

The study, ‘Melatonin and Atopy: Role in Atopic Dermatitis and

Asthma’ was published in the International Journal of Molecular
Sciences in 2014. It showed that the immunoregulatory action of
melatonin could be effective in the management of allergic diseases.

This study was based on the concept that the abnormal activation of
the immune system in patients with eczema could lead to excessive
free radical production, which might also be associated with reduced
melatonin secretion and depressed activities of other antioxidant
enzymes, as is the case in several other inflammatory diseases.

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Several skin disorders, including eczema, are accompanied by the

activation and infiltration of mast cells that release pro-
inflammatory and vasoactive mediators. There is experimental data
suggesting that melatonin supplementation might inhibit the
development of atopic eczema by reducing the level of total IgE
antibodies and proinflammatory mediators like interleukins. In these
cases, melatonin would regulate and influence the immune response.
This role of melatonin supplementation as an immunomodulatory
agent could be effective in the management of atopic eczema and
help patients derive significant relief from the symptoms in a safe
and effective manner. [11]

Furthermore, the safety of melatonin, our miracle molecule, has been

confirmed in asthmatic patients, and perhaps someday doctors might
consider its routine use in bronchial asthma.

Melatonin may have important immunostimulatory actions in

allergic diseases, in addition to its well-known antioxidant and
cytoprotective effects in several inflammatory conditions. The
activation of the immune system leads to free radical production,
which is associated with decreased melatonin levels and depressed
antioxidant enzyme activities in several inflammatory diseases.
Many skin disorders, including atopic dermatitis, are accompanied
by infiltration and activation of mast cells, which release vasoactive
and proinflammatory mediators.

Allergic asthma is a condition characterized by bronchial

hyperresponsiveness and the presence of IgE antibodies in response
to inhaled allergens; often there are also enhanced total serum IgE
levels. Melatonin could, however, act as a pro-inflammatory agent
in asthma, leading to bronchial constriction. The safety of melatonin
as a sleep-inducing agent has been confirmed in asthmatic subjects,
but its routine use is not recommended in bronchial asthma. [12]

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Can melatonin help to manage the symptoms

of psoriasis?
Melatonin may affect the morbidities that lead to the development
of psoriasis by producing an anti-inflammatory and
immunomodulatory effect. Psoriasis is a common skin condition
that causes the skin cells to build up and form white silvery scales.
This condition is also marked by intense itchiness of the skin and
dryness. This condition is believed to be an immune system problem.
The common triggers include infections, mental stress, and cold
exposure. While the most common symptom of Psoriasis is rashes
on the skin, sometimes the rash may involve the joints and nails.
This indicates that psoriasis could be linked to widespread internal
disruptions in the body that affect tissues other than just the skin.
From my experience, normally always a gut connection in these
cases.

This is why treatment needs to be on a deeper and more

comprehensive level. Working on the body at the cellular level so
that the underlying anomalies affecting the immune system and
sleep issues are corrected. Yet, the immunoregulatory properties of
melatonin have been found to be effective in this regard.

One study has revealed how melatonin acts when administered to

patients with immunological diseases affecting the skin like

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psoriasis. This study, ‘Exploring the Physiological Link between

Psoriasis and Mood Disorders' published in the Dermatology
Research And Practices in 2015 revealed that the anti-inflammatory
properties of melatonin could play a key role in reversing the
pathologies responsible for causing Psoriasis.

This study is based on the concept that inflammatory cytokines are

not the only biomarkers that link depression and psoriasis.
Depression may also be associated with the disruption in the
secretion of melatonin. By reducing the levels of pro-inflammatory
substances like TNF-, IL-8, and IL-6, melatonin might attenuate the
severity of inflammatory disorders like psoriasis. This study further
noted that melatonin dysregulation is common in patients with
Psoriasis Vulgaris.

The disruptions in the cyclic secretion of melatonin would

contribute to the skin inflammation observed in patients with
Psoriasis. Moreover, nighttime melatonin levels are also found to be
significantly lower in people with psoriasis.

It’s also interesting to note that in patients with depression, reduced

melatonin levels coupled with the dysfunctional circadian rhythm
might affect the secretion of the melanocyte-stimulating hormone
that is linked to a high risk of seborrhea and psoriasis. We also see
this with cases with CIRS due to mold exposure and these conditions
are typically linked.

This suggests that supplementing with this miracle molecule might

provide patients with adequate relief from the symptoms of psoriasis
by addressing the underlying problem and not just treating
symptoms.

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Deep sleep and regeneration of tissues and skin

health

Deep sleep is linked to

faster and more efficient
regeneration of the body’s
tissues. Remember we
discussed earlier, that as
you age, your skin loses its
elasticity? It is because the
production of collagen and
elastin reduces as age
increases. Now with aging, even the skin cells begin to degenerate at a
faster rate than new cells can regenerate. And this is why, in spite of the
body’s best efforts, the skin starts looking older and older. I also told you
earlier that one of the best ways to boost your skin health and achieve that
vibrant glow, even during older age, is to use melatonin. Why?

Because melatonin has the potential to act both directly and indirectly on
your skin and stimulate the regeneration of new cells as well as new
collagen and elastin.

I came across one research study that shows melatonin has the ability to
support regeneration in the skin and several other tissues of the body. The
study, ‘Tissue regeneration: Impact of sleep on stem cell regenerative
capacity’ was published in the Life Sciences un in 2018. It showed that the
circadian rhythm of the body orchestrates several cellular functions,
including metabolism, cell division, cell migration, and intracellular
biological processes through how much melatonin the cells receive. The
physiological changes occurring in your body during sleep are believed to
promote the perfect microenvironment suitable for the proliferation,
migration, and differentiation of the stem cells.

While we slumber, our body repairs tissues, cleans out metabolic wastes,
and heals DNA that has suffered inflammation and oxidative stress. Every

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cell in our body is repaired and restored in some way while we are
sleeping. Also, new cells and tissues are created from stem cells and these
cells are then used as a scaffolding for forming new tissue that can replace
the old skin damaged by aging and all the stresses from the preceding days
and weeks.

These effects are mediated directly by the circadian clock genes, as well
as indirectly by hormones like melatonin and cortisol. For instance, when
your body is exposed to darkness in the late evening hours, the melatonin
secretion would be enhanced allowing the stem cells to be activated in
order to replace all necessary cells.

A new study, ‘Circadian Rhythm, and the Skin: A Review of the

Literature’ published in the Journal of Clinical and Aesthetic Dermatology
in 2019 demonstrated how sleep can promote tissue repair and a
regenerative process. That mechanism works primarily through melatonin.
Before we fall asleep, our body begins producing a high level of
melatonin, which signals the production of messenger molecules that can
activate circadian genes promoting tissue regeneration. That’s not all,
melatonin also lowers our body temperature, which in turn, causes our
metabolic activity to become slower to allow more of the available energy
to be channelized into the repair processes. [13]

This correlation between melatonin and the circadian rhythm, and its
effects on tissue regeneration in the skin matrix could provide us answers
to how we can slow down or at least reverse some of the effects of aging.

What these studies suggest, is that the ability of melatonin to promote sleep
and reset the circadian rhythm could reverse the age clock of your skin by
stimulating it to regenerate new cells through your own stem cells. So, if
you sleep well, your skin is going to regenerate faster and produce new
cells that can replace the dead, damaged, or degenerated cells. These new
cells would help your skin look younger, firmer, and more youthful.

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Supplementing with melatonin for gut health

Can improving your skin by taking

melatonin really be that simple?
And, how much melatonin should
you take for good signaling and
gut health?

I would offer that the melatonin

necessary for sleep is much lower
than levels needed for gut health. In fact, I often tell my patients that
we are not giving you melatonin just for sleep with the super
physiological dosing. Seeing as gut melatonin is 400 times higher
than the amount released in the brain through the pineal gland, it
makes sense to use much higher levels than what we use for sleep.
Also, consider the large intestines as the primary location for your
microbiome, and that unless you have SIBO, you should have zero
bacteria growing in your small intestines. That means the melatonin
within the large intestines or colon is what can move the needle most
on a healthy microbiome.

This is what brings us to suppositories and the benefit of

administering melatonin directly to this area. Keep in mind studies
show oral melatonin dosing is only 2.5% absorbed, so using it in an
alternative route of delivery can be more beneficial for this reason.

Next, I feel liposomal delivery can be a great route for those who
would prefer an oral option. We have had some cases where we used
both due to the delivery to both the upper and lower GI tract. Dosing
of 100-200 mg and even higher can be both safe and effective for
improving the gut-sleep-skin axis. It may not be necessary to do this
high-level dosing for long periods and can be alternated for days,
weeks, or months at a time to create a positive internal change that

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can improve even the worst of skin conditions.

Melatonin can also be applied directly to the skin in a cream. This

can be done before bedtime or throughout the day. Even though
some melatonin will be absorbed systemically through the
transdermal route, melatonin used while in the presence of natural
light will not generally lead to tiredness. I have found using a
melatonin-based cream on my face and body to be one of the most
effective strategies I’ve encountered both personally, as well as with
many patients. Nevertheless, for individuals with poor gut health,
high-level dosing with liposomal and/or suppositories should be the
primary options.

Conclusion

It is clear that melatonin can be incredibly helpful for skin health.

When one takes care of their inner health it is expressed in the outer
layers of health as well. That's why melatonin works so well because
it supports so many aspects of inner health and vitality, which
ultimately show with improved skin. Moreover, melatonin also
serves to protect the skin from oxidative stress.

There is also a benefit to applying melatonin as a cream directly to

the skin's surface. MitoZen.com will be introducing a product called
Mitoskin in the near future, which's going to be a combination of
some of the most powerful antioxidants as well as absorbable
melatonin.

I have been personally utilizing this on my own skin and trialing on

close friends and family with spectacular results. I've also found that
supplementing with melatonin has prevented me from burning and
instead manage to acquire a nice tan. All of my life I have gotten
terrible burns, even after being in the sun for 30 or 45 minutes. Now,
I can be out in the sun virtually all day and still not burn due to
melatonin's protecting abilities.

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Chapter 14: Melatonin Toxic
Factors
EMF, Light Pollution & Drugs That Deplete
Melatonin

Melatonin is just as useful for our body as it is vulnerable to the

effect of adverse factors like EMF, “melatonin toxic” substances,
and light pollution. When vitality and overcoming disease are the
priority of your life, it becomes equally important for you to protect
your melatonin.
Melatonin is produced in your pineal gland, the cells in your gut,
and each and every cell in your body to deal with stress, and
therefore it’s important to consider a method to protect it against
“Melatonin Toxic Factors”. These melatonin toxic factors are
known to cause immense damage to your health simply by depleting
your melatonin and robbing you of your primary stress protection
and restorative sleep.
Let's take a deep dive into “Melatonin Toxic Factors” and explore
what they are and how we can make changes in our lives to improve
melatonin, vitality, life span, and overcome diseases.

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What are melatonin toxic factors?

If you have trouble with sleep or find

yourself at the receiving end of
infections just too frequently, or are
suffering from one of many diseases
linked to inflammation or oxidative
stress, you might consider melatonin as
a supplement. Melatonin is secreted in
the pineal gland and all cells of the body
in adequate amounts. This is the body's own natural way of
enhancing its stress defense mechanisms. But, this melatonin,
though produced in adequate amounts, may simply get depleted,
used up, or destroyed if you are not careful enough.
Sometimes, your pineal gland just may not produce enough
melatonin. This can occur if your lifestyle and habits do not allow
this gland to function optimally. In short, it all depends on how you
work toward improving the melatonin levels and preventing the
depletion linked to reduced secretion and increased usage.
Meaning that you need to be aware of these factors first so that you
can adopt measures to protect yourself against them. Here are some
of the main toxic factors that we’ll be discussing throughout this
chapter:
● Light pollution (avoiding blue and green lights after sunset)
● EMF (Electromagnetic Pollution)
● Drugs (melatonin Toxic drugs)
● Food and Nutrients (natural substances that are Melatonin toxic)
● Sleep habits and environment (body temp, bed, pillow.
● Dietary and Dinner time factors (foods that are melatonin toxic &
eating too late)
● Sleep Drugs that prevent deep and REM

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Too much artificial light can reduce melatonin

secretion

We are in a new era where we

have multiple artificial light
sources bombarding our
retinas 24/7 that simulate the
effects of natural light and
influence an active “wake”
response, thus decreasing
your production of melatonin
in the same way natural
sunlight would do. Natural
sunlight in the morning and during the day is the most powerful
signal to building up melatonin, and darkness is the primary signal
to releasing this molecule so that it can exercise its function by
helping you with cellular stress,
chronic infections, cancer,
toxins like heavy metals,
regeneration of your body, and a
healthy brain and nervous
system. For instance, if you have
typical lights in your bedroom,
you’re getting lots of blue and
green within that white light.
This will confuse your nervous
system into thinking that it is still
the daytime, and it will release
hormones such as cortisol that
will ramp up your wakefulness.
Your eyes can’t tell the difference between artificial lights and
natural lights. Therefore, if the lighting arrangement in your house
is too bright, the rays entering the eyes will send signals to your
brain indicating it is still daytime, when, in reality, it is nighttime.
This would disrupt the circadian rhythm and melatonin secretion.

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Exposure to these lights creates a sense of alertness in the brain,

encouraging it to modify the body’s functions and hormonal
signaling in a way that’s favorable for you during the daytime,
however, this is catastrophic toward sleep and melatonin release.
Modifying the lighting arrangement in your house, especially in the
areas where you spend time during the evening becomes a very
important melatonin enhancing strategy. For example, I would
advise you to have red lights in your bedroom so that when you go
to bed, your brain would be signaled to get ready for sleep according
to the reduced exposure to the blue and green light spectrum, thus
signaling the secretion of melatonin to be normally released as it
would ideally happen during the nighttime.
Another “melatonin must'' may be to place dimmer switches around
the house, so that you can dim the lights during evening hours when
you’re not doing any form of activity that requires brightness.
Companies also make Bluetooth-enabled lights that you can control
from your phone! How convenient right?
The dimmers are not the best alternative though,
red-light lamps are, as I have found for my own
home. What I have
done is purchased
cheap remote control
plug outlets adaptors.
You can get these
online at Amazon.com
for $20-30. While you're
online get yourself some
red-light bulbs as well to
go into your lamps. Lamo
are easy to find at lowes or
home depot. See the images here of my own home
and how I set my home up for nighttime lighting.
See the red rope light that I have attached with
plastic ties to the railings both inside and outside of
my house, so I don't have to be exposed to bright
light after the sun goes down. This protects my
circadian rhythm and natural melatonin production.

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If your bedroom lights are too

bright, when you go to sleep,
these light rays would enter
your eyes and reach the retina
where signals will be sent to
the brain to shut down the
melatonin production. Once
melatonin production
declines, you will find
yourself feeling more alert
without any feeling of sleepiness. Without
adequate levels of melatonin secreted in your
brain, you will have difficulty falling asleep.
This highlights the remarkable effects the
bright lights vs dim lights create on the
melatonin levels in your body.
Now, let's talk about technology and how it
affects your melatonin.

Technology Pollution:

Although technology is
supposed to be helpful, and
in many ways is, it is also
dangerous. This is more so
the case when it comes to
the latest technologically
advanced. that allow us to
have access to a whole
entire world of information,
right at our fingertips. I’m
talking about smartphones, computers, laptops, smart TVs, and everything
else in between. These technologies or commodities have revolutionized
our lives in so many ways, but they’ve most definitely caught our health
and priorities off guard.

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These gadgets are harmful primarily due to the blue light they emit. This
blue light can do much more damage to your melatonin levels. If you
haven’t heard of blue
light, let me first
introduce you to what
it is and how it affects
your melatonin and
sleep.

I came across research

that was published in
Molecular Vision in
2016 which highlights the effects of blue light quite well. This study,
‘Effects of blue light on the circadian system and eye physiology’ was
aimed at assessing the impact of light-emitting diodes (LEDs) on sleep and
melatonin secretion. This study also analyzed the effect of blue light on
the body’s internal biological clock called the circadian rhythm by
interfering with the physiology of the eyes.

Ultimately, the study concluded that LEDs that have been commonly used
to provide illumination in domestic, commercial, and industrial
environments can hamper melatonin secretion significantly. LEDs are also
used in computers, televisions, smartphones, laptops, and tablets. The light
emitted by these LEDs often appears white to us, yet, the truth is that LEDs
have a peak emission range of blue light (400 to 490 nm), and this is the
reason why they are called blue light.

The accumulating evidence has indicated that the exposure of the body to
blue light can affect several physiologic functions, by inducing
photoreceptor damage. This is the reason why it is important to consider
and analyze the spectral output of the LED-based light sources to avoid
the dangers associated with blue light exposure.

This study demonstrated that blue light from smartphones, television

screens, and laptops emitted in the range of 460 to 480 nm can do
significant damage to our sleep pattern by reducing melatonin secretion
and causing disruption in the circadian rhythm.

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As I mentioned earlier the exposure to bright lights in your living room

and bedroom during late evening hours could prevent you from sleeping
well. These light rays can enter the eyes and suppress melatonin secretion
by signaling the brain that it is daytime.

But, the impact of blue light

from electronic gadgets like
smartphones is much higher
than the effects of these bright
lights. It’s not uncommon for
adult men and women and even
children to stay glued to their
smartphones for different
purposes during the evening
hours. Some of you may be using smartphones to check out the latest news
and some might be just watching videos and movies on the OTT platforms.
In children, it is commonly observed that they spend a lot of time playing
games on smartphones, laptops, or tablets before bedtime. Whereas
teenagers are likely to spend their time catching up with friends and
chatting with them on social media platforms. These activities can increase
your exposure to blue light at a time of the day when you should ideally
be shutting down your exposure to ANY form of screen-based technology.

These habits can cause a sharp decline in the production of melatonin in

the pineal gland as it is primarily determined by the amount of exposure
to light and affected by the day-night cycle of the earth. As a result, you
will not only experience difficulty sleeping but also be deprived of the
natural antioxidant, anti-inflammatory, and immunity-boosting benefits of
this sleep hormone.

Consistent with these results, it was also found that in older people, acute
or short-term exposure to blue light could significantly decrease their
alertness and suppress their sleep and melatonin production more severely
as compared to the younger people.

The decline in melatonin secretion in elderly individuals might worsen

inflammation and oxidative stress in the brain tissues putting them at risk
of degenerative diseases like Alzheimer's and Parkinson’s. This also

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explains why they might experience a lower level of alertness when they
use smartphones during nighttime. The blue light from these devices can
reduce the efficiency of brain functions and trigger faster cognitive decline
due to which their memory, attention span, focus, and ability to stay alert
are affected. This is another very important reason why everyone,
including older people, should minimize the use of devices that release
blue light. [1]

Let me reveal a few more ways by which blue light can affect your
health and increase your risk of diseases.

Top health risks of blue light:

● Insomnia
I already told you that blue light exposure, especially at
night, can lower the secretion of melatonin, which controls
your sleep-wake cycles. The brighter the light and the longer
the time of exposure, the lesser would be the melatonin
secreted in your brain. Needless to say, the lowered
production of melatonin would contribute to the risk of
insomnia as a result of which you will find yourself staying
awake for several hours even after you have switched off
your smartphones, ultimately feeling sleep deprived and
unrefreshed!

● Stress and depression

This duo of mental health diseases could be right around the
corner waiting for you if you're not careful and take steps to

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minimize your exposure to blue light in the evening and at

night. The exposure to blue lights could lower melatonin
levels causing stimulation of the release of the stress
hormone called cortisol in the nervous system. This hormone
is already infamous for making us feel stressed out even
without any apparent reason. Cortisol would make you prone
to anxiety disorders and even depression. So, it could be
more mental health issues for you if you’re not serious about
reducing your exposure to blue light!

● Weight gain
If you’re trying to lose weight, blue light could create
obstacles for you. I say this because I recently came across an
interesting study, ‘Night shift work at specific age ranges
and chronic disease risk factors’ that has specifically shown
how blue light contributes to obesity and prevents weight
loss. [2]

Exposure to blue light could reduce melatonin secretion in

your brain and create imbalances in the levels of hunger
hormones, such as ghrelin and leptin, thus enabling
unwanted weight gain. The decline in melatonin production
and the disruptions in the levels of ghrelin and leptin could
increase your hunger, slow down fat burning, and reduce
calorie use by your body. As a result, you could find losing
weight much harder, or nearly impossible. Additionally,
exposure to blue light may also increase your BMI, waist
circumference, and height ratios.

● Increases diabetes risk

Exposure to blue light could further worsen your risk of
diabetes and diabetic complications, both directly and
indirectly. Blue light could raise your risk of diabetes by
affecting carbohydrate metabolism. It might further prevent

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the efficient utilization of sugars from foods and keep your

blood glucose levels higher making you more dependent on
insulin injections and oral anti-diabetes drugs.

Blue light may also create disturbances in your blood sugar

levels by preventing the optimum secretion of melatonin.
The reduced melatonin levels could affect the synthesis of
insulin in the pancreas. At the same time, it may also worsen
insulin resistance. Both of these effects could cause you to
have persistently elevated blood sugar levels putting you at
risk of diabetes and more serious complications of this
disease.

● Affects cardiac functions

Blue light might even affect the functions of vital organs like
the heart and brain. Blue light could disrupt your sleep
affecting the internal biological clock of your body. This
could put muscle cells of the heart out of sync increasing
your risk of cardiac diseases, such as myocardial infarction
(heart attacks), and cardiomyopathies (enlargement of the
walls of the heart).

The cardiac functions would also be hampered due to the

loss of melatonin. The reduced melatonin secretion
following blue light exposure would result in the decline in
the amount of energy received by the cardiac muscles
making them less efficient. This would reduce the efficiency
of the heart and prevent it from pumping out enough blood
during each contraction. This effect of reduced melatonin on
the heart functions can affect the health of your heart, as well
as other vital organs like the brain, kidneys, and gut leading
to serious implications. This could be easily avoided by
protecting your melatonin by reducing your use of
smartphones and laptops at night.

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● Affect your eyesight

Exposure to blue light, specifically at night might contribute
to vision loss, by triggering the development of macular
degeneration. It may bring about the destruction of cells in
the retina. The blue light entering your eyes may also trigger
inflammation of the delicate retina. The retina is the surface
or a mirror on which the image of what is there in front of
you is formed. The damage to retinal tissues could affect
your eyesight and increase your risk of macular
degeneration.

The reduced melatonin level caused due to exposure to blue

light may also increase your risk of another eye disorder
called glaucoma. In patients with glaucoma, the functional
cells in the retina tend to become susceptible to the damage
caused by blue light causing a faster worsening of the
condition.

Moreover, if you have had cataract surgery recently, you

have one more reason to protect your melatonin levels
against the effect of blue light. Watching television and
using smartphones should be strictly avoided for a few days
or weeks after cataract surgery, in order to enable the tissues
of the eyes to heal completely. Exposure to blue light from
electronic gadgets might slow down recovery after cataract
surgery, putting you at the risk of postoperative
complications.

These are just some of the many negative health effects of

blue light. You can protect your melatonin levels by
minimizing your use of these gadgets, especially after
evening hours and at night.

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How to protect your melatonin from the

harmful effect of blue light?
Now that you have realized how dangerous blue light can be, you must be
worried thinking about how to keep yourself safe and protected from it.
Here are some tips that would help you safeguard your melatonin from
exposure to blue light:

● Avoid extended exposure to artificial lights after evening hours

and sunset by closing the curtains and shades to block the
streetlights.
● Use dimmer lights or set up red light lamps throughout your house
after dinner to lower the light exposure.
● ‘Power Down’ and avoid the use of electronic gadgets at least 2
hours before bedtime, and that includes your smartphones and
laptops too.

How does the electromagnetic field interfere

with melatonin secretion?
Electromagnetic field or EMF is another culprit responsible for
causing depletion in the levels of melatonin secreted in your body.
The dangers of EMFS are just as severe as those caused by blue light
emission from electronic gadgets. But before we jump into the
negative effects of EMFs, let us first find out what exactly EMF
means.

What are electromagnetic fields?

Electromagnetic fields refer to the combination of invisible
magnetic and electric fields of forces that exist in our surrounding
atmosphere. These forces are generated by natural phenomena such
as the Earth’s magnetic field and also by human activities, primarily
through the use of electricity. Power lines, mobile phones, and
computer screens are some examples of equipment that generate and
emit electromagnetic fields.

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Some of the man-made

electromagnetic fields
are able to reverse their
directions at a regular
interval of time. The
frequencies of these
fields may range from
extremely high radio
frequencies, as in the
case of mobile phones, intermediate frequencies from computer
screens, or extremely low frequencies that are generated by power
lines.

The term static is used to refer to the fields whose frequencies do

not alter with time. They usually have a very low frequency. Static
magnetic fields are commonly used in medical imaging tests and are
generated by appliances that use a direct current. This information
goes on to indicate how difficult it is for us to avoid exposure to
electromagnetic fields and can therefore develop related
complications due to continual bombardment.

After an in-depth review of

various scientific reports, it
is obvious that there exists a
close link between exposure
to electromagnetic fields and
the risk of adverse health
effects.

Let’s take a look at how

EMFs could affect your
melatonin levels and why it
is necessary to protect
yourself against these
invisible forces:

A comparative study, ‘Pineal melatonin level disruption in humans

due to electromagnetic fields and ICNIRP limits’ published in the

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Radiation Protection Dosimetry in 2013 has revealed that the

exposure to EMF could be highly counterproductive for the
melatonin levels secreted in the pineal gland.

This study recognized the classification of electromagnetic fields as

possibly carcinogenic agents for humans by the IARC (International
Agency for Research on Cancer). IARC issued a warning indicating
the potential of EMFs to transform normal cells into cancerous cells.
Also, owing to the higher utilization of electricity in our day-to-day
life, exposure to EMF with a power frequency in the range of 50 to
60 Hz could be unavoidable.

This study was aimed at assessing whether exposure to EMF could

affect melatonin levels and worsen the likelihood of developing
cancers further. The finding of this research concluded that man-
made EMFs might influence the functions of the pineal gland. The
pineal gland is likely to sense or perceive the EMFs as light, and as
a consequence, it may be encouraged to stop melatonin production.
This incorrect perception of EMFs by the pineal gland is considered
to be a major factor responsible for the decline in the production of
melatonin.

In this review, more than 100 experimental data points from animal
and human studies assessing the changes in the melatonin levels
following exposure to the power-frequency magnetic and electric
fields were analyzed. The results were compared with the maximum
limit recommended by the ICNIRP (International Committee of
Non-Ionizing Radiation Protection). Moreover, a comparison of the
results was made with the findings of existing experimental studies
to assess the biological effects of magnetic fields to quantify the
severity of complications.

The results have drawn attention to the importance of limiting

exposure to EMFs. The observations made by this study were
consistent with that of earlier research conducted to evaluate the
effects of EMF on cancer risk and melatonin production.

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It was further confirmed at a later

date that varying degrees of
disruptions in melatonin secretion
may occur due to the exposure to
EMFs of weak frequencies. And
this may possibly lead to more
severe long-term health effects in
humans. [3]

Look at the penetration of EMF into the brain when one uses a cell phone.
The penetration is well within the range to be affecting the pineal gland.
This can have detrimental effects on melatonin which affects the overall
circadian rhythm. It seems children are more susceptible to this than older
adults.

Protecting yourself at night while you sleep

form EMF
Using a carbon-based paint in your
bedroom is one option to minimize the
EMF exposure while you sleep which
could protect your melatonin as well as
other harmful effects of EMF exposure. I
painted my bedroom while we were
remodeling it whereas even before the
flooring went in the carbon paint was coated around all of the walls and
floors. I find it hard to get a good signal in my bedroom which is
sometimes inconvenient, but it is an inconvenience I am willing to live
with knowing how harmful EMFs are to our health. Keep in mind if you
do this that you want to minimize the
use of your cell phone within the space
as the radiation coming off of your
phone or ricochet and bounce around
the room a bit more than typical. I still
occasionally use my phone in my
bedroom however I am definitely
putting it on airplane mode before bed

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every night. Like many people I use my cell phone as my alarm clock so
it sits next to my bed. Putting your phone on airplane mode at night is
important of course unless there is some sort of need for you to be
communicated with. For instance some people need to leave their phone
on in case their children might call late in the evening if there was some
emergency. Outside of that I think the phone should be turned off.

There are companies that make

clothing that protects and shields
from EMF. They also produce
cabs that might be important to
shield your brain and pineal gland
in particular. This might be a
viable option for some people especially at night. If you were exposed to
a lot of EMS during the day, then these could be something to consider as
well but I feel that nighttime is probably the most important where we
should be shielding and protecting ourselves from these harmful
microwaves.

How to properly set up your bedroom for

maximum melatonin and sleep quality.

Take a look at the image here of my bedroom

showing a lamp with a red-light bulb and remote
control are located where I can reach it from in my
bed. The remote controls
all the lights in the
bedroom and down my
stairs to the living room.
find the remote controls to
be very helpful so I can
simply lean over and turn them off when I'm
ready to go to sleep. Also the red lamp that I
could reach from my bed is nice so that I could
turn it on and off by hand and see my way to the

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bathroom late at night. This way I don't have to turn on any bright lights
containing blue or green colors which will tell my brain that it is morning
which will interrupt my sleep and melatonin production.

Important points to consider for EMF

protection at night.
● If you use your cell phone as an alarm clock, then turn it on
airplane mode at night.
● I'm sort of shielding such as a carbon-based paint for your
bedroom or a silver lining canopy.
● Turn off your Wi-Fi router at night. Consider the placement of
your Wi-Fi router to minimize exposure as well.
● Be careful of electronics that might be around your bed that he
met a Wi-Fi signal. An example is CPAP machines or other
electronic gadgets now have Wi-Fi continuously being admitted.
● Don't wear any EMF admitting wearable devices such as the new
watches from Apple. If possible, turn them on airplane mode if
you're using them for tracking sleep.
● Consider EMF shielding clothing and caps that will protect at
night while you're sleeping.

Should you avoid sunlight completely to

protect your melatonin?

So far, we’ve discussed how you can

avoid exposure to bright lights in order
to protect your melatonin levels. But,
protecting your melatonin is a bit
tricky. It is not as simple as just
avoiding exposure to bright lights or
EMFs. The negative effect of bright light on melatonin production is
actually limited to the late evening hours or nighttime. So, it would be very

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wrong to assume that you need to avoid sunlight completely. In fact, doing
so might put you at a risk for other health issues like vitamin D deficiency.
So, ultimately this all comes down to how to regulate your exposure to
sunlight so that it is neither too high nor too low.

In order to increase your melatonin naturally, your body requires a certain

amount of sunlight. This is because sunlight can stimulate the secretion of
another hormone called serotonin, which is a precursor of melatonin. After
sunset, the leftover serotonin could be converted into melatonin, which is
why you need to have ample exposure to sunlight during the daytime to
make sure enough serotonin is created to support the production of
melatonin later.

Sunlight exposure may also stimulate the secretion of cortisol that could
keep you awake during the daytime so that by the time night approaches,
your body would circle back to the phase of sleep and start stimulating
melatonin once again.

All these mechanisms involved in the secretion of melatonin, serotonin,

and cortisol occur in a cyclical manner depending on the day-night phases
created by the earth's rotation. Let me explain this with the help of a study
that has beautifully described the importance of sunlight for maintaining
health.

This study, “Benefits of Sunlight: A Bright Spot for Human Health’ was
published in the Environmental Health Perspectives in 2008. The purpose
of this study was to establish the importance of exposure to sunlight for
maintaining bodily functions and bust the common misconception that sun
rays are harmful to our health. Moreover, this study was also focused on
revealing both the sides of sunlight exposure - the advantages as well as
the disadvantages - so that people can make the right decisions about how
much exposure to sunlight is necessary. This approach is expected to help
us derive the benefits of sun exposure without experiencing any adverse
complications like sunburns and skin cancers.

This study is based on the fact that humans are diurnal creatures,
programmed to be outdoors when the sun is shining and at home in bed
during the night. This is the reason why melatonin production begins when

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it becomes dark and stops upon the optic exposure to the bright daylight.
This pineal hormone is considered the key pacesetter for most of the
body’s activities related to the circadian rhythm. Furthermore, the same
study also confirmed that the diurnal variation in the levels of melatonin
also plays a key role in countering cancer, inflammation, infections, and
auto-immunity.

When our body is exposed to sunlight or bright artificial lights in the

morning, the nocturnal melatonin production in the evening tends to occur
a bit sooner. This can allow us to enter into a deep phase of sleep more
easily once we hit the bed.

Melatonin secretion also shows seasonal variations that could be relative

to the availability of sunlight, with the hormone being produced for a
longer duration of time in the winter months as compared to that in the
summer. The melatonin secretion phase advancement caused by the
exposure to bright sunlight in the morning could be effective against
insomnia, seasonal affective disorder (SAD), and premenstrual syndrome.

The secretion of serotonin, which is a melatonin precursor, is also affected

by the exposure to daylight. Serotonin is normally produced during the
daytime and is converted to melatonin later when it becomes dark. High
melatonin levels usually correspond to longer nights and shorter days,
while a high serotonin level in the presence of melatonin usually reflects
shorter nights and longer days indicating longer exposure to UV radiation.
Also, moderately high levels of serotonin might lead to an improvement
in moods allowing you to stay calm yet focused.

This is why; seasonal affective disorder is commonly linked to lower

serotonin levels during the daytime as well as with the phase delay in the
melatonin production during the nighttime.

The study concluded that our skin can also produce serotonin and convert
it into melatonin and that several types of skin cells have receptors for both
melatonin and serotonin. This suggests exposure to sunlight is essential
for the production of serotonin.

Our modern-day penchant for indoor activities and staying up past dusk
could reduce nocturnal melatonin production, taking our sleep-wake cycle

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far away from being healthy and robust. Also, the sunlight our body can
receive from being outside on summer days is much brighter than what we
are likely to experience by being indoors. For this reason, it’s important
for people working indoors to get outside periodically. This can have a
major positive impact on the melatonin rhythms and result in
improvements in sleep pattern, mood, energy, and overall sleep quality.

Moreover, people in jobs that prevent them from having adequate sunlight
exposure can use full-spectrum lighting to stimulate serotonin secretion.
Going shades-free while in the sunlight, even for just 10 to 15 minutes,
could confer significant health benefits. [4]

Seasonal changes & melatonin

Seasonal change is another factor that can affect your melatonin levels.
During the fall and winter, there is less light. So, your body will naturally
produce a high level of melatonin.

At some point or another, you must have experienced how hard it is to get
out of bed during the cold winter months. Don’t worry, we’ve all had
those days!

But, interestingly enough, it’s not just the cold that makes you feel like
staying in bed for longer. This is where melatonin comes into the picture.
The increased secretion of melatonin makes you feel sleepy causing you
to curl up in bed until late in the morning hours. Now you can explain
away those lazy days without feeling guilty, right? But, as the season
changes, your body might have a harder time adjusting to the change in
the levels of sunlight exposure. For example, as spring and summer
approach, you might find yourself staying awake for several hours at night

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without any desire to sleep. This may happen due to the decline in the
secretion of melatonin during the bright spring and summer days.

The increase in your body’s exposure to sunlight, which is not only

brighter but also shines for longer, would dip your melatonin levels
sharply. As it is bright and sunny outside until late in the evening, your
brain won’t send signals to the pineal gland to start secreting melatonin.
As a result, the time of the secretion of melatonin would also be delayed.
So, instead of, say at 4 pm or 5 pm on winter days, your body will start
secreting melatonin at about 6 pm to 7 pm on summer days.

Our bodies will need time to adjust to the new routine based on the reduced
sunlight exposure during the daytime of this season. So, even after the
winter or fall begins, you’ll notice how you’re unable to sleep well, at least
for a few days. Later, as your body gets attuned to the reduced exposure
to the brightness during the daytime or the reduced duration of the daylight
availability, it will start producing more melatonin. Studies aimed at
checking the impact of different seasons and their effect on melatonin
levels have confirmed these findings. One study, ‘Melatonin and seasonal
rhythms’ published in the Journal of Biological Rhythms in 1997 has
helped to analyze the change in the secretion of melatonin in the pineal
gland due to seasonal variations.

According to this study, the seasonal changes in the lengths of the nightfall
(scotoperiod) can induce a parallel or proportional change in the duration
of the secretion of melatonin. This study has shown that when the duration
of nighttime increases, as happens during winters and fall, there is also a
rise in the duration for which melatonin is secreted in the pineal gland. The
increased duration for which the body is exposed to the darkness due to
the late sunrise and early sunset during these seasons allows the body to
secrete more melatonin.

These variations in the duration of nocturnal melatonin secretions, in turn,

might trigger a seasonal change in your behavior. It is primarily found to
affect your sleep-wake cycle.

Moreover, this study confirmed that the response of the RHP

(retinohypothalamic-pineal) axis to bright light is highly conserved in our

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bodies. So, in a human body, the secretion of melatonin is interrupted

when we are exposed to lights during the nocturnal phase of its secretion.
This means in most individuals, the RHP axis is capable of detecting the
change in the length of the nighttime, allowing the body to make a
proportional adjustment in the duration of the nocturnal secretion of
melatonin. This is why you will find each person responding to the change
of season in a different manner. While one person may find it too difficult
to fall asleep during the initial days of the summer months, some people
may be able to adjust to the change of season with ease.

This variation in the response could be attributed to the body's ability to

improve the duration and amount of melatonin secretion in spite of a
limited or reduced amount of darkness the body is exposed to. So, even
when the sunlight is bright, the body is capable of regulating the response
of the RHP axis so that the secretion of melatonin in the pineal gland is
restored. This can allow the person to sleep well even during the summer
months.

Moreover, the RHP axis also helps to regulate the production of the type
of melatonin messages that the body can use to trigger the seasonal change
in behavior of a person in terms of the circadian rhythm. This has been
shown in naturalistic research, in which the melatonin profiles of a group
of participants were compared in winter and summer, and even in
experimental research in which the melatonin profile was compared after
long-term exposure to the varying duration of artificial "nights".

These studies revealed that individuals living in a modern urban

environment tend to differ in the degree or extent to which the intrinsic
duration of the secretion of melatonin can respond to the seasonal change
in the duration of the solar night. The duration was measured based on the
exposure of the body to constant dim light. It was found that the change in
the intrinsic duration of the production of melatonin that is induced by the
change in the scotoperiod can be significantly correlated with the change
in the intrinsic timing of the offset of the secretion of this hormone in the
morning and is weakly correlated with the change in the intrinsic timing
of the onset of its secretion in the evening.

This finding has suggested that the differences in the ways in which an

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individual is exposed to the morning light in different seasons could affect

his responsiveness to the change in the duration of experimental or natural
scotoperiods. So, as the duration of the nighttime or darkness changes
when the season transitions from the summer to the winter or vice versa,
the body would modify the secretion of melatonin both in the morning and
evening to adjust to the reduced or increased duration of the nighttime.

Nevertheless, the response of each individual to the change in the

melatonin secretion and the subsequent response to adjust the melatonin
levels may be different.

This indicates that the human RHP axis is clearly capable of detecting the
change in the length of the nighttime. But the body may take a variable
time to adjust to the change in the season, and until it’s attuned to the new
season, the person may continue to experience the same sleep-wake cycle
that he was used to before the transition into the new season. [5]

The point here is the melatonin levels are bound to change - both increase
or decrease - each time the weather changes. But, your body will take its
own time to adjust to the change in the amount of exposure. Meaning, it
might take you about a week or two to start getting better sleep as your
body starts producing more melatonin when the season changes from
summer to winter.

The problem here is that it

isn’t possible for us to avoid
the change of season. If you
are struggling with sleep
issues or want to have your
melatonin levels improved to
enhance your body's ability
to fight inflammation or
oxidative stress, there is little
you can do to stop the seasons from changing. If this is something that’s
bothering you, then the answer is simple. You may not be able to change
the weather, but you can definitely trick your body into believing it’s the
winter season by simply reducing your sunlight exposure after the late
evening hours. If you suffer from insomnia, my advice is to avoid going

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outdoors in the evening hours. It's best for you to stay indoors after evening
hours as this is where you can manage the lighting arrangements so that
your body is not exposed to bright lights. Moreover, I normally advise my
patients to use dark shades for their windows. That way, after say, 5 or 6
pm, you can pull down the shades so that the bright light from outside,
whether sunlight or streetlights, doesn’t enter your house.

The reduced exposure to lights, even when there is bright sunlight outside,
will help your body produce good amounts of melatonin. So, when you
actually hit the bed, your pineal gland would have secreted enough
melatonin allowing you to rest peacefully. Lastly, there’s one more thing
you can do in the summer months to protect your melatonin levels, and
that is to minimize your use of smartphones and laptops. We already
discussed the reasons why these gadgets are not good for your melatonin
production. The blue light from these gadgets can prevent your brain from
sending signals to the pineal gland to start secreting melatonin. This effect
could be more severe in the summer months. Therefore, as the season
changes from winter to summer, it's time for you to further minimize your
use of smartphones, laptops, and similar tech that has bright screens.

To sum things up:

Seasonal changes require you to switch up your routine so that the effect
of change in light exposure does not have any adverse impact on the
melatonin secreted in your pineal gland. You may find it difficult to follow
the tips laid out in this chapter in the beginning. But, once you get a hang
of it, you’ll know exactly what you need to do for a smooth seasonal
transition.

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Too Much Caffeine

This probably will not come as a surprise to most of you because we

already know that caffeine is a stimulant and it can prevent us from
sleeping well. You’ve most likely heard doctors advising patients to limit
their intake of coffee to ensure they can get some sound sleep.

Not only does it provide a wake-promoting effect that we crave, but also
makes us feel more alert and awake. This is why; coffee shops have
become a place for business meetings and social gatherings making the
beverage easily available for us at any time. Unfortunately, the easy
availability of coffee has also made today's generation of young men and
women sleep-deprived. In fact, the survey conducted by the National
Coffee Association of the U.S.A. has found that nearly 83% of Americans
drink coffee several times a day.

Moreover, an average cup of coffee contains anywhere from 50 to 560 mg

of caffeine. And the grand-size cup of coffee often contains more than 300
mg of caffeine. The caffeine in coffee is quickly absorbed into the
bloodstream. Coffee’s half-life is about 3.5 to 5 hours as discovered by the
sleep medicine researchers and in a study published in the journal of Sleep
Medicine. Also, caffeine can start to affect our bodies quite quickly, in
fact, it can reach the peak level in your blood in just 30 to 60 minutes of
consumption.

After drinking a cup of coffee, you

can expect to stay wide awake for at
least 5 hours or even more. This
clearly means even if you have a cup
of coffee at say 5 pm or 6 pm, you’ll

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still experience difficulty sleeping if you go to bed around 9 or 10 pm.

But what most people don’t know is that caffeine can also suppress
melatonin secretion, which is actually why it can help people to stay awake
up. Drinking coffee to refresh yourself in the morning or after a stressful
meeting is absolutely fine. But, to drink a cup of coffee in the evening just
to feel better is a strict no.

The mechanism of action of caffeine is the antagonism or inhibition of the

activity of adenosine receptors in the central nervous system. Adenosine
is a kind of sleep promoter. It works by increasing melatonin secretion in
the pineal gland. When you drink a cup of coffee, the caffeine in it blocks
adenosine from binding to its receptor promoting wakefulness. It is clear
that this effect of caffeine could cause you to remain alert for several hours,
and thus the overall quality and duration of your sleep would be affected.

Because even a cup of coffee would

be enough to reduce your melatonin
secretion. And this would not just
keep you wide awake, but also
prevent you from experiencing any
of the other long lists of benefits that
this sleep hormone has to offer. If
you’re curious to know what happens to your melatonin when you drink
coffee, just read the next research example.

The study, ‘The effects of coffee consumption on sleep and melatonin

secretion’ published in Sleep Medicine in 2002, specifically examined the
effects of caffeinated beverages on the quality of sleep, based primarily on
how it affects melatonin secretion.

Melatonin secretion is regulated by neurotransmitters, which can be

affected by the excessive consumption of caffeine. In the first part of this
study, 6 volunteers were asked to drink either regular coffee or
decaffeinated in a double-blind manner. This idea was to not get
influenced or prejudiced due to being aware of what they drank.

Later, after 7 days, they were asked to drink the alternate beverage. The
sleep parameters of these participants were assessed with the help of

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actigraphy. The urine samples of these participants were assessed every 3

hours for the quantitation of 6-SMT (6-sulfatoxymelatonin), which is the
main metabolite of melatonin passed in the urine. In the 2nd part of the
research, it was found that the subjects, who drank either regular coffee or
decaffeinated beverage, had differences in the amounts of 6-SMT in the
urine.

The results of this study indicated that drinking caffeinated coffee caused
a sharp decline in the total duration of sleep and the quality of sleep,
compared to drinking the decaffeinated beverage. There was also an
increase in the duration of sleep induction in participants who drank
coffee, as compared to those who drank decaffeinated coffee. The
caffeinated drink caused a decline in the excretion of 6-SMT in the urine
throughout the next night.

These results have confirmed the widely held belief that the consumption
of coffee can interfere with the quantity and quality of sleep. In addition,
it was also found that the intake of caffeine can decrease the 6-SMT
excretion. This suggests that people who suffer from sleep issues should
strictly avoid caffeinated beverages during the evening hours.

Conclusion

Melatonin plays an important role in the protection of the pineal

gland and the chemistry involved in melatonin release.

I think some of the easiest lifestyle changes to make are the ones
described in this chapter, such as setting your house up with red light
lamps and remote controls and using blue-blocking sunglasses when
the sun goes down while you're watching TV or looking at your
cellphone or computer screen. Turning the brightness down on your
computer and cell phone screen is also important in addition to the
blue glasses. I only wish we could turn the brightness down on our
television sets, but it does not seem like this technology has caught
up with our health needs quite yet.

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Try to minimize the EMFs at your home office by using old fashion
wires to connect and keep your cell phone away from you and off of
your body, especially when you're not using it. Another easy thing
to consider is turning off your Wi-Fi router at night. Moreover, there
are lots of exciting new products being brought to market, such as
carbon-based paint as well as silver-lined canopies that can be used
to protect you from harmful EMFs while you sleep.

Most importantly, go out and get sun during the daytime without
sunglasses and avoid artificial light at night to improve your
circadian rhythm and melatonin release. We live in such a stressful
high-tech environment which includes light and EMF pollution,
among other stressors, that have negative effects on our melatonin
production.

Even with all of the lifestyle changes described in this chapter, it is

obvious that supplementing with melatonin makes sense, as just the
aging process itself and having birthdays is enough to produce
massive declines in melatonin. When you stack those natural age
declines on top of all of these other subsequent stressors you start to
set the stage for a lot of the diseases we are seeing in our
technologically advanced and industrialized world.

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Chapter 15: Melatonin For
Children
Autism, ADHD, Infections & Behavior

My own “Pain to Purpose” story.

I have a special connection with this chapter as I feel if melatonin was

given to me as a child, it would have been beneficial in more than one way.

After being expelled from two schools I was placed into special education
classes and diagnosed with ADHD and dyslexia. I remember my mother
crying while speaking with the administrator as we both sat around the
conference table as they told her there were no other options available for
me. We lived in Hawaii at the time, and little did I know I was about to be
placed into classes with kids much worse off than I was.

I endured these special education classes until I was taken out by my

parents just before high school. The system still wanted me in these
classes, but I had plenty enough of being teased and looked down upon by
the other kids in the “normal’ classes.

Obviously, things worked out well for me over time and I believe those
challenges lead me to become the person I am today. They say strong
winds lead to strong timber. My strong winds were not the ADHD, nor the
dyslexia…really. My problems would be revealed to me over time as 2

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main contributing factors. Both issues I now feel melatonin would have
helped. These two factors were in fact, severe food allergies and exposure
to neurotoxins.

When I was in my 20’s I found out that I was allergic to gluten and dairy,
and when I stopped consuming them it was like a miracle for me and my
brain. Over the years voiding them has improved my energy and ability to
focus greatly. Now when I consume either of these food’s I go into a
zombie state with severe brain fog. Most likely this was why I couldn’t sit
still and learn when I was younger. No wonder I had ADHD! Food
sensitivities are considered “inflammatory stresses'' as the immune system
is seeing gluten and dairy as a foreign invader, like an infection. This
inflammation is due to a bad gut (leaky gut and poor microbiome) which
causes the immune reaction. The allergen would have then caused
inflammation throughout my body, and in particular, to the brain, leading
to enhancement of the ADHD challenges.

Refer back to chapters 5 & 11 for how this works and how melatonin can
support the gut, allergies, and immune system.

Besides the allergies, I also was born and raised for my first 2 years of life
on Camp Lejeune in the early 70’s, which at the time was the epicenter of
the worst environmental toxic water contamination in US history. The
contamination primarily included perchloroethylene (PCE),
trichloroethylene (TCE), dichloroethylene (DCE), vinyl chloride, and
benzene. Very nasty chemicals that settled into my central nervous system.

Much has now been learned about how these chemicals can cause cancer
as well as challenge the developing nervous system. My father has recently
been diagnosed with Leukemia, my mother has developed debilitating
arthritis, and both parents have autoimmune thyroid conditions. It’s
difficult to say how much this exposure has affected my own nervous
system, but hard to rule out the possibility that it contributed to my ADHD
and Dyslexia. It could have been that the effects to my nervous system led
to the poor gut function, and then that subsequently led to the food
allergies. You see it’s not the symptom that is usually the problem, it's
usually deeper and involves an underlying breakdown in the proper
function of the body.

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Although I’ve done lots to clear these toxins from my system over the
years, I now know that I would have greatly benefited from melatonin
during this toxic exposure. You see melatonin has been shown in studies
to protect the brain during various toxic exposures, such as heavy metals
and harmful drugs like amphetamines. If only my parents knew about the
miracle molecule when I was growing up, maybe things would have been
much different for us all?

If you’re a parent and you have kids with these challenges you now have
this powerful knowledge. I feel like my past challenges or my “Pain to
Purpose” story has led me to discover answers to these problems that I am
passing on to you so that you and your children won’t have to suffer the
same way I did.

So how do we gain our circadian rhythm in

utero and as babies?

When we are very young, we rely on our mother to provide the signaling
to our circadian rhythm through the hormones in her breast milk or even
placental transfer. This important function of entrainment to the light/dark
cycle becomes fully functional by 3 months of age. [1] Entrainment may
also be important for development, seeing as a mother whose sleep is not
disturbed by a baby on a different circadian rhythm will improve her
caregiving and low melatonin production in mothers of some autistic
children. [2]

The benefits of melatonin are certainly not limited to adults. Many people
are surprised to hear melatonin supplementation can also be of benefit for
children, as there are times when various stresses can have adverse effects
neurologically and cause a decline in their melatonin levels. There are also
times when pulsing higher doses of melatonin can support things like the
immune system during an infection, heavy metal toxicity, mold exposure,
respiratory diseases, and any child who might suffer from sleep disorders
or learning and behavioral disorders due to the reduced melatonin levels.

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Melatonin can be effective for the

management of health issues in
children and there are a few
conditions that have been
scientifically studied, which we’ll be
diving further into throughout this
chapter.

Severe respiratory distress syndrome

Studies have revealed that melatonin

could be effective for relieving the
symptoms of severe respiratory
distress syndrome in premature
infants. The ability of melatonin to
support immunomodulation, along
with its anti-oxidation action would
reduce swelling and inflammation in
the respiratory passages. This can help to improve breathing in infants.

Additionally, the inhibition of the pro-inflammatory mediators or

cytokines through the melatonin mechanisms (discussed in chapter 5 & 6)
can be of benefit to severe respiratory distress syndrome, especially in
premature infants.

I came across one study, ‘Melatonin in bacterial and viral infections with
a focus on sepsis: a review’ published in Recent Patents on Endocrine,
Metabolic, and Immune Drug Discovery in 2012. This study shows that
melatonin could be effective in fighting various viral and bacterial
infections in the respiratory system in children. The administration of
melatonin supplements has been shown to control chlamydial infections,
and the infective conditions induced by Mycobacterium tuberculosis.

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The specific mechanisms of the

antimicrobial action of melatonin are
discussed in great detail in chapter 5
and 6, so if you need to review, please
do that now. But, if you want the
short version here it is:

Inflammation runs wild due to out-

of-control oxidation. Melatonin has a
powerful antioxidant or inhibitory effect on free radical formation. This
molecule is normally produced in the energy-producing units in each cell,
yet mitochondria and infections can shunt this energy to 10% of what is
normally created from oxygen and glucose. This lack of energy to the
immune cells causes it to decrease the ability to fight the infection which
then causes the inflammation to run wild. This is called a cytokine storm.
It goes even deeper in the lungs as melatonin can also slow the duplication
of bacteria and viruses, thereby, preventing faster growth and
multiplication of microorganisms within the respiratory tissue. Meaning,
that it would render the bacteria and viruses unable to survive thus causing
the infection to clear within a shorter period.

Besides, melatonin may also be effective in the management of sepsis in

newborns and premature infants. This effect has been demonstrated in
several animal models, showing the action of melatonin supplementation
in septic shock. The protective action of melatonin against sepsis has been
attributed to its antioxidant and immunomodulating properties, as well as
its inhibitory effect against the activation and production of pro-
inflammatory mediators. Basically, this means that melatonin helps to
calm down the cytokine storm and allows the immune cells to work harder.

The results of this study have provided evidence linking the use of
melatonin to faster improvement in premature infants diagnosed with
severe respiratory distress syndrome or septic shock. Furthermore,
melatonin also offers great therapeutic potential in the treatment of multi-
organ failure associated with septic shock in critically ill patients. [3]

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This research clearly

demonstrates that
melatonin can be
beneficial for children
and infants born
prematurely. Why
then is melatonin not
used regularly for
these conditions? And
why has the public not
been informed about
it while lives are being lost due to the massive stressors, we now deal with
that suppress melatonin?

ADHD & Autism related sleep disorders

Other pediatric conditions that have benefited from melatonin

supplementation include sleep disorders of various origins, autism
spectrum disorders, and epilepsy, including febrile seizures. One study,
‘Clinical uses of melatonin in pediatrics’ published in the International
Journal of Pediatrics in 2011 revealed some amazing results in the use case
of melatonin when administered to children.

This study has analyzed the results of several clinical trials aimed at
assessing the effects of melatonin supplementation in children, focused
mostly on a variety of kinds of sleep disorders.

Melatonin was found to be beneficial for the treatment of dyssomnias,

particularly delayed sleep phase syndrome. This means children who
suffer from different forms of sleep problems, such as inability to fall
asleep and disturbed sleep at night, would be able to enjoy a sound and
undisturbed sleep routine following melatonin supplementation. It would
also prevent the delayed sleep phase syndrome, which means melatonin
would help them fall asleep within a much shorter period once they hit the
bed.

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Box: My suggestion would be to give kids, who suffer from an inability to

fall asleep, lower doses such as 3-20 mg about 2-4 hours before their
bedtime. Disturbed sleep at night might also be helped with melatonin in
this same dosing schedule or even higher such as 20-60 mg. Of course,
this is meant to be only a
guide and not a substitute
for medical advice, as you
should always consult your
doctor before starting any
supplement.

The benefits of melatonin

are found to be pronounced
in children who suffer from learning and behavioral disorders, like I did,
such as attention-deficit hyperactivity (ADHD), and even autism spectrum
disorders. The sleep disturbances associated with these conditions are
linked to the imbalances in the psychological, emotional, and neurological
disturbances. Melatonin could support the health and functions of the
nervous system. Moreover, melatonin can further have a positive impact
on the brain due to how metabolically sensitive it is. Kids have an
incredible energy requirement
as they are in growth and on top
of that they also have many of
the same stressors we have as
adults. Melatonin can restore
the normal functions of the
brain by protecting the energy it
needs.

Febrile seizures and epilepsy have also been found to be susceptible to

treatment with melatonin. These supplements can be used alone or in
combination with conventional anti-epileptic drugs. Melatonin would
prevent the progression of brain damage in children with epilepsy and
seizures, thus improving the quality of their life.

In newborns, particularly in those who are delivered preterm,

supplementation with melatonin would reduce oxidative stress linked with
asphyxia, sepsis, respiratory distress, and surgical distress. Moreover, the

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administration of melatonin to infants would help them adapt to the sleep-

wake cycles of adults. It would improve their nocturnal sleep allowing
them to set their circadian rhythm to that of adults, including their parents.
This effect of melatonin could be of great relief to parents, especially first-
time moms and dads, who struggle to adapt to the sleep-wake cycle of the
newborn baby, which is often not in sync with the day-night cycle of the
earth. [4]

Role of melatonin in the management of

learning and behavioral disorders

In recent years there has been a sharp spike in the incidence of learning
and behavioral disorders like Autism and ADHD (Attention deficit
hyperactivity disorders). We spoke earlier about entrainment which is an
extremely important aspect of the development of the baby's circadian
rhythm. A mother whose sleep is disturbed by a baby on a different
circadian rhythm can cause issues to her ability to pass along the signaling
for the development of the pineal gland and melatonin receptors being
formed which create the baby’s circadian rhythm. Supplementing the
mother with melatonin might solve this issue. Most importantly, giving
the mother melatonin during the third and fourth trimesters when the
neonate’s melatonin receptors begin to function. [5]

Studies aimed at assessing the therapeutic role of melatonin in the

management of these conditions have exciting and amazing results.

One study, ‘Updated View on the Relation of the Pineal Gland to Autism
Spectrum Disorders’ published in the Frontiers in Endocrinol in 2019 has
provided evidence linking the use of melatonin supplementation with
improved performance of children with autism and ADHD.

This study is primarily focused on evaluating how the higher risk of autism
could be associated with pineal gland malfunctioning. It is believed that
the abnormal functioning of the pineal gland can result in the lower

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production of melatonin, due to which the development of autism could

be triggered. This hypothesis is supported by observations revealing a low
concentration of melatonin in children with autism. It was found that
nearly 65% of children with autism have less than 50% of the average
value of melatonin.

Also, sleeplessness has a higher prevalence of nearly 50 to 80% in autistic

children, as compared to just 9 to 50% in normal children of the same age.

Moreover, studies have shown that exogenous supplementation with

melatonin could be highly beneficial for reducing the time until the onset
of sleep and improving sleep duration.

This means the treatment of autistic children with melatonin could

enhance the quality and duration of their sleep while also reducing the time
taken to fall asleep. This benefit of melatonin may also be effective in the
management of other behavioral disorders like ADHD, which is marked
by hyperactive and impulsive behaviors. The reduced sleep onset latency
period brought about with the help of melatonin supplements could reduce
the hyperactive behaviors
of ADHD children and
even improve their focus
and attention span.

There is a strong genetic

link to explain the benefits
of melatonin in children
with autism or ADHD.
Genetically, the autism-
linked mutations are usually found in the genes that encode the key
enzymes for melatonin synthesis, such as AANAT (Arylalkylamine N-
acetyltransferase), and ASMT (Acetylserotonin O-methyltransferase).
The reduced expression of the genes encoding AANAT is also a
characteristic finding in children with autism. These genetic abnormalities
have been found even in the genes encoding the 2 melatonin receptors
called MT1 and MT2.

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This suggests that the higher incidence of autism in children with

melatonin dysfunctions could be genetic in origin. One of the best ways to
reverse the effects of these mutations is to improve melatonin levels in the
brain, which could be achieved easily through the use of melatonin
supplementation. It is advisable that parents speak to their health care
providers about melatonin supplementation for children with learning and
behavioral disorders.

Besides, there is also the need to explore the link between melatonin,
DMT, and autism. Because researchers have begun speculating on
the possibility of the abnormal metabolism of N-dimethyltryptamine
(DMT), from the pineal gland, causing aberrant neuroplasticity or
abnormalities related to the neural connectivity in autistic patients.
It has been previously suggested that the abnormal neural plasticity-
like cortical overgrowth and dendritic spine dysgenesis are common
neurological symptoms in children with autism. The abnormal

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activation of the mTOR (mammalian target of rapamycin) is

proposed as the primary cause for the abnormal neurological
development linked to autism. Fasting to inhibit mTOR might be
worth considering in addition to melatonin. Moreover, it was also
suggested that the disruptions in the activities of the BDNF (brain-
derived neurotrophic factor) through TrkB (tyrosine kinase B)
signaling pathways may play a role in the initiation and propagation
of autism.

Interestingly, the disruptions in the synthesis of melatonin in

children with autism have been found to be associated with a rise in
the secretion of melatonin precursors, N-acetylserotonin (NAS), and
serotonin. NAS works as an agonist for the TrkB receptors and so,
in conjunction with serotonin, it can contribute to the abnormal
plasticity of the neurons in autism.

The pineal gland can become non-functional

and calcified due to fluoride in children

One of the defense

mechanisms protecting the
body against the effects of
fluoride toxicity seems to be
its deposition in calcified
tissues. The symptoms of
excessive fluoride
accumulation in bones and
teeth are known and well documented, classified as skeletal
fluorosis and dental fluorosis, respectively.

Calcium deposition into the pineal gland is similar to that found in

bones. The process of calcium accumulation in the pineal gland is
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initiated in childhood and even in newborns.

Calcification is accompanied by a reduction in melatonin

synthesis. Hence, the conclusion that pineal gland calcification has
an indirect effect on the production and secretion of this hormone.
The image here shows the severe calcification of the pineal.

In light of this science, it may make sense to limit fluoride intake

by avoiding drinking most municipal water sources, which have
been fortified with fluoride, as well as many conventional kinds of
toothpastes. Furthermore, fluoride is also used in pesticides and
some chemicals used to create non-stick compounds for pots and
pans. Eating organic foods and avoiding processed foods can also
reduce fluoride consumption.

Dr. John’s Comment:

I can't overstress the importance of pineal gland health, and
the impact fluoride and calcification can have on melatonin
production, especially in children. In fact, I've dedicated an
entire chapter of this book (chapter 17) to the pineal gland
because I firmly believe that this gland plays a vital role in
our wellbeing and overall health.

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Conclusion

Using melatonin supplementation with children might at first

surprise many people, as it is considered to be unnecessary. Children
actually require lots of melatonin, maybe much more than adults do
as they are going through very high metabolic activities with
growth.

There are multiple headwinds to kids producing their own melatonin

in order to keep up with the demand the body requires to buffer
stress. Some of these stressors include toxins, like when I was
exposed to toxins in Camp Lejeune, our kids are now exposed to
mercury in seafood and vaccines, pesticides, aluminum, and many
other industrial chemicals and solvents. Melatonin would work to
protect this delicate developing nervous system in this toxic world
we live in.

Another big stressor to consider is light pollution. Kids are on their

iPhones and iPads after the sunsets, which are preventing them from
the normal sleep-wake cycle which will ultimately suppress
melatonin production. Moreover, the electromagnetic stresses that
we have today are much greater than at any other time in our history.
It is unknown how severe the health risks will be with 5G, and yet
our kids are bombarded with an onslaught of these potentially
melatonin-killing invisible EMF stressors. Also consider the general
stress level of many mothers in today’s world, and how they are not
training their kids for a normal circadian rhythm because they don’t
have a strong signal of their own to transfer. On top of all that, there
are also genetic considerations.

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What is the bottom-line regarding melatonin for

children?

There probably was not a need for melatonin 50 or 100 years ago,
however, in today’s world it might be a necessary tool for parents,
pediatricians, and alternative healthcare practitioners that work with
children to consider.

One of my close colleagues and friend Dr. Dan Pompa works closely
with children and performs detox protocols with them using
products he’s developed. We are collaborating with various
protocols in order to safely detox many harmful substances from the
nervous system in particular.

By using various binders and chelating agents, many afflictions we

see with children can be improved by including some of these detox
protocols. A multi-modal approach needs to be used with many
conditions we see, specifically developmental and neurological
problems with children.
These are some of my bullet points to consider:

● Food Sensitivities and Gut Health.

● Chronic Infections (EBV, Lyme Mold)
● Environmental Toxins and Biotoxin Illness
● Poor Sleep Hygiene (light pollution)
● Lack of Proper Physical Activity and Brain Activation for
brain development (See Disconnected Kids by Dr. Robert
Melillo)
● EMF Exposure
● Cranial Bone Issues (See Functionalcranialrelease.com)

I hope this chapter opens the eyes of parents to the incredibly long list of
benefits that melatonin has to offer. I also really hope that this chapter
helps kids to avoid the challenges I went through personally. My journey

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would have been much different if I was given melatonin as a child, but as
I said earlier, my pain might have led to my purpose to learn what I can
about health through my own personal journey. Melatonin has been a big
part of my healing, even though it was somewhat “late to the party”.

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Chapter 16: Melatonin For
Diabetes
We have discussed so many
ways melatonin works to
support energy through your
mitochondria. When you
look at various diseases like
diabetes, which is a
metabolic disorder dealing
with energy, it's no surprise
that our miracle molecule has shown to be effective in the
management of diabetes both type 1 and 2. Besides supporting
cellular energy, melatonin is important for the prevention of
complications that are linked to the lack of sleep. Particularly poor
sleep resulting from mental stress, hormonal imbalances, and
immunological dysfunctions.

It is surprising to note that type 2 diabetes is one of the major

complications in people who suffer from insomnia. Insulin and
melatonin are very intimately connected as we will dive into this
science-rich chapter.

Melatonin lowers A1c

This study, ‘Melatonin Use in

Patients with Type 2 Diabetes and
Insomnia’ published in the
Endocrine Web showed that

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melatonin supplementation cannot just help to improve the sleep

pattern of patients with diabetes but also improve their glycemic
control.

This study was conducted on 11 men and 25 women in a double-

blind, randomized, crossover study design. The age of the
participants was between 46 and 77 years. The study participants
were treated with melatonin or a placebo for about three weeks
during the 1st phase. This was followed by a one-week washout
period, after which, the participants crossed over for 3 weeks of
treatment with other preparations. This was the second phase of the
research. All supplements were taken about 2 hours before bedtime
for three weeks which might work best for lower melatonin dosing
and is not necessary with supra physiological dosing schedules in
my view.

During the extension period of 5 months, the study participants were

administered melatonin in nightly doses. The sleep habits of these
men and women were monitored objectively. The measures of
certain markers for the assessment of glycemic control and
inflammation were noted. The levels of the parameters measured at
the baseline and also at the end of the study included fasting blood
glucose, C-peptide, fructosamine, glycosylated hemoglobin
(HbA1c), triglycerides, total cholesterol, high-density lipoprotein
(HDL), and low-density lipoprotein (LDL) cholesterol, insulin, and
some antioxidants.

Following about 5 months of melatonin use, it was noticed that the

mean HbA1c was significantly lower in the test group as compared
to the baseline. A significant improvement in the HbA1C levels was
found in the patients suggesting that melatonin supplementation
helped improve their diabetes control. There was a decline in the
HbA1C level in patients who were treated with melatonin without
any significant change in the HbA1C levels in the control group that
was administered a placebo. The HbA1C level is considered one of

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the vital parameters of glycemic control in patients with diabetes.

Having HbA1C levels within normal limits indicates a long-term
improvement in the body’s response to the treatment or other efforts
like a change in the diet or lifestyle habits. HbA1C is believed to
provide an average estimation of glycemic control over the past 3
months. The improvement in the HbA1C level in these patients has
provided a strong foundation suggesting the efficacy of melatonin
supplements for the management of diabetes.

The researchers concluded that the short-term use of melatonin

might improve sleep maintenance in patients with type 2 diabetes
and insomnia without interfering with the metabolism of glucose
and lipids. But the long-term use of melatonin could produce a
beneficial effect on the HbA1c levels, suggesting an improved
glycemic control. [1]

What if diabetes is genetic? researchers have also discovered that

increasing the levels of the sleep hormone melatonin through
supplementation may reduce the ability of the insulin-producing
cells in the pancreas to release insulin. Also, they have found that
the effect could be stronger in patients who carry particular gene
variants that are linked to a higher risk of type 2 diabetes.

These findings suggest the use of melatonin supplements could be

helpful support in people having a genetic predisposition to
developing diabetes. To begin with, it might seem to you that
melatonin can make it worse for patients with diabetes to control
their blood sugar levels as it reduces the ability of the tissues of the
pancreas to release insulin. But this is not so. In fact, it can actually
control how much insulin is released by the pancreas so that you can
achieve optimum control over your blood sugar levels. And this is a
highly unique effect of melatonin that is difficult or nearly
impossible to achieve with any other treatment or drug. Trust me if
Big Pharma could patent melatonin, it would be all over the news!

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Patients who use melatonin supplements on a regular basis are able

to achieve better control over their diabetes as this sleep hormone
helps to regulate the secretion and release of insulin by your
pancreas. It basically works by regulating the metabolic activities
that are controlled by the body’s circadian rhythm. The increased
melatonin levels in the body ensure the various metabolic functions
occurring in the body including the breakdown and absorption of
sugars, production and release of insulin, and the production of
hunger hormones like ghrelin and leptin are well controlled. This
allows the body to regulate when and how much insulin is secreted
in the body thereby improving glycemic control.

One consideration is if an individual was involved in intermittent

fasting, they might find melatonin supplementation to help them fast
through its insulin regulation, but also supporting hunger and
cravings through ghrelin and leptin. Makes a good argument for
melatonin during fasting programs like MitoFast.

These findings have been supported by one study that was recently
published in the Hormone Molecular Biology and Clinical
Investigation. This research, ‘Hormone Molecular Biology and
Clinical Investigation’ explains the exact mechanism of action of
melatonin that could help in the fight against type 1 and type 2
diabetes. [2]

According to the researchers who

conducted this study, diabetes is
commonly associated with the
excessive production of free
radicals during metabolic
processes. The increased oxidative
stress creates a state of imbalance
between the body's natural
antioxidants and free radicals. The excess free radicals can produce
several harmful effects on the body's vital organs including the

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pancreas, resulting in cell death. It might reduce the ability of the

pancreas to secrete insulin in the required amount in response to the
increase in the levels of blood sugar. As a result, the elevated blood
glucose level fails to fall, which should ideally have happened if
insulin was released by the pancreas. This failure of the body to
control the blood sugar levels as a part of its metabolic functioning
can increase your risk of diabetes.

Moreover, melatonin might play a significant role in reducing

oxidative stress by acting as an antioxidant. It is the body's own free
radical scavenger that can attack and destroy the reactive oxygen
species released during various metabolism processes as a result of
which the damage to the cells of the pancreas is inhibited. This
would restore the normal functions of the pancreas allowing this
gland to start secreting insulin in adequate amounts in order to
enable efficient glucose metabolism. This is how by using melatonin
supplements, diabetes and its complications can be avoided.

Recall the mitochondria and the effect melatonin has on supporting

that intracellular structure where energy is made? Well, this is the
epicenter of where oxidation occurs and the cells in the pancreas are
very metabolically active and when there is lots of energy being
produced due to high energy demand you need lots of antioxidants
to quench this process. This is where melatonin supports the
pancreas and many other cells in your body. Melatonin may also
stimulate the production of other antioxidants such as glutathione.
These miracles of melatonin are one of the most effective natural
anti-diabetic treatments people can choose in order to protect
themselves against the risk of complications caused due to diabetes.
[3] [4]

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Why is melatonin considered the silent

regulator of glucose homeostasis?

In human organisms, the circadian regulation for the metabolism of

carbohydrates is essential for maintaining glucose homeostasis and
ensuring optimum energy balance. An imbalance in glucose
metabolism and insulin production has been linked to a variety of
metabolic diseases including obesity, type 2 diabetes, metabolic
syndrome, and cardiovascular diseases.

Melatonin, the pineal hormone, could serve as the key mediator

molecule for integrating the cyclic environment and regulate the
circadian distribution of the behavioral and physiological processes
occurring in the body to promote the optimization of energy balance
and blood glucose levels.

One study has reviewed the interplay between the modulatory

physiological effects of melatonin on glucose homeostasis and the
metabolic imbalance, from the endocrinological perspective. [5]

The remarkable effect of melatonin supplementation in the

regulation of metabolic processes involved in the breakdown of
glucose can be observed from the chronobiological perspective,
considering this hormone to be a major synchronizer for maintaining
the internal circadian order of the physiological processes occurring
during energy generation.

This study, “Melatonin: A Silent Regulator of the Glucose

Homeostasis” was conducted and published recently in 2017 with
an aim to evaluate the role of melatonin as a natural molecule that
can support carbohydrate metabolism in the body. Let us have a look
at the findings of this study and what it has revealed about the
functional synergism between melatonin and insulin.

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Synergy between insulin & melatonin

The scientific literature has stated

that the first experimental injections
of pineal extracts had led to
hypoglycemia, indicating that the
extracts might increase glucose
tolerance, and support muscular and
hepatic glycogenesis. In other
words, if the extract mimics an active pineal and if the pineal is
active such as at night while melatonin is high there is metabolic
where you would expect better glucose regulation and tolerance.

The metabolic disruptions caused due to the absence of melatonin

in patients with a pinealectomized state are characterized by the
presence of a diabetogenic syndrome that can be depicted by
reduced glucose tolerance as well as insulin resistance. Both of these
states tend to be expressed peripherally in tissues such as the liver,
fat cells, and skeletal muscles. The effects may also be evident
centrally, at the level of the brain, or to be more precise the
hypothalamus. This pathological picture could be reverted by using
melatonin in the form of supplements through melatonin
replacement therapy.

In addition to these dramatic findings, this study has also revealed

that glucose intolerance, insulin resistance, and other metabolic
disorders may be seen in certain pathological and physiological
states associated with a reduction in melatonin levels in the body.
These findings are observed in cases that are linked to the
development of diseases as a result of aging, shift work, increase in
environmental illumination during the nighttime, and the
phenomenon of increased light pollution. Maybe we need to start
wearing those blue blocking glasses?

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The melatonin replacement therapy is expected to alleviate most of

these abnormalities and restore health thereby promoting normal
glucose metabolism in patients with diabetes.

Emphasizing the functional synergism between insulin and

melatonin, it is considered that pinealectomy-induced glucose
intolerance and insulin resistance could be related to the mechanistic
consequence of the decline in melatonin secretion. This is often
perceived at the cellular level as a deficiency in the insulin-signaling
pathways and the reduction in certain gene expressions and protein
content. This study has shown that melatonin, by acting through the
MT1 membrane receptors, can induce rapid tyrosine
phosphorylation and stimulate the tyrosine kinase beta-subunits of
insulin receptors. This can help in overcoming a number of
intracellular transduction steps during the insulin-signaling
pathways and help patients with diabetes achieve better control over
their blood sugar levels. [6] In a nutshell you have melatonin
receptors in your pancreas called MT-1 which connect melatonin to
improved blood sugar control.

Melatonin’s metabolic epigenetic regulation

and pleiotropic effects

Melatonin produces a great influence on diabetes and the associated

metabolic imbalances by regulating insulin secretion, and by
scavenging the reactive oxygen species. It also protects the
pancreatic β-cells of Langerhans that are known to be highly
susceptible to oxidative damage.

It is universally accepted that industrial and social pressures, like

working in shifts, can oppose the physiological circadian order that
determines the occurrence of chronic illnesses, like diabetes.

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In diabetes mellitus, the neurohumoral circadian rhythm is

chronically impaired resulting in desynchronization of the cellular
order in the body's healthy tissues as well as between the body and
the external environment causing dysfunction between insulin and
melatonin.

Diabetes mellitus has also been associated with a phase shift in the
body’s cardiac circadian clock. This is why; shift workers have an
increased risk of diabetes that could be linked to the alterations in
metabolic and cardiovascular intracellular circadian clock
dysfunctions.

Loss of synchronization typically occurs due to sleep pattern and

during the change in the exposure to light at different times of the
day, including at night, due to a phenomenon called the “light-at-
night pollution.” In addition, changes in meal-times can cause
challenges with these natural synchronization issues. These forms
of dys-synchronization are commonly observed in patients with
diabetes mellitus, indicating the role of melatonin in triggering the
development of this condition.

Moreover, the melatonin-insulin synergism is also evident in the

form of the incubation of isolated visceral adipocytes, one of the
peripheral functions of insulin being accentuated by the effect of
melatonin.

This is proof that the adipose tissues are the peripheral targets of
melatonin that help in the regulation of the body's overall
metabolism including that of fats and carbohydrates. Similarly, it is
demonstrated that melatonin activation by MT2 receptors in
adipocytes can modulate the glucose uptake and absorption by these
cells. Considering the physiology of adipose tissues, it is possible to
demonstrate the synergistic effects of melatonin on the other actions
of insulin in addition to its role in glucose uptake.

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Insulin-induced synthesis of leptin and its release in the isolated

adipocytes can also be potentiated by the effect of the MT1-
mediated melatonin. This sleep hormone can regulate several other
aspects of adipocyte biology, which can influence lipidemia, energy
metabolism, and body weight, through its regulatory effect on
lipolysis, adipocyte differentiation, lipogenesis, and fatty acids
uptake.

These findings point to the possible role of melatonin in controlling

insulin secretion, glucose and fat metabolism, glucose uptake by
cells, and the reduction of oxidative damage. These studies have
provided evidence linking the reduced melatonin levels due to
reasons like working in shifts or an inability to get refreshing sleep
to a higher risk of diabetes. This underlines the importance of
replenishing the melatonin levels through supplementation in order
to restore healthy metabolic functions and prevent the risk of
diabetes.

Melatonin also exerts another unique effect on the metabolism of

carbohydrates, considering the targets it stimulates for improving
glucose uptake in the muscle cells by inducing the phosphorylation
of the insulin receptor substrate-1 via MT2 signaling.

Also, melatonin therapy enables the MT2 receptors to be expressed

in hepatocytes and elevates glucose release in the liver.

Another critical site for the actions of melatonin in reference to

regulating energy metabolism includes the pancreatic islets wherein
it influences the synthesis and release of insulin and glucagon.

Several immunocytochemical and molecular studies have

demonstrated the presence of the melatonin receptors MT1/MT2 in
the islets of Langerhans in the pancreatic tissue. The MT1 and MT2-
mediated melatonin effect has been found to decrease the glucose-
induced insulin secretion in the isolated pancreatic islets and

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insulinoma beta-cells.

Melatonin can influence the exocytosis of insulin by the β-cells as

was demonstrated in experiments through the nonhydrolyzable GTP
(guanosine-5′-trisphosphate) analog and a melatonin antagonist
called the luzindole both of which have the potential to inhibit the
melatonin effect on the secretion of insulin in the islets.

The intracellular signaling transduction pathways of the β-cell in the

pancreas influenced by melatonin through the MT1 and MT2
membrane receptors also include cGMP, cAMP, and IP3 signaling
mechanisms.

The activation of the receptors resulting in the inhibition of the

forskolin- and glucose-induced insulin secretion, indicates that
melatonin does work by inhibiting the cAMP and adenylate cyclase
systems and helps to reduce the PKA content.

The pineal indolamine may induce the IGF-1 receptor

phosphorylation that participates in maintaining the integrity of islet
cells of the pancreas. Moreover, it has been suggested that melatonin
may also stimulate glucagon secretion and synthesis. These findings
further confirm the role of melatonin in diabetes management.

These actions of melatonin are essential for building the circadian

profile of insulin release and secretion, and the synchronization of
the pancreatic metabolic rhythm with the circadian rhythm. It should
be noted that even insulin has the ability to regulate the melatonin

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synthesis by the pineal gland by potentiating the norepinephrine-

induced melatonin secretion.

Interestingly, the link between melatonin and diabetes might be

based on the observation that insulin production is inversely
proportional to the melatonin concentration in the plasma. These 2
hormones, insulin and melatonin, exhibit a well-regulated circadian
rhythm, though there is a negative correlation between the dynamics
of their syntheses.

The decrease in the

abnormally regulated
melatonin secretion
has been related to a
high risk of diabetes,
which indicates that
melatonin signals are
critical for
maintaining glucose
homeostasis. In
people with diabetes,
endogenous glucose
production and
gluconeogenesis exhibit circadian rhythm that imposes an
abnormality in the fasting blood glucose that does not exist in
healthy individuals with normal levels of melatonin.

Melatonin can also inhibit the glucose-mediated release of insulin

by the pancreatic cells emphasizing the activities it performs in
supporting the functions of insulin. Besides EMF and chronic stress,
the suppression of melatonin by nocturnal light exposure may work
as a trigger for the development of type 2 diabetes in these cases as
explained in the picture below:

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Pathological consequences of melatonin

depletion linked to diabetes

As an addition to the regulatory effect of melatonin on the processes

involved in energy and carbohydrate metabolism, research has
recently demonstrated that intrauterine metabolic programming may
get disturbed due to the deficiency of melatonin in pregnant women.
The children of mothers who suffer from the deficiency of melatonin
may present with glucose intolerance and insulin resistance along
with a delay in the glucose-induced secretion of insulin by the
pancreatic islets. As a result, the risk of diabetes is higher in these
children.

This provides a clear evidence

that melatonin plays a vital role
in metabolic epigenetic
regulation. In other words, the
environmental stresses causing a
change in our genes can be avoided by having melatonin on board.

Robustness is the effect I would say best explains melatonin.

Robustness is a major characteristic involved in the ability to adapt,
survive, and reproduce.

Metabolic dysfunctions are considered

to induce a breakdown in the robustness
of the biological systems, due to which
the continuous maintenance of the
body's physiological functions is
disrupted. This can lead to internal
disturbances in the body’s metabolism
resulting in the development of
diabetes.

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Moreover, melatonin can act as a powerful chronobiotic, in such

cases, and regulate the metabolic processes such that the activity and
the feeding phase of the daytime are synchronized with higher
insulin sensitivity, and the rest of the fasting phase is synchronized
with the insulin-resistant phase. In fact, melatonin can be the key
mediator molecule in these mechanisms and induce nictemeral
integration of the behavioral physiological processes. It can support
the modulation of body weight regulation and energy balance, all of
which are crucial for preventing diabetes.

A chronobiotic is defined as an agent that can cause phase

adjustment of the body clock. Such a chronobiotic nature of energy
metabolism and energy balance is often depicted by the 2 separated
phases existing during a 24-hour period of the day and night cycle.
The first phase is characterized by eating and the process of energy
harvesting resulting in an increased energy intake, followed by its
utilization, and storage. This period is associated with high glucose
tolerance and a higher peripheral and central sensitivity to insulin. It
is marked by an elevated secretion of insulin, with increased glucose
uptake by insulin-sensitive tissues. It also leads to faster and more
efficient glycogen synthesis, muscular and hepatic glycolysis,
inhibition of hepatic gluconeogenesis, faster adipose tissue
lipogenesis, and more efficient adiponectin production.

In contrast, the second phase, which is the rest and sleep phase of
the day, is marked by a fasting period that requires the body to use
the stored energy for maintaining and supporting cellular
homeostasis. The energy is also used for exhibiting insulin
resistance, accentuating hepatic glycogenolysis and
gluconeogenesis, leptin secretion, and adipose tissue lipolysis.

Hormones other than melatonin that exert a modulatory effect on

these cellular metabolisms, such as glucocorticoids, catecholamines,
and growth hormone also present a circadian rhythmic fluctuation
in their secretion and activities. Melatonin, by acting as an

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orchestrating factor in this circadian organization of metabolic

processes, helps to prepare and modify the peripheral and central
metabolic tissues so that they can respond to the action of these
hormones efficiently.

It is these effects of melatonin that further help in regulating the

metabolism of carbohydrates both in the daytime and night-time
thereby protecting us against the risk of diabetes.

The anti-obesogenic effects of melatonin:

The Melatonin Darkness Diet

Melatonin has been shown to increase calorie usage! Investigators

believe this increased calorie usage is due to more accumulation of
brown fat. Unlike white fat (the most common type of body fat) that
stores energy, brown fat contains many more mitochondria which
make them more energy-producing. This powerful brown fat is very
desirable and is a great source of energy when we need it. Especially
for those following a ketogenic diet where they teach themselves to
use fat as a fuel
source versus the
sugars in most
carbohydrate-rich
western diets.

We use whole
body cryotherapy
in our clinic and
one of the biggest
benefits of “Cryo”
is this increased
brown fat. This
allows for an indirect benefit to the heart and brain as well as they
can draw from this strong source of fuel.

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Studies show animals who have had the pineal gland removed
became overweight, and supplementation of melatonin reversed that
weight gain. Furthermore, middle-aged fat animals given melatonin
showed decreased weight and visceral fat late in life. These changes
were not seen if melatonin was not given.

The anti-obesogenic effects of melatonin are, in part, the result of

the regulatory role of this hormone on the balance of energy, mainly
acting on the regulation of energy mobilization from the body's
stores and energy expenditure through things like brown fat
production.

It is demonstrated that in young and healthy individuals, melatonin

supplementation therapy may reduce the long-term body weight
gain and the extent of the visceral fat deposits. Keep in mind the
visceral fat is the most stressful to the body and leads to more
diseases.

Supplementation of melatonin can indeed lower your body weight.

It is believed to work by inducing the reestablishment of circadian
distribution of energy metabolism, and insulin signaling pathway
reinstatement through melatonin receptors.

My weight loss challenge:

● Supplement with high-dose melatonin

● Try cryotherapy or even cold showers in addition to
melatonin to increase brown fat.
● Use the ketogenic diet to teach your body to use fat as energy
such as a 5:1:1 fasting/diet program (5 days of ketogenic, 24
hour fast, protein and carb loading day).
● Practice eating window of 6-10 hours each day so that
fasting teaches your body to use fat as a fuel source.
● Consider the Mito Fast program.

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Fasting for Diabetes

Dr. Jason Fung, the author of the book
Diabetes Code, has shown fasting can
make dramatic changes or cure diabetes.
He has a program that has proven to
reverse both type 1 and 2 diabetes. He
considers diabetes type 2 as a cell full of
glucose where it can't store anymore so
the insulin receptors stop working.

Due to too many carbohydrates in the diet, your cells can become
overloaded with sugar. By fasting the glucose out of our cells in the
form of stored fat, we create a metabolic signal that allows insulin
receptors to function properly.

His work has been revolutionary, and

our clinic has embraced his finding by
introducing more fasting protocols for
our patients. Besides melatonin, I feel
fasting, as well as a program that
includes days of eating a ketogenic diet,
makes good sense as a program to treat
diabetes. A 5:1:1 program is where one
would do a ketogenic diet 5 days a week
followed by a 24 hour fast and then a
carb-loading day. Dr. Fung currently
uses 2-3 24hr fasting days per week as
his core diabetes program.

It is clear these programs work more effectively with melatonin

supplementation. These fasting and diet variation programs work
well to keep the body working toward a balance that stresses the
systems in a way that makes them stronger. It seems that

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maintaining the same diet each and every day is not the best strategy
to live a long and healthy life. It comes back to hormesis, where
stress in the right dosage gives a net gain in health. For more on Dr.
Fung see his website here.

Ketogenic Diet & Diabetes

Metabolic flexibility is the key to a healthy body and healthy blood

sugar. When I say metabolic flexibility what I mean is the ability to
swing between creating cellular energy
through both fast and proteins, and
sugars and carbohydrates. These are 2
separate pathways, and the body
typically becomes addicted to sugars
and carbohydrates.

Imagine the difference between getting food out of your refrigerator

versus having to go downstairs into your basement and pull food
that is frozen and needs to be defrosted out of the freezer. There is
much more energy in the freezer once you get it out and defrosted
than there is in the refrigerator. This is the same thing that happens
to us with regards to carbohydrates. Because we include them as the
majority of the standard American diet it is common that the body
becomes very efficient at using sugars and carbohydrates as fuel
sources and simply stores the fat for later. Therefore, what I mean
when I say metabolically flexible is that your body could either go
to the freezer or to the refrigerator at will.

When folks first start venturing into a ketogenic diet, they will find
themselves with their blood sugar crashing because they are unable
to get the food out of the freezer. Once the body learns how to
liberate that food out of the deep freeze then one can fast for

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extended periods of time or skip meals, and simply switch into

ketosis where the body is using ketones from fat that is either
through the diet or from stored sources in adipose cells.
In this study ‘A low-carbohydrate, ketogenic diet to treat type 2
diabetes’ a ketogenic improved glycemic control in patients with
type 2 diabetes such that diabetes medications were discontinued or
reduced in most participants. [6]

A ketogenic diet for type 1 diabetes may not be the best

monotherapy. The fasting protocols that Dr. Jason Fung has
developed appropriately combined with a ketogenic diet hold the
most promise. A ketogenic diet alongside intermittent fasting or
extended fasting, when combined with melatonin supplementation,
is a winning combination.

Ben Azaidi founder of keto camp has recently released a book called
Keto Flex. This book provides a lot of insight into some of the
concepts regarding variations throughout the week in order to stress
various systems and create metabolic flexibility. There are wide-
reaching benefits to this approach including neurological health, gut
and microbiome health, cardiovascular health, and of course
metabolic resilience, which would play into diabetes quite well.

If you're going to be using hormesis, which is a stress that is

provided in the right dosage stimulating the body to respond for a
net gain in health, melatonin is your best friend in this instance.
Melatonin is the primary support system the body relies on when
there is stress. Remember the early research with the rodents where
they were living stress-free, and the researchers couldn't see a
difference with melatonin supplementation? It wasn't until they
stressed the rodents in those tubes with the pinholes that they started
to see melatonin's benefit, where it mitigated a variety of different
diseases and extended lifespan in these rodents.

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Including melatonin particularly in a high dose could be a powerful

synergy alongside some of these more contemporary therapies for
diabetes, such as fasting and a ketogenic diet.

Conclusion

Melatonin is a key modulatory molecule that can assure a healthy

metabolism, optimization of energy balance, as well as body weight
regulation.

Melatonin acts by potentiating both the peripheral and central

insulin action by supporting the regulation of insulin-signaling
pathways. Melatonin is also found to be responsible for maintaining
adequate energy balance by regulating energy flow and energy
expenditure by causing production of better brown fat.

Melatonin synchronizes the 2 major metabolic phases that exist 24-

hour period of the day-night cycle including the activity/
feeding/wakefulness state against the rest/fasting/sleep phase.
Basically, you're using energy during the day and storing it as you
feed. During the night you are pulling energy in the form of glucose
out to use to heal and repair the body.

The decline in the synthesis of melatonin can occur due to

physiological processes such as aging, and pathologies associated
with events like shiftwork and an illuminated environment during
the night-time. This can induce insulin resistance, sleep
disturbances, glucose intolerance, and metabolic circadian
disorganization. This would depict a state of metabolic imbalance,
and chrono-disruption aggravating the glycemic control and your
general health.

The evidence that melatonin can induce insulin secretion and

improve β-cell functions has provided a strong foundation

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supporting the use of melatonin supplements as an effective

therapeutic approach for the reestablishment of glucose
homeostasis. The scientific proofs support the evidence that
melatonin replacement therapy, when carried out adequately, in
terms of dosage, formulations, and the time of the administration,
could contribute to maintaining efficient blood glucose levels in
patients with diabetes and help restore the chronobiotic order needed
for achieving a robust healthy state in the body. [7] [8] [9]

Consider using fasting and ketogenic diet strategies for diabetes in

addition to melatonin.

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Chapter 17: Pineal Gland
The seat of melatonin production
& much more

Your pineal gland functions at its highest between 1 and 4 am each

night. Melatonin is produced in the enigmatic pineal gland, usually
in response to darkness and that’s why it’s famously coined the
hormone of darkness.
Shaped like a pinecone, the
pineal gland is deeply seated
within the brain. This small
gland has ignited the
imagination of philosophers,
scholars as well as spiritual
leaders from different cultures
and religions.

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The pineal gland is dubbed as “the seat of the soul” or the “third
eye” and conceptualized as the ‘tranquilizing organ’. [1] [2] [3]
Interestingly, researchers have suggested that the pineal gland and
its hormonal product, melatonin, are possibly associated with
improved longevity. Moreover, the pineal gland dysfunctions or
failure is what is believed to initiate or accelerate the aging process.
This small gland is extremely vital for our health and lifespan. The
pineal also releases DMT which is associated with feelings of love
and connection to others. A paper published in 2018 by researchers
in the U.K. purported that DMT simulates the near-death
experience, wherein people report the sensation of transcending
their bodies and entering another realm. It's no wonder the pineal is
considered so important, as these 2 hormones are crucial when it
comes to health.
I was an expert guest on a film called Psychedelics Revealed and
although I don’t advocate using DMT recreationally, I am a
proponent of using psychedelic medicines in the right setting to
work through emotional trauma and to become more spiritually
aware through a profound experience that some of these medicines
can provide. Many of which work through the DMT pathways and
the pineal gland! [4] [5] [6] [7]
Dr. Joe Dispenza teaches his students to
use a particular breath to improve the
pressures around the pineal gland. I’ve
taken his advanced course and it is
something very powerful that creates a
similar experience to being on
psychedelics. There is a feeling of
universal connection, love, and
gratitude for being alive. This
connection with the “divine source” is the experience I assume all

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religions speak about.

Becoming more aware of this energy or “doorway” can allow you
to be connected to something that many religions speak of that unite
us all in an energy that is not yet detectable with modern science.
That's the best I can do to explain, as I know some might read this
and think it's a bit “woo-woo” but there is no denying the events
taking place at these events and the studies soon to be published
through Dispenza’s meditation practices.
NASA scientists are seeing
changes in the blood of these
meditators. Tiny vesicles
called exosomes found in the
plasma of the meditator’s
were mixed with epithelial
cells. They then introduced
the COVID-19 virus and
compared these cells to a
control group without the
meditator’s exosomes. The COVID-19 virus was unable to enter the
epithelial cells mixed with the meditator plasma. In contrast, the
control group cells that were not from meditators were infected

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severely. They found tiny vesicles in much higher amounts in the

blood of these meditators which are called exosomes.
Exosomes are packets of RNA which carry information to other
cells and parts of the body. Scientists are attributing these exosomes
to explain some of the remarkable changes within these meditators.
Changes that range from virtually every disease known.
What I’m speaking of is spontaneous healing that occurs due to this
heightened connection through the pineal and the other energy
centers that run through the body. We use exosomes in my practice
to heal various injuries and degenerative conditions that occur in the
body. Such as osteoarthritis or even stroke. These exosomes are
taken from the placentas of healthy mothers.
These exosomes can be injected just like stem cells, as exosomes are
the healing substances delivered by stem cells regardless. Therefore,
by bypassing the need for the stem cells to deliver the exosomes they
can simply be isolated and injected with great results in many
applications.
So, is it possible when we connect with your pineal with certain
intentionality’s, such as to heal a foot or your brain that the body
responds by releasing exosomes that will carry the information you
intend?
I believe this is what's happening. If you look at the graph showing
the energy spectrum and what a small part of it is the “visible light”
you can appreciate there are so many frequencies and wavelengths
we are not aware of.
Is it possible the pineal is more of a radio receiver? Do the crystals
becoming activated through the CSF creating an energy field that
allows us to tap into a source that can allow for powerful changes in
our health?

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Pineal & CSF Flow

This image of the flow of CSF shows how the circulation goes
through what's called ventricles in the brain. These ventricles are
like canals carrying the life-giving nutrients the CSF delivers to the
brain and spinal cord. The pineal sits right at the end of the 3rd
ventricle and CSF has most of its pressure around it and the pituitary.
Take a look at this MRI showing the red areas as the most active.

What Dr. Dispenza teaches is a

breath that directs your CSF
into the pineal by locking down
your muscles from the base of
your pelvis or perineum up the
spine and throat toward the
pineal. There is a pumping
action upon a full inhale with
intentionality to the pineal

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gland. This is creating hydrostatic

pressure to the pineal, which Dr.
Dispenza has been discovered in
the literature to be involved in an
activation to the crystalline
structure inside the pineal.
There seems to be a piezoelectric
effect from the hydrostatic
pressure of CSF as it interacts with
the crystalline structures within the
pineal.
Piezoelectric is defined as the ability of certain materials to generate
an electric charge in response to applied mechanical stress. I always
say you're either a swamp or a river and this means better
circulation, better health, and the pineal can become a victim or a
victor due to good or poor circulation.
Doing things like this pineal breath Dr. Dispenza teaches might hold
some promise to improving pineal health, as well as detoxing many
of the chemicals that interfere with pineal gland function such as
fluoride, which has been proven to create calcifications.

DMT The Spirit Molecule

DMT or N, N-Dimethyltryptamine is so powerful that it was dubbed

the “spirit molecule” for its spiritual awakening–type trips. It's
defined as a chemical substance
that occurs in many plants and
animals and is a derivative and a
structural analog of tryptamine.
DMT is used as a recreational
psychedelic drug and prepared by
various cultures for ritual purposes
as an entheogen such as with Ayahuasca. Ayahuasca is traditionally

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prepared using two plants called Banisteriopsis caapi and

Psychotria Viridis. The latter contains DMT while the former
contains MAOIs, which prevent certain enzymes in your body from
breaking down DMT.
DMT may also be released when we dream. It’s also believed to be
released during birth and death. This release of DMT at death may
be responsible for those mystical experiences seen with Dispenza’s
work and psychedelic drugs such as psilocybin and LSD. Trace
amounts of DMT have been shown in rat pineal glands. [8]
The pineal gland in humans produces a small amount and it's
uncertain if the pineal is a large enough source of DMT to be
psychoactive. My personal belief is that DMT can be released by a
healthy pineal. Keep in mind 80% of us have calcified pineals and
therefore, a healthy pineal is fairly rare, thus meaning that studies
on typical pineal glands might not reflect the potential in certain
individuals. In fact, it's quite possible that the pineal can produce
more DMT than what scientists have seen thus far given the right
circumstance.
Dr. Dispenza’s work as well as other anecdotal methods to activate
your “third eye” such as: breathing methods, yoga, meditation,
taking certain supplements, doing a detox or cleanse, using crystals
and various vibrations tuned to certain frequencies might hold the
answers.
Dr. Rick Strassman wrote a book on DMT
called “The Spirit Molecule: A Doctor's
Revolutionary Research into the Biology of
Near-Death and Mystical Experiences”. In this
amazing book, Strassman sees DMT
consistently producing near-death and mystical
experiences with his volunteers. Many reported
encounters with intelligent nonhuman
presences, aliens, angels, and spirits. Nearly all
felt that the sessions were among the most
profound experiences of their lives.

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The pineal gland commonly becomes non-

functional and calcified as we age
In 80% of adult humans, the pineal gland contains calcifications
defined as “corpora arenacea” or “brain sand”. [9]

One of the defense mechanisms protecting the body against the

effects of fluoride toxicity seems to be its deposition in calcified
tissues. The symptoms of excessive fluoride accumulation in bones
and teeth are known and well
documented, classified as
skeletal fluorosis and dental
fluorosis, respectively.

Calcium deposition into the

pineal gland is similar to that
found in bones. The process of
calcium accumulation in the
pineal gland is initiated in childhood and even in newborns.
Calcification is accompanied by a reduction in melatonin synthesis.
Hence, the conclusion that pineal gland calcification has an indirect
effect on the production and secretion of this hormone. The image
here shows the severe calcification of the pineal.

In light of this science, it may make sense to limit fluoride intake by

avoiding drinking most municipal water sources, which have been
fortified with fluoride, as well as many conventional toothpastes.
Furthermore, fluoride is also used in pesticides and some chemicals
used to create non-stick compounds for pots and pans. Eating
organic foods and avoiding processed foods can also reduce fluoride
consumption.

This study might support avoiding fluoride fluoride ‘Fluoride-Free

Diet Stimulates Pineal Growth in Aged Male Rats’. [10]

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How to detox your pineal gland

Besides melatonin, there are a few supplements that can be helpful.

Here are the ones I found to be most relevant:

● Iodine is a mineral found in sea vegetables, like seaweed or

kelp. This vital mineral assists the thyroid gland in
regulating hormones and is one of the most efficient
removers (chelators) of heavy metals from the body. Iodine
chelates heavy metals such as mercury, lead, cadmium, and
aluminum, as well as fluoride.

● Shilajit is plant material produced over millions of years

from plants preserved in dark crevices of the Himalayan
Mountains. Shilajit forms a thick resin that’s packed with 85
different trace minerals including fulvic acid. Fulvic acid
helps eliminate toxins and heavy metals, supporting the
decalcification process.

● Turmeric is another excellent supplement for your pineal

gland detox. This study in Pharmacogn Magazine shows
that curcumin, the active ingredient in turmeric, can prevent
and potentially reverse the damage from fluoride exposure.
[11]

● Chaga Mushrooms: The Chinese call it the “King of Plants.”

In Siberia, it’s the “Gift from God.” And for the Japanese,
it’s the “Diamond of the Forest.” Not bad for wood-rotting
fungus! Hundreds of scientific studies have demonstrated
the potent effects of the Chaga mushroom on the immune,
hormonal, and central nervous systems. Studies in Finland
and Russia found that Chaga is an efficient anti-tumor
agent as well as antiviral. Chaga provides us with
phytochemicals, nutrients, and melanin. The pineal gland
uses melanin to help shield us from UV light. From my
research, the Siberian Chaga appears to be the most potent

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with the highest recorded levels of antioxidants according to

the ORAC Scale. [12] [13] [14] [15]

● K2 or factor X: Intestinal microflora in animal tissues

produces vitamin K1 & 2. You can find it in organ meats,
fermented dairy products, like cheese or butter (grass-fed
butter), sauerkraut, and marine oils.

In 1945, the “Isaac Newton of Nutrition,” a former dentist

named Weston Price, described a vitamin-like compound
that plays a major role in:
● Growth
● Reproduction
● Brain function
● Tooth decay prevention
● Protection against calcification of the arteries

● Tamarind: One study and a follow-up study from the early

2000s demonstrated that tamarind increased the excretion of
fluoride in urine compared to the control group. The
researchers believe tamarind may even be able to reverse the
effects of skeletal fluorosis caused by ingesting fluoride.
[16] [17]

● Green Superfoods: Finally, eating raw, green foods that are

rich in chlorophyll will also help chelate heavy metals from
your blood while nourishing it. Chlorophyll-dense foods like
chlorella, spirulina, and wheatgrass also increase oxygen
levels, repair damaged tissue, and boost the immune system.

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Conclusion
The pineal is an important gland and might play many roles beyond
melatonin production. It may also serve as a connection to a
“source” or a divine higher power.
It is now being proven in science that the pineal via its piezoelectric
effect through the pressures CSF imposed on the gland may be like
a radio receiver. Moreover, the pineal may allow us to have the
ability to access information in the form of extremely high
frequencies.
In other words, the pineal gland may serve as a connection with a
force we might classify as mystical, holy, divine, God or the creator.
However, one chooses to call this force or energy; it's difficult to
deny its existence.
Information may be at the root of this connection and this might
explain the dramatic changes in blood with the healing exosomes
being discovered with meditators which are connecting and
activating the pineal gland through Dr. Joe Dispenza’s work.

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Chapter 18: Supra-Physiological
Dosing
Dosing Ideas, Conclusion & Final Words on Melatonin
The Silver Bullet & Why Melatonin Is So Important Today

Is melatonin the silver bullet?

We have all heard the term “Silver Bullet”. From Wikipedia: “folklore, a
bullet cast from silver is often one of the few weapons that are effective
against a werewolf or witch.
The term is also a metaphor for
a simple, seemingly magical,
solution to a difficult problem:
for example, penicillin was a
silver bullet that allowed
doctors to treat and successfully
cure many bacterial infections.”
With all the powerful aspects melatonin is involved with inside your body
and how it works to protect you especially during stress it seems that
melatonin should absolutely carry this badge of honor as being a Silver
Bullet against stress and diseases caused by stress. We discussed stresses
as mental-emotional, chemical, physical or structural, microbial, and
electromagnetic stress. These stressors are worse now than 10 years ago
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and especially when compared to how our parents grew up. Moreover,
they will only get worse over time due to the reckless advance of
technology and the ability for tech to allow us to be even more productive
and “busy” 24/7.

"Taking melatonin may extend your healthy,

productive life span. I personally take 100mg every
night! As we age, our body produces less and less
melatonin, depriving you of this sleep-enhancing, free
radical scavenging, heart calming, immune-
stimulating, cancer-fighting hormone- in short
depriving you of one of your body's best defenses
against aging. Replenishing your supply of this vital
hormone may allow you to live longer and allow you
to avoid crippling diseases such as arthritis, diabetes,
heart disease, cancer, Alzheimer's, and Parkinson's.
The possibility of this is more than wishful thinking.
Laboratory studies show that giving melatonin to
aging animals has extended their lifespan by as much
as 20%"

Russel Reiter, MD, PhD

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Why melatonin isn’t more well known?

Our healthcare system being

sold out to Big Pharma and
the revolving door in
Washington allowing drugs
and drug companies to
destroy the true intentions of
what a health care system is
supposed to stand for versus an FDA that has a design based on
keeping the population in a constant state of consumption of Big
Pharma’s products. Cures are not popular molecules for these
companies to study as the ROI or return on investment is not great
enough. Yes, that’s right, your health is not the most important goal
for this, a behemoth of a system called Big Pharma. It is a group of
executives that sit around and strategize how to best capitalize.
Keeping you in a disease state taking their drug day after day month
after month and year after year, making sure their shareholders are
happy and their stock price elevated.

Look at our current situation with COVID-19 and how censorship

has not allowed anything except vaccines to be heard over social
media as well as news channels. I personally know friends and
businesses that have been shut down for speaking up about natural
solutions to raising the immune system, as well as natural antivirals.

A good example is colloidal silver which has a tremendous antiviral

effect and is completely safe to consume. Companies and people
who were trying to educate the public about this are either being
thrown in jail or silenced another way. Ozone is another therapy.

I had Dr. Frank Shallenberger on my YouTube channel called

CellularReset and the interview was taken down due to not

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conforming to the community standards and or violating spreading

misinformation on COVID-19. And of course, melatonin has not
gotten its deserving recognition. It's been covered on a couple of
small news outlets and various papers here and there, but wouldn't
you think that Dr. Fauci or other prominent voices would be
encouraging the public to consume such a safe and effective
hormone?

Dangers of using sleeping pills?

Sleeping pills are the 3rd leading

cause of death in the United
States. In fact, I’d go as far as
saying that sleeping pills are
criminal in my mind. According
to ScienceDaily, based on an
article published in the British
Medical Journal, “Feb. 27, 2012 — People are relying on sleeping
pills more than ever to get a good night's rest, but a new study by
Scripps Clinic researchers links the medications to a 4.6 times
higher risk of death and a significant increase in cancer cases
among regular pill users.” [1]

This is just speaking to the overall health risk and danger

medications for sleep have in general.

The Pharmacy Times printed a story stating, “Sleeping pill users in

the middle third (of sleeping pill consumption) had a 20% increased
risk of developing cancer, whereas those in the top third of users had
a 35% increased risk. Zolpidem users in the top third had a 28%
increased risk of major cancer. Temazepam users in the middle third
had a 44% increased risk of major cancer, and users in the top third
had a 99% increased risk. The study’s results indicated that the

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increased risk of death and developing cancer associated with

sleeping pill use was not attributable to pre-existing diseases.” [2]

That means these medications CAUSED

CANCER in these cases. By extrapolating
their findings to the entire US population,
the researchers estimate that sleeping pills
may have been associated with 320,000 to
507,000 excess deaths in 2010. Did you
read that? 3-500,000 deaths! That makes
sleeping pills the THIRD LEADING
CAUSE OF DEATH in the United States,
just 13% behind cancer.

But wait, here’s the real kicker! If sleeping pills are associated with
these numbers and cancer is a clear side effect, how many cases of
the 600,000 cancer deaths a year are due to sleeping pills? The
numbers start to blur, but it is clear these medications are causing
much more harm than potential good.

Don't support them by using them, someone's life, if not your own
may be on the line.

To see the bigger picture and the tremendous danger these drugs
represent we have to consider that according to the U.S. Center for
Disease Control (CDC), 2,468,435 people died in the U.S. alone in
2010. If this estimate is accurate, it means that 13% to 20.5% of
those deaths may have been associated with sleeping pills.

Again, a 460% higher risk of death, potentially contributing to

20.5% of all the deaths each year, and a 99% potential increase in
cancer for a non-life-threatening condition is insane.

It is time for melatonin and other natural sleep-promoting options to

shine. Sleep is like a symphony and it has a flow of changes from

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light sleep, deep sleep, and REM. If someone were to be knocked

out by Mike Tyson then placed next to a person sleeping soundly,
they might look the same. However, when each person got up they
would feel quite different. The person waking up after an Ambien or
any of the other conventional sleeping pills will not have
experienced the same level of restful sleep when compared to an
individual who’d slept naturally.

In fact, many sleeping pills actually suppress melatonin, and when

one considers the powerful effects of melatonin as a cancer inhibitor
it makes sense that suppressing natural melatonin production will
increase cancer risks. Also, we have discussed many diseases and
negative aspects of health caused by poor sleep. Low melatonin
leads to poor sleep and many acute and chronic diseases.

Route of delivery: melatonin supplementation

One major consideration

regarding supplementing
with melatonin is the
different routes of delivery
or administration. Of
course, the most common
is oral supplementation.
Like with all oral routes of
delivery melatonin must
have indoor gastric acid
and pancreatic enzymes before it is then metabolized through the
liver. This is the reason in this study that oral administration of
melatonin only demonstrated a 2.5 % absorption rate. [3]

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By contrast, an intravenous or subcutaneous injection may bypass

hepatic metabolism for what's called “first pass” through the liver.

When I was first introduced to the term peak plasma it was when I
was considering beginning using glutathione suppositories during
my personal journey with chronic Lyme disease and mold illness.
At the time I didn't know what was wrong with me and I just knew
that I had massive inflammation in my body. After looking at the
role of glutathione in the body I knew this would be a helpful
nutrient, however, I wasn't interested in regular visits to a doctor’s
office to receive these intravenously. It was then that I discovered
suppositories.

Suppository delivery

I began using glutathione

suppositories and noticing
the drastic improvement in
my condition I decided to try
intravenous administration.
What I found was I actually
had a better response with the
suppositories than I did with
the procedure that can cost
$150 and two hours of my Picture provided by Advanced Biome Corp.

day to go to the doctor’s

office. This got my attention and wanted to understand why the
suppositories seem to work better. This is where the concept of peak
plasma had the answers to my question.

The term peak plasma is simply referring to maximal blood levels

of a certain nutrient after it is administered. This is where one can
look at various routes of administration and judge the most effective

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in order to promote the most absorption into the body.

With this in mind let's look at a study by Kennaway and Seamark

which showed that subcutaneous injection of melatonin quickly
leads to high peak plasma levels, but it declines rapidly. By contrast,
oral administration leads to a lower but longer lasting and constant
peak plasma melatonin level.

DeMuro demonstrated that intravenous injection of melatonin can

reach a much higher serum peak plasma levels of melatonin
concentration when compared to oral administration. However, the
half-life of melatonin in the serum showed no significant difference
between these two different routes of administration. What this
means is that the routes of melatonin administration will influence
the peak plasma level of melatonin but not the half-life of melatonin.
This means melatonin will last just as long-circulating in the blood
no matter what route of delivery of administration you use.

What about liposomal delivery?

Liposomal delivery systems, with their advanced nutrient

bioavailability, are becoming more popular. There are over 65,000 peer
reviewed published studies on liposomal delivery. They are utilized in
medicine for the delivery of vaccines, hormones, enzymes, vitamins and
botanicals.
Liposomes are tiny lipid bubbles
about the width of a single human
hair. They are made out of the same
type of fat as our own cell membranes
called phospholipids. Liposomes are
stable and can carry both water and
fat-soluble nutrients. When
formulated correctly, they can Figure 1: mage of orange melatonin
facilitate absorption as soon as they molecule contained within a liposome

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land on the tongue, and can help protect breakdown by digestive acids,
enzymes and first pass through the liver. Because they are made of the
same lipids that compose our own cell membranes, they may assist
nutrients to gain access into the cell membrane and optimize cellular
support.
Liposomal technology like suppository has been said to provide the power
of intravenous therapy. Because of enhanced delivery and absorption,
nutrients delivered in liposomal form at lower doses may offer equal or
greater efficacy than higher doses provided in forms that are less
bioavailable.[8],[9]
Their potency is impressive. In liposomal form, the absorption of
melatonin or glutathione can compare to that of intravenous formulations
and appears to help maintain intracellular storage.[10],[11] Even better,
the phospholipids in liposomes are therapeutic. They help nourish every
cell membrane by providing the lipids needed to function optimally and
flush out toxins that accumulate there.

With all of the documentation, many have concluded that a very

high pharmacological dose of melatonin under the supervision of a
physician or healthcare provider in the therapy of various conditions
should be safe and acceptable. Melatonin protects us under stress
therefore it might make sense to supplement melatonin under times
of stress or when our body is dealing with various disease
conditions. The aging process seems to be slowed through the
supplementation of melatonin and for those looking to simply be
healthier and live longer than the use of melatonin supplementation
may make sense in this situation as well.

Being the author of this book, I've made it evident and stated it
before that I take 100 mg to 200 mg of melatonin each night
personally. I either take it in a suppository or in a liposomal delivery
forum which is much more absorbable than the 2.5 % oral
absorption. I have done this for nearly 2 years now and have never
felt better. This may not be for everyone and it is certainly important
that this is discussed with your healthcare provider before you start

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something like a super physiological melatonin dosing schedule.

For the vast majority of people reading this book these high doses
would be safe and very effective in supporting the body and brain in
a wide range of natural stress and disease states.

Recap of all the ways melatonin can support

your health
● Degenerative Neurological Disease

● Memory and Cognitive Problems

● Immune System Weakness; Susceptibility to Infections: both acute and

chronic

● Autoimmune Diseases

● Digestive Diseases

● Skin Conditions

● Premature Aging

● Mood, Mental/Emotional Conditions

● Cancer

● Liver Disease

● Cardiovascular Disease

● Sexual Decline and Infertility

● Low-Stress Resistance, Poor Mitochondrial Function

● Autism & Childhood Development Issues

● Metabolic diseases like Diabetes

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I think it's important to

consider at this point that
we are no longer really
living in a natural
environment. In the past,
we did not have to deal
with this unnatural green
and blue light emitting
from our cell phones,
computers, televisions,
and the lighting in our homes. We did not have to deal with the
melatonin-destroying medications that some of us are on. We did
not have to deal with the electromagnetic stress that lowered our
melatonin levels, and hopefully, after reading this book you've
chosen to turn your Wi-Fi router off at night. Moreover, we also
have not evolved to have to deal with all of the chemical toxins in
our environment.

Technology has created a situation for us to be ultra-productive with

our mobile devices, being able to run a business through a handheld
device creates a situation where there is never really downtime and
unless we make it so. I am just as guilty of this as anybody, as it
becomes an addiction to be more and more productive and to share
your life with others on social media instead of taking time to enjoy
quiet and peace.

Lastly, there is the lack of sunshine on our skin and into our eyes
which allow us to store melatonin only to be dumped when we are
in complete darkness. Avoiding the sun and wearing sunglasses is a
massive headwind to us producing and releasing the maximum
amount of melatonin each night.

Indeed, we are living in a much more stressful time in many regards

than we have been evolutionarily able to evolve to handle with
regards to the production of melatonin allowing us to buffer these

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stressors. I for one would not be without my melatonin after taking

into account all of the facts presented in the research we've discussed
throughout this book.

Conclusion

I've been working on this book for nearly

a year and a half, and it has been a labor
of love, and there has been a tremendous
feeling of purpose to deliver this
information to the world. Although there
have been a couple of other very well-
written books on melatonin there has
been new research since those were
published and I felt that a holistic and
naturopathic viewpoint on integrating
melatonin to support various health
concerns was needed.

I honestly can't think of one condition that wouldn't benefit from

supplementing with melatonin as it has such a wide range and
diverse and positive effect on so many aspects of health through the
stress responses. Just think of all the changes that have occurred over
the years with the invention of light bulbs and artificial light,
harmful EMFs, drugs, toxins in our water supply, chemicals from
plastics in our food and water, poor air quality, aluminum, mercury-
laden fish and other heavy metals, GMO’s, pesticide and chemical-
laden food, microbiome destroying antibiotics, technologies that
adrenalize us throughout the day and superbugs like COVID-19.

In our current state of a global pandemic, we also have concerns

with the safety and efficacy of the experimental vaccines that are
being forced on us. With the isolation, social distancing, and fear-
based media it is no wonder people are suffering from many mental
and emotional afflictions.

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There has never been a more appropriate time for the widespread
use of melatonin. Of course, it is my opinion that high dose
supraphysiological dosing in many cases might be the most effective
use of the miracle molecule. Through my own biohacking
experiences using supraphysiological melatonin dosing I have
literally done months at 800 mg and I've had nothing but positive
effects in my resilience to stress. I have also not found any
challenges when abruptly discontinuing the use, which supports the
research showing that it doesn't shut down our own production, but
also on a personal level I find this to be true.

I'm certainly not advocating everybody go out and start

supplementing that much melatonin right away, and as always, my
advice would be to find a doctor that understands melatonin who can
help guide you with an appropriate dosing schedule and protocol
created for your unique case.

Unfortunately, there are not enough doctors that know of the

incredibly long list of benefits melatonin has to offer. Yet, other
prominent physicians like Dr. Joe Mercola, Dr. Russell Reiter, and
Dr. Frank Shallenberger share my viewpoint after digging into the
research, as I have.

Indeed, it is a time for melatonin's miracle story to be told and this

was my intention with this book. Now that you have the knowledge
regarding melatonin, the miracle molecule, it is your responsibility
to share this with the people that you love and care about.

Thank you for reading my book and I hope that the information you
have acquired from this book helps you to be healthier, live longer,
and be more resilient to stress.

When we are healthier, we're happier and when we're happier we

treat ourselves better. When we treat ourselves better, we treat other
people better. When we treat other people better, other people are
happier, and the world is a better place for it. Let us use melatonin
to become healthier and happier and start the cascade into creating
a better world for us all.

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