13 Ketogenic low-carbohydrate diets have no

metabolic advantage over nonketogenic low-

carbohydrate diets.
Johnstone CS, et al. Am J Clin Nutr. 2006 May;83(5):1055-
61. [Medline]

14 Split decisions: meat-heads unite!

By Alan Aragon
Copyright © May 1st, 2008 by Alan Aragon
Home: www.alanaragon.com/researchreview
Correspondence: [email protected]

2 ‘Berried’ in hope: a scientific look at antioxidants

and the implications of exotic fruit juice marketing.
By Alan Aragon

8 Protein co-ingestion stimulates muscle protein

synthesis during resistance type exercise.
Beelen M, et al. Am J Physiol Endocrinol Metab. 2008 Apr
22; [Epub ahead of print] [Medline]

9 Body Composition and Fitness during Strength

and/or Endurance Training in Older Men.
Sillanpaa E, et al. Med Sci Sports Exerc. 2008
May;40(5):950-958. [Medline]

10 Minimal nutrition intervention with high-

protein/low-carbohydrate and low-fat, nutrient-
dense food supplement improves body composition
and exercise benefits in overweight adults: A
randomized controlled trial.
Lockwood CM, et al. Nutr Metab (Lond). 2008 Apr
21;5(1):11 [Epub ahead of print] [Medline]

11 Effect of a pre-exercise energy supplement on the

acute hormonal response to resistance exercise.
Hoffman JR, et al. J Strength Cond Res. 2008 Apr 15;
[Epub ahead of print] [Medline]

12 Magnesium therapy for periodic leg movements-

related insomnia and restless legs syndrome: an
open pilot study.
Homyak M, et al. Sleep. 1998 Aug 1;21(5):501-5. [Medline]

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 1 
 the assay methodology used. This is why single tests for
antioxidant capacity can only give a limited view of the big
‘Berried’ in hope: a scientific look at antioxidants and picture. More on this later.
the implications of exotic fruit juice marketing.
By Alan Aragon THE PARADOXICAL ROLE OF OXIDATION

Correlation with Disease

INTRODUCTION & DEFINITIONS
At the micro level, ROS have been observed to damage nucleic
In This Article acid, and directly injure cells via lipid peroxidation in the
membranes.2 As well; oxidative stress can result in changes in
The word “antioxidant” immediately conjures the perception of ion balance which can cause disturbances in cell volume. At the
disease-fighting, anti-aging miracle agents. It’s become a very macro level, oxidative stress is a clinically important
marketable (and profitable) buzzword in both the lay and the phenomenon because it’s been correlated with a range of
academic press. So, the common leap of logic is that a diet must diseases including cancer,3 cardiovascular disease,4 cognitive &
be packed to the max with antioxidants in order to be optimal for neuronal decline,5 macular degeneration,6 and osteoporosis.7 As
health. And of course, more is better when it comes to a matter of fact, there’s what’s known as the free radical theory
antioxidants, right? In the following sections I’ll take a look at of aging, also called the free radical hypothesis of aging. First
the claims and the research behind products that have made their proposed in 1956 by Denham Harman,8 this theory states that
way to stardom based on purported antioxidant effects. This free radicals produced from aerobic respiration are the
article will start off on a technical/theoretical note, and steadily underlying cause of age-related disease, and ultimately, death.
morph into the nitty-gritty. But before I open up Pandora’s box, However, the challenge to this theory is that increased
let’s get an introductory grip on the fundamentals. production of reactive species may merely be the result of age-
related diseases, and not necessarily their cause. Let’s look at the
Fundamental Shop Talk dual function of oxidative by-products, and why oxidation
cannot be blanketly viewed as a bad thing.
Most people casually throw around the terms “oxidation”
“oxidative stress” and “antioxidant” without having a vague clue Preventive & Defensive Effects
of what they actually mean. Just a warning to those who have
mentally blocked out their chemistry classes – this section will With all this talk about preventing free radical-induced cellular
resurrect those mentally traumatic times. In the chemical sense, damage and disease, the redeeming functions of reactive species
oxidation can be broadly defined as the loss of electrons (from are often overlooked. Under normal healthy conditions, cells
an atom, molecule, or ion). Reduction – a gain in electrons – contain both antioxidants and their counterparts (ROS/RNS).
occurs as a result of oxidation. Those who truly want to nit-pick Redox homeostasis, or the balancing act of redox signalling is
at these working definitions will point out that electron transfer tightly controlled, much like the body’s self-regulation of pH.4
may or may not occur despite changes in oxidation state. Indeed, there are instances when the generation of oxidative
stress is beneficial. For example, increased ROS/RNS generated
Since oxidation and reduction are inseparable phenomena, the at sites of trauma or inflammation can destroy biological agents
chemical reactions involving them are coined redox reactions; an attempting an invasion of the affected tissues. Another
abbreviation of oxidation-reduction. Redox is a perpetual interesting example is a nitric oxide-donating aspirin currently
process within all cells of the human body; it’s an indispensable investigated for its potential as a cancer-preventive agent. In an
aspect of the transfer of energy. The negative connotation of ironically elegant mechanism, it induces a state of oxidative
oxidation is perhaps rooted in its potential to result in the stress wherein cancer cells are destroyed via apoptosis or
overproduction of reactive oxygen species (ROS – free radicals, necrosis.9,10
oxygen ions, and peroxides) as well as reactive nitrogen species
(RNS – nitric oxide and its metabolites) which can damage cells. NATURE VERSUS MANUFACTURE
Oxidative stress, a term often interchanged with oxidative
damage, can be defined as a marked excess of ROS/RNS Antioxidant Supplements on Trial
production despite the body’s attempts to defend against it.
“...it was thought that manipulation of oxidative stress should
Antioxidants act as agents that suppress the effects of ROS/RNS. reflect an effective improvement in the treatment of heart disease
Barry Halliwell, one of the most prolific (and sensible) patients. Unfortunately, not a single pathophysiologic
researchers in the area of oxidative stress, defines an antioxidant achievement in the field of oxidative stress has had a significant
as “any substance that delays, prevents or removes oxidative impact on the cardiologic therapy so far.”
damage to a target molecule”.1 Antioxidants can be
biosynthesized (created by the body), and their primary The above quote by Ceconi et al is another way of saying that
manifestations, at least in mammalian cells, are catalase, we have failed miserably at treating or preventing heart disease
glutathione peroxidase, and superoxide dismutase. According to with antioxidant supplementation.11 The most widely used
Halliwell, ranking any compound or agent’s antioxidant ability antioxidant vitamins (beta-carotene, C, & E) have been
is not a simple thing, since this can vary greatly depending upon

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 2 
ineffective in most controlled intervention trials, and have even of course, the business opportunity. Everyone has been invited to
been seen to increase mortality, cardiovascular risk, and/or a “meeting”. For the few who haven’t been to one, an MLM
cancer risk.12 To top things off, recent systematic reviews and meeting typically follows a format rooted in basic sales 101:
meta-analyses concur that supplementing the diet with these Bait the prospect by invitation to a gathering that appears
vitamins has no effect on disease prevention, and may even unimposing; even fun. Then, sit the prospect down, and present
increase mortality.13-16 The limitations of this research lie mainly the painful downsides of the prospect’s current situation. Then,
in the heterogeneity of the subjects with respect to state of present a solution: a one-of-a-kind product, whose exorbitant
disease versus fitness. Not to mention, epidemiological studies price is completely justified by its unparalleled quality. While
are typically swamped with uncontrolled variables. you’re at it, promise wealth and prosperity with very little time
Nevertheless, the data as a whole just about nullifies the and effort required. Show the success stories and rags-to-riches
therapeutic potential of supplementing the diet with these testimonials. Finally, ask for the sale. Closing the sale involves
particular compounds. signing up the prospect as either a distributor or a customer. The
advent of food-based MLM adds the extra selling point of
Whole Foods for the Win? improving health and longevity via ‘natural’ means.

Digging into the literature, I was surprised to find that fruit and Superfoods to the Rescue
vegetable intakes’ correlation with decreased disease risk was
not the absolute landslide I expected. The majority of research “Superfood” is likely a mass media-born term whose origin
indicates that higher intakes of fruit and vegetable lower the would be next to impossible to track down. It’s based on the
incidence of cardiovascular disease,17-21 stroke,22-24 and lung idea that certain foods are more nutrient-dense (or have more
cancer.25 However, results have been disappointing for lowering biologically active nutrients for disease prevention) than others,
the risk for cancers of the ovary, prostate, kidney, pancreas, and thus deserve the moniker. Functional foods or
breast, and colon.26-33 Despite this inconsistency, one thing is Nutraceuticals are more common terms thrown around in
certain: whole fruits and vegetables have never been observed to scientific circles, presumably since they sound less dramatic and
increase disease risk or mortality like the supplemental more clinical, but the basic definitions are the same.
antioxidant vitamins did, and they consistently show cardio- Phytochemicals and Zoochemicals are protective compounds in
protective benefits. plant and animal foods, respectively. In the peer-reviewed
literature, ‘functional’ foods such as fatty fish/fish oil, garlic, tea,
So what’s the discrepancy of effects between the whole foods olives/olive oil, red wine, cruciferous vegetables, and tomatoes
and the pills all about? It may be a case of either spotlighting the have received a great deal of press for their disease-preventive
wrong agent, or simply missing much of the agents responsible potential.34,35 My main point of contention with the concept of
for the beneficial effects. Blood levels of a nutrient (in our case functional food is the fact that all foods are integrally functional
an antioxidant such as beta-carotene or the like) might be found within the context of a balanced diet if they provide calories
in high concentrations in folks who consume higher amounts of and/or essential nutrients for health. It’s impossible to use a
food rich in the given nutrient. Consumption of such foods may single parameter (such as antioxidant capacity) to rank foods on
be correlated with decreased disease risk, but that’s exactly the a hierarchy of effectiveness against inherently complex diseases
crux of the disconnect: correlation does not equal causation, and whose causes are multifactorial.
errors can crop up as a result of even the most careful
assumptions. Berry Profitable: Mangosteen, Noni, Acai... (Oh My)

Foods in their unprocessed state are highly complex in terms of The class of superfood we’re focused on in this essay is the
both nutrient content and the interplay/synergy of nutrients and recently coined crop of superfuits. There’s no doubt in my mind
structural components. So, while it would be convenient to that the superfruit (and as a result, the superjuice) market is
isolate and dose up on a single nutrient or set of nutrients that we making a killing. According to a recent article in the Los
presume are cardio- or cancer-protective, these nutrients may Angeles Times online, Tahitian Noni International Inc. sold $2
either be – a) inactive outside of the natural matrix of the food, billion worth of noni juice in its first 10 years by 2006. This
or b) not the correct protective agents at all in the first place. article also reports that an executive of XanGo (a major
Since there are hundreds, if not thousands of potential agents to mangosteen juice distributor) announced at a recent convention
choose from in any given food species, this error isn’t an easy that since its 2002 launch, their product has exceeded a
one to avoid. So, in our attempt to further the art of preventive cumulative $1 billion. Pomegranate juice sales by POM
medicine by isolating antioxidant nutrients for supplementation, Wonderful have hit $50 million since 2003, according to Goliath
the data brings us back to square one: it’s better to eat the whole business research. MonaVie is a Utah-based company that sells
damn fruit or veggie. an acai berry juice blend. Although the company has only been
around since 2005, they’ve gotten some hefty national publicity
FRUITS OF OPPORTUNITY on Fox News (more than once) and the Rachel Ray Show. Acai
is also listed as the #1 superfood on Oprah’s website, receiving
Almost everyone reading this knows or has known someone in this unofficial ranking by pop diet book author Dr. Nicholas
multi-level marketing (MLM). Picture that bright-eyed, near- Perricone.
crazed enthusiasm of the distributor describing the product, and

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 3 
SCIENCE IS SKEPTICAL picrylhydrazyl (DPPH), and ferric reducing antioxidant power
(FRAP). Antioxidant potency, inhibition of LDL oxidation, and
In Vitro Versus In Vivo total polyphenol content were factored into the ranking. Here are
the beverages in the following order from greatest antioxidant
Is all of this hype justified, or is it all a steamy crock of butt- capability to least:
nuggetry? The short answer is that there is no short answer, but
one thing is certain: large leaps of faith are being made by 1) Pomegranate juice 6) Acai juice
consumers. Berries are among the most concentrated sources of 2) Red wine 7) Cranberry juice
polyphenols, tannins, and stilbenoids. Collectively, these 3) Concord grape juice 8) Orange juice
compounds have anticancer, anti-inflammatory, neuroprotective, 4) Blueberry juice 9) Iced tea beverages
and antioxidant properties.36 The most widely studied class of 5) Black cherry juice 10) Apple juice
phytochemicals in berries are flavanols, a type of flavonoid, The above data serves to further reinforce the folly of limiting
which is a subclass under parent category of polyphenols. In our assessment/judgement of foods based on ORAC alone. It
vitro (in the test tube), flavanols have powerful, specifically also begs the question, is a $40 bottle of MonaVie acai juice
measurable antioxidant effects, inhibiting the damaging effects blend really better than a $2 bottle of Charles Shaw merlot? I
of a wide range of reactive species. However, it has been don’t think so.
difficult to determine whether or not the in vitro effects of these
compounds occur in vivo (in the body) to any clinically relevant Research Supports Fruit, but Not Necessarily Juice
degree. This may be due to their metabolic fate during
absorption, which can involve significant degradation into The research on the potential effects of fruit juice is still very
simpler chemical species whose original biologic effects have preliminary, but so far it’s been hit and miss. In a 3-year study
been drastically altered or removed. Given this, it’s not very by Aviram et al, pomegranate juice was seen to reduce blood
surprising that in vivo antioxidant effects of antioxidant-rich pressure, LDL oxidation, and carotid artery thickness in patients
foods (and supplements) have been a frustrating mix of positive, with carotid artery stenosis.39 In this same trial, the juice also
neutral, and even pro-oxidative.12 Although it's generally increased paraoxonase-1 (PON1) activity. PON1 is a high-
accepted that antioxidant effects must contribute in some way to density lipoprotein-associated enzyme that prevents adverse
the cardio-protective benefits of fruits and vegetables, the actual oxidative modification of low-density lipoprotein. Thus, lowered
degree to which they contribute is unknown. As we’ll see next, PON1 is linked with increased risk for cardiovascular disease.
it’s also tough to quantify via standard analytical methods.
In contrast to the pomegranate results in the diseased population,
ORAC is Not the Oracle Bazzano et al investigated the correlation between fruit,
vegetable, and fruit juice intake and the development of type-2
Oxygen radical absorbance capacity (ORAC) has been a huge diabetes in 71,346 female nurses who at the start of the study (18
buzzword in both lay and clinical circles. Pop diet books treat years ago) were free of disease.40 An increase of 3 total daily
ORAC as if it’s the ultimate judgement of a food’s worth. Juice servings of fruit and vegetable consumption was not associated
salesmen pump up their products based on ORAC ranking. As with development of diabetes. An increase of 1 daily serving of
always, things are never so simple. ORAC measures the degree green leafy vegetable consumption was associated with a
and rate of free radical quenching, or inhibition of oxidation slightly lower risk of developing diabetes. And now for the
effects. The main problem with ORAC is its lack of specificity.37 kicker – an increase of only 1 daily serving of fruit juice was
It measures the antioxidant capacity of a solution, but offers no associated with an increased risk of diabetes.
meaningful compositional information. Being a non-specific
assessment, ORAC does not account for flavanol content – or For those who don’t lend much credence to correlational
general phenolic content for that matter. This is especially research, a recent controlled intervention trial by Dalgard et al
limiting, since as previously mentioned, foods rich in phenolic examined the effect of orange juice, blackcurrant juice, and
compounds (which include flavonoids) have a stronger link to vitamin E supplementation on Paraoxonase-1 (PON1) activity in
disease prevention than antioxidants per se. Put differently, patients with peripheral artery disease.41 Participants received
ORAC values do not account for compounds in foods that may two of four possible treatments: 1) 250 ml orange juice and 250
exert health effects completely independent of antioxidation. To ml blackcurrant juice; 2) 15 mg vitamin E; 3) 250 ml orange
quote an enlightening review by Robbins et al, 37 juice and 250 ml blackcurrant juice and 15 mg vitamin E; or 4)
carbohydrate placebo. PON1 activity was unaffected by the juice
“The ORAC tends to be the preferred method to determine or vitamin E treatments, therefore, no effect on disease risk or
antioxidant capacity in foods and is considered an indicator for prevention was seen.
potential biologic activity although the link between antioxidant
capacity and protective health effects has yet to be clearly Adverse Potential of Noni & Mangosteen Juice
established.”

Speaking of going beyond ORAC testing, Seeram et al assessed The Polynesia-based noni fruit has a uniquely dichotomous
various antioxidant-rich beverages according to ORAC as well reputation in the literature. Research on this food is still scarce,
as 3 other tests:38 trolox equivalent antioxidant capacity (TEAC), but it has shown anti-inflammatory potential in rodents as well
free radical scavenging capacity by 2,2-diphenyl-1- as inhibitory effects on breast cancer and neuroblastoma cells in

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 4 
vitro.42 However, serious concerns arose in 2005 after two • While it would be convenient to dose up on a single nutrient
published case studies pointed toward a hepatotoxic effect.43 A or set of nutrients presumed to be disease-preventive, these
29-year-old man with previous hepatitis developed sub-acute nutrients may either be inactive once removed from food, or
hepatic failure after consuming 1.5 L noni juice over 3 weeks, they may not be the correct protective agents in the first place.
resulting in urgent liver transplantation. The other case report
was a 62 year-old woman without previous liver disease, who Fruits of Opportunity
developed acute hepatitis after consuming 2 L noni juice for a 3-
month period. Shortly after these case reports were released, two • The superfood concept is based on the idea that certain foods
reviews by researchers employed by Tahitian Noni International are more nutrient-dense (or have more biologically active
(a major seller of noni Juice) were published.44,45 The reviews nutrients for disease prevention) than others, and thus
basically dismissed the adverse case reports as anomalies that deserve the moniker. Superfood and functional food share the
likely did not have a causal relationship with noni juice same basic definition.
consumption, which they believe is actually liver-protective. In a • It may be misleading to call any food “functional” since all
more recently published case study, mangosteen juice, noted for foods are integrally functional within the context of a
its anti-inflammatory properties,46 was recently seen to cause balanced diet if they provide calories and/or essential
severe lactic acidosis in one patient.47 Again, this is bound to be nutrients for health.
written off (especially by the mangosteen juice industry) as an • Compared to a relative consistency of positive effects in vitro
anomalous event, but it’s still worth storing in the consumer (in the test tube), in vivo (in the body) effects of polyphenols
caution file. have been mixed and inconclusive.
• Though ORAC may be a popular method for judging a
SUMMARY food’s antioxidant capacity, it’s far from comprehensive.
• When all is said and done, the link between antioxidant
Definitions capacity and protective health effects has yet to be clearly
established in the first place.
• Oxidation can be broadly defined as the loss of electrons.
• Compared to the consistently positive outcomes in research
• Reduction – a gain in electrons – occurs as a result of
on whole fruits, the effects of fruit juice have been a mixture
oxidation.
of positive, negative, and neutral.
• Oxidative stress, a term often interchanged with oxidative
• Noni and mangosteen juice both have spawned published
damage, can be defined as an excessive production of cell-
case studies of acute adverse effects, although juice industry-
damaging reactive species (which include free radicals).
employed researchers have dismissed them as anomalous.
• Antioxidants act as agents that suppress the cell-damaging
effects of reactive species.
CONCLUSION
Dual Role of Oxidation
“Antioxidant” has become a standard, almost mundane
• Reactive species (also called oxygen radicals or nitrogen marketing term. As such, its actual definition and technical
radicals) can damage cells at both the surface and nucleic implications are often ignored or misinterpreted. “Superfoods”
levels. have their benefits, but their most noticeable effect is their
• Oxidative stress is linked with a wide range of chronic and ability to slim down your bank account at a rapid rate. The best
degenerative diseases, including the aging process in general. practical advice is to realize that all fruits have a multitude of
• Under normal healthy conditions, cells contain a self- health-protective compounds, many of which have not yet been
regulating balance of both antioxidants and oxidants. identified. It’s not necessary to go to the exotic ends of the earth,
• Increased production of reactive species resulting from or reach the end of your finances to attain “special” fruit
oxidation can destroy invading pathogens at site of products that promise longevity and a markedly better quality of
inflammation, thus protecting the body. life than the ones you currently enjoy. While certain fruits might
have greater ORAC than others, they may come up short in other
• In an example related to the above principle, nitric oxide-
indexes of disease prevention. So, nix the antioxidant
donating aspirin induces a state of oxidative stress wherein
supplements, and attempt to achieve a reasonable variety of
cancer cells are destroyed via apoptosis or necrosis.
fruits (and vegetables). Strive to have a minimum of 2 different
types of fruit per week, and two servings of fruit per day. I
Nature Versus Manufacture
realize that’s asking a lot from some folks. Above all, the best
• The most widely used antioxidant vitamins (beta-carotene, C, bet is to stick to the fruits you like the taste of, because chances
& E) have been ineffective in most controlled intervention are, those are the ones you’ll consistently consume. I’ll end with
trials, and have been observed to increase mortality, another bit of scientific wisdom from Barry Halliwell:12
cardiovascular risk, and/or cancer risk. “To me, dietary polyphenols are typical xenobiotics,
• Whole fruits and vegetables have never been observed to metabolized as such and rapidly removed from the circulation.
increase disease risk or mortality like the supplemental They may be beneficial in the gut in the correct amounts. But too
antioxidant vitamins did, and they consistently show cardio- much may not be good and thus, I suggest that one should be
protective benefits. content with eating a good diet for now.”

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 5 
 6. Hollyfield JG, et al. Oxidative damage-induced inflammation
SPECIAL RESOURCE: THE BIG LISTS 48,49 initiates age-related macular degeneration. Nat Med. 2008
For those of you who are intent on ranking foods, Feb;14(2):194-8. [Medline]
regardless of the points I made in my article. 7. Sheweita SA, Khoshhal KI. Calcium metabolism and
____________________________________________ oxidative stress in bone fractures: role of antioxidants. Curr
Drug Metab. 2007 Jun;8(5):519-25. [Medline]
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ƒ The total antioxidant content of 1120 food samples 10. Rigas B. The use of nitric oxide-donating nonsteroidal anti-
from the USDA National Food and Nutrient inflammatory drugs in the chemoprevention of colorectal
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for your health? Cardiovasc Res. 2007 Jan 15;73(2):341-7.
ƒ Stability of antioxidants in food composites during [Medline]
storage (for 0–65 wk) at –80°C 13. Bjelacovik G, et al. Mortality in randomized trials of
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ƒ Total antioxidant concentrations of cereals prevention: systematic review and meta-analysis. JAMA.
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association among 1104 cases in a prospective study of Feb;46(2):688-93. [Medline]
130544 men in the European Prospective Investigation into 47. Wong LP, Klemmer PJ. Severe lactic acidosis associated
Cancer and Nutrition (EPIC). Int J Cancer. 2004 with juice of the mangosteen fruit Garcinia mangostana. Am
Mar;109(1):119-24. [Medline] J Kidney Dis. 2008 May;51(5):829-33. [Medline]
30. Weikert S, et al. Fruits and vegetables and renal cell 48. Halvorsen BL, et al. Content of redox-active compounds (ie,
carcinoma: findings from the European prospective antioxidants) in foods consumed in the United States. Am J
investigation into cancer and nutrition (EPIC). Int J Cancer. Clin Nutr. 2006 Jul;84(1):95-135. [Medline]
2006 Jun 15;118(12):3133-9. [Medline] 49. Halvorsen BL, et al. A systematic screening of total
31. Larsson SC, et al. Fruit and vegetable consumption in antioxidants in dietary plants. J Nutr. 2002 Mar;132(3):461-
relation to pancreatic cancer risk: a prospective study. 71. [Medline]
Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):301-5.
[Medline]
32. van Gils CH, et al. Consumption of vegetables and fruits
and risk of breast cancer. JAMA. 2005 Jan 12;293(2):183-
93. [Medline]
33. Michels KB, et al. Prospective study of fruit and vegetable
consumption and incidence of colon and rectal cancers. J
Natl Cancer Inst. 2000 Nov 1;92(21):1740-52. [Medline]
34. Breslow JL. n-3 fatty acids and cardiovascular disease. Am
J Clin Nutr. 2006 Jun;83(6 Suppl):1477S-1482S. [Medline]
35. Kris-Etherton PM, et al. Bioactive compounds in foods:
their role in the prevention of cardiovascular disease and
cancer. [Medline]
36. Seeram NP. Berry fruits: compositional elements,
biochemical activities, and the impact of their intake on
human health, performance, and disease. J Agric Food
Chem. 2008 Feb 13;56(3):627-9. [Medline]
37. Robbins RJ, et al. Analysis of flavanols in foods: what
methods are required to enable meaningful health
recommendations? J Cardiovasc Pharmacol. 2006;47 Suppl
2:S110-8. [Medline]
38. Seeram NP, et al. Comparison of antioxidant potency of
commonly consumed polyphenol-rich beverages in the
United States. J Agric Food Chem. 2008 Feb 27;56(4):1415-
22. [Medline]
39. Aviram M, et al. Pomegranate juice consumption for 3 years
by patients with carotid artery stenosis reduces common
carotid intima-media thickness, blood pressure and LDL
oxidation. Clin Nutr. 2004 Jun;23(3):423-33. [Medline]

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 7 
 particularly athletic protocol (2 hours of resistance training) was
measured, you’d think that they would incorporate a dietary
Protein co-ingestion stimulates muscle protein protocol supportive of such a regime. This was not the case.
synthesis during resistance type exercise.
Protein (for the whole day) in the control group amounted to
Beelen M, et al. Am J Physiol Endocrinol Metab. 2008 Apr 22;
78 g. For an average subject weight of 69 kg, this puts the
[Epub ahead of print] [Medline]
protein intake at 1.1g/kg, which is still below the range
PURPOSE: To investigate the impact of protein co-ingestion suggested for athletes by a number of authoritative sources. For
with carbohydrate on muscle protein synthesis during resistance the range of athletes on the strength-endurance continuum,
exercise. METHODS: 10 healthy males were studied in the Tipton et al recommends 1.2-1.7g/kg,1 the International Society
evening after consuming a standardized diet throughout the day. of Sports Nutrition’s position stand indicates 1.4-2.0g/kg,2 and
Subjects participated in 2 experiments: 0.15g/kg/hr carbohydrate noted author/practitioner Lyle McDonald recommends 2.5-
(CHO) or 0.15 g/kg/hr carbohydrate with protein hydrolysate 3.0g/kg.3 In close agreement with McDonald, I’ve seen athletes
(CHO + PRO) during a 2hr resistance exercise session. Subjects thrive optimally at 2.0-3.0g/kg. The latter range of protein intake
received a bolus of test drink prior to and every 15 min during not only distances athletes from deficiency, it also takes care of
exercise. Continuous intravenous tracer infusions were used. any beneficial effects that extra protein might have that hasn’t
Blood and muscle biopsies were collected to assess whole-body been covered in the current literature, which has mainly been
and muscle protein synthesis rates during exercise. RESULTS: concerned with maintaining nitrogen balance in non-dieting
Protein co-ingestion lowered whole-body protein breakdown athletes. Collectively, these recommendations yield an average
rates by 8.4%, compared to the ingestion of carbohydrate only, of 2.1g/kg (which coincidentally has been the de facto
and augmented protein oxidation and synthesis rates by 77 and recommendation in the trenches for nearly a half-century). This
33%, respectively. Whole-body net protein balance was negative works out to 48% more than the present study’s protein
in CHO, whereas a positive net balance was achieved following allotment. Even if we limited the comparison to the peer-
the CHO+PRO treatment (-4.4 vs 16.3 micromol phe/kg/hr, reviewed stuff, it’s still 30% more than this trial’s allotment.
respectively). Mixed muscle protein fractional synthetic rate
Back to our study, during exercise, both groups received a
(FSR) was 49% higher following protein co-ingestion.
0.15g/kg bolus of carbohydrate every 15 minutes, and the
CONCLUSION: Even in a fed state, protein co-ingestion
experimental group was given additional protein at an average of
stimulates whole-body and muscle protein synthesis rates during
1.4g with each carbohydrate dose. This amounted to an extra
resistance type exercise. SPONSORSHIP: None listed.
21g protein hydrolysate in the experimental group by the end of
Study Strengths the trial. This dose was enough to prevent the negative protein
balance seen in the carb-only group. The composition of each
Hydrostatic weighing was used. Although, if this was a chronic meal prior to testing was not specified, but the macronutrient
effect study measuring changes in body composition, DXA proportion of the diet was 62% carbohydrate, 13% protein, and
would have been preferred, especially since getting the 26% fat. While this “standard” breakdown may be fine for
procedure done on the small sample (10 subjects) wouldn’t endurance athletes on double the calories, it’s potential for
necessarily have broken the budget. Muscle protein balance was insufficient protein for strength athletes and dieters is obvious.
comprehensively assessed, versus limiting the assessment to
protein synthesis as done in other studies. The final meal of the The timing of each meal and snack prior to testing was not
day before testing, as well as the meals/snacks on the day of specified, with the exception of the final meal, which was
testing were provided by the lab. finished 2 hrs prior to arriving at the lab. During the infusion of
the metabolic tracers prior to blood sampling and muscle biopsy,
Study Limitations
another hour elapsed before the exercise protocol was engaged.
Sample size was small, so the crossover design helped mitigate This created a lag period of 3 hrs. Given that a total 78g of
that fault somewhat. These subjects were untrained, and yet they protein was consumed by the control group throughout the day
were put through a 2-hour full-body resistance training session prior to testing, it’s safe to assume that it was spread over a
(what?!). I can see 60-90 minutes of resistance training being minimum of 3 meals, containing roughly 25-30g protein. Think
realistic and even a bit lengthy for most noncompetitive trainees. about this: 25-30g protein ingested 3 hours prior to a 2-hour
2 hours (even minus the 10-minute warm-up) is unrealistic for resistance training bout is not only sub-optimal, but it’s a highly
the unconditioned. unlikely practice amongst competitive and recreational strength
athletes. I typically recommend the following pre-workout
Comment/Application protein dosing: 0.25g/lb within a solid meal finished 60-90
In concept, this trial is wonderful. It steps up to fill a minutes before training, or 0.25g/lb in a shake ingested within
longstanding void in sports nutrition research by testing the 60 minutes of training. This would diminish, if not completely
effect of mid-training protein intake in the nonfasted state. This negate the need to compensate for poor pre-workout protein
differs from reams of research that has tested subjects first thing timing and dosage, as was the case with mid-training protein
in the morning on an empty stomach. The present trial even hydrolysate ingestion. As a final note, one of the researchers
takes things a step further by testing subjects in the evening after responsible designing this study works for DSM Specialty
all the day’s meals are consumed. However, this grand concept Foods, whose product PeptoPro® (better yet, PeptoBro) was the
is marred by some crucial design flaws. First of all, given that a protein supplement used in this trial.
Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 8 
Body Composition and Fitness during Strength and/or Comment/Application
Endurance Training in Older Men.
My first thoughts are that a 2-day-per-week program, whether
Sillanpaa E, et al. Med Sci Sports Exerc. 2008 May;40(5):950- it’s endurance training, strength training, or both, is insufficient
958. [Medline] in total volume to make much of an impact on body composition
in folks who otherwise are sitting at a desk when they’re not
PURPOSE: To examine adaptations in body composition and sitting on a couch watching TV. Indeed, this is apparent when
physical fitness during a 21-week strength and/or endurance looking at the subjects’ starting and ending stats after 21 weeks:
training period in 40-65-yr-old men, and to compare the
usefulness of different methods for the analysis of body
Parameter Group Change after 21 weeks
composition. METHODS: 53 men were randomized into the
endurance training (E), strength training (S), combined strength DXA Caliper BIA
and endurance training (SE), or control (C) groups. S and E % Body fat Endurance -2.1 -1.7 -2.3
trained 2 and SE 2 x 2 times a week for strength and endurance. Strength -1.9 -1.8 -1.5
Combination -1.7 -1.9 -1.4
RESULTS: Percentage of fat decreased similarly in all training
Control +0.1 -1.0 -1.3
groups. Fat% measured by DXA at baseline and its change ____________________________________________________
correlated with those recorded by bio-impedance, skinfolds, and
waistline. Lean mass in legs increased only in S (as seen by Waist (cm) Endurance -2.7
Strength -2.7
DXA), but the thickness of vastus lateralis and intermedius Combination -1.8
measured by ultrasound increased (7-11%) in all training groups, Control -0.4
and that of triceps brachii increased in S (22%) and SE (20%).
Maximal concentric force increased significantly in S, SE, and E Weight (kg) Endurance -1.5
(by 22, 23, and 7%), and maximal oxygen uptake increased in Strength -0.9
both E (11%) and SE (11%). CONCLUSIONS: Waist Combination -0.6
circumference and skinfold thickness seem to reasonably assess Control -0.2
changes in percent body fat. However, only DXA was able to
separate small differences between the groups in training- An odd outcome was the combination group’s lack of greater
induced changes in lean body mass. Combined strength and weight loss with 4 days per week of exercise (versus the 2 days
endurance training is of greater value than either alone in per week in the endurance and strength groups). The authors
optimizing body composition or improving physical fitness in themselves speculated that this was due to “a possible increase
older men. SPONSORSHIP: Ministry of Education, Finland, in energy uptake”, translation: an increase in face-stuffage.
and the Central Finland Health Care District (Jyva skyla,
Finland). Without dietary control measures imposed, it’s clear that
compensatory increases in food intake occurred in order for the
Study Strengths changes to be that small. Let’s keep in mind that on average,
these subjects at baseline were a weight of 76 kg (167.2 lb) at
I have a personal affinity for this study since I’ll be 40 years old 25.4% body fat. In 21 weeks, none of the groups lost more than
in about 3.5 blinks of an eye. Another strength of this trial is the 2% body fat than the control group, which did no exercise at all.
concept of weights versus cardio, versus both. It provides food
for thought for folks who have a liking for one mode of training The endurance and combination groups experienced an equal
but not the other. It also forces them to come up with solutions increase in VO2 max, but not so with strength training alone. The
for reconciling the shortcomings of their training programs. degree to which sheer volume (as opposed to mode of exercise)
Furthermore, accurately and consistently tracking body contributed is open for speculation. Maximal strength, measured
composition progress is a challenge that constantly nags both by 1-repetition maximum, increased by 22% in the combination
fitness practitioners & anyone involved with altering body group and 23% in the strength group. This indicates that there
composition. This trial addresses some of those issues. Both the was little if any competition between the strength and endurance
resistance training and the endurance training protocols were gains in the combination group. This outcome is in agreement
closely supervised and periodized into three 7-week phases, with previous research showing that strength and endurance
progressively increasing volume and intensity. adaptations can happen concurrently.4 I’ll add to this that
strength training can benefit endurance performance, but not
Study Limitations necessarily vice versa.5.6
As commonly seen with exercise studies, the dietary control is A notable adaptation was that the endurance group increased
missing. In fact, the word “diet” is completely absent from the its one-rep max by 7% in the leg extension as well as the bench
text. The problem is that body composition flux is equally press, indicating a systemic strength increase (albeit a small one)
determined by dietary intake, not just exercise output. Although since the upper body was not specifically trained. This right here
the investigators came up with some useful data, half of the is also an explicit example of the “newbie effect” where any
equation is unaccounted for in this trial. Aside from this blooper, kind of training – endurance, strength, or other – tends to
the trial was well conceived and executed. improve performance across a number of parameters, despite an
absence of specifically imposed demand.

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 9 
 So, it now boils down to the spotting the shortcomings in the
authors’ interpretation and application of the results, which I’ll
Minimal nutrition intervention with high-protein/low- discuss, among other things.
carbohydrate and low-fat, nutrient-dense food
Comment/Application
supplement improves body composition and exercise
benefits in overweight adults: A randomized controlled As noted by the authors, the use of meal replacement powders
trial. (MRPs) is an established method for lowering various markers
Lockwood CM, et al. Nutr Metab (Lond). 2008 Apr 21;5(1):11 of disease risk. In previous research, MRPs have consistently
[Epub ahead of print] [Medline] succeeded at minimizing the dietary decision-making process,
thus enhancing long-term compliance.7,8 The interesting and
PURPOSE: To examine 10 weeks of combined aerobic + unique aspect of this trial that separates it from similar
resistance exercise (EX) versus exercise + minimal nutrition predecessors was the high degree of autonomy given to the
intervention designed to alter the macronutrient profile, in the subjects. The timing of MRP consumption, as well as its
absence of energy restriction, using a high-protein/low- incorporation into the diet was left solely to the subjects’
carbohydrate/low-fat, nutrient-dense food supplement. discretion. And as mentioned, the subjects were instructed to eat
(EX+MRP). METHODS: 38 overweight subjects were assigned the rest of their diet ad libitum (as desired).
to either a control group (CON), EX, or EX+MRP. EX and
EX+MRP participated in a resistance + endurance training. The results were dramatically in favor of the exercising group
EX+MRP consumed 1 shake/day (weeks 1 and 2) and 2 using the MRP for endurance capacity, blood lipid profile (with
shakes/day (weeks 3-10). RESULTS: EX+MRP significantly the exception of triacylglycerols which surprisingly were
decreased total energy, carbohydrate and fat intake and increased unaffected), and body composition. Another interesting result
protein and fiber intake. EX and EX+MRP decreased fat mass, was a lack of difference in strength gains between the exercising
with a greater decrease in EX+MRP than EX and CON. Muscle groups. The authors conceded that improvements in the MRP
mass increase only reached significance in EX+MRP. Only group were attributable to the superior (and well-established)
EX+MRP significantly improved absolute VO2max. Time-to- satiating effect of protein, which led to a decreased intake of the
exhaustion during treadmill testing increased in EX but was other macronutrients (carb and fat intake dropped by 71 g and
significantly less than in EX+MRP. Total cholesterol and LDL 23 g, respectively) and thus total calories dropped from 2166 to
decreased only in the EX+MRP. Total chol-to-HDL ratio, 1854. The decreased caloric consumption occurred alongside a
decreased significantly in both exercise groups. 32.4% increased net amount of protein (from 86.3 g to 131.3 g),
CONCLUSION: Without dietary restrictions, a high- setting the stage for better lean mass support in addition to
protein/low-carb/low-fat, MRP modified ad libitum greater fat oxidation than the other groups.
macronutrient and energy intake, improved adaptations to Throughout the trial, the control group and the exercising MRP-
exercise, and reduced the variability of individual responses for free group had a protein intake of roughly 1.0g/kg while the
fat mass, muscle mass and time-to-exhaustion. All 3 effects MRP group had a touch over 1.5g/kg. As we’ve seen as an
occurred in 100% of EX+MRP subjects. SPONSORSHIP: increasingly common theme, this was the case of a marginally
Phillips Performance Nutrition, LLC (Golden, CO) adequate protein intake versus one that was closer to ideal. Since
Study Strengths this was the ad libitum intake of the groups, it was eye-opening
to see that this population inadvertently consumed just under the
Here’s another conceptually interesting study. The idea of bottom of the range considered minimally adequate for athletes.
minimal nutritional intervention is appealing because the “no- This illustrates the point that, contrary to the message parroted
brainer” simplicity factor is very powerful when it comes to by medical and health professionals at large, adequate protein
dietary adherence. Complexity and constant calculating only intake for optimal training adaptations are not always being
work long-term for a small sector of the public. On the dietary easily met or exceeded by the general overweight public.
control front, food logs were analyzed with computer software.
All body composition assessments were done after a 12-hour The MRP used in this trial was Full Strength® by Phillips
fast. A multi-compartmental approach was used to measure Performance Nutrition (also the study’s sponsor). It’s very
body composition, using a combination of dual-energy X-ray similar macronutritionally to the traditional MRPs marketed to
absorptiometry (DEXA), air displacement plethysmography the sports/fitness crowd. 1 packet has 40g protein, 25g
(ADP), and bioimpedance spectroscopy (BIS). Training included carbohydrate, 5g fat, the full spectrum of vitamins and minerals,
both strength and endurance training, and was supervised by 6 g fiber, and a few “bonus” ingredients which are usually inert.
ACSM and NSCA-certified trainers. Since it’s designed to replace meals, its price reflects that, at
roughly $3.00 per serving. Since the active agent is protein, if
Study Limitations you wanted to apply this study’s results and maintain the
This study was actually well-designed, and it measured what it convenience and no-brainer compliance factor, this can easily be
aimed to measure under the intended circumstances. One could done by buying a whey protein powder in bulk (5 lbs or more).
argue that the subjects were overweight newbies, so the results Instead of paying 7.5 cents per gram of protein, you’ll be paying
are potentially limited to that population. However, it can also be 2 cents per gram. At 20 g per scoop of whey protein, 2-4
postulated that this is the population that needs this type of scoops/day would be the protein equivalent of 1-2 MRP packets,
protocol the most (exercise + simplistic dietary modification). minus the superfluous ingredients.

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 10 
Effect of a pre-exercise energy supplement on the acute limitation was the placement of the trial in the morning after an
hormonal response to resistance exercise. overnight fast. While this can eliminate potential variability in
subjects’ pre-test blood substrate levels, it also doesn’t
Hoffman JR, et al. J Strength Cond Res. 2008 Apr 15; [Epub necessarily reflect the reality of many athletes, who typically
ahead of print] [Medline] consume a mixed-macronutrient breakfast, and thus train in a fed
PURPOSE: To examine the effect of a pre-exercise energy state. Finally, as an acute study, questions remain about what
sport drink on the acute hormonal response to resistance long-term training adaptations that may or may not occur.
exercise. METHODS: 8 experienced resistance-trained men
Comment/Application
were randomly provided either a placebo (P: maltodextrin) or the
supplement (S: combination of branched chain amino acids As with any industry-funded supplement study, I try to see if
(BCAA), other essential amino acids (EAA), creatine, taurine, there’s any substance behind the inevitable agenda. Of all the
caffeine, and glucuronolactone). Subjects performed 6 sets of no ingredients, creatine would most likely be the active ergogenic
more than 10 repetitions of the squat exercise at 75% of their 1- agent. However, both groups creatine loaded (20g/day for 7
rep maximum (1RM) with 2 minutes of rest between sets. Blood days) prior to testing, eliminating that variable. The authors
draws occurred at baseline pre-exercise, immediately post- (IP), speculate that, since BCAA and creatine aren’t known to acutely
15 minutes post- (15P), and 30-minutes post (30P) exercise for affect exercise performance, the active ergogenic must be one or
measurement of serum growth hormone, total and free a combination of the caffeine, taurine, and glucuronolactone.
testosterone, cortisol, and insulin concentrations. RESULTS: The big question is, which one(s) contributed? Perhaps the
Although significant differences were seen only at set 5, the total bigger question is whether we should really care anyway, since
number of repetitions and training volume tended (p = 0.08) to the actual performance enhancement was so minuscule
be higher with S compared to P. Serum growth hormone and (approximately 1 repetition more than the placebo treatment on
insulin concentrations were significantly higher at 15P and IP, the 5th set of 6 sets of squats).
respectively, in S compared to P. CONCLUSION: Pre-exercise
energy S consumed 10 minutes before resistance exercise can Caffeine’s ability to increase endurance capacity is well-
enhance acute exercise performance by increasing the number of established. However, research on its ability to acutely affect
reps performed and the total volume of exercise. This resulted in strength or anaerobic capacity has yielded a mixed bag of
a significantly greater increase in both growth hormone and positive9-11 and negative (no-effect) outcomes.12-15 In the present
insulin concentrations, indicating an augmented anabolic study, the product (Amino Shooters) contained 110 mg caffeine.
hormone response to this pre-exercise S. SPONSORSHIP: A single dose was given within 500 mL water, 10 minutes prior
Champion Nutrition (Concord, CA). to warming up for exercise testing, which began 20 minutes after
ingesting the supplement. Previous caffeine dosing/timing
Study Strengths
protocols average roughly triple this dose (5 mg/kg), and a
“Experienced resistance-trained” subjects were used for this greater lag time between ingestion and testing (30-60 minutes),
trial, although this qualification was never clearly defined in the to allow the caffeine to reach peak plasma levels. Given this, it’s
text. At any rate, using experienced subjects was appropriate for highly unlikely that caffeine was the primary ergogenic agent.
the purpose of eliminating the beginner effect wherein a wide
range of protocols will work regardless. It was also appropriate To date, taurine has only a single study showing its performance
to use trained subjects because this population would benefit effect on humans.16 Zhang et al examined its effect on exercise-
most from supplementation since they’re closer to their genetic induced oxidative stress, and as exercise performance measures
limits for performance, and supplementation would be warranted in untrained subjects. Taurine increased time-to-exhaustion,
as a means to counteract plateaus. maximal oxygen consumption, and maximal workload. It should
be noted that his trial was funded by Taisho Pharmaceutical, a
Study Limitations major manufacturer of taurine. Also, this trial was neither
blinded nor placebo-controlled. It’s also crucial to note that the
The sample size was particularly small (n=8). However, an taurine dose was 6g/day for 7 days. This is a far cry from the
attempt to alleviate this was via crossover; both sets of subjects present study’s single pre-exercise dose of 1.5g. As a matter of
got a chance to be tested under experimental conditions after a fact, in a recent study by Armenanto et al,17 20g taurine for 7
“wash-out” phase. A glaring flaw in this trial was a lack of days (used as a placebo control for creatine loading) did not
dietary control. There was exactly none. Scrolling back to improve push-up performance despite the very high dose.
Beleen study in this issue (nutrition & exercise section), you’ll Finally we have glucuronolactone, which basically puts the
notice that the final meal the night before testing, in addition to “Bull” in Red Bull. It’s included in various energy drinks whose
the dietary intake the day of the trial was standardized and active agent is caffeine. Glucuronolactone has zero scientific
provided by the lab. Although this degree of control is rare, there evidence that it imparts any ergogenic effects on its own, but I
should have been a minimum degree of control imposed on diet suppose it makes any ingredient list look cutting-edge.
in the present trial, since the test involved an endurance-oriented
strength test. In other words, the trial assessed total volume of Considering the inclusion of unsubstantiated ingredients, the
repetitions, and not maximal strength. Since it boiled down to a miniscule performance increase, and the questionable benefit of
volume game, it’s possible that the diet’s influence on glycogen physiological pulses of insulin and growth hormone beyond that
content could have influenced the outcomes. But since this elicited by the existing training and diet, Amino Shooters might
factor was unaccounted for, it remains a confounder. Another best be suited for trashcan target practice.

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 11 
 authored a study showing the benefit of ZMA on strength,
power, and testosterone levels in football players.18 The problem
Magnesium therapy for periodic leg movements-related with this study is twofold; in addition to holding a patent on
insomnia and restless legs syndrome: an open pilot ZMA, Conte’s company funded the study. Recently, a better
study. controlled trial with a supervised resistance training protocol
found no effect of ZMA on strength, body composition, and
Homyak M, et al. Sleep. 1998 Aug 1;21(5):501-5. [Medline] hormonal markers of anabolism and catabolism.19
PURPOSE: To examine the effect of oral magnesium therapy The RDA for magnesium for adults is 400-420 mg for men, and
on symptoms in patients with moderate restless leg syndrome 310-320 mg for women.20 Requirements decrease slightly with
(RLS) and/or periodic limb movements during sleep (PLMS) age. In the present study, subjects took a nightly magnesium
METHODS: In an open clinical and polysomnographic study in dose of 12.4 mmol (297 mg). This dose was relatively well-
10 patients (mean age 57 years; 6 men, 4 women) suffering from tolerated; no major side effects were reported other than
insomnia related to PLMS (n = 4) or mild-to-moderate RLS (n = occasional mild diarrhea in some, but not all subjects. The
6). Magnesium was administered orally at a dose of 12.4 mmol chemical form used was magnesium oxide, which has been seen
in the evening over a period of 4-6 weeks. RESULTS: to have poor bioavailability compared to magnesium chloride,
Following magnesium treatment, PLMS associated with arousals magnesium lactate and magnesium aspartate.21 Without any
(PLMS-A) decreased significantly (17 vs 7 events per hour of dietary accounting, it’s impossible to know whether or not this
total sleep time. PLMS without arousal were also moderately dose was providing a pharmacologic/therapeutic surplus, or
reduced (PLMS per hour of total sleep time was 33 vs 21). merely correcting a pre-existing magnesium deficiency.
Sleep efficiency improved from 75% to 85%. In the group of
patients estimating their sleep and/or symptoms of RLS as The possible mechanisms of action involved with magnesium’s
improved after therapy, the effects of magnesium on PLMS and improvement of RLS/PLMS symptoms are mostly speculative at
PLMS-A were even more pronounced. CONCLUSION: Our this point, but it likely involves the central nervous system
study indicates that magnesium treatment may be a useful (CNS). Magnesium is known to have a suppressive effect on
alternative therapy in patients with mild or moderate RLS-or neuronal excitability, antagonizing calcium flow and the
PLMS-related insomnia. Placebo-controlled investigations excitatory activity of N-methyl-D-aspartate (NMDA). It also
regarding the role of magnesium in the pathophysiology of RLS has an agonistic effect on gamma-aminobutyric acid (GABA), a
and need to be performed. SPONSORSHIP: None listed. neurotransmitter that inhibits stimulation of the CNS.

Study Strengths The authors of the present study reported that the motivation to
conduct the study was to see whether anecdotal evidence would
In order to minimize potential confounding variables, thorough be refuted or supported. Lo and behold, the anecdotes gained
exclusion criteria was imposed. Subjects with abnormal ECG, support, albeit by a trial that had no blinding or placebo control.
EEG readings were excluded from recruitment. Also excluded In more recent research on its therapeutic effect, Held et al saw a
were patients taking benxodiazepine-based hypnotics or any waved (“creeping”) oral dose of 10-30 mmol (240-720mg)
other psychotropic drugs. Those with uremia, chronic bronchitis, magnesium sulfate reverse age-related neuroendocrine and sleep
anemia, or pregnancy were also excluded since those conditions EEG abnoralities.22 By possibly a similar CNS-based
are known to cause symptomatic RLS. mechanism, oral magnesium oxide was observed prevent
Study limitations tension-type headaches in children.23 Given this evidence, it
appears that magnesium deficiency may be a contributing factor
The big limitation here is a complete lack of blinding on both the to disrupted sleep in certain individuals. Due to a lack of dietary
part of the participants and the investigators. That is, both parties control in this area of research, whether pharmacological doses,
were aware of who was receiving the magnesium treatment and rather than deficiency-preventive doses are the real ticket
who was not. Double-blinding this experiment would have lent a remains to be confirmed. Regardless, it seems that magnesium
hell of a lot more credibility to the results, and it would have supplementation is a safe alternative therapy to sleep
been relatively simple to do. Oh well, I suppose pilot studies are medications, whose risk-to-benefit ratio are likely higher than
allowed some slack, but this is quite a critical design flaw. This doses of magnesium within the IOM-based upper tolerable limit
made the patients’ self-reporting of sleep quality an especially (UL) of 350 mg (14.6 mmol).20 Note that this amount applies to
useless bit of data; it’s a good thing that objective supplemental magnesium, not existing magnesium in the diet.
instrumentation (polysomnography; measurement of electrical
activity at various anatomical locations) was used as well. In terms of practical application, the first step would be to get a
grip on what might be preoccupying your night-time thoughts
Comment/Application.
and stressing you out – get those issues resolved first. The 2nd
I chose to review this study because it’s the first one referenced line of defense would be to make sure you’re getting at least
in the ZMA (zinc, magnesium aspartate) supplement ads when 50% of the RDA for magnesium through a daily multivitamin. If
the “better sleep” claim is made. ZMA is marketed towards the above two steps, in addition to a balanced, varied diet don’t
athletes for its purported sleep benefits and enhancement of work, moderate the intake of stimulants by cutting back on
muscular size and strength via hormonal mechanisms. The brand Starbucks. If that doesn’t work, try dosing magnesium within the
associated with ZMA is SNAC, a company owned by Victor upper limit of 350 mg, but always consult with your physician
Conte, former owner of the now-defunct Balco Labs. Conte co- first so you don’t blame me for any surprise contraindications.

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 12 
Ketogenic low-carbohydrate diets have no metabolic vitamins, and electrolytes) registered a gain in lean mass while
advantage over nonketogenic low-carbohydrate diets. decreasing bodyfat by 32%.24 That’s impossible – but that seems
to be the nature of BIA assessment.
Johnstone CS, et al. Am J Clin Nutr. 2006 May;83(5):1055-61.
[Medline] Comment/Application

PURPOSE: To compare weight loss and biomarker change in Nurtrient Ketogenic Non-Ketogenic
adults on a ketogenic low-carbohydrate (KLC) diet or a Kcals 1500 1500
nonketogenic low-carbohydrate (NLC) diet. METHODS: 20 Carbohydrate 33 g, 9% 157 g, 42%
adults [mean BMI = 34.4] were randomly assigned to the KLC Sugar 10 g 85 g
Protein 125 g, 33% 117 g, 31%
(60% of energy as fat, beginning with approximately 5% of Fat 100 g, 60% 50 g, 30%
energy as carbohydrate) or NLC (30% of energy as fat; SFA 35 g, 21% 13 g, 8%
approximately 40% of energy as carbohydrate) diet. During the MUFA 34 g, 20% 16 g, 10%
6-wk trial, participants were sedentary, and 24-h intakes were PUFA 14 g, 8% 7 g, 4%
Cholesterol 620 mg 230 mg
strictly controlled. RESULTS: Mean weight losses were 6.3 kg Fiber 15 g 30 g
and 7.2 kg in KLC and NLC dieters, respectively. Fat losses
Values are listed as: unit of mass, percentage of total kcals
were 3.4 and 5.5 kg in KLC and NLC dieters, respectively.
These outcomes did not differ significantly by group after 6 wk. The body composition outcomes of this trial were interesting and
Blood beta-hydroxybutyrate in the KLC dieters was 3.6 times highly contrary to what the keto advocates would like to have
that in the NLC dieters at week 2, and LDL cholesterol was seen. Looking at the numbers above, its clear that the main
directly correlated with blood beta-hydroxybutyrate. Overall, differences were fat intake, and to a lesser degree, fiber. You can
insulin sensitivity and resting energy expenditure increased and almost picture Sears rubbing his hands together letting out a Dr.
serum gamma-glutamyltransferase concentrations decreased in Evil-esque laugh as his Atkins competition not only failed at
both diet groups during the 6-wk trial. However, inflammatory beating the The Zone in fat/weight loss, but adverse effects were
risk and perceptions of vigor were more adversely affected by only seen in the keto group. Although not to a statistically
the KLC than by the NLC diet. CONCLUSIONS: KLC and significant degree, the non-keto group actually lost more total
NLC diets were equally effective in reducing body weight and weight than the keto group. Body fat loss was also
insulin resistance, but the KLC diet was associated with several insignificantly better in the non-keto group, although I tend to
adverse metabolic and emotional effects. The use of ketogenic not trust BIA assessments. Another interesting tidbit in line with
diets for weight loss is not warranted. SPONSORSHIP: our “statistically insignificant” theme here is that the non-keto
Inflammation Research Foundation (founded and operated by group had a slightly lower protein intake – and still more than
Barry Sears, author of The Zone diet). held its own. These results further support the idea that as long
as protein is sufficient, variations in carbohydrate and fat
Study Strengths
proportion will have very little impact on body composition.
The introductory text did a good job of making the point that not This especially applies to the sedentary population, who don’t
all low-carbohydrate diets are created equal, and that the current utilize carbohydrate for training performance adaptations like the
literature is lacking tightly controlled comparisons of low- athletic population does.
carbohydrate diets with adequate protein, but differing in fat Even when one group has a distinct protein intake advantage,
content/ketogenicity. Perhaps the greatest strength of this trial outcomes can still be very similar, as long as calories are
was its degree of dietary control; all food and drinks were matched, and protein is not grossly underdone. To illustrate this,
provided by the lab. This measure is rarely seen because it’s Luscombe-March et al recently compared a diet consisting of
painstaking and expensive. At this point it’s safe to assume that 29% fat (46 g) & 34% protein (136 g) with an equicaloric diet
Barry Sears is a financial rock star, or one heck of a resourceful containing 50% (76 g) fat & 20% protein (67g) in obese
guy (probably both) since he was able to independently fund this subjects.25 No differences were found in body composition
trial. Physical activity variability was controlled as well changes between the groups as determined by DXA, the gold
(although subjects were instructed to remain sedentary). standard of assessment.
Study Limitations Back to our study, one of the subjects in the keto group dropped
out in the first week due to heart arrhythmias. The diet could
Body composition was determined by the Tanita Body have been a coincidence or a contributor to this, who knows.
Composition Analyzer TBF-300A, a bioelectrical impedance Predictably, subjective ratings of emotion, mood state, and the
analyzer (BIA). Picture the bathroom scale that “zaps” an desire to be physically active were higher in the non-keto group.
imperceptible current through your feet and spits out an estimate There authors were concerned about the increased inflammatory
of your body fat percent. This is disappointing. Not only has this risk markers in the keto group. Finally, no fabled “metabolic
method shown questionable results in research, it has given advantage” was seen in the keto group, since there were no
wacky readings in my personal experience, as well as from differences in the effects of either diet resting energy
observations in others. Body water flux heavily influences BIA expenditure or respiratory quotient. Now all we need is a study
readings. A memorable example of the drastic error potential of such as this one, with a supervised exercise program, on both
BIA is a study by Faintuch et al, where non-obese subjects trained athletes and the obese population. My guess is that the
undergoing a 42 day hunger strike (consuming only water, athletic population will do better on all parameters without keto.
Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 13 
 Classic Sample Splits

Split decisions: meat-heads unite! In the following routines, only resistance training elements are
By Alan Aragon listed. Cardio-respiratory training can be either left out or added
depending on individual goals/preferences. My objective here is
Online there’s been a recent resurgence of discussion about not as much to provide specific plans for verbatim reference as it
bodypart splits versus whole-body training. I suppose you can is to spark your imagination for creating or adapting new
call it vanity versus functionality. Bodybuilders are more protocols. Here are my sample resistance training splits from one
focused on building muscles for aesthetics, whereas the coaches of the earliest incarnations of the Girth Control syllabus:
and bookworms tend to focus more on integrating movements
for better function (for whatever sport). Of course there’s a Full-Body, Intraweek Periodized
legion of folks on the continuum between the two extremes. The
following routines will hopefully have a little something for all Mon Full body, light effort
of you. I used to include a section similar to this in an ancient Tue Off
edition of Girth Control when it was simply a continuing Wed Full body, moderate effort
education syllabus. I have since removed it because I felt it was Thu Off
about 8 years out of date; not to mention, I admittedly was Fri Full body, max-effort
influenced by the semi-recent trend of bodypart split-bashing, so Sat Off
I pulled it from the book. However, I came across it recently and Sun Off
now I regret not leaving it in there. Good thing I have AARR to
resurrect it. Before I list the routines, I’d like to quote some keen Basic Low-Frequency Split
insight by Richard Ellis (A.K.A. Fireproof), owner/operator of Mon chest, back
Clutch Fitness: Tue off
Wed legs, abs
First thing to keep in mind is the training should be Thu off
geared towards your sport/goals. So someone training to Fri arms, shoulders
be a Strongman will do things differently than a track Sat off
athlete. And a bodybuilder may train differently than a Sun off
powerlifter. etc.

But given than in general, you are looking to increase Push-Pull, 6-on, 1-off
muscle (hypertrophy) and strength, there's probably a This program is not suited for busy folks who have jobs/lives,
hierarchy of foundational principles before you really but it’s worth listing because it’s a viable option just like all of
need to worry about the details. the others.
The body can be split in many ways, and spread out in Mon Chest, triceps, anterior delts
many ways. Most people equate "bodypart splits" to Tue Back, biceps, posterior delts
doing 1-2 bodyparts per day, which takes a week to get Wed Legs, abs
through the whole body. Add in rest time and you end up
working your muscles once every 7-10 days. I agree this
Thu Chest, triceps, anterior delts
is NOT ideal for naturals. Fri Back, biceps, posterior delts
Sat Legs, abs
But some people call a "Push / Pull" split "bodypart Sun Off
training." And if you did Push / Pull / off / Push / Pull / off
/ off, you are hitting each muscle twice per week which is
GREAT frequency. So this would great for naturals. And
steroid users would probably grow even better in a Basic Upper/Lower
scenario like this. This is an old standby that packs a good combination of
convenience and simplicity without compromising volume and
So be careful when you say "bodypart training" - it can frequency. It’s one of my favorites (if not my absolute fave for
mean different things to different people. But in general, the time being), so you’ll see a bunch of variations of it.
to accomplish reasonable frequency, I like to either split
the body up in thirds or halves or do full-body work. Mon Upper body
When splitting up the body, you can do it based on Tue Lower body
PLANES of movement, or areas of the body. There are
pros and cons to each, but in terms of hypertrophy, I
Wed Off
don't see it making a difference, if frequency, rest, and Thu Upper body
loading are the same. Fri Lower body
Sat Off
But to repeat what I started with - you have split up your Sun Off
training by parts of the body, right? Since one could
argue that any training, apart from full-body training, is
"bodypart splits" - be careful about dismissing it without
understanding what the person means.

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 14 
Newer Splits Push/Pull-Upper/Lower Variant

These puppies consist of a mix of old and new ideas. I hope Mon Upper body push
everyone realizes that the permutations are endless. Tue Lower body, anterior focus
Wed Off
Upper/Lower Variation Thu Upper body pull
Mon Upper body – high tension (low reps) Fri Lower body, posterior focus
Tue Lower body – high tension (low reps) Sat Off
Wed Off Sun Off
Thu Upper body – low tension (moderate to high reps)
Fri Lower body – low tension (moderate to high reps)
Sat Off Wrapped Up Like a Deuce
Sun Optional ancillary work Here’s my adaptation of a 2-day/week resistance training
regime with 2 days cardio, designed for non-specific general
fitness.
High Frequency, Failure Progression Mon Upper body, general strength/hypertrophy
This regime works best with low volume, 1-2 exercises per Tue Low-moderate intensity endurance-type cardio
muscle/movement, 2-3 sets per exercise. Wed Off
Mon Upper body – no sets to failure Thu Lower body, general strength/hypertrophy
Tue Lower body – no sets to failure Fri Off
Wed Upper body – last set per exercise to failure Sat Full-body, low rest, high rep bodyweight circuits
Thu Lower body – last set per exercise to failure Sun Off
Fri Upper body – all work sets to failure
Sat Lower body – all work sets to failure
Sun Off

Lower frequency, Failure & Rep Manipulation

Mon Upper body – last set per exercise to failure, high reps
Tue Lower body – last set per exercise to failure, high reps
Wed Off
Thu Upper body – all work sets to failure, low reps
Fri Upper body – all work sets to failure, low reps
Sat Off
Sun Off

Upper, Lower, Full (saw this first on bodyrecomposition.com)

Mon Upper body
Tue Off
Wed Lower body
Thu Off
Fri Full body
Sat Off
Sun Off

Mixed Split (an adaptation of something I saw in Layne

Norton’s log at bodybuilding.com)
Mon Chest
Tue Back
Wed Legs
Thu Upper body
Fri Lower body
Sat Off
Sun Off

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 15 
 18. Brilla LR, Conte V: Effects of a novel zinc-magnesium
formulation on hormones and strength. J Exerc Physiol
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Sports Sci. 2004 Jan;22(1):65-79. [Medline] 19. Wilborn CD, et al. Effects of Zinc Magnesium Aspartate
2. Campbell B, et al. International Society of Sports Nutrition (ZMA) Supplementation on Training Adaptations and
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2007 Sep 26;4:8. [Medline] Nutr. 2004;1:12-20. [JISSN]
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athlete and coach. 1st ed. Lyle McDonald Publishing; 2007. Health. Magnesium factsheet. [NIH-ODS]
[Publisher’s Site] 21. Firoz M, Graber M. Bioavailability of US commercial
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9. Anselme F, et al. Caffeine increases maximal anaerobic
power and blood lactate concentration. Eur J Appl Physiol
Occup Physiol. 1992;65(2):188-91. [Medline]
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performance in trained and untrained swimmers. Eur J Appl
Physiol Occup Physiol. 1992;64(4):377-80. [Medline]
11. Beck TW, et al. The acute effects of a caffeine-containing
supplement on strength, muscular endurance, and anaerobic
capabilities. J Strength Cond Res. 2006 Aug;20(3):506-10.
[Medline]
12. Collomp K, et al. Effects of caffeine ingestion on
performance and anaerobic metabolism during the Wingate
Test. Int J Sports Med. 1991 Oct;12(5):439-43. [Medline] For those of you who need a motivational kick in the ass, and
13. Hoffman JR, et al. Effect of nutritionally enriched coffee don't mind gushy moments, see Carnegie Melon University
consumption on aerobic and anaerobic exercise professor Randy Pausch give his most recent lecture entitled
performance. J Strength Cond Res. 2007 May;21(2):456-9. Time Management.
[Medline]
14. Roberts MD, et al. Effects of ingesting JavaFit Energy Here’s Randy’s home page, as well as his update page that
Extreme functional coffee on aerobic and anaerobic fitness chronicles his current battle with cancer.
markers in recreationally-active coffee consumers. J Int Soc
Sports Nutr. 2007 Dec 8;4:25. [Medline]
15. AstornioTA, et al. Effect of caffeine ingestion on one-
repetition maximum muscular strength. Eur J Appl Physiol.
2008 Jan;102(2):127-32. Epub 2007. [Medline]
16. Zhang M, et al. Role of taurine supplementation to prevent Thanks once again for getting your brains filled with another
exercise-induced oxidative stress in healthy young men. AARR issue. If you have any questions, comments, suggestions,
Amino Acids. 2004 Mar;26(2):203-7. [Medline] bones of contention, cheers, jeers, any feedback at all, send it
17. Armentando MJ, et al. The effect and safety of short-term over to [email protected]. All suggestions are taken very
creatine supplementation on performance of push-ups. Mil seriously. I want to make sure the publication continues to stand
Med. 2007 Mar;172(3):312-7. [Medline] alone in its excellence.

Alan Aragon’s Research Review, May, 2008                                           [Back to Contents]                  Page 16