Advances in Nutraceuticals and Functional Foods Concepts

and Applications - 1st Edition

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vi About the Editors

researcher in the research group of Professor Sabu Thomas, Vice Chancellor,

a renowned scientist in this area who has sustained international acclaims
for his work in polymer science and engineering, polymer nanocomposites,
elastomers, polymer blends, interpenetrating polymer networks, polymer
membranes, green composites and nanocomposites, nanomedicine, and
green nanotechnology. She completed her PhD in Chemistry at Mahatma
Gandhi University under Dr. Thomas’s guidance. She has visited many
foreign universities as a part of her research activities and has published
over 15 research articles and over 20 book chapters. She has edited ten books
with leading publishers, including Elsevier, Springer, Wiley, and the Royal
Society of Chemistry. Dr. Balakrishnan has received a number of national
and international presentation awards. She also worked as a guest lecturer
in chemistry at the Department of Chemistry, Morning Star Home Science
College, Angamaly, Kerala, India.
Contents

Contributors...................................................................................................... ix
Abbreviations .................................................................................................... xiii
Preface .............................................................................................................. xvii

1. Introduction to Functional Foods and Nutraceuticals ........................ 1

Luana Pulvirenti and Angela Paterna

2. Advanced Nanocarriers for Nutraceuticals Based on Structured

Lipid and Nonlipid.................................................................................. 29
Shafiullah, Syed Wadood Ali Shah, Ismail Shah, Shujat Ali, Aziz Ullah,
Samiullah Burki, and Mohammad Shoaib

3. Nanoparticulate Approaches for Improved Nutrient Bioavailability .. 59

Abdul Qadir, Mohd. Aqil, and Dipak Kumar Gupta

4. Adulteration and Safety Issues in Nutraceuticals and Functional

Foods ........................................................................................................ 79
Shujat Ali, Syed Wadood Ali Shah, Muhammad Ajmal Shah, Muhammad Zareef,
Muhammad Arslan, Md. Mehedi Hassan, Shujaat Ahmad, Imdad Ali, Mumtaz Ali,
and Shafi Ullah

5. Nutraceuticals‑Loaded Nano‑Sized Delivery Systems: Potential

Use in the Prevention and Treatment of Cancer .................................. 105
Mohammed Jafar, Syed Sarim Imam, Sultan Alshehri, Chandra Kala, and
Ameeduzzafar Zafar

6. Nutrition Nutraceuticals: A Proactive Approach for Healthcare ....... 123

Conor P. Akintola, Dearbhla Finnegan, Niamh Hunt, Richard Lalor,
Sandra O’Neill, and Christine Loscher

7. Bioactive Proteins and Peptides as Functional Foods ......................... 173

Deepa Thomas and M. S. Latha

8. News and Trends in the Development of Functional Foods:

Probiotic Dairy and Non‑Dairy Products ............................................. 199
Eliane Maurício Furtado Martins, Wellingta Cristina Almeida do Nascimento
Benevenuto, Aurélia Dornelas de Oliveira Martins, Augusto Aloísio Benevenuto
Junior, Isabela Campelo de Queiroz, Thainá de Melo Carlos Dias, Daniela
Aparecida Ferreira Souza, Daniele De Almeida Paula, and Maurílio Lopes Martins
viii Contents

9. Microencapsulation: An Alternative for the Application of

Probiotic Cells in the Food and Nutraceuticals Industries ................. 239
Daniele De Almeida Paula, Carini Aparecida Lelis, and Nataly De Almeida Costa

10. Nutraceuticals‑Based Nano‑Formulations: An Overview

Through Clinical Validations ................................................................. 277
Shelly Singh and Shilpa Sharma

11. Growth Patterns, Emerging Opportunities, and Future Trends in

Nutraceuticals and Functional Foods.................................................... 311
Asad Ur Rehman, Salman Akram, and Thierry Vandamme

Index.................................................................................................................. 347
Contributors

Shujaat Ahmad
Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal, Dir (Upper),
Khyber Pakhtunkhwa, Pakistan

Conor P. Akintola
Immune Modulation Group, School of Biotechnology, Dublin City University, Dublin, Ireland

Salman Akram
University of Strasbourg, CNRS 7199, Faculty of Pharmacy, 74 Route du Rhin, CS – 60024, 67401
ILLKIRCH CEDEX, France

Imdad Ali
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences,
University of Karachi, Karachi – 75270, Pakistan

Mumtaz Ali
Department of Chemistry, University of Malakand, Khyber Pakhtunkhwa – 18800, Pakistan

Shujat Ali
School of Food and Biological Engineering, Jiangsu University, Zhenjiang – 212013, P. R. China;
College of Electrical and Electronic Engineering, Wenzhou University, Wenzhou 325035, PR China,
E-mail: [email protected]

Sultan Alshehri
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

Mohd. Aqil
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard
(Deemed University), M. B. Road, New Delhi – 110062, India, E-mail: [email protected]

Muhammad Arslan
School of Food and Biological Engineering, Jiangsu University, Zhenjiang – 212013, P. R. China

Wellingta Cristina Almeida do Nascimento Benevenuto

Federal Institute of Southeast of Minas Gerais, Food Science and Technology Department
(DCTA/IF Sudeste MG), Rio Pomba, MG, CEP – 36180-000, Brazil

Samiullah Burki
Department of Pharmacology, Faculty of Pharmacy, Federal Urdu University of Arts,
Science, and Technology, Karachi, Pakistan

Nataly De Almeida Costa

Department of Food Technology, Federal University of Viçosa (UFV), P.H. Rolfs Avenue, Campus,
Viçosa – 36570-900, MG, Brazil

Thainá de Melo Carlos Dias

Federal Institute of Southeast of Minas Gerais, Food Science and Technology Department
(DCTA/IF Sudeste MG), Rio Pomba, MG, CEP – 36180-000, Brazil

Dearbhla Finnegan
Immune Modulation Group, School of Biotechnology, Dublin City University, Dublin, Ireland
x Contributors

Dipak Kumar Gupta

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard
(Deemed University), M. B. Road, New Delhi – 110062, India

Md. Mehedi Hassan

School of Food and Biological Engineering, Jiangsu University, Zhenjiang – 212013, P. R. China
Niamh Hunt
Immune Modulation Group, School of Biotechnology, Dublin City University, Dublin, Ireland

Syed Sarim Imam

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

Mohammed Jafar
Assistant Professor, Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman
Bin Faisal University, P.O. Box – 1982, Dammam – 31441, Saudi Arabia, Mobile: +966502467326,
E-mail: [email protected] [email protected]

Augusto Aloísio Benevenuto Junior

Federal Institute of Southeast of Minas Gerais, Food Science and Technology Department
(DCTA/IF Sudeste MG), Rio Pomba, MG, CEP – 36180-000, Brazil
Chandra Kala
Faculty of Pharmacy, Maulana Azad University, Jodhpur – 342802, Rajasthan, India

Richard Lalor
Fundamental and Translational Immunology Group, School of Biotechnology, Dublin City University,
Dublin, Ireland

M. S. Latha
Department of Chemistry, Sree Narayana College, Chathannur, Kollam, Kerala, India; Department of
Chemistry, Sree Narayana College, Kollam, Kerala, India, E-mail: [email protected]
Carini Aparecida Lelis
Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC),
Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ, 21941-598,
Brazil

Christine Loscher
Immune Modulation Group, School of Biotechnology, Dublin City University, Dublin, Ireland

Aurélia Dornelas de Oliveira Martins

Federal Institute of Southeast of Minas Gerais, Food Science and Technology Department (DCTA/IF
Sudeste MG), Rio Pomba, MG, CEP – 36180-000, Brazil

Eliane Maurício Furtado Martins

Federal Institute of Southeast of Minas Gerais, Food Science and Technology Department (DCTA/IF
Sudeste MG), Rio Pomba, MG, CEP – 36180-000, Brazil, E-mail: [email protected]

Maurílio Lopes Martins

Federal Institute of Southeast of Minas Gerais, Food Science and Technology Department (DCTA/IF
Sudeste MG), Rio Pomba, MG, CEP – 36180-000, Brazil

Sandra O’Neill
Fundamental and Translational Immunology Group, School of Biotechnology, Dublin City University,
Dublin, Ireland, E-mail: [email protected]

Angela Paterna
Institute of Biophysics, National Research Council, Via Ugo La Malfa – 153,90146, Palermo, Italy
Contributors xi

Daniele De Almeida Paula

Federal Institute of São Paulo (IFSP), Campus Avaré - Av. Professor Celso Ferreira da Silva, 1333,
Jardim Europa, CEP 18707-150, SP, Brazil, E-mail: [email protected]

Luana Pulvirenti
Department of Chemical Sciences, University of Catania, Viale Andrea Doria-6, 95125, Catania, Italy
[Dipartimento di Scienze Chimiche, Università Degli Studi di Catania, Viale A. Doria – 6,95125,
Catania, Italy], E-mail: [email protected]
Abdul Qadir
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard
(Deemed University), M. B. Road, New Delhi – 110062, India
Isabela Campelo de Queiroz
Federal Institute of Southeast of Minas Gerais, Food Science and Technology Department
(DCTA/IF Sudeste MG), Rio Pomba, MG, CEP – 36180-000, Brazil

Asad Ur Rehman
University of Strasbourg, CNRS 7199, Faculty of Pharmacy, 74 Route du Rhin, CS – 60024, 67401
ILLKIRCH CEDEX, France; University of Paris Descartes, UTCBS CNRS UMR 8258-INSERM
U1267, Faculty of Pharmacy, 4 Avenue de l’Observatoire, Paris – 75006, France

Shafiullah
Department of Pharmacy, University of Malakand, Chakdara, Dir Lower – 18300, Khyber
Pakhtunkhwa, Pakistan, E-mail: [email protected]

Ismail Shah
Department of Pharmacy, Abdulwali Khan University, Mardan – 23200, Khyber Pakhtunkhwa, Pakistan

Muhammad Ajmal Shah

Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Government College University,
Faisalabad, Pakistan
Syed Wadood Ali Shah
Department of Pharmacy, University of Malakand, Chakdara, Dir Lower – 18300,
Khyber Pakhtunkhwa – 18800, Pakistan

Shilpa Sharma
Department of Biological Sciences and Engineering, Netaji Subhas University of Technology, Dwarka,
New Delhi, India

Mohammad Shoaib
Department of Pharmacy, University of Malakand, Chakdara, Dir Lower – 18300,
Khyber Pakhtunkhwa, Pakistan

Shelly Singh
Department of Biological Sciences and Engineering, Netaji Subhas University of Technology,
Dwarka, New Delhi, India

Daniela Aparecida Ferreira Souza

Federal Institute of Southeast of Minas Gerais, Food Science and Technology Department
(DCTA/IF Sudeste MG), Rio Pomba, MG, CEP – 36180-000, Brazil

Deepa Thomas
Research and Post Graduate Department of Chemistry, Bishop Moore College, Mavelikara,
Alappuzha, Kerala, India
Aziz Ullah
Department of Pharmaceutics, Faculty of Pharmacy, Gomal University, D.I. Khan,
Khyber Pakhtunkhwa, Pakistan

Shafi Ullah
Department of Pharmacy, University of Malakand, Khyber Pakhtunkhwa – 18800, Pakistan;
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences,
University of Karachi, Karachi – 75270, Pakistan, E-mail: [email protected]
Thierry Vandamme
University of Strasbourg, CNRS 7199, Faculty of Pharmacy, 74 Route du Rhin, CS – 60024, 67401
ILLKIRCH CEDEX, France
Ameeduzzafar Zafar
Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Aljouf, Saudi Arabia

Muhammad Zareef
School of Food and Biological Engineering, Jiangsu University, Zhenjiang – 212013, P. R. China
Abbreviations

ABC ATP-binding cassette

ACE angiotensin-converting enzyme
ACE angiotensin I-enzyme
ADA American Dietetic Association
Ag silver
AI artificial intelligence
ALA alpha-linoleic acid
ARA arachidonic acid
Au gold
AuNPs gold nanoparticles
BDPP bioactive dietary polyphenol preparations
CAG compound annual growth
CAGR compound annual growth rate
CAPE caffeic acid phenethyl ester
CCPs caseinophosphopeptides
CD Crohn’s disease
CdS cadmium sulfide
CLA conjugated linoleic acid
CLNA conjugated α-linolenic acid
CPSC consumer product safety commission
CST critical solution temperature
CVD cardiovascular diseases
DALYs disability-adjusted life years
DE dextrose equivalent
DHA docosahexaenoic acid
DIM diindolylmethane
DPP4 dipeptidyl peptidase-IV
DSC differential scanning calorimetry
DTA differential thermal analysis
EC European Commission
EE encapsulation efficiency
EFSA European Food Safety Authority
EGCG epigallocatechin gallate
EGFR epidermal growth factor receptor
xiv Abbreviations

EMS eosinophilia-myalgia-syndrome
Eos essential oils
EPA eicosapentaenoic acid
EPA Environmental Protection Agency
EPS exopolysaccharides
FAO Food and Agriculture Organization
FAS fatty acid synthase
FDA Food and Drug Administration
FIM foundation for innovation in medicine
FOSHU foods for specified health use
FPHs fish protein hydrolysates
FSA Food Standards Agency
Gas glycoalkaloids
GI gastrointestinal
GIP glucose-dependent insulinotropic polypeptide
GIT gastrointestinal tract
GLP-1 glucagon-like peptide-1
GRAS generally recognized as safe
HCl hydrochloric acid
HSE health service executive
IBD inflammatory bowel disease
IBS inflammatory bowel syndrome
IGFR insulin-like growth factor receptor
IL interleukin
ILSI International Life Sciences Institutes
IPP Ile-Pro-Pro
IPP isopentenyl diphosphate
JECFA Joint FAO/WHO Expert Committee on Food Additives
LAB lactic acid bacteria
LCST lower critical solution temperature
LMP low methoxyl pectin
LUVs large unilamellar vesicles
MEP methylerythritol phosphate
Met-S metabolic syndromes
MLV multilamellar vesicles
MMPs matrix metalloproteinases
MPS mononuclear phagocyte system
MRP multidrug resistance protein
MTSG1 mitochondrial tumor suppressor 1
Abbreviations xv

MVA mevalonic acid

NA nicotinic acid
NCDs non-communicable diseases
NEs nanoemulsions
NIOSH National Institute for Occupational Safety and Health
NLCs nanostructured lipid carriers
NPs nanoparticles
NREA Nutraceutical Research and Education Act
NSAIDs non-steroidal anti-inflammatory drugs
O/W oil-in-water
O/W/O oil-in-water-in-oil
OCP office of combination products
OSHA Occupational Safety and Health Administration
OsLu lactulose-derived oligosaccharide
PA palmitic acid
PAA poly(acrylic acid)
PAAM poly(acrylamide-co-butyl methacrylate)
PBS phosphate buffer solution
PC phosphatidylcholine
PCADK poly(cyclohexane-1,4-diyl acetone dimethylene ketal)
PCL polycaprolactone
Pd palladium
PDEAEM poly(N,N9-diethylaminoethyl methacrylate)
PDEAM poly(N,N-diethylacrylamide)
PDMAEMA poly[2-(dimethylamino)ethyl methacrylate]
PE phosphotidyl ethanolamine
PECs polyelectrolyte complexes
PEG poly(ethylene glycol)
PGA poly(glycolic acid)
PK polyketals
PLA polylactic acid
PLGA poly(lactic-co-glycolic acid)
PNIPAM poly(N-isopropylacrylamide)
PNPs polymeric nanoparticle systems
PPARγ peroxisome proliferator-activated receptors
Pt platinum
PUFAs polyunsaturated fatty acids
PVCL poly(N-vinylcaprolactam)
xvi Abbreviations

PVCL-PVA-PEG polyvinyl caprolactam-polyvinyl acetate-polyethylene

glycol
RA rheumatoid arthritis
RES reticuloendothelial system
RESS rapid expansion of supercritical solution
RNA ribonucleic acid
ROS reactive oxygen species
SERS surface-enhanced Raman spectroscopy
siRNA small interfering RNA
SLN solid lipid nanoparticles
SMEDDS self-micro emulsifying drug delivery system
SOD superoxide dismutase
SUVs small unilamellar vesicles
T2DM type 2 diabetes mellitus
TEM transmission electron microscopy
TJs tight junctions
TMC N-trimethyl chitosan
TNF tumor necrosis factor
TNF-α tumor necrosis factor-alpha
UC ulcerative colitis
UCST upper critical solution temperature
US United States
USA United States of America
USDA US Department of Agriculture
USPTO US Patent and Trademark Office
VEGF vascular endothelial growth factor
VPP val-pro-pro
W/O/W water-in-oil-in-water
WHO World Health Organization
Preface

In recent years there is a growing interest in nutraceuticals, which provide

health benefits and are alternative to modern medicine. Nutrients, herbals,
and dietary supplements are significant constituents of nutraceuticals which
make them instrumental in maintaining health, act against various disease
conditions, and thus promote the quality of life. The explosive growth,
research developments, lack of standards, marketing zeal, quality assurance,
and regulation will play a vital role in its success or failure.
The demand for foods with a positive impact on human health and well­
ness has exploded globally over the past two decades. This growth is driven
by socioeconomic and scientific factors, including increases in population,
disposable income, life expectancy, and healthcare costs. Advancements
also enhance the market for healthier foods in our understanding of dietary
bioactive ingredients and their effects on various aspects of human health at
a systems and molecular level. This book examines the rapidly growing field
of functional foods to prevent and manage chronic and infectious diseases. It
attempts to provide a unified and systematic account of functional foods by
illustrating the connections among the different disciplines needed to under­
stand foods and nutrients, mainly: food science, nutrition, pharmacology,
toxicology, and manufacturing technology. Advances within and among all
these fields are critical for the successful development and application of
functional foods. Chapters in the present volume explore the varied sources,
biochemical properties, metabolism, health benefits, and safety of bioactive
ingredients. Special emphasis is given to linking the molecular and chemical
structures of biologically active components in foods to their nutritional
and pharmacological effects on human health and wellness. In addition to
discussing scientific and clinical rationales for different sources of functional
foods, the book also explains in detail the scientific methodologies used to
investigate the functionality, effectiveness, and safety of bioactive ingredi­
ents in food.
CHAPTER 1

Introduction to Functional Foods and

Nutraceuticals
LUANA PULVIRENTI1 and ANGELA PATERNA2
1
Department of Chemical Sciences, University of Catania,
Viale Andrea Doria-6, 95125, Catania, Italy
2
Institute of Biophysics, National Research Council,
Via Ugo La Malfa – 153,90146, Palermo, Italy

ABSTRACT

Nowadays, the term functional food gained more attention, especially by the
younger generations, since are certainly more informed about the increasingly
close correlation between food and health. This term was first used in Japan
in 1980 and since that time it has been possible to record a growing interest
from the scientific community around the world, in order to clarify their
potential role in the prevention of chronic diseases and in the maintenance of
good health of a population with a longer life expectancy than in the past. In
this context, this chapter aims to offer a simple and comprehensive overview
about definitions and classifications of functional food. Furthermore, atten­
tion was focused on the close relationship that exists between the chemical
composition of a food in terms of ‘functional’ chemical compounds known
today as nutraceuticals, and the ability of the food to play a functional role.

1.1 INTRODUCTION

Today, the common thought is that foods together with a good lifestyle may
be able to prevent diseases or physiological disorders. This belief is actu­
ally much older than might think, and even Hippocrates about 2500 years
ago claimed, “Let food be thy medicine and medicine be thy food.” The
2 Advances in Nutraceuticals and Functional Foods

aforementioned concept is particularly felt mostly by the younger generations,

who represent a new class of consumers, of course, more health-conscious
than before. More in general people take more into account the strict rela­
tionship between diet and health. The reason is that they are more informed
about it, thanks also to many scientific and popular magazines, tv programs,
social media posts, and blogs which often deal with topics concerning the
content of bioactive chemical substances in foods and their potential activity
as chemopreventive agents of degenerative diseases. Therefore, these foods
defined ‘functional foods’ are considered desirable in a good diet. The term
‘functional foods,’ used for the first time in Japan in 1980 [1, 2], includes
every food or food ingredients exerting a nutritional function but at the same
time express promising healthy effect when eaten regularly in a varied diet
[3]. The above consideration allows to enclose in this group not processed
foods such as fruit and vegetable, but also foods formulated with a specific
health purpose.
In recent years a renew attention has been registered on functional foods
from researchers in the world working in different fields of science due to
a growing global interest for these foods. Indeed, the fields of investiga­
tion involving functional foods are manifold and often linked together; for
example, using on Scopus.com the index term ‘functional food’ about 61.000
documents (articles, chapters, and books) were found, published between
1980 and 2019, with an increasing number of publication year by year,
confirming the growing scientific interest. Furthermore, it is noteworthy
that analyzing quickly the results of search by subject area, it is possible to
observe that this topic involves many scientific fields (Figure 1.1).
Therefore, it is not surprising that the functional foods development has
required interconnection with related field like food chemistry, biology,
nutrition, pharmacology, and statistics [4].
In this context, important contributions have been made by many epide­
miological studies reported in literature with the purpose to evaluate the
relationship between diet habits and the risk of contracting a large share
of the global diseases, through conditions such as high blood pressure and
elevated blood glucose and cholesterol levels. Two famous examples are the
Mediterranean-style diet and high-fat diets, also well known as the French
paradox, incorporating moderate red wine intake are reported to benefit to
human health [5]. In particular French paradox refers to the lower risk of the
French people towards cardiovascular diseases (CVD), despite their high fat
diet, attributed to their habitual but moderate consumption of red wine. Also,
the Mediterranean-style diet, expressed by a reduced drinking of alcohol, a
Introduction to Functional Foods and Nutraceuticals 3

balanced eating of meat and its subproducts, an increased ingestion of fruits,

vegetables, and extra-virgin olive oil, is widely recognized to have beneficial
effects on CVD.

FIGURE1.1 Total number of articles (a) by year; and (b) subject area.
Source: Published from: 1980 to 2019 at Scopus.com using the index term ‘functional food.’

Nowadays, is commonly approved that the helpful outcomes of functional

foods can be attributed to the chemical substances’ characteristic of their
composition, well known with the term ‘nutraceuticals,’ for which it was
registered an increased interest corroborated by the growth of the nutraceu­
tical trend aiding the growth of the global market. The global nutraceutical
market size was valued to grow from about $209 billion in 2017 to $373
billion in 2025, predicting a spread at a CAG (compound annual growth) rate
of 8.3% over the estimated period [6].
The growing scientific interest in the development of functional foods
and nutraceuticals also goes hand in hand with the increased life expectancy
average at the global level (around 70–80 years), and with the necessity in
maintaining a good overall health status in the years. Therefore, both are
considered a valid and safe help that together with a healthy lifestyle they
can prevent chronic diseases, very frequent in the elderly.