GLOBAL RELEVANCE OF FUNCTIONAL FOODS SECURITY FOR HEALTH PROMOTION AND DISEASE PREVENTION

Abstract

Food security, as defined by the United Nations’ Committee on World Food Security, means that all people, at all times, have physical, social, and economic access to sufficient, safe, and healthy food that meets their food preferences and dietary needs for an active and healthy life. Food insecurity is defined as the disruption of food intake or eating patterns because of lack of money and other resources. Functional food security means that people should eat not only enough food but also foods that can cause health promotion and diseases prevention. The diets should contain foods that can serve all the qualities of a healthy diet.

Full text

See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/360124633
IJCN-2022;22 (1);1-45. International Journal of Clinical Nutrition, ISSN-
Canada, Open Access
Book · March 2022
CITATIONS
0
READS
8
1 author:
Some of the authors of this publication are also working on these related projects:
Role of Functional Food Security in Global Health View project
Nutrition in Health and Disease View project
Ram B Singh
Halberg Hospital And Research Institute,Moradabad, India
411 PUBLICATIONS3,277 CITATIONS
SEE PROFILE
All content following this page was uploaded by Ram B Singh on 23 April 2022.
The user has requested enhancement of the downloaded file.

International Journal of
CLINICAL NUTRITION (IJCN)
A publication of the International college of nutrition, India
2022 * VOLUME 22, * NUMBER 1 Url: https://ijcnworld.com/ ISSN 0971-9210
2022
International College of Nutrition Since 1998
ISSN 0971-9210 www. www.ijcnworld.com
2022, Volume 22, N 1
Quarterly
Editor in Chief: Dr R B Singh
eISSN-Canada
ISSN 2816-5705.

International Journal of
CLINICAL NUTRITION (IJCN)
A publication of the International college of nutrition, India
2022 * VOLUME 22, * NUMBER 1 Url: https://ijcnworld.com/ ISSN 0971-9210
TABLE OF CONTENTS
View Point:
GLOBAL RELEVANCE OF FUNCTIONAL FOODS SECURITY FOR HEALTH PROMOTION AND
DISEASE PREVENTION 1
R B Singh1, S S Rastogi2, MA Niaz3, HS Buttar4, Ghizal Fatima5
Editorial:
ANCIENT CONCEPTS OF NUTRITION AND FOODs 7
RG Singh1, R B Singh2, Late S S Rastogi3, O P Sharma4
Editorial:
EVOLUTIONARY DIET AND MEDITERRANEAN STYLE DIETS 11
Fabian De Meester, Agnieszca Wilczynska, D W Wilson, Ram B Singh
FATS AND OILS WITH REFERENCE TO INDIAN CLARIFIED BUTTER 14
Narsingh Verma1, Elena Kharlitskaya2, Sergey Chibisov3, Radzhesh Agarval4
THE SEVEN COUNTRY STUDY: THE FIRST STUDY TO RELATE DIET WITH RISK OF
CARDIOVASCULAR DISEASE 19
Kiarash Moshiri1, Mahmood Moshiri2, Dominik Pella3, Daniel Pella4, R B Singh5
YOU ARE WHAT YOU EAT AND YOUR FATHER AND MOTHER EAT 23
Adrian Isaza1, Ghazi Halabi2, RB Singh3
THE CONCEPT OF FUNCTIONAL FOODS AND FUNCTIONAL FARMING: (4F) IN THE DISEASE
PREVENTION AND HEALTH PROMOTION 28
Ekasit Onsaard1, Toru Takahashi2, MA Manal3, Galal Elkilany4, Krasimira Hristova5,Kiarash Moshiri6
FLAVONOIDS CONSUMPTION AND THE RISK OF CARDIOVASCULAR DISEASES 34
R B Singh1, S S Rastogi2, MA Niaz3, HS Buttar4, Ghizal Fatima5
FOOD INDUSTRY, FOOD MANUFACTURING AND HEALTH 39
Lekh Juneja, Takahashi Toru, Rie Horuichi
MODERATE CONSUMPTION OF ALCOHOL AND THE FRENCH PARADOX 45
Krasimira Hristova1, Adrian Isaza2, Maria Abramova3, R B Singh4, Toru Takahashi5

International Journal of
CLINICAL NUTRITION (IJCN)
A publication of the International college of nutrition, India
2022 * VOLUME 22, * NUMBER 1 Url: https://ijcnworld.com/ ISSN 0971-9210
Registered in 1998, as: International Journal of Clinical Nutrition (IJCN), by The ISSN National Centre, India, National
Science Library, CSIR-NIScPR, 14 Satsang Vihar Marg, New Delhi - 110067, Ph.: 011- 26863759.
Publishers: International College of Nutrition, www.icnhealthfoods.com
It is the aim of IJCN to help advance research in the world of nutrition by publishing
papers on the following topics:
Components.
1. Editorials and Commentaries (1-3pages with 5-15 references);4-6 in each issue.
2. Cardiovascular and Nutrition News.100-500 words on any area of nutrition.
3. Clinical Reviews.2-3 each issue;10-20pages (Mini reviews-10 pages,50 references) with not more than 100 references,10%
references,> 2 years old for all the components of IJCN.
4. Contributions from Future Cardiologists and Nutritionists (2-3 each issue); Experiences of the residents and PhD scholars,
related to nutrition, ;2-3 pages with 5 references.
5. Original Research Articles.5-10 articles each issue with 5-10 pages with references, not more than 50.
6. Brief Reports: Papers on cases , case reports with less scientific but acceptable methods.2pages,<10 references.
7. World Heart Forum/World Nutrition Forum : Letters to the editor on articles published in any indexed journal of the world
and any interesting brief report not exceeding one page. Criticism of the policy makers of each country especially western
world because the whole world follows the west.- one page,5 references.
8. International College of Nutrition Highlights: News from the members.
9. Pharma and Food Health Forum: Injustice done with Food companies and Pharma companies doing unethical practices
would be highlighted by impartial experts, preferably from experts of pharmaceutical and instrument manufacturing
companies to give them voice for benefit of the people,s health.
10. Calendar of Conferences.
SECTIONS, TO BE COVERED IN THE IJCN:
1. Epidemiology of Food intakes, physical activity, yoga, meditation, yogasan, acue puncture, acue pressure, holistic health,
Nutrition and Prevention.
2. Chronobiodiology and Chronomics.
3. Nutrition and Lifestyle in diseases.
4. Nutrition in Clinical Medicine.
5. Cardiovascular Sciences( Molecular: biochemistry and biology and nutrition).
6. Functional Food Security, Food Security
7. Pharmacotherapy, nutraceuticals
8. Electrophysiology
9. Echocardiography
10. Nuclear medicine
11. Pediatric Cardiology and Nutrition
12. Nutrition in pregnancy and infancy
13. Geriatric Nutrition
14. Nutrition in health in women
15. Nutritional Rehabilitation and prehabilitation
16. Nutritional Intervention
17. Food and Health. Functional foods and Genetically Modified foods
18. physical training, Prayer

International Journal of
CLINICAL NUTRITION (IJCN)
A publication of the International college of nutrition, India
2022 * VOLUME 22, * NUMBER 1 Url: https://ijcnworld.com/ ISSN 0971-9210
EDITORIAL BOARD OF THE IJCN
Editor in Chief:
Late Dr T K Basu, PhD, FICN (Canada)
Dr R B Singh, MD. FICN (India), ijcnworld@ijcnworld.com,
Dr Jaipaul Singh (UK), <jaipsingh10@gmail.com>
Editors:
• Dr Adrian Isaza (USA), <adrian.isaza@usat.edu>
• Dr G Cornelissen, PhD (USA), <corne001@umn.edu>
• Dr Daniel Pella, MD (Slovakia), <daniel.pella.sk@gmail.com>
• Dr Galal Eldin Najib Elkilany,MD,(USA), <galal.elkilany@gmail.com>
• Dr Shaw Watanabe, MD, PhD (Japan), <watashaw@lifescience.or.jp>
• Dr Jaipaul Singh, PhD, DSc (UK), <jaipsingh10@gmail.com>
Associate Editors
• Dr HS Buttar (Canada), <hsbuttar@bell.net>
• Dr LR Juneja (Japan), <lekhjuneja@gmail.com>
• Dr M Moshiri (Canada), <moshiri@nextpharmainc.com>
• Dr Takahashi (Japan), <tkhstr111@gmail.com>
• Dr Narsingh Verma (India)
Assistant Editors:
• Dr Manohar Garg (Australia), <Manohar.Garg@newcastle.edu.au>
• Dr NH Hadi, MD, PhD (Iraq) , <drnajahhadi@yahoo.com>
• Dr Jan Fedacko (Slovakia), <janfedacko@hotmail.com>
• Dr Ghizal Fatima, PhD, FICN (India), <ghizalfatima8@gmail.com>
• Dr Krasimira Hritova, MD, PhD, (Bulgaria), <khristovabg@yahoo.com>
Consulting Editors:
• Dr Iliot Berry, MD, PhD, FICN (Hon),(Israel)
• Dr Fabien De Meester PhD, FICN (Belgium)
• Dr Raimar Loebenberg (Canada), <raimar@ualberta.ca>
Statistical Editor:
• Dr DW Wilson (UK), <douglas.w.wilson@hotmail.com>
Managing Editors:
• Dr JP Sharma, PhD, FICN
• Dr R B Singh (Responsibility of contents)
Technical Editor:
Dr Radzhesh Agarval, MD, PhD (Moscow), <radzhesh@agarval.com>
CONTACT US.
Dr R B Singh, MD,FICN,FICC, FIACS
Tsim Tsoum Institute, ul. Golebia 2, 31-007 Krakow, POLAND, email: rbs@ijcnworld.com,
Publication charges (2021, 2022): US$100.00 or equal INR, per article up to 5 printed pages.
No publication charges for Open access for the previous years 2011-2020
Information for the Advertisers:
Black and white US$250.00 full page, US$500.00 color per issue; For 4 issues in 2005, US$1000.00 and US$2000.00
respectively.

International Journal of
CLINICAL NUTRITION (IJCN)
A publication of the International college of nutrition, India
2022 * VOLUME 22, * NUMBER 1 Url: https://ijcnworld.com/ ISSN 0971-9210
INSTRUCTIONS TO AUTHORS.
IJCN is the journal of ICN and ICC and would consider publication of manuscripts for its various sections, pertaining to
Nutrition, health and disease as well as cardiovascular diseases.
Manuscripts should be addressed to Professor R B Singh, MD, FICN, FICC (Please send smaller files)
Editorial Policy:
The IJCN disapproves the submission of same article simultaneously to different journals for consideration as well as
duplicate publication. Opinions expressed in the articles published in the IJCN, are those of the authors and not necessarily
of the editor. Neither the editors, nor the publisher guarantees, warrants or endorses any product or service advertised in
the journal. The accepted papers, would be edited, without altering the meaning to improve clarity and sense. Every
manuscript submitted to IJCN, would be scrutinized, by two or more refries before publication.
Guidelines for Manuscript Submission:
The manuscript should be prepared,in accordance with the uniform requirements for manuscripts submitted to biomedical
journals,compiled by the International Committee of Medical Journal Editors (N Engl J Med,1997,336:309-315.).
We need three complete sets of manuscripts, typed in double space,on one side of the page, throughout. The manuscript
should be arranged in order;Covering letter,title page with authors and their affiliations, abstract structured, introduction,
methods, results, discussion, acknowledgements, references, tables and legends to illustrations. Three sets of illustrations
in three separate envelope, should be attached at the end.The pages of the manuscript should be numbered consequitively,
beginning with the title page.It is important to submit an electronic version of manuscript,3.5 inch, diskette/CD, along
With the printed copies, to facilitate printing by the publisher.
Covering Letter.
All authors or corresponding author on behalf of all, should take the responsibility of signing the covering letter, indicating
that all agree with the contents, and all have participated in the study or in the writing of manuscript and the article is
entirely submitted to IJCN.
Copy Rights. Acceptance of the manuscript for publication in the ICN ,implies transfer of copyright to the publisher but
authors can use the material elsewhere after giving full reference if IJCN..
References:
A full list of references should be included at the end of the article.The references should conform to the Vancouver style
and should be numbered,consecutively in the order,in which they first appear in the text.These should be given in
parentheses( ).References cited only in the tables should be numbered in accordance with a sequence established by the
first identification in the text of a particular table or illustration.Personal communications, unpublished articles should not
be cited as references,though these may be mentioned in the text in parentheses.Abstract should not be used as references
unless,it is very important.
Examples:
1.Articles in Journals. Authors surname followed by first and middle name initials,title of paper,name of journal,year of
publication,volume,page number of beginning-and last page of the article.Include the names of all authors,if there are 5
or less.If six or more,the first 3 followed by et al. The title of the journal should be abbreviated according to the style,
used in the Index Medicus. e.g Singh RB,Cornelissen G,Weydahl A et al. Circadian heart rate and blood pressure
variability
Considered for research and patient care.Int J Cardiology 2003,87:9-28.
2.Articles in books.Authors,title,edition,publisher,city,year,pages.
eg.Singh RB, Rastogi SS.Nutritional Aspects of Hypertension. International College of Nutrition,
Moradabad,India,1989,p-
3.Chapter in book. Authors, chapter title, book title, edition, editors, publishers, city, year, pages. e g
Otsuka K, Shobgo M, Kozo M et al. Chronomes,aging and disease. Ecological Destruction, Health and Development:
Advancing Asian Paradigms. Furukawa H, Nishibuchi M, Kono Y, Kaida Y(eds),Kyoto University Press, Japan
2004,p367-394.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 1 ~
View Point:
GLOBAL RELEVANCE OF FUNCTIONAL FOODS SECURITY FOR
HEALTH PROMOTION AND DISEASE PREVENTION
R B Singh1, S S Rastogi2, MA Niaz3, HS Buttar4, Ghizal Fatima5
1,3 Medical Hospital and Research Center, Moradabad, India
2 Diabetes Research Center, New Delhi, India
4 University of Ottawa, Faculty of Medicine, Ottawa, Ontario
5 Canada; Era Medical College, Lucknow, India
Correspondence
Dr Ram B Singh, MD, FICN
Medical Hospital and Research Center,
Civil Lines, Moradabad (UP)244001, India
Abstract: Food security, as defined by the United Nations’ Committee on World Food Security, means that all people, at
all times, have physical, social, and economic access to sufficient, safe, and healthy food that meets their food
preferences and dietary needs for an active and healthy life. Food insecurity is defined as the disruption of food intake or
eating patterns because of lack of money and other resources. Functional food security means that people should eat not
only enough food but also foods that can cause health promotion and diseases prevention. The diets should contain foods
that can serve all the qualities of a healthy diet.
Key words: Nutrient intake policy, nutrient rich foods, food safety, food quality.
Introduction. Food security, as defined by the United
Nations’ Committee on World Food Security, means
that all people, at all times, have physical, social, and
economic access to sufficient, safe, and healthy food
that meets their food preferences and dietary needs
for an active and healthy life [1-3]. In the next few
decades, a changing climate, growing global
population, rising food prices, and environmental
stressors will have significant yet uncertain impacts
on food security. Strategies on adaptation and policy
responses to global change, including options for
handling water and land use patterns, food trade,
postharvest food processing, and food prices and
safety are urgently needed [4-8]. There is an unmet
need to work on food security includes analysis of
cash transfers, promotion of sustainable agricultural
technologies, building resilience to shocks, and
managing trade-offs in food security, such as
balancing the nutritional benefits of meat against the
ecological costs of its production [9-11]. Food
insecurity is defined as the disruption of food intake
or eating patterns because of lack of money and other
resources. Very low food security: “Reports of
multiple indications of disrupted eating patterns and
reduced food intake, means very low grade of food
security [11-14]. This viewpoint aims to highlight
functional food security in the light of WHO and FAO
agenda.
World Health Organization and Food and
Agriculture Organization Agenda
We greatly appreciate the honorable WHO
experts for developing guidelines for increased
consumption of fruits, vegetables and legumes in
1990 [15]); and later guidelines to provide Functional
Foods by Mark Wahlqvist and Niayana
Wattanapenpaiboon for prevention of NCDs in 2003
[16]. Despite lack of attention by FAO of the UNO to
encourage greater production of Functional Foods
during 1990 to date, WHO continued its efforts for
having increased availability of Functional Foods at
affordable cost by its active participation in the
International Congress on Nutrition 1992 (World
declaration on nutrition,1992) organized by FAO
(http://www.fao.org/docrep/v7700t/v7700t02.htm)
as well as in the 2nd International Congress on
Nutrition 2014, where WHO was a co-planner [2].
World Health Organization (WHO) and United
Nations Children's Fund (UNICEF), to propose
options on the meaning and different uses, if any, of
the terms "Food Security", "Food Security and
Nutrition", "Food and Nutrition Security" and
"Nutrition Security" to the CFS Session for the
standardization of the official terminology that the
Committee should use [3-6]. This document responds
to that request. It presents a brief review of the
historical evolution in the understanding of
underlying concepts and then summarizes current
usage of the various terms under review[6-10]. It
examines and proposes various options that the
Committee may consider for standardizing its official
terminology. 2. Over the years numerous

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 2 ~
formulations and conceptual frameworks have been
put forward to define food security and nutrition and
their inter-relationship. Some key terms used in this
document are included in Annex 1, in addition to an
annotated list of the most seminal works related to the
topic under discussion in Annex 2. An effort has been
made to use this body of literature to distil the
essential meaning of key terms and to suggest a way
of thinking about them that will allow public
discourse to move forward in an integrated and
constructive manner.
All work towards the eradication of food
insecurity, hunger and malnutrition, consistent with
the right to adequate food and the right to be free from
hunger. To ensure a successful outcome of this
multidisciplinary goal, professionals and policy
makers across relevant disciplines and sectors need to
speak the same language[3-6]. The terms under
discussion have evolved over several decades, based
on different perspectives by leading professional
communities of practice, especially nutrition and
public health experts and professional groups
working in the socio-economic, food and agriculture
domains. iii) There is wide recognition of the four
dimensions of food security - availability, access,
utilization and stability - and the three main
determinants of nutrition security - access to food,
care and feeding, and health and sanitation. iv) The
terms may take on a different meaning when applied
at global or national levels versus household or
individual levels. v) In those cases where translation
is an issue caution is in order to ensure the agreed
upon language is adhered to; it is also noted that in
certain languages countries may choose not to use the
combined term in their national contexts. vi) While
there is significant overlap in the content of the
multidisciplinary definitions of food security and
nutrition security, some communities of practice will
feel more comfortable with one term or the other.
Mutual agreement and acceptance of a common term,
endorsed and recommended by CFS, will greatly
facilitate future communication, decisions and
actions that support the eradication of food insecurity,
hunger and malnutrition.
In the 1st International Conference on Nutrition
(ICN), representatives from 159 countries and the
European Community, 15 United Nations
organizations and 144 Non-Governmental
Organizations participated[2]. The 2nd International
Conference on Nutrition (ICN2) was a high-level
inter-governmental meeting that focused global
attention on addressing malnutrition including over-
nutrition and related NCDs. Over 2200 participants
attended the meeting, including representatives from
more than 170 governments, 150 representatives from
civil society and nearly 100 from the business
community. Our group from the International College
of Nutrition (India, Canada), International College of
Cardiology (Slovakia); as well as The Tsim Tsoum
Institute (Krakow, Poland) have been aggressively
bringing up their view points, by planning
conferences, and publications to attract the attention
of FAO to encourage the world to produce Functional
Foods to gain Functional Food Security rather than
Food Security. Food Security without emphasis on
Functional Foods is the major cause of epidemic of
cardio-metabolic diseases (CMDs) and other chronic
diseases which is the important message the editors
are giving in this volume; Functional Food Security
in Global Health [17].
The Global Nutrition Report, includes the
Rome Declaration, a Framework for Action
reaffirming the commitments made at the first
International Conference on Nutrition in 1992, the
World Food Summits in 1996 and 2002[6-8], as well
as in relevant international targets and action plans,
including the WHO 2025 Global Nutrition Targets
and the WHO Global Action Plan for the Prevention
and Control of NCDs 2013-2020. The purpose is to
instill a sense of urgency to achieve these goals which
appears to be difficult unless substantial attention is
given to produce functional foods in the world to
achieve Functional Food Security at an affordable
cost in both developed as well as developing and
under developed countries. The Rome Declaration
includes commitments to eradicate hunger and all
forms of malnutrition, to increase investments in
effective interventions, and to develop coherent
policies to enhance sustainable food systems[8]. A
delegation of civil society organizations described the
recommendations as “weak and non-binding”, and
suggested that governments have not set the bar any
higher than the first ICN meeting in 1992. Others
have pointed to the inadequate attention given to the
issue of sustainable diets and food systems. We share
the same views, which are clear by review of the
Rome Declaration statement: “all forms
malnutrition.” without mentioning over-nutrition and
NCDs. Such description decreases the gravity of this
slow moving disaster of obesity and related diseases
[9].
It is noteworthy that both WHO and FAO who
have joined hands to educate the world about the
utility and necessity of functional foods for
prevention of NCDs which is clear from 2017
websites of these agencies [13-15]. The emphasis on
the need for functional food production, labeling of
nutrient contents and the need for food biodiversity in
the diet are interesting. However, there is
overemphasis on under nutrition which is more

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 3 ~
political due to poor distribution and lack of
implementation of government policies, despite
adequate availability of food in the world. We agree
that optimal nutrition is fundamental to human health
and total health; social, physical, mental and spiritual
health and well being. However, we are not surprised
from the estimates from the UN-FAO, that about 805
million people which is more than a tenth of the
global population, remain chronically
undernourished. Despite all the efforts from UN-
FAO, only slow progress has been made in the
reduction of under nutrition, the world now also faces
growing epidemics of overweight, obesity, and diet-
related NCDs. It should be noted that decline in under
nutrition and the emergence of the epidemic of NCDs
are natural transitions occurring during poverty to
affluence which cannot be prevented by emphasizing
on Food Security; unless the governments and other
stakeholders are provided with appropriate health
education related to foods, to make such policies to
educate the worldwide food industry and populations.
There is transition in food security from food
production to food availability and utilization. Figure
1.
Figure 1. Food production and avaaaailability, stability, utilization and healthiness.(Adapted from Sudesh
Adhikari. Food security: Pillars, Determinants and Factors Affecting It. Nutrition and Metabolism 2018).
The fact is well known to WHO and FAO experts and
reflected by the broad scope of the Global Nutrition
Report, the authors noting that the coexistence of
different forms of malnutrition is the “new normal”
[15-16]. However, this is not “new normal”; and it has
been ignored due to over emphasis on under nutrition
and hunger which are expected to disappear on their
own with enhanced economic development in
developing and under developed nations. People with
increased income will thereby have the economic
ability to buy and consume quality food. The Global
Nutrition Report concludes that progress towards
World Health Assembly 2025 targets for maternal
and child nutrition is too slow; although many
countries have made substantial advances on some
indicators, which appears to be wrong. Since people
have not been educated about Food Security;
therefore, all such children would land up in to
increased susceptibility to NCDs, at younger
adulthood by increased consumption of fast foods.
Improvements in nutritional status of mother and
children can contribute substantially to Sustainable
Development Goals (UNO) related to poverty, health,
education, gender, and employment; but, it would be
possible only by Functional Food Security, not just
Food Security [15]. In both the WHO-FAO websites
(13,14), it is not clear how much Total Food and
Functional Food was available in the world in
previous years and how much total food would be
required in future to achieve the UNO targets of 2025
Sustainable Development Goals (15). There is an
interaction of functional foods with functional

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 4 ~
farming as well with other diet and lifestyle factors.
Figure 2, 3
Landmark Studies; Why Functional Food
Security?
The Seven Country Study was the first major
study which reported that dietary fat is a risk factor
for cardiovascular diseases (CVDs), coronary artery
disease (CAD) and stroke [15-19] . However, it is not
the quantity but the quality of fat which may be
responsible for CVDs and other chronic diseases.
Further analysis of data revealed that flavonoids and
omega-3 fatty acid contents of foods can explain the
cause of variation in the risk of CAD and cancers in
the seven countries; lower risk in Japan and
Mediterranean countries; and greater risk in northern
European countries and USA where diets are rich in
fast foods with majority of the population having
Food Security [18,19].
Figure 2. Functional foods and functional farming.
(Adapted from Singh et al, J Cardiol and Therapy
2018.).
Figure 3. Interaction of diet and lifestyle
factors in the pathogenesis of diseases
The North Karelia Project with 20 year
results and experiences showed that heart disease
mortality has declined in Finland by 55% among men
and 68% among women between 1972 and
1992[20,21].The total fat content of the Finnish diet
changed from 38% of energy to 34%, saturated fat
from 21 to 16%, and polyunsaturated fat from 3 to 5%
and the intake of cholesterol decreased by 16%. A
shift from boiled to filtered coffee could have further
decreased serum cholesterol by 0.3 mmol/liter (11
mg/dl). Thus, these changes together could explain
the total change in serum cholesterol, which has been
on average 1.0 mmol/liter (38 mg/dl). Fruit and
vegetable consumption increased two- to three-fold
during this time period. It is clear that dietary changes
seem to explain the decrease in serum cholesterol
reduction in inflammation which has contributed to
the dramatic decline in coronary heart disease
mortality in Finland. There are six randomized,
controlled trials with adequate sample size that have
been published showing beneficial effects of diet on
risk of CVDs [18-21]. Landmark clinical trials
published after the Seven Country Study and the
North Karelia Project, provided a proof that
intervention with diet can cause significant decline in
CVDs [17,22]. Effects of changes in fat, fish and fiber
intakes on death and myocardial infarction in the Diet
and Re-infarction Trial (DART) and the effect of
Mediterranean style diets in the Lyon Heart study
revealed that mortality can be reduced by dietary
interventions, without a decrease in serum cholesterol
(18,20). The Indian Experiment and the Indo-
Mediterranean Diet Heart study reported that that
diets rich in vegetables, fruits, nuts and whole grain
legumes in conjunction with mustard oil (rape seed)
can cause significant decline in CVDs, in patients
after coronary artery disease [17]. Further cohort
studies in a large number of subjects showed that

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 5 ~
Mediterranean style diets can cause significant
decline in mortality and increase the survival [18-20].
The consumption of these diets may be associated
with greater intake of antioxidant polyphenolics and
flavonoids and omega-2 fatty acids, fiber and
vitamins which are known to decrease oxidative
stress and inflammation and may have anti platelet
effects [19-21].
Functional Food Security
Functional Food Security may be defined as
a state of food availability in a country, when
functional foods are available at affordable cost to
all the segments of the society. Food is regarded
“functional” if consumed as part of a usual diet;
providing benefits to one or more target functions in
body, beyond basic inherent nutrition. The first
functional food products were launched in Japan
where a food category called FOSHU (Foods for
Specific Health Use) was established in 1991 to
reduce the increasing health-care costs. Antioxidant
and redox systems require certain amounts of
vitamins as well as non-vitamin components like
polyphenols. Antioxidant and redox functions are
important for all cells and tissues; however
beneficial effects have not been proven except when
consumed as a component of fresh fruit and
vegetables. Gastrointestinal function including: the
balancing of colonic microflora and control of
nutrient bioavailability, food transit time, immune
activity, endocrine activity, mucosal motility and
epithelial cell proliferation. The food components
present in the functional foods may influence moods
and behavior as well as cognitive and physical
performances. There is regulation of metabolism of
macronutrients-carbohydrates, amino acids and
fatty acids and the related hormonal regulation e.g.
insulin/glucagon balance. Consuming Functional
Dairy Products with targeted therapeutic benefits to
inhibit TMAO, can be a tasteful way of healthy life,
free from CVDs and cancers. Functional Food
Security appears to be adequate to address all the
challenges of global malnutrition, including under
nutrition and micronutrient deficiencies, as well as
overweight, obesity, and diet-related NCDs [17-24].
More specific targets covering all of these issues are
needed to galvanize funders, countries, and others to
address these fundamental challenges.
In brief, there is adequate food availability
in the world but the distribution to country and
communities as well as individuals is not uniform.
The farmers need education what to grow to serve
the functional food security rather than industrial
food security. The food manufactured by the
industry do not serve the goals of functional foods.
The sustainable development agenda should include
the right to grow and manufacture functional foods.
The advocacy for adequate nutrition should be fully
integrated for example, sustainability has to be well
enough defined to make such integration
meaningful world-widely.
Ethical clearance and Informed Consent. Not required because its not a original article.
Authors contributions. All the authors contributed equally.
Acknowledgements are given to International College of Nutrition for providing logistic support to write this article.
Conflict of interest. There is no conflict of interest among authors.
Funding. No especial grant given by any agency.
REFERENCES
[1]. Food Security, https://www.fao.org/3/md776e/md776e.pdf
1992 accessed January 2001
[2]. Chambers, R. and Conway, G.R. (1992). Sustainable rural
livelihoods: practical concepts for the 21st century.
Institution of Development Studies. Brighton. FAO and
WHO
[3]. International Conference on Nutrition - World Declaration
and Plan of Action for Nutrition. Rome. December 1992
IFAD/UNICEF (1992). Household Food Security:
Concepts, Indicators, and Measurements. A Technical
Review. By S. Maxwell and T. Frankenberger.
USAID,1`1992
[4]. USAID Policy Determination – Definition of Food
Security. PD-19 April 13, 1992. Washington D.C. 1992
[5]. Quisumbung, A.R. et al. (1995). Women: The Key to Food
Security. IFPRI Food Policy Report. Washington D.C.
Cited in Kennert, K., ed., 2005. Achieving Food and
Nutrition Security. In WEnt Feldafing. GTZ Eschborn and
DWHH Bonn. 1996 FAO (1996).
[6]. The Sixth World Food Survey. Rome. FAO (1996). Rome
Declaration on World Food Security and World Food
Summit Plan of Action. Available online at:
http://www.fao.org/DOCREP/003/W3613E/W3613E00.H
TM 1998 FAO (1998).
[7]. CFS: 98/5. 24th Session. Guidelines for National FIVIMS:
Background and Principles. Rome. Frankenberger T. and
McCaston. M. (1998). From Food Security to Livelihood
Security: the Evolution of Concepts. CARE USA. Atlanta.
WHO (1998) Technical Report Series 880.
[8]. Preparation and use of food-based dietary guidelines. Joint
FAO/WHO consultation, Nicosia 1995
[9]. UN ECOSOC (1999). Committee on Economic, Social and
Cultural Rights. The right to adequate food. (Art.11):
12/050/99.E/C.12/1999/5, CESCR General Comment 12.
Geneva.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 6 ~
[10]. FAO (1999). “Commonly used terms,” p. 11 in SOFI. State
of Food Insecurity in the World (SOFI). Rome. 2000
[11]. DFID (2000). Proceeding from the Forum on
operationalizing sustainable livelihoods approaches. Siena,
7-11 March 2000.
[12]. FAO (2000). The State of Food and Agriculture: Food
Security and Nutrition in the Last 50 Years. Rome. Gross
R., et al (2000). The four dimensions of food and nutrition
security: definitions and concepts. GTZ version, April
2000. Available online at: FAO, In Went
http://www.foodsec.org/DL/course/shortcourseFA/en/pdf/
P-01_RG_Concept.pdf 2002
[13]. FAO and WHO (2002) Codex Alimentarius Commission,
Procedural Manual 11th edition
[14]. WHO, Diet, Nutrition, and Prevention of Chronic Diseases.
Report of a WHO Study Group. WHO, Geneva 1990.
[15]. ICN Second International Congress on Nutrition.
http://www.fao.org/about/meetings /icn2/en/ accessed
January 2001.
[16]. Singh, RB; Rastogi, SS; Verma, R; Bolaki, L; Singh, R;
Ghosh, S. An Indian experiment with nutritional
modulation in acute myocardial infarction. Am J Cardiol.,
1992, 69, 879-85.
[17]. Keys A, Aravanis C, Blackburn H, Buzina R, Djordjević
BS, Dontas AS, Fidanza F, Karvonen MJ, Kimura N,
Menotti A, Mohacek I, Nedeljković S, Puddu V, Punsar S,
Taylor HL, Van Buchem FSP. Seven Countries. A
multivariate analysis of death and coronary heart disease.
Cambridge, MA; Harvard University Press, ISBN: 0-674-
80237-3, 1980. 381 pp.
[18]. Hertog MGL, Kromhout D, Aravanis C, Blackburn H,
Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A,
Nedeljkovic S, Pekkarinen M, Simic BS, Toshima H,
Feskens EJM, Hollman PCH, Katan MB. Flavonoid intake
and long-term risk of coronary heart disease and cancer in
the Seven Countries Study.Arch Intern Med 1995;155:381-
386.
[19]. Puska P, Tuomilehto J, Nissinen A, Vartiainen E, eds.
The North Karelia Project. 20 year results and
experiences. Helsinki: University Press, 1995.
[20]. Pietinen P, Vartiainen E, Seppänen R, Aro A, Puska P.
Changes in diet in Finland from 1972 to 1992: impact on
coronary heart disease risk. Preventive Medicine 1996;
25:243-50.
[21]. Burr ML, Fehily AM, Gilbert JF. Effects of changes in fat,
fish and fiber intakes on death and myocardial infarction:
Diet and Re-infarction Trial(DART).Lancet 1989,ii:757-61
[22]. Singh, RB, Rastogi, SS;Verma, R;Laxmi, B;Singh,
R;Ghosh, S;Niaz, MA. Randomized, controlled trial of
cardio protective diet in patients with acute myocardial
infarction: results of one year follow up. BMJ, 1992, 304,
1015-9.
[23]. de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL,
Monjaud I, Guidollet J, Touboul P, Delaye J.
Mediterranean alpha-linolenic acid-rich diet in secondary
prevention of coronary heart disease. Lancet. 1994,
343(8911):1454-9. Erratum in: Lancet 1995,345
(8951):738

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 7 ~
Editorial:
ANCIENT CONCEPTS OF NUTRITION AND FOODs
RG Singh1, R B Singh2, Late S S Rastogi3, O P Sharma4.
1 Department of Medicine, IMS, BHU, Varanasi-5, India
2,4 Medical Hospital and Research Center, Moradabad, India
3
Diabetes Research Center (New Delhi, India
Correspondence
Prof. Dr R G Singh, MD, DM, FICN
Department of Medicine, IMS, BHU, Varanasi-5, India
Abstract: Food security, as defined by the United Nations’ Committee on World Food Security, means that all people, at
all times, have physical, social, and economic access to sufficient, safe, and healthy food that meets their food
preferences and dietary needs for an active and healthy life. Food insecurity is defined as the disruption of food intake or
eating patterns because of lack of money and other resources. Functional food security means that people should eat not
only enough food but also foods that can cause health promotion and diseases prevention. The diets should contain foods
that can serve all the qualities of a healthy diet.
Key words: Nutrient intake policy, nutrient rich foods, food safety, food quality.
Abstract. Food has been considered important in the pathogenesis and prevention of non-communicable Diseases (NCDs)
from the ancient period. Food as a source of healing was known to ancient physicians: Hippocrates (Greece, 600BCE),
Confucius (China, 512BCE), Charaka and Sushruta (India, 600 BCE) (1). Charaka tasted the urine of the patients and
found sugar to diagnose “Madhumeh” (diabetes mellitus), Sushruta was a surgeon, who observed fat deposits in the
channels carrying blood to the heart and named it “Madrog” in patients dying due to heart attacks. Hippocrates proposed
that “lets food be our medicine”, whereas Confucius, the Chinese philosopher taught his students, “The higher the quality
of foods, the better and never rely upon the delicacy of cooking”. Thus a dietary guideline by Confucius, based on
experience, observation and thinking was given as; “cereals, the basic, fruits the subsidiary, meat the beneficial and
vegetable the supplementary”.
Key words. Diet, ancient experts, health, food quality.
Introduction. According to ancient Vedas, the span
of human civilization has been divided in to four
periods, namely, Satayuga, Treata, Dwaper and
Kalayuga. Humans were free from diseases in
Satayuga and the life expectancy was approximately
600 years. In Treata, the life expectancy reduced to
300 years, while in Dwaper to 200 years and finally
in Kalayuga, it is reduced to 100 years. However,
according to the modern concept, the life expectancy
of the ancient man was hardly 30 years, because
causes of deaths were mainly fall, bites, drowning and
killing during hunting or other natural calamities but
it has never been beyond 100 years. It is possible that
the life expectancy appears to be dependent on
physical, social, mental and spiritual health of the
human beings. Decrease in physical activity, increase
in mental strain, pollution, dietary changes, tobacco
consumption, alcoholism and lack of humanity
appear to be important contributing factors for
decrease in life expectancy [1-8]. It is also known that
length and brightness of the telomeres present on
chromosomes are important determinants of
longevity and survival. It is possible that telomeres
were much larger in the ancient period indicating life
expectancy more than 100 years.
Ancient Knowledge. Food has been considered
important in the pathogenesis and prevention of non-
communicable Diseases (NCDs) from the ancient
period. Food as a source of healing was known to
ancient physicians: Hippocrates (Greece, 600BCE),
Confucius (China, 512BCE), Charaka and Sushruta
(India, 600 BCE) (1). Charaka tasted the urine of the
patients and found sugar to diagnose “Madhumeh”
(diabetes mellitus), Sushruta was a surgeon, who
observed fat deposits in the channels carrying blood to
the heart and named it “Madrog” in patients dying due
to heart attacks. Hippocrates proposed that “lets food be
our medicine”, whereas Confucius, the Chinese
philosopher taught his students, “The higher the quality
of foods, the better and never rely upon the delicacy of
cooking”. Thus a dietary guideline by Confucius, based
on experience, observation and thinking was given as;
“cereals, the basic, fruits the subsidiary, meat the
beneficial and vegetable the supplementary”. According
to WHO (1990), the concept of eating a diet rich in
animal food, and preference for meat and greasy food
was well shaped in China (2). However, possibly the
meat was considered to be rich in healthy nutrients (w-
3 fatty acids and flavonoids) and from running animals
(healthy fatty acid composition); and the total fat intake
remained within desirable limits and was not excessive
as in the Western countries (3-6). In the 7th century BC,

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 8 ~
the adverse effects of salt was known to a Chinese
physician, who proposed that “increased consumption
of salt may cause hardening of the pulse”.
Figure 1. Ancient physicians in India, Sushruta (Surgeon), Charak (Physician).(5th century BCE)
Much before these statements by ancient physicians,
diet has been implicated for health and disease in
ancient scripture Srimad Bhagwadgita (3000 BCE).
The first two lines in each of the four verses are in
Sanskrit followed by its English translation (1).
Aayuh satvabalarogyam, sukhpreetiviverchanah,
Rasyah snigdhah sthirah hradyah aharah
satvikpriyah [1].
The sattvic foods are full of juice, good in taste and
increase longevity, wisdom, power, health,
happiness, peace and love.
Yktaharviharasya, yuktachetasya karmasu
Yktaswapnavbodhasya, yogo bhavati duhkhaha[1].
Yoga is protective against grief to those who have
disciplined diet and lifestyle and controlled behavior;
sleep and awakening.
Katvamlalavanatyusnteekshanaruksha vidahinah
Ahar rjassyestah, dukhahshokmaypradah [1].
The foods that are bitter, acid, fried, hot, pungent and
dry, give rise to grief, mental stress and diseases.
Yatyaman gatarasam, pootiparyushitachya yat,
Uchhistamapi chamedhyam, bhojanam tamspriyam
[1].
Foods that are cold, prickled, putrefied and preserved
are lured to criminals and give rise to criminal
tendency and behavior.
The pre-historic concept of diet and nutrition is
absolutely based on archeological studies, which are
likely to ignore vegetable component of early man’s
diet, because remains of vegetable food in
archeological sites are far less spectacular and rather
more difficult to identify compared to animal bones.
However, more recent archeological studies with
introduction of modern technology share the same
views that have already been proposed in the
traditional nutrition [3,4]In ancient scriptures of
India, dietary patterns such as Sattvic, Rajasik and
Tamasic have been described of which the sattvic
dietary pattern appears to be similar to prudent dietary
patterns (Appendix 1) [5].
Appendix 1. Dietary advice in ancient Ayurveda. (Maha-anaarany Upanishad, 5000 BCE)
1. Sattvic diet. Advised to saints. Contains fresh fruits and vegetables, sprouted grains, legumes, roots, tubers,
nuts, cow milk, curd, and honey.It would enhance, longevity, health, happiness and spirituality and possible
survival may be 100-150 years. Good for mental, social and spiritual health.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 9 ~
2. Rajasic diet. Advised to kings and fighters. Contains fruits, vegetables, nuts, meats from hunted animals,
clarified butter, butter, curd, honey, spices, wines. Its spicy, hot, bitter, sour and pungent foods, which are not as
easily digestible as Sattvic food. Items such as red meat, red lentils, toor lentils, white pulse lentils, black and
green gram, chickpeas, spices such as chilies and black pepper and stimulants such as broccoli, cauliflower,
spinach, onion and garlic, tea, coffee, tobacco, soda, alcohol, chocolate, sour apples, pickles and sugars. It denotes
activity, decision-making, energy that is required for tasks and mental robustness. Rajasic food energises almost
all the systems, specially the nervous system and the mind are to help you push beyond capacity and capability.
Rajasic (originating from the word ‘Raja’, meaning king, means king. However, it also encourages aggression
and makes one more domineering.
It may cause excitement, confidence and increase intelligence with life expectancy of about 100 years. Good for
physical, mental and social health.
3. Tamasic diet. Not advised. Contains high fat fried foods, rich in salt, sugar, spices, chillies, onion, garlic, meats
from big tamed animals, butter and liquor. This diet makes one dull, enhances anger and criminal tendency and
impedes spiritual progress. Tamasic foods include meat, fish, mushrooms, overripe and under-ripe fruits and
vegetables. In addition, some fermented foods like vinegar, bread, pastries, cakes, alcohol and even leftovers and
stale food are considered Tamasic. Life expectancy was much lower. Bad for health.
Maharshi-Satyartha-Prakash, https://www.aryasamajjamnagar.org/ satyarth_prakash_eng.htm, Wikipedia.
Maharshi dayananda Saraswati, Satyartha Prakash, treats of Conduct - Desirable and Undesirable; Diet -
Permissible and Forbidden.
(https://www.aryasamajjamnagar.org/satyarth_prakash_eng.htm#google_vignette, accessed January 2021).
In the Indian Worship Era, (3000BCE) Panchamitra
(five divine nectars) containing.
1. Cow milk,
2. Curd/yogurt (probiotic),
3. honey (flavonoids),
4. basil leaves(flavonoids) and
5. water from river ganga (rich in antibacterial
phage types) were advised for long life, peace
and immortality. Lactobacilli
and Bifidobacteria, available for human use,
may also be present possibly, in panchamrit and
yogurt. Figure 2.
Figure 2. Verse in Sanskrit mentioning value and content of ancient yogurt.(3000BCE)
Panchamrita' is a traditional method of mixing five
natural foods as given above; milk, ghee, curd, honey
and dry fruits. These are used in Hindu and Jain
worship rituals. It is also used as a technique in
Ayurveda. Modi's 'Panchamrita' promises include:
India will get its non-fossil energy capacity to 500
gigawatt by 2030. Regular intake of panchamrit may
mprove Immunity, physical strength, promotes
emotional and mental health, mproves skin and hair
complexion. It appears to be a brain tonic because it
may provide beneficial effect on memory, grasping
power and creative abilities.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 10 ~
In brief, ancient concept of nutrition indicate that they
may have potential in the prevention of non-
communicable diseases which need cohort studies
and controlled trials.
Ethical clearance and Informed Consent. Not required because its not a original article.
Authors contributions. All the authors contributed equally.
Acknowledgements are given to International College of Nutrition for providing logistic support to write this article.
Conflict of interest. There is no conflict of interest among authors.
Funding. No especial grant given by any agency.
REFERENCES
[1]. Loomis WF. Skin pigment regulation of vitamin D
biosynthesis in man. Science 1967; 157: 501-6.
[2]. Lee RB. What hunters do for a living: A comparative study.
In: Lee RB, Devore I, Eds. Man the Hunter, Aldine:
Chicago 1968; 41-3
[3]. Simopoulos AP. Is Insulin Resistance Influenced by
Dietary Linoleic Acid and Trans Fatty Acids?. Free Radic
Biol Med 1994; 17: 367-72

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 11 ~
Editorial:
EVOLUTIONARY DIET AND MEDITERRANEAN STYLE DIETS
Fabian De Meester, Agnieszca Wilczynska, D W Wilson, Ram B Singh
The Tsim Tsoum Institute, Krakow, Poland
Correspondence
Fabien De Meester, PhD, FICN
The Tsim Tsoum Institute, Krakow, Poland, fdm@tsimtsoum.net
Abstract: The man started farming, about 10,000 years ago, with the technical development and upgradation of agriculture.
Therefore, for about 99% of the time during which man has been evolving from primate precursors, leading towards hunter-
gathering [1-5]. Apparently, our bodies have evolved well adapted for doing what hunter-gatherers do and eating what
they eat and also to “when” they were eating. The food consumption pattern of the Indian hunter-gatherers has some
similarity with the food consumed by other hunter-gatherers; vegetables, leaves, nuts, tubers, fruits, whole grains, eggs,
fish, honey. Indian Kurichia hunter-gatherers are known to be non-vegetarians. The Columbus concept of diet means that
humans evolved on a diet that was low in saturated fat and the amount of w-3 and w-6 fatty acids was quite equal, while
having nutrient rich foods.
Key words: Hunter-gatherers, foods, farming, meals.
Introduction. It is important to focus on the diet and
lifestyle of Homo sapiens and their predecessors,
namely Homo erectus and Homo habilis to
understand evolutionary diet, who were primarily
vegetarians. Hunting developed gradually when man
moved away from the other primates and skilled in
tool making, while developing social groups; hunting
bands and large families [1-5.] The man started
farming, about 10,000 years ago, with the technical
development and upgradation of agriculture.
Therefore, for about 99% of the time during which
man has been evolving from primate precursors,
leading towards hunter-gathering [1-5]. Apparently,
our bodies have evolved well adapted for doing what
hunter-gatherers do and eating what they eat and also
to “when” they were eating. Thus, it has been
proposed that the original skin color of man was
brown, providing protection from the sun, and
possibly white man evolved after settlement in
Northern Europe because brown skin probably might
have predisposed vitamin D deficiency causing
rickets [1, 2]. That is why, in the present discussion,
the authors describe and introduce the diet and
lifestyle of Indian hunter-gatherers for the first time
to western literature in view of assessing the merits
and demerits of the same to coordinate with modern
concept of Nutrition.
After development of agriculture, about
10,000 years ago; food was easily available and
stored. Thus, for about 99% of the time, human has
been evolving from primate precursors to
agriculturist, leading towards hunter-gathering life
style [3,4]. Apparently, our bodies have evolved well
adapted for doing what hunter-gatherers did and
eating what they ate and also “when” they were eating
[3]. But the major changes in the diet have occurred
after 1910 with rapid wave of urbanization and
industrialization that had significant impacts on
health and diseases.
Archiological Concepts of Nutrition. A basic
concept of evolution in relation to health promotion
has been that the genetic makeup of contemporary
humans shows minor difference from that of the
modern humans who appeared in Africa between
100,000 and 50,000 years ago [4-6]. The human
evolution has been comparatively rapid during the
past 50,000 years, as revealed by the molecular
geneticists. There have been marked changes in the
food supply with the development of agriculture
about 10,000 years ago from now. However, only
non-significant change in our genes occurred, during
the past 10 century, due to presence of w-3 fatty acids,
essential amino acids, antioxidants, vitamins and
minerals in the diet. The spontaneous mutation rate
for nuclear DNA is estimated at 0.5% per million
years. Hence, over the past 10,000 years there has
been time for very little change in our genes, possibly
0.005%. Our genes appear to be similar to the genes
of our ancestors during the Paleolithic period 40,000
years ago, the time when our genetic profile was
established. Man appears to live in a nutritional
environment which completely differs from that for
which our genetic constitution was selected.
However, during the last 100-160 years, dietary
intakes have changed significantly, causing increased
intake of saturated fatty acids (SFA), trans fatty acids
and linoleic acid and decrease in w-3 fatty acids, from
grain fed cattle, tamed at farm houses, rather than

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 12 ~
meat from running animals. In general, there is
increase in the intake of refined carbohydrates and
decrease in the intake of complex carbohydrates,
essential amino acids, minerals, vitamins and
antioxidants. There is marked reduction in
consumption of w-3 fatty acids, antioxidants,
vitamins and minerals and proteins and significant
increase in the intakes of carbohydrates, (mainly
refined,), fat (saturated, trans fat, linoleic acid) and
salt compared to Paleolithic period [4-6]. These
dietary changes in conjunction with sedentary
behavior, mental strain, pollution, tobacco
consumption and alcoholism, particularly after 1910,
during the last 100 years may have caused damage to
our genes, leading to emergence of non-
communicable diseases.
Figure 1. Dietary changes from Homo sapiens to Huntergatherers and modern men ( adapted from reference
7)
The protective effects of Paleolithic diets in
the form of Mediterranean diet, Indo-Mediterranean
diet, Japanese diet, and DASH diet have been
documented in the several previous studies. The
traditional concepts of nutrition, particularly, Rajasic
diet and the foods consumed by Indian hunter-
gatherers also support the consumption of natural
foods, similar to these diets. These studies have
clearly demonstrated the beneficial impacts of these
diets, against coronary artery disease, hypertension,
type 2 diabetes mellitus and cancers. The Columbus
concept of diet means that humans evolved on a diet
that was low in saturated fat and the amount of w-3
and w-6 fatty acids was quite equal [7]. Nature
recommends to ingest fatty acids in a balanced ratio
(polyunsaturated:saturated=w-6:w-3=1:1)as part of
dietary lipid pattern in which monounsaturated fatty
acids (M) is the major fat(P:M:S=1:6:1). These ratios
represent the overall distribution of fats in a natural
untamed environment. (www.columbus-
concept.com). The Columbus foods include egg,
milk, meat, oil, whole grain foods, all rich in w-3 fatty
acids, similar to wild foods, consumed about 160
years ago.
Food Intakes Among Indian Hunter-gatherers.
The food consumption pattern of the Indian
huntergatherers has some similarity with the food
consumed by other hunter-gatherers; vegetables,
leaves, nuts, tubers, fruits, whole grains, eggs, fish,
honey. Indian Kurichia hunter-gatherers are known to
be non-vegetarians. Meat is taken mostly from the
untamed animals and the time of hunting was
possibly, early in the morning, at sun rise when
animals come for drinking of water at the river banks.
They are fond of taking fresh meat that is hunted by
themselves for consumption. Since the government of
India has imposed ban on hunting in the forest, their
meat intake is now drastically reduced as given in the
appendix 2 and tables. Dietary intakes assessed by 3-
days dietary recall, were recorded in a questionnaire,
by the dietitian and by asking food intake frequency
in the last one month. Food models, food measures

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 13 ~
and food portions were showed to individuals with
the help of an educated Kurichia, who knew both the
languages, during dietary assessments. The dishes
taken by Kurichias will predominantly occupy with
green leaves like Cassia tora, Alternanthera sessilis
etc, vegetable like hydrocotyle, clerodendron,
nymphaea nouchali and roots like ceropegia and
elaeocarpus [9,10]. In fact, sugar is a recent addition
during the last 50 years. The main foods are; brown
rice, seasonal green leaves and fruits, roots and
tubers, fish, and butter milk. Alcohol and tobacco
intakes are considered evils which are uncommon.
These foods are rich sources of w-3 fatty acids,
antioxidants, essential amino acids, vitamins and
minerals and soluble fiber and are low in saturated fat,
w-6 fat and trans fat. Sugar is the only refined
carbohydrate. The food and nutrient intakes among
Kurichias appear to have similarity with the food
intakes among Hunter-gatherers living in the other
parts of the world. (Table 1)
Table 1. Food consumption pattern and meals among Indian hunter-gatherers
Morning: Most take milk or nothing but few prefer to have black tea (Fresh tea leaves that is available in their paddy
fields will be taken, boiled in the water and then take with sugar)
Breakfast: Majority of the people (around 95%) prefer to have Gangi in the morning for about 200 g to 300 g. (Gangi:
Brown rice mixed with Ragi and then kept over night in the water for fermentation and then take the semi solid mixed
with water). This will be supplemented with some self made pickle.
Lunch: They prefer to have brown rice only (cultivated from their fields without use of fertilizers). Rice cooked (200-
300g) will be supplemented with green leaves (100-200g, seasonally available) and a fried fish, 100-200g (fresh water)
available in their canals. They take some quantity of seasonal fruits, 100-200g daily.
Evening: Few people prefer to have black tea (Fresh tea leaves that is available in their paddy fields will be taken,
boiled in the water and then take with sugar)
Night: They prefer to have
brown rice only (yielded from their fields only). Rice will be supplemented with seasonal
green leaves (100-200g/day) and a fried fish(150-300day) available in their canals and buttermilk (100-300ml). They
take some quantity of fruit (100-200g).
(Personal Communication by KK Reddy, RB Singh, 2001
In brief, the diets of Hunter-gatherers were
close to Paleilithic diet which has some similarity
with Mediterranean diet. It has high omega-3 fatty
acids and flavonoids and fiber as well as
micronutrients. The Columbus concept of diet means
that humans evolved on a nutrient rich diet that was
low in saturated fat and the amount of w-3 and w-6
fatty acids was quite equal. Nature recommends to
ingest fatty acids in a balanced ratio
(polyunsaturated:saturated=w-6:w-3=1:1)as part of
dietary lipid pattern in which monounsaturated fatty
acids (M) is the major fat(P:M:S=1:6:1).
Ethical clearance and Informed Consent. Not required because its not a original article.
Authors contributions. All the authors contributed equally.
Acknowledgements are given to International College of Nutrition for providing logistic support to write this article.
Conflict of interest. There is no conflict of interest among authors.
Funding. No especial grant given by any agency.
REFERENCES
[1]. Loomis WF. Skin pigment regulation of vitamin D
biosynthesis in man. Science 1967; 157: 501-6.
[2]. Lee RB. What hunters do for a living: A comparative study.
In: Lee RB, Devore I, Eds. Man the Hunter, Aldine:
Chicago 1968; 41-3.
[3]. Singh RB, De Meester F, Wilczynska A. The Tsim Tsoum
approaches for prevention of cardiovascular diseases.
Cardiology Research and PracticeVolume, 2010, ArticleID,
824938, 18pages, doi:10.4061/2010/824938.
[4]. Eaton SB, Eaton SB III, Sinclair AJ, Cordain I, Mann NJ.
Dietary intake of long chain polyunsaturated fatty acids
during the Paleilithic period. In: Simopoulos AP Ed. The
return of w-3 fatty acids in the food supply. Land based
Animal Food Products and their Health Effects. World Rev
Nutr Dietetics 1998; 83: 12-23
[5]. Eaton SB, Konner M. Paleolithic nutrition. A consideration
of its nature and current implications. N Engl J Med.
1985;312(5):283–289.
[6]. Eaton SB, Konner M, Shostak M. Stone agers in the fast
lane: chronic degenerative diseases in evolutionary
perspective. Amer J Med 1988. 84:739-749.
[7]. De Meester F. Wild-type land based foods in health
promotion and disease prevention: the LDL-CC:HDL-CC
model. In: Wild Type Foods in Health Promotion and
Disease Prevention, Ed. Fabien De Meester, RR Watson,
Humana Press, NJ 2008, 3-20.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 14 ~
FATS AND OILS WITH REFERENCE TO INDIAN CLARIFIED BUTTER
Narsingh Verma1, Elena Kharlitskaya2, Sergey Chibisov3, Radzhesh Agarval4
1 Kings George Medical College, Lucknow, India
2,3 Peoples Friendship University of Russia, Moscow, Russian Federation
4 Technomed Holdings LLC Publishing House, Moscow, Russian Federation
Correspondence
Dr Sergey Chibisov, MD, PhD,FICN
Peoples Friendship University of Russia,
Moscow, Russia. Сергей Чибисов, kalcna@mail.ru
Abstract: Oils and fats are also called lipids, that are
found in foodstuffs of plant and animal origin. It is seeds of the
plants which provide the vegetable oils and fats, such as rape or mustard or soya bean oil from related seeds of plants.
Cooking oil is basically processed from the animal, plant, or synthetic fat which is used in frying, baking and other types
of cooking. India Ghee (In Sanskrit: Ghratam, is a class of clarified butter that originated in the Indus valley, approximately
500 BCE. It seems that it is better compared to butter because it solidifies at higher temperature compared to butter.
Key words: Fatty acids, lipids, saturated fat, animal fat
Introduction. Humans learned how to produce fire,
at around 250,000 BCE [1]. It was the time when
people used animal fats as edible oils for the purpose
of cooking of foods. Man has been using edible oils
for cooking with saturated fat from animals ever since
most of man existence. Interestingly, cardiovascular
disease was virtually non-existent until the use of oil
from seeds in the 19th century [1]. Oils and Fats are
also called lipids. They are found in foodstuffs of
plant and animal origin. It is seeds of the plants which
provide the vegetable oils and fats, such as rape or
mustard or soya bean oil and certain fruit, such as
avocado pears and olives, and from oleaginous fruit,
such as walnuts, almonds and hazelnuts. They are the
reserves of plants energy source. Here the aim is to
discuss the origin and the
Role of fats and oils in health and diseases.
Research on evolution of cooking revealed that, man
used a dino drumstick roasting on a stick procedure
before they were introduced to cooking oil. It is
possible that it could have been the first cooking
procedure which occurred thousands of years ago.
Another archetype, to a cauldron on a fireplace was
actually combined with water into some stew or
porridge. It is observed that, for millennia, the
majority of foods were basically eaten raw, roasted or
boiled.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 15 ~
Figure 1. Cooking methods in ancient word.(https://www.tutorialspoint.com/when-did-people-start-using-edible-oils-
for-cooking-food-how-did-people-cook-food-before-edible-oils-are-introduced-to-human-food, reference 1)
Cooking Oils. Cooking oil is basically processed
from the animal, plant, or synthetic fat which is used
in frying, baking and other types of cooking. It is also
used in the preparation of food items and developing
flavor in which heat is not involved, such as for bread
dips, dressing of salad, and therefore it may be termed
as more accurately edible oil[1]. A Swedish chemist,
discovered that glycerol could be obtained from olive
oil by heating it with litharge (lead monoxide) (C.W.
Scheele,1779). However, it was in 1815 that
the French chemist demonstrated the chemical nature
of fats and oils (Michel-Eugène Chevreul, 1786–
1889). The beneficial effects of oils depend on the
fatty acid content and flavonoids present in these oils.
Fatty acid composition of oils are given in figures 1-
4.
Figure 2. fats and oils and their fatty acid contents.
Figure 3. Fatty acid composition of edible oils.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 16 ~
Figure 4. Fatty acid composition of oils.(modified from Indian Food Composition Tables, ICMR)
Indian Clarified Butter.
India Ghee (In Sanskrit: Ghratam), is a class of
clarified butter that originated in the Indus valley,
approximately 500 BCE. It is commonly used in
cuisine of the Indian subcontinent, Middle Eastern
cuisine, traditional medicine. In religious rituals.
ghee, also spelled ghi, and in Sanskrit ghraṭa, and
Ghratam. Thus, clarified butter, appears to be a staple
food on the Indian subcontinent, that has been utilized
for thousands of years in Ayurveda as a therapeutic
agent. In ancient India, as well as in recent decades,
even today, ghee hasbeen the preferred cooking oil,
but CVDs were rare in India before 1950s.
Interestingly, several communities outside
the Indian subcontinent make ghee. Egyptians make
a product called samna baladi, meaning 'countryside
ghee', identical to ghee in terms of process and result,
but commonly made from water buffalo milk instead
of cow's milk, and white in color. The recipe is
considered to have come from South Asia during
ancient times of the Pharaoh as revealed in
inscriptions and could be the result of Mitanni and
Hittite kingdoms, which predate the existence of
Greeks. Thus Indians are the first to make clarified
butter The darkened milk solids that are created
during the process are considered a delicacy called
morta, which is a salty condiment used sparingly as a
spread, or as an addition on fava dishes. Regular
samna is also made from cow's milk in Egypt and is
often yellowish in colour. Ghee is also used by
various peoples in the Horn of Africa. Tesmi (in
Tigrinya language) is the clarified butter prepared in
the country of Eritrea. The preparation is similar to
that of ghee, but the butter is oftentimes combined
with garlic and other spices found native to the area.
In North Africa, Maghrebis take this one step further,
ageing spiced ghee for months or even years,
resulting in a product called smen. It's also common
in Western Africa especially among the Hausa and
Fulanis. It's called Manshanu meaning Cow's oil. In
Ethiopia, niter kibbeh is used in much the same way
as ghee, but with spices added during the process that
result in distinctive tastes.
Clarified Butter as Cooking Oil in India. Clarified
butter as a cooking oil, is the most widely used food
in India, apart from oils. Like any clarified butter,
ghee is composed almost entirely of fat, 62% of
which consists of saturated fats[2-5]. It is also
contains oxidized cholesterol: 259 μg/g, or 12.3% of
total cholesterol, which has been proposed to
predispose atherosclerosis among Indians living in
UK [6 ]. It has negligible amounts of lactose and
casein and is, therefore, acceptable to most who have
a lactose intolerance or milk allergy. In the last
several decades, ghee has been implicated in the
increased prevalence of coronary artery disease
(CAD) in Asian Indians due to its content of saturated
fatty acids and cholesterol and, in heated ghee,
cholesterol oxidation products [6]. Sharma et al, in a
previous experiment, reported, a model for the
general population, showing no effect of 5 and 10%
ghee-supplemented diets on serum cholesterol and
triglycerides [2]. However, results of the previous
research showed an increase in serum total
cholesterol and triglyceride levels when fed a 10%
ghee-supplemented diet [2]. In another study, he

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 17 ~
investigated the effect of 10% dietary ghee on
microsomal lipid peroxidation, as well as serum lipid
levels in Fischer inbred rats to assess the effect of
ghee on free radical mediated processes that are
implicated in many chronic diseases including CVDs
[2]. The findings revealed that 10% dietary ghee fed
for 4 weeks did not have any significant effect on
levels of serum total cholesterol, but did increase
triglyceride levels in Fischer inbred rats. Ghee at a
level of 10% in the diet did not increase liver
microsomal lipid peroxidation or liver microsomal
lipid peroxide levels [2]. Animal studies have
reported many beneficial effects of ghee, including
dose-dependent decreases in serum total cholesterol,
low density lipoprotein (LDL), very low density
lipoprotein (VLDL), and triglycerides; decreased
liver total cholesterol, triglycerides, and cholesterol
esters; and a lower level of nonenzymatic-induced
lipid peroxidation in liver homogenate [2-5]. Similar
results were seen with heated (oxidized) ghee which
contains cholesterol oxidation products [2,7]. High
doses of medicated ghee may reduce serum
cholesterol, triglycerides, phospholipids, and
cholesterol esters in psoriasis patients.
In a cross-sectional surveys including 1769
rural (894 men and 875 women) and 1806 urban (904
men and 902 women), aged 25-64 years of age, in
North India, the total prevalence of CAD based on
clinical history and electrocardiogram was
significantly higher in urban compared to rural men
(11.0 vs. 3.9%) and women (6.9 vs. 2.6%),
respectively[8]. Food consumption patterns showed
that important differences in relation to CAD were
higher intake of total visible fat, milk and milk
products, meat, eggs, sugar and jaggery in urban
compared to rural subjects. Prevalence of CAD, in
relation to visible fat intake showed a higher
prevalence rate with higher visible fat intake in both
sexes and the trend was significant for total
prevalence rates both for rural and urban men and
women. Subgroup analysis among urban (694 men
and 694 women) and rural (442 men and 435 women)
subjects consuming moderate to high fat diets showed
that subjects eating trans fatty acids plus clarified
butter or those consuming clarified butter as total
visible fat had a significantly higher prevalence of
CAD, compared to those consuming clarified butter
plus vegetable oils in both rural (9.8, 7.1 vs. 3.0%)
and urban (16.2, 13.5 vs. 11.0%) men as well as in
rural (9.2, 4.5 vs. 1.5%) and urban (10.7, 8.8 vs.
6.4%) women. This indicated that clarified butter
could be better than trans fatty acids.A study on a
rural population in India revealed a significantly
lower prevalence of coronary heart disease in men
who consumed higher amounts of ghee [9]. The
association between intake of dietary fat, specifically
Indian ghee, and prevalence of CAD and risk factors
as study was undertaken on a rural population in
Rajasthan [9]. The average amount of clarified butter
consumed in a month was determined among; 782
males (39%) which was 1 kg or more ghee per month
(group 1). Another group of subjects; 1200 (61%)
consumed less than 1 kg per month (group 2). Group
1 males were significantly younger, more literate and
had more weight and body-mass index, who
consumed significantly more calories, saturated and
mono-unsaturated fats while the consumption of
polyunsaturated fats was similar in the two groups.
Fatty acid intake analysis showed that group 1 males
consumed more mono-unsaturated (n-9) fatty acids
than group 2. Intake of polyunsaturated n-3 and n-6
fatty acids was similar. There was significantly lower
CAD prevalence in men who consumed > kg ghee per
month (odds ratio = 0.23, 95% confidence limits 0.18-
0.30, p < 0.001). Multivariate analysis confirmed this
association (p < 0.001) indicating that clarified butter
may have beneficial effects. Previous studies, on
Maharishi Amrit Kalash-4 (MAK-4), an Ayurvedic
herbal mixture containing ghee, showed no effect on
levels of serum cholesterol, high density lipoprotein
(HDL), LDL, or triglycerides in hyperlipidemic
patients who ingested MAK-4 for 18 weeks[2].
MAK-4 inhibited the oxidation of LDL in these
patients [2]. It is possible based on literature there are
no harmful effects on moderate consumption of ghee
in the general population. It seems that the increased
susceptibility of Indians living in urban areas and
among Indian immigrants to affluent countries may
be due to increased use of vegetable ghee and trans
fat present in the manufactured foods by the food
industry that are often consumed by affuluent Indians.
Therefore, it seems that findings in the literature are
controversial about the beneficial effects of clarified
butter, outlined in the ancient Ayurvedic texts and the
therapeutic use of ghee for thousands of years among
Indians [10-12].
In brief, olive oil, rape seed oil or canola oil, mustard
oil have been found beneficial in the prevention of
CVDs, including CAD. It seems that there is an unmet
need to find out the role of clarified butter in the
pathogenesis and prevention of CVDs.
Ethical clearance and Informed Consent. Not required because its not a original article.
Authors contributions. All the authors contributed equally.
Acknowledgements are given to International College of Nutrition for providing logistic support to write this article.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 18 ~
Conflict of interest. There is no conflict of interest among authors.
Funding. No especial grant given by any agency.
REFERENCES
[1]. Fats and oils. https://www.tutorialspoint.com/when-did-
people-start-using-edible-oils-for-cooking-food-how-did-
people-cook-food-before-edible-oils-are-introduced-to-
human-food
[2]. Sharma H, Zhang X, and Dwivedi C. The effect of ghee
(clarified butter) on serum lipid levels and microsomal lipid
peroxidation. Ayu. 2010; 31(2): 134–140.,doi:
10.4103/0974-8520.72361
[3]. Rajorhia GS. Ghee. In: Macrae R, Robinson RK, Sadler MJ,
editors. Encyclopedia of Food Science. Vol. 4. London:
Academic Press; 1993. pp. 2186–99. [Google Scholar]
[4]. Sserunjogi ML, Abrahamsen RK, Narvhus J. A review
paper: Current knowledge of ghee and related products. Int
Dairy J. 1998;8: 677–88.
[5]. Dwivedi C, Crosser AE, Mistry VV, Sharma HM. Effects
of dietary ghee (clarified butter) on serum lipids in rats. J
Appl Nutr. 2002;52:65–8
[6]. Jacobson, MS. (19 September 1987). "Cholesterol oxides in
Indian ghee: possible cause of unexplained high risk of
atherosclerosis in Indian immigrant populations". Lancet
1987; 2 (8560): 656–658. doi:10.1016/s0140-
6736(87)92443-3
[7]. Kumar MV, Sambaiah K, Lokesh BR.
Hypocholesterolemic effect of anhydrous milk fat ghee is
mediated by increasing the secretion of biliary lipids. J Nutr
Biochem. 2000;11:69–75.
[8]. Singh RB, Niaz MA, Ghosh S, Beegom R, Rastogi V,
Sharma JP, et al. Association of trans fatty acids (vegetable
ghee) and clarified butter (Indian ghee) intake with higher
risk of coronary artery disease in rural and urban
populations with low fat consumption. Int J Cardiol . 1996;
56: 289–98.
[9]. Gupta R, Prakash H. Association of dietary ghee intake
with coronary heart disease and risk factor prevalence in
rural males. J Indian Med Assoc. 1997;95:67–69
[10]. Nutrition data for Butter oil, anhydrous (ghee) per 100 gram
reference amount". US Department of Agriculture,
National Nutrient Database. May 2016. Retrieved 12 March
2018.
[11]. Otaegui-Arrazola, A.; Menéndez-Carreño, M.; Ansorena,
D.; Astiasarán, I. (December 2010). "Oxysterols: A world
to explore". Food and Chemical Toxicology. 48 (12): 3289–
3303. doi:10.1016/j.fct.2010.09.023. hdl:10171/22994.
ISSN 1873-6351. PMID 20870006.
[12]. Heid, Markham (22 April 2019). "Is Ghee Healthy? Here's
What the Science Says". Time. Retrieved 10 April 2021.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 19 ~
THE SEVEN COUNTRY STUDY: THE FIRST STUDY TO RELATE DIET
WITH RISK OF CARDIOVASCULAR DISEASE
Kiarash Moshiri1, Mahmood Moshiri2, Dominik Pella3, Daniel Pella4, R B Singh5
1,2 Next Pharma Inc, Thornhill, Canada
3,4 PJ Safaric University, Kosice, Slovakia
5 Halberg Hospital and Research Institute, Moradabad, India
Correspondence
Dr Mahmood Moshiri, MD, PhD, FICN
Next Pharma Inc. President and CEO
175 Commerce Valley Drive West,
Suite #350, Thornhill, ON, CANADA. Phone: 416-450-6414
Email: moshiri@nextpharmainc.com
Introduction. The Seven Countries Study, which
was planned by Dr Ancel Keys, is the first major
study to investigate the association of diet and
lifestyle factors with risk of cardiovascular disease
(CVDs), across contrasting countries and cultures for
a long period of time. Ancel Keys (1904 – 2004)
planned the Seven Countries Study in 1958, after
exploratory research on the relationship between
eating pattern and the prevalence of coronary artery
disease(CAD) in Greece, Italy, Spain, South Africa,
Japan, and Finland. Figure 1.
Principal investigators. The Seven
Country Study.1958
1. USA: Henry Taylor, Henry
Blackburn, David Jacobs
2. Finland: Martti Karvonen, Aulikki
Nissinen
3. Netherlands: Frans van Buchem,
Daan Kromhout
4. Italy: Flaminio Fidanza, Vittorio
Puddu, Alessandro Menotti
5. Greece: Christos Aravanis, Andy
Dontas
6. Yugoslavia: Croatia: Ratko Buzina;
Serbia: Bozidar Djordevic, Srecko
Nedeljkovic
7. Japan: Noboru Kimura, Hironori
Toshima
Figure 1. Seven Countries that participated in the Seven country
Study. (Adapted from: https://www.sevencountriesstudy.com/about-
the-study/countries/
Figure 2. Investigators in the Seven Country Study.
Since purpose to examine the effects of
variations in diet and lifestyle factors with CVDs, the
subjects, in the Seven Countries were chosen from the
cultures apparently contrasting in diets, lifestyle,

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 20 ~
eating habits, levels of risk factors, and incidence of
and mortality from CAD, though the latter was
unknown. The sample size of the subjects and number
were not statistically representative of the
correspondent countries and the subjects chosen was
partly on the basis of convenience. However, the
objective was to recruit all men of a civic department,
aged 40 to 59 years at the time of first examination.
The cultures showed differences in their diet qualities
and there were corresponding variations seen in
saturated fat, serum cholesterol, and incidence of
CAD after 5 and 10 years of follow-up [1]. Figure 3
Figure 3. Serum cholesterol and mortality duet coronary disease.
The Seven Country Study, determined fatty
acids in duplicates of the foods eaten at home among
samples of the 16 cohorts in 1960s. The statistical
analyses of data began with finding out the
associations among average saturated fat intake,
average levels of serum cholesterol and CAD
incidence rates in the various cohorts. After follow
up of 5 years, it showed strong associations among
the average saturated fat intake, average serum
cholesterol level and mortality rates due to CAD in
various cohorts (population level, cohort level, or
‘ecological relationships’) [2-4]. However, the
conclusions for individuals could not be drawn from
these results. But, these correlations are most valuable
in estimating the potential of population prevention.
Diet and Mortality in the Severn Country Study.
The Seven Countries Study, comprising 11,579 men
aged 40-59 years and "healthy" at entry, revealed that
after 15 years, 2,288 subjects died [4]. There were
differences in death rates among cohorts which may
be due to variations in the diets. Differences in mean
age, blood pressure, serum cholesterol, and smoking
habits "explained" 46% of variance in death rate from
all causes, 80% from coronary heart disease, 35%
from cancer, and 45% from stroke. However,
differences in mortality rates, were not related to
cohort differences in mean relative obesity, body
weight, and physical activity. Mortality rates were
related positively to average percentage of dietary
energy from saturated fatty acids, negatively to %
dietary energy from monounsaturated fatty acids, and
were unrelated to dietary energy percentage from
polyunsaturated fatty acids, proteins, carbohydrates,
and alcohol. The mortality rates were also negatively
related to the ratio of monounsaturated to saturated
fatty acids. The intake of oleic acid accounted for
almost all differences in monounsaturates among
cohorts. All-cause and CAD mortality rates were low
in cohorts with olive oil as the main fat[4].
Cross-Cultural Correlations After 25 and 50
Years Follow-Up. The cross-cultural associations
were repeated using 25-year and 50-year CAD
mortality data for serum cholesterol and saturated fat
intake and later extended with associations on
carbohydrates, flavonoids, and dietary patterns.
The Seven Countries Study examined the
relationship between trends in coronary deaths and
changes in blood cholesterol during follow up of 25
years [5]. Sixteen cohorts of men aged 40-59 years
from seven countries were followed, to find out
deaths over 25 years. The levels of Cholesterol were
obtained at year 10, and an indicator of cholesterol

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 21 ~
change during the first 10 years, increased the
association. A negative and significant interaction
was shown between baseline population cholesterol
levels and their 10-year change. As an indicator of
acceleration in mortality, cholesterol change over 10
years was also positively correlated (partial R-square
0-44) with the ratio of 25-year to 5-year deaths.
Conclusions It is possible that, late CAD death rates
are largely 'explained' by changes in blood cholesterol
levels during the early phases of the study, mainly due
to increases in lower cholesterol levels among some
cohorts [54]. The cohorts of men were examined, and
their average values of saturated fat intake and serum
cholesterol levels were calculated. Also, the number
of men who died from CAD or developed a non-fatal
heart attack during 5 years of follow-up per 100 men
at risk was calculated for each cohort. The
associations among saturated fat, serum cholesterol
and CAD incidence deal with average group
values and therefore the graphs say nothing about
individual risk. The average saturated fat intake and
serum cholesterol level levels at baseline, and the 5-
year incident CAD per cohort.
Figure 3. Saturated fat intake and serum cholesterol.( Adapted from reference 1).
The baseline Seven Countries Study data
showed a strong cross-sectional correlation between
average saturated fat intake and average serum
cholesterol level of 14 cohorts [1,5]. The average
intake of saturated fat varied between 3% of energy
in Japan and 22% in Eastern Finland. The average
serum cholesterol levels varied between 160 mg/dl
(4 mmol/l) in Japan and 270 mg/dl (7 mmol/l) in
Eastern Finland. The following conclusion can be
drawn from this graph: the cohorts with a high intake
of calories from saturated fat have also a high serum
cholesterol level. And cohorts with a low intake have
also a low cholesterol level. This does not say that a
high intake of saturated fat causes a high serum
cholesterol level, but rather that there is an association
at the population level which may or may not be
causal. It is not only the average saturated fat intake
and the average serum cholesterol values differed
largely among the cohorts but also the incident CAD
i rates. The average intake of saturated fat at baseline
was strongly correlated with the 5-year CHD
incidence rates of 13 cohorts. This graph shows nicely
the higher the saturated fat intake the higher the CHD
incidence and the lower the saturated fat intake the
lower the CHD incidence. Similar correlations were
also found using 10-year CHD mortality rates.
Study findings.
In brief, it is possible that that the Seven
Countries Study generated an incredible amount of
information. The main topic of interest was CVDs,
which was expanded with research into healthy aging
after 1984
Acknowledgements are given to concerned experts who kindly made this website to educate the world.
Ethival clearance and Informed Consent. Not required because its not a original article.
Authors contributions. All the authors contributed eqally.
Acknowledgements are given to International College of Nutrition for providing logistic support to write this article.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 22 ~
Conflict of interest. There is no conflict of interest among authors.
Funding. No especial grant given by any agency.
REFERENCES
[1]. Ancel Keys Launched the Seven Countries Study
(https://www.sevencountriesstudy. com/about-the-
study/investigators/ancel-keys/ accessed February 2022.
[2]. Verschuren WMM, Jacobs DR, Bloemberg BPM,
Kromhout D, Menotti A, Aravanis C, Blackburn HW,
Buzina R, Dontas AS, Fidanza F, Karvonen MJ,
Nedeljkovic S, Nissinen A, Toshima H. Serum total
cholesterol and long-term coronary heart disease mortality
in different cultures. Twenty-five year follow-up of the
Seven Countries Study. JAMA 1995;274:131-136.
[3]. Hoogen PC van den, Feskens EJ, Nagelkerke NJ, Menotti
A, Nissinen A, Kromhout D, for the Seven Countries Study
Research Group. The relation between blood pressure and
mortality due to coronary heart disease among men in
different parts of the world. N Engl J Med; 2000; 342;1-8.
[4]. Keys A, Menotti A, Karvonen MJ, Aravanis C, Blackburn
H, Buzina R, Djordjevic BS, Dontas AS, Fidanza F, Keys
MH, et al. The diet and 15-year death rate in the seven
countries study. Am J Epidemiol. 1986 Dec;124(6):903-15.
doi: 10.1093/oxfordjournals.aje.a114480. PMID: 3776973.
[5]. Menotti A, Blackburn H, Kromhoutf D, Changes in
population cholesterol levels and coronary heart disease
deaths in seven countries. European Heart Journal (1997;
18: 566-571 Further Reading.
[6]. Hertog MGL, Feskens EJM, Hollman PCH, Katan MB,
Kromhout D. Dietary antioxidant flavonoids and risk of
coronary heart disease. The Zutphen Elderly Study. Lancet
1993;342:1007-1012. Impact factor = 59.1 Citations: 3268
[7]. Kromhout D, Bosschieter EB, De Lezenne Coulander C.
The inverse relation between fish consumption and 20-year
mortality from coronary heart disease. N Engl J Med
1985;312:1205-1209. Impact factor = 70.7 Citations: 1857
[8]. Hertog MGL, Kromhout D, Aravanis C, Blackburn H,
Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A,
Nedeljkovic S, Pekkarinen M, Simic BS, Toshima H,
Feskens EJM, Hollman PCH, Katan MB. Flavonoid intake
and long-term risk of coronary heart disease and cancer in
the Seven Countries Study. Arch Intern Med
1995;155:381-386. Impact factor = 20.8* Citations: 1437
[9]. Keys A, Karvonen MJ, Kimura N, Fidanza F, Taylor HL.
Indexes of relative weight and obesity. J Chron Dis
1972;25:329-343.
[10]. Blackburn H, Keys A, Simonson E, Rautaharju P, Punsar
S. The electrocardiogram in population studies – a
classification system. Circulation 1960;21:1160-1175.
[11]. Keys A, Menotti A, Karvonen MJ, Aravanis C, Blackburn
H, Buzina R, Djordjevic BS, Dontas AS, Fidanza F, Keys
MH, Kromhout D, Nedeljkovic S, Punsar S, Seccareccia F,
Toshima H. The diet and 15-year death rate in the Seven
Countries Study. Am J Epidemiol 1986;124:903-915.
Impact factor = 4.5 Citations: 1173
[12]. Knoops KTB, Groot LCPGM de, Kromhout D, Perrin AE,
Moreiras-Varela O, Menotti A, Staveren WA van.
Mediterranean diet, lifestyle factors and 10-year mortality
in elderly European men and women. The HALE project.
JAMA 2004;292:1433-1439. Impact factor = 51.3
Citations: 985
[13]. Keli SO, Hertog GL, Feskens EJM, Kromhout D. Dietary
flavonoids, antioxidant vitamins and incidence of stroke.
The Zutphen Study. Arch Intern Med 1996;156:637-642.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 23 ~
YOU ARE WHAT YOU EAT AND YOUR FATHER AND MOTHER EAT
Adrian Isaza1, Ghazi Halabi2, RB Singh3
1Everglade University, Tampa, USA
2Halberg Cardiac Center, Alay, Lebanon
3
Halberg Hospital and Research Institute, Moradabad, India
Correspondence
Dr Ghazi Halabi, MD, PhD
Halberg Cardiac Center, Alay, Lebanon, Email: ghazi@ghazihalabi.com
Introduction:

 

      
 
      









 




 




,(

)

The above verse is in Sanskrit to be read as:
ahamannamahamannamahamannam|, ahamannādo 2'hamannādo
2āhamannādaḥ| ahaṁ ślokakṛdahaṁ ślokakṛdahaṁ ślokakṛt| ahamasmi
prathamajā ṛtā3sya pūrvaṁ devebhyo'mṛtasya nā3bhāyi |yo mā dadāti sa ideva
mā3vāḥ| ahamannamannamadantamā3dmi| ahaṁ viśvaṁ
bhuvanamabhyabhavā3m |suvarna jyotīḥ | ya evaṁ veda | ityupaniṣat|
English Translation.(I am What, I am Eating)
I am food! I am food! I am food! I am the eater of food! I am the eater! I am the
eater! I am he who maketh Scripture! I am he who maketh! I am he who maketh!
I am the firstborn of the Law; before the gods were, I am, yea at the very heart
of immortality. He who giveth me, verily he preserveth me; for I being food, eat
him that eateth. I have conquered the whole world and possessed it, my light is
as the sun in its glory.” Thus he singeth, who hath the knowledge. This verily is
Upanishad, the secret of the Veda
The above verse is from the ancient Indian
Upanishads [1]: It appears to be similar to modern
concept proposed by other experts. “You are what
you eat, the saying goes. and, according to two new
genetic studies, you are what your mother, father,
grandparents and great-grandparents ate, too [2-4].
The familiar aphorism “Dis-moi ce que tu manges, je
te dirai qui tu es” (“Tell me what you eat, I will tell
you who you are”) or its popular paraphrase “You are
what you eat” is number four in a list at the beginning
of volume 1 of Brillat-Savarin’s Physiologie du Goût
[2]. But Brillat-Savarin’s third aphorism bears
attention as well: “La destinée des nations dépend de
la manière dont elles se nourissent” (“The destiny of
nations depends on how they eat and when they eat).
The findings, which involve epigenetics, may
help explain the increased genetic risk that children
face the problems, compared to their parents for
diseases such as obesity, insulin resistance, metabolic
syndrome and diabetes mellitus (DM) and
cardiovascular diseases (CVDs). It seems that poor
dietary habits may be crucial for our progeny, despite
having healthy eating habits. However, it is well
known that eating diets and lifestyle would not
change the sequence of DNA, but it may have a
profound effect on gene expression; switch-on or
switch-of the expression of genes via the possibilities
encoded on DNA. Therefore, changing eating habits
to healthy foods can turn on or off certain genetic
markers which play a major role in the pathogenesis
of CVDs and DM, life or death, and possibly in health
promotion [3-5]. This article aims to highlight the role
of nutrients and energy intake of parents on off-
springs.
Experimental Studies in Mice.
The dietary nutrients among human adults
induce changes in all cells including sperm in males
and egg cells in females, which are passed to off-
springs. It is known that children born to mothers
during the Dutch famine at the end of World War II
had susceptibilities to various diseases later in life,
such as glucose intolerance and CVDs, which
depended on the timing and extent of nutrient and
energy deficiency during pregnancy.In landmark
experiments, it has been demonstrated that Agouti
gene in mice controls hair color and is under the
influence of a developmentally regulated hair cycle-
specific promoter in exon 2[3,5]. The gene can switch
ON at a specific time during hair follicle cell
development to produce an agouti coat with a yellow
stripe in otherwise dark hair. Figure 1.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 24 ~
Figure 1. Laboratory agouti mice (left)
gave birth to young (right) that differed
markedly in appearance having obesity
and yellow fur and disease susceptibility.
(Adapted from reference 4, Watters E.
DNA Is Not Destiny: The New Science of
Epigenetics. Discoveries in epigenetics are
rewriting the rules of disease, heredity, and
identity. The Sciences Nov 22, 2006).
It is clear that epigenetic changes alter the
physical structure of DNA or surface of the gene.
DNA methylation, histone modification, mRNA
alteration, length of telomere etc are examples of
epigenetic alterations. There is addition of a methyl
group, or a "chemical cap," to part of the DNA
molecule, after DNA methylation, which prevents
certain genes from being expressed. During the
histone modification, the epigenetic regulation alters
gene expression to promote compensatory
adjustments in metabolism. These early adaptive
epigenetic changes have consequences later in life
when the metabolic changes no longer coincide with
the external environment, resulting into CVDs and
DM. These alterations may also predispose type 1
DM among infants and children which already have
concerned genes. The paternal epigenetic inheritance
influences the pathophysiology, indicating that
another epigenetic mark apart from methylation of
DNA may be incompletely cleared in the
heterozygous knockout offspring [3]. This may lead
to epigenetic inheritance and phenotype such as
obesity and metabolic syndrome..
There is evidence that a mutant form of this
gene; Avy , may convert the fur of the animal yellow
due to alteration in nutrients such as vitamin B12,
pyridoxine, betain and predispose toward becoming
fat and developing diabetes and cancer [3-5] [163,
164]. However, if the same mice with
mutations, administered food supplements with extra
methyl groups, bear non-obese brown pups that may
live longer. [165].
It seems that in the yellow obese mouse, the
mutant agouti gene is un-methylated and turned on all
the times, while in the brown mouse, the gene is
completely methylated and hence shut down. It is
clear that, the color of these agouti mice acts like a
sensor for the amount of methylation of DNA, found
in the color gene. It has been reported from
Netherland, that in affected pregnant women and their
off-springs, two DMRs—carnitine
palmitoyl transferase 1A (CPT1A) and insulin
receptor (INSR) genes to be associated with
birthweight and LDL cholesterol levels[5]. [166]. It
was later on observed after few years, that
methylation of the IGF2 gene was reduced and
remained decreased in subjects whose mothers were
starved in the first trimester of pregnancy and
remained normal in individuals whose mothers
experienced starvation in the later periods of
pregnancy. It is clear that the environmental factors,
can change a fetal epigenome and eventually the
long-term fate of an offspring.
It is well known that phenotype of animals
may be modified by the nutritional modulations
through epigenetic mechanisms [3,6-11]. As a key
and central component of epigenetic network, DNA
methylation is labile in response to nutritional
influences [11]. Alterations in DNA methylation
profiles can lead to changes in gene expression,
resulting in diverse phenotypes with the potential for
decreased growth and health. Here, I reviewed the
biological process of DNA methylation that results in
the addition of methyl groups to DNA; the possible
ways including methyl donors, DNA
methyltransferase (DNMT) activity and other
cofactors, the critical periods including prenatal,
postnatal and dietary transition periods, and tissue
specific of epigenetic modulation of DNA
methylation by nutrition and its mechanisms in
animals. Figure 2.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 25 ~
Figure 2. Conceptual model of the nutritional
epigenomics, showing changed epigenomics
markings resulting from nutritional exposures.
(Adapted from reference 11).
Dietary Modulators of Methylation. Diet has
several precursors for donating methyl radical
for DNA and protein methyltransferases S-
Adenosylmethionine (SAM) which is
synthesized in the methionine cycle [11-15].
These nutritiona precursors; folate, methionine,
choline, betaine and vitamins B2, B6 and B12,
enter at different sites in the methionine pathway
and contribute to the net synthesis of SAM. Thus,
decrease in the methyl donors may result in decreased synthesis of SAM with global DNA hypomethylation,
and vice versa [14,15]. Experimental studies have demonstrated about the effects of methyl donors on DNA
methylation [16,17].
It seems that, dietary deficiency in methyl donors may produce global DNA hypomethylation in
rodents [18-]. Similarly, maternal diet supplemented with methyl donors increases DNA methylation in
specific loci [19-21]. The methylation patterns of DNA may be altered by methyl donors, but little is known
about the necessary doses and the exact durations of dietary exposure or depletion contributing changes in
epigenetic marks[11]. Previous studies found a more complex scenario. Indicating that low protein or 50%
global malnutrition during gestation in mice led to both hyper- and hypo-methylation at specific loci in the
offspring [22,23]. There is an unmet need to find out the amount of methyl-donors which is reduced in these
specific studies, because it is commonly accepted that undernutrition correlates with reduced methyl-donor
availability.
DNA Methyltransferase Activity. It is well known that DNMT require SAM as a cofactor for their full
activation. Methyl donors from the diet may contribute to modulate DNMT activity by changing the
intracellular concentration of SAM. Besides an indirect regulation of DNA methylation patterns through
modulation of SAM pools, several compounds can also directly influence the expression or activity of DNMT
[25]. Evidence of a competitive inhibition of DNMT activity has been demonstrated for the (−)-
epigallocatechin-3-gallate (EGCG), polyphenol in green tea, or the genistein present in soybean [26-29].
Myricetin can also decrease DNA methylation by inhibiting SssI DNMT.
Figure 3. Genetic response to diet and
nutrients indicating directly inhibiting
enzymes; histone acetylation complex
that catalyze DNA methylation or
histone modifications, or by altering
the availability of substrates necessary
for those enzymatic reactions such as
activation or repression of
transcription (modified from [3]).
It seems that unlike a gene mutation, all of the
epigenetic inputs to the DNA environment should be
forgotten when a newly formed
embryo begins to divide. All
epigenetic marks are erased during the
process of meiosis or cell division,
however its not completely correct.
The chromatin is like the chemical
soup in which DNA operates, which
could be under influence of nutrients.
It is possible that apart from creating
epigenetic marks, Singh's group speculates that these

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 26 ~
nutrients also can cause expression of the gene
sequence, both good and bad. The information we
inherit from our parents is in the form of DNA,
however, it may be more than just DNA that is
inherited. Because what we inherit from parents are
chromosomes, and chromosomes are only 50 percent
DNA. It is possible that eating more omega-3 fatty
acids, flavonoids, choline, betaine, folic acid and
vitamin B12, by mothers and fathers, possibly can
alter chromatin state with increased expression of
gene sequence causing beneficial effects, leading to
birth of a 'super baby' with long life and lower risk of
diabetes and metabolic syndrome [6,8,30]. The cells
in an early state of development are more prone to
epigenetic changes from nutrition than adult cells,
hence the most notable changes are seen fetuses and
infants. Genetic response to diet and nutrients
indicating directly inhibiting enzymes; histone
acetylation complex that catalyze the process can be
seen in the figure 3.
In brief, epigenetics refers to changes in gene
expression from environmental factors such as diet.
This phenomenon is different from a mutation,
because epigenetic changes lie not in the DNA itself
but rather in its surface and surroundings. These are
the enzymes and other chemicals that orchestrate how
a DNA molecule unwinds its various sections to make
proteins or even new cells[28,29]. Previous studies
have shown how nutrition dramatically alters the
health and appearance of otherwise identical mice.
The mouse clones implanted as embryos in separate
mothers will have radical differences in fur color,
weight, and risk for chronic diseases depending on
what that mother was fed during pregnancy. Thus the
nutrients or deficiency of nutrients alters the DNA
environment in such a way that the identical DNA in
these mouse clones expressed itself in very different
ways. It is not clear how information is remembered
from one generation to next generation. It seems half
of the characteristics are carried out by DNA and the
other half is made up of protein molecules, and
micronutrients which carry the epigenetic marks and
information.
Ethical clearance and Informed Consent. Not required because its not a original article.
Authors contributions. All the authors contributed equally.
Acknowledgements are given to International College of Nutrition for providing logistic support to write this article.
Conflict of interest. There is no conflict of interest among authors.
Funding. No especial grant given by any agency.
References
[1]. Indian Upanishads
https://upanishads.org.in/upanishads/7/3/10/5, 5000 BCE
[2]. Your Diet Affects Your Grandchildren's DNA, Scientists
Say. https://www. livescience. com/21902-diet-
epigenetics-grandchildren.html, accessed March 2022.
[3]. Bernal AJ, Murphy SK, Jirtle RL. Mouse models of
epigenetic inheritance. Chapter 12, Handbook of
Epigenetics, The New Molecular and Medical Genetics.
2011; Pages 233-249
[4]. Watters E. DNA Is Not Destiny: The New Science of
Epigenetics. Discoveries in epigenetics are rewriting the
rules of disease, heredity, and identity. The Sciences Nov
22, 2006.https:// www.discovermagazine.com/the-
sciences/dna-is-not-destiny-the-new-science-of-
epigenetics accessed March 2022.
[5]. Brillat-Savarin JA. Aphorisms 3 and 4. In: Taste
physiology, or, Meditations on transcending gastronomy.
Theoretical, historical, and up-to-date work dedicated to
Parisian gastronomes. Paris: A. Soutelet Co. Vol. I, 1926.
[6]. Singh RB, Lee JY, Fedacko J et al. Epigenetic inheritance
of hypertension. World Heart J 2016; 8: 79-88.
[7]. Singh RB, Singh AK, Shaan E Alam, De Meester F,
Fedacko F, Dharwadkar SM, Juneja LR, Wilson DW.
Effects of omega-3 fatty acids on genetic expressions. In:
De Meester F, Watson RR, Zibadi S, eds. Omega-6/3
Fatty Acids, Functions, Sustainability, Strategies, and
Perspectives. New York: Humana Press, Springer; 2013.
pp. 27-52.
[8]. Lee JY, Azar SH. Effects of perinatal protein-NaCl diets
on offspring’s blood pressure and renal function in Lewis
rats. The Open Hyperten J 2013; 5: 1-11
[9]. Singh RB, Singh AK, Shaan E Alam, De Meester F,
Fedacko F, Dharwadkar SM, Juneja LR, Wilson DW.
Effects of omega-3 fatty acids on genetic expressions. In:
De Meester F, Watson RR, Zibadi S, eds. Omega-6/3
Fatty Acids, Functions, Sustainability, Strategies, and
Perspectives. New York: Humana Press, Springer; 2013.
pp. 27-52.
[10]. Robert A Waterland RA, Jirtle RL .Early nutrition,
epigenetic changes at transposons and imprinted genes,
and enhanced susceptibility to adult chronic
diseases.Nutrition 2004; 20(1):63-8
[11]. Zhang N. Epigenetic modulation of DNA methylation by
nutrition and its mechanisms in animals. Animal Nutrition,
2015; 1: 144-151.
https://doi.org/10.1016/j.aninu.2015.09.002.
[12]. J.C. Mathers. Session 2: personalised nutrition.
Epigenomics: a basis for understanding individual
differences?Proc Nutr Soc, 2008; 67: 390-394
[13]. Alam, S.E., Singh, R.B., Gupta, S., Dherange, P., De
Meester, F., Wilczynska, A., Dharwadkar, S., Wilson, D.,
and Hungin, P.Nutritional aspects of epigenetic
inheritance. Canadian Journal of Physiology and
Pharmacology, 90(8): 989–994, doi:10.1139/Y2012-105.
[14]. Feil R, M.F. Fraga. Epigenetics and the environment:
emerging patterns and implications Nat Rev
Genet, 13 (2012), pp. 97-109
[15]. McKay JA, J.C. Mathers. Diet induced epigenetic changes
and their implications for health Acta Physiol, 202 (2011),
pp. 103-118
[16]. Cordero P, F. Milagro, J. Campion, J. Martinez. Maternal
methyl donors supplementation during lactation prevents

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 27 ~
the hyperhomocysteinemia induced by a high-fat-sucrose
intake by dams. Int J Mol Sci, 14 (2013), pp. 24422-24437
[17]. Cordero P, F.I. Milagro, J. Campion, J.A. Martinez.
Supplementation with methyl donors during lactation to
high-fat-sucrose-fed dams protects offspring against liver
fat accumulation when consuming an obesogenic diet. J
Dev Orig Health Dis, 5 (2014), pp. 385-395
[18]. Mehedint MG, C.N. Craciunescu, S.H. Zeisel. Maternal
dietary choline deficiency alters angiogenesis in fetal
mouse hippocampus.Proc Natl Acad Sci U S
A, 107 (2010), pp. 12834-12839.
[19]. Waterland
RA, M. Travisano, K.G. Tahiliani, M.T. Rached, S. Mirza.
Methyl donor supplementation prevents transgenerational
amplification of obesity. Int J Obes, 32 (2008), pp. 1373-
1379.
[20]. Li W, M. Jiang, Y. Xiao, X. Zhang, S. Cui, G. Huang.
Folic acid inhibits tau phosphorylation through regulation
of PP2A methylation in SH-SY5Y cells. J Nutr Health
Aging, 19 (2015), pp. 123-129.
[21]. Farias
N, N. Ho, S. Butler, L. Delaney, J. Morrison, S. Shahrzad,
et al. The effects of folic acid on global DNA methylation
and colonosphere formation in colon cancer cell lines. J
Nutr Biochem, 26 (2015), pp. 818-826
[22]. Heijmans
BT, E.W. Tobi, A.D. Stein, H. Putter, G.J. Blauw, E.S. Su
sser, et al.Persistent epigenetic differences associated with
prenatal exposure to famine in humans. Proc Natl Acad
Sci U S A, 105 (2008), pp. 17046-17049
[23]. Waterland RA, R. Kellermayer, E. Laritsky, P. Rayco-
Solon, R.A. Harris, M. Travisano, et al. Season of
conception in rural gambia affects DNA methylation at
putative human metastable epialleles. Plos
Genet, 6 (2010), p. e1001252
[24]. Mukherjee N, A.P. Kumar, R. Ghosh. DNA methylation
and flavonoids in genitourinary cancers. Curr Pharmacol
Rep, 1 (2015), pp. 112-120
[25]. Fang M, D. Chen, C.S. Yang. Dietary polyphenols may
affect DNA methylation J Nutr, 137 (2007), pp. 223S-
2285
[26]. Vanhees
K, S. Coort, E.J.B. Ruijters, R.W.L. Godschalk, F.J. van
Schooten, S.B.V.W. van Doorn-Khosrovani. Epigenetics:
prenatal exposure to genistein leaves a permanent
signature on the hematopoietic lineage. FASEB
J, 25 (2011), pp. 797-607.
[27]. Xie
Q, Q. Bai, L.Y. Zou, Q.Y. Zhang, Y. Zhou, H. Chang, et
al.. Genistein inhibits DNA methylation and increases
expression of tumor suppressor genes in human breast
cancer cells.Genes Chromosom Cancer, 53 (2014),
pp. 422-431
[28]. Zampieri
M,F, Ciccarone, R. Calabrese, C. Franceschi, A. Bürkle, P.
CaiafaReconfiguration of DNA methylation in aging.
Mech Ageing Dev (2015),http://dx.doi.org/10.1016/ j.
mad. 2015.02.002
[29]. Lee WJ, J. Shim, B.T. Zhu. Mechanisms for the inhibition
of DNA methyltransferases by tea catechins and
bioflavonoids. Mol Pharmacol, 2005’ 68: 1018-1030.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 28 ~
THE CONCEPT OF FUNCTIONAL FOODS AND FUNCTIONAL FARMING:
(4F) IN THE DISEASE PREVENTION AND HEALTH PROMOTION
Ekasit Onsaard1, Toru Takahashi2, MA Manal3, Galal Elkilany4, Krasimira Hristova5,Kiarash Moshiri6
1 Faculty of Agriculture Ubon Ratchathani University,Warinchumrab, Ubonratchathani, Thailand
2 Graduate School of Health Sciences, Fukuoka Women's University, Fukuoka
3 United Arab University, Ajnam, UAE
4 Dibba Hospital, Fujareh, UAE
5 National Heart Hospital, Sofia, Bulgaria
6 International College of cardiology,Thornhill, Canada
Correspondence
Asst. Prof. Ekasit Onsaard, PhD.
Department of Agro-Industry, Faculty of Agriculture
Ubon Ratchathani University
Warinchumrab, Ubonratchathani
Thailand 34190
Abstract: After Rome meeting in 2014, on Dec 1-3,2014, food, nutrition and agricultural scientists as well as physicians
and epidemiologists from several countries were also present in the 18th World Congress on Clinical Nutrition organized
by Ubon Ratchathani Unive
rsity and International College of Nutrition. It is clear that there is opportunity to make
nutrition, a central part of the post-
2015 sustainable human and agricultural development agenda to provide slowly
absorbed functional foods (FF) and functional far
ming(FF) that are rich in nutrients (4 F). The efforts are adequate to
address the many challenges of global malnutrition; which is a major risk factor of cardiovascular diseases (CVDs) and
other chronic diseases. Increased dietary intake of energy rich western foods; foods salt, trans fat, saturated fat and refined
carbohydrates and preserved meats in conjunction with physical inactivity are known to enhance all the risk factors leading
to non-communicable (NCDs).However, diets rich in functional foods are protective. Hence, there is an unmet need to
encourage functional cropses or functional farming for better food security and prevention of malnutrition.
Key words: Agriculture, healthy foods, healthy cropse, nutrient, disease.
Introduction. In 2014, government ministers and
other participants from around the world were
gathered in Rome, Italy for the 2nd International
Conference on Nutrition organized by WHO and the
FAO [1]. On Dec 1-3,2014, food, nutrition and
agricultural scientists as well as physicians and
epidemiologists from several countries were also
present in the 18th World Congress on Clinical
Nutrition organized by Ubon Ratchathani University
and International College of Nutrition [2]. It is clear
that there is opportunity to make nutrition, a central
part of the post-2015 sustainable human and
agricultural development agenda to provide slowly
absorbed functional foods (FF) and functional
farming(FF) that are rich in nutrients (4 F). These
efforts might ensure that the goals and targets set are
adequate to address the many challenges of global
malnutrition; including under-nutrition as well as
obesity which are major risk factors of cardiovascular
diseases (CVDs); hypertension, coronary artery
disease (CAD, stroke and heart failure and other
chronic diseases; type 2 diabetes mellitus, cancer,
chronic respiratory diseases, bone and joint diseases
and neurodegenerative diseases. We also find an
opportunity in developing an international consensus
on how to approach to prevent malnutrition, for the
prevention of CVDs and other chronic diseases, so
that there is no increase in human susceptibility to
these diseases (3).Sofia declaration also proposed to
policy makers, health professionals and general
population, particularly mothers to learn functional
food rich Mediterranean-like diet and then to
introduce and promote this specific diet to existing
patients, prospective outpatients, and their family
members to concentrate on pregnant mothers, infants
and children as well as elderly for interventions,
particularly in middle and lower income countries
where CVDs and other chronic diseases are rapidly
emerging [3,4].
Diet and Disease Prevention. CVDs emerge in a
sequence during transition from poverty to affluence
and ageing of the populations [3,4-8]. Some of the
NCDs such as coronary artery disease (CAD) and
chronic respiratory diseases related to tobacco
consumption are more common among lower income
and lower-middle-income countries, despite modest
increase in overweight and obesity. The modern diets
and lifestyle have been adopted by increased number
of people and populations in the Western world and
in the urban populations of middle-income countries

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 29 ~
in the last few decades [3,4,8]. These diets are known
to predispose the epidemic of NCDs. Cardiovascular
disease (CVD), diabetes mellitus, obesity, cancer,
autoimmune diseases, rheumatoid arthritis, asthma
and depression are associated with increased
production of thromboxane A2 (TXA2), leucotrienes,
prostacyclin, interleukins-1 and 6, tumor necrosis
factor-alpha and C-reactive proteins [8]. Increased
dietary intake of energy rich foods containing high
trans fat, saturated fat and w-6 fat and refined
carbohydrates in conjunction with physical inactivity
are known to enhance all these biomarkers which
have adverse pro-inflammatory effects resulting into
NCDs (9-15). Industrialization and urbanization due
to economic development and affluence in
association with greater availability of foods,
especially ready prepared foods, to populations in
middle and high income countries has resulted in to
rapid increase in the CVDs. Figure 1.
Figure 1. Transition from poverty to
affluence and development of risk
factors of chronic diseases.
However these foods are high in
energy and fat as well as in trans fat
but poor in nutrient density, resulting
in to a decrease in the consumption of
omega-3 fatty acids, vitamins,
flavonoids, minerals as well as in
essential and nonessential amino acids
and significant increase in the intakes
of carbohydrates, (mainly refined), fat
(saturated, trans fat and linoleic acid)
and salt compared to the early peasants
and Paleolithic period [5-7]. The
protein or amino acid intake was 2.5
fold greater (33 vs. 13%) in the
Paleolithic diet of Homo sapiens
compared to modern Western diet consumed by Homo economicus populations(8-10. It has been estimated
that diets of Homo sapiens were characterized by higher intakes by essential and non-essential amino acids,
calcium, potassium, magnesium, flavonoids and w-3 fatty acids whereas modern Western diet of Homo
economicus has excess of energy-rich refined carbohydrates, w-6, trans fat and saturated fat and low in
protective nutrients. There is marked change in food and nutrient intakes, during the last 100-160 years causing
increased intake of saturated fatty acids (SFA), trans fatty acids and linoleic acid and meat from grain fed
cattle, tamed at farm houses, rather than meat from running animals [5-10].
Mortality Due to Chronic Diseases. The burden of death and disability attributable to CVDs and other chronic
diseases is rising in all middle- and high-income countries, because of the rapid changes in the diet and lifestyle
patterns [11,12]. Millions of deaths occur every year due to lack of health education and poor public health
policies. CVDs are a great challenge to health care experts and governments and appear to be an underlying
cause for poverty as well as threat to human, social, and economic development. The 36·1 million deaths per
year as a result of CVDs and other chronic diseases represent almost two out of three deaths per year
worldwide. 22·4 million of these deaths arise in the poorest countries, and 13·7 million in high-income and
upper-middle-income countries [11]. Approximately, two-thirds (63%) of premature deaths in adults (aged
15–69 years), and three of four of all adult deaths are attributable to CVDs and other chronic diseases.
Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes
of death, 1990–2013: by the Global Burden of Disease Study 2013, has also confirmed greater burden of CVDs
and other chronic diseases. [12]. In United States, causes and timing of death in extremely premature infants
from 2000 through 2011 revealed that undernutrition and infection and enterocolitis are major causes of death.
However those who survive are future candidate for development of CVDS and type 2 diabetes in adult life
because poor nutrition during fetal life and infancy is a risk factor for adult diseases.
Functional foods and functional farming (4 f). Functional foods (F F) may be defined as foods which contain
certain nutrients that can address some physiological mechanism in our body in providing the benefit.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 30 ~
Functional farming (F F) means that foods produced
by farming either by alteration in soil, or by genetic
engineering or plant breeding should be functional
foods. Functional foods are characterized with
high nutrient density and low energy which
can influence physical and mental
performance as well as psychosocial behavior
that are characteristics of total health,
including cardiovascular health [3-6].
Functional foods are rich in omega-3 fatty
acids, vitamins, polyphenolics, minerals as
well as in essential and nonessential amino
acids and lower in energy. The production of
functional foods and functional farming (4 F)
worldwide can increase the dimension of
increased consumption of functional foods and
their benefits on total health in general,
cardiovascular health in particular, as well as
global health [5-7].Large scale use of
fertilizers and biotechnology for rapid growth
of crops for greater yield of foods, refining and
processing of foods, storing and distributing them has
become widespread in the continuous search of a
better economic model in high income and middle
income countries [5-7]. The challenge for food
industry is to develop functional foods in the factory
which should be slowly absorbed and have a low
glycemic index because functional farming alone can
not serve the demand. Figure 2
Figure 2. Mechanism
of action of healthy and
unhealthy foods.
Figure 3. Attributes of functional foods and
functional farming.
Foods for Health Promotion. The prevalence of a
healthy lifestyle among individuals with CVDs in
high-, middle- and low-income countries revealed
that only little is known about adoption of healthy diet
and lifestyle behaviors among individuals with these
problems [16]. A large, prospective cohort study
involving 153 996 adults, aged 35 to 70 years, from
628 urban and rural communities in 3 high-income
countries (HIC), 7 upper-middle-income countries
(UMIC), 3 lower-middle-income countries (LMIC),
and 4 low-income countries (LIC) is excellent [16].

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 31 ~
Among 7519 individuals with self-reported coronary disease (past event: median, 5.0 [interquartile range
{IQR}, 2.0-10.0] years ago) or stroke (past event: median, 4.0 [IQR, 2.0-8.0] years ago), 18.5% (95% CI,
17.6%-19.4%) continued to smoke; only 35.1% (95% CI, 29.6%-41.0%) undertook high levels of work- or
leisure-related physical activity, and 39.0% (95% CI, 30.0%-48.7%) had healthy diets; Overall, 52.5% (95%
CI, 50.7%-54.3%) quit smoking (by income country classification: 74.9% [95% CI, 71.1%-78.6%] in HIC;
56.5% [95% CI, 53.4%-58.6%] in UMIC; 42.6% [95% CI, 39.6%-45.6%].
Table 1. Singh’,s functional food portfolio for health promotion and disease prevention. (For vegetarian,
replace with soya bean, pulses, cottage cheese and yogurt).
In LMIC; and 38.1% [95% CI, 33.1%-43.2%] in LIC). Levels of physical activity increased with increasing
country income but this trend was not statistically significant. The lowest prevalence of eating healthy diets
was in LIC (25.8%; 95% CI, 13.0%-44.8%) compared with LMIC (43.2%; 95% CI, 30.0%-57.4%), UMIC
(45.1%, 95% CI, 30.9%-60.1%), and HIC (43.4%, 95% CI, 21.0%-68.7%). About 14.3% (95% CI, 11.7%-
17.3%) did not undertake any of the 3 healthy lifestyle behaviors and 4.3% (95% CI, 3.1%-5.8%) had all 3.
It is clear that among a sample of patients
with a CVDs, from countries with varying income
levels, the prevalence of healthy lifestyle behaviors
was low, with even lower levels in poorer countries
indicating that health education via changing a policy
could be important. However these low income
populations continue to have occupational, cultural
and traditional health behavior which has been
protective against CVDs. However, the threat of
policies from Western world is rapidly emerging
because of lack of government policies in changing
the health behavior in these countries, leading to
epidemic of obesity. Figure 4.
Figure 4. Transition in health from homo erectus to modern man with obesity.
Greek epic prospective heart study revealed
the anatomy of health effects of Mediterranean diets
showing beneficial effects of fruits, vegetables, whole
grains, nuts, fish and olive oil [17]. Effects of fat
modified and fruits vegetable enriched diets on blood
lipids among 610 subjects with high cardiovascular
Functional foods
Amount, g/day
Foods
Nutrient/mechanism
Fruits
200-300
Apple, grapes, guava, berries
Flavonoids, vit C,
Vegetables
200-300
Green leaves, gourds
Flavonoids, carotenoids
Nuts
30-50
Walnuts, almond, peanuts
Amino acids, -3 in walnut, low glycemic index,
MUFA
Whole grains
400-500
Gram, beans, peas, millets,
soybean, pulses, porridge
Flavonoids, amino acids, complex
carbohydrates
Fish, sea foods
50-100g
Salmon, any oily fish, e g
mackerel
-3, amino acids, selenium, CoQ10
Poultry
50-100
Egg-quail & hen, chicken,
duck
Amino acids, fatty acids
Curd/yogurt
100-200
Prebiotic, probiotics
Immunity, gut microbiome
Spices
10-20
Turmeric, fenugreek, cumin,
coriander
Flavonoids, minerals
Miscellaneous
5-10g
Cocoa, tea, coffee
Flavanols, polyphenols
Fats and oils
30-100
Olive, mustard/canola
Polyphenols, Flavonoids, -3, MUFA

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 32 ~
risk in the Indian diet heart study showed that subjects
eating Mediterranean diet had significant decrease in
all the risk factors compared to those eating low fat
diet [18]. Randomized, controlled intervention trials
with Mediterranean style foods, such as the Indian
Experiment of Infarct Survival [19,20], The Lyon diet
heart study[21] and the Indo-Mediterranean diet heart
study [22] revealed that consumption of
Mediterranean style diets caused significant declines
in CVDs in the intervention group compared to
control group. Effect of low w-6/w-3 fatty acid ratio
Paleolithic style diet in 404 patients with acute
coronary syndromes revealed that after 2 years, there
was a significant decline in all cause mortality and
cardiovas cular events compared to low fat diet group
[23]. The PREDIMED study among 7747 subjects,
aged 55-80 years, with high cardiovascular risk
revealed that after a follow 4.8 years, there was a
significant decline in the cardiovascular events in
intervention groups receiving Mediterranean style
foods with olive oil or with nuts, compared to low fat
diet [24]. In clinical practice, this approach for
individual patients as well as for populations and
other methods, may be a roadmap for future [25], in a
clinical situation when antioxidant vitamin
supplementation have failed to provide any benefits
(26). This approach appears to be beyond a traditional
payer and beyond CMS's role in improving
population health [27]. Wearable devices could be
facilitators for compliance but not the drivers, of
health behavior change which would depend on
social, mental, spiritual health of the population and
public health policies of the governments [28].
In brief, it is clear that there is a robust evidence in favor of 4 F in the prevention of CVDs by eating
Mediterranean style foods rich in polyphenolics, omega-3 fatty acids, vitamins, minerals as well as essential
and nonessential amino acids.
Ethical clearance and Informed Consent. Not required because its not a original article.
Authors contributions. All the authors contributed equally.
Acknowledgements are given to International College of Nutrition for providing logistic support to write this article.
Conflict of interest. There is no conflict of interest among authors.
Funding. No especial grant given by any agency.
References.
[1]. 2nd International Conference on Nutrition, WHO and FA0,
Rome, Italy, Nov 19-21,2014
(http:/www.fao.org/about/meetings/icn2/en/)
[2]. 18th World Congress on Clinical Nutrition; Agriculture,
Food and Nutrition and Wellness, Abstracts, Dec 1-3,2014,
Ubon Ratchathani University University, Thailand (Pages
14-20)
[3]. ICC-ICN Expert Group. Sofia declaration for prevention of
cardiovascular diseases and type 2 diabetes mellitus: a
scientific statement of the international college of
cardiology and international college of nutrition. World
Heart J 2014;6:89-107.
[4]. Krasimira Hristova, MD, PhD;* Ivy Shiue, PhD;* Daniel
Pella, MD,PhD; RB Singh, MD; Hilton Chaves, MD, PhD;
Tapan K Basu, PhD; Lech Ozimek, PhD; SS Rastogi, MD;
Toru Takahashi, PhD; Douglous Wilson, DSc; Fabien
DeMeester, PhD; Sukhinder Cheema, PhD; Manohar Garg,
PhD; HS Buttar, PhD; Adarsh Kumar, MD; Svetoslav
Handjiev, PhD; Germaine Cornelissen, PhD; Ivo Petrov,
MD, PhD, Branislav Milovanovic, Sofia declaration on
trasition of prevention strategies for cardiovascular diseases
and diabetes mellitus in developing countries: a statement
from the international college of cardiology and
international college of nutrition. Nutrition 2014;
doi.10.1016/j.nut.2013.12.013
[5]. Singh RB, Reddy KK, FedackoJ, De MeesterF,
WilczynskaA and D.W. Wilson, Ancient concepts in
nutrition and diets in hunter-gatherers. The Open Nutra J
2011;4:130-135
[6]. FAO. UNO. The State of Food and Agriculture: Sustainable
Food Systems for Food Security and Nutrition
http://www.fao.org/ docrep/ meeting/ 028/mg413e01.pdf
[7]. Singh RB, De Meester F, Wilczynska A, Takahashi T,
Juneja L, Watson RR. Can a changed food industry prevent
cardiovascular and other chronic diseases. World Heart J
2013;5:1-8.
[8]. Singh RB, Takahashi T, Nakaoka T, Otsuka K,Toda E,
Shin HH, Kyu Lee M, Beeharry V, Hristova K, Fedacko
J, Pella D, De Meester F, Wilson DW, Juneja LR.
Nutrition in transition from Homo sapiens to Homo
economicus. The Open Nutra J 2013;6:6-17.
[9]. De Meester F. Wild-type land based foods in health
promotion and disease prevention: the LDL-CC:HDL-CC
model. In: Wild TypeFoods in Health Promotion and
Disease Prevention, Ed. Fabien DeMeester, RR Watson,
Humana Press, NJ 2008, 3-20.
[10]. De Meester F. Progress in lipid nutrition.In Simopoulos AP,
De Meester F (eds), A Balanced Omega-6/Omega-3 Fatty
acid Ratio.Cholesterol and Coronary Heart Disease. World
Rev Nutr Diet, Basel, Karger 2009; 100:110-121.
[11]. WHO mortality and burden of disease estimates for WHO
member states in 2008, Geneva, World health organization
2010
[12]. Naghavi M, Wang H, Lozano R, Davis A et al. Global,
regional, and national age-sex specific all-cause and cause-
specific mortality for 240 causes of death, 1990–2013: a
systematic analysis for the Global Burden of Disease Study
2013. The Lancet. 2014 Dec 17. doi: 10.1016/S0140-
6736(14)61682-2.
[13]. Patel RM, Kandefer S, Walsh MC, Bell EF et al. Causes
and timing of death in extremely premature infants from
2000 through 2011. N Engl J Med 2015; 372:331-
340January 22, 2015DOI: 10.1056/NEJMoa1403489

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 33 ~
[14]. Lindeberg S. Food and Western Disease: Health and
Nutrition from an Evolutionary Perspective. Chichester,
UK: Wiley-Blackwell; 2010
[15]. Feeding the world sustainably. The Lancet,2014; 384:1721.
,November 2014; doi:10.1016/S0140-6736(14)62054-7
Cite or Link Using DOI
[16]. The PURE Investigators. Prevalence of a healthy lifestyle
among individuals with cardiovascular disease in high-,
middle- and low-income countries: The Prospective Urban
Rural Epidemiology (PURE) Study. JAMA. 2013 Apr
17;309(15):1613-1621
[17]. Trichopoulou A, Bamia C, Trichopoulos D. Anatomy of
health effects of Mediterranean diets. Greek epic
prospective heart study. BMJ 2009;338: Cite this as: BMJ
2009;338:b2337, doi: 10.1136/bmj.b2337
[18]. Singh RB, Rastogi SS, Niaz MA, Ghosh S, Singh R: Effects
of fat modified and fruits vegetable enriched diets on blood
lipids in the Indian diet heart study. Am. J. Cardiol, 1992,
69: 869-874
[19]. Singh RB, Rastogi SS, Verma R,Bolaki L, Singh R,Ghosh
S. An Indian experiment with nutritional modulation in
acute myocardial infarction. Am. J. Cardiol. 1992; 69 : 879-
85.
[20]. Singh RB, Rastogi SS, Verma R, Laxmi B, Singh R,Ghosh
S, Niaz MA. Randomized, controlled trial of
cardioprotective diet in patients with acute myocardial
infarction : results of one year follow up. BMJ
1992;304:1015-9.
[21]. De Lorgeril M, Renaud S, Mamelle N et al. Mediterranean
alpha-linolenic acid-rich diet in secondary prevention of
coronary heart disease. The Lancet, vol. 343, no. 8911, pp.
1454–1459, 1994.
[22]. Singh RB, Dubnov G, Niaz MA,Ghosh S,Singh R,Rastogi
SS,Manor O,Pella D,Berry EM. Effect of an Indo-
Mediterranean diet on progression of coronary disease in
high risk patients: a randomized single blind trial. Lancet
2002,360:1455-1461.
[23]. Singh RB, Fedacko J, Vargova V, Pella D, Niaz MA, Ghosh
S. Effect of Low W-6/W-3 Fatty Acid Ratio Paleolithic
Style Diet in Patients with Acute Coronary Syndromes: A
Randomized, Single Blind, Controlled Trial, World Heart J
2012;4:71-84.
[24]. PREDIMED Study Investigators. Primary prevention of
cardiovascular disease with a Mediterranean diet. N Engl J
Med 2013; DOI:10.1056/NEJMoa1200303.
[25]. Antman EM, Jessup M. Clinical Practice Guidelines for
chronic cardiovascular disorders: A roadmap for the future.
JAMA. 2014;311(12):1195-1196.
doi:10.1001/jama.2014.1742
[26]. Darlenska TH, Handjiev S. Antioxidant vitamins and the
heart. World Heart J 2014;6:179-184.
[27]. Kassler WJ, Tomoyasu N, and Conway PH. Beyond a
traditional payer — CMS's role in improving population
health. N Engl J Med 2015; 372:109-111January
8,2015DOI: 10.1056/NEJMp1406838
[28]. Patel MS, Asch DA, Volpp KG. Wearable devices as
facilitators, Not drivers, of health behavior change. JAMA.
Published online January 08, 2015.
doi:10.1001/jama.2014.14781
[29].

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 34 ~
FLAVONOIDS CONSUMPTION AND THE RISK OF
CARDIOVASCULAR DISEASES
Arunporn Itharat1, Galal Elkilany2, RB Singh3, Krasimira Hristova4, Omar Shehab5
1Department of Applied Thai Traditional Medicine, Thammasat University, Kluangnueng, Pathumthani, Thailand
2 International College of Cardiology, LaPlace, USA
3Halberg Hospital and Research Institute, Moradabad, India
4 University National Heart Hospital; Sofia, Bulgaria
5Tawam Hospital, Al Ain, UAE
Correspondence
Dr Arunporn Itharat, Department
of Applied Thai Traditional Medicine,
Thammasat University, Kluangnueng, Pathumthani, Thailand; iarunporn@gmail.com
Abstract: Despite decline in cardiovascular diseases (CVDs) and corresponding decline in mortality attributed to coronary
artery disease (CAD) and stroke, CVDs remain the leading causes of death. The risk of CAD and type 2 diabetes(T2DM)
is significantly higher in South-West Asia compared to all other countries of the world. The International College of
Nutrition Expert group considers that dietary factors, including flavonoids and omega-3 fatty acids, are critical in the
pathogenesis and prevention of deaths due to CVDs. Diets that are high in flavonoids by their nature have higher nutritional
quality, characterized with more fruits, nuts, spices and vegetables, such as the Mediterranean and Japanese diets. In many
studies, other nutrients have not been considered to account for possible confounding by overall diet quality; fruit and
vegetable intake, fiber or other nutrients that may track with flavonoid intake with better diet quality. Cohort studies
indicate that flavonoid intake is significantly and inversely associated with risk of CVDs and T2DM.
Key words: Foods, fiber, polyphenolics, antioxidants, oxidative stress.
Introduction. Despite nuerous advances in the
management of cardiovascular diseases (CVDs) and
corresponding decline in mortality attributed to
coronary artery disease (CAD) and stroke, CVDs
remain the leading causes of death [1, 2]. The risk of
CAD and type 2 diabetes is significantly higher in
South-West Asia compared to all other countries of
the world [2]. More than seventeen million deaths
each year may be due to CVD, accounting for 30% of
all deaths, and CVD incidence continues to increase
in low- and middle-income countries, where 80% of
CVD deaths occur [1, 2]. The International College
of Nutrition Expert group considers that dietary
factors, including flavonoids and omega-3 fatty acids,
are critical in the pathogenesis and prevention of
deaths due to CVDs [4]. Improvements in US diet
helped in reducing the disease burden and lower
premature deaths during 1999-2012 [4]. However,
overall diet remains poor in most countries of the
world [3, 4]. Increased consumption of fruits,
vegetables, nuts, whole grains and olive oil/mustard
oil are an important part of diets associated with lower
CVD risk [3, 4]. Since these foods are rich in
antioxidant flavonoids, omega-3 fatty acids, fiber,
vitamins and both essential and non-essential amino
acids, the mechanism relating intake of these foods to
CVD risk is still uncertain [3, 4]. In several
epidemiological studies, dietary flavonoids, a class of
polyphenols found in a large array of plant foods and
herbs, have been examined as potential components
associated with CVD risk, which is assessed in this
review.
Clinical Evidence. The association of flavonoid
intake with risk of CVDs was examined in earlier
studies,, but many of these studies had one or more
limitations. Only a few flavonoid classes were
examined in most of the previous studies. Diets that
are high in flavonoids by their nature have higher
nutritional quality, characterized with more fruits and
vegetables, such as the Mediterranean and Japanese
diets. In many studies, other nutrients have not been
considered to account for possible confounding by
overall diet quality; fruit and vegetable intake, fiber
or other nutrients that may track with flavonoid intake
with better diet quality [3, 4]. In long-term follow-up
studies, flavonoid intake was based on a single
reference assessment, allowing the potential for
regression dilution bias.
The relationship between incident CVD and
CAD and long-term intake of individual flavonoid
classes based on a more complete flavonoid database
was examined [4]. Most flavonoids are found in
plant-based foods; hence the overall diet quality of
those who ingest more flavonoids is likely to be better
than those consuming fewer flavonoids. Flavonoid-
rich foods are also rich in certain nutrients, i.e.,
potassium, magnesium, fiber, lignans, phytosterols
and isoflavons, which are known to reduce CVD risk.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 35 ~
These foods may be lower in other nutrients having
adverse effects, such as saturated fat, trans-fat and
omega-6 fat and salt, that may increase CVD risk.
Potential confounding by overall dietary quality or
other specific dietary factors may be associated with
flavonoid intake and may bring about false-positive
associations. Findings from the epidemiological
studies are inconsistent regarding the association
between flavonol intake and risk of stroke. A meta-
analysis of cohort studies that provided relative risk
(RR) estimates with 95% confidence intervals (CIs)
for the association between flavonol intake and risk
of stroke included eight studies, with 5228 stroke
cases among 280,174 participants [6]. A significant
association was observed between highest flavonol
intake and reduced risk of stroke (RR=0.86; 95% CI:
0.75-0.99). An increase in flavonol intake of 20 mg/d
was associated with a 14% decrease in the risk of
developing stroke (RR=0.86; 95% CI: 0.77-0.96). A
higher consumption of flavonol was associated with
a reduced risk of stroke among men, but no such
association was noted in women. Our results support
recommendations for higher consumption of
flavonol-rich foods to prevent stroke.
A more recent study of 2880 subjects, mean
age 54 years, examined the association of long-term
consumption of six flavonoid classes and the
incidence of CVD and CAD, using a comprehensive
flavonoid database and repeated measures of intake
[7]. After an average follow-up of 14.9 years, there
were 518 CVD and 261 CAD events. The results from
this study indicate that the observed association
between flavonol intake and CVD risk may be a
consequence of better overall diet. The strength of
this non-significant association was also consistent
with relative risks observed in previous meta-
analyses, and therefore a modest benefit of flavonol
intake on CVD risk cannot be ruled out. Only
flavonol intake was significantly associated with a
lower risk of CVD incidence (hazard ratios (HR) per
2·5-fold flavonol increase=0·86, P trend=0.05). A
further adjustment for total fruit and vegetable intake
and overall diet quality attenuated this observation
(HR=0.89, P trend=0.20 and HR=0.92, P trend=0.33,
respectively).
Clinical evidence for the association of
dietary flavonoid intake with CVD risk factors is still
scarce. The National Health and Nutrition
Examination Survey (NHANES) 2007–2012
included 4042 US adults aged 19 years and older in a
cross-sectional survey [8]. This study showed that
higher flavonoid intake was associated with improved
CVD risk factors but these associations were
moderate in strength. After adjusting for covariates,
increased HDL-cholesterol was associated with
higher total flavonoid intake (0.54 % change). TAG
and TAG:HDL-cholesterol ratio were inversely
associated with anthocyanidin (−1.25 % change for
TAG; −1.60 % change for TAG:HDL-cholesterol
ratio) and total flavonoid intakes (−1.31 % change for
TAG; −1.83 % change for TAG:HDL-cholesterol
ratio), respectively. Insulin and homoeostasis model
assessment for insulin resistance (HOMA-IR) were
inversely associated with flavone (for insulin, −3.18
% change; 95 % CI −5.85, −0.44; for HOMA-IR,
−3.10 % change; 95 % CI −5.93, −0.19) and
isoflavone intakes (for insulin, −3.11 % change; 95 %
CI −5.46, −0.70; for HOMA-IR, −4.01 % change; 95
% CI −6.67, −1.27). Body mass index (BMI) was
negatively associated with anthocyanidin intake
(−0.60 % change).
The results of these observational studies
remain controversial; hence the present study was
conducted to evaluate the association between dietary
flavonoid intake and CVD risk by conducting a
systematic review of fourteen prospective cohort
studies [9]. The consumptions of anthocyanidins
(RR=0.89, 95 % CI: 0.83, 0.96), proanthocyanidins
(RR=0.90, 95 % CI: 0.82, 0.98), flavones (RR=0.88,
95 % CI: 0.82, 0.96), flavanones (RR=0.88, 95 % CI:
0.82, 0.96) and flavan-3-ols (RR=0.87, 95 % CI: 0.80,
0.95) were inversely associated with the risk of CVD
when comparing the highest and lowest categories of
intake. A similar association was observed for
flavonol intake and CVD risk. The summary RR for
CVD for every 10 mg/d increment in flavonol intake
was 0.95 (95 % CI: 0.91, 0.99). This study indicates
that the dietary intake of six classes of flavonoids,
namely flavonols, anthocyanidins,
proanthocyanidins, flavones, flavanones and flavan-
3-ols, significantly decreases the risk of CVD [9].
In a further meta-analysis, twenty
publications from twelve prospective cohorts have
evaluated associations between flavonoid intake and
incidence or mortality from CVD among adults in
Europe and the United States [10]. CAD mortality
was the commonest outcome, and four of eight cohort
studies reported significant inverse associations for at
least one flavonoid class (multivariate adjusted p
[trend] < 0.05). Three of seven cohorts reported that
greater flavonoid intake was associated with lower
risk of incident stroke. It was difficult to compare the
effects of two flavonoids because of variability in the
flavonoid classes included, demographic
characteristics of the populations, outcomes assessed,
and length of follow-up. The most commonly
examined flavonoid classes were flavonols and
flavones combined (11 studies) and only one study
examined all seven flavonoid classes. The flavonol
and flavone classes were most strongly associated

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 36 ~
with lower CAD mortality [10]. The hypothesis that
flavonoid intake is associated with lower CVD
incidence and mortality requires further study. The
association between flavonoid intake and CVD
mortality was examined among participants in a
large, prospective US cohort including 38,180 men
and 60,289 women, mean age 70 and 69 years
respectively, in the Cancer Prevention Study II
Nutrition Cohort [11]. After follow-up of 7 years,
1589 CVD deaths in men and 1182 CVD deaths in
women occurred. Men and women
with total flavonoid intake in the top (compared with
the bottom) quintile had a lower risk of fatal CVD
(RR=0.82; 95% CI: 0.73, 0.92; P-trend = 0.01). Five
flavonoid classes (anthocyanidins, flavan-3-ols,
flavones, flavonols, and proanthocyanidins) were
individually associated with lower risk of fatal CVD
(all P-trend < 0.05). In men, total flavonoid intake
was more strongly associated with stroke mortality
(RR=0.63; 95% CI: 0.44, 0.89; P-trend = 0.04) than
with CAD (RR=0.90; 95% CI: 0.72, 1.13).
The above evidence further confirms the
earlier observations made that flavonoid intake was
associated with lower risk of death from CVD [12].
Most inverse associations appeared with intermediate
intakes, suggesting that even relatively small amounts
of flavonoid-rich foods may be beneficial. In an
earlier study, flavonoid content (flavonoids quercetin,
kaempferol, myricetin, apigenin, and luteolin) in
various foods (tea, wine, vegetables and fruits) was
measured. The flavonoid intake was assessed among
805 men aged 65-84 years. The major sources of
intake were tea (61%), onions (13%), and apples
(10%) and the intake at the outset was 25.9 mg daily.
After follow-up of 5 years, 43 men died of CAD.
Flavonoid intake (analyzed in tertiles) was
significantly inversely associated with mortality from
coronary heart disease (p for trend =0.015). The
relative risk of coronary heart disease mortality in the
highest versus the lowest tertile of flavonoid intake
was 0.42 (95% Cl: 0.20-0.88). The consumption of
tea, onions, and apples was also inversely related to
CAD mortality, but these associations were weaker.
Flavonoids in regularly consumed foods such as tea,
onion, apples, grapes and guava may reduce the risk
of death from CAD in elderly men.
In a randomized, double-blind, placebo-
controlled 8-week-long clinical trial, among 48 post-
menopausal women, with pre- and stage 1
hypertension, half of the subjects were randomly
assigned to receive either 22 g freeze-dried blueberry
powder or 22 g control powder [13]. After 8 weeks,
systolic blood pressure (131±17 vs. 138±14 mmHg,
P<0.05) and diastolic blood pressure (75±9 vs. 80±7
mmHg, P<0.01), as well as brachial-ankle pulse wave
velocity (1,401±1221 vs. 498±179 cm/second;
P<0.01) were significantly lower than values at start.
Significant (P<0.05) group × time interactions were
found in the blueberry powder group, whereas there
were no changes in the group receiving the control
powder. Nitric oxide concentrations were greater
(15.35±11.16 μmol/L, P<0.01) in the blueberry
powder group at 8 weeks compared with values at
start (9.11±7.95 μmol/L), whereas there were no
changes in the control group. Daily blueberry
consumption may reduce blood pressure and arterial
stiffness, which may be due, in part, to increased
nitric oxide production by the flavonoid content of
blueberries.
Flavonoid-Rich Foods in the Diet. Food
consumption patterns from the European Food Safety
Authority (EFSA) and the FLAVIOLA Food
Composition Database aimed at
estimating intake of flavonoids indicate that the main
sources of anthocyanidins, flavanols, flavanones,
flavones, flavonols, proanthocyanidins, theaflavins
and thearubigins in the European Union are tea, fruits
(apples, pears and grapes), vegetables (onion), cocoa,
coffee and spices [14]. Mean (±SEM) intake of total
flavonoids in Europe was 428±49 mg/d, of which
136±14 mg/d were monomeric compounds. Gallated
flavan-3-ols (53±12 mg/d) were the main contributor
[14]. The lowest flavonoid intake was observed in
Mediterranean countries (monomeric compounds:
95±11 mg/d). Habitual consumption of flavonoids in
Europe may be below the amounts found to have a
significant health effect.
Tropical plants could be major sources of
certain flavonoids (myricetin, quercetin, kaempferol,
luteolin, and apigenin), as revealed in a study of 62
edible tropical plants [15]. The highest total flavonoid
content was in onion leaves (1497.5 mg/kg quercetin,
391.0 mg/kg luteolin, and 832.0 mg/kg kaempferol),
followed by Semambu leaves (2041.0 mg/kg), bird
chili peppers (1663.0 mg/kg), black tea (1491.0
mg/kg), papaya shoots (1264.0 mg/kg), and guava
(1128.5 mg/kg). The major flavonoid in these plant
extracts is quercetin, followed by myricetin and
kaempferol. Luteolin could be detected only in
broccoli (74.5 mg/kg dry weight), green chili peppers
(33.0 mg/kg), bird chili peppers (1035.0 mg/kg),
onion leaves (391.0 mg/kg), belimbi fruit (202.0
mg/kg), belimbi leaves (464.5 mg/kg), French bean
(11.0 mg/kg), carrot (37.5 mg/kg), white radish (9.0
mg/kg), local celery (80.5 mg/kg), limau purut leaves
(30.5 mg/kg), and dried asam gelugur (107.5 mg/kg).
Apigenin was found only in Chinese cabbage (187.0
mg/kg), bell pepper (272.0 mg/kg), garlic (217.0
mg/kg), belimbi fruit (458.0 mg/kg), French peas

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 37 ~
(176.0 mg/kg), snake gourd (42.4 mg/kg), guava
(579.0 mg/kg), wolfberry leaves (547.0 mg/kg), local
celery (338.5 mg/kg), daun turi (39.5 mg/kg), and
kadok (34.5 mg/kg). In vegetables, quercetin
glycosides predominate, but glycosides of
kaempferol, luteolin, and apigenin are also present.
Fruits contain almost exclusively quercetin
glycosides, whereas kaempferol and myricetin
glycosides are found only in trace quantities.
Flavonoids are present in the plant cells to protect the
cells (14-16). The calyces of Hibiscus sabdariffa
contain a number of flavonoids gossypetin,
hibiscetine and sabdaretine, ascorbic acid, mucilage,
calcium citrate, etc which have antihypertensive
hypoglycemic and anti heart failure effects as well as
beneficial in other CVDs (18,19). , the analysis
included 39 and 36 patients from the experimental
and control group, respectively. In a controlled trial,
the results showed that H. sabdariffa was able to
decrease the systolic blood pressure from 139.05 to
123.73mm Hg (ANOVA p < 0.03) and the diastolic
BP from 90.81 to 79.52mm Hg (ANOVA p < 0.06).
A study by Itharat group on Hibiscus sabdariffa
extract demonstrated that an oral administration at
the doses of 50, 100 and 200 mg/kg body weight for
270 days does not cause chronic toxicity in rat. After
14 days of a single oral administration of this agent as
a test substance 5,000 mg/kg body weight showed no
acute toxicity (20).
Mechanism of Action. Flavonoids are known to
prevent oxidation of low-density lipoprotein
cholesterol and other lipoproteins which become
more atherogenic after oxidation [12]. Beta cells of
pancreas and endothelial cells are highly susceptible
to damage by free radical-induced inflammation,
resulting into insulin resistance and diabetes as well
as atherosclerosis [8, 12]. Flavonoid intake may bring
about a decrease in endothelial damage which may be
associated with increased bradykinin and nitric oxide
release and decrease in platelet aggregation.
Nicotinamide adenine dinucleotide (NAD) is found in
all living cells in an oxidized form (NAD+) and a
reduced form (NADH) [16]. The main function of
NAD in cells is modulating cellular redox status by
carrying electrons from one reaction to another.
Hyperglycemia decreases NAD+ concentrations,
which is important in oxidative metabolism, by
activation of the polyol pathway and by over-
activation of poly(ADP-ribose)-polymerase (PARP).
The protective role of three structurally related
flavonoids (rutin, quercetin, and flavone) was
examined during high glucose conditions in an in
vitro model using human umbilical vein endothelial
cells (HUVECs). This study provides evidence that
flavonoids are also able to protect endothelial cells
against a high glucose-induced decrease in NAD [16].
Flavonoids are able to inhibit aldose reductase, the
key enzyme in the polyol pathway. This protective
effect of flavonoids on NAD+ concentrations is a
combination of the flavonoids' ability to inhibit both
PARP activation and aldose reductase enzyme
activity. The study also shows that flavonoids, by a
combination of these effects, maintain the redox state
of the cell during hyperglycemia which can to
ameliorate vascular complications in diabetes [16].
Antioxidants flavonoids prevent the oxidation of
cholesterol which is important in the pathogenesis
and prevention of atherosclerosis and CVDs
[17,21,22].
In brief, increased consumption of flavonoids above 400mg/day or more may be protective against
CVDs. Randomized, controlled intervention trials are necessary to confirm this finding.
Ethical clearance and Informed Consent. Not required because its not a original article.
Authors contributions. All the authors contributed eqally.
Acknowledgements are given to International College of Nutrition for providing logistic support to write this article.
Conflict of interest. There is no conflict of interest among authors.
Funding. No especial grant given by any agency.
References
[1]. Shepard D, Roth G, Vanderzanden A, Naghavi M, Murray
CJL. Ischemic heart disease worldwide, 1990 to
2013: estimates from the Global Burden of Disease Study
2013. Circ Cardiovasc Qual Outcomes 2015; 8 (4): 455-
456.
[2]. Shehab A, Elkilany G, Singh RB, Hristova K, Chaves H,
Cornelissen G, Otsuka K. Coronary risk factors in South
West Asia. Editorial, World Heart J 2015; 7: 21-23.
[3]. Hristova K, Pella D, Singh RB, Dimitrov BD, Chaves H,
Juneja L, Basu TK, Ozimek L, Singh AK, Rastogi SS,
Takahashi T, Wilson DW, De Meester F, Cheema S,
Milovanovic B, Buttar HS, Fedacko J, Petrov I, Handjiev
S, Wilczynska A, Garg ML, Shiue I, Singh RK. Sofia
Declaration for prevention of cardiovascular diseases and
type 2 diabetes mellitus: a scientific statement of the
International College of Cardiology and International
College of Nutrition. World Heart J 2014; 6: 89-106.
[4]. Wang DD, Li Y, Chiuve SE, Hu FB, Willett WC.
Improvements in US diet helped reduce disease burden and
lower premature deaths, 1999-2012; overall diet remains
poor. Health Affairs (Millwood) 2015; 34: 1916-1922.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 38 ~
[5]. Rangel-Huerta OD, Pastor-Villaescusa B, Aguilera CM,
Gil A. A systematic review of the efficacy of bioactive
compounds in cardiovascular disease: phenolic
compounds. Nutrients 2015; 7: 5177-5216.
[6]. Wang ZM, Zhao D, Nie ZL, Zhao H, Zhou B, Gao
W, Wang LS, Yang ZJ. Flavonol intake and stroke risk: a
meta-analysis of cohort studies. Nutrition 2014; 30 (5):
518-523. doi: 10.1016/j. nut.2013.10.009.
[7]. Jacques PF, Cassidy A, Rogers G, Peterson JJ, Dwyer JT.
Dietary flavonoid intakes and cardiovascular incidence in
the Framingham Offspring Cohort. Br J Nutr 2015; 114 (9):
1496–1503.
[8]. Kim K, Vance TM, Chun OK. Greater flavonoid intake is
associated with improved CVD risk factors in US adults. Br
J Nutr 2016 Mar 2:1-8. [Epub ahead of print]
doi:10.1017/S0007114516000519.
[9]. Wang X, Ouyang YY, Liu J, Zhao G. Flavonoid intake and
risk of CVD: a systematic review and meta-analysis of
prospective cohort studies. Br J Nutr 2014 Jan 14; 111(1):
1-11.
[10]. Peterson JJ, Dwyer JT, Jacques PF, McCullough ML.
Associations between flavonoids and cardiovascular
disease incidence or mortality in European and US
populations. Nutr Rev. 2012; 70 (9): 491-508.
[11]. McCullough ML, Peterson JJ, Patel R, Jacques PF, Shah R,
Dwyer JT. Flavonoid intake and cardiovascular disease
mortality in a prospective cohort of US adults. Am J Clin
Nutr. 2012; 95 (2): 454-464.
[12]. Hertog MG, Feskens EJ, Hollman PC, Katan MB,
Kromhout D. Dietary antioxidant flavonoids and risk of
coronary heart disease: the Zutphen Elderly Study. The
Lancet 1993; 342: 1007-1011.
[13]. Johnson SA, Figueroa A, Navaei N, Wong A, Kalfon
R, Ormsbee LT, Feresin RG, Elam ML, Hooshmand
S, Payton ME, Arjmandi BH. Daily blueberry consumption
improves blood pressure and arterial stiffness in
postmenopausal women with pre- and stage 1-
hypertension: a randomized, double-blind, placebo-
controlled clinical trial. Acad Nutr Diet 2015; 115 (3): 369-
377. doi: 10.1016/j.jand.2014.11.001.
[14]. Vogiatzoglou A, Mulligan AA, Lentjes MA, Luben RN,
Spencer JP, Schroeter H, Khaw KT, Kuhnle GG. Flavonoid
intake in European adults (18 to 64 years). PLoS One 2015;
10 (5): e0128132.
[15]. Miean KH, Mohamed S. Flavonoid (myricetin, quercetin,
kaempferol, luteolin, and apigenin) content of edible
tropical plants. J Agric Food Chem 2001; 49 (6): 3106–
3112. DOI: 10.1021/jf000892m
[16]. Boesten DMPHJ, von Ungern-Sternberg SNI, den Hartog
GJM, Bast A. Protective pleiotropic effect of flavonoids on
NAD+ Levels in endothelial cells exposed to high glucose.
Oxidative Medicine and Cellular Longevity 2015; Article
ID 894597, 7 pages. doi:10.1155/2015/89459717.
[17]. Singh RB, Niaz MA, Takahashi T, De Meester F,
Wilczynska A, Saboo B,Maheshwari A, Cornelissen G,
Singh J, Telessy IG. Hypercholesterolemia: a disease of the
brain. In: Watson RR, de Meester F, eds. Handbook of
Cholesterol; Biology, Function and Role in Health and
Disease. Wageningen Academic Publishers, The
Netherlands, 2016. pp. 17-36.
[18]. Odigie IP, Ettarh RR, Adigun SA. Chronic administration
of aqueous extract of Hibiscus sabdariffaattenuates
hypertension and reverses cardiac hypertrophy in 2K-1C
hypertensive rats. J Ethnopharmacol.2003;86:181–185.
[19]. Herrera-Arellano A, Flores-Romero S, Chavez-Soto MA,
Tortoriello J. Effectiveness and tolerability of a
standardized extract from Hibiscus sabdariffa in patients
with mild to moderate hypertension: a controlled and
randomized clinical trial. Phytomedicine. 2004;11:375–
382.
[20]. Seewaboon S, Itharat A, Khonsung P, Lertprasertsuke N,
Jaijoy K. (2013) Toxicity Studies of the Water Extract from
the Calyces of Hibiscus Sabdariffa L. in Rats. Afr J Tradit
Complement Altern Med. 2013; 10(4): 122–127.
[21]. Itharat A, Onsaard E, Singh RB, Chauhan AK, Shehab O.
Flavonoids consumption and the heart. World Heart J 2016;
8: 103-108.
[22]. Noad RL, Rooney C, McCall D, Young IS, McCance D,
McKinley MC, Woodside JV, McKeown PP. Beneficial
effect of a polyphenol-rich diet on cardiovascular risk, A
randomised control trial. Heart. 2016;102(17):1371-1379.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 39 ~
FOOD INDUSTRY, FOOD MANUFACTURING AND HEALTH
Lekh Juneja1, Takahashi Toru2, Rie Horuichi3
1Kameda Seika Co Ltd, Tokyo, Japan
2Graduate School of Heath Sciences, Fukuoka, Japan.
3Department of Food science and Nutrition, Faculty of human Environmental Sciences, Mukagawa Women’s University,
Japan
Correspondence
Dr Lekh Juneja, PhD, FICN
Executive Vice President
KAMEDA SEIKA CO., LTD. Tokyo, Japan.
Email: lekhjuneja@gmail.com
Abstract: Apart from refined and sweetened foods, manufactured by the food industry, some of the most common foodstuffs;
bacon, sausage, and ham are once again found to be key foods driving the association between meat consumption and the
world's most common disease
s. The food industry do not give sufficient consideration in producing foods that have low
glycemic index and a mix of variety of foods, to achieve food diversity which are most important in health promotion. There
is an unmet need to develop new food preservation technologies to prevent the excessive use food preservatives.
Key words: Glycemic index, food diversity, fiber, whole grains.
Introduction. Previously a books published on how
diet causes and prevents diseases (1-3). Many of these
book authors, concluded that dietary changes can
improve physical, mental, social and spiritual health,
by altering the ratio of omega-6/omega-3 fatty acids
in the tissues, resulting in to a healthy human being
[1-3]. Apart from these seminal volumes, six original
research studies have been published in the last one
year by the famous investigators from all over the
world, giving the same message, that a Mediterranean
style diet particularly with low w-omega-6/omega-3
ratio of fatty acids near 1:1, is protective [4-9]. It
seems logical to advise such diets, for prevention of
morbidity and mortality due to non-communicable
disease (NCDs), which in the view of WHO and
International College of Cardiology, is taking away
resources, funds and brains that could have been
allocated for human development (10). The
prevalence rates of major NCDs; cardiovascular
disease (CVD), cancer, type 2 diabetes and chronic
obstructive pulmonary diseases (COPD) are rapidly
increasing in almost all countries and are now among
the world's biggest killers [9,10]. NCDs are
polygenic and multifactorial and pose a major
challenge to the health, well-being and prosperity of
populations across the world, and cause unnecessary
suffering and premature death [10-15]. The
contributing factors are multifaceted, complex. They
include health behavior related to population ageing,
urbanization, the globalization of trade and
marketing, and the resulting progressive increase in
unhealthy patterns of living [11-16].
Some of the most beloved foodstuffs; bacon,
sausage, and ham are once again found to be key
foods driving the association between meat
consumption and the world's most common diseases
[4]. In this large study, involving 10 countries and
almost half a million men and women, high
consumption of processed meat by middle-aged
adults was associated with a nearly two fold greater
risk of all-cause mortality, compared with low
consumption, over a mean of 12 years. Risk of
cardiovascular death, after rigorous modeling, was
increased by more than 70% among people eating
more than 160 g/day, as compared with those eating
10 to 19.9 g/day. Risk of cancer deaths was also 43%
higher among the highest consumers of processed
meats. The interesting point was that a signal of
increased mortality was seen among the highest
consumers of red meat in general, the risk for red
meat was much lower that of processed meats and
lost statistical significance after correction for
measurement error. With the same adjustments and
corrections, high processed-meat consumption was
associated with an 18% greater risk of all-cause
mortality. It seems that processed meats tend to
contain more peroxidized fatty acids, including
saturated fat and salt, than unprocessed meat (where
the fat is often trimmed off), as well as more oxidized
cholesterol and additives, as part of the smoking or
curing process which may be carcinogenic or
precursors to carcinogenic processes and atherogenic.
Heme iron is another mechanism, which may interact
with oxidized products linking meat consumption to
cardiovascular disease (CVD) risk. Eating unhealthy
diets go hand in hand with other unhealthy behaviors,

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 40 ~
including smoking, low physical-activity levels, and
low consumption of fruits and vegetables leading to
NCDs [1-15].
Food Health and Diseases. The REGARD study
enrolled black and white Americans aged 45 years or
older between 2003-2007 [5]. The factor analysis
identified five dietary patterns: Convenience"
(Chinese and Mexican foods, pasta, pizza), Plant-
based" (fruits, vegetables, legumes), and Southern"
(fried foods, organ meats, sweetened beverages),
Sweets/Fats" (desserts, added sugars, sweet snacks)
and Alcohol/Salads" (alcohol, fats, vegetables).
Subjects with a higher adherence to the Southern
dietary pattern, experienced a 41% increased risk of
stroke (comparing Q4 to Q1: HR=1.41; 95% CI =
1.07, 1.85). However, higher adherence to the plant-
based pattern was associated with a 29% reduction in
stroke risk (comparing Q4 to Q1: HR=0.71; 95% CI
= 0.55, 0.91). The trend across quartiles was <0.001
indicating a dose response for adherence to each
pattern. Adding socio-economic status, smoking,
physical activity and total energy (calories) intake to
the models attenuated the association but the direction
remained the same and persisted in sub-group
analysis examining only ischemic strokes. The
Convenience, Sweets, and Alcohol patterns were not
associated with stroke risk. The present study
suggests that foods common to US Southern cuisine
such as fried foods and sweetened beverages may
increase the risk of stroke, while diets rich in legumes,
fruits, vegetables, and fish may reduce stroke risk.
Interventions focusing on increasing plant-based
foods and fish while reducing fried foods and
sweetened beverages are needed [5].
Long-term data from two large studies might
have more people considering a switch to
vegetarianism, as processed and unprocessed meat
consumption is associated with a significantly
increased risk of all-cause CVD mortality, death from
cancer [4,5]. After adjustment for multiple risk
factors, eating one additional serving of meat daily
was associated with a 16% increase in the risk of
cardiovascular mortality and a 10% increased risk of
death from cancer. The PREDIMED Study comprised
of a total of 7447 persons, aged 55 to 80 years;
including 57% women [6]. A primary end-point
event occurred in 288 participants. The multivariable-
adjusted hazard ratios were 0.70 (95% confidence
interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to
0.96) for the group assigned to a Mediterranean diet
with extra-virgin olive oil (96 events) and the group
assigned to a Mediterranean diet with nuts (83
events), respectively, versus the control group (109
events). Among high risk subjects, a Mediterranean
diet supplemented with extra-virgin olive oil or nuts
reduced the incidence of major cardiovascular events
(6).The Sydney Diet Heart Study included 458 men
aged 30-59 years with a recent coronary event (7).
The intervention group received replacement of
dietary saturated fats (from animal fats, common
margarines, and shortenings) with omega 6 linoleic
acid (from safflower oil and safflower oil
polyunsaturated margarine). Controls received no
specific dietary instruction or study foods and all non-
dietary aspects were designed to be equivalent in both
groups. An intention to treat, survival analysis
approach to compare mortality outcomes by group
showed that the intervention group (n=221) had
higher rates of death than controls (n=237) (all cause
17.6% v 11.8%, hazard ratio 1.62 (95% confidence
interval 1.00 to 2.64), P=0.05; cardiovascular disease
17.2% v 11.0%, 1.70 (1.03 to 2.80), P=0.04; CAD
16.3% v 10.1%, 1.74 (1.04 to 2.92), P=0.04).
Inclusion of these recovered data in an updated meta-
analysis of linoleic acid intervention trials showed
non-significant trends toward increased risks of death
from CAD (hazard ratio 1.33 (0.99 to 1.79); P=0.06)
and CVDs (1.27 (0.98 to 1.65); P=0.07). It is
remarkable that substituting dietary linoleic acid in
place of saturated fats increased the rates of death
from all causes, as well as CAD, and CVD. An
updated meta-analysis of linoleic acid intervention
trials showed no evidence of cardiovascular benefit.
These are the complications of meta analysis and
funded research. These findings could have important
implications for worldwide dietary advice to
substitute omega- 6 linoleic acid, or omega-3 fatty
acids or polyunsaturated fats in general to alter the
w-6/w-3 ratio to 1:1 [3].
A randomized, single blind, controlled trial
was carried out on 406 patients with acute coronary
syndromes (ACS) diagnosed following WHO criteria
[8]. An experimental intervention group received
Paleolithic style diet characterized by fruits,
vegetables, whole grains, almonds and walnuts and
the control group fat modified according to the
National Cholesterol Education Program Step 1
(prudent) diet. Main outcome measures were
compliance with experimental diets at one year and
all cause mortality and its association with omega-
6/omega-3 fatty acid ratio after a follow up of two
years. The experimental group received significantly
greater amount of fruits, vegetables and whole grains,
almonds, walnuts, and mustard oil and lower amount
of refined bread, biscuits and sugar and butter and
clarified butter compared to control diet group at one
year of follow up. Intervention group was also
advised fish and forbidden red meat intake. Total
adherence score to Paleolithic style diet and prudent

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 41 ~
diet were significant in both the groups. Omega-
6/Omega-3 fatty acid ratio of the diet which was
much higher before entry to the study (32.5±3.3), was
brought down to significantly lower content in the
Paleolithic style diet group A (n = 204, compared to
control group diet B (n = 202) at entry to the study (
3.5± 0.76 vs. 24.0± 2.4 KJ/day, p<0.001). The fatty
acid ratio remained significantly much lower in the
experimental group compared to control group after
one year of follow up (4.4±0.56 vs. 22.3±2.1,KJ/day,
p<0.001). Total mortality was 14.7% in the
Paleolithic style diet group and 25.2% in the control
group, after a follow up of two years. The association
omega-6/omega-3 ratio of fatty acids with mortality
showed a gradient in both the groups independently,
as well as among total number of deaths. A lower
omega-6/omega-3 ratio of fatty acids from 1-10 was
associated with a significantly lower mortality
whereas increase in omega-6/omega-3 fatty acid ratio
to more than 10 was associated with an increasing
trend in mortality; 1.7% at ratio less than 5 and 19.9%
at ratio 30. In a further study, randomly selected
records of death of 2222 (1385 men and 837 women)
decedents, aged 25-64 years, were examined [9]. The
score for intake of prudent foods was significantly
greater and the ratio of omega-6/omega-3 fatty acids
of the diet significantly lower for deaths due to
‘injury’ and accidental causes compared to deaths due
to non-communicable diseases (NCD). Multivariate
logistic regression analysis revealed that after
adjustment for age, total prudent foods (OR,CI:
1.11;1.06-1.18 men; 109;1.04-1.16 women) as well
as fruits, vegetables, legumes and nuts (1.07; 1.02-
1.12 men; 1.05; 1.99-1.11 women) were
independently, inversely associated whereas Western
type foods (1.02; 0.95-1.09 men; 1.00; 0.94-1.06
women); meat and eggs(1.00-0.94-1.06 men; 0.98;
0.93-1.04 women) and refined carbohydrates (0.98;
0.91-1.05 men, 0.95; 0.89-1.02 women) and high
omega-6/omega-3 ratio of fatty acids were positively
associated with deaths due to NCDs. Increased intake
of high omega-6/omega-3 ratio Western type foods
and decline in prudent foods intake may be a risk
factor for deaths due to NCDs.
It is clear from above scientific evidence [1-
9], that there is a robust case to develop functional
foods by the food industry for prevention of NCDs.
Such products should have similar effects on human
nutrition and metabolism as natural Paleolithic style
foods or Mediterranean style foods, without any
adverse effects of foods additives and food
processing. There is need to educate the food industry
and agriculture scientists to develop functional foods
characterized with low glycemic index and optimal
amount of soluble fiber, vitamins, minerals,
antioxidant flavanoids, essential and nonessential
amino acids and a balanced ratio of omega-6/omega-
3 fatty acids, similar to the notional Paleolithic diet
[15-17].In earlier studies, these foods and nutrients
rich in the Paleolithic style and Mediterranean style
diets have been found to be protective against NCDs
[15-17]. Similarly, a change in agricultural policy is
desirable to produce foods which are rich in above
nutrients and can simulate Paleolithic foods.
Table 1, from a previous study showed that, there was
a significant decrease in the prudent food
consumption among victims dying due to NCDs
compared to those dying due to other causes (4)
(Table 1).
Table 1. Food Intakes and w-6/w-3 Fatty Acid Ratio of Diet in Relation to Causes of Death Based on
Assessment by Dietary Diaries of the Spouse and Questionnaires filled by the Nutritionist.
Causes of Death
Prudent Diet Western
Western Type
Diet
Total Foods
Score
w-6/w-3 Ratio
n=1385
Men (Mean± Standard deviation) g/day
Injury-accidents (n=215)
892±252
202±22
1094±302
7.93±2.8 31
31.3± 5.3
Communicable Diseases.(n=372)
806±237
256±28
1062±198
7.26±2.7
38.2± 6.6
NCDs
Malignant (n=77)
715±241
412±53
1127±311
6.44±2.5
42.2± 6.8
Circulatory (n= 406)
757±245
437±47
1194±318
6.81±2.6
45.3±8.3
Chronic lung diseases (97)
705±202
405±41
1110±302
6.25±2.2
42.0± 7.4
Kidney diseases (n=163)
617±188
505±55
1122±325
5.72±1.8
41.8±6.1
Diabetes (n=23)
605±175
522±61
1127±334
5.65±1.7
41.6±5.7
Kendall's ȶ
0.045*
0.048**
0.025
0.041*
0.042*
n=837
Women (Mean± Standard deviation) g/day
Injury-accidents (n= 139)
822±234
186±23
1008±224
8.40±2.2
25.5± 5.7
Communicable diseases (n=194)
736±237
218±33
954±201
7.51±1.9
34.5± 5.6
NCDs(n=502)
Malignant (n=54)
657±197
305±35
962±221
6.70±1.8
41.6± 6.8
Circulatory (n= 240)
655±205
332±41
987±218
6.68±1.7
44.5± 7.5
Chronic lung diseases (n=95)
660±180
382±48
1029±180
6.12±1.3
40.0± 6.5
Renal diseases (n=87)
565±155
380±130
995±165
5.57±1.1
39.7± 6.8
Diabetes (n=26)
553±146
387±135
940±153
5.53±1.1
40.0±6.5

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 42 ~
Kendall's ȶ
0.041*
0.067**
0.024
0.043*
0.041*
Values are mean (Standard deviation), *=P<0.01,**=P<0.001. by comparison of food consumption among victims
dying due to NCDs and with victims dying of injury and accidents among both sexes. Ref. 4..
The food industry should explore the
possibility of adding these nutrients which have been
reported to have nitric oxide activating effects [15-
22]. Dietary supplements such as resveratrol and
epicatechin present in wines and fruit juices and
flavanols rich in cocoa as well as ,w-3 fatty acids, can
protect against adverse effects of food processing.
Some of the spices such as turmeric, cumin, chillies,
garlic and onion rich in antioxidants could be
incorporated in the functional foods making them
more functional and healthy. They also provide
additional beneficial effects on cardiovascular health,
insulin resistance and memory dysfunction [14-17].
In a recent meta-analysis of randomized controlled
trials, supplementation with probiotics in critically ill
adult patients was found to be associated with a
reduction in the incidence of ICU-acquired
pneumonia and ICU length of stay [23]. Data from a
total of 13 trials including 1,439 patients were
included in the analysis. While probiotic
administration was not associated with a significant
reduction in ICU (OR=0.85) or hospital (OR=0.90)
mortality, or shorter duration of mechanical
ventilation (-0.18 days) or a shorter hospital length of
stay (-0.45 days), probiotics were associated with a
reduction in incidence of ICU-acquired pneumonia
(OR=0.58) and shorter stay in the ICU (-1.49 days).
This study indicates that this approach appears to be
useful for the food industry to develop superfoods by
further modifications of probiotics with omega-3
fatty acids, flavanols by adding cocoa, walnuts and
black raisins.
In a systematic review of studies which
included the results from 14 human studies [7]
]prospective, 3 cross-sectional, 1 controlled, 3 case-
control) and 13 animal studies, found that dietary
omega-6 to omega-3 fatty acid ratio can influence
brain composition (24), Alzheimer's disease
pathology, and behavior (as according to animal
studies), and revealed an association between the
omega-6 to omega-3 ratio, cognitive decline, and
incidence of dementia. This review supports growing
evidence of a positive association between the dietary
omega-6/omega-3 ratio and the risk of Alzheimer's
disease. A recent study involving 3,457 children aged
8 to 15 years, out of which 354 had reduced birth
weight (25). Systolic blood pressure was found to be
1.1 mm Hg higher in those with reduced (less than
10th centile) compared with normal birth weight, and
pulse pressure was significantly higher (3.4 mm Hg)
in children with reduced birth weight. Those with
reduced birth weight who were in the highest tertile
of EPA and DHA intake were found to have
significantly lower systolic blood pressure (-4.9 mm
Hg) and pulse pressure (-7.7 mm Hg), than those with
normal birth weight. These data are consistent with
the hypothesis that long-chain omega-3 fatty acids
reduce blood pressure in those with impaired fetal
growth.
Table 2. The ten qualities of the high quality foods.
Qualities of foods
Examples of foods
1.Slowly absorbed foods; low glycemic
Nuts, vegetables, whole grains
2.Food Diversity.
Whole grains, beans, vegetables
3.High Nutrient density.
Nuts, vegetables, whole grains
4..No trans fat
Grilled foods, boiled foods
5. No/low sugar refined
Guava, apples, papaya, oranges
6.Low salt
Fruits, vegetables, nuts
7.Moderate fat
Nuts, pulses, beans, green leaves
8.High fiber with beneficial effects on gut microbiota.
Vegetables, whole grains, fruits
9. .Non per-oxidized foods
Fresh foods, without frying.
10.Foods requiring mastication, day time eating.
Whole grains like porridge, nuts, fruits, snacks with
millets, white meats.
Adapted from reference 29
Further efforts should be made to educate the
people and industry on protective effects of spices,
and fruits and to consider adding nitric oxide
activating agents like epicatechin and flavones as well

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 43 ~
as omega-3 fatty acids in foods to provide additional
beneficial effects. Apart from food industry,
agriculture should be made functional by developing
functional foods, using plant breeding and genetic
engineering to enhance protective nutrients in the
foods [26-30].
Some experts from European Union have
proposed “ Mind, Body Index= BMI” to address total
health because physical, social, mental and spiritual
health may depend on body composition. It is
remarkable that animals including man in the wild do
not suffer overweight but Homo economicus do suffer
[10]. Even modern husbandry animals do not do so.
This is in contrast to companion pets. The human part
– the clever mind – appears responsible for the
disease due to poor social, mental and spiritual health
in the western world. It is important to analyze facts
as primary and secondary risk factors. Food is here
secondary. It contributes, yet not causes the problem.
Just as cholesterol contributes, but does not cause
heart disease. (www.columbus-concept.com). Once
understood and accepted, such a basic principle
allows one to take the right decision about prevention
of CVDs and other chronic diseases.
In brief, food industry needs drastic changes
to produce and promote slowly absorbed functional
foods containing low omega-6/omega-3 fatty acid
ratio, vitamins, antioxidants, fiber, flavanols and
essential and non-essential amino acids, preferable by
using food stuffs rich in these ingredients. Because in
earlier studies, supplementation with vitamins and
antioxidants showed no beneficial effects on health
and diseases. Public and industry should demand no
tax subsidy to lower the cost of such foods.
Ethical clearance and Informed Consent. Not required because its not a original article.
Authors contributions. All the authors contributed equally.
Acknowledgements are given to International College of Nutrition for providing logistic support to write this article.
Conflict of interest. There is no conflict of interest among authors.
Funding. No especial grant given by any agency.
References
[1]. De Meester F, Zibadi S, Watson RR. Modern Dietary Fat
Intakes in Disease Promotion. Humana Press,
Springer,(www.springer.com) New York 2010
[2]. DeMeester F, Wild-type land based foods in health
promotion and disease prevention: the LDL-CC:HDL-CC
model. In: Wild Type Foods in Health Promotion and
Disease Prevention, editors Fabien DeMeester and RR
Watson, Humana Press, NJ 2008,p 3-20.
[3]. De Meester F, Watson RR, Sherma Zibadi, Editors, Omega-
6/3 Fatty acids;Functions, Sustainability Strategies and
Perspectives. Humana Press, Spernger,
(www.springer.com), New York 2012
[4]. Rohrmann S, Overvad K, Bueno-de-Mesquita HB, et al.
Meat consumption and mortality. Results from the
European Prospective Investigation into Cancer and
Nutrition. BMC Med 2013
[5]. Judd SE, Orlando Gutierrez O, Kissela BM, et al. Southern
diet pattern increases risk of stroke while plant-based
pattern decreases risk of stroke in the REGARDS study.
International Stroke Conference 2013; February 7, 2013;
Stroke. 2013; 44: A144
[6]. PREDIMED Study Investigators. Primary prevention of
cardiovascular disease with a Mediterranean diet. N Engl J
Med 2013; February 25, 2013, DOI:
10.1056/NEJMoa1200303
[7]. Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-
Hong SF, Faurot KR, Suchindran CM, et al. Use of dietary
linoleic acid for secondary prevention of coronary heart
disease and death: evaluation of recovered data from the
Sydney Diet Heart Study and updated meta-analysis. BMJ
2013;346:e8707. Cite this as: BMJ 2013;346:e8707
[8]. Singh RB, Fedacko J, Vargova V, Pella D, Niaz MA, Ghosh
S. Effect of low W-6/W-3 fatty acid ratio Paleolithic style
diet in patients with acute coronary syndromes: A
randomized, single blind, controlled trial, World Heart J
2012;4:71-84.
[9]. Fedacko J, Vargova V, Singh RB, Anjum B, Takahashi T,
Tongnuka M, Dharwadkar S, Singh S, Singh V, Kulshresth
SK, De Meester F, Wilson DW. Association of high w-6/w-
3 fatty acid ratio diet with causes of death due to non-
communicable diseases among urban decedents in North
India. The Open Nutra Jour 2012;5:113-123.
[10]. WHO. Mortality and burden of disease estimates for WHO
Member States in 2008. Geneva: World Health
Organization, 2010.
[11]. Singh RB, Takahashi T, Nakaoka T, Otsuka K,Toda E,
Shin HH, Kyu Lee M, Beeharry V, Hristova K, Fedacko
J, Pella D, De Meester F, Wilson DW, Juneja LR.
Nutrition in transition from Homo sapiens to Homo
economicus. The Open Nutra J 2013;6: (in press).
[12]. Moodie R, Stuckler D, Monteiro C, Sheron N, Thamarangsi
, Lincoln P, Casswel S on Behalf of the Lancet NCD Group.
Profits and pandemics: prevention of harmful effects of
tobacco, alcohol, and ultra-processed food and drink
industries. The Lancet, Early Online Publication, 12
February 2013,doi:10.1016/S0140-6736(12)62089.
[13]. The "Heart Disease and Stroke Statistics--2013 Update"
and the Need for a National Cardiovascular Surveillance
System Circulation.2013;127:21-23.
[14]. U. S. Health In International Perspective. Shorter Lives,
Poorer Health. National Academy of Sciences, USA 2013.
( For the report on US healthdisadvantage see
http://www.nap. edu/catalog.php?record_id=13497;For the
US prevention strategysee
http://www.healthcare.gov/prevention/nphpphc/strategy/re
port.pdf.
[15]. Editorial. Wealth but not health in USA. Lancet
2013;381:177. doi:10.1016/S0140-6736(13)60069-0

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 44 ~
[16]. Singh RB, Anjum B, Takahashi T, Martyrosyan DM, Pella
D, De Meester F, Wilson DW, SSD Beehari, Keim M,
Shastun S. Poverty is not the absolute cause of deaths due
to noncommuni- cable diaseses NCDs. World heart J
2012;4: (in press).
[17]. Toda E, Toru T, Singh RB, Alam SE et al. Can low w-6/w-
3 ratio Paleolithic style diet stop cardiovascular diseases?
Tissue is the Issue. Amer. Med. J. 2012;3:183-193.
[18]. De Lorgeril M, Renaud S, Mamelle N et al. Mediterranean
alpha-linolenic acid-rich diet in secondary prevention of
coronary heart disease. The Lancet, vol. 343, no. 8911, pp.
1454–1459, 1994.
[19]. Singh RB, Dubnov G, Niaz MA,Ghosh S,Singh R,Rastogi
SS,Manor O,Pella D,Berry EM. Effect of an Indo-
Mediterranean diet on progression of coronary disease in
high risk patients: a randomized single blind trial. Lancet
2002,360:1455-1461.
[20]. Singh RB, Rastogi SS, Ghosh S, Niaz MA, Singh R, Verma
R, Randomised controlled trial of cardioprotective diet in
patients with recent acute myocardial infarction results of
one year follow up.BMJ 1992; 304: 1015-1019. PMID:
1586782
[21]. Singh RB, Kumar A, Neki NS, Pella D, Rastogi SS,Basu
TK, Otsuka K, De Meester F, Wilson DW. Acharya SN,
Juneja L, Takahashi T,Diet and Lifestyle Guidelines and
Desirable Levels of Risk Factors for Prevention of
Cardiovascular Disease and Diabetes among Elderly
Subjects. A Revised Scientific Statement of the
International College of Cardiology and International
College of Nutrition-2011, World Heart J 2011;3:305-320.
[22]. Hristova K, Nakaoka T, Otsuka K, Fedacko J, Singh R,
Singh RB, De Meester F, Wilczynska A, Wilson DW.
Perspectives on Chocolate Consumption and Risk of
Cardiovascular Dis-eases and Cognitive Function. The
Open Nutraceuticals Journal,2012, 5, 207-212.
[23]. Barraud D, Bollaert PE, Gibot S; Impact of the
Administration of probiotics on mortality in critically ill
Adult patients: A meta-analysis of randomized controlled
trials. Chest 2013;143:646-55.
[24]. Loef M, Walach H. The omega-6/omega-3 ratio and
dementia or cognitive decline: a systematic review on
human studies and biological evidence. J Nutr Gerontol
Geriatr, 2013; 32: 1-23.
[25]. Skilton MR, Raitakari OT, Celermajer DS.High Intake of
Dietary Long-Chain ω-3 Fatty Acids Is Associated With
Lower Blood Pressure in Children Born With Low Birth
Weight: NHANES 2003-2008. Hypertension. 2013 Mar 4.
[Epub ahead of print]PMID:23460284
[26]. Singh RB, De Meester F, Wilzynska A, et al. Can a changed
food industry agricultural policy prevent cardiovascular
and other chronic diseases? World Heart J 2013;5:1-8.
[27]. Petersen K, Davis K, Rogers C, Proctor D, West S, Kris-
Etherton P, A Culinary dose of herbs and spices improves
24-Hour blood pressure in adults at risk for cardiometabolic
diseases: A randomized, crossover, controlled-feeding
study, Current Developments in Nutrition, Volume 5, Issue
Supplement_2, June 2021, Page 359,
[28]. Kristina Petersen, Penny Kris-Etherton, Samantha
Anderson, Jeremy Chen See, Connie Rogers, David
Proctor, Sheila West, Regina Lamendella, Herbs and Spices
Modulate Gut Microbiota Composition: A Randomized,
Crossover, Controlled-Feeding Study, Current
Developments in Nutrition, Volume 5, Issue Supplement_2,
June 2021, Page 360, ]https://
doi.org/10.1093/cdn/nzab037_070
[29]. Singh RB, Bawareed OA , Chibisov S, Kharliskaya E ,
Abramova M , and Magomed M. The ten characteristics of
a high quality diet with reference to circadian dysfunction?
World Heart J 2021; 13: 207-212.
[30]. Singh RB, Bawareed OA, Yulia G, Chibisov S, Magomed
M. When to eat, how often to eat, what to eat and how to
eat. World Heart J 2021; 13: 17-20.
[31].

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 45 ~
MODERATE CONSUMPTION OF ALCOHOL AND THE FRENCH PARADOX
Krasimira Hristova1, Adrian Isaza2, Maria Abramova3, R B Singh4, Toru Takahashi5
1University National Heart Hospital, Sofia, Bulgaria
2Everglade University, Tampa, USA
Correspondence
Dr Adrian Isaza, MD, PhD
Everglade University, Tampa, USA, Email: adrian.isaza@usat.edu>
Abstract: The mortality due to coronary artery disease (CAD) is 36% lower than the USA and 39% lower than the UK. In
contrast, mortality from all causes is only 8% lower than in the USA and 6% than in the UK, owing to a high level of cancer
and violent deaths. In a previous study of 34,000 middle-aged men from Eastern France with a follow-up of 12 years, Serge
Renaud et al observed that for 48 g of alcohol as mostly wine/day as the mean intake, mortality from cardiovascular
diseases(CVD) was lower by 30%, all-cause mortality was decreased by 20%, but mortality by cancer and violent death
was increased compared with abstainers. The health benefits of alcohol and wine have showed that moderate consumption
is associated with a decrease in all-cause and CVD mortality. Va
rious populations and alcoholic beverages This
observation has been made in different populations in different degrees. Alcoholic beverages may favorably influence
cardiac risk potential actions on lipids, platelets, antioxidants, polyphenols, fibrinolysis, and neuronal factors. Some
studies also indicate that the perceived benefit of alcoholic beverages in general, and wine in particular, could be due to
the socioeconomic confounders. Aging of whiskey increases 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging
activity which may provide less harm or may be more useful if consumed in moderation. It seems, that it is not currently
possible to define the role of wine in human health, unless more rigorous randomized, controlled trials are available.
Key words: Alcohol, cardiovascular disease, coronary disease, antioxidant, flavonoids.
Introduction. The incidence and mortality rates from
coronary artery disease(CAD) in France are very low
compared to UK and Sweden, despite the fact that
saturated fat intakes, serum cholesterol, blood
pressure and prevalence of smoking are not lower in
France. The relative immunity of the French to CAD
has been attributed to their moderate alcohol
consumption and to their consumption of antioxidant
nutrients and vegetables, and the wine [1]. It is
possible that the custom of drinking wine with the
meal may confer protection against some of the
adverse effects of the food.
The French Paradox. The CAD mortality is 36%
lower than the USA and 39% lower than the UK. In
contrast, mortality from all causes is only 8% lower
than in the USA and 6% than in the UK, owing to a
high level of cancer and violent deaths [2]. In a
previous study of 34,000 middle-aged men from
Eastern France with a follow-up of 12 years Serge
Renaud et al observed that for 48 g of alcohol (mostly
wine) per day as the mean intake, mortality from
cardiovascular diseases was lower by 30%, all-cause
mortality was reduced by 20%, but mortality by
cancer and violent death was increased compared
with abstainers [3]. Thus the so-called 'French
Paradox' is: a low mortality rate specifically from
cardiovascular diseases(CVDs) which may be due
mainly to the regular consumption of wine, along
with meals. The mean energy supplied by fat was
38% in Belfast and 36% in Toulouse in 1985–86. In
1995–97, the percentage of energy from fat was 39%
in Toulouse according to a representative population
survey.
Figure 1. Dr Serge C Renaud.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 46 ~
Wine is an alcoholic beverage made from
fermented grapes and represents the most consumed
recreational drink of the Mediterranean basin. In a
chemical view, wine consists primarily of water and
ethanol along with nutrients which makes the French
Paradox [4,5]. In addition, wine contains many other
substances such as polyphenols and such as phenolic
acids; gallic acid, caffeic acid, p-coumaric acid, etc.,
stilbenes; trans-resveratrol and flavonoids; catechin,
epcatechin, quercetin, rutin, myricetin, etc [4]. which
provide a pleasant taste and flavor with a beneficial
effect on health. The health benefits of wines are
commonly attributed to a high content of
polyphenols, exerting a potential effect as
antioxidants. In an earlier study, phenolic compounds
of 14 pomace samples originating from red and white
wine making were characterized [4]. In the skin and
seeds, up to 13 anthocyanins, 11 hydroxybenzoic and
hydroxycinnamic acids, and 13 catechins and
flavonols as well as 2 stilbenes were identified and
quantified. The skin of the grape was found to be rich
sources of anthocyanins, hydroxycinnamic acids,
flavanols, and flavonol glycosides, whereas flavanols
were mainly present in the seeds. It seems that,
besides the lower amount of anthocyanins in white
grape pomace, no principal differences between red
and white grape varieties were observed [4].
Beneficial and Adverse Effects of Alcohol. The
health benefits of alcohol and wine have showed that
moderate consumption is associated with a decrease
in all-cause and CVD mortality [6]. Various
populations and alcoholic beverages This observation
has been made in different populations in different
degrees [6]. There are multiple mechanisms by which
alcoholic beverages may favorably influence cardiac
risk potential actions on lipids, platelets,
antioxidants, fibrinolysis, and neuronal factors.
Some studies also indicate that the perceived benefit
of alcoholic beverages in general, and wine in
particular, could be due to the socioeconomic
confounders. It seems, that it is not currently possible
to define the role of wine in human health, unless
more rigorous randomized, controlled trials are
available.
Some studies have found greater health
benefits for red rather than white wine, probably
because red wine contains more polyphenols than
white wine and these are thought to be particularly
protective against CVDs [6]. However, the main
component of wine is ethanol, which is known to
causes damage and functional impairments in several
organs of the body. Alcohol drinking may be
characterized by intoxication symptoms of the central
nervous system (CNS), associated with behavioral
changes, poor motor coordination and impaired brain
activity due to a direct ethanol action on synthesis,
release and signaling of several neurotransmitters,
including glutamate, serotonin and GABA[7-10]. It
seems that an acute, chronic and prenatal exposure,
may also affect the synthesis and release of biological
mediators, such as growth factors[9]. Growth factors
are naturally occurring substances able to stimulate
cellular growth, proliferation, healing, and cellular
differentiation. Among these factors, the presence of
neurotrophins such as nerve growth factor (NGF) and
brain derived neurotrophic factor (BDNF) may be
dramatically affected by ethanol consumption [10].
There are several unexpected actions of NGF which
indicate that developmental effects are only one
aspect of the biology of NGF and include effects on
the immune, endocrine, cardiovascular and
reproductive systems [8,10]. The effects of BDNF are
similar to those of NGF but with a more direct action
on neuronal cells. The biological effects of NGF are
mediated through two distinct classes of cell surface
receptors: TrkA and the shared p75 neurotrophin
receptor [7]. BDNF, the second neurotrophin, is a
growth factor expressed in a range of tissue and cell
types, such as CNS, motor neurons, PNS, the retina
and peripheral tissues such as liver and gut [10].The
biological activity of BDNF is mediated by binding
TrkB receptors and plays a key role in sustaining
dendritic branching and dendritic spine morphology,
memory regulation, synaptic plasticity and long-term
potentiation[10]. Experimental study in rat, found an
upregulation of BDNF which could potentially
represent a neuroprotective mechanism activated
following alcohol exposure or stress [10]. The results
indicate that stress and alcohol exposure may have
both overlapping and unique effects on BDNF, and
highlight the need for the stress of intubation to be
taken into consideration in studies that implement this
route of drug delivery.
It’s known that red wine and white wine have
different effects on health, probably due to the
different polyphenol composition. In mammals, they
differentially affect neurotrophin levels and could
cause diverse types of damage whether administered
in acutely, chronically or during gestation. The
different effects of red wine consumption compared
with other alcoholic beverages at the CNS level but
not in the other tissues are probably due to the
components of red wine, reinforcing the hypothesis
that the presence of polyphenols in red wine is able to
limit some of the harmful effects of ethanol.
Interestingly, white wine also is able to affect NGF
expression but with more harmful effects compared

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 47 ~
to red wine as shown by a study carried out in rats in
which daily intragastric administration of 40 g/kg of
white wine (10 vol%) for 16 consecutive weeks
induces NGF decrease in the hippocampus, as well
decreased ChAT activity and immunopositivity in the
septum [9,10].
In women ethanol consumption during
gestation may be the cause of Fetal Alcohol Spectrum
Disorders (FASD) in newborns, which is a continuum
of various permanent birth defects caused by the
mother's consumption of alcohol during pregnancy.
The prevalence of FASD is very difficult to establish
in the western communities where alcohol use is
common. It has been estimated that from 1 up to 4
percent of children in the western countries have
FASD or other alcohol-related birth defects [10].
However, a lower prevalence has been found in
countries consuming wine which may be due to
protective effects of polyphenols. Examinations of
genes, showed a continuum of long-lasting molecular
effects that are not only timing specific but are also
dose dependent; with even moderate amounts causing
significant alterations. There is no known safe
amount of alcohol or safe time to drink alcohol during
pregnancy. Ethanol consumption during pregnancy
may cause neuronal cell death in the offspring by
affecting neurotrophins including NGF and BDNF
and their receptors, TrkA and TrkB, respectively. The
trophic factors may be severely affected by early
ethanol exposure in the fetus in the central nervous
system as well as in other target organs of ethanol
intoxication as liver, testis, kidney, thyroid and other
glands.
Blomster et al should be appreciated for
producing most interesting data which may be used
for prevention of complications of alcoholism in
patients with type 2 diabetes [11] (1). It is known that
wine consumption can provide protection against
adverse effects of alcohol due to presence of
flavonoids which have antiplatelet effects [12] (2).
The concept of French paradox was formulated by
French epidemiologists in the 1980s but became
more popular after its description by Serge Renaud in
1992 [12].
Figure 2. Dr Serge Renaud in good mood along with his student and friends.
In several studies on cause specific mortality
from Russia, alcohol-attributable mortality varied by
year [13-15]. The exponential nature of the relation
between average alcohol consumption and mortality
has also been demonstrated in a later study from
Russia [13]. This study revealed that substantial
numbers of people report drinking three or more half-
litre bottles of vodka per week. However, the
exponential curves for dose-response relations
between average volume of alcohol consumption and
the mortality risk of various diseases is not fully
explained which may be due to presence of
confounders. These confounders may be either
protective factors or other coexisting causes of death
and health behavior patterns which may be
responsible for variability. How many subjects
consume red or white wine and how many times in a
week, because wine appears to be a functional food if
taken in moderation. It would also be interesting to
study the effect of moderate alcohol verses drinking
more than 10 drinks per week, because moderate
drinking appears to be protective against CVDs.It

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 48 ~
should be noted that aging of whiskey increases 1,1-
diphenyl-2-picrylhydrazyl (DPPH) radical
scavenging activity which may provide less harm or
may be more useful if consumed in moderation [16].
In later years, alcohol was a cause of more
than half of all deaths among Russians, at ages 15 to
54 years [13]. Alcohol accounted for most of the large
fluctuations in Russian mortality, and alcohol and
tobacco accounted for the large difference in adult
mortality between Russia and Western Europe. It is
not clear that how common is the health behavior
pattern among Russians from these studies, although
tobacco intake was considered a risk factor [11-13].
It would be interesting to know the prevalence of
wine consumption, prudent dietary pattern, moderate
physical activity, no tobacco and active prayer to
relieve mental stress which may be important
confounders for protection against CVDs and to
explain the cause of Russian paradox which is similar
to French paradox [2,3,12-16]. Effects of resveratrol
which is rich wines, on cerebral blood flow variables
and cognitive performance in humans in a double-
blind, placebo-controlled, crossover investigation
reported beneficial outcome [15]. Moderate alcohol
intake increases HDL-C, and decreases CRP, IL-
6,TNF-alpha, lipoprotein(a), plasminogen activator
inhibiter-1,insulin resistance and provides antiplatelet
effects. These beneficial effects are enhanced by
omega-3 fatty acids, whereas eating excess of lecithin
and TMAO, may decrease these beneficial effects of
both the agents [12,15-17]. Increased intake of cocoa
products, prebiotics and Mediterranean style foods
have been demonstrated to be protective against risk
of CVDs and cancer [18-20].
In a more recent study, benefits of wine
consumption were particularly evident in participants
who drank predominantly wine (cardiovascular
events aHR 0.78, 95% CI 0.63–0.95, P = 0.01; all-
cause mortality (HR 0.77, 95% CI 0.62–0.95, P =
0.02) [19]. Compared with patients who reported no
alcohol consumption, those who reported heavy
consumption had dose-dependent higher risks of
cardiovascular events and all-cause mortality [19].
Greater the intake of alcohol, higher the risk of these
chronic diseases and deaths due to these problems.
Excess of alcohol consumption causes decrease in
vitamin B1, B6 and B12 as well as in folic acid,
antioxidants vitamins A,E ,C and beta carotene,
flavonoids, amino acids, coenzyme Q10, l- carnitine,
omega-3 fatty acids as well as in minerals Mg, K, Ca,
Cr, Zn, Se from various tissues of the body.
Alcoholism also has a direct adverse effects
on cell membrane, mitochondria and genes.
Alcoholic cirrhosis, fatty liver, cardiomyopathy,
hypertriglyceridemia, hyperuricemia, oxidative stress
and inflammation are well known adverse effects of
alcoholism. It also damages the brain causing
dementia, depression and psychosis. However,
moderate alcohol intake up to 10 drinks per week may
have beneficial effects on the risk of all these
problems. Western diet rich in omega-6 fat (sun
flower oil, corn oil, saiflower oil, soya bean oil), trans
fat, saturated fat and refined carbohydrates and low in
w-3 fatty acids, vitamins, antioxidants and amino
acids is known to cause all above diseases. Therefore,
western diet in conjunction with alcoholism doubles
the risk of deaths due to chronic diseases whereas
increased consumption of Mediterranean diets, cocoa
and probiotics can reduce the adverse effects of
alcoholism. If the diet is rich in all these nutrients,
these chronic diseases can be decreased. However, it
is not possible for general population to eat adequate
fruits, vegetables, legumes and nuts (walnuts rich in
w-3)and olive oil and rape seed oil (w-3 rich) which
are rich sources of above nutrients. There is need to
add omega-3 fatty acids and polyphenols in the
alcohol to decrease these adverse complications and
deaths because it seems to be central in the above
mechanism. Alcohol drains some DHA (w-3 fat) and
flavonoids and other endogenous antioxidants from
the cells of the brain, heart, arteries, liver, beta cells
of pancreas, stomach, duodenum and ileum and breast
in females, predisposing these organs to above
chronic diseases. Vodka can be made healthful if
enriched with short chain fatty acids or alpha
linolenic acid, polyphenols and cocoa which can
repair this deficiency. It is like a cleaning drink for
the all the organs of the body. If standard Vodka is
40% alcohol, then we need +/- 1-g DHA per 500-ml
bottle. Eating designers foods with low w-6/w-3 ratio
of 1:1 plus flavonoids may also decrease the adverse
effects of alcoholism and may enhance the beneficial
effects of moderate alcohol intake. In a recent study,
patients with type 2 diabetes, moderate alcohol use,
particularly wine consumption, was associated with
reduced risks of CVD events and all-cause mortality
[19].
In brief, moderate intake of wine, in particular red wine with high concentration of polyphenols may
provide beneficial effects. However, intake of ethanol above 100 ml more than 5 days in a week can cause
increased risk of CVDs and cancer as well as all cause morbidity and mortality.

International journal of clinical nutrition ISSN: 0971-9220
Volume 22, Number 1 © 2022 International college of clinical nutrition, India
~ 49 ~
Ethical clearance and Informed Consent. Not required because its not a original article.
Authors contributions. All the authors contributed equally.
Acknowledgements are given to International College of Nutrition for providing logistic support to write this article.
Conflict of interest. There is no conflict of interest among authors.
Funding. No especial grant given by any agency.
References
[1]. Burr ML. Explaining the French paradox. J R Soc Health.
1995 Aug;115(4):217-9. doi:
10.1177/146642409511500404. PMID: 7562866.
[2]. Renaud S, Gueguen R. The French paradox and wine
drinking. Novartis Found Symp. 1998;216:208-17;
discussion 217-22, 152-8. doi:
10.1002/9780470515549.ch13
[3]. Renaud SC and Gueguen R, Schenker J, Houtaud AD.
Alcohol and mortality in middle-aged men from eastern
France. Epidemiology 1998; 9: 184-188.
[4]. Kammerer D, Claus A, Carle R, Schieber A. Polyphenol
screening of pomace from red and white grape varieties
(Vitis vinifera L.) by HPLC-DAD-MS/MS. J Agric Food
Chem. 2004 Jul 14;52(14):4360-7. doi: 10.1021/jf049613b.
[5]. Ferrières J. The French paradox: lessons for other
countries. Heart. 2004;90(1):107-111.
doi:10.1136/heart.90.1.107
[6]. Lindberg ML, Amsterdam EA. Alcohol, Wine, and
cardiovascular health. Clin Cardiol 2008; 31: 347-51.
[7]. Ceci FM, Ferraguti G, Petrella C, et al. Nerve Growth
Factor in Alcohol Use Disorders. Curr Neuropharmacol.
2021;19(1):45-60.
[8]. White A, Hingson R. The burden of alcohol use: excessive
alcohol consumption and related consequences among
college students. Alcohol Res. 2013;35(2):201-218.
[9]. Shastun S, Abramova M, Singh RB, et al. The French
paradox and the Russian paradox. World Heart J 2014;
6:237-240.
[10]. Boschen KE, Criss KJ, Palamarchouk V, Roth TL,
Klintsova AY. Effects of developmental alcohol exposure
vs. intubation stress on BDNF and TrkB expression in the
hippocampus and frontal cortex of neonatal rats. Int J Dev
Neurosci.,2015;43:16-24.
[11]. Blomster JI, Zoungas S, Chalmers J, Li Q, Chow CK et al.
The Relationship Between Alcohol Consumption and
Vascular Complications and Mortality in Individuals With
Type 2 Diabetes Mellitus. Diabetes Care Published online
before print. February 27, 2014, doi:10.2337/dc13-2727
[12]. Renaud S, deLorgeril M, Wine, alcohol, platelets and the
French paradox for coronary heart disease. Lancet
1992;339:1523-1526.
[13]. Zaridze D, Lewington S, Boroda A, et al. Alcohol and
mortality in Russia: prospective observational study of
151 000 adults. Lancet 2014. published online Jan
31.http://dx. doi.org/10.1016/S0140-6736(13)62247-3.
[14]. Zaridze D, Brennan P, Boreham J, et al. Alcohol and
cause-specific mortality in Russia: a retrospective case-
control study of 48 557 adult
deaths. Lancet 2009; 373: 2201-2214.
[15]. Leon DA, Chenet L, Shkolnikov V, et al. Huge variation in
Russian mortality rates 1984—94: artefact, alcohol, or
what?. Lancet1997; 350: 383-388.
[16]. Aoshima H, Tsunoue H, Koda H, Kiso Y. Aging of whiskey
increases 1,1-diphenyl-2-picrylhydrazyl radical scavenging
activity. Journal of Agricultural and Food Chemistry.
2004;52(16):5240–5244.[
[17]. Kennedy DO, Wightman EL, et al, Effects of resveratrol on
cerebral blood flow variables and cognitive performance in
humans: a double-blind, placebo-controlled, crossover
investigation," Am J Clin Nutr, 2010 March 31;
[18]. Hristova K, Nakaoka T, Otsuka K, Fedacko J, Singh R,
Singh RB, De Meester F, Wilczynska A, Wilson DW.
Perspectives on chocolate consumption and risk of
cardiovascular diseases and cognitive function. The Open
Nutraceuticals Journal, 2012, 5, 207-212.
[19]. Barraud D, Bollaert PE, Gibot S; Impact of the
administration of probiotics on mortality in critically ill
adult patients: A meta-analysis of randomized controlled
trials. Chest 2013;143:646-55.
[20]. PREDIMED Study Investigators. Primary prevention of
cardiovascular disease with a Mediterranean diet. N Engl J
Med 2013; February 25, 2013, DOI:
10.1056/NEJMoa1200303

Prof. Dr R B Singh, MD,FICN,FICC
Ph.: +91 99977 94102
E-mail: rbs@ijcnworld.com
Halberg Hospital and Research Instirtute,
Civil Lines, Opp. Wilsonia College,
Moradabad (UP) 244001, India
View publication statsView publication stats