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Personalized Nutrition as
Medical Therapy for
High-Risk Diseases
Personalized Nutrition as
Medical Therapy for
High-Risk Diseases

Edited by
Nilanjana Maulik
First edition published 2020

by CRC Press
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Boca Raton, FL 33487-2742

and by CRC Press

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© 2020 Taylor & Francis Group, LLC

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This book is dedicated to my late father for his continuous support,
love and trust. He taught me to be an independent and determined
person. Without his encouragement and dedication, I would never
have been able to achieve my objectives and succeed in life.
Contents
Preface.......................................................................................................................ix
Acknowledgments......................................................................................................xi
Editor...................................................................................................................... xiii
Contributors.............................................................................................................. xv

Chapter 1 Introduction...........................................................................................1
Dilip Ghosh

Chapter 2 Personalized Nutrition: The New Era of Nutrition............................... 5

Diego Accorsi, Seetur R. Pradeep, Jennifer Hubbard,
Rajesh Lakshmanan, Nilanjana Maulik and Mahesh Thirunavukkarasu

Chapter 3 Personalized Nutrition in Cardiovascular Disease: From

Concept to Realization........................................................................25
Marcella O’Reilly, Sarina Kajani, Sean Curley, Sarah Mahayni,
Helen M. Roche and Fiona C. McGillicuddy

Chapter 4 Nutraceuticals for Hypertension Control............................................ 61

Balázs Varga, Mariann Bombicz, Andrea Kurucz and Béla Juhász

Chapter 5 Roles of Daily Diet and Beta-Adrenergic System in the

Treatment of Obesity and Diabetes................................................... 113
Ebru Arioglu Inan and Belma Turan

Chapter 6 High Carbohydrate Diet-Induced Metabolic Syndrome in the

Overweight Body: Association between Organ Dysfunction and
Insulin Resistance............................................................................. 153
Belma Turan and Erkan Tuncay

Chapter 7 Caloric Restriction in Obesity and Diabetic Heart Disease.............. 183

Edith Hochhauser, Maayan Waldman and Michael Arad

Chapter 8 Personalized Nutrition in Children with Crohn Disease..................209

Andrew S. Day

vii
viii Contents

Chapter 9 Personalized Nutrition in Chronic Kidney Disease: A New

Challenge.......................................................................................... 225
Giorgina Barbara Piccoli

Chapter 10 Personalized Nutrition in Hypercholesterolemia ............................. 263

Aktarul Islam Siddique and Nalini Namasivayam

Chapter 11 Omega-3 Fatty Acids in the Prevention of Maternal and

Offspring Metabolic Disorders ........................................................ 283
Olatunji Anthony Akerele and Sukhinder Kaur Cheema

Chapter 12 Challenges to the Clinical Implementation of Personalized

Nutrition ........................................................................................... 303
Diego Accorsi and Nilanjana Maulik

Chapter 13 The Importance of Personalized Nutrition in Psychological

Disorders .......................................................................................... 313
Gulsah Kaner Tohtak
Index...................................................................................................................... 339
Preface
Nutrition has a signifcant impact on human health. For many years, it has been
known that a variety of plants used in traditional medicine and their products
have properties that allow them to act as genomic modulators, such as the natu-
ral phytochemicals used to reduce toxicity due to radiation or chemotherapy. The
Mediterranean Diet has similarly received substantial scientifc attention due to its
anti-infammatory effects. Diet infuences the expression of the genome, and experts
now suggest that personalizing an individual’s diet based on his or her biological
profle (called personalized nutrition) could improve health and lifestyle.
Evidence suggests that people metabolize nutrients differently based on their
genetic, epigenetic and metabolic profles. For example, nutrition researchers have
been long puzzled over the fact that people living in the Arctic, who consume a
diet consisting of fatty fsh and meat, have a lower incidence of heart attacks. After
conducting substantial research, scientists have identifed several gene variants in
the Inuit population that assist in breaking down fatty acids more easily. Caffeine is
another example of an ingredient that frequently makes headlines with news media,
either celebrating its health benefts for some or highlighting adverse effects related
to heart risk in others.
Since the advent of the human genome project, nutrient-gene connections have
become a hot topic of research interest, especially in medical science, and several
studies have explored the importance of interactions between genes, diet and life-
style. Similar interactions have been observed between food and the metabolome,
epigenome, exposome (external infuences such as the environment and behavior)
and even the gut microbiome. The picture that has emerged from all of these studies
indicates that not only is it important to eat ‘good’ food, but it is also essential to eat
foods that are ‘right’ for you. Therefore, medical therapists have started to consider
personalized nutrition as a possible therapeutic modality with several preclinical
studies demonstrating the potential of this novel approach. However, although inter-
est in the feld is growing, it is in its infancy, and more research is necessary to fur-
ther understand the complex relationships between nutrition, environment, lifestyle
and the genome.
Other than those afficted with certain medical conditions such as gluten intol-
erance and diabetes, food products currently available in the market are generally
based on the specifc preferences of consumers rather than genetic and biologic
factors. However, as consumers become more aware of the inherent susceptibili-
ties carried in their genes, they have begun to demand products more suitable to
their specifc circumstances. Nutritional advice by clinicians is similarly generic and
guided by a handful of parameters such as lipid profles, blood glucose levels, blood
pressure and BMI. Recent studies focused on understanding personalized dietary
advice have found individual-level advice to be more fruitful than population-based
nutritional advice, however. Therefore, we believe that a better understanding of the
role of personalized nutrition in healthy mindbody and lifestyle modifcations is an

ix
x Preface

important challenge because, in the near future, personalized nutrition is likely to

change how we determine food choices.
This book addresses the role and importance of personalized nutrition in daily
life within 13 relevant and focused contributions from world-renowned scientists
in the feld. This reference book is likely to be of interest to all healthcare-related
professionals, nutritionists, biochemists, biologists, primary care-related physicians
and dieticians to heighten their awareness about the importance of this feld of study,
since personalized nutrition, while not yet ready for practice, may soon become a
valuable therapeutic and/or preventative option for individuals at high risk.

Nilanjana Maulik, PhD, FAHA, FACN

Department of Surgery
University of Connecticut School of Medicine
Farmington, CT-06001, USA
Acknowledgments
Developing and editing a book is both harder and more rewarding than I ever could’ve
imagined. This book would not have been possible without the hard work and
dedication of my colleague, Mahesh Thirunavukkarasu, PhD, Assistant Professor,
Department of Surgery, UConn Health, Farmington, Connecticut. He communicated
with the authors on a daily basis and assisted me in editing the volume. His efforts
were instrumental in completing the book on time. A very special thanks to Diego
Accorsi, MD, the greatest cover page designer I could ever imagine.
I am also eternally grateful to the fellows, residents and colleagues for their help
and support. I would also like to extend my heartfelt appreciation to my mother,
brothers and my husband who encouraged and helped me to complete the book.
Lastly, I would like to express my deepest gratitude to all of the authors for their
remarkable contributions. I thank you all.

xi
Editor
Nilanjana Maulik is a well-established and highly reputed cardiovascular scientist.
She is an expert in the feld of vascularization and cardiac regeneration and develops
therapeutic strategies for ischemic heart disease. Her laboratory has identifed impor-
tant pro-angiogenic molecules that play an important role in therapeutic angiogenesis
using various preclinical models and disease conditions. Her research has advanced
knowledge in the areas of angiogenesis and revascularization of the ischemic myo-
cardium. Dr Maulik received her PhD in Biochemistry from Calcutta University,
India. After completion of her PhD, Dr Maulik joined the Department of Surgery at
University of Connecticut Health as a research fellow. She has continued her service
there as a faculty member, and was promoted to tenured professor. Dr Maulik also
serves as a faculty member in the Cell Biology graduate program at the University
of Connecticut Health. She has been heavily involved in NIH-funded research all
her career. She also serves as an expert (cardiovascular) in the NIH study sections
regularly; she frequently gives invited lectures at national and international scien-
tifc conferences. She has trained more than 150 scientists/fellows/residents, most
of whom are actively engaged in professional careers all over the world. Dr Maulik
is a member of several prestigious societies including the Federation of American
Societies for Experimental Biology (FASEB), the American Heart Association
(AHA), the International Society of Heart Research (ISHR), the American College
of Nutrition (ACN) and the International College of Angiology (ICA). Presently,
she is on the editorial boards of several major cardiovascular journals and served
as Editor-in-Chief of the prestigious journal Molecular Biology Reports (Springer
Press). She is a Fellow of the International Academy of Cardiovascular Sciences
(IACS, Canada), ACN and AHA. She has published more than 210 original peer-
reviewed articles and almost 36 book chapters. She has also edited four books on
epigenetics, nutrition and cardiovascular diseases for CRC/Springer Press. Lastly,
Dr Maulik has organized several international conferences, symposia and delivered
more than 125 lectures all around the world.

Nilanjana Maulik, PhD, FAHA, FACN

Professor, Department of Surgery, University
of Connecticut Health, Farmington Avenue,
Farmington, Connecticut

xiii
Contributors
Diego Accorsi Dilip Ghosh
School of Medicine Nutriconnect
University of Connecticut Western Sydney University,
Farmington, Connecticut Australia

Olatunji Anthony Akerele Edith Hochhauser

Department of Biochemistry Felsenstein Medical Research Institute
Memorial University Sackler School of Medicine
St. John’s, Newfoundland and Labrador, Tel Aviv University, Israel
Canada
Jennifer Hubbard
Michael Arad School of Medicine
Sheba Medical Center University of Connecticut
Sackler School of Medicine Farmington, Connecticut
Tel Aviv University, Israel
Béla Juhász
Ebru Arioglu Inan University of Debrecen
Ankara University Hungary
Ankara, Turkey
Sarina Kajani
Mariann Bombicz UCD School of Medicine
University of Debrecen University College Dublin
Hungary Dublin, Ireland

Sukhinder Kaur Cheema Gulsah Kaner Tohtak

Department of Biochemistry İzmir Katip Çelebi University
Memorial University İzmir, Turkey
St John’s, Newfoundland and Labrador,
Canada Andrea Kurucz
University of Debrecen
Sean Curley Hungary
UCD School of Medicine
University College Dublin Rajesh Lakshmanan
Dublin, Ireland School of Medicine
University of Connecticut
Andrew S. Day Farmington, Connecticut
University of Otago, Christchurch
Christchurch, New Zealand

xv
xvi
Sarah Mahayni
UCD School of Public Health
University College Dublin
Dublin, Ireland
Nilanjana Maulik
School of Medicine
University of Connecticut
Farmington, Connecticut
Fiona C. McGillicuddy
UCD School of Medicine
University College Dublin
Dublin, Ireland
Nalini Namasivayam
Annamalai University
Annamalainagar
Tamil Nadu, India
Marcella O’Reilly
UCD School of Public Health
University College Dublin
Dublin, Ireland
Giorgina Barbara Piccoli
Università di Torino
Turin, Italy
Centre Hospitalier Le Mans
Le Mans, France
Helen M. Roche
UCD School of Public Health
University College Dublin
Dublin, Ireland
Contributors
Seetur R. Pradeep
School of Medicine
University of Connecticut
Farmington, Connecticut
Aktarul Islam Siddique
Annamalai University,
Annamalainagar,
Tamil Nadu, India
Mahesh Thirunavukkarasu
School of Medicine
University of Connecticut
Farmington, Connecticut
Erkan Tuncay
Ankara University
Ankara, Turkey
Belma Turan
Ankara University
Ankara, Turkey
Balazs Varga
University of Debrecen
Hungary
Maayan Waldman
Sheba Medical Center
Sackler School of Medicine
Tel Aviv University, Israel
 1 Introduction
Dilip Ghosh

CONTENTS
1.1 Introduction ...................................................................................................... 1
1.2 What Does Personalization Mean?................................................................... 2
1.3 Where to Go from Here? ..................................................................................2
1.4 Medicalization of Food..................................................................................... 2
1.5 The Genome-Based Health Concept ................................................................ 3
1.6 Way Forward.....................................................................................................3
References..................................................................................................................4

1.1 INTRODUCTION
Today’s nutritional and dietary supplement market is considerably different than it
was 10–15 years ago. Consumer demands for healthy foods have been changing
considerably every year, particularly in the last decade. More and more, consum-
ers believe that foods with specifc functionality contribute directly to their health.
Foods today are not only considered as a vehicle to satisfy hunger and to provide
necessary nutrients but also to prevent nutrition-related diseases and improve physi-
cal and mental well-being. In this scenario, functional food and active ingredients
play an outstanding role. From an economic perspective, this increasing demand on
such foods/nutrition can be justifed by the increasing cost of healthcare, the steady
increase in life expectancy, including infants, and the aspiration and desire of older
people for improved quality of their later years (Roberfroid 2000).
In the 21st century humankind is facing a global pandemic of diet-related chronic
disease and preventable disorders that include cardiovascular disease, obesity and dia-
betes, cancers, osteoporosis and myriad infammatory disorders. These are the leading
cause of the global healthcare burden. Virtually most of these disorders are diet-related
and, not surprisingly, are not responding well to pharmaceutical intervention. The
heavily burdened and eroding healthcare system is in need of an etiology-based model
that addresses the underlying molecular basis of a patient/consumer’s dysfunction and
develops therapeutic and preventive strategies that will include the biochemical-molec-
ular individuality of each person. A genetic predisposition model of health and disease
is emerging from the Human Genome Project that opens up etiology-based care and
will be almost equivalent to the current evidence-based pharmaceutical framework.
The current medical model of genetic determinism is now being challenged by
the emerging concept of genetic susceptibility which enables one to change one’s
health trajectory through the judicious use of diet and lifestyle. In this scenario, inno-
vative, evidence-based food/nutritional and dietary supplements have a signifcant
role in changing our destiny.

1
2 Personalized Nutrition as Medical Therapy for High-Risk Diseases

1.2 WHAT DOES PERSONALIZATION MEAN?

Personalization of nutrition advice is often proposed as one of the most promising
approaches. In recent years, most of the health intervention research and methods
on the effect of personalization show that advice targeted to an individual’s physical
parameters, lifestyle and environmental situation is more effective in infuencing
their health behavior than general information.
It is evident that several dietary components have been recognized to modulate
gene and protein expression and thereby metabolic pathways, homeostatic regulation
and presumably health and disease. In addition, genes also contribute largely to dif-
ferent responses to diet exposure, including interindividual variations in the occur-
rence of adverse reactions. Major potential areas where development of personalized
foods/nutritionals are realistically possible include type 2 diabetes and obesity, mood
foods, Infammatory Bowel Disease (IBD) and disorders of ageing where diet-gene
relationship has been extensively studied.

1.3 WHERE TO GO FROM HERE?

Human desire for individuality is not new. It is embedded in all ancient civiliza-
tions and traditional healthcare system such as Traditional Chinese medicine and
the Indian Ayurvedic system. All traditional medical systems are descriptive and
phenomenological—it typically diagnoses patients using concepts based on the rela-
tionship between signs and symptoms. In Western-style modern medicine model the
concept of ‘one disease—one target—one-size-fts-all’ is shifting towards more per-
sonalization, including the use of multiple therapeutic agents and the consideration
of nutritional, psychological and lifestyle factors when deciding the best course of
treatment. This strategic shift in medical practice is being linked with the discipline
of systems science and systems biology in the biomedical domain. Systems science
aims to understand both the connectivity and interdependency of individual compo-
nents within a dynamic and non-linear system, as well as the properties that emerge
at certain organizational levels. The concepts and practices of systems biology align
very closely with those of traditional Asian medicine as well as the very idea of
‘health’ of the current World Health Organization defnition. Now we know individ-
ual dietary components can modulate and change gene function. Based on the robust
evidence, healthcare professionals are now able to control gene-specifc physiological
expression with specifc dietary intervention. This hypothesis has just become more
attainable for more people due to rising prosperity, particularly in emerging markets.
Moreover, the tremendous technological advancement reduces the gap between desire
and reality by reaching more cost-effective personalized products and services.

1.4 MEDICALIZATION OF FOOD

Since ancient times plants, herbs and other natural products have been used as healing
agents. Advances in organic chemistry from the early 19th century have enabled the
preparation of numerous synthetic medicines. Yet, the majority of the medicinal sub-
stances available today have their origin in natural compounds. The best-known example
Introduction 3

is aspirin (acetylsalicylic acid), originally derived from the bark of the white willow tree.
Other examples include the immunosuppressive cyclosporines, the anthracycline antibi-
otics and the HMG-CoA reductase inhibitors, commonly known as statins. Traditionally,
pharmaceuticals have been used to cure diseases or to alleviate the symptoms of disease.
Nutrition, on the other hand, is primarily aimed at preventing diseases by providing the
body with the optimal balance of macro- and micronutrients needed for good health.
Due to the emerging knowledge of disease, medicines are now increasingly being
used to lower risk factors, and thereby to prevent chronic diseases. Prime examples
are blood pressure-lowering and blood lipid-lowering agents which reduce the risk of
cardiovascular disease. The appearance of functional foods and dietary supplements
on the market has further blurred the distinction between pharma and nutrition.
However, it is important to distinguish the target and effective outcome of pharma
and nutra intervention.

1.5 THE GENOME-BASED HEALTH CONCEPT

Nutritional genomics is a promising new research and development area and as a
young and blue-sky science, it is also associated with intense debate. With high
hope to many researcher’s nutritional genomics is closely associated with ‘personal-
ized nutrition,’ in which the diet of an individual is customized based on their own
genomic/genetic information, to optimize health and prevent the onset of disease. In
this context ‘nutritional genomics is largely concerned with elucidating the interac-
tive nature of genomic, dietary and environmental factors and how these interactions
impact on health outcomes’ (Brown and van der Ouderaa 2007).
Scientists have determined that genetic expression is infuenced by ‘endogenous and
exogenous factors and therefore particularly prone to nutritional imprinting’ (Ruemmele
and Garnier-Lengline 2012). Moreover, nutrition and genes interact in two different
ways. The term ‘nutrigenomics,’ where the impact of nutritional factors on gene regula-
tion and expression is considered. The other way, ‘nutrigenetics,’ examines the infuence
genetic variation has on, or predetermines, nutritional requirements. Both interactions
are important considerations for designing a personalized nutrition concept.
Traditionally (and in most of the cases currently), nutrition counseling and rec-
ommendations have been offered based on population. An example of such a rec-
ommendation is the dietary reference values for calcium: adults between 19 and
60 years of age should consume 1,000 mg per day. This recommendation does not
account for individual genetic variations in the ability to absorb and metabolize this
mineral. Another example is that of ‘dietary interventions as primary prevention to
reduce the risk of cardiovascular disease’ (de Roos 2013). Without a valid popula-
tion-based strategy, the population-based intervention does not address the possibil-
ity of subgroups’ differences in response to the intervention. Personalized nutrition
would address such individual variations.

1.6 WAY FORWARD

Currently, personalized medicine and nutrition are not extensively applied on a
routine basis at patients’ clinics and by their carers: doctors, nurses, dietitians or
4 Personalized Nutrition as Medical Therapy for High-Risk Diseases

nutritionists. Recent studies published in last few years not only underline the thera-
peutic potential of lifestyle interventions but are also generating valuable insights in
the complex and dynamic transition from health to disease continuum.
This book discusses the recent developments in the pharmaceutical-nutrition
interface and relevant mechanisms, including receptors and other targets. A few
clinical practice-based examples are cited in this book.
Several dedicated chapters deal with nutraceutical intervention to manage or treat
physiological conditions and diseases such as cardiovascular disease, hypertension,
Crohn’s disease, chronic kidney disease, hypercholesteremia, maternal and offspring
metabolic disorders and psychological disorders. Two more interesting areas covered
in this book are the role of caloric restriction in obesity and diabetic heart disease
and the effect of high carbohydrate diet-induced metabolic syndrome in the over-
weight body.
It is evident that pharmaceutical industry will beneft from nutritional genomics
knowledge and a physiological approach that puts health above diseases and medical
conditions (Ghosh, Skinner et al. 2007). This will help us to get a better understand-
ing about the transition between health, homeostatic resilience and chronic disease,
to develop better and more tailored treatment options. The personalized nutrition
market is in many ways an unknown space for the ‘Big Pharma’ players. To over-
come this weakness, they are taking on strategic partnerships, collaborations and
acquisitions. As a result, we should expect further partnerships between big pharma
companies and tech start-ups enabling them to be in this growing trend for personal-
ized products.
Experience shows that commercial providers are keen to proceed to the market
with products before the scientifc evidence is established. This can only be checked
if there are national and international agreed guidelines for using genotype-based
advice in personalized nutrition. The Food4Me consortium (Grimaldi, van Ommen
et al. 2017) has proposed such guidelines recently, but the research and regulatory
communities have to evaluate and agree on the proposed guidelines.

REFERENCES
Brown, L. and F. van der Ouderaa (2007). “Nutritional genomics: food industry applications
from farm to fork.” Br J Nutr 97(6): 1027–1035.
de Roos, B. (2013). “Personalised nutrition: ready for practice?” Proc Nutr Soc 72(1): 48–52.
Ghosh, D., M. A. Skinner, et al. (2007). “Pharmacogenomics and nutrigenomics: synergies
and differences.” Eur J Clin Nutr 61(5): 567–574.
Grimaldi, K. A., B. van Ommen, et al. (2017). “Proposed guidelines to evaluate scientifc
validity and evidence for genotype-based dietary advice.” Genes Nutr 12: 35.
Roberfroid, M. B. (2000). “Concepts and strategy of functional food science: the European
perspective.” Am J Clin Nutr 71(6 Suppl): 1660S–1664S; discussion 1674S–1665S.
Ruemmele, F. M. and H. Garnier-Lengline (2012). “Why are genetics important for nutrition?
Lessons from epigenetic research.” Ann Nutr Metab 60(3 Suppl): 38–43.
 2 The New Era of Nutrition
Personalized Nutrition

Diego Accorsi, Seetur R. Pradeep, Jennifer

Hubbard, Rajesh Lakshmanan, Nilanjana
Maulik and Mahesh Thirunavukkarasu

CONTENTS
2.1 Introduction ......................................................................................................5
2.1.1 Defning Personalized Nutrition........................................................... 6
2.1.2 Origins of Personalized Nutrition as a Formal Scientifc Ideology......6
2.2 Theoretical Basis for Personalized Nutrition ................................................... 8
2.3 Current Perspectives on Personalized Nutrition...............................................8
2.3.1 Nutrient-Gene Interactions ...................................................................9
2.3.1.1 Biomarkers.............................................................................9
2.3.2 Altering Human Behavior .................................................................. 13
2.3.3 Age and Stages of Life........................................................................ 16
2.3.4 Gender................................................................................................. 16
2.3.5 Environment: The Exposome ............................................................. 19
2.3.5.1 The Microbiome................................................................... 19
2.3.6 Personalized Nutritional Strategies for Athletic Performance ...........20
2.4 Closing Remarks.............................................................................................20
Abbreviations ...........................................................................................................20
References................................................................................................................ 21

2.1 INTRODUCTION
Diet and nutrition have historically been regarded as important factors in the promo-
tion and maintenance of health throughout the entire life span and had until very
recently played a leading role in the management of disease, according to epide-
miological studies (Kussmann and Fay 2008). For example, Hippocrates, heralded
as the father of modern medicine, once said: ‘Let the food be thy medicine and the
medicine be thy food.’ Since then our understanding of the specifc microbiological
mechanisms through which nutrition contributes to overall health and disease con-
tinues to grow but, with the advent of pharmacotherapy, nutrition has taken a back-
seat as a tool to improve health in modern medicine. Nutritional recommendations
for the otherwise healthy often follow a generalized, ‘one-size-fts-all’ approach
aimed primarily at weight loss, while formal nutritional guidelines as prescribed
by clinicians apply only to subpopulations at risk, such as diabetics, while failing to

5
6 Personalized Nutrition as Medical Therapy for High-Risk Diseases

account for an individual’s unique characteristics. Enter the concept of personalized

nutrition, which in essence attempts to identify fuctuations from the baseline, and
correct these deviations through individualized nutritional recommendations using
state-of-the-art technologies to track and process unique and essential biological and
environmental variables (Kussmann and Fay 2008). Put more simply; it is not only
about eating ‘good’ food, but also about eating food that is ‘right’ for you (Rucker
2019). This chapter has two primary objectives: to defne personalized nutrition, as
well as exploring its relevance and importance in the 21st century by highlighting a
few popular topics of discussion.

2.1.1 DEFINING PERSONALIZED NUTRITION

There is no clear-cut defnition for personalized nutrition, but in general, it may be
thought to include three important tenets. Firstly, it is the provision of nutritional
advice adapted to an individual’s unique internal and external infuences. It is noth-
ing but a specially tailored recommendation of a dietary habit for an individual to
maintain good health and lifestyle. Secondly, personalized nutritional interventions
can only be effective if they translate into behavioral change towards a healthy life-
style. And lastly, personalized nutrition should be equally applicable to a healthy
individual in order to improve overall public health, as well as patients afficted
with, or susceptible to, specifc medical conditions (Ordovas, Ferguson et al. 2018).
Because of its origins during the exciting period of genomic sequencing, the term
still partially overlaps with some closely related terms such as nutrigenomics, nutri-
genetics, gene-food interactions, etc. (Table 2.1), but it is important to note that since
then personalized nutrition has become very multifaceted and includes an individ-
ual’s behavior, dietary habits/cultural infuence, food availability, phenotypic and
genetic makeup, metabolism and even the microbiome. Some of these terms will be
explained in further detail later in this chapter.

2.1.2 ORIGINS OF PERSONALIZED NUTRITION AS A FORMAL SCIENTIFIC IDEOLOGY

American biochemist Roger J. Williams (1893–1988), known for his work on B
vitamins, made one of the frst mentions of the gene food interaction in an article
published in 1950 entitled “Concept of genetotrophic disease.” In short, Williams
believed that ‘a genetotrophic disease is one which occurs if a diet fails to provide
suffcient supply of one or more nutrients required at high levels because of the
characteristic genetic pattern of the individual concerned’ (Kraemer, Cordaro et
al. 2016; Williams, 1950). At the time, the infuence of genetics was a new medi-
cal concept that was thought to be the basis of many conditions, and though this
paved the way for the personalization of medical treatment in general, the underlying
mechanisms were still unknown, and the tools necessary to put ideas into practice
were still undiscovered. Therefore, the concept was to remain in a dormant stage
until the advent of human genome sequencing, which heralded a boom in research
focusing on gene-phenotype and gene-environment interactions. Soon after, the term
‘personalized nutrition’ surfaced as an entity unto itself, which extended the use of
genetic data from the creation of new therapeutic approaches to the improvement
Defning Personalized Nutrition 7

TABLE 2.1
Descriptors and Defnitions
In common with other scientifc felds in their early development, multiple concepts and descriptors are
used in personalized nutrition, sometimes without rigorous defnition. In addition to the term personalized
nutrition, many other terms are used—for example, precision nutrition, stratifed nutrition, tailored
nutrition and individually tailored nutrition. We have attempted to group the descriptors as follows:
• Stratifed and tailored nutrition are similar (if not synonymous). These approaches attempt to group
individuals with shared characteristics and to deliver nutritional intervention/advice that is suited to
each group.
• Personalized nutrition and individually tailored nutrition mean similar things and go a step further by
attempting to deliver nutritional intervention/advice suited to each individual.
• Precision nutrition is the most ambitious of the descriptors. It suggests that it is possible to have
suffcient quantitative understanding about the complex relationships between an individual, his/her
food consumption and his/her phenotype (including health) to offer nutritional intervention/advice,
which is known to be individually benefcial. The degree of scientifc certainty required for precision
nutrition is much greater than that required for the other approaches.
• Nutrigenetics is an aspect of personalized nutrition that studies the different phenotypic responses (i.e.
weight, blood pressure, plasma cholesterol or glucose levels) to a specifc diet (i.e. low fat or
Mediterranean diets), depending on the genotype of the individual.
• Nutrigenomics involves the characterization of all gene products affected by nutrients and their
metabolic consequences.
• Exposome is the collection of environmental factors, such as stress, physical activity and diet, to
which an individual is exposed and which may affect health. As one moves from stratifed to
personalized to precision nutrition, it becomes necessary to apply more and more dimensions or
characteristics to achieve the desired goal. For example, stratifcation could be undertaken using one,
or a few, dimensions such as age, gender or health status. In contrast, given the complexity of
relationships between individual diet and phenotype, deployment of a wide range of dimensions/
characteristics, perhaps including ‘big data’ approaches, would be necessary to achieve the goal of
precision nutrition. An exception to this broad generalization is the management of inborn errors of
metabolism such as phenylketonuria, where ‘precision nutrition’ can be achieved using information on
a single characteristic—that is, genotype.
• Epigenomics is a branch of genomics concerned with the epigenetic changes (methylation, histone
modifcation, microRNAs) that modify the expression and function of the genetic material of an
organism.
• Metabolomics is the scientifc study and analysis of the metabolites (usually restricted to small
molecules, i.e. <900 daltons) produced by a cell, tissue or organism.
• Microbiomics is the study of the microbiome, the totality of microbes in specifc environments (i.e.
the human gut).

Ordovas, Ferguson et al. (2018)

of nutritional management. In a report by the Institute for the Future in Palo Alto,
2003, a suggestion was made that within a decade most adults would make at least
part of their nutritional choices based on knowledge of their genetic makeup and
inherent susceptibilities to different foods. While this prediction did not come to
fruition in its entirety by the proposed deadline, that decade did see the beginnings
of formalized, funded personalized nutritional research, including the Food4Me
8 Personalized Nutrition as Medical Therapy for High-Risk Diseases

consortium, which eventually led a fve-year project, the largest to date, exploring
various elements involved in personalized nutrition using complex multidisciplinary
approaches (Kraemer, Cordaro et al. 2016).

2.2 THEORETICAL BASIS FOR PERSONALIZED NUTRITION

In recent years, the emergence of advances in the feld of nutrition and health,
such as epigenomics, metabolomics, microbiomics, the study of how the environ-
ment affects the individual (i.e. the “exposome”), accessible data collection tech-
nologies such as mobile apps and ftness trackers, and cutting edge analytical tools,
have enabled us to study multiple factors simultaneously to predict an individual’s
response to dietary interventions (Siroux, Agier et al. 2016). As a result, research
has since surfaced to reveal a signifcant amount of interindividual variability in
response to dietary intervention (Mathers 2019). For example, it is widely known
that drastic changes in blood glucose concentrations after a meal (glycemia) can be
detrimental. Zeevi, Korem et al. (2015) proved in one of their studies that despite
the provision of standardized meals, there is signifcant interindividual variability
in blood glucose levels. This is unsurprising as it is well established that glycemic
response is determined not only by the type or quantity of food consumed but also
by the attributes of the individual consuming the food (Vega-Lopez, Ausman et
al. 2007). Selecting glycemia as their parameter/outcome of interest they set out to
examine whether or not their predictive tool would be successful at deriving indi-
vidually tailored nutritional intervention based on individual characteristics such
as blood-work, anthropometry and gut microbiome. This predictive tool called the
‘Personalized Nutrition Predictor,’ was shown to anticipate with fair accuracy the
glycemic response of individual subjects to different meals. Very recently, authors
Mendes-Soares, Raveh-Sadka et al. (2019) used a similar model in their study which
involved 327 individuals. They similarly observed that the inclusion of data gath-
ered from each individual was more likely to accurately predict postprandial blood
glucose concentration than using energy and/or carbohydrate content of foods alone
(Mendes-Soares, Raveh-Sadka et al. 2019). To date, however, only a handful of high
level, human dietary intervention studies have tested the concept of personalized
nutrition in a clinically relevant setting.

2.3 CURRENT PERSPECTIVES ON PERSONALIZED NUTRITION

The idea of personalized nutrition is that individual nutritional advice will be more
effective at reaching target goals than the more generic approaches which are the
basis for most current dietary interventions. This idea may fundamentally change
the way consumers make food choices that ft with lifestyle preferences and health
goals. Most studies that have contributed to the scientifc basis for personalization of
nutrition are based on genetics, which, along with the metabolome and microbiome,
represent biological or ‘intrinsic’ factors. This includes an understanding of the bio-
logical response to dietary modifcations, whether single component (e.g. low fat, low
cholesterol, low sodium, etc.) or whole diet interventions, and their effect on indica-
tors of health and disease risk (Biesiekierski, Livingstone et al. 2019). While it is true
Defning Personalized Nutrition 9

that in recent years much attention has been paid to deciphering the human genome
and its infuence on disease risk, genes are only a small part of a very broad picture.
There are many other factors, both intrinsic and extrinsic, such as age, stage of life
(pregnant, lactating, etc.), sex, race, ethnicity and cultural or religious backgrounds,
which can infuence the effect of diet on the body (Ordovas, Ferguson et al. 2018).
Due to the inherent complexity of analyzing all the factors that make an individual
unique, the biggest challenge of personalized nutrition is its study and execution in
real-life situations. Therefore, the process will not only require an understanding of
an individual’s genetic makeup and susceptibility, but also biological substantiation
of an individual’s responses to food/nutrient consumption manifested as changes in
specifc measurable parameters (biomarkers, microbiota), analysis of sociobehav-
ioral patterns, food choice and availability, troubleshooting obstacles at all points
in the pipeline, and clear demarcation of objectives to inspire and facilitate eating
pattern modifcation (Ordovas, Ferguson et al. 2018).

2.3.1 NUTRIENT-GENE INTERACTIONS

Heralding back to the origins of personalized nutrition, the diet-gene interaction is
perhaps the most researched aspect of the feld, with several examples of researched
gene-food interactions published to date (Table 2.2). Though individuals share the
clear majority of their genes in common, the relatively few differences are enough
to cause signifcant alterations in phenotype, including the way individuals respond
to their diet. Changes to phenotype may evoke changes in behavior, physiological
characteristics or susceptibility to diseases as well. Of these genetic differences held
accountable for phenotypic diversity, it is increasingly apparent that single nucleotide
polymorphisms (SNPs), the most known and common genetic variations between the
human beings, will be a key factor.
The study of diet-gene interactions can be loosely sub-classified into two
distinct study areas: nutrigenetics and nutrigenomics. Nutrigenetics deals with
how genetic makeup influences the way nutrients are acquired, metabolized
and stored, while nutrigenomics is the study of how food components influ-
ence gene expression. Nutrigenetics plays more of a preventative role, gener-
ally delineating the foods that should be avoided because they could place the
individual at risk for disease. On the other hand, nutrigenomics also has the
potential to transform diet into a therapeutic tool to treat diseases, similar to
pharmaceutical drugs. It is based on identification of genetic risk factors and
targeting of key players of gene expression at any given stage, to up- or down-
regulate the effects of certain genes.

2.3.1.1 Biomarkers
In order to monitor changes to an individual’s physiology and gene expression, it
becomes necessary to use biomarkers; these can represent certain physiologic
parameters such as blood pressure, components of the metabolome, or may also
be one of many molecules involved in the complex cascades responsible for gene
expression. The most valuable biomarkers are those that are easy/cheap to obtain and
measure. It is also necessary to defne a normal range that equates to the “healthy
10 Personalized Nutrition as Medical Therapy for High-Risk Diseases

TABLE 2.2
Summary of Genetic Variants That Modify the Association between Various
Dietary Factors and Performance-Related Outcomes
Gene (RS Function Dietary Dietary Performance-Related
Number) Factor Sources Outcome
CYP1A2 Encodes CYP1A2 Caffeine Coffee, tea, Cardiovascular health,
(rs762551) liver enzyme: soda, energy endurance (Clenin et
metabolizes drinks, al., 2015; Haas &
caffeine; identifes caffeine Brownlie, 2001;
individuals as fast supplements Palatini et al., 2009;
or slow metaboliz- Soares, Schneider,
ers Valle, & Schenkel,
2018)
ADORA2A Regulates myocardial Caffeine Coffee, tea, Vigilance when fatigued,
(rs5751876 oxygen demand; soda, energy sleep quality (Begas,
increases coronary drinks, Kouvaras, Tsakalof,
circulation via caffeine Papakosta, &
vasodilation supplements Asprodini, 2007;
Ghotbi et al., 2007;
Hunter, St Clair
Gibson, Collins,
Lambert, & Noakes,
2002; Yang, Palmer, &
de Wit, 2010)
BCMO1 Converts pro-vitamin Vitamin A Bluefn tuna, Visuo-motor skills and
(rs11645428) A carotenoids hard goat immunity (Czarnewski,
toVitamin A cheese, eggs, Das, Parigi, &
mackerel, Villablanca, 2017;
carrots, Ferrucci et al., 2009;
sweet potato Garvican et al., 2014;
Lietz, Lange, &
Rimbach, 2010; Lietz,
Oxley, Leung, &
Hesketh, 2012; Palidis,
Wyder-Hodge, Fooken,
& Spering, 2017)
MTHFR Produces the Folate Edamame, Megaloblastic anemia
(rs1801133) enzyme methylene- chicken liver, and hyperhomocystein-
tetrahydrofolate lentils, emia risk (Curro et al.,
reductase, which is asparagus, 2016; Dinc, Yucel,
involved in the black beans, Taneli, & Sayin, 2016;
conversion of folic kale, Goyette et al., 1994;
acid and folate into avocado Guinotte et al., 2003)
their biologically
active form,
L-methylfolate
(Continued )
Defning Personalized Nutrition 11

TABLE 2.2 (CONTINUED)

Summary of Genetic Variants That Modify the Association between Various
Dietary Factors and Performance-Related Outcomes
Gene (RS Function Dietary Dietary Performance-Related
Number) Factor Sources Outcome
HFE Regulates intestinal Iron Beef, chicken, Hereditary hemochroma-
(rs1800562 iron uptake fsh, organ tosis (Marjot, Collier, &
and meats (heme Ryan, 2016; Pantopou-
rs1799945) iron); almonds, los, Porwal, Tartakoff,
parsley, spinach & Devireddy, 2012;
(non-heme Recalcati, Minotti, &
iron) Cairo, 2010)
TMPRSS6 Regulate the peptide Iron Beef, chicken, Iron-defciency anemia
(rs4820268), hormone, hepcidin, fsh, organ risk (Allen et al., 2008;
TFR2 which controls iron meats (heme Benyamin et al., 2009;
(rs7385804), absorption iron); Cannell, Hollis,
TF almonds, Sorenson, Taft, &
(rs3811647) parsley, Anderson, 2009; Garcia
spinach et al., 2014; Soranzo et
(non-heme al., 2009; Vidoni, Pettee
iron) Gabriel, Luo, Simon-
sick, & Day, 2018)
FUT2 Involved in vitamin Vitamin B12 Clams, Megaloblastic anemia
(rs602662) B12 cell transport oysters, and hyperhomocystein-
and absorption herring, emia (Reardon & Allen,
nutritional 2009)
yeast, beef,
salmon
GSTT1 (Ins/ Plays a role in Vitamin C Red peppers, Circulating ascorbic acid
Del) vitamin C strawberries, levels mitigate
utilization via pineapple, exercise-induced ROS
glutathione oranges, production (Braakhuis,
S-transferase broccoli 2012; Shaw, Lee-Bar-
enzymes thel, Ross, Wang, &
Baar, 2017)
GC GC encodes vitamin Vitamin D Salmon, white Circulating 25(OH)D
(rs2282679) D-binding protein, fsh, rainbow levels impacting
and CYP2R1 involved in binding trout, halibut, immunity, bone health,
(rs10741657) and transporting milk infammation, strength
vitamin D to tissues; training and recovery
CYP2R1 encodes (Barker, Schneider,
the enzyme vitamin Dixon, Henriksen, &
D 25-hydroxylasein- Weaver, 2013;
volved in vitamin D Larson-Meyer & Willis,
activation 2010; Thomas, Erdman,
& Burke, 2016; Wang et
al., 2010; Yucha C, 2003)
(Continued )
12 Personalized Nutrition as Medical Therapy for High-Risk Diseases

TABLE 2.2 (CONTINUED)

Summary of Genetic Variants That Modify the Association between Various
Dietary Factors and Performance-Related Outcomes
Gene (RS Function Dietary Dietary Performance-Related
Number) Factor Sources Outcome
GC (rs7041 GC encodes vitamin Calcium Yogurt, milk, Bone/stress fracture risk
and rs4588 D-binding protein, cheese, frm Muscle contraction,
involved in binding tofu, canned nerve conduction, blood
and transporting salmon (with clotting (Barker et al.,
vitamin D to tissues; bones), 2013; Larson-Meyer &
Vitamin D is edamame Willis, 2010; Thomas et
required for calcium al., 2016; Wang et al.,
absorption 2010; Yucha C, 2003)
PEMT Involved in Choline Eggs, beef, Muscle or liver damage,
(rs12325817) endogenous choline poultry, fsh, reduced neurotransmitters
synthesis via the shrimp, (Elsawy, Abdelrahman, &
hepatic phosphati- broccoli, Hamza, 2014; Kohlmeier,
dylethanolamine salmon da Costa, Fischer, &
N-methyl-transferase Zeisel, 2005; Zeisel,
pathway 2006; Zeisel et al., 1991)
MTHFD1 Encodes protein Folate/ Folate: Muscle or liver damage,
(rs2236225) involved in Choline Edamame, reduced neurotransmit-
trifunctional chicken liver, ters (Elsawy et al., 2014;
enzyme activities lentils, Kohlmeier et al., 2005)
related to metabolic asparagus,
handling of choline black beans,
and folate kale, avocado
Choline: Eggs,
beef, poultry,
fsh, shrimp,
broccoli,
salmon
FTO Precise function Protein/ Protein: chicken, Optimizing body
(rs1558902/ undetermined; plays SFA:PUFA beef, tofu, composition (Knapik,
rs9939609) a role in metabolism salmon, cottage 2015; Krieger, Sitren,
and has been cheese, lentils, Daniels, & Langkamp-
consistently linked milk, Greek Henken, 2006)
to weight, BMI and yogurt
body composition SFA: cheese,
butter, red
meat, baked
goods
PUFA: faxseed
oil, grape seed
oil, sunfower
oil
(Continued )
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