Nutrogenomics and Exercise

NUTROGENOMICS &EXERCISE
AMNA NASEER
97-ag-628
M.Sc(HONS)1st SEMESTER
FOOD & NUTRITION
UNIVERSITY OF AGRICULTURE
ASSIGNMENT PRESENTED TO:
DR.ALI RAZA
Nutrigenomics research:
A review Article in Journal of Food Science and Technology -
Mysore- · June 2013
DOI: 10.1007/s13197-012-0775-z
CITATIONS
44
READS
5,031
2 authors:
Some of the authors of this publication are also working on these related projects:
Non Dairy food products View project
Confectionery food products View project
Neeha V S
1 PUBLICATION 44 CITATIONS
SEE PROFILE
Priyamvadah Kinth
National Institute of Science Technology and Development Studies
2 PUBLICATIONS 64 CITATIONS
SEE PROFILE
All content following this page was uploaded by Neeha V S on 27 May 2014.
The user has requested enhancement of the downloaded file.
REVIEW-INVITED ARTICLE
Nutrigenomics research: a review
V. S. Neeha & Priyamvadah Kinth
Revised: 29 June 2012 / Accepted: 2 July 2012 / Published online: 19 July 2012
# Association of Food Scientists & Technologists (India) 2012
Abstract The excitement about nutrigenomics comes from
a growing awareness of the potential for modifications of
food or diet to support health and reduce the risk of dietrelated
diseases. It is an emerging field that tends to unfold
the role of nutrition on gene expression which brings together
the science of bioinformatics, nutrition, molecular
biology, genomics, epidemiology, and molecular medicine.
The present review focuses on nutrigenomics research and
to find out India’s status with respect to other countries. It
covers the general overview of nutrigenomics, its associated
diseases, and the role of SNP in gene alteration, diet supplementation
and public awareness. It is understood that
with the increasing changes in the food habits and life styles,
people are becoming more prone to diet related disorders.
Therefore there is an urgent need to boost more research in
this field to help people in understanding the relationship
between diet and health, and to ensure that everyone benefits
from the genomic revolution.
Keywords Nutrigenomics . Diet-gene interaction .
Nutrition . Food supplement . Diabetes . Obesity
Introduction
“The new science of nutrigenomics teaches us what specific
foods tell your genes. What you eat directly determines the
geneticmessages your body receives. Thesemessages, in turn,
control all the molecules that constitute your metabolism: the
molecules that tell your body to burn calories or store them. If
you can learn the language of your genes and control the
messages and instructions they give your body and your
metabolism, you can radically alter how food interacts with
your body, lose weight, and optimize your health.” (Mark
Hyman 2006)
Origin of nutrigenomics The concept that diet influences
health is an ancient one. Nutrigenomics includes known
interactions between food and inherited genes, called ‘inborn
errors of metabolism,’ that have long been treated by
manipulating the diet. One such example is Phenylketonuria
(PKU); it is caused by a change (mutation) in a single gene.
Affected individuals must avoid food containing the amino
acid phenylalanine. Another example is lactose intolerance,
majority of adults in the world are lactose intolerant, meaning
that they cannot digest milk products, because the gene
encoding lactase, the enzyme that breaks down lactose, is
normally ‘turned off after weaning. However some 10,000–
12,000 years ago a polymorphism in a single DNA nucleotide
appeared among northern Europeans. This single nucleotide
polymorphism—a SNP—resulted in the continued
expression of the lactase gene into adulthood. This was
advantageous because people with this SNP could utilize
nutritionally-rich dairy products in regions with short growing
seasons and with the revolution in molecular genetics in
the late twentieth century, scientists set out to identify other
genes that interact with dietary components. By the 1980s
companies were commercializing nutrigenomics. The
Human Genome Project of the 1990s, which sequenced
the entire DNA in the human genome, jump-started the
science of nutrigenomics. By 2007 scientists were discovering
numerous interrelationships between genes, nutrition,
and disease.
Nutrigenomics brings along new terminology, novel experimental
techniques and a fundamentally new approach to
nutrition research, such as high-throughput technologies that
enables the global study of gene expression in a cell or
organism.
Nutrigenomics would require a collaborative effort from
people in genetics and the industries of public health, food
V. S. Neeha (*) : P. Kinth (*)
NISCAIR (National Institute of Science Communication and
Information Resources),
14 – Satsang Vihar Marg, Spl. Institutional Area,
New Delhi 110067, India
e-mail: neehafoodtech@gmail.com
e-mail: bioinformatics.priya@gmail.com
J Food Sci Technol (May–June 2013) 50(3):415–428
DOI 10.1007/s13197-012-0775-z
science and culinary. It’s very easy to make good-tasting
food. Put some lard or butter in it, and it’s going to taste good.
The challenge is how to take the fat out and create healthful
but also good-tasting food.” Therefore a shift in public health
is greatly needed, and with an increasing incidence of obesity
and chronic diseases such as type-2 diabetes, nutrigenomics
might prove to be the panacea in the future.
Increasing rates of chronic disease
World health scenario Despite the worldwide increasing
rates, chronic diseases remain surprisingly neglected in the
global health agenda. Because of changes in dietary and
lifestyle habits—a phenomenon that can be linked to the
whole globalization process—developing countries now face
a fast “epidemiological accumulation” of non-communicable
and infectious diseases and must cope with urgent and
competing health priorities. Non-communicable diseases
(NCDs)—especially cardiovascular diseases, cancers, chronic
respiratory diseases and diabetes—caused 60 % deaths globally
in 2005 (approximately 35 million deaths). Total deaths
from NCDs are projected to increase by a further 17 % over
the next 10 years. By 2020, it is predicted that NCDs will
account for 80 % of the global burden of disease, causing
seven out of every 10 deaths in developing countries. This
places a considerable (double) burden on limited health budgets,
particularly in emerging economies. Thus the promises of
nutrigenomics must be addressed with respect to this current
growing epidemic, both in developed and developing
countries (Gobard and Hurlimann 2009).
India’s health scenario In India, the rates of fatal diseases
are lower than those seen in Western countries. However,
this rate is rising with increasing migration of rural population
to cities and changes in lifestyles (Rao 2001; Shetty
2002; Sharma and Majumdar 2009). In recent decades,
consumption of food grains also has shifted from coarse
grains to refined rice and wheat (Sinha et al. 2003) (Table 1).
India has some of the highest Coronary Heart Disease
(CHD) rates in the world, with urban rates being three times
higher than rural rates. In addition, rates for obesity (Fig. 3a
and b) and diabetes are increasing dramatically in urban
areas and in high-income rural residences (Sinha et al.
2003) (Fig. 1). Obesity is related to several chronic diseases,
including type-2 diabetes, hypertension, cardiovascular diseases,
various types of cancers and psychosocial problems.
The major reasons for its development are changing lifestyles
and food habits. Diet appears to be related to the high
rates of CHD, obesity, and diabetes (Hossain et al. 2007;
Kaput et al. 2007); although a genetic component may exist
in some cases (Fig. 2). Therefore, a general awareness of
diet and diet related problems leading to gene alteration has
to be known and for this nutrigenomics should be studied
extensively (Fig. 3).
Global status of nutrigenomics research (as per Scopus
database)
Country-wise and subject-wise analysis To unravel the
mystery of these chronic diseases, nutrigenomics work is
booming in many parts of the world. According to Scopus
database, US and UK have the highest contribution, while
India is in 16th position, suggesting that nutrigenomics research
in India is still in the infancy. This data was obtained
by giving the following search terms: “Nutrigenomics”,
“Nutrigenetics”, and “Diet-gene interaction” in Scopus database.
A total of 1072 recordswere obtained whichwere refined
on the basis of document type. The 769 records obtained after
refining were then analysed. The contribution of top 20
countries shows that India has only 14 papers while US and
UK have 210 and 97 papers respectively as per the Scopus
results (Fig. 4). Subject-wise analysis shows that nutrigenomics
work is mainly done in the fields of Medicine;
Biochemistry, Genetics and Molecular Biology; Agricultural
and Biological Sciences and Nursing (Fig. 5).
Objective
The present review aims at giving an insight on the nutrigenomics
research (focusing on India) so as to bring
& public awareness about the changing lifestyle and food
habits,
& how nutrigenomics can contribute in making life longer,
healthier and better,
& encourage more research in this field.
Methodology
A literature search on nutrigenomics focusing on India was
conducted by using various databases: Web of Science, Bio
Table 1 Change in dietary pattern
Nutrients Paleolithic diet Modern Diet
Protein ~ 30–40 % 10–20 %
Carbohydrates ~ 35 % 60–70 %
Sugars ~ 2–3 % 15 %
Fats ~ 30–35 % 30–35 %
Saturated fats ~ 7.5 % 15–30 %
Trans-fat < 1 % 5–10 % of fats
Omega-6/omega-3 ~ 2:1 10–20:1
Source: Melvyn A Sydney-Smith
416 J Food Sci Technol (May–June 2013) 50(3):415–428
Med Central, Taylor & Francis, PubMed, Science Direct,
Springer and National Center for Biotechnology
Information (NCBI) and Scopus Database to find out the
global status of nutrigenomics research. The study used the
following search terms: Nutrigenomics India, Nutrigenetics,
Diet-gene Interaction, Gene-Environment Interaction, and
Nutraceutical etc. We also examined bibliographies of all
studies for other potential citations. Although these databases
covered many papers on Diet-gene interaction but few
papers were found on nutrigenomics work in India. Other
than nutrigenomics we have also reviewed some of the
works done in the areas of diet supplementation, deficiency
diseases, diet-gene interaction, dietary guidelines etc.
Nutrigenomics overview
Throughout the 20th century, Nutritional Science focused
on finding vitamins (Ghoshal et al. 2003) and minerals
(Menon et al. 2010), defining their use and preventing the
deficiency diseases (Gopalan 1992; Godbole et al. 2009;
Rao 2001; Naushad et al. 2010) that they caused. As nutrition
related health problems of the developed world shifted
to overnutrition, obesity (Raj et al. 2007) and type-2 diabetes
(Mohan et al. 2007a, b), the focus of modern medicine
and of Nutritional Science changed. To prevent the development
of these types of disease, nutrition research is investigating
on how nutrition can optimize and maintain
cellular, tissue, organ and whole body homeostasis. This
requires understanding how nutrients act at the molecular
level which in turn involves a multitude of nutrient-related
interactions at the gene, protein and metabolic levels. As a
result, nutrition research shifted from Epidemiology and
Physiology to Molecular Biology and Genetics and nutrigenomics
was born.
Nutrigenomics involves the characterisation of gene
products, their physiological function and their interactions.
It focuses on the effect of nutrients on genome, proteome,
0 10 20 30 40 50 60 70 80
Diabetic Subjects
2000
2006
2025
2030
Year
Diabetic Subjects in India (million)
Fig. 1 Estimated number of
Diabetic subjects in India.
Source: Mohan et al.
2007a, b
Estimated mortality from coronary heart disease (CHD)
0
500,000
1,000,000
1,500,000
2,000,000
2,500,000
3,000,000
3,500,000
2000 2005 2010 2015
Years
Death in age groups (%) Total deaths
20-29
30-39
40-49
50-59
60-69
Fig. 2 Estimated mortality
from coronary heart disease.
Source: Trehan 2006
J Food Sci Technol (May–June 2013) 50(3):415–428 417
metabolome (Fig. 6) and explains the relationship between
these specific nutrients and nutrient-regimes on human
health.
Overall, a Nutrigenomic approach provides:
& a snapshot showing genes that are switched on/off (the
genetic potential) at any given moment;
& a view of how gene/protein networks may collaborate to
produce the observed response; and
& the method to determine the influence of nutrients on
gene/protein expression.
It is hoped that by building up knowledge in this area, it
will promote an increased understanding of how nutrition
influences metabolic pathways and homeostatic control,
which will then be used to prevent the development of
chronic diet related diseases such as obesity and type-2
diabetes (Ramachandran 2006; Kandaswamy 2011; Pathak
et al. 2000).
Nutrigenomics research tools
The new tools now available in the post-genomic era opens
a new future for nutritionists to screen the genetic background,
to monitor the transcriptome, proteome and metabolome
and to ultimately develop dietary strategies which are
22%
78%
31%
69%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Men 2005 Men 2015
Overweight
Not overweight
21%
79%
29%
71%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Women 2005 Women 2015
Overweight
Not overweight
a
b
Fig. 3 a Projected prevalence
of overweight males in India
aged 30 years or more, 2005
and 2015. Source: WHO
Report b Projected prevalence
of overweight females in India
aged 30 years or more, 2005
and 2015. Source: WHO
Report
0
50
100
150
200
250
United States
United Kingdom
Spain
Netherlands
Canada
France
Italy
Germany
New Zealand
Switzerland
Australia
Japan
China
Ireland
Denmark
India
Greece
Sweden
Poland
South Korea
Countries
No. of Papers
Fig. 4 Country-wise
contribution to nutrigenomics
research. Source: Scopus
Database
targeted to supply the optimum nutrition for single individuals.
These tools are the focus of the emerging field of
nutrigenomics.
The use of microarray technologies—the main tools of
transcriptomics, has allowed new information concerning
the physiological effect of different dietary proteins, of
omega-3 polyunsaturated fatty acids and dietary conditioning
of colon cancer. DNA microarray technology and quantitative
real time Polymerase Chain Reaction (PCR) have
successfully evaluated the interactions between diet and
genes measured as changes in genetic expression. The use
of proteomics tools (mainly two-dimensional electrophoresis)
revealed new information concerning the protein composition
of egg and poultry meat proteins, the effect of
dietary methionine on breast-meat accretion, the toxicity of
dioxin and the safe use of transgenic crops in animal nutrition.
Metabolomic analysis allowed the detection of changes
in the biochemical profiles of plasma and urine from pigs
fed different diets and the determination of metabolite profiles
in the liver of rats used as an animal model to characterize
the toxicity of triazol fungicides. In livestock species,
the microarray technology was discussed and reviewed as
potential nutrigenomics tools, in context to its economic
benefits and improvement of the food quality and safety in
dairy and meat industries. This widely utilized microarray or
DNA chip technology in nutrigenomics research enables not
only the simultaneous screening of large number of genes,
giving a comprehensive picture of the variation of gene
expression patterns, but will also provide explanations for
complex regulatory interactions, such as those between dietnutrients
and genes (Zduńczyk and Pareek 2009).
Single nucleotide polymorphism How nutrients influence
the consequence of gene expression i.e. synthesis of
mRNA (transcriptomics), protein synthesis (Proteomics)
and metabolite production (metabolomics) was explained
by Munshi and Duvvuri (2008) by giving the example of
Genetic Polymorphism (SNPs) which may be partially responsible
for variations in individual’s response to bioactive
food components. The role of various nutrients on gene
expression occurring normally in body and its application
to various aspects was also studied by Siddique et al. (2009).
Through molecular biology and the tools of genomics, scientists
have identified genes responsible for production of
nutritionally important proteins such as digestive enzymes,
transport molecules responsible for carrying nutrients and
cofactors at their site of use. A number of relatively common
SNPs are known to influence nutrient requirements. An
example comes from work on SNPs that modified the risk
of developing organ dysfunction when humans were fed
diets low in choline. Premenopausal women [carriers of a
very common SNP (Methylenetetrahydrofolate dehydrogenate
MTHFD1-G1958A)] were 15 times as likely as noncarriers
to develop signs of choline deficiency on a low-
0
50
100
150
200
250
300
350
400
450
500
Medicine
Biochemistry, Genetics and Molecular Biolog
Agricultural and Biological Sciences
Nursing
Pharmacology, Toxicology and Pharmaceutics
Environmental Science
Chemistry
Immunology and Microbiolog
Engineering
Multidisciplinary
Veterinary
Chemical Engineering
Social Sciences
Undefined
Neuroscience
Mathematics
Business, Management and Accounting
Health Professions
Psychology
Computer Science
No. of papers
Subjects
Fig. 5 Subject-wise
contribution to nutrigenomics
research. Source: Scopus
Database
Nutrient
Intake
Disease
Prevention
and
Positive
Health
Outcome
Genomics Proteomics Metabolomics
Fig. 6 Nutrigenomics approach in disease prevention
choline diet. The risk of having a child with a neural tube
defect increased 4 times in mothers with this SNP, compared
with women eating diets in the highest quartile for choline
intake (Table 2). Zeisel (2011) also suggested that maternal
dietary choline modulates fetal brain development in rodent
models.
A growing interest in preventive medicine among people
led to scientific research on alternative therapies, with particular
emphasis on nutritional approaches to health and
wellness. One such newly developed technology is the
development of SNP array which helps to identify unique
haplotypes. Majeed and Prakash (2006) discussed the role
of nutraceuticals in health and diseases. Nutrigenomics,
which investigates the interaction between diet and development
of diseases based on an individual’s genetic profile,
would provide scientific validity to such approaches.
Mitra et al. (2005) focused on single nucleotide polymorphisms
(SNPs) and its associated diseases (Cancer,
Obesity, Diabetes, Cardio Vascular Diseases (CVD),
Neural Tube Defect (NTD), Leukemia, Down syndrome,
Spina bifida) (Table 2) and have also emphasized the interaction
between folate nutrition and folate-dependent enzyme
polymorphism (folate nutrigenomics). Ghodke et al. (2011)
also profiled SNPs across intracellular folate metabolic
Table 2 Nutrient deficiency diseases and preventive food sources
Nutrients Gene Alteration Deficient Diet-Disease Potential Food Intake
Folic acid (Vitamin B9) Chromosome break and
hampers DNA repair/
methylation
Cancer, heart disease, brain
dysfunction, male infertility,
leukemia
Liver, kidney, egg yolk, asparagus pea,
cowpeas, lentils, peanuts, spinach,
beetroot, broccoli, orange
Vitamin B12 (Cobalamin) Chromosome break and
hampers DNA repair/
methylation
Same as folic acid, memory loss Liver, sardines, salmon, clam, beef, milk,
cheese, yoghurt
Vitamin B6 (Pyridoxine) Same as folic acid Spinach, potato, bell peppers, turnip,
mushroom, garlic, cauliflower,
banana, chicken, pork, beef, salmon,
tuna, turkey
Niacin (Vitamin B3) Hampers DNA repair Nerve problem, memory loss Pork, tuna, prawns,
kidney, liver,
poultry, carrots, turnips and celery,
mushrooms, beans, almonds, wheat
products, rice bran, as well as milk
and other dairy products
Vitamin E (Tocopherols) Mimics radiation damage Colon cancer, heart disease,
immune dysfunction
Tomato, spinach, broccoli, blueberries,
mangoes, kiwi, papaya, almonds,
hazelnuts, peanuts, wholegrain cereals
and vegetable oils
Vitamin D (Calciferol) Prevent gene variation Colon, breast, prostate cancer Beef liver, cod liver
oils, salmon,
mackerel, tuna, egg orange juice,
cow milk, yogurt, cheese
Zinc Chromosome breaks Brain and immune dysfunction Oysters, beef, crab, pork, lobster,
chicken, spinach, broccoli, cashew
nuts, almond, milk, cheese, yogurt
Fatty acids Alters gene expression Obesity, CVD, Diabetes Salmon, sardines, herring, mackerel,
soyoil, sunflower oil, palm oil,
flaxseeds, rapeseeds, peanuts, walnuts,
almonds, mustard seeds, cloves,
oregano, cauliflower, broccoli
Flavonoids Alters gene expression Cancer Onion, green bean, broccoli, curly kale,
endive, celery, cranberry, orange juice,
grape fruits, lemons, red, blue and purple
berries, peppers, tomatoes and eggplants
Vitamin A(Retinol) Repression of PEPCK gene Termination of pregnancy
and fetal death
Carrots, spinach, turnip, kale, apricots,
Cantaloupe, bell pepper, Papaya, mango,
peach, beef liver, chicken liver
Protein Alters gene expression Kwashiorkor, marasmus Egg, milk, soya milk, tofu, yoghurt,
cheese,
broccoli, almonds, peanuts, cashew, poultry
*Food sources abundant in respective nutrients are only mentioned
CVD Cardio Vascular Diseases; PEPCK phosphoenolpyruvate carboxykinase
pathway in healthy Indians (Fig. 7). The role of folate,
vitamin B12 and homocysteine levels in acute lymphoblastic
leukemia, suggest that gene-environment interaction may
be an important factor in the development of acute lymphoblastic
leukemia (Adiga et al. 2008).
Biomarkers Nutrigenomics is a revolutionary way of viewing
the food, just for not sustenance, but as a pharmaceutical
capable of reversing disease and stalling the rigors of ageing
(Bhatt and Sharma 2011). A part of the approach, nutrigenomics
involves finding markers of the early phase of diet
related diseases; this is the phase at which intervention with
nutrition can return the patient to health (Ramesha et al.
2010; Lau et al. 2008; Kore et al. 2008; Murray et al. 2010).
Markers can manipulate gene expression through use of
nutrients or their combinations so as to improve productive
as well as overall animal performance. The discoveries of
these markers related to economically important traits like
milk, meat, wool production etc., whose expression can be
improved by dietary regimes, are needed today in nutrigenomic
research. This will help in sustainable livestock production.
By targeting specific genes through nutritional
manipulation, it may be possible to get the desired livestock
performance in terms of health as well as production (Kore
et al. 2008). Coudron et al. (2006) illustrated the potential
discovery of molecular markers using Perillus bioculatus
(F.) (Heteroptera: Pentatomidae), when reared on an optimal
vs. suboptimal diet, and analyzed the presence of differentially
expressed genes resulting from the treatment.
Biomarkers identified from this research could lead to development
of a simple and rapid method for evaluating the
quality and fitness of insect populations in the laboratory
and in the field, leading to more efficient methods for rearing
insects, as well as the production of high quality insects.
In the broadest perspective, these developments will likely
lead to more effective use of biological control methods and
improvements in agricultural sustainability. Ramesha et al.
(2010) utilized ten PCR-SSR (Polymerase Chain Reaction -
Simple Sequence Repeats) microsatellite markers to gain better
understanding on genotyping of certain nutrigenomic gene
loci in nutritionally efficient silkworm breeds/hybrids. They
used nutritionally efficient silkworm strains as a marker assisted
selection or gene transmission in silkworm breeding programs
and found that this developed molecular analysis in
silkworm could be utilized for the benefit of farmers in
Sericulture industry and also emphasized the future prospects
of silkworm functional mechanism in nutrigenomics studies.
Nutrigenomics is surely expected to be the next wave for
food industry, even though only a few practical ideas have
emerged. One business model is the development of customized
nutraceuticals based on specific genetic profiles.
Another model may be foods for specified health use, which
are already on the Japanese market. In Japan, about 350
items have been approved as food for specified health use
by the Japanese Ministry of Health, Labor and Welfare.
Each item has a specific health claim, such as food for
hypertension, high cholesterol, diabetes, etc. based on clinical
studies. All products have been developed based on
scientific analysis and data, even though not on the genetic
level yet. The food industry recognizes the need for nutrigenomics
research as a basis for developing the concept of
“personalized diets,” for identifying molecular biomarkers
A 1298C variant of 5, 10
methylenetetrahydrofolate
reductase gene
C677 T variant of 5, 10
methylenetetrahydrofolate
reductase gene
Spina bifida, Leukemia
A 2756G variant of
methionine synthase gene
Colon cancer, Spina bifida (NTD), Down
Syndrome, Leukemia, Oral cleft, CVD,
Complication of pregnancy
Single
Nucleotide
Polymorphism
A66G variant of methionine
synthesis gene
C1420T variant of serine
hydroxymethyletransferase
gene
2R3R variant of thymidylate
synthatase gene
Thromboembolic diseases
Spina bifida, Down syndrome
Leukemia
Leukemia
C1561T variant of glutamate May affect cardiovascular diseases
carboxypeptidase gene
Fig. 7 Single Nucleotide
Polymorphism, its associated
gene alteration and diseases.
Source: Modified from Mitra et
al. (2005)
or new bioactive food ingredients, and for validating the
effectiveness of these bioactive ingredients as functional
food components or nutraceuticals. An important aim of
nutrigenomics research is to study genome-wide influences
of nutrition, with specific focus on the role of metabolic
stress in the genesis of the metabolic syndrome, the collection
of phenotypes combining inflammation, metabolic
stress, insulin resistance, and diabetes. This goal is rather
ambitious, but is based on the idea that nutrition should
focus primarily on health and disease prevention and be
complementary to pharmacological therapy, which targets
the pathophysiological aspects of disease. To realize this
goal, new genomics-based phenotypical biomarkers are
needed that allow early detection of the onset of disease
or, ideally, the predisease state of the metabolic syndrome, a
condition referred to as metabolic stress. To approach this
complex condition, molecular nutrition research on organspecific
dietary response patterns using transgenic and
knock-out mouse models is combined with genomic technologies
(Afman and Muller 2006).
Nutrigenomics & diseases
Nutrigenomics is widely used for studying heart-related
disorders (Singh et al. 2002; Sivasankaran 2010; Rastogi
et al. 2004) as well as diet-related disorders. The higherincome
group who consumed excess fat and calorie-rich
food had an increased prevalence of diabetes compared to
the lower income group. In addition, visible fat consumption
and physical inactivity showed a cumulative effect on increasing
the prevalence of diabetes. Gene-diet interaction
studies revealed that the adiponectin gene polymorphism
contributed to insulin resistance and diabetes and this was
exaggerated in those consuming diets with higher glycemic
loads (Mohan et al. 2007a, b).
Gomase et al. (2009) explained genomics and its new
aspects in cancer research. This study gave a broader idea of
its history, strategies, technology, applications and current
research. SNP array has significant impact on the genetic
analysis of human disorders. It can be used to measure both
DNA polymorphism and dosage recommendations. SNP
arrays are an ideal platform for identifying both somatic
and germline genetic variants that lead to cancer. Nair and
Pillai’s (2005) review article on Human papillomavirus
(HPV) and disease mechanisms provided a number of critical
observations associated with the role of HPV in cervical
and oral cancer. Diet–gene interactions are also likely to
contribute considerably to the observed inter-individual variations
in cancer risk. This is in response to exposures to the
nutritional factors that have the potential to promote or
protect against cancer.
An investigation was carried out to know the role of
parental folate pathway SNPs in altering the susceptibility
to neural tube defects in 50 couples with NTDs offspring
and 80 couples with normal pregnancy outcome. Naushad et
al. (2010) observed high incidence of NTDs in South India
where consanguinity is common and vitamin deficiencies
were reported, which indicate the role of genetic and nutritional
factors as the possible etiological factors specifically
pointing towards folate metabolism. This study indicates
significant gene-gene interactions between different loci
and thus, highlights the importance of multiple loci in folate
pathway for predicting the risk of NTD. They also emphasized
the need to investigate gene-nutrient interactions for
more precise risk prediction. A review of Indian literature on
NTDs focusing on the role of folate and vitamin B12 nutrition
and common genetic polymorphisms in 1-carbon metabolism
was also conducted by Godbole et al. (2009). This
study highlighted the importance of folic acid and vitamin
B12 and the need for large studies in the area of genenutrient
interaction in association with NTD in India.
The effects of chronic feeding of different diets containing
vanaspati (trans fatty acid (TFA) rich), palm oil (saturated
fatty acid (SFA) rich) and sunflower oi l
(polyunsaturated fatty acid (PUFA) rich) at 10 % level on
11b-HSD1 gene expression in rat retroperitoneal adipose
tissue was reported. The diets rich in trans fatty acids and
saturated fatty acids increased 11b-HSD1 gene expression in
Retroperitoneal White Adipose Tissue (RPWAT) of rats as
compared PUFA enriched diet. This increased the local
amplification of glucocorticoids than PUFA-rich diets.
Thus, the increased local conversion of inactive to active
glucocorticoids in adipose tissue increased the risk of developing
obesity and insulin resistance (Prasad et al. 2010).
Diacylglycerol (DAG) rich mustard oil is capable of reducing
arteriosclerotic factors like total cholesterol and non-
LDL (low-density lipoprotein) cholesterol and increase antiatheroscleotic
factor such as high-density lipoprotein (HDL)
cholesterol (Dhara et al. 2011). Another study addressed the
hypothesis that some dietary fatty acids may attenuate the
proinflammatory insulin resistant state in obese adipose
tissue. The potential antidiabetic effect of a c9, t11-CLA–
enriched diet (cis-9, trans-11–conjugated linoleic acid) was
determined, focusing on the molecular markers of insulin
sensitivity and inflammation in adipose tissue of ob/ob
C57BL-6 mice, a well-characterized model of obesity and
insulin resistance. Feeding the c9, t11-CLA– enriched diet
improved glucose and insulin metabolism compared with
the control linoleic acid–rich diet. This evidence suggests
that it may be possible to reduce the impact of obesityinduced
insulin resistance with nutrient-based antiinflammatory
strategies (Moloney et al. 2007). An 8-week
study on mice demonstrated that HFD (High Fat Diet)
induces obesity, reduces whole-body insulin sensitivity and
decreases insulin sensitivity of heart, muscle and visceral fat
deposits (Wilde et al. 2009). The dietary combination of fish
protein and fish oil decreased the contents of serum triacylglycerol,
serum cholesterol, liver triacylglycerol and liver
cholesterol in addition to altering liver lipid fatty acid composition.
These effects are partly due to the increase in fecal
cholesterol, bile acid excretion, and increased enzyme activities
of fatty acid β-oxidation in the liver. These data
suggest that combined intake of fish protein and fish oil
lead to both hypocholesterolemic and hypotriglyceridemic
effects in serum and the liver, while sole intake of fish
protein or fish oil decrease only cholesterol and triglyceride
levels, respectively and it may play a beneficial role in the
prevention of lifestyle-related diseases (Hosomi 2011).
Dhaka et al. (2011) have also proved the direct connection
of trans fatty acids with cardiovascular diseases, breast
cancer, shortening of pregnancy period, risks of preeclampsia,
disorders of nervous system and vision in infants, colon
cancer, diabetes, obesity and allergy. Kaur et al. (2012)
found that essential fatty acids (like α-Linolenic acid, eicosapentaenoic
acid and docosahexaenoic acid) reduced the
risk of these diseases.
Pro-resolving and anti-inflammatory mediator products
of murine 12/15-lipoxygenase (LOX) (lipid-oxidising
enzymes) exhibit potent actions on vascular inflammation
and protect against the progression of atherosclerosis (uncontrolled
inflammation). Merched et al. (2011) determined
whether augmenting dietary lipids modulates the body’s
endogenous anti-inflammatory pro-resolving mechanisms
and promotes atherosclerosis. Conditions of aggressive accelerated
atherosclerosis induced by a Western diet usurp
the protective function of 12/15-LOX expression and bioactive
mediator production, lead to a heightened proinflammatory
burden. These studies demonstrated that 12/
15-LOXs provide endogenous anti-inflammatory signals
and protection during normal progression of atherogenesis
mediated by downstream products, such as LXs (lipoxins),
protectins, and D-series resolvins, effects that seem to be
totally annulled in the presence of Western-diet-induced
hyperlipidemia.
Nutrigenomics & diet supplementation
Today we live in a nutritional environment that is very
different from the environments to which we had genetically
adapted. Major changes in our food supply accompanied the
domestication of animals and the agricultural revolution
about 10,000 years ago. Later, the Industrial Revolution
and developments in food technology brought about further
major changes in the composition of foods, one of the most
important of which was a change in the quantity and quality
of the various fatty acids. Srinivasarao et al. (1997) study
was primarily aimed at determining the magnitude of
changes in long chain fatty acids, polyunsaturated fatty
acids, and molar ratios of cholesterol to phospholipids in
synaptosomal membranes, in response to feeding of different
dietary fats (safflower, mustard, peanut, and coconut
Oil) by using discontinuous sucrose density gradient
ultracentrifugation.
Diet is an important factor in cancer etiology and prevention.
Ayurveda medicine prescribes many plant-based medicines
for the treatment of cancer. Sinha et al. (2003)
conducted a symposium on cancer risk and diet in India
and explained the possible dietary and other factors associated
with cancer. Turmeric has shown to be a potent antioxidant
and anti-inflammatory agent with additional promise
as a chemo-preventive agent.
The contribution of various factors including macronutrients
and recommendations for obesity management has
been studied (Kumar and Singh 2009). Jeyakumar et al.
(2005) reported Vitamin A as a known regulator of adipose
tissue growth. The chronic dietary vitamin A supplementation
at a high dose effectively regulates adipose tissue mass
both in lean and obese phenotypes of the WNIN/Ob strain.
Vitamin A is also required for normal embryonic and fetal
development, as well as maintenance of the fully differentiated
state in the adult. Ghoshal et al. (2003) investigated the
effect of vitamin A depletion on the developing liver
(mouse) by examining the phosphoenolpyruvate carboxykinase
(PEPCK) gene as a prototype retinoid-responsive gene
(Table 2). Singh et al. (1994) reported the effect of low
energy, fruit and vegetable enriched diet on central obesity
and other disturbances associated with glucose intolerance
in patients after acute myocardial infarctions in the randomized
trial.
HCA-SX or Super Citrimax, a novel derivative of HCA
(dried fruit rind of Garcinia cambogia, also known as
Malabar tamarind), is a unique source of (−)-hydroxycitric
acid (HCA). It is safe when taken orally and is bioavailable
in the human plasma. Under the experimental conditions,
Roy et al. (2004) demonstrated that HCA-SX supplement
has been observed to be conditionally effective in weight
management and lowered abdominal fat leptin expression in
experimental animals as well as in humans. In 2008, Lau
and his co-workers also showed that supplementation of
HCA and niacin-bound chromium (III) (NBC) is safe and
efficacious for weight loss.
The use of new bioactive foods and nutraceuticals in
cardio-protection and management is growing (Sharma and
Singh 2010). Thompkinson et al. (2012) indicated that foods
rich in omega-3 fatty acids, antioxidant vitamins and fibres
may be beneficial for cardio-vascular health. Kamra et al.
(2005) conducted an experiment for studying bioactive dietary
components and their physiological activity in the intact
organisms and the role of diet in cancer prevention. He
found out that fish oils, nutraceuticals in vegetable fat-free
diets and restricted life style enhances cardio-protection and
plays a major role in positive gene regulation.
Genomics and proteomics offer new tools for better understanding
the genetics of male infertility. The review by
Singh and Jaiswal (2011) provides insights into the plausible
chromosomal, genetic and epigenetic alterations, which
may result into infertile phenotype. In this paper they have
revealed the application of nutrigenomics in Male Infertility.
SNP arrays will be useful in getting a more general overview
of changes in whole genome of infertile men and
especially in the X chromosome. Folate, Vitamin B12 and
Zinc supplementation was found to have a positive effect on
spermatozoa number and motility. This was also observed
by Dhillon et al. (2007) by conducting a case–control study,
in which they included 179 oligoasthenoteratozoospermia
patients and 200 fertile men.
A dialyzed aqueous extract of fenugreek seeds was investigated
in vivo for hypoglycaemic potential and its
effects on insulin signalling pathways in the primary targets
of insulin, adipocytes and liver cells, were examined in
vitro, by the use of mechanism-based innovative contemporary
strategies. Vijayakumar et al. (2005) experimentally
demonstrated that a dialyzed aqueous extract of fenugreek
seeds possesses hypoglycaemic properties and that it stimulates
insulin signalling pathways in adipocytes and liver
cells. The hypolipidemic effect of a novel thermostable
extract of fenugreek seeds (TEFS) has been studied in vitro
by employing differentiating and differentiated 3T3-L1
cells, and HepG2 cells cultured in normal or sterolenriched
conditions and suggested that the TEFS may have
potential application in the management of dyslipidemia and
its associated metabolic disorders (Vijayakumar et al. 2010).
The isolation of microsomal ω-6-desaturated gene (fad2-
1) from soybean was carried out (Kishore et al. 2006) for
improving soybean seed oil profile, making it nutritionally
more beneficial and stable for human consumption. Psoyatose
supplementation results in an increased transcription
of fibroin mRNA leading to an increased silk production
of Bombyx mori L. Raman et al. (2007) demonstrated
that soyprotein extract supplementation is of importance in
regulating the fibroin gene expression at transcriptional
level. Nutrigenomic analysis of intestinal response to partial
soybean meal (SBM) replacement in juvenile Atlantic halibut
(Hippoglossus hippoglossus L.) showed that there is no
significant difference between fish fed with the fish meal
(FM) and SBM diets (Murray et al. 2010).
A successful attempt of fortifying human diets with natural
α - tocopherol by taking recourse to genetic engineering
of an important oilseed crop, Brassica juncea was described
by Yusuf and Sarin (2006). α -Tocopherol intakes in excess
of the recommended daily allowance (RDA) are associated
with decreased risk of cardiovascular diseases, improved
immune function, slowing of the progression of a number
of degenerative human.
Curcumin and its dietary source turmeric are important for
the prevention and/or treatment of diabetic retinopathy. The
vascular-endothelial-growth-factor (VEGF) expression analyzed
by both real time polymerase chain reaction (PCR)
and immunoblotting showed that curcumin and its dietary
source turmeric can inhibit VEGF expression in strepotzotocin
(STZ)-induced diabetic rat retina (Mrudula et al. 2007).
Kumar et al. (2009) also investigated the antiglycating potential
of cumin in vitro and its ability tomodulate the chaperonelike
activity of α-crystallin vis-à-vis the progression of diabetic
cataract in vivo. Through slit lamp examination, they
revealed that cumin has antiglycating properties that may be
attributed to the modulation of chaperone activity of α-
crystallin, thus delaying cataract in STZ-induced diabetic rats.
AMP-activated protein kinase (AMPK) has become one
of the most important key elements in energy control, appetite
regulation, myogenesis, adipocyte differentiation, and
cellular stress management. Metformin, an insulin sensitizing
agent, is known to lower insulin resistance and enhance
metabolic profile, with an additional weight reduction capacity,
via activation of AMPK. A high-fat diet is correlated
with a decreased expression of mRNA for the AMPK-α2
isoform as well as AMPK phosphorylation with consequent
decreased activity of this enzyme in skeletal muscle, leading
to decreased glucose uptake, meanwhile in adipose tissue it
promotes preadipocyte differentiation, lipolysis and the secretion
of adipokines (TNFα),perpetuating the process.
Foods with low glycemic index may be beneficial in regulating
body weight in two ways: first by promoting satiety
and secondly by increasing fatty acid oxidation, both
explained by the action of AMPK. A high-protein diet is
capable of controlling food intake due to enhanced proopiomelanocortin
(POMC) expression and repression of neuropeptide
Y (NPY) in the hypothalamus, via activation of
mTOR (mammalian target of rapamycin) and low phosphorylation
rates of AMPK. Therefore dietary components can
greatly affect the activity of AMPK (Rojas et al. 2011).
Nutrigenomics & public awareness
Addressing the genetics and nutritional genomics knowledge
gap will help in eradicating the social issues, create more
awareness, confidence and trust among the public. Public
concerns over nutrigenomics are relevant to science and to
the food industry. Past and present food scares, such as genetically
modified, demonstrate the importance of addressing
public concerns sooner rather than later, and of taking the
social issues around science as seriously as technical ones.
Regulation is necessary both to ensure responsible use of
research and to assure the public that products can be trusted.
Manufacturers need regulation and public engagement both
for the guidance they provide and to demonstrate a will to
improve the safety, reliability and health benefits of their
products Sherwood (2006).
Public awareness programmes The relationship between
changing lifestyles, nutritional status of the Indian population
and formulation of appropriate programmes and strategies
for public awareness was explained by Rao (2001). A
Genomics Policy Executive Course was conducted by
Acharya et al. (2004) that provided a forum for stakeholders
to discuss the relevance of genomics for health in India. The
course goals were to familiarize participants with the implications
of genomics for health in India; analyze and debate
policy and ethical issues; and develop a multi-sectoral opinion
leaders’ network to share perspectives.
To overcome diet related diseases and promote health,
Krishnaswamy (2008) found that it is essential to develop
and implement Food Based Dietary Guidelines (FBDG). In
this post genomic era, the genes we inherit cannot be altered,
but certainly one can change its response to the environment
(dietary) and obtain the desired results. A multidisciplinary
group comprising nutritionists, agriculturists, technologists,
home scientists, dieticians etc. was constituted to develop
FBDG. Healthy food choices are central in the prevention of
both under and over nutrition, and the ultimate objective of
FBDGs is to grow what is needed and preserve what is
required (Fig. 8).
The future perspectives of nutrigenomics foods; its
benefits and risks were explained by Ghosh (2009).
Nutrigenomics is an emerging science with high consumer
expectations, but the major concerns are twofold. First,
it is doubtful whether the goal of matching foods to
individual genotypes to improve the health of those individuals
can be attained or not. Secondly, the entry of
personalized nutrigenomics foods in world’s food markets
depends on numerous hurdles being overcome: some
scientific in nature, some technical and others related to
consumer, market or ethical issues.
The emerging paradigms of nutritional genomics as they
relate to the functional food market were discussed by
Ghosh (2010). He emphasized on the consumer acceptance
and market penetration of the product based on this concept
to improve human nutrition and health and thereby deliver
societal and economic benefits. Later Ghosh and
Gorakshakar (2010) emphasized on the goal of integrating
genetics into the public health in India and Aswini and
Varun (2010) also gave a general awareness about the new
gene-based technologies that can be easily utilized by the
modern healthcare units.
Conclusion
Trends, based on current and projected data, indicate that India
is facing considerable challenges as under-nutrition evolves
Fig. 8 Food dietary guidelines
into over-nutrition as the community becomes developed.
India has some of the highest CHD rates in the world,
with urban rates being three times higher than rural rates.
In addition, rates for obesity and diabetes are increasing
dramatically in urban areas and in high-income rural residents.
This increasing number of diet related disorders in
India (obesity, cardio-vascular diseases, diabetes, neural
tube defects, etc.) has led us to investigate the nutrigenomics
research in India.
The literature collected so far shows that, India has a keen
interest in the field of nutrigenomics. In the year 2005, 2008
and 2009 Indian authors gave a broader description of
nutrigenomics. They have well explained the mechanism,
the basic concept of nutrigenomics and how nutrients influence
the gene expression. In 2004, a course was conducted
that provided a forum for stakeholders to discuss the relevance
of genomics for health in India. But after that, no
awareness programme was carried out. In 2008 and 2010
the authors described about the future perspectives of nutrigenomics
and gave an insight on the role of genetics in
public health. It has been noticed that from 2002 onwards
various studies on diseases related to insufficient diet, lack
of physical activity and changing lifestyles were conducted,
but only few work were done in the area of nutrigenomics.
Thus, more research work will enhance consumer confidence,
awareness and a better future, which in turn will
upgrade the country’s status.
Convincing evidence about the interaction of nutrients,
genetic variations and health implications is still uncertain.
We see this as the future, nutrigenomics concept does make
sense, but we are still far from personalised nutrition. The
literature search on “nutrigenomics” using various databases
concludes that there is a high hope and need of nutrigenomics
in India. This study shows that more research work and
increasing awareness can possibly help in the prevention of
nutritional and other non communicable disorders. Hence,
the early identification of at-risk individuals and appropriate
intervention in the form of weight reduction, changes in
dietary habits and increased physical activity could greatly
help to prevent, or at least delay the onset of dietary disorders
in India.
The ultimate aim of this emerging field of science is
prevention than cure. This is very similar to the dictum of
Hippocrates - Father of Medicine (460–360 BC), who said
“Leave your drug in the chemist’s pot if you can heal the
patient with food”.
Acknowledgement The authors acknowledge the guidance and support
of Dr. G. Mahesh and Prof. A K Chawla for their constant
guidance, supervision & support in completing this paper. Our thanks
and appreciations also go to our colleague, Priyanka Singh who has
willingly helped us out with her abilities. Lastly, we would like to
thank our organization, CSIR-NISCAIR which gave us the platform to
do this study.
References
Acharya T, Kumar NK, Muthuswamy V, Daar AS, Singer PA (2004)
Harnessing genomics to improve health in India—An executive
course to support genomics policy. Health Research Policy and
Systems 2:1–13
Adiga MNS, Chandy S, Ramaswamy G, Appaji L, Krishnamoorthy L
(2008) Homocysteine, vitamin B12 and folate status in pediatric
acute lymphoblastic leukemia. Indian J Pediatr 7:235–238
Afman L, Muller M (2006) Nutrigenomics: from molecular nutrition to
prevention of disease. J Am Diet Assoc 106(4):569–576
Aswini YB, Varun S (2010) Genetics in public health: rarely explored.
Indian Journal of Human Genetics 16:47–54
Bhatt SN, Sharma AD (2011) Nutrigenomics: a non—conventional
therapy. International Journal of Pharmaceutical Sciences
Review and Research 8(2):100–105
Coudron TA, Yocum GD, Brandt SL (2006) Nutrigenomics: a case
study in the measurement of insect response to nutritional quality.
Entomol Exp Appl 121:1–14
Dhaka V, Gulia N, Ahlawat KS, Khatkar BS (2011) Trans fats—
sources, health risks and alternative approach—A review. J
Food Sci Technol 48(5):534–541
Dhara R, Dhar P, Ghosh M(2011) Dietary effects of diacylglycerol rich
mustard oil on lipid profile of normocholesterolemic and hypercholesterolemic
rats. J Food Sci Technol. doi:10.1007/s13197-
011-0388-y
Dhillon VS, Shahid M, Husain SA (2007) Associations of MTHFR
DNMT3b 4977 bp deletion in mtDNA and GSTM1 deletion, and
aberrant CpG island hypermethylation of GSTM1 in nonobstructive
infertility in Indian men. Molecular Human
Reproduction 13(4):213–222
Ghodke Y, Chopra A, Shintre P, Puranik A, Joshi K, Patwardhan B
(2011) Profiling single nucleotide polymorphisms (SNPs) across
intracellular folate metabolic pathway in healthy Indians. Indian J
Med Res 133:274–279
Ghosh D (2009) Future perspectives of nutrigenomics foods: benefits
vs. risks. Indian Journal of Biochemistry & Biophysics 46:31–36
Ghosh D (2010) Personalised food: how personal is it? Genes Nutr
5:51–53
Ghosh K, Gorakshakar A (2010) Integration of modern genetic knowledge
and technology into public health in India. Indian Journal of
Human Genetics 16:45–46
Ghoshal S, Pasham S, Odom DB, Furr HC, McGrane MM (2003)
Vitamin A depletion is associated with low phosphoenolpyruvate
carboxykinase mRNA levels during late fetal development and at
birth in mice. J Nutr 133:2131–e
Gobard B, Hurlimann T (2009) Nutrigenomics for global health:
ethical challenges for underserved populations. Current
Pharmacogenomics and Personalized Medicine 7(3):205–14
Godbole K, Deshmukh U, Yajnik C (2009) Nutri-genetic determinants
of neural tube defects in India. Indian Pediatrics
46:467–475
Gomase VS, Tripathi AK, Tagore S (2009) Genomics: new aspect of
cancer research. International Journal of Systems Biology 1
(1):01–19
Gopalan C (1992) The contribution of nutrition research to the control
of under nutrition: the Indian experience. Annu Rev Nutr 12:1–17
Hosomi R (2011) Effect of combination of dietary fish protein and fish
oil on lipid metabolism in Rats. J Food Sci Technol. doi:10.1007/
s13197-011-0343-y
Hossain P, Kawar B, Nahas ME et al (2007) Obesity and diabetics in
the developing world—A growing challenge. N Engl J Med
356:213–215
Hyman M (2006) Book on Ultra-metabolism: the simple plan for
automatic weight loss. Atria Books, New York, p 24
Jeyakumar SM et al (2005) Vitamin A supplementation induces adipose
tissue loss through apoptosis in lean but not in obese rats of
the WNIN/Ob strain. Journal of Molecular Endocrinology
35:391–398
Kamra A, Kalavapudi S, Sudhakaran TR et al (2005) Exfoliated
colonic epithelial cells: surrogate targets for evaluation of bioactive
food components in cancer prevention. J Nutr 135(11):2719–
2722
Kandaswamy R (2011) Genetic variations in the FTO gene are associated
with type 2 diabetes and obesity in south Indians (CURES-
79). Diabetes Technol Ther 13(1):33–42
Kaput J et al (2007) Application of nutrigenomic concepts to type 2
diabetes mellitus. Nutr Metab Cardiovas 17:89–103
Kaur N, Chugh V, Gupta AK (2012) Essential fatty acids as functional
components of foods- a review. J Food Sci Technol. doi:10.1007/
s13197-012-0677-0
Kishore K, Sinha SK, Kumar R, Gupta NC, Dubey N, Sachdev A
(2006) Isolation and characterization of microsomal ω-6-
desaturase gene (fad2-1) from soybean. Indian J Exp Biol
45:390–397
Kore KB, Pathak AK, Gadekar YP (2008) Nutrigenomics: emerging
face of molecular nutrition to improve animal health and production.
Vet world 1(9):285–286
Krishnaswamy K (2008) Developing and implementing dietary guidelines
in India. Asia Pac J Clin Nutr 17:66–69
Kumar A, Singh RP (2009) Obesity: prevalence, manifestations and
dietary patterns—A review. J Food Sci Technol 46(4):287–299
Kumar PA et al (2009) Delay of diabetic cataract in rats by the
antiglycating potential of cumin through modulation of α-
crystallin chaperone activity. Journal Nutr Biochem 20(7):553–
562
Lau FC, Bagchi M, Sen C, Roy S, Bagchi D (2008) Nutrigenomics
analysis of diet-gene interactions on functional supplements for
weight management. Curr Genomics 9:239–251
Majeed M, Prakash L (2006) Nutraceuticals and the Future
of Medical Science. http://www.drmajeed.com/articles/
2006NutraceuticalsAndTheFuture.pdf. Accessed 15 February
2011
Melvyn A Sydney-Smith Nutrition Medicine: Genes, Nutrition &
Health. www.nutritionmedicine.org/Files/Genes_Nutrition.ppt
Menon B, Harinarayan CV, Raj MN, Vemuri S, Himabindu G, Afsana
TK (2010) Prevalence of low dietary calcium intake in patients
with epilepsy: a study from South India. Neurol India 58:209–212
Merched AJ, Serhan CN, Chan L (2011) Nutrigenetic disruption of
inflammation-resolution homeostasis and atherogenesis. J
Nutrigenet Nutrigenomics 4:12–24
Mitra et al (2005) Nutrigenomics: a new frontier. http://www.apiindia.org/
images/stories/pdf/medicine_update_2005/chapter_182.pdf.
Accessed 25 January 2011
Mohan V, Sandeep S, Deepa R, Shah B, Varghese C (2007a)
Epidemiology of type 2 diabetes: Indian scenario. Indian J Med
Res 125:217–230
Mohan V, Sudha V, Radhika G, Radha V, Rema M, Deepa R (2007b)
Gene-environment interactions and the diabetes epidemic in
India. Forum Nutr 60:118–126
Moloney F et al (2007) Antidiabetic effects of cis-9, trans-11–conjugated
linoleic acid may be mediated via anti-inflammatory effects
in white adipose tissue. Diabetes 56:574–582
Mrudula T et al (2007) Effect of curcumin on hyperglycemia-induced
vascular endothelial growth factor expression in streptozotocininduced
diabetic rat retina. Biochem Bioph Res Co 361(2):528–
532
Munshi A, Duvvuri VS (2008) Nutrigenomics: looking to DNA for
nutrition advice. Indian J Biotechnol 7:32–40
Murray HM, Lall SP, Rajaselvam R et al (2010) A nutrigenomic
analysis of intestinal response to partial soybean meal
replacement in diets for juvenile Atlantic halibut, Hippoglossus
hippoglossus, L. Aquaculture 298:282–293
Nair S, Pillai MR (2005) Human papillomavirus and disease mechanisms:
relevance to oral and cervical cancers. Oral Dis 11:350–
359
Naushad SM, Radha A, Devi R (2010) Role of parental folate pathway
single nucleotide polymorphisms in altering the susceptibility to
neural tube defects in South India. J Perinat Med 38:63–69
Pathak P, Srivastava S, Grover S (2000) Development of food products
based on millets, legumes and fenugreek seeds and their suitability
in the diabetic diet. Int J Food Sci Nutr 51(5):409–414
Prasad SSSV, Kumar SSJ, Kumar PU, Qadri SS, Vajreswari A (2010)
Dietary fatty acid composition alters 11β-hydroxysteroid dehydrogenase
type 1 gene expression in rat retroperitoneal white
adipose tissue. Lipids Health Dis 9(111):1–5
Raj M, Sundaram KR, Paul M, Deepa AS, Kumar RK (2007) Obesity
in Indian children: time trends and relationship with hypertension.
Natl Med J India 20(6):288–293
Ramachandran A (2006) The Indian diabetes prevention programme
shows that lifestyle modification and metformin prevent type 2
diabetes in Asian Indian subjects with impaired glucose tolerance
(IDPP1). Diabetologia 49:289–297
Raman C, Manohar SL, Xavier N, Krishnan M (2007) Expression of
silk gene in response to P-soyatose (hydrolyzed soy bean protein)
supplementation in the fifth instar male larvae of Bombyx Mori.
Journal of Cell and Molecular Biology 6(2):163–174
Ramesha C, Kumari SS, Anuradha CM, Lakshmi H, Kumar CS (2010)
Nutrigenomic analysis of mulberry silkworm (Bombyx mori L.)
strains using Polymerase Chain Reaction - Simple Sequence
Repeats (PCR-SSR). International Journal for Biotechnology
and Molecular Biology Research 1(7):92–100
Rao S (2001) Nutritional status of Indian population. J Bioscience 26
(4):481–489
Rastogi T, Reddy KS, Vaz M et al (2004) Diet and risk of ischemic
heart disease in India. Am J Clin Nutr 79:582–592
Rojas J et al (2011) AMPK as target for intervention in childhood and
adolescent obesity. Journal of Obesity. doi:10.1155/2011/252817
Roy S, Bagchi D, Bagchi M, Khanna S, Sen CK, Rink C, Phillips C
(2004) Body weight and abdominal fat gene expression profile in
response to a novel hydroxycitric acid-based dietary supplement.
Gene Expression 11:251–262
Scopus Database http://www.scopus.com/home.url?null
Sharma M, Majumdar PK (2009) Occupational life style diseases: an
emerging issue. Indian J Occup Environ Med 13(3):109–112
Sharma R, Singh RB (2010) Bioactive foods and nutraceutical supplementation
criteria in cardiovascular protection. Open Nutraceuticals
J 3:141–153
Sherwood D (2006) Nutrigenomics: public concerns and commercial
interests. Agro Food Ind Hi Tech 17(4):56–57
Shetty PS (2002) Nutrition transition in India. Public Health Nutr 5
(1A):175–172
Siddique RA, Tandon M, Ambwani T, Rai SN, Atreja SK (2009)
Nutrigenomics: nutrient-gene interactions. Food Rev Int 25
(4):326–345
Singh K, Jaiswal D (2011) Human male infertility: a complex multifactorial
phenotype. Reprod Sci 18(5):418–425
Singh RB, Niaz MA, Ghosh S (1994) Effect on central obesity and
associated disturbances of low-energy, fruit- and vegetableenriched
prudent diet in North Indians. Postgrad Med J 70:895–
900
Singh RB, Dubnov G et al (2002) Effect of an Indo- Mediterranean diet
on progression of coronary artery disease in high risk patients
(Indo-Mediterranean diet heart study): a randomized single-blind
trial. Lancet 360:1455–1461
Sinha R et al (2003) Cancer risk and diet in india. J Postgrad Med
49:222–228
Sivasankaran S (2010) The cardio-protective diet. Indian J Med Res
132(5):608–616
Srinivasarao P et al (1997) Lipid composition and fatty acid
profiles of myelin and synaprosomal membranes of rat brain
in response to the consumption of different fats. J Nutr
Biochem 8(9):527–534
Thompkinson DK, Bhavana V, Kanika P (2012) Dietary approaches
for management of cardio-vascular health- a review. J Food Sci
Technol. doi:10.1007/s13197-012-0661-8
Trehan N (2006) Cardiovascular disease trends in India. http://
www.chroniccareindia.org/documents/Naresh_Trehan.pdf
Vijayakumar MV et al (2005) The hypoglycaemic activity of
fenugreek seed extract is mediated through the stimulation
of an insulin signalling pathway. Brit J Pharmacol 146:41–
48
Vijayakumar MVet al (2010) Hypolipidemic effect of fenugreek seeds
is mediated through inhibition of fat accumulation and upregulation
of LDL receptor. Obesity 18(4):667–674
WHO Report: The impact of chronic disease in India. http://
www.who.int/chp/chronic_disease_report/media/india.pdf
Wilde JD et al (2009) An 8-week high-fat diet induces obesity and
insulin resistance with small changes in the muscle transcriptome
of C57BL/6J mice. J Nutrigenet Nutrigenomics 2:280–291
Yusuf MA, Sarin NB (2006) Antioxidant value addition in human
diets: genetic transformation of Brassica juncea with γ-TMT gene
for increased α-tocopherol content. Transgenic Res 16:109–113
Zduńczyk Z, Pareek CS (2009) Application of nutrigenomics tools in
animal feeding and nutritional research. J Anim Feed Sci 18:3–16
Zeisel Steven H (2011) Nutritional genomics: defining the dietary
428 J Food Sci Technol (–June 2013) 50(3):415–428
requirement and effects of choline. J Nutr 141:531–534
View publicationJournal ListFront Nutrv.6; 2019PMC6389634
Logo of fnut
Front Nutr. 2019; 6: 8.
Published online 2019 Feb 19. doi: 10.3389/fnut.2019.00008
PMCID: PMC6389634
PMID: 30838211
Sport Nutrigenomics: Personalized Nutrition for Athletic Performance

Nanci S. Guest,1,2 Justine Horne,3 Shelley M. Vanderhout,1,2 and
Ahmed El-Sohemy1,2,*
Author information Article notes Copyright and License information Disclaimer
This article has been cited by other articles in PMC.
Go to:
Abstract
An individual's dietary and supplement strategies can influence markedly their physical
performance. Personalized nutrition in athletic populations aims to optimize health, body
composition, and exercise performance by targeting dietary recommendations to an individual's
genetic profile. Sport dietitians and nutritionists have long been adept at placing additional
scrutiny on the one-size-fits-all general population dietary guidelines to accommodate various
sporting populations. However, generic “one-size-fits-all” recommendations still remain. Genetic
differences are known to impact absorption, metabolism, uptake, utilization and excretion of
nutrients and food bioactives, which ultimately affects a number of metabolic pathways.
Nutrigenomics and nutrigenetics are experimental approaches that use genomic information and
genetic testing technologies to examine the role of individual genetic differences in modifying an
athlete's response to nutrients and other food components. Although there have been few
randomized, controlled trials examining the effects of genetic variation on performance in
response to an ergogenic aid, there is a growing foundation of research linking gene-diet
interactions on biomarkers of nutritional status, which impact exercise and sport performance.
This foundation forms the basis from which the field of sport nutrigenomics continues to
develop. We review the science of genetic modifiers of various dietary factors that impact an
athlete's nutritional status, body composition and, ultimately athletic performance.
Keywords: nutrigenomics, nutrigenetics, personalized nutrition, athletic performance, genetic

testing, sports nutrition, caffeine, ergogenic aids
Go to:
Introduction
Sport and exercise performance are significantly influenced by nutrition, yet individuals respond
differently to the same foods, nutrients and supplements consumed. This holds true for a variety
of ages, ethnicities, and level of skill, and whether the goal is optimizing physical activity for
health and fitness or for high performance sport. The importance of a personalized sports
nutrition plan was highlighted in the recent “Nutrition and Athletic Performance” Joint Position
Statement by the American College of Sports Medicine, the Academy of Nutrition and Dietetics
and the Dietitians of Canada, which states that “Nutrition plans need to be personalized to the
individual athlete… and take into account specificity and uniqueness of responses to various
strategies” (1). These strategies encompass overall dietary patterns, macronutrient ratios,
micronutrient requirements, eating behaviors (e.g., nutrient timing), and the judicious use of
supplements and ergogenic aids.
The paradigm shift, away from the one-size-fits-all group approach and toward personalization
for the individual, is moving nutrigenomics research from basic science into practice. While it
has long been recognized that genetics play an influential role in determining how an athlete
responds to foods and nutrients, the surge in research into gene-diet interactions over the past
decade has provided a scientific basis for this hypothesis through various research initiatives and
the corresponding increase in published studies. Genetic variants affect the way we absorb,
metabolize, utilize and excrete nutrients, and gene-diet interactions that affect metabolic
pathways relevant to health and performance are now widely recognized (2). Personal genetic
testing can provide information that will guide recommendations for dietary choices that are
more effective at the individual level than current dietary advice, which has been set by
government agencies and other health and sport organizations. Disclosure of genetic information
has also been shown to enhance motivation and behavior change and strengthen adherence to the
dietary recommendations provided (2–6). Although athletes tend to exhibit higher levels of
motivation in general (7), nutrition professionals still encounter significant barriers to behavior
change when counseling athletes on the adoption of beneficial sports nutrition practices (8, 9). A
recent systematic review found that when genetic information included actionable advice,
individuals were more likely to change health behaviors, including their dietary choices and
intakes (10).
The practical application of the scientific knowledge gained from research on health and
performance is to enable athletes to utilize genetic test results for personalized nutrition in an
actionable manner. The demand for genetic testing for personalized nutrition and associated
performance outcomes by athletes and active individuals is growing, and there is an increased
need for dietitian-nutritionists, fitness professionals, coaches, and other sports medicine
practitioners to understand the current evidence in this developing field (11–14). The sport
environment is dynamic, progressive, innovative, and extremely competitive. Providing athletes
with individually tailored dietary and other performance-related information based on their DNA
could yield a competitive edge. The growing body of science in nutrition and genetics is the
foundational building block by which practitioners can help athletes reach their genetic potential
through implementation of dietary and supplement strategies that are aligned to their genetic
makeup (Figure 1). Scientific advancements along with increased interest in genetic testing have
resulted in a necessary growth for professional support, where tools for proficient and
knowledgeable nutrition counseling based on genetics are now more widely available. For
example, the Dietitians of Canada now offer a course on “Nutrigenomics: Genetic testing for
personalized nutrition” as part of their online Learning-on-Demand portal.
An external file that holds a picture, illustration, etc.
Object name is fnut-06-00008-g0001.jpg
Figure 1
The nutrigenomics approach to sport nutrition. An athlete is exposed to a food, beverage,

nutrient or bioactive. A genetic variant such as a single nucleotide polymorphism (SNP)
associated with that exposure modifiers the individual's requirement for or response to that
exposure. Their unique response depends on their version of the gene or “genotype.” For
example, in the CYP1A2 rs726551 SNP, individuals with the AA genotype (fast metabolizers)
experience a positive or “improved” response (i.e., performance) to caffeine. Individuals with the
CYP1A2 AC or CC genotype experience no effect or impaired performance, respectively, from
caffeine use (19).
Personalized nutrition, based on an individual's genotype, is not a novel concept, and there are
several examples of rare (e.g., phenylketonuria) and common (e.g., lactose intolerance) genetic
variants that require specific dietary strategies to manage (15). Although genetic testing is well-
established in the clinical setting, there is a growth in opportunities to improve health, wellness
and sport performance in athletes through nutrition-focused genetic testing. In the ongoing
battles against dangerous supplements (16) and unprecedented numbers of doping violations (17,
18), the sport science community is seeking novel, yet evidence-based, approaches for athletes to
gain a competitive edge which are safe, effective and legal. Personalized nutrition is not limited
to the identification of genetic variants. Genotype is one aspect of personal information that can
be used to individualize dietary advice. An individual's genetic profile as it relates to diet should
be used combination with other relevant information such as sex, age, anthropometrics, health
status, family history, and socioeconomic status along with dietary preferences and the presence
of food intolerances or allergies. Accompanying blood work is also useful to evaluate current
nutrition status and for ongoing monitoring.
Personalized dietary and supplement advice derived from genetic testing should be based on
clear and defensible interpretations of relevant research studies. Traditional genome-wide
association studies (GWAS) can be used to identify associations between genotypes and
outcomes of interest such as blood levels of a micronutrient. However, the utility of such
markers in providing actionable information on dietary advice is limited because it is not known
what dietary intakes are required to counter effects of the genetic variant(s). For example,
although a genetic variant that has been associated with low serum values of a vitamin is
identified, a specific recommendation for intakes to prevent the risk of deficiency or to alleviate
low levels of this micronutrient may remain undetermined. Such studies require the appropriate
design that demonstrates how a genetic variant modifies the response to dietary intake on the
outcome trait of interest and perhaps identify responders and non-responders. Genetic markers
related to a performance trait, such as aerobic capacity or power, also provide little information
on what factors could be used to improve the trait of interest.
With the exception of investigations exploring genetic variation and supplemental caffeine,
which have been shown to modify endurance exercise outcomes (19, 20), there are few
performance studies that have examined the role of genetics and other dietary factors on athletic
outcomes. A gene-diet interaction may not be associated directly with a quantifiable performance
outcome, such as increased aerobic capacity, speed or strength, but rather with intermediate
biomarkers or phenotypes, such as body composition or circulating vitamin D levels, which are
independent determinants of athletic performance, injury-risk and post-training recovery (1, 21–
24). For example, it is well-known that low iron stores impact hemoglobin production which in
turn decreases the oxygen carrying capacity of the blood, leading to a lack of oxygen to working
muscles and resulting in impaired muscle contraction and aerobic endurance (21). As such,
genetic markers that impact iron stores in response to intake can indirectly affect performance
through the oxygen carrying capacity of hemoglobin (25, 26).
Sport Nutrigenomics Vs. Talent Identification and Exercise Prescription
In an effort to achieve specific sport goals, there is generally considerable overlap in the
development of complementary training and dietary plans for athletes (27–29). However, it is
essential to underscore the distinction between the strength of evidence supporting DNA-based
advice for personalized nutrition vs. that for fitness programming. Despite the fervent interest
and ubiquity of commercial genetic testing to assess and improve exercise or sport performance
(30–32), it should be noted that there is a lack of evidence encompassing exercise prescription
and talent identification, such as the ability to predict the likelihood for the next generation of
Olympians (33, 34). Similarly, at this time there is insufficient evidence to recommended
training protocols (strength or endurance) based on genotype or polygenic scores, that target
specific fitness, weight loss or sport goals (35–38). The practical and ethical considerations of
genetic testing for sports performance have also been described (39).
Some commercial genetic tests claim to use proprietary algorithmic approaches to prescribe
training protocols based on evidence reported in peer-reviewed research (35). Although this may
provide some initial supportive documentation for differing responses to training based on
genotype, much larger sample sizes and improved methodologies are required, and should be
pursued (36). The approach by which individuals are categorized as having an “endurance” or
“power” advantage by genotype or being “responders” and “non-responders” to different training
protocols, requires transparency and standardization across the field to avoid potential bias and to
allow other researchers to replicate a study's methodology (37). Attempts to replicate studies to
test training outcomes based on genotype require the use of the identical scoring systems and it
appears that essential details of methods for grading of the strength of scientific evidence used in
these scoring systems are not reported (35).
There is a considerable amount of ongoing research investigating individual variation in response

to exercise training, however, sport and exercise genomics is still in its early stages and clinical
or sport utility is lacking (36, 40–44). Mainstream testing for personalized training or exercise
prescription based on genotype is not currently supported as a scientifically-sound approach,
although it is likely to be a common and viably employed coaching tool within the next decade
(35–37, 43, 44).
Go to:
Genes Associated With Sport Nutrition
The objective of this review is to examine the scientific evidence on specific nutrients and food
bioactives whereby genetic variants appear to modify individual responses related to athlete
health and athletic performance. Although many studies reviewed herein have not been studied
in athletes exclusively, they have been carried out in healthy individuals. Accordingly, several
studies outlined reflect optimal health, body composition and nutritional status, which for
athletes, provides the foundation for athletic success. Genetic variation impacting response to
various micro- and macronutrients, as well as bioactives such as caffeine, on performance-related
traits will be reviewed (Table 1).
Table 1
Summary of Genetic Variants that modify the association between various dietary factors and
performance-related outcomes.
Gene (rs number) Function Dietary factor Dietary sources Performance-related

outcome
CYP1A2 (rs762551) Encodes CYP1A2 liver enzyme: metabolizes caffeine; identifies

individuals as fast or slow metabolizers Caffeine Coffee, tea, soda, energy drinks,
caffeine supplements Cardiovascular health, endurance (21, 22, 57, 58)
ADORA2A (rs5751876) Regulates myocardial oxygen demand; increases coronary

circulation via vasodilation Caffeine Coffee, tea, soda, energy drinks, caffeine
supplements Vigilance when fatigued, sleep quality (49, 51–53)
BCMO1 (rs11645428) Converts provitamin A carotenoids to Vitamin A Vitamin A

Bluefin tuna, hard goat cheese, eggs, mackerel, carrots, sweet potato Visuomotor
skills and immunity (93, 95, 98–101)
MTHFR (rs1801133) Produces the enzyme methylenetetrahydrofolate reductase, which is

involved in the conversion of folic acid and folate into their biologically active form, L-
methylfolate Folate Edamame, chicken liver, lentils, asparagus, black beans, kale, avocado
Megaloblastic anemia and hyperhomocysteinemia risk (112, 116–118)
HFE (rs1800562 and rs1799945) Regulates intestinal iron uptake Iron Beef, chicken,
fish, organ meats (heme iron); almonds, parsley, spinach (non-heme iron) Hereditary
hemochromatosis (130–132)
TMPRSS6 (rs4820268), TFR2 (rs7385804), TF (rs3811647) Regulate the peptide

hormone, hepcidin, which controls iron absorption Iron Beef, chicken, fish, organ meats
(heme iron); almonds, parsley, spinach (non-heme iron) Iron-deficiency anemia risk (24, 27,
120, 123–125)
FUT2 (rs602662) Involved in vitamin B12 cell transport and absorption Vitamin B12
Clams, oysters, herring, nutritional yeast, beef, salmon Megaloblastic anemia and
hyperhomocysteinemia (142)
GSTT1 (Ins/Del) Plays a role in vitamin C utilization via glutathione S-transferase enzymes
Vitamin C Red peppers, strawberries, pineapple, oranges, broccoli Circulating
ascorbic acid levels
Mitigate exercise-induced ROS production (153, 155)
GC (rs2282679) and CYP2R1 (rs10741657) GC encodes vitamin D-binding protein, involved in

binding and transporting vitamin D to tissues; CYP2R1 encodes the enzyme vitamin D 25-
hydroxylase involved in vitamin D activation Vitamin D Salmon, white fish, rainbow
trout, halibut, milk Circulating 25(OH)D levels impacting immunity, bone health,
inflammation, strength training and recovery (1, 162, 164, 166, 168)
GC (rs7041 and rs4588) GC encodes vitamin D-binding protein, involved in binding and
transporting vitamin D to tissues; Vitamin D is required for calcium absorption Calcium
Yogurt, milk, cheese, firm tofu, canned salmon (with bones), edamame Bone/stress
fracture risk
Muscle contraction, nerve conduction, blood clotting (162, 164, 166, 168)
PEMT (rs12325817) Involved in endogenous choline synthesis via the hepatic

phosphatidylethanolamine N-methyltransferase pathway Choline Eggs, beef, poultry,
fish, shrimp, broccoli, salmonMuscle or liver damage, reduced neurotransmitters (174, 175, 185,
186)
MTHFD1 (rs2236225) Encodes protein involved in trifunctional enzyme activities related

to metabolic handling of choline and folate Folate/CholineFolate: Edamame, chicken liver,
lentils, asparagus, blck beans, kale, avocado
Choline: Eggs, beef, poultry, fish, shrimp, broccoli, salmon Muscle or liver damage, reduced
neurotransmitters (185, 186)
FTO (rs1558902/rs9939609) Precise function undetermined; plays a role in metabolism and has
been consistently linked to weight, BMI and body composition Protein/SFA:PUFA
Protein: chicken, beef, tofu, salmon, cottage cheese, lentils, milk, Greek yogurt
SFA: cheese, butter, red meat, baked goods
PUFA: flaxseed oil, grape seed oil, sunflower oil Optimizing body composition (190, 191)
TCF7L2 (rs7903146) Involved in expression of body fat Fat Nuts/seeds, butter, oils,
cheese, red meat, high-fat dairy Optimizing body composition (192, 193)
PPARγ2 (rs1801282) Regulates adipocyte differentiation MUFA Macadamia nuts, almond

butter, peanut butter, olive oil, canola oil, sesame oilOptimizing body composition (194)
Open in a separate window
Caffeine
Caffeine, found naturally occurring in several plant species including coffee, tea, cocoa, and
guarana, is widely used in sport as a performance enhancer or ergogenic aid often in the form of
caffeinated tablets, gels or chews.
In the field of nutrigenomics, caffeine is the most widely researched compound with several
randomized controlled trials investigating the modifying effects of genetic variation on athletic
performance (19, 20, 45). Numerous studies have investigated the effect of supplemental
caffeine on exercise performance, but there is considerable inter-individual variability in the
magnitude of these effects (46–48), or in the lack of an effect (49, 50) when compared to
placebo. These inter-individual differences appear to be partly due, to variation in genes such as
CYP1A2 and possibly ADORA2, which are associated with caffeine metabolism, sensitivity and
response (51).
Over 95% of caffeine is metabolized by the CYP1A2 enzyme, which is encoded by the CYP1A2
gene (52). The−163A>C (rs762551) single nucleotide polymorphism (SNP) has been shown to
alter CYP1A2 enzyme activity (53–55), and has been used to identify individuals as “fast” or
“slow” metabolizers of caffeine. Individuals who are considered slow metabolizers, that is with
the AC or CC genotype, have an elevated risk of myocardial infarction (56), hypertension and
elevated blood pressure (57, 58), and pre-diabetes (59), with increasing caffeinated coffee
consumption, whereas those with the AA genotype (fast metabolizers) do not appear to carry
these risks.
The largest caffeine and exercise study to date (19), examined the effects of caffeine and
CYP1A2 genotype, on 10-km cycling time trial performance in competitive male athletes after
ingestion of caffeine at 0 mg, 2 mg (low dose) or 4 mg (moderate dose) per kg body mass. There
was a 3% improvement in cycling time in the moderate dose in all subjects, which is consistent
with previous cycling time trial studies using similar doses (46, 60). However, there was a
significant caffeine-gene interaction where improvements in performance were seen at both
caffeine doses, but only in those with the AA genotype who are “fast metabolizers” of caffeine.
In that group, a 6.8% improvement in cycling time was observed at 4 mg/kg, which is >2–4%
mean improvement seen in several other cycling time trial studies, using similar doses (46, 60–
65). Among those with the CC genotype, 4 mg/kg caffeine impaired performance by 13.7%, and
in those with the AC genotype there was no effect of either caffeine dose (19). The findings are
consistent with a previous study (20), which observed a caffeine-gene interaction and improved
time trial cycling performance with caffeine only in those with the AA genotype.
Some previous endurance-type studies either did not observe any impact of the CYP1A2 gene on
caffeine-exercise studies (66, 67), or reported benefits only in slow metabolizers (45). There are
several reasons that may explain discrepancies in study outcomes including smaller sample sizes
(<20 subjects) that cause very low numbers and/or no subjects with the CC genotype (45, 67,
68), and shorter distance or different type (power vs. endurance) of performance test (45),
compared to those that reported improved endurance after caffeine ingestion in those with the
AA genotype of CYP1A2 (19, 20). The effects of genotype on performance appear to be most
prominent during exercise of longer duration or an accumulation of fatigue (aerobic or muscular
endurance) (69, 70). Fast metabolizers may quickly metabolize caffeine and achieve the benefits
of caffeine metabolites as exercise progresses, or override the short duration of negative impacts
(the initial stages of exercise), whereas the adverse effects of restricted blood flow and/or other
impacts of adenosine blockage in slow metabolizers are likely to remain for a longer duration
(71, 72). Indeed, in a study of basketball performance in elite players, caffeine improved
repeated jumps (muscular endurance; an accumulation of fatigue), but only in those with the AA
genotype, however, there was no genotype effect in the other two performance components of
the basketball simulation (73). Similarly, a cross-over design of 30 resistance-trained men found
that caffeine ingestion resulted in a higher number of repetitions in repeated sets of three
different exercises, and for total repetitions in all resistance exercises combined, which resulted
in a greater volume of work compared to placebo conditions, but only in those with the CYP1A2
AA genotype (74). Taken together, the weight of the evidence supports the role of CYP1A2 in
modifying the effects of caffeine ingestion on aerobic or muscular endurance-type exercise.
The ADORA2A gene is another potential genetic modifier of the effects of caffeine on
performance. The adenosine A2A receptor, encoded by the ADORA2A gene, has been shown to
regulate myocardial oxygen demand and increase coronary circulation by vasodilation (71, 72).
The A2A receptor is also expressed in the brain, where it regulates glutamate and dopamine
release, with associated effects on insomnia and pain (75, 76). The antagonism of adenosine
receptors by caffeine could differ by ADORA2A genotype, resulting in altered dopamine
signaling (51). Dopamine has been associated with motivation and effort in exercising
individuals, and this may be a mechanism by which differences in response to caffeine are
manifested (77–79).
One small pilot study has examined the effect of ADORA2A genotype (rs5751876) on the
ergogenic effects of caffeine under exercise conditions (80). Twelve female subjects underwent a
double-blinded, crossover trial comprising two 10-min cycling time trials following caffeine
ingestion or placebo. Caffeine benefitted all six subjects with the TT genotype but only one of
the six C allele carriers. Further studies are needed to confirm these preliminary findings and
include a larger sample to distinguish any effects between the different C allele carriers (i.e., CT
vs. CC genotypes).
Sleep is recognized as an essential component of physiological and psychological recovery from,

and preparation for, high-intensity training in athletes (81, 82). The ADORA2A rs5751876
genotype has also been implicated, by both objective and subjective measures, in various
parameters of sleep quality after caffeine ingestion in several studies (83–86). Adenosine
promotes sleep by binding to its receptors in the brain, mainly A1 and A2A receptors, and
caffeine reverses these effects by blocking the adenosine receptor, which promotes wakefulness
(83). This action, as well as the potency of caffeine to restore performance (cognitive or
physical) in ecological situations, such as highway-driving during the night (87), support the
notion that the adenosine neuromodulator/receptor system plays a major role in sleep–wake
regulation. This action of caffeine may also serve athletes well under conditions of jetlag, and
irregular or early training or competition schedules. Psychomotor speed relies on the ability to
respond, rapidly and reliably, to randomly occurring stimuli which is a critical component of
most sports (88). Genetic variation in ADORA2A has been shown to be a relevant determinant
of psychomotor vigilance in the rested and sleep-deprived state and modulates individual
responses to caffeine after sleep deprivation (85). In support of this notion, individuals who had
the TT genotype for ADORA2A rs5751876 consistently had faster response times (in seconds)
than C allele carriers after ingesting 400 mg caffeine during a sustained vigilant attention task
after sleep loss (85).
Consistent with the “adenosine hypothesis” of sleep where the accumulation of adenosine in the
brain promotes sleep, caffeine prolongs the time to fall asleep, decreases the deep stages of non-
rapid-eye movement (nonREM) sleep, reduces sleep efficiency, and alters the waking and sleep
electroencephalogram (EEG) frequencies, which reliably reflect the need for sleep (89–91).
Although additional research in this area is warranted, genetic variation appears to contribute to
subjective and objective responses to caffeine on sleep. Carriers of the ADORA2A (rs5751876)
C allele have greater sensitivity toward caffeine-induced sleep disturbance compared to those
with the TT genotype (84). Taken together, it appears that individuals with the TT genotype for
the rs5751876 SNP in the ADORA2A gene may have better performance outcomes, faster
response times and less sleep disturbance following caffeine ingestion.
Vitamin A
No studies have examined the role of genetic modifiers of vitamin A status directly on athletic
performance, however, there are several important functions of this micronutrient that are
associated with optimal health, immunity and performance in athletes.
Vitamin A is a fat-soluble vitamin, which plays a key role in both vision (92) and immunity (93)
in its biologically active forms (retinal and retinoic acid). Vitamin A has diverse immune
modulatory roles; hence, vitamin A deficiency has been associated with both immune
dysfunctions in the gut, and several systemic immune disorders (93). Vitamin A is also a
powerful antioxidant, protecting eyes from ocular diseases and helping to maintain vision (92).
High-performance athletes appear to have superior visual abilities based on their capacity to
access distinct visual skills, such as contrast sensitivity, dynamic acuity, stereoacuity, and ocular
judgment, needed to accomplish interceptive actions (e.g., hand-eye coordination) and resolve
fine spatial detail, which is required by many sports (94, 95). In addition, slow visuomotor
reaction time (VMRT) has been associated with musculoskeletal injury risk in sporting situations
where there are greater challenges to visual stimulus detection and motor response execution
(96). These visuomotor skills are key contributors to enhanced sport performance, and
accordingly, require exceptional eye health.
Deficiencies of certain micronutrients such as vitamin A decrease immune defense against

invading pathogens and can cause the athlete to be more susceptible to infection. Low energy
availability (dieting), poor food choices, jetlag, physical and psychological stress, and exposure
to pollution and foreign pathogens in air, food and water while traveling can result in a
deterioration in immune function and increased susceptibility to illness (97). Athletes following
high volume, high intensity training and competition schedules are also known to have more
frequent upper respiratory tract infections (URTI) compared to both sedentary and moderately
exercising populations (97).
Upon absorption, provitamin A carotenoids are readily converted to vitamin A by the BCMO1
enzyme expressed in enterocytes of the intestinal mucosa (98). β-Carotene is the most abundant
provitamin A carotenoid in the diet and the conversion of beta-carotene to retinal or retinoic acid
is necessary for vitamin A to exert its biological functions. The rs11645428 variant in the
BCMO1 gene affects circulating plasma carotenoid levels by impacting the conversion of dietary
provitamin A carotenoids to active forms of vitamin A in the small intestine (99). Individuals
with the GG genotype are inefficient at this conversion, and may be at higher risk for vitamin A
deficiency (100). These individuals are considered low responders to dietary β-carotene so
consuming enough dietary pre-formed vitamin A (or supplements for vegans), can help to ensure
that circulating levels of active vitamin A are adequate to support vision, immunity and normal
growth and development.
Anemia-Related Micronutrients: Iron, Folate, and Vitamin B12
There is an abundance of research demonstrating the adverse effects of low iron storage and
anemia on athletic performance (23, 101–103). The estimated prevalence of anemias and low
levels of iron, folate, and vitamin B12 appear to be higher in elite-level athletes than in the
general population, and these deficiencies can have significant negative impacts on performance
(22, 23, 104–107). The most common symptoms of this disorder are fatigue, weakness and, in
extreme cases, shortness of breath or palpitations (103).
The importance of iron to athletes is established through its biological role in supporting the
function of proteins and enzymes essential for maintaining physical and cognitive performance
(108). Iron is incorporated into hemoglobin and myoglobin, proteins responsible for the transport
and storage of oxygen. Iron-deficiency anemia is the most common type of anemia among
athletes, who have higher iron requirements due to increased erythropoietic drive through higher
intensities and volumes of training. The female athlete is at particular risk of iron deficiency due
to menstruation and generally, a lower total energy or food intake compared to males (107, 109).
Along with dietary intake, footstrike hemolysis, gastrointestinal bleeding, exercise-induced
inflammation, non-steroidal autoinflammatory drug (NSAID) use and environmental factors such
as hypoxia (altitude), may influence iron metabolism in athletes of both sexes (23). Macrocytic
anemias, which occur when erythrocytes are larger than normal, are generally classified into
megaloblastic or nonmegaloblastic anemia. Megaloblastic anemia is caused by deficiency or
impaired utilization of vitamin B12 and/or folate, whereas non-megaloblastic macrocytic anemia
is caused by various diseases, and will not be discussed here (110). Other factors that are
associated with anemia risk include genetic variation, which can alter micronutrient metabolism,
transport or absorption, and can be used to identify individuals at risk of inadequate levels of
vitamin B12, folate and iron stores.
Performance improvements are usually seen with the treatment of anemia (23, 103, 104), which
is related to improvements in symptoms such as general feelings of fatigue and weakness,
difficulty exercising, and in more severe cases, dyspnea and palpitations (103).
Hyperhomocysteinemia, which can result from low folate and/or vitamin B12 intake, may also
increase the risk of skeletal muscle malfunction, including muscle weakness and muscle
regeneration, and will be discussed further below (111).
Folate
Methylene tetrahydrofolate reductase (MTHFR) is the rate-limiting enzyme in the methyl cycle,
and is encoded by the MTHFR gene (112). The C677T (rs1801133) polymorphism in the
MTHFR gene has been associated with low serum and red blood cell folate as well as elevated
plasma homocysteine levels, which is an independent risk factor for cardiovascular disease
(CVD) (113, 114). Several studies in athletic and non-athletic populations have shown that
individuals with the CT or TT genotype are at an increased risk of low circulating folate levels
when their diet is low in folate (115–118).
Although there are no studies examining performance outcomes related to MTHFR genotypes or
dietary folate intake, hyperhomocysteinemia has been shown to be associated with diminished
muscle function (111). Several studies conducted in older adults have found a significant
association between elevated plasma homocysteine concentrations and declined physical
function (119–122), which may be mediated by a reduction in strength (120). Compared to those
with the rs1801133 CC genotype, individuals with TT genotype and possibly the CT genotype
may be at a greater risk for hyperhomocysteinemia, although this may not be causative for lower
physical performance (111, 119, 120). However, soccer players and sedentary individuals with
the CC genotype have been shown to have more favorable body composition and performance
measures such as aerobic and anaerobic threshold rates, compared to carriers of the T allele
(118).
Iron Overload
Genetic variation associated with serum iron levels involves several genes such as HFE,
TMPRSS6, TFR2, and TF (25, 117, 123–128). The HFE gene is involved in the regulation of
intestinal iron uptake (129), and variations in this gene, which are not very common, have been
shown to increase the risk for hemochromatosis or iron overload (124, 130). Excess iron may be
toxic to tissues and cells because highly reactive “free” iron reacts with reactive oxygen species
(ROS) such as superoxide and hydrogen peroxides, or lipid peroxides to produce free radicals
(131). In turn, these free radicals can cause cell and tissue damage (including muscle) and,
ultimately, lead to cell death (132). Elevated biomarkers of iron such as ferritin and transferrin
are more common in those who are genetically predisposed to iron overload based on the HFE
gene variant (22, 124). Interestingly, athletes with the rare HFE (rs1800562) AA genotype,
which is associated with an increased risk for hemochromatosis, may be at a genetic advantage to
excel in sport if iron levels are at the high end of the normal range, but not excessive to cause
tissue damage. Notably, several studies have found that certain variants of the HFE gene that
increase risk of iron overload are more common in elite-level athletes compared to the general
population, suggesting this may be beneficial for performance (133–135).
Two SNPs in the HFE gene (rs1800562 and rs1799945) can be used to predict risk of hereditary
hemochromatosis. Based on the combination of variants from these two SNPs, individuals can be
categorized as having a high, medium, or low risk for iron overload (124, 128). While genetic
risk for iron overload may have a favorable impact on performance, it is necessary for athletes
with a medium or high risk to avoid iron supplementation as this could lead to adverse health
outcomes (124) and diminished performance.
Low Iron Status
Three main SNPs: TMPRSS6 (rs4820268), TFR2 (rs7385804), TF (rs3811647) can be used to
assess genetic risk for low iron status, primarily due to their involvement in regulating the
expression of hepcidin, which is a peptide hormone that controls iron absorption (25, 123, 127).
Iron-deficiency anemia impairs performance by reducing oxygen-carrying capacity, but a
number of reports indicate that iron deficiency without anemia may affect physiological
performance and work capacity as well (21), particularly in women who experience iron
deficiency more frequently (22, 23).
There is a fine balance in achieving and maintaining adequate, but not excessive, iron levels for
optimal performance. Individuals with the GG genotype in the TMPRSS6 gene have an
increased risk of low transferrin saturation and hemoglobin, compared to those who are carriers
of the A allele (25, 26, 123, 136). In the TF gene, individuals have a greater risk for low ferritin
and elevated transferrin when they possess the AA genotype (25, 123, 136). Variation in the
TFR2 gene can impact hematocrit, mean corpuscular volume, and red blood cell count where
individuals with the CC genotype have an increased risk of low serum levels (25). Utilizing
algorithms to assess various genotype combinations, these genes can help to determine an
individual's overall risk for low iron status, which can lead to iron-deficiency anemia, and can be
used to target dietary iron intake. Although iron supplementation is common and frequently
prescribed in athletes, many individuals are at risk of taking iron supplements in excess (22, 137,
138). Although iron supplements are commonly “prescribed” by healthcare professionals and
nutritionists (139, 140), excess iron stored in skeletal muscle may not only be dangerous to the
health of the athlete (124, 141), but also can lead to oxidative stress and the formation of free
radicals, and reduced athletic performance (135, 142, 143).
Vitamin B12
Vitamin B12 is also associated with RBC formation and aerobic capacity. Megaloblastic anemia
results from vitamin B12 deficiency and is associated with elevated homocysteine, and results in
general feelings of fatigue and weakness. Megaloblastic anemia limits the blood's oxygen
carrying capacity, thus reducing its availability to cells (144). Variation in the FUT2 gene
(rs602662) has a significant impact on serum B12 levels where individuals with GG or GA
genotypes possess the greatest risk for low serum vitamin B12 levels, but only when the diet is
low in bioavailable sources of vitamin B12 (145). This is consistent with previous genome-wide
association studies, which found that individuals with the AA genotype had significantly higher
concentrations of serum vitamin B12 compared to carriers of the G allele (145).
Vitamin C
Vitamin C is a water-soluble antioxidant that aids in the reduction of exercise-induced free-

radical production (146). The production of potentially harmful ROS (147–149) in athletes is
greater than in non-athletes due to the massive increases (up to 200-fold at the level of skeletal
muscle) in oxygen consumption during strenuous exercise (146, 150). Vitamin C
supplementation was once thought to mitigate this risk; however, studies have shown that excess
vitamin C supplementation during endurance training can blunt beneficial training-induced
physiological adaptations, such as muscle oxidative capacity and mitochondrial biogenesis and
may actually diminish performance (148, 149, 151, 152). Dietary consumption of vitamin C, up
to 250 mg daily from fruits and vegetables, is likely sufficient to reduce oxidative stress without
having a negative effect on performance (151, 153). Additionally, collagen is a key constituent
of connective tissue such as tendons and ligaments, and vitamin C is necessary for collagen
production. This suggests that vitamin C may play a role in muscle growth and repair (154, 155).
Indeed, a recent landmark study examining collagen synthesis in athletes, reported that adding a
gelatin and vitamin C supplement to an intermittent exercise protocol improves collagen
synthesis and could play a beneficial role in injury prevention and accelerate musculoskeletal,
ligament, and/or tendon tissue repair (155).
The relationship between dietary vitamin C and circulating levels of ascorbic acid depend on an
individual's GSTT1 genotype (156). Individuals who do not meet the Recommended Dietary
Allowance (RDA) for vitamin C are significantly more likely to be vitamin C deficient (as
assessed by serum ascorbic acid levels) than those who meet the RDA, but this effect is much
greater in individuals with the GSTT1 Del/Del genotype than those with the Ins allele (156).
Genetic testing can help to identify athletes who may be at the greatest risk of low circulating
vitamin C (ascorbic acid) levels in response to intake. These low circulating ascorbic acid levels
may, in turn, diminish performance through an increased risk of high ROS and diminished
muscle or connective tissue repair. Although studies have identified associations between
circulating ascorbic acid concentrations and vitamin C transporters, SVCT1 and SVCT2, which
are encoded by SLC23A1 and SLC23A2 (157), there is no evidence that response to vitamin C
intake differs by genotype (158). As such, the use of variants in SLC23A1 and SLC23A2 to
make personalized dietary recommendations is not supported by the studies to date.
Vitamin D
There are no studies that link genetic modifiers of vitamin D status on athletic performance
outcomes; however, there are several functions of this vitamin that are associated with bone
health, immunity, recovery from training and various performance variables. Genetic
determinants of circulating 25-hydroxyvitamin D (25(OH)D) can influence each of these factors
thereby influencing performance.
Vitamin D is essential to calcium metabolism, increasing calcium absorption for optimal bone
health (1), which is relevant to all athletes, but particularly those participating in sports with a
high risk of stress fracture (159–161). Research comparing individuals with sufficient levels to
insufficient or deficient levels of 25(OH)D has shown that it helps to prevent injury (159–161),
promote larger type II muscle fiber size (24), reduce inflammation (162), reduce risk of acute
respiratory illness (159, 160) enhance functional rehabilitation (162), thereby optimizing
recovery and acute adaptive responses to intense training through reduced inflammation and
increased blood flow (163, 164).
Two genes that have been shown to impact vitamin D status are the GC gene and the CYP2R1
gene (165, 166). Variations in the GC and CYP2R1 genes are associated with a greater risk for
low serum 25(OH)D. In one study (165), where 50% of participants took vitamin D supplements,
only 22% of the participants had sufficient serum 25(OH)D levels. In the remaining 78% who
had insufficient levels, also only about half (47%) took vitamin D supplements. Within this
population, vitamin D supplementation only explained 18% of the variation, compared to 30%
from genetics, suggesting that genetics may play a greater role than supplementation in
determining risk for low 25(OH)D levels (165). Out of the four genotypes analyzed, only
CYP2R1 (rs10741657) and GC (rs2282679) were significantly associated with vitamin D status.
Specifically, participants with the GG or GA genotype of CYP2R1 (rs10741657) were nearly
four times more likely to have insufficient vitamin D levels. Those with the GG genotype of the
GC gene (rs2282679) were significantly more likely to have low vitamin D levels compared to
those with the TT genotype (165). These results were consistent with findings from previous
studies, including the Study of Underlying Genetic Determinants of Vitamin D and Highly
Related Traits (SUNLIGHT), which found significance on a genome-wide basis in 15 cohorts
with over 30,000 participants between three genetic variants including CYP2R1 (rs10741657)
and GC (rs2282679) on vitamin D status. Not surprisingly, the number of risk variants that the
participants possessed was directly related to their risk for vitamin D insufficiency (166). These
findings demonstrate that genetic variation may be more impactful than supplementation intakes
and behaviors on determining risk for vitamin D insufficiency.
Calcium
Although studies linking calcium intake, genetics and bone fracture has not been conducted in
athletes specifically, genetic variation as it relates to risk of calcium deficiency and fracture risk
have been studied in a large cohort of individuals, described below (167). Calcium is necessary
for growth, maintenance and repair of bone tissue and impacts maintenance of blood calcium
levels, regulation of muscle contraction, nerve conduction, and normal blood clotting (168). In
order to absorb calcium, adequate vitamin D intake is also necessary. Inadequate dietary calcium
and vitamin D increases the risk of low bone mineral density (BMD) and stress fractures. Low
energy intakes, and menstrual dysfunction in female athletes, along with low vitamin D and
calcium intakes further increase the risk of stress fractures in both males and females (169–171),
and stress fractures are common and serious injuries in athletes (172).
Some individuals do not utilize dietary calcium as efficiently as others and this may depend on
variations in the GC gene. In one study (167), subjects (n = 6,181) were genotyped for two SNPs
in the GC gene, rs7041 and rs4588, and calcium intake was assessed in relation to the
participants' risk for bone fracture (167). In the entire sample of participants, only a small
increased risk of bone fracture was observed for individuals homozygous for the G allele of GC
(rs7041) and the C allele of GC (rs4588). However, in participants with low dietary calcium
intake (<1.09 g/day) and who were homozygous for the G allele of rs7041 and the C allele of
rs4588, there was a 42% increased risk of fracture compared to other genotypes. No differences
between genotypes were found in participants with high dietary calcium intakes (167). These
findings suggest that calcium intake recommendations could be based on GC genotype in
athletes to help prevent stress fracture.
Choline
Choline was officially recognized as an essential nutrient by the Institute of Medicine (IOM) in
1998 (173). Choline plays a central role in many physiological pathways including
neurotransmitter synthesis (acetylcholine), cell-membrane signaling (phospholipids), bile and
lipid transport (lipoproteins), and methyl-group metabolism (homocysteine reduction) (174).
Human requirements for choline are dependent on gender, age and physical activity level as well
as genetics. Choline is produced in the body in small amounts, however, de novo synthesis of
choline alone is not sufficient to meet human requirements for optimal health (174, 175). The
liver and muscles are the major organs for methyl group metabolism, and choline deficiency has
been shown to cause both liver and muscle damage (176, 177). Signs of choline deficiency are
identified through elevated serum creatine phosphokinase (CPK), a marker of muscle damage
(178, 179), and abnormal deposition of fat in the liver, which may result in non-alcoholic fatty
liver disease (NAFLD) (176, 180). Reductions in plasma choline associated with strenuous
exercise such as triathlons and marathon running have been reported (181, 182). Acetylcholine, a
neurotransmitter involved in learning, memory, and attention, depends on adequate choline and a
reduction in the release of this neurotransmitter may contribute to the development of fatigue and
exercise performance impairment (181–183). Choline supplementation may also improve lipid
metabolism, as it has been associated with more favorable body composition (184) and the
ability to aid rapid body mass reduction in weight class sports (185).
Common genetic variants in choline (PEMT gene) and a folate pathway enzyme (MTHFD1)
have been shown to impact the metabolic handling of choline and the risk of choline deficiency
across differing nutrient intakes (178, 186, 187). The relationship between genetic variants in
folate metabolism and choline requirement may arise from the overlapping roles of folate and
choline in methionine and phosphatidylcholine (PC) biosynthesis. PC is critical for the structural
integrity of cell membranes and cell survival, and methionine is an essential amino acid that
plays a critical role in human metabolism and health (187, 188). The MTHFD1 rs2236225 SNP,
which is associated with folate metabolism, has been shown to increase the demands for choline
as a methyl-group donor, thereby increasing dietary requirements for this nutrient (188).
Individuals that are A allele carriers of the MTHFD1 gene have been shown to develop signs of
choline deficiency and organ (liver and muscle) dysfunction compared to those with the GG
genotype (186, 188, 189).
While humans can make choline endogenously via the hepatic phosphatidylethanolamine N-
methyltransferase (PEMT) pathway, a SNP in the PEMT gene (rs12325817) has been shown to
influence the risk of choline deficiency and the partitioning of more dietary choline toward PC
biosynthesis at the expense of betaine synthesis (used a methyl donor) (186). Individuals who are
C allele carriers of the PEMT gene have been shown to develop signs of choline deficiency and
organ (liver and muscle) dysfunction compared to those with the GG genotype (178).
Athletes by nature experience muscle damage through high volume and high intensity training
(195). A deficient or suboptimal status of choline may place additional stressors on an athlete's
ability to recover, repair and adapt to their given training stimulus.
Macronutrients and Body Composition
Several aspects of physique such as body size, shape and composition contribute to the success
of an athlete, in most sports. In the athletic population, body composition is often the focus for
change, as it can be easily manipulated through diet as both total energy intake and
macronutrient composition (192, 196). Variations in macronutrient intake can significantly
impact both body fat percentage and lean mass (29, 190, 193, 197–199), as well as performance,
where macronutrient manipulation has long been used to partition calories to be used for specific
goals across different sports (196).
Although research examining dietary factors and genetics has revealed that manipulation of
dietary fat and protein intakes may have greater modifying effects on body composition than
carbohydrates, all macronutrients serve a critical purpose. Carbohydrates provide a key fuel for
the brain, CNS and working muscles, and the amount and timing of intake impacts sport
performance over a large range of intensities (200, 201). Adequate dietary protein is essential for
strength and lean body mass accretion, while also playing a relevant role in preserving lean body
mass during caloric restriction and immune function (29, 202, 203). Dietary fat provides energy
for aerobic activities and is required for the absorption of fat-soluble vitamins (204). Recent
research shows that percent energy intake from protein and fat can be targeted to the individual
based on genetic variation for optimizing body weight and composition (190, 193, 197–199).
Percent energy from carbohydrates should be guided by fuel needs for training and competition
while also considering targeted protein and fat intakes based on genetic variation.
Protein
The FTO gene is also known as the ‘fat mass and obesity-associated gene’ since it has been
shown to impact weight management and body composition (194, 199, 205, 206). Dietary
interventions may mitigate genetic predispositions associated with a higher body mass index
(BMI) and body fat percentage, as determined by genetic variation in the FTO gene. Specifically,
the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) multicenter trial
found that carrying an A allele of the FTO gene (rs1558902–a surrogate marker for rs9939609)
and consuming a high protein diet was associated with a significantly lower fat mass at the 2-
year follow up period compared to carrying two T alleles. Importantly, participants with the AA
genotype (lesser effects in those with AT genotype) who were following the high protein diet
protocol had significantly greater losses of total fat mass, total adipose tissue, visceral adipose
tissue, lower total percent fat mass and percent trunk fat, compared to those following a lower
protein diet protocol (199). Other studies have shown similar results where dietary protein intake
was shown to be protective against the effect of the FTO risk variants on BMI and waist
circumference (194). A randomized controlled trial (RCT) in 195 individuals showed that a
hypocaloric diet resulted in greater weight loss in rs9939609 A allele carriers than noncarriers in
both higher and lower protein diets, although metabolic improvements improved in all genotypes
in the higher protein diets (205). Athletes who possess the AA genotype of the FTO gene at
rs1558902 would benefit the most in terms of consuming a moderate-to-high protein diet (at least
25% of energy from protein) to optimize body composition. Greater lean mass in athletes has
been associated with improved performance in strength and power sports, as well as some
endurance events, and a decreased risk for injuries (191, 207). For those athletes who do not
possess the response variant (i.e., greater fat loss with higher protein intakes), following a diet
with moderate protein intake (~15–20% energy), to achieve and maintain an ideal body
composition is important to note, as excess protein calories may be counterproductive toward
this goal. In this instance, dietary goals for optimal performance may be better met by
substituting protein energy for other macronutrients such as carbohydrates for fuel, fiber,
prebiotics and other micronutrients, or by increasing intakes of essential fats.
Dietary Fat
Dietary fat, an essential component of the human diet, provides energy for aerobic endurance
exercise and is necessary for the absorption of the fat-soluble vitamins A, D, E, and K.
Independent of total energy intake, the percentage of energy derived from fat in an athlete's diet
can impact body composition, based on genetic variation (204). Individuals possessing the TT
genotype of TCF7L2, transcription factor 7 like 2, at rs7903146 appear to benefit from
consuming a lower percent of total energy from fat (20–25% of energy) to optimize body
composition (198). Specifically, participants with the TT genotype lost more fat mass when they
were consuming a low-fat diet, compared to a high-fat diet (40–45% of energy) (198). Moreover,
individuals with the CC genotype in rs7903146 who consumed lower-fat diets actually lost
significantly more lean mass, suggesting that these individuals should avoid low-fat nutrition
interventions (197) in order to optimize body composition for athletic performance (191, 207).
Body composition can, therefore, be optimized by targeting fat intake based on genetic variation
in the TCF7L2 gene.
Monounsaturated Fat
Recommendations for fat intake can be further targeted to the different types of fats comprising
total dietary fat. Athletes with the GG or GC genotype of the PPARγ2 gene at rs1801282 would
benefit from a weight loss intervention that specifically targets body fat, while preserving lean
body mass. Such individuals have been shown to demonstrate an enhanced weight loss response
when consuming > 56% of total fat from monounsaturated fatty acids (MUFAs) compared to
those with the GG or GC genotype who consume < 56% of total fat from MUFAs. These results
have not been found in those with the CC genotype of PPARγ2 at rs1801282 (208).
MUFAs can be targeted in athletes who are aiming to decrease their body fat. It is well-known
that a lower body fat percentage is associated with enhanced performance in most sports (191,
207), however, sport clinicians must be cautious about nutrition recommendations aimed at
reducing body fat. Striving for very low levels of body fat is highly correlated with the Relative
Energy Deficiency in Sport (RED-S) syndrome in both females and males, which refers to
‘impaired physiological functioning caused by relative energy deficiency and includes
impairments of metabolic rate, menstrual function, bone health, immunity, protein synthesis and
cardiovascular health (209).
Saturated Fat and Polyunsaturated Fat
A nested case-control study found that the ratio of dietary saturated fatty acids (SFA) to
polyunsaturated fatty acids (PUFA) influenced the risk of obesity associated with the TA and AA
variants of the FTO gene at rs9939609 (210). Specifically, participants possessing the A allele
had a significantly higher BMI and waist circumference (WC) compared to TT homozygotes, but
only when intakes of SFA were high and PUFAs were low. When participants with the A allele
consumed < ~15% of energy from SFA and had a higher dietary PUFA:SFA ratio, there were no
significant differences in WC and BMI between this group and participants with the TT genotype
of rs9939609 (210). These findings have implications for nutrition counseling impacting body
composition (abdominal fat specifically) and BMI. Athletes with the TA or AA genotype may
have a greater risk for accumulating excessive abdominal fat. An athlete can mitigate this risk by
aiming to consume <10% of energy from SFA (to also account for heart health) and > 4% of
energy from PUFAs, resulting in a PUFA:SFA ratio of at least 0.4 (210).
Go to:
Summary
This paper provided an overview of the current science linking genetic variation to nutritional or
supplemental needs with a focus on sport performance. One of the ultimate goals in the field of
personalized sport nutrition is the design of tailored nutritional recommendations to improve
direct and indirect factors that influence athletic performance. More specifically, personalized
nutrition pursuits aim to develop more comprehensive and dynamic nutritional and supplement
recommendations based on shifting, interacting parameters in an athlete's internal and external
(sport) environment throughout their athletic career and beyond.
Currently, there are few gene-diet interaction studies that have directly measured performance
outcomes and been conducted in competitive athletes, so this should be a focus of future
research. However, it has been established that serum levels and/or dietary intakes of several
nutrients and food bioactives can impact overall health, body composition and in turn result in
modest to sizable modifying effects in athletic performance. The strongest evidence to date
appears to be for caffeine on endurance performance with several trials demonstrating the
modifying effects of genetic variants with sports performance outcomes. Genetic testing for
personalized nutrition may, therefore, be an additional tool that can be implemented into the
practice of sport clinicians, nutritionists and coaches to guide nutritional counseling and meal
planning with the aim of optimizing athletic performance.
Go to:
Author Contributions
NG and AE-S conceived of the original idea for the review and NG wrote the first draft. All
authors contributed to the writing and editing of the manuscript. AE-S secured funding.
Conflict of Interest Statement
AE-S is the Founder and holds shares in Nutrigenomix Inc. NG is on the Science Advisory
Board of Nutrigenomix Inc. SV was a paid employee and remains a paid consultant with
Nutrigenomix. The remaining author declares that the research was conducted in the absence of
any commercial or financial relationships that could be construed as a potential conflict of
interest.
Go to:
Footnotes
Funding. Funding support for this review was provided by Mitacs and Nutrigenomix Inc.
Go to:
References
1. Thomas DT, Erdman KA, Burke LM. American college of sports medicine joint position
statement. nutrition and athletic performance. Med Sci Sports Exerc. (2016) 48:543–68.
10.1249/MSS.0000000000000852 [PubMed] [CrossRef] [Google Scholar]
2. Nielsen DE, El-Sohemy A. Disclosure of genetic information and change in dietary intake: a
randomized controlled trial. PLoS ONE (2014) 9:e112665. 10.1371/journal.pone.0112665 [PMC
free article] [PubMed] [CrossRef] [Google Scholar]
3. Hietaranta-Luoma HL, Tahvonen R, Iso-Touru T, Puolijoki H, Hopia A. An intervention study

of individual, apoE genotype-based dietary and physical-activity advice: impact on health
behavior. J Nutrigenet Nutrigenomics (2014) 7:161–74. 10.1159/000371743 [PubMed]
[CrossRef] [Google Scholar]
4. Livingstone KM, Celis-Morales C, Navas-Carretero S, San-Cristobal R, Macready AL,

Fallaize R, et al. . Effect of an Internet-based, personalized nutrition randomized trial on dietary
changes associated with the Mediterranean diet: the Food4Me Study. Am J Clin Nutr. (2016)
104:288–97. 10.3945/ajcn.115.129049 [PubMed] [CrossRef] [Google Scholar]
5. Celis-Morales C, Marsaux CF, Livingstone KM, Navas-Carretero S, San-Cristobal R, Fallaize

R, et al. . Can genetic-based advice help you lose weight? Findings from the Food4Me European
randomized controlled trial. Am J Clin Nutr. (2017) 105:1204–1213. 10.3945/ajcn.116.145680
[PubMed] [CrossRef] [Google Scholar]
6. El-Sohemy A. Only DNA-based dietary advice improved adherence to the Mediterranean diet
score. Am J Clin Nutr. (2017) 105:770. 10.3945/ajcn.116.149021 [PubMed] [CrossRef] [Google
Scholar]
7. Keegana RJ, Harwood CG, Spray CM, Lavalleec D. A qualitative investigation of the
motivational climate in elite sport. Psychol Sport Exerc. (2014) 15:97–107.
10.1016/j.psychsport.2013.10.006 [CrossRef] [Google Scholar]
8. Spronk I, Heaney SE, Prvan T, O'Connor HT. Relationship between general nutrition
knowledge and dietary quality in elite athletes. Int J Sport Nutr Exerc Metab. (2015) 25:243–51.
10.1123/ijsnem.2014-0034 [PubMed] [CrossRef] [Google Scholar]
9. Garcia-Roves PM, Garcia-Zapico P, Patterson AM, Iglesias-Gutierrez E. Nutrient intake and
food habits of soccer players: analyzing the correlates of eating practice. Nutrients (2014)
6:2697–717. 10.3390/nu6072697 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
10. Horne J, Madill J, O'Connor C, Shelley J, Gilliland J. A systematic review of genetic testing
and lifestyle behaviour change: are we using high-quality genetic interventions and considering
behaviour change theory? Lifestyle Genom. (2018) 11:49–63. 10.1159/000488086 [PubMed]
11. Kicklighter JR, Dorner B, Hunter AM, Kyle M, Pflugh Prescott M, Roberts S, et al. .
Visioning report 2017: a preferred path forward for the nutrition and dietetics profession. J Acad
Nutr Diet. (2017) 117:110–127. 10.1016/j.jand.2016.09.027 [PubMed] [CrossRef] [Google
Scholar]
12. Collins J, Adamski MM, Twohig C, Murgia C. Opportunities for training for nutritional
professionals in nutritional genomics: what is out there? Nutr Diet. (2018) 75:206–18.
10.1111/1747-0080.12398 [PubMed] [CrossRef] [Google Scholar]
13. Abrahams M, Frewer L, Bryant E, Stewart-Knox B. Factors determining the integration of

nutritional genomics into clinical practice by registered dietitians. Trends Food Sci Technol.
(2017) 59:139–47 10.1016/j.tifs.2016.11.005 [CrossRef] [Google Scholar]
14. Cormier H, Tremblay BL, Paradis AM, Garneau V, Desroches S, Robitaille J, et al. .
Nutrigenomics-perspectives from registered dietitians: a report from the Quebec-wide e-
consultation on nutrigenomics among registered dietitians. J Hum Nutr Diet. (2014) 27:391–400.
10.1111/jhn.12194 [PubMed] [CrossRef] [Google Scholar]
15. Gorman U, Mathers JC, Grimaldi KA, Ahlgren J, Nordstrom K. Do we know enough? A
scientific and ethical analysis of the basis for genetic-based personalized nutrition. Genes Nutr.
(2013) 8:373–81. 10.1007/s12263-013-0338-6 [PMC free article] [PubMed] [CrossRef] [Google
Scholar]
16. Maughan RJ. Quality assurance issues in the use of dietary supplements, with special
reference to protein supplements. J Nutr. (2013) 143:1843S−7S. 10.3945/jn.113.176651
17. Pitsiladis Y, Ferriani I, Geistlinger M, de Hon O, Bosch A, Pigozzi F. A holistic antidoping

approach for a fairer future for sport. Curr Sports Med Rep. (2017) 16:222–4.
10.1249/JSR.0000000000000384 [PubMed] [CrossRef] [Google Scholar]
18. de Hon O, Kuipers H, van Bottenburg M. Prevalence of doping use in elite sports: a review
of numbers and methods. Sports Med. (2015) 45:57–69. 10.1007/s40279-014-0247-x [PubMed]
19. Guest N, Corey P, Vescovi J, El-Sohemy A. Caffeine, CYP1A2 genotype, and endurance
performance in athletes. Med Sci Sports Exerc. (2018) 50:1570–8.
20. Womack CJ, Saunders MJ, Bechtel MK, Bolton DJ, Martin M, Luden ND, et al. . The
influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine. J Int Soc Sports
Nutr. (2012) 9:7. 10.1186/1550-2783-9-7 [PMC free article] [PubMed] [CrossRef] [Google
Scholar]
21. Haas JD, Brownlie TIV. Iron deficiency and reduced work capacity: a critical review of the
research to determine a causal relationship. J Nutr. (2001) 131:676S−688S; discussion 688S-
690S. 10.1093/jn/131.2.676S [PubMed] [CrossRef] [Google Scholar]
22. Clenin G, Cordes M, Huber A, Schumacher YO, Noack P, Scales J, et al. . Iron deficiency in
sports-definition, influence on performance and therapy. Swiss Med Wkly. (2015) 145:w14196.
10.4414/smw.2015.14196 [PubMed] [CrossRef] [Google Scholar]
23. DellaValle DM. Iron supplementation for female athletes: effects on iron status and
performance outcomes. Curr Sports Med Rep. (2013) 12:234–9.
10.1249/JSR.0b013e31829a6f6b [PubMed] [CrossRef] [Google Scholar]
24. Cannell JJ, Hollis BW, Sorenson MB, Taft TN, Anderson JJ. Athletic performance and
vitamin D. Med Sci Sports Exerc. (2009) 41:1102–10. 10.1249/MSS.0b013e3181930c2b
25. Pichler I, Minelli C, Sanna S, Tanaka T, Schwienbacher C, Naitza S, et al. . Identification of

a common variant in the TFR2 gene implicated in the physiological regulation of serum iron
levels. Hum Mol Genet. (2011) 20:1232–40. 10.1093/hmg/ddq552 [PMC free article] [PubMed]
26. Du X, She E, Gelbart T, Truksa J, Lee P, Xia Y, et al. . The serine protease TMPRSS6 is
required to sense iron deficiency. Science (2008) 320:1088–92. 10.1126/science.1157121 [PMC
27. Garcia M, Martinez-Moreno JM, Reyes-Ortiz A, Suarez Moreno-Arrones L. Garcia AA,

Garciacaballero M. Changes in body composition of high competition rugby players during the
phases of a regular season; influence of diet and exercise load. Nutr Hosp. (2014) 29:913–21.
10.3305/nh.2014.29.4.7227 [PubMed] [CrossRef] [Google Scholar]
28. Pyne DB, Sharp RL. Physical and energy requirements of competitive swimming events. Int
J Sport Nutr Exerc Metab. (2014) 24:351–9. 10.1123/ijsnem.2014-0047 [PubMed] [CrossRef]
[Google Scholar]
29. Longland TM, Oikawa SY, Mitchell CJ, Devries MC, Phillips SM. Higher compared with
lower dietary protein during an energy deficit combined with intense exercise promotes greater
lean mass gain and fat mass loss: a randomized trial. Am J Clin Nutr. (2016) 103:738–46.
10.3945/ajcn.115.119339 [PubMed] [CrossRef] [Google Scholar]
30. Guth LM, Roth SM. Genetic influence on athletic performance. Curr Opin Pediatr. (2013)
25:653–8. 10.1097/MOP.0b013e3283659087 [PMC free article] [PubMed] [CrossRef] [Google
Scholar]
31. Mattsson CM, Wheeler MT, Waggott D, Caleshu C, Ashley EA. Sports genetics moving
forward: lessons learned from medical research. Physiol Genomics (2016) 48:175–82.
10.1152/physiolgenomics.00109.2015 [PubMed] [CrossRef] [Google Scholar]
32. Varley I, Patel S, Williams AG, Hennis PJ. The current use, and opinions of elite athletes and
support staff in relation to genetic testing in elite sport within the UK. Biol Sport. (2018) 35:13–
9. 10.5114/biolsport.2018.70747 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
33. Webborn N, Williams A, McNamee M, Bouchard C, Pitsiladis Y, Ahmetov I, et al. . Direct-

to-consumer genetic testing for predicting sports performance and talent identification:
consensus statement. Br J Sports Med. (2015) 49:1486–91. 10.1136/bjsports-2015-095343 [PMC
34. Roth SM. Critical overview of applications of genetic testing in sport talent identification.
Recent Pat DNA Gene Seq. (2012) 6:247–55. 10.2174/187221512802717402 [PubMed]
35. Jones N, Kiely J, Suraci B, Collins DJ, de Lorenzo D, Pickering C, et al. . A genetic-based
algorithm for personalized resistance training. Biol Sport. (2016) 33:117–26.
10.5604/20831862.1198210 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
36. Vlahovich N, Hughes DC, Griffiths LR, Wang G, Pitsiladis YP, Pigozzi F, et al. . Genetic
testing for exercise prescription and injury prevention: AIS-Athlome consortium-FIMS joint
statement. BMC Genomics (2017) 18(Suppl. 8):818. 10.1186/s12864-017-4185-5 [PMC free
article] [PubMed] [CrossRef] [Google Scholar]
37. Karanikolou A, Wang G, Pitsiladis Y. Letter to the editor: a genetic-based algorithm for
personalized resistance training. Biol Sport. (2017) 34:31–33. 10.5114/biolsport.2017.63385
[PMC free article] [PubMed] [CrossRef] [Google Scholar]
38. Vlahovich N, Fricker PA, Brown MA, Hughes D. Ethics of genetic testing and research in
sport: a position statement from the Australian Institute of Sport. Br J Sports Med. (2017) 51:5–
11. 10.1136/bjsports-2016-096661 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
39. Williams AG, Wackerhage H, Day SH. Genetic testing for sports performance, responses to
training and injury risk: practical and ethical considerations. Med Sport Sci. (2016) 61:105–19.
10.1159/000445244 [PubMed] [CrossRef] [Google Scholar]
40. Mann TN, Lamberts RP, Lambert MI. High responders and low responders: factors
associated with individual variation in response to standardized training. Sports Med. (2014)
44:1113–24. 10.1007/s40279-014-0197-3 [PubMed] [CrossRef] [Google Scholar]
41. Williams CJ, Williams MG, Eynon N, Ashton KJ, Little JP, Wisloff U, et al. . Genes to
predict VO2max trainability: a systematic review. BMC Genomics (2017) 18(Suppl. 8):831.
10.1186/s12864-017-4192-6 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
42. Yan X, Eynon N, Papadimitriou ID, Kuang J, Munson F, Tirosh O, et al. . The gene SMART
study: method, study design, and preliminary findings. BMC Genomics (2017) 18(Suppl. 8):821.
43. Pitsiladis YP, Tanaka M, Eynon N, Bouchard C, North KN, Williams AG, et al. . Athlome
Project Consortium: a concerted effort to discover genomic and other “omic” markers of athletic
performance. Physiol Genomics (2016) 48:183–90. 10.1152/physiolgenomics.00105.2015 [PMC
44. Ahmetov II, Fedotovskaya ON. Current progress in sports genomics. Adv Clin Chem. (2015)
70:247–314. 10.1016/bs.acc.2015.03.003 [PubMed] [CrossRef] [Google Scholar]
45. Pataky MW, Womack CJ, Saunders MJ, Goffe JL, D'Lugos AC, El-Sohemy A, et al. .
Caffeine and 3-km cycling performance: effects of mouth rinsing, genotype, and time of day.
Scand J Med Sci Sports. (2016) 26:613–9. 10.1111/sms.12501 [PubMed] [CrossRef] [Google
Scholar]
46. Ganio MS, Klau JF, Casa DJ, Armstrong LE, Maresh CM. Effect of caffeine on sport-
specific endurance performance: a systematic review. J Strength Cond Res. (2009) 23:315–24.
10.1519/JSC.0b013e31818b979a [PubMed] [CrossRef] [Google Scholar]
47. Higgins S, Straight CR, Lewis RD. The effects of preexercise caffeinated coffee ingestion on
endurance performance: an evidence-based review. Int J Sport Nutr Exerc Metab. (2016)
26:221–39. 10.1123/ijsnem.2015-0147 [PubMed] [CrossRef] [Google Scholar]
48. Graham TE, Spriet LL. Performance and metabolic responses to a high caffeine dose during
prolonged exercise. J Appl Physiol. (1985). (1991) 71:2292–8. [PubMed] [Google Scholar]
49. Hunter AM, St Clair Gibson A, Collins M, Lambert M, Noakes TD. Caffeine ingestion does
not alter performance during a 100-km cycling time-trial performance. Int J Sport Nutr Exerc
Metab. (2002) 12:438–52. 10.1123/ijsnem.12.4.438 [PubMed] [CrossRef] [Google Scholar]
50. Roelands B, Buyse L, Pauwels F, Delbeke F, Deventer K, Meeusen R. No effect of caffeine
on exercise performance in high ambient temperature. Eur J Appl Physiol. (2011) 111:3089–95.
10.1007/s00421-011-1945-9 [PubMed] [CrossRef] [Google Scholar]
51. Yang A, Palmer AA, de Wit H. Genetics of caffeine consumption and responses to caffeine.
Psychopharmacology (Berl). (2010) 211:245–57. 10.1007/s00213-010-1900-1 [PMC free article]
52. Begas E, Kouvaras E, Tsakalof A, Papakosta S, Asprodini EK. In vivo evaluation of

CYP1A2, CYP2A6, NAT-2 and xanthine oxidase activities in a Greek population sample by the
RP-HPLC monitoring of caffeine metabolic ratios. Biomed Chromatogr. (2007) 21:190–200.
10.1002/bmc.736 [PubMed] [CrossRef] [Google Scholar]
53. Ghotbi R, Christensen M, Roh HK, Ingelman-Sundberg M, Aklillu E, Bertilsson L.

Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype
relationship in Swedes and Koreans. Eur J Clin Pharmacol. (2007) 63:537–46. 10.1007/s00228-
007-0288-2 [PubMed] [CrossRef] [Google Scholar]
54. Djordjevic N, Ghotbi R, Bertilsson L, Jankovic S, Aklillu E. Induction of CYP1A2 by heavy

coffee consumption in Serbs and Swedes. Eur J Clin Pharmacol. (2008) 64:381–5.
10.1007/s00228-007-0438-6 [PubMed] [CrossRef] [Google Scholar]
55. Koonrungsesomboon N, Khatsri R, Wongchompoo P, Teekachunhatean S. The impact of

genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis.
Pharmacogenomics J. (2017) 18:760–8. 10.1038/s41397-017-0011-3 [PubMed] [CrossRef]
[Google Scholar]
56. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype, and
risk of myocardial infarction. JAMA (2006) 295:1135–41. 10.1001/jama.295.10.1135 [PubMed]
57. Palatini P, Ceolotto G, Ragazzo F, Dorigatti F, Saladini F, Papparella I, et al. . CYP1A2

genotype modifies the association between coffee intake and the risk of hypertension. J
Hypertens. (2009) 27:1594–601. 10.1097/HJH.0b013e32832ba850 [PubMed] [CrossRef]
[Google Scholar]
58. Soares RN, Schneider A, Valle SC, Schenkel PC. The influence of CYP1A2 genotype in the
blood pressure response to caffeine ingestion is affected by physical activity status and caffeine
consumption level. Vascul Pharmacol. (2018) 106:67–73. 10.1016/j.vph.2018.03.002 [PubMed]
59. Palatini P, Benetti E, Mos L, Garavelli G, Mazzer A, Cozzio S, et al. . Association of coffee
consumption and CYP1A2 polymorphism with risk of impaired fasting glucose in hypertensive
patients. Eur J Epidemiol. (2015) 30:209–17. 10.1007/s10654-015-9990-z [PubMed] [CrossRef]
[Google Scholar]
60. Desbrow B, Biddulph C, Devlin B, Grant GD, Anoopkumar-Dukie S, Leveritt MD. The
effects of different doses of caffeine on endurance cycling time trial performance. J Sports Sci.
(2012) 30:115–20. 10.1080/02640414.2011.632431 [PubMed] [CrossRef] [Google Scholar]
61. Skinner TL, Jenkins DG, Taaffe DR, Leveritt MD, Coombes JS. Coinciding exercise with
peak serum caffeine does not improve cycling performance. J Sci Med Sport. (2013) 16:54–9.
10.1016/j.jsams.2012.04.004 [PubMed] [CrossRef] [Google Scholar]
62. Saunders B, de Oliveira LF, da Silva RP, de Salles Painelli V, Goncalves LS, Yamaguchi G,
et al. . Placebo in sports nutrition: a proof-of-principle study involving caffeine supplementation.
Scand J Med Sci Sports. (2016) 27:1240–7. 10.1111/sms.12793 [PubMed] [CrossRef] [Google
Scholar]
63. Jenkins NT, Trilk JL, Singhal A, O'Connor PJ, Cureton KJ. Ergogenic effects of low doses of
caffeine on cycling performance. Int J Sport Nutr Exerc Metab. (2008) 18:328–42.
10.1123/ijsnem.18.3.328 [PubMed] [CrossRef] [Google Scholar]
64. Graham-Paulson T, Perret C, Goosey-Tolfrey V. Improvements in cycling but not

handcycling 10 km time trial performance in habitual caffeine users. Nutrients (2016) 8:E393
10.3390/nu8070393 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
65. Bortolotti H, Altimari LR, Vitor-Costa M, Cyrino ES. Performance during a 20-km cycling
time-trial after caffeine ingestion. J Int Soc Sports Nutr. (2014) 11:45. 10.1186/s12970-014-
0045-8 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
66. Algrain HA, Thomas RM, Carrillo AE, Ryan EJ, Kim C-H, Lettan RBII, et al. The Effects of
a Polymorphism in the cytochrome P450 CYP1A2 gene on performance enhancement with
caffeine in recreational cyclists. J Caffeine Res. (2016) 6:34–39. 10.1089/jcr.2015.0029
67. Salinero JJ, Lara B, Ruiz-Vicente D, Areces F, Puente-Torres C, Gallo-Salazar C, et al.

CYP1A2 Genotype variations do not modify the benefits and drawbacks of caffeine during
exercise: a pilot study. Nutrients (2017) 9:E269 10.3390/nu9030269 [PMC free article]
68. Joy E, De Souza MJ, Nattiv A, Misra M, Williams NI, Mallinson RJ, et al. . 2014 female
athlete triad coalition consensus statement on treatment and return to play of the female athlete
triad. Curr Sports Med Rep. (2014) 13:219–32. 10.1249/JSR.0000000000000077 [PubMed]
69. Doherty M, Smith PM. Effects of caffeine ingestion on exercise testing: a meta-analysis. Int J
Sport Nutr Exerc Metab. (2004) 14:626–46. 10.1123/ijsnem.14.6.626 [PubMed] [CrossRef]
[Google Scholar]
70. Shen JG, Brooks MB, Cincotta J, Manjourides JD. Establishing a relationship between the
effect of caffeine and duration of endurance athletic time trial events: a systematic review and
meta-analysis. J Sci Med Sport. (2018) 22:232–8. 10.1016/j.jsams.2018.07.022 [PubMed]
71. Higgins JP, Babu KM. Caffeine reduces myocardial blood flow during exercise. Am J Med.
(2013) 126:730 e1–8. 10.1016/j.amjmed.2012.12.023 [PubMed] [CrossRef] [Google Scholar]
72. Namdar M, Schepis T, Koepfli P, Gaemperli O, Siegrist PT, Grathwohl R, et al. . Caffeine
impairs myocardial blood flow response to physical exercise in patients with coronary artery
disease as well as in age-matched controls. PLoS ONE (2009) 4:e5665.
10.1371/journal.pone.0005665 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
73. Puente C, Abian-Vicen J, Del Coso J, Lara B, Salinero JJ. The CYP1A2−163C>A
polymorphism does not alter the effects of caffeine on basketball performance. PLoS ONE
(2018) 13:e0195943 10.1371/journal.pone.0195943 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
74. Rahimi R. The effect of CYP1A2 genotype on the ergogenic properties of caffeine during
resistance exercise: a randomized, double-blind, placebo-controlled, crossover study. Ir J Med
Sci. (2018) 12:1–9. 10.1007/s11845-018-1780-7 [PubMed] [CrossRef] [Google Scholar]
75. Fried NT, Elliott MB, Oshinsky ML. The role of adenosine signaling in headache: a review.
Brain Sci. (2017) 7:30. 10.3390/brainsci7030030 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
76. Urry E, Landolt HP. Adenosine, caffeine, and performance: from cognitive neuroscience of
sleep to sleep pharmacogenetics. Curr Top Behav Neurosci. (2015) 25:331–66.
10.1007/7854_2014_274 [PubMed] [CrossRef] [Google Scholar]
77. Meeusen R, Roelands B, Spriet LL. Caffeine, exercise and the brain. Nestle Nutr Inst
Workshop Ser. (2013) 76:1–12. 10.1159/000350223 [PubMed] [CrossRef] [Google Scholar]
78. Salamone JD, Farrar AM, Font L, Patel V, Schlar DE, Nunes EJ, et al. . Differential actions
of adenosine A1 and A2A antagonists on the effort-related effects of dopamine D2 antagonism.
Behav Brain Res. (2009) 201:216–22. 10.1016/j.bbr.2009.02.021 [PMC free article] [PubMed]
79. Salamone JD, Correa M, Ferrigno S, Yang JH, Rotolo RA, Presby RE. The
psychopharmacology of effort-related decision making: dopamine, adenosine, and insights into
the neurochemistry of motivation. Pharmacol Rev. (2018) 70:747–62. 10.1124/pr.117.015107
80. Loy BD, O'Connor PJ, Lindheimer JB, Covert SF. Caffeine is ergogenic for adenosine A2A
receptor gene (ADORA2A) T Allele Homozygotes: a pilot study. J Caffeine Res. (2015) 5:73–
81. 10.1089/jcr.2014.0035 [CrossRef] [Google Scholar]
81. Reilly T, Edwards B. Altered sleep-wake cycles and physical performance in athletes.
Physiol Behav. (2007) 90:274–84. 10.1016/j.physbeh.2006.09.017 [PubMed] [CrossRef]
[Google Scholar]
82. Robson-Ansley PJ, Gleeson M, Ansley L. Fatigue management in the preparation of

Olympic athletes. J Sports Sci. (2009) 27:1409–20. 10.1080/02640410802702186 [PubMed]
83. Nunes RA, Mazzotti DR, Hirotsu C, Andersen ML, Tufik S, Bittencourt L. The association
between caffeine consumption and objective sleep variables is dependent on ADORA2A
c.1083T>C genotypes. Sleep Med. (2017) 30:210–5. 10.1016/j.sleep.2016.06.038 [PubMed]
84. Retey JV, Adam M, Khatami R, Luhmann UF, Jung HH, Berger W, et al. . A genetic
variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity
to caffeine effects on sleep. Clin Pharmacol Ther. (2007) 81:692–8. 10.1038/sj.clpt.6100102
85. Bodenmann S, Hohoff C, Freitag C, Deckert J, Retey JV, Bachmann V, et al. .

Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on
neurobehavioural performance and sleep EEG after sleep deprivation. Br J Pharmacol. (2012)
165:1904–13. 10.1111/j.1476-5381.2011.01689.x [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
86. Byrne EM, Johnson J, McRae AF, Nyholt DR, Medland SE, Gehrman PR, et al. . A genome-
wide association study of caffeine-related sleep disturbance: confirmation of a role for a common
variant in the adenosine receptor. Sleep (2012) 35:967–75. 10.5665/sleep.1962 [PMC free
87. Philip P, Taillard J, Moore N, Delord S, Valtat C, Sagaspe P, et al. . The effects of coffee and
napping on nighttime highway driving: a randomized trial. Ann Intern Med. (2006) 144:785–91.
10.7326/0003-4819-144-11-200606060-00004 [PubMed] [CrossRef] [Google Scholar]
88. Drummond SP, Bischoff-Grethe A, Dinges DF, Ayalon L, Mednick SC, Meloy MJ. The
neural basis of the psychomotor vigilance task. Sleep (2005) 28:1059–68.
10.1093/sleep/28.9.1059 [PubMed] [CrossRef] [Google Scholar]
89. Landolt HP, Retey JV, Tonz K, Gottselig JM, Khatami R, Buckelmuller I, et al. . Caffeine
attenuates waking and sleep electroencephalographic markers of sleep homeostasis in humans.
Neuropsychopharmacology (2004) 29:1933–9. 10.1038/sj.npp.1300526 [PubMed] [CrossRef]
[Google Scholar]
90. Landolt HP, Werth E, Borbely AA, Dijk DJ. Caffeine intake (200 mg) in the morning affects
human sleep and EEG power spectra at night. Brain Res. (1995) 675: 67–74. 10.1016/0006-
8993(95)00040-W [PubMed] [CrossRef] [Google Scholar]
91. Landolt HP, Dijk DJ, Gaus SE, Borbely AA. Caffeine reduces low-frequency delta activity in
the human sleep EEG. Neuropsychopharmacology (1995) 12:229–38. [PubMed] [Google
Scholar]
92. Braakhuis A, Raman R, Vaghefi E. The association between dietary intake of antioxidants
and ocular disease. Diseases (2017) 5. 10.3390/diseases5010003 [PMC free article] [PubMed]
93. Czarnewski P, Das S, Parigi SM, Villablanca EJ. Retinoic acid and its role in modulating
intestinal innate immunity. Nutrients (2017) 9. 10.3390/nu9010068 [PMC free article] [PubMed]
94. Gao Y, Chen L, Yang SN, Wang H, Yao J, Dai Q, et al. . Contributions of visuo-oculomotor
abilities to interceptive skills in sports. Optom Vis Sci. (2015) 92:679–89.
10.1097/OPX.0000000000000599 [PubMed] [CrossRef] [Google Scholar]
95. Palidis DJ, Wyder-Hodge PA, Fooken J, Spering M. Distinct eye movement patterns enhance
dynamic visual acuity. PLoS ONE (2017) 12:e0172061. 10.1371/journal.pone.0172061 [PMC
96. Wilkerson GB, Simpson KA, Clark RA. Assessment and training of visuomotor reaction
time for football injury prevention. J Sport Rehabil. (2017) 26:26–34. 10.1123/jsr.2015-0068
97. Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, Bishop NC, et al. Position
statement. Part one: immune function and exercise. Exerc Immunol Rev. (2011) 17:6–63.
[PubMed] [Google Scholar]
98. Lietz G, Lange J, Rimbach G. Molecular and dietary regulation of beta,beta-carotene 15,15'-
monooxygenase 1 (BCMO1). Arch Biochem Biophys. (2010) 502:8–16.
10.1016/j.abb.2010.06.032 [PubMed] [CrossRef] [Google Scholar]
99. Ferrucci L, Perry JR, Matteini A, Perola M, Tanaka T, Silander K, et al. . Common variation
in the beta-carotene 15,15'-monooxygenase 1 gene affects circulating levels of carotenoids: a
genome-wide association study. Am J Hum Genet. (2009) 84:123–33.
10.1016/j.ajhg.2008.12.019 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
100. Lietz G, Oxley A, Leung W, Hesketh J. Single nucleotide polymorphisms upstream from
the beta-carotene 15,15'-monoxygenase gene influence provitamin A conversion efficiency in
female volunteers. J Nutr. (2012) 142:161S–5S. 10.3945/jn.111.140756 [PubMed] [CrossRef]
[Google Scholar]
101. Garvican LA, Saunders PU, Cardoso T, Macdougall IC, Lobigs LM, Fazakerley R, et al. .
Intravenous iron supplementation in distance runners with low or suboptimal ferritin. Med Sci
Sports Exerc. (2014) 46:376–85. 10.1249/MSS.0b013e3182a53594 [PubMed] [CrossRef]
[Google Scholar]
102. DellaValle DM, Haas JD. Iron supplementation improves energetic efficiency in iron-
depleted female rowers. Med Sci Sports Exerc. (2014) 46:1204–15.
103. Sacirovic S, Asotic J, Maksimovic R, Radevic B, Muric B, Mekic H, et al. . Monitoring and
prevention of anemia relying on nutrition and environmental conditions in sports. Mater
Sociomed. (2013) 25:136–9. 10.5455/msm.2013.25.136-139 [PMC free article] [PubMed]
104. Myhre KE, Webber BJ, Cropper TL, Tchandja JN, Ahrendt DM, Dillon CA, et al. .
Prevalence and Impact of Anemia on Basic Trainees in the US Air Force. Sports Med Open
(2015) 2:23. 10.1186/s40798-016-0047-y [PMC free article] [PubMed] [CrossRef] [Google
Scholar]
105. Martinsson A, Andersson C, Andell P, Koul S, Engstrom G, Smith JG. Anemia in the
general population: prevalence, clinical correlates and prognostic impact. Eur J Epidemiol.
(2014) 29:489–98. 10.1007/s10654-014-9929-9 [PubMed] [CrossRef] [Google Scholar]
106. Latunde-Dada GO. Iron metabolism in athletes–achieving a gold standard. Eur J Haematol.
(2013) 90:10–5. 10.1111/ejh.12026 [PubMed] [CrossRef] [Google Scholar]
107. Dubnov G, Foldes AJ, Mann G, Magazanik A, Siderer M, Constantini N. High prevalence
of iron deficiency and anemia in female military recruits. Mil Med. (2006) 171:866–9.
10.7205/MILMED.171.9.866 [PubMed] [CrossRef] [Google Scholar]
108. McClung JP. Iron, zinc, and physical performance. Biol Trace Elem Res. (2018)
10.1007/s12011-018-1479-7. [Epub ahead of print]. [PubMed] [CrossRef] [Google Scholar]
109. Pedlar CR, Brugnara C, Bruinvels G, Burden R. Iron balance and iron supplementation for
the female athlete: a practical approach. Eur J Sport Sci. (2018) 18:295–305.
10.1080/17461391.2017.1416178 [PubMed] [CrossRef] [Google Scholar]
110. Nagao T, Hirokawa M. Diagnosis and treatment of macrocytic anemias in adults. J Gen
Fam Med. (2017) 18:200–204. 10.1002/jgf2.31 [PMC free article] [PubMed] [CrossRef] [Google
Scholar]
111. Veeranki S, Tyagi SC. Defective homocysteine metabolism: potential implications for
skeletal muscle malfunction. Int J Mol Sci. (2013) 14:15074–91. 10.3390/ijms140715074 [PMC
112. Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, et al. Human
methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification.
Nat Genet. (1994) 7:551 10.1038/ng0694-195 [PubMed] [CrossRef] [Google Scholar]
113. Mennen LI, de Courcy GP, Guilland JC, Ducros V, Bertrais S, Nicolas JP, et al. .
Homocysteine, cardiovascular disease risk factors, and habitual diet in the French
Supplementation with Antioxidant Vitamins and Minerals Study. Am J Clin Nutr. (2002)
76:1279–89. 10.1093/ajcn/76.6.1279 [PubMed] [CrossRef] [Google Scholar]
114. Rasmussen LB, Ovesen L, Bulow I, Knudsen N, Laurberg P, Perrild H. Folate intake,
lifestyle factors, and homocysteine concentrations in younger and older women. Am J Clin Nutr.
(2000) 72:1156–63. 10.1093/ajcn/72.5.1156 [PubMed] [CrossRef] [Google Scholar]
115. Solis C, Veenema K, Ivanov AA, Tran S, Li R, Wang W, et al. . Folate intake at RDA
levels is inadequate for Mexican American men with the methylenetetrahydrofolate reductase
677TT genotype. J Nutr. (2008) 138:67–72. 10.1093/jn/138.1.67 [PMC free article] [PubMed]
116. Curro M, Di Mauro D, Bruschetta D, D'Amico F, Vecchio M, Trimarchi F, et al. . Influence

of MTHFR polymorphisms on cardiovascular risk markers in elite athletes. Clin Biochem.
(2016) 49:183–5. 10.1016/j.clinbiochem.2015.08.014 [PubMed] [CrossRef] [Google Scholar]
117. Guinotte CL, Burns MG, Axume JA, Hata H, Urrutia TF, Alamilla A, et al. .
Methylenetetrahydrofolate reductase 677C–>T variant modulates folate status response to
controlled folate intakes in young women. J Nutr. (2003) 133:1272–80. 10.1093/jn/133.5.1272
118. Dinc N, Yucel SB, Taneli F, Sayin MV. The effect of the MTHFR C677T mutation on
athletic performance and the homocysteine level of soccer players and sedentary individuals. J
Hum Kinet. (2016) 51:61–69. 10.1515/hukin-2015-0171 [PMC free article] [PubMed]
119. Swart KM, Enneman AW, van Wijngaarden JP, van Dijk SC, Brouwer-Brolsma EM, Ham
AC, et al. . Homocysteine and the methylenetetrahydrofolate reductase 677C–>T polymorphism
in relation to muscle mass and strength, physical performance and postural sway. Eur J Clin
Nutr. (2013) 67:743–8. 10.1038/ejcn.2013.97 [PubMed] [CrossRef] [Google Scholar]
120. Vidoni ML, Pettee Gabriel K, Luo ST, Simonsick EM, Day RS. Relationship between
homocysteine and muscle strength decline: the baltimore longitudinal study of aging. J Gerontol
A Biol Sci Med Sci. (2018) 73:546–551. 10.1093/gerona/glx161 [PMC free article] [PubMed]
121. van Schoor NM, Swart KM, Pluijm SM, Visser M, Simsek S, Smulders Y, et al. . Cross-
sectional and longitudinal association between homocysteine, vitamin B12 and physical
performance in older persons. Eur J Clin Nutr. (2012) 66:174–81. 10.1038/ejcn.2011.151
122. Rolita L, Holtzer R, Wang C, Lipton RB, Derby CA, Verghese J. Homocysteine and
mobility in older adults. J Am Geriatr Soc. (2010) 58:545–50. 10.1111/j.1532-
5415.2010.02718.x [PMC free article] [PubMed] [CrossRef] [Google Scholar]
123. Benyamin B, Ferreira MA, Willemsen G, Gordon S, Middelberg RP, McEvoy BP, et al. .
Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. Nat
Genet. (2009) 41:1173–5. 10.1038/ng.456 [PMC free article] [PubMed] [CrossRef] [Google
Scholar]
124. Allen KJ, Gurrin LC, Constantine CC, Osborne NJ, Delatycki MB, Nicoll AJ, et al. . Iron-
overload-related disease in HFE hereditary hemochromatosis. N Engl J Med. (2008) 358:221–30.
10.1056/NEJMoa073286 [PubMed] [CrossRef] [Google Scholar]
125. Soranzo N, Spector TD, Mangino M, Kuhnel B, Rendon A, Teumer A, et al. . A genome-
wide meta-analysis identifies 22 loci associated with eight hematological parameters in the
HaemGen consortium. Nat Genet. (2009) 41:1182–90. 10.1038/ng.467 [PMC free article]
126. Chambers JC, Zhang W, Li Y, Sehmi J, Wass MN, Zabaneh D, et al. . Genome-wide
association study identifies variants in TMPRSS6 associated with hemoglobin levels. Nat Genet.
(2009) 41:1170–2. 10.1038/ng.462 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
127. Benyamin B, McRae AF, Zhu G, Gordon S, Henders AK, Palotie A, et al. . Variants in TF
and HFE explain approximately 40% of genetic variation in serum-transferrin levels. Am J Hum
Genet. (2009) 84:60–5. 10.1016/j.ajhg.2008.11.011 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
128. Ganesh SK, Zakai NA, van Rooij FJ, Soranzo N, Smith AV, Nalls MA, et al. . Multiple loci
influence erythrocyte phenotypes in the CHARGE Consortium. Nat Genet. (2009) 41:1191–8.
10.1038/ng.466 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
129. Morgan EH, Oates PS. Mechanisms and regulation of intestinal iron absorption. Blood
Cells Mol Dis. (2002) 29:384–99. 10.1006/bcmd.2002.0578 [PubMed] [CrossRef] [Google
Scholar]
130. Marjot T CJ, Ryan JD. What is HFE haemochromatosis?. Br J Hosp Med. (2016) 77:C91–
95. 10.12968/hmed.2016.77.6.C91 [PubMed] [CrossRef] [Google Scholar]
131. Pantopoulos K, Porwal SK, Tartakoff A, Devireddy L. Mechanisms of mammalian iron

homeostasis. Biochemistry (2012) 51:5705–24. 10.1021/bi300752r [PMC free article] [PubMed]
132. Recalcati S, Minotti G, Cairo G. Iron regulatory proteins: from molecular mechanisms to
drug development. Antioxid Redox Signal. (2010) 13:1593–616. 10.1089/ars.2009.2983
133. Chicharro JL, Hoyos J, Gomez-Gallego F, Villa JG, Bandres F, Celaya P, et al. . Mutations
in the hereditary haemochromatosis gene HFE in professional endurance athletes. Br J Sports
Med. (2004) 38:418–21. 10.1136/bjsm.2002.003921 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
134. Habte K, Adish A, Zerfu D, Kebede A, Moges T, Tesfaye B, et al. . Iron, folate and vitamin
B12 status of Ethiopian professional runners. Nutr Metab. (2015) 12:62. 10.1186/s12986-015-
135. Hermine ODG, Genty V, Marquet LA, Fumagalli G, Tafflet M, Guillem F, et al. . Eighty
percent of French sport winners in Olympic, World and Europeans competitions have mutations
in the hemochromatosis HFE gene. Biochimie (2015) 119:1–5. 10.1016/j.biochi.2015.09.028
136. Tanaka T, Roy CN, Yao W, Matteini A, Semba RD, Arking D, et al. . A genome-wide
association analysis of serum iron concentrations. Blood (2010) 115:94–6. 10.1182/blood-2009-
137. Colombani PC MC. Energie- und Nährstoffaufnahme im Schweizer Spitzensport – eine

erste Bestandsaufnahme zu Beginn des zweiten Jahrtausends. Sportmed Sporttraumatol. (2003)
51:7–16. [Google Scholar]
138. Mettler S, Zimmermann MB. Iron excess in recreational marathon runners. Eur J Clin Nutr.
(2010) 64:490–4. 10.1038/ejcn.2010.16 [PubMed] [CrossRef] [Google Scholar]
139. Diehl K, Thiel A, Zipfel S, Mayer J, Schnell A, Schneider S. Elite adolescent athletes' use
of dietary supplements: characteristics, opinions, and sources of supply and information. Int J
Sport Nutr Exerc Metab. (2012) 22:165–74. 10.1123/ijsnem.22.3.165 [PubMed] [CrossRef]
[Google Scholar]
140. Petroczi A, Naughton DP, Mazanov J, Holloway A, Bingham J. Performance enhancement

with supplements: incongruence between rationale and practice. J Int Soc Sports Nutr. (2007)
4:19. 10.1186/1550-2783-4-19 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
141. De Matos LD, Azevedo LF, Vieira ML, Nomura CH, Hamerschlak N, Pinho JR, et al. The
use of exogenous iron by professional cyclists pervades abdominal organs but not the heart. Int J
Cardiol. (2013) 167:2341–3. 10.1016/j.ijcard.2012.11.041 [PubMed] [CrossRef] [Google
Scholar]
142. Reardon TF, Allen DG. Iron injections in mice increase skeletal muscle iron content, induce
oxidative stress and reduce exercise performance. Exp Physiol. (2009) 94:720–30.
10.1113/expphysiol.2008.046045 [PubMed] [CrossRef] [Google Scholar]
143. Messner DJ, Rhieu BH, Kowdley KV. Iron overload causes oxidative stress and impaired
insulin signaling in AML-12 hepatocytes. Dig Dis Sci. (2013) 58:1899–908. 10.1007/s10620-
013-2648-3 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
144. Aslinia F, Mazza JJ, Yale SH. Megaloblastic anemia and other causes of macrocytosis. Clin
Med Res. (2006) 4:236–41. 10.3121/cmr.4.3.236 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
145. Hazra A, Kraft P, Selhub J, Giovannucci EL, Thomas G, Hoover RN, et al. . Common
variants of FUT2 are associated with plasma vitamin B12 levels. Nat Genet. (2008) 40:1160–2.
10.1038/ng.210 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
146. Powers SK, Radak Z, Ji LL. Exercise-induced oxidative stress: past, present and future. J
Physiol. (2016) 594:5081–92. 10.1113/JP270646 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
147. Reid MB. Reactive oxygen species as agents of fatigue. Med Sci Sports Exerc. (2016)
48:2239–46. 10.1249/MSS.0000000000001006 [PubMed] [CrossRef] [Google Scholar]
148. Draeger CL, Naves A, Marques N, Baptistella AB, Carnauba RA, Paschoal V, et al. .
Controversies of antioxidant vitamins supplementation in exercise: ergogenic or ergolytic effects
in humans? J Int Soc Sports Nutr. (2014) 11:4. 10.1186/1550-2783-11-4 [PMC free article]
149. Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, et al. .
Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers
training-induced adaptations in endurance performance. Am J Clin Nutr. (2008) 87:142–9.
10.1093/ajcn/87.1.142 [PubMed] [CrossRef] [Google Scholar]
150. Taghiyar M, Darvishi L, Askari G, Feizi A, Hariri M, Mashhadi NS, et al. . The effect of
vitamin C and e supplementation on muscle damage and oxidative stress in female athletes: a
clinical trial. Int J Prev Med. (2013) 4(Suppl. 1):S16–23. [PMC free article] [PubMed] [Google
Scholar]
151. Peternelj TT, Coombes JS. Antioxidant supplementation during exercise training: beneficial
or detrimental? Sports Med. (2011) 41:1043–69. 10.2165/11594400-000000000-00000
152. Vidal K, Robinson N, Ives SJ. Exercise performance and physiological responses: the
potential role of redox imbalance. Physiol Rep. (2017) 5:e13225. 10.14814/phy2.13225 [PMC
153. Braakhuis AJ. Effect of vitamin C supplements on physical performance. Curr Sports Med
Rep. (2012) 11:180–4. 10.1249/JSR.0b013e31825e19cd [PubMed] [CrossRef] [Google Scholar]
154. Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for
vitamin C intake. JAMA (1999) 281:1415–23. 10.1001/jama.281.15.1415 [PubMed] [CrossRef]
[Google Scholar]
155. Shaw G, Lee-Barthel A, Ross ML, Wang B, Baar K. Vitamin C-enriched gelatin
supplementation before intermittent activity augments collagen synthesis. Am J Clin Nutr.
(2017) 105:136–43. 10.3945/ajcn.116.138594 [PMC free article] [PubMed] [CrossRef] [Google
Scholar]
156. Cahill LE, Fontaine-Bisson B, El-Sohemy A. Functional genetic variants of glutathione S-

transferase protect against serum ascorbic acid deficiency. Am J Clin Nutr. (2009) 90:1411–7.
10.3945/ajcn.2009.28327 [PubMed] [CrossRef] [Google Scholar]
157. Eck P, Erichsen HC, Taylor JG, Yeager M, Hughes AL, Levine M, et al. . Comparison of
the genomic structure and variation in the two human sodium-dependent vitamin C transporters,
SLC23A1 and SLC23A2. Hum Genet. (2004) 115:285–94. 10.1007/s00439-004-1167-x
158. Cahill LE, El-Sohemy A. Vitamin C transporter gene polymorphisms, dietary vitamin C and
serum ascorbic acid. J Nutrigenet Nutrigenomics (2009) 2:292–301. 10.1159/000314597
159. Angeline ME, Gee AO, Shindle M, Warren RF, Rodeo SA. The effects of vitamin D
deficiency in athletes. Am J Sports Med. (2013) 41:461–4. 10.1177/0363546513475787
160. Halliday TM, Peterson NJ, Thomas JJ, Kleppinger K, Hollis BW, Larson-Meyer DE.
Vitamin D status relative to diet, lifestyle, injury, and illness in college athletes. Med Sci Sports
Exerc. (2011) 43:335–43. 10.1249/MSS.0b013e3181eb9d4d [PubMed] [CrossRef] [Google
Scholar]
161. Ruohola JP, Laaksi I, Ylikomi T, Haataja R, Mattila VM, Sahi T, et al. . Association
between serum 25(OH)D concentrations and bone stress fractures in Finnish young men. J Bone
Miner Res. (2006) 21:1483–8. 10.1359/jbmr.060607 [PubMed] [CrossRef] [Google Scholar]
162. Larson-Meyer DE, Willis KS. Vitamin D and athletes. Curr Sports Med Rep. (2010) 9:220–
6. 10.1249/JSR.0b013e3181e7dd45 [PubMed] [CrossRef] [Google Scholar]
163. Barker T, Henriksen VT, Martins TB, Hill HR, Kjeldsberg CR, Schneider ED, et al. .
Higher serum 25-hydroxyvitamin D concentrations associate with a faster recovery of skeletal
muscle strength after muscular injury. Nutrients (2013) 5:1253–75. 10.3390/nu5041253 [PMC
164. Barker T, Schneider ED, Dixon BM, Henriksen VT, Weaver LK. Supplemental vitamin D
enhances the recovery in peak isometric force shortly after intense exercise. Nutr Metab. (2013)
10:69. 10.1186/1743-7075-10-69 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
165. Slater NA, Rager ML, Havrda DE, Harralson AF. Genetic Variation in CYP2R1 and GC
Genes Associated With Vitamin D Deficiency Status. J Pharm Pract. (2015) 30:31–6.
10.1177/0897190015585876 [PubMed] [CrossRef] [Google Scholar]
166. Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, et al. . Common
genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet
(2010) 376:180–8. 10.1016/S0140-6736(10)60588-0 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
167. Fang Y, van Meurs JB, Arp P, van Leeuwen JP, Hofman A, Pols HA, et al. . Vitamin D
binding protein genotype and osteoporosis. Calcif Tissue Int. (2009) 85:85–93. 10.1007/s00223-
009-9251-9 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
168. Yucha C. Guthrie D. Renal homeostasis of calcium. Nephrol Nurs J. (2003) 30:621–6; quiz
627–8. [PubMed] [Google Scholar]
169. Lappe J, Cullen D, Haynatzki G, Recker R, Ahlf R, Thompson K. Calcium and vitamin d
supplementation decreases incidence of stress fractures in female navy recruits. J Bone Miner
Res. (2008) 23:741–9. 10.1359/jbmr.080102 [PubMed] [CrossRef] [Google Scholar]
170. Nieves JW, Melsop K, Curtis M, Kelsey JL, Bachrach LK, Greendale G, et al. . Nutritional
factors that influence change in bone density and stress fracture risk among young female cross-
country runners. PM R (2010) 2:740–50; quiz 794. 10.1016/j.pmrj.2010.04.020 [PubMed]
171. Patel DS, Roth M, Kapil N. Stress fractures: diagnosis, treatment, and prevention. Am Fam
Physician. (2011) 83:39–46. [PubMed] [Google Scholar]
172. McInnis KC, Ramey LN. High-risk stress fractures: diagnosis and management. PM R
(2016) 8(3 Suppl.):S113–24. 10.1016/j.pmrj.2015.09.019. [PubMed] [CrossRef] [Google
Scholar]
173. Food and Nutrition Board I.o.M. Dietary Reference Intakes for Thiamin, Riboflavin,
Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington,
DC (1998). [Google Scholar]
174. Zeisel SH. Choline: critical role during fetal development and dietary requirements in
adults. Annu Rev Nutr. (2006) 26:229–50. 10.1146/annurev.nutr.26.061505.111156 [PMC free
175. Zeisel SH, Da Costa KA, Franklin PD, Alexander EA, Lamont JT, Sheard NF, et al. .
Choline, an essential nutrient for humans. FASEB J. (1991) 5:2093–8.
10.1096/fasebj.5.7.2010061 [PubMed] [CrossRef] [Google Scholar]
176. Resseguie ME, da Costa KA, Galanko JA, Patel M, Davis IJ, Zeisel SH. Aberrant estrogen
regulation of PEMT results in choline deficiency-associated liver dysfunction. J Biol Chem.
(2011) 286:1649–58. 10.1074/jbc.M110.106922 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
177. da Costa KA, Kozyreva OG, Song J, Galanko JA, Fischer LM, Zeisel SH. Common genetic
polymorphisms affect the human requirement for the nutrient choline. FASEB J. (2006)
20:1336–44. 10.1096/fj.06-5734com [PMC free article] [PubMed] [CrossRef] [Google Scholar]
178. da Costa KA, Corbin KD, Niculescu MD, Galanko JA, Zeisel SH. Identification of new
genetic polymorphisms that alter the dietary requirement for choline and vary in their
distribution across ethnic and racial groups. FASEB J. (2014) 28:2970–8. 10.1096/fj.14-249557
179. da Costa KA, Badea M, Fischer LM, Zeisel SH. Elevated serum creatine phosphokinase in
choline-deficient humans: mechanistic studies in C2C12 mouse myoblasts. Am J Clin Nutr.
(2004) 80:163–70. 10.1093/ajcn/80.1.163 [PubMed] [CrossRef] [Google Scholar]
180. Fischer LM, daCosta K.A., Kwock L, Stewart PW, Lu TS, Stabler SP. et al.. Sex and
menopausal status influence human dietary requirements for the nutrient choline. Am J Clin
Nutr. (2007) 85:1275–85. 10.1093/ajcn/85.5.1275 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
181. Conlay LA, Sabounjian LA, Wurtman RJ. Exercise and neuromodulators: choline and
acetylcholine in marathon runners. Int J Sports Med. (1992) 13(Suppl. 1):S141–2. 10.1055/s-
2007-1024619 [PubMed] [CrossRef] [Google Scholar]
182. Jager R, Purpura M, Kingsley M. Phospholipids and sports performance. J Int Soc Sports
Nutr. (2007) 4:5. 10.1186/1550-2783-4-5 [PMC free article] [PubMed] [CrossRef] [Google
Scholar]
183. Meeusen R, Watson P, Hasegawa H, Roelands B, Piacentini MF. Central fatigue: the
serotonin hypothesis and beyond. Sports Med. (2006) 36:881–909. 10.2165/00007256-
200636100-00006 [PubMed] [CrossRef] [Google Scholar]
184. Gao X, Wang Y, Randell E, Pedram P, Yi Y, Gulliver W, et al. . Higher dietary choline and
betaine intakes are associated with better body composition in the adult population of
newfoundland, Canada. PLoS ONE (2016) 11:e0155403. 10.1371/journal.pone.0155403 [PMC
185. Elsawy G, Abdelrahman O, Hamza A. Effect of choline supplementation on rapid weight

loss and biochemical variables among female taekwondo and judo athletes. J Hum Kinet. (2014)
40:77–82. 10.2478/hukin-2014-0009 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
186. Kohlmeier M, da Costa KA, Fischer LM, Zeisel SH. Genetic variation of folate-mediated
one-carbon transfer pathway predicts susceptibility to choline deficiency in humans. Proc Natl
Acad Sci USA. (2005) 102:16025–30. 10.1073/pnas.0504285102 [PMC free article] [PubMed]
187. Ganz AB, Klatt KC, Caudill MA. Common genetic variants alter metabolism and influence
dietary choline requirements. Nutrients (2017) 9:E837. 10.3390/nu9080837 [PMC free article]
188. Ganz AB, Shields K, Fomin VG, Lopez YS, Mohan S, Lovesky J, et al. . Genetic
impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine
production at the expense of betaine synthesis. FASEB J. (2016) 30:3321–33.
10.1096/fj.201500138RR [PMC free article] [PubMed] [CrossRef] [Google Scholar]
189. Zeisel SH. Nutritional genomics: defining the dietary requirement and effects of choline. J
Nutr. (2011) 141:531–4. 10.3945/jn.110.130369 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
190. Krieger JW, Sitren HS, Daniels MJ, Langkamp-Henken B. Effects of variation in protein
and carbohydrate intake on body mass and composition during energy restriction: a meta-
regression 1. Am J Clin Nutr. (2006) 83:260–74. 10.1093/ajcn/83.2.260 [PubMed] [CrossRef]
[Google Scholar]
191. Knapik JJ. The importance of physical fitness for injury prevention: part 2. J Spec Oper
Med. (2015) 15:112–5. [PubMed] [Google Scholar]
192. Nascimento M, Silva D, Ribeiro S, Nunes M, Almeida M, Mendes-Netto R. Effect of a
nutritional intervention in Athlete's body composition, eating behaviour and nutritional
knowledge: a comparison between adults and adolescents. Nutrients (2016) 8:E535.
10.3390/nu8090535 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
193. Goss AM, Goree LL, Ellis AC, Chandler-Laney PC, Casazza K, Lockhart ME, et al. .
Effects of diet macronutrient composition on body composition and fat distribution during
weight maintenance and weight loss. Obesity (Silver Spring). (2013) 21:1139–42.
10.1002/oby.20191 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
194. Merritt DC, Jamnik J, El-Sohemy A. FTO genotype, dietary protein intake, and body weight
in a multiethnic population of young adults: a cross-sectional study. Genes Nutr. (2018) 13:4.
195. Bartolomei S, Sadres E, Church DD, Arroyo E, Gordon JA, III, Varanoske AN, et al. .
Comparison of the recovery response from high-intensity and high-volume resistance exercise in
trained men. Eur J Appl Physiol. (2017) 117:1287–98. 10.1007/s00421-017-3598-9 [PubMed]
196. Aragon AA, Schoenfeld BJ, Wildman R, Kleiner S, VanDusseldorp T, Taylor L, et al. .
International society of sports nutrition position stand: diets and body composition. J Int Soc
Sports Nutr. (2017) 14:16. 10.1186/s12970-017-0174-y [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
197. Mattei J, Qi Q, Hu FB, Sacks FM, Qi L. TCF7L2 genetic variants modulate the effect of
dietary fat intake on changes in body composition during a weight-loss intervention. Am J Clin
Nutr. (2012) 96:1129–36. 10.3945/ajcn.112.038125 [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
198. Grau K, Cauchi S, Holst C, Astrup A, Martinez JA, Saris WH, et al. . TCF7L2 rs7903146-
macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic
diet. Am J Clin Nutr. (2010) 91:472–9. 10.3945/ajcn.2009.27947 [PubMed] [CrossRef] [Google
Scholar]
199. Zhang X, Qi Q, Zhang C, Smith SR, Hu FB, Sacks FM, et al. . FTO genotype and 2-year
change in body composition and fat distribution in response to weight-loss diets: the POUNDS
LOST Trial. Diabetes (2012) 61:3005–11. 10.2337/db11-1799 [PMC free article] [PubMed]
200. Beelen M, Cermak NM, van Loon LJ. [Performance enhancement by carbohydrate intake
during sport: effects of carbohydrates during and after high-intensity exercise]. Ned Tijdschr
Geneeskd. (2015) 159:A7465. [PubMed] [Google Scholar]
201. Marquet LA, Brisswalter J, Louis J, Tiollier E, Burke LM, Hawley JA, et al. . Enhanced
Endurance Performance by Periodization of Carbohydrate Intake: “Sleep Low” Strategy. Med
Sci Sports Exerc. (2016) 48:663–72. 10.1249/MSS.0000000000000823 [PubMed] [CrossRef]
[Google Scholar]
202. Naclerio F, Larumbe-Zabala E. Effects of whey protein alone or as part of a multi-

ingredient formulation on strength, fat-free mass, or lean body mass in resistance-trained
individuals: a meta-analysis. Sports Med. (2016) 46:125–37. 10.1007/s40279-015-0403-y
203. Wu G. Dietary protein intake and human health. Food Funct. (2016) 7:1251–65.
10.1039/C5FO01530H [PubMed] [CrossRef] [Google Scholar]
204. Noland RC. Exercise and regulation of lipid metabolism. Prog Mol Biol Transl Sci. (2015)
135:39–74. 10.1016/bs.pmbts.2015.06.017 [PubMed] [CrossRef] [Google Scholar]
205. de Luis DA, Aller R, Izaola O, Primo D, Urdiales S, Romero E. Effects of a

high-protein/low-carbohydrate diet versus a standard hypocaloric diet on weight and
cardiovascular risk factors: Role of a Genetic Variation in the rs9939609 FTO Gene Variant. J
Nutrigenet Nutrigenomics (2015) 8:128–36. 10.1159/000441142 [PubMed] [CrossRef] [Google
Scholar]
206. Antonio J, Knafo S, Kapoor R, Tartar JL. A fat mass and obesity-associated gene
polymorphism influences fat mass in exercise-trained individuals. J Int Soc Sports Nutr. (2018)
15:40. 10.1186/s12970-018-0246-7 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
207. Beck B, Carstairs GL, Billing DC, Caldwell JN, Middleton KJ. Modifiable anthropometric
characteristics are associated with unilateral and bilateral carry performance. J Strength Cond
Res. (2016). 10.1519/JSC.0000000000001504 [PubMed] [CrossRef] [Google Scholar]
208. Garaulet M, Smith CE, Hernandez-Gonzalez T, Lee YC, Ordovas JM. PPARgamma
Pro12Ala interacts with fat intake for obesity and weight loss in a behavioural treatment based
on the Mediterranean diet. Mol Nutr Food Res. (2011) 55:1771–9. 10.1002/mnfr.201100437
209. Mountjoy M, Sundgot-Borgen JK, Burke LM, Ackerman KE, Blauwet C, Constantini N, et
al. . IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update. Br J
Sports Med. (2018) 52:687–97. 10.1136/bjsports-2018-099193 [PubMed] [CrossRef] [Google
Scholar]
210. Phillips CM, Kesse-Guyot E, McManus R, Hercberg S, Lairon D, Planells R, et al. . High
dietary saturated fat intake accentuates obesity risk associated with the fat mass and obesity-
associated gene in adults. J Nutr. (2012) 142:824–31. 10.3945/jn.111.153460 [PubMed]
Articles from Frontiers in Nutrition are provided here courtesy of Frontiers Media SA
Formats:
Article | PubReader | ePub (beta) | PDF (864K) | Citation
Share
Share on Facebook FacebookShare on Twitter TwitterShare on Google Plus Google+
Save items
View more options
Similar articles in PubMed
Guide and Position of the International Society of Nutrigenetics/Nutrigenomics on Personalised

Nutrition: Part 1 - Fields of Precision Nutrition.
[J Nutrigenet Nutrigenomics. 2016]
Nutrigenomics and nutrigenetics.
[Iran J Public Health. 2010]
Nutrigenomics and personalized nutrition: science and concept.
[Per Med. 2008]
Proteomics in nutrition: status quo and outlook for biomarkers and bioactives.
[J Proteome Res. 2010]
[Childhood feeding, chronic-degenerative disease in adults, and nutrigenomics].
[Pediatr Med Chir. 2007]
See reviews...
See all...
Cited by other articles in PMC
Protein Supplements and Their Relation with Nutrition, Microbiota Composition and Health: Is
More Protein Always Better for Sportspeople?
[Nutrients. 2019]
See all...
Links
PubMed
Taxonomy
Recent Activity
American College of Sports Medicine Joint Position Statement. Nutrition and Athletic
Performance.
[Med Sci Sports Exerc. 2016]
Disclosure of genetic information and change in dietary intake: a randomized controlled trial.
[PLoS One. 2014]
Only DNA-based dietary advice improved adherence to the Mediterranean diet score.
[Am J Clin Nutr. 2017]
Relationship Between General Nutrition Knowledge and Dietary Quality in Elite Athletes.
[Int J Sport Nutr Exerc Metab. 2015]
Review Nutrient intake and food habits of soccer players: analyzing the correlates of eating
practice.
[Nutrients. 2014]
A Systematic Review of Genetic Testing and Lifestyle Behaviour Change: Are We Using High-
Quality Genetic Interventions and Considering Behaviour Change Theory?
[Lifestyle Genom. 2018]
Visioning Report 2017: A Preferred Path Forward for the Nutrition and Dietetics Profession.
[J Acad Nutr Diet. 2017]
Nutrigenomics - perspectives from registered dietitians: a report from the Quebec-wide e-

consultation on nutrigenomics among registered dietitians.
[J Hum Nutr Diet. 2014]
Caffeine, CYP1A2 Genotype, and Endurance Performance in Athletes.

Do we know enough? A scientific and ethical analysis of the basis for genetic-based personalized
nutrition.
[Genes Nutr. 2013]
Review Quality assurance issues in the use of dietary supplements, with special reference to
protein supplements.
[J Nutr. 2013]
A Holistic Antidoping Approach for a Fairer Future for Sport.
[Curr Sports Med Rep. 2017]
Review Prevalence of doping use in elite sports: a review of numbers and methods.
[Sports Med. 2015]
The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine.
[J Int Soc Sports Nutr. 2012]
Performance.
Review Iron deficiency and reduced work capacity: a critical review of the research to determine
a causal relationship.
[J Nutr. 2001]
Review Athletic performance and vitamin D.
Identification of a common variant in the TFR2 gene implicated in the physiological regulation
of serum iron levels.
[Hum Mol Genet. 2011]
The serine protease TMPRSS6 is required to sense iron deficiency.
[Science. 2008]
Changes in body composition of high competition rugby players during the phases of a regular
season; influence of diet and exercise load.
[Nutr Hosp. 2014]
Higher compared with lower dietary protein during an energy deficit combined with intense
exercise promotes greater lean mass gain and fat mass loss: a randomized trial.
Review Genetic influence on athletic performance.
[Curr Opin Pediatr. 2013]
The current use, and opinions of elite athletes and support staff in relation to genetic testing in
elite sport within the UK.
[Biol Sport. 2018]
Direct-to-consumer genetic testing for predicting sports performance and talent identification:
Consensus statement.
[Br J Sports Med. 2015]
Critical overview of applications of genetic testing in sport talent identification.
[Recent Pat DNA Gene Seq. 2012]
See more ...
A genetic-based algorithm for personalized resistance training.
[Biol Sport. 2016]
Genetic testing for exercise prescription and injury prevention: AIS-Athlome consortium-FIMS
joint statement.
[BMC Genomics. 2017]
Letter to the editor: A genetic-based algorithm for personalized resistance training.
[Biol Sport. 2017]
Genetic testing for exercise prescription and injury prevention: AIS-Athlome consortium-FIMS
joint statement.
[BMC Genomics. 2017]

High responders and low responders: factors associated with individual variation in response to
standardized training.
[Sports Med. 2014]
See more ...
Caffeine and 3-km cycling performance: Effects of mouth rinsing, genotype, and time of day.
[Scand J Med Sci Sports. 2016]
Review Effect of caffeine on sport-specific endurance performance: a systematic review.
[J Strength Cond Res. 2009]
See more ...
In vivo evaluation of CYP1A2, CYP2A6, NAT-2 and xanthine oxidase activities in a Greek
population sample by the RP-HPLC monitoring of caffeine metabolic ratios.
[Biomed Chromatogr. 2007]
Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype

relationship in Swedes and Koreans.
[Eur J Clin Pharmacol. 2007]
The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and
meta-analysis.
[Pharmacogenomics J. 2018]
Coffee, CYP1A2 genotype, and risk of myocardial infarction.
[JAMA. 2006]
See more ...

Review Effect of caffeine on sport-specific endurance performance: a systematic review.
The effects of different doses of caffeine on endurance cycling time trial performance.
[J Sports Sci. 2012]
Performance during a 20-km cycling time-trial after caffeine ingestion.
CYP1A2 Genotype Variations Do Not Modify the Benefits and Drawbacks of Caffeine during
Exercise: A Pilot Study.
[Nutrients. 2017]
Caffeine and 3-km cycling performance: Effects of mouth rinsing, genotype, and time of day.
[Scand J Med Sci Sports. 2016]
2014 female athlete triad coalition consensus statement on treatment and return to play of the
female athlete triad.
Effects of caffeine ingestion on exercise testing: a meta-analysis.
Establishing a relationship between the effect of caffeine and duration of endurance athletic time
trial events: A systematic review and meta-analysis.
[J Sci Med Sport. 2019]
Review Caffeine reduces myocardial blood flow during exercise.

[Am J Med. 2013]
Caffeine impairs myocardial blood flow response to physical exercise in patients with coronary
artery disease as well as in age-matched controls.
[PLoS One. 2009]
The CYP1A2 -163C>A polymorphism does not alter the effects of caffeine on basketball
performance.
[PLoS One. 2018]
The effect of CYP1A2 genotype on the ergogenic properties of caffeine during resistance
exercise: a randomized, double-blind, placebo-controlled, crossover study.
[Ir J Med Sci. 2019]
Review Caffeine reduces myocardial blood flow during exercise.
[Am J Med. 2013]
Caffeine impairs myocardial blood flow response to physical exercise in patients with coronary
artery disease as well as in age-matched controls.
[PLoS One. 2009]
Review The Role of Adenosine Signaling in Headache: A Review.
[Brain Sci. 2017]
Review Adenosine, caffeine, and performance: from cognitive neuroscience of sleep to sleep
pharmacogenetics.
[Curr Top Behav Neurosci. 2015]
See more ...
Review Altered sleep-wake cycles and physical performance in athletes.
[Physiol Behav. 2007]
Review Fatigue management in the preparation of Olympic athletes.
[J Sports Sci. 2009]
The association between caffeine consumption and objective sleep variables is dependent on
ADORA2A c.1083T>C genotypes.
[Sleep Med. 2017]
A genome-wide association study of caffeine-related sleep disturbance: confirmation of a role for

a common variant in the adenosine receptor.
[Sleep. 2012]
The effects of coffee and napping on nighttime highway driving: a randomized trial.
[Ann Intern Med. 2006]
The neural basis of the psychomotor vigilance task.
[Sleep. 2005]
Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on

neurobehavioural performance and sleep EEG after sleep deprivation.
[Br J Pharmacol. 2012]
Caffeine attenuates waking and sleep electroencephalographic markers of sleep homeostasis in

humans.
[Neuropsychopharmacology. 2004]
Caffeine reduces low-frequency delta activity in the human sleep EEG.
[Neuropsychopharmacology. 1995]
A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual
sensitivity to caffeine effects on sleep.
[Clin Pharmacol Ther. 2007]
The Association between Dietary Intake of Antioxidants and Ocular Disease.
[Diseases. 2017]
Review Retinoic Acid and Its Role in Modulating Intestinal Innate Immunity.
[Nutrients. 2017]
Contributions of Visuo-oculomotor Abilities to Interceptive Skills in Sports.
[Optom Vis Sci. 2015]
Distinct eye movement patterns enhance dynamic visual acuity.
[PLoS One. 2017]

Assessment and Training of Visuomotor Reaction Time for Football Injury Prevention.
[J Sport Rehabil. 2017]
Review Position statement. Part one: Immune function and exercise.
[Exerc Immunol Rev. 2011]
Review Molecular and dietary regulation of beta,beta-carotene 15,15'-monooxygenase 1

(BCMO1).
[Arch Biochem Biophys. 2010]
Common variation in the beta-carotene 15,15'-monooxygenase 1 gene affects circulating levels

of carotenoids: a genome-wide association study.
[Am J Hum Genet. 2009]
Single nucleotide polymorphisms upstream from the β-carotene 15,15'-monoxygenase gene

influence provitamin A conversion efficiency in female volunteers.
[J Nutr. 2012]
Review Iron supplementation for female athletes: effects on iron status and performance
outcomes.
Intravenous iron supplementation in distance runners with low or suboptimal ferritin.
Monitoring and prevention of anemia relying on nutrition and environmental conditions in

sports.
[Mater Sociomed. 2013]
See more ...
Review Iron, Zinc, and Physical Performance.
[Biol Trace Elem Res. 2019]
High prevalence of iron deficiency and anemia in female military recruits.
[Mil Med. 2006]
Review Iron balance and iron supplementation for the female athlete: A practical approach.
[Eur J Sport Sci. 2018]
outcomes.
Review Diagnosis and treatment of macrocytic anemias in adults.
[J Gen Fam Med. 2017]
outcomes.
Monitoring and prevention of anemia relying on nutrition and environmental conditions in

sports.
[Mater Sociomed. 2013]
Prevalence and Impact of Anemia on Basic Trainees in the US Air Force.
[Sports Med Open. 2015]
See more ...
Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation

identification.
[Nat Genet. 1994]
Homocysteine, cardiovascular disease risk factors, and habitual diet in the French
Supplementation with Antioxidant Vitamins and Minerals Study.
Folate intake, lifestyle factors, and homocysteine concentrations in younger and older women.
See more ...
Review Defective homocysteine metabolism: potential implications for skeletal muscle

malfunction.
[Int J Mol Sci. 2013]

Homocysteine and the methylenetetrahydrofolate reductase 677C-->T polymorphism in
relation to muscle mass and strength, physical performance and postural sway.
[Eur J Clin Nutr. 2013]
Homocysteine and mobility in older adults.
[J Am Geriatr Soc. 2010]
Relationship between Homocysteine and Muscle Strength Decline: The Baltimore Longitudinal
Study of Aging.
[J Gerontol A Biol Sci Med Sci. 2018]
The effect of the MTHFR C677T mutation on athletic performance and the homocysteine level
of soccer players and sedentary individuals.
[J Hum Kinet. 2016]
Methylenetetrahydrofolate reductase 677C-->T variant modulates folate status response to

controlled folate intakes in young women.
[J Nutr. 2003]
Common variants in TMPRSS6 are associated with iron status and erythrocyte volume.
[Nat Genet. 2009]
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
[Nat Genet. 2009]
Review Mechanisms and regulation of intestinal iron absorption.
[Blood Cells Mol Dis. 2002]
Iron-overload-related disease in HFE hereditary hemochromatosis.
[N Engl J Med. 2008]
Review What is HFE haemochromatosis?
[Br J Hosp Med (Lond). 2016]

Review Mechanisms of mammalian iron homeostasis.
[Biochemistry. 2012]
Review Iron regulatory proteins: from molecular mechanisms to drug development.
[Antioxid Redox Signal. 2010]
See more ...
Iron-overload-related disease in HFE hereditary hemochromatosis.
[N Engl J Med. 2008]
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
[Nat Genet. 2009]
[Nat Genet. 2009]
Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin

levels.
[Am J Hum Genet. 2009]
See more ...
The serine protease TMPRSS6 is required to sense iron deficiency.
[Science. 2008]
[Nat Genet. 2009]
A genome-wide association analysis of serum iron concentrations.

[Blood. 2010]
Review Iron deficiency in sports - definition, influence on performance and therapy.
[Swiss Med Wkly. 2015]
Iron excess in recreational marathon runners.
[Eur J Clin Nutr. 2010]
Elite adolescent athletes' use of dietary supplements: characteristics, opinions, and sources of
supply and information.
Performance enhancement with supplements: incongruence between rationale and practice.
See more ...
Review Megaloblastic anemia and other causes of macrocytosis.
[Clin Med Res. 2006]
Common variants of FUT2 are associated with plasma vitamin B12 levels.
[Nat Genet. 2008]
Review Exercise-induced oxidative stress: past, present and future.
[J Physiol. 2016]
Review Reactive Oxygen Species as Agents of Fatigue.
Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers

training-induced adaptations in endurance performance.
The effect of vitamin C and e supplementation on muscle damage and oxidative stress in female
athletes: a clinical trial.
[Int J Prev Med. 2013]
Controversies of antioxidant vitamins supplementation in exercise: ergogenic or ergolytic effects

in humans?
Review Antioxidant supplementation during exercise training: beneficial or detrimental?
[Sports Med. 2011]
Exercise performance and physiological responses: the potential role of redox imbalance.
[Physiol Rep. 2017]
Review Effect of vitamin C supplements on physical performance.
Criteria and recommendations for vitamin C intake.
[JAMA. 1999]
Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen

synthesis.
Functional genetic variants of glutathione S-transferase protect against serum ascorbic acid
deficiency.
Comparison of the genomic structure and variation in the two human sodium-dependent vitamin
C transporters, SLC23A1 and SLC23A2.
[Hum Genet. 2004]
Vitamin C transporter gene polymorphisms, dietary vitamin C and serum ascorbic acid.
Performance.
Review The effects of vitamin D deficiency in athletes.
[Am J Sports Med. 2013]
Association between serum 25(OH)D concentrations and bone stress fractures in Finnish young
men.
[J Bone Miner Res. 2006]
Review Athletic performance and vitamin D.
See more ...
Genetic Variation in CYP2R1 and GC Genes Associated With Vitamin D Deficiency Status.
[J Pharm Pract. 2017]
Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
[Lancet. 2010]
Vitamin D binding protein genotype and osteoporosis.
[Calcif Tissue Int. 2009]
Review Renal homeostasis of calcium.
[Nephrol Nurs J. 2003]
Calcium and vitamin d supplementation decreases incidence of stress fractures in female navy
recruits.
[J Bone Miner Res. 2008]
Review Stress fractures: diagnosis, treatment, and prevention.
[Am Fam Physician. 2011]
Review High-Risk Stress Fractures: Diagnosis and Management.
[PM R. 2016]
Vitamin D binding protein genotype and osteoporosis.
[Calcif Tissue Int. 2009]
Review Choline: critical role during fetal development and dietary requirements in adults.
[Annu Rev Nutr. 2006]
Choline, an essential nutrient for humans.
[FASEB J. 1991]
Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction.
[J Biol Chem. 2011]
Common genetic polymorphisms affect the human requirement for the nutrient choline.
[FASEB J. 2006]
Identification of new genetic polymorphisms that alter the dietary requirement for choline and
vary in their distribution across ethnic and racial groups.
[FASEB J. 2014]
Elevated serum creatine phosphokinase in choline-deficient humans: mechanistic studies in

C2C12 mouse myoblasts.
Sex and menopausal status influence human dietary requirements for the nutrient choline.
Exercise and neuromodulators: choline and acetylcholine in marathon runners.
[Int J Sports Med. 1992]
Phospholipids and sports performance.
Review Central fatigue: the serotonin hypothesis and beyond.
[Sports Med. 2006]
Higher Dietary Choline and Betaine Intakes Are Associated with Better Body Composition in
the Adult Population of Newfoundland, Canada.
[PLoS One. 2016]
See more ...
[FASEB J. 2014]
Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to

choline deficiency in humans.
[Proc Natl Acad Sci U S A. 2005]
Review Common Genetic Variants Alter Metabolism and Influence Dietary Choline
Requirements.
[Nutrients. 2017]
Genetic impairments in folate enzymes increase dependence on dietary choline for

phosphatidylcholine production at the expense of betaine synthesis.
[FASEB J. 2016]
Review Nutritional genomics: defining the dietary requirement and effects of choline.
[J Nutr. 2011]
Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to

choline deficiency in humans.
[Proc Natl Acad Sci U S A. 2005]
[FASEB J. 2014]
Comparison of the recovery response from high-intensity and high-volume resistance exercise in
trained men.
[Eur J Appl Physiol. 2017]
Effect of a Nutritional Intervention in Athlete's Body Composition, Eating Behaviour and

Nutritional Knowledge: A Comparison between Adults and Adolescents.
[Nutrients. 2016]
Review International society of sports nutrition position stand: diets and body composition.
See more ...

Review [Performance enhancement by carbohydrate intake during sport: effects of carbohydrates
during and after high-intensity exercise].
[Ned Tijdschr Geneeskd. 2015]
Enhanced Endurance Performance by Periodization of Carbohydrate Intake: "Sleep Low"

Strategy.
Effects of Whey Protein Alone or as Part of a Multi-ingredient Formulation on Strength, Fat-

Free Mass, or Lean Body Mass in Resistance-Trained Individuals: A Meta-analysis.
[Sports Med. 2016]
Review Dietary protein intake and human health.
[Food Funct. 2016]
Review Exercise and Regulation of Lipid Metabolism.
[Prog Mol Biol Transl Sci. 2015]
Effects of variation in protein and carbohydrate intake on body mass and composition during
energy restriction: a meta-regression 1.
See more ...
<i>FTO</i> genotype, dietary protein intake, and body weight in a multiethnic population of
young adults: a cross-sectional study.
[Genes Nutr. 2018]
FTO genotype and 2-year change in body composition and fat distribution in response to weight-
loss diets: the POUNDS LOST Trial.
[Diabetes. 2012]
Effects of a High-Protein/Low-Carbohydrate Diet versus a Standard Hypocaloric Diet on Weight

and Cardiovascular Risk Factors: Role of a Genetic Variation in the rs9939609 FTO Gene
Variant.
A fat mass and obesity-associated gene polymorphism influences fat mass in exercise-trained
individuals.
The Importance of Physical Fitness for Injury Prevention: Part 2.
[J Spec Oper Med. 2015]
Modifiable Anthropometric Characteristics Are Associated With Unilateral and Bilateral Carry
Performance.
Review Exercise and Regulation of Lipid Metabolism.
[Prog Mol Biol Transl Sci. 2015]
TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk

randomized hypoenergetic diet.
TCF7L2 genetic variants modulate the effect of dietary fat intake on changes in body
composition during a weight-loss intervention.
Performance.
PPARγ Pro12Ala interacts with fat intake for obesity and weight loss in a behavioural treatment
based on the Mediterranean diet.
[Mol Nutr Food Res. 2011]

Performance.
IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update.
[Br J Sports Med. 2018]
High dietary saturated fat intake accentuates obesity risk associated with the fat mass and
obesity-associated gene in adults.
[J Nutr. 2012]
Support CenterSupport Center
Simple NCBI Directory
GETTING STARTED
NCBI Education
NCBI Help Manual
NCBI Handbook
Training & Tutorials
Submit Data
RESOURCES
Chemicals & Bioassays
Data & Software
DNA & RNA
Domains & Structures
Genes & Expression
Genetics & Medicine
Genomes & Maps
Homology
Literature
Proteins
Sequence Analysis
Taxonomy
Variation
POPULAR
PubMed
Bookshelf
PubMed Central
BLAST
Nucleotide
Genome
SNP
Gene
Protein
PubChem
FEATURED
Genetic Testing Registry
GenBank
Reference Sequences
Gene Expression Omnibus
Genome Data Viewer
Human Genome
Mouse Genome
Influenza Virus
Primer-BLAST
Sequence Read Archive
NCBI INFORMATION
About NCBI
Research at NCBI
NCBI News & Blog
NCBI FTP Site
NCBI on Facebook
NCBI on Twitter
NCBI on YouTube
Privacy Policy
External link. Please review our privacy policy.
NLMNIHDHHSUSA.gov
National Center for Biotechnology Information, U.S. National Library of Medicine
8600 Rockville Pike, Bethesda MD, 20894 USA
Policies and Guidelines | ContactA Novel Approach to the Nutrigenetics and Nutrigenomics of
Obesity and Weight Management
Article (PDF Available) in Current Oncology Reports 18(7) · July 2016 with 1,799 Reads
DOI: 10.1007/s11912-016-0529-6
Cite this publication
Yael T. Joffe
Christine Houghton
22.72The University of Queensland
Abstract
Nutrigenetics and nutrigenomics, as well as diet and exercise, play an important role in the
development and treatment of obesity and its comorbidities. If an individual’s susceptibility to
becoming obese and their responsiveness to weight loss interventions are to be understood, then
it needs to be addressed at a molecular and metabolic level, including genetic interaction. This
review proposes a three-pillar approach to more fully comprehend the complexity of diet-gene
interactions in obesity. Peroxisomal proliferating-activated receptor gamma (PPARG) and
mitochondrial uncoupling protein-1 (UCP-1) are explored in detail. Illustrating how an
understanding of nutritional biochemistry, nutrigenomics, and nutrigenetics may be the key to
understanding differences observed in the obese phenotype that vary both within and across
populations.
Discover the world's research
15+ million members
118+ million publications
700k+ research projects
Join for free
Content uploaded by Christine Houghton
Author content
Content may be subject to copyright.
Download full-text PDF
INTEGRATIVE CARE (C LAMMERSFELD, SECTION EDITOR)
A Novel Approach to the Nutrigenetics and Nutrigenomicsof

Obesity and Weight
ManagementYael T. Joffe1,2&Christine A. Houghton3#Springer
Science+Business Media New York 2016Abstract Nutrigenetics and
nutrigenomics, as well as diet andexercise, play an important role in the development and
treatmentof obesity and its comorbidities. If an individual’s susceptibilityto becoming obese and
their responsiveness to weight loss inter-ventions are to be understood, then it needs to be
addressed at amolecular and metabolic level, including genetic interaction.This review proposes
a three-pillar approach to more fully com-prehend the complexity of diet-gene interactions in
obesity.Peroxisomal proliferating-activated receptor gamma (PPARG)and mitochondrial
uncoupling protein-1 (UCP-1) are exploredin detail. Illustrating how an understanding of
nutritional bio-chemistry, nutrigenomics, and nutrigenetics may be the key tounderstanding
differences observed in the obese phenotype thatvary both within and across
populations.Keywords Nutrigenomics .Nutrigenetics .Nutritionalbiochemistry .Obesity .Weight
loss .PPARG .UCP-1IntroductionObesity, a chronic low-grade inflammatory condition, is asso-
ciated with the development of many comorbidities includingcardiovascular disease (CVD), type
2 diabetes, and a numberof cancers [1]. The complexity of this chronic disorder be-comes more
apparent, exhibiting a multifactorial etiology[2]. Lifestyle factors such as diet and exercise
continue to berecognized to play an important role in the development andprogression of obesity
and its comorbidities. However,nutrigenetics and nutrigenomics also contribute to the
obesephenotype, interacting with the genome to regulate the devel-opment and progression of
obesity and its comorbidities.These complex interactions may explain differences observedin the
obese phenotype that vary both within and acrosspopulations [3–6].While the interest in obesity
by both researchers andpractitioners continues to grow, the approach is at bestdisjointed,
employing either expansive genome-wide as-sociation studies (GWAS) or focusing on a few
genes, afew nutrients, or a single behavioral intervention. Thisarticle does not address whether or
not the field ofnutritional genomics is ready for clinical weight man-agement. Rather, this article
proposes a Bbig pictureîn how researchers and clinicians may better approachthe complexity of
obesity.Nutrigenetics and Nutrigenomics—Knowthe DifferenceMany clinicians, and
surprisingly, academics as well, areunable to differentiate between nutrigenetics
andnutrigenomics. What is often referred to as nutrigenomicsis in fact nutrigenetics. In this
article, we use the termnutritional genomics to mean both nutrigenetics andnutrigenomics (see
the box: Defining the DifferenceBetween Nutrigenetics and Nutrigenomics).This article is part of
the Topical Collection on Integrative Care*Yael T. Joffeyael@manukascience.co.za1Manuka
Science, 17 Roeland Square, Drury Lane, CapeTown, SouthAfrica2Department of Nutritional
Sciences, School of Health RelatedProfessions, Rutgers School of Dental Medicine, Newark, NJ,
USA3School of Human Movement Studies, University of Queensland,Brisbane, Queensland,
AustraliaCurr Oncol Rep (2016) 18:43 DOI 10.1007/s11912-016-0529-6
The Heritability of ObesityLarge family-based studies in different populations have con-sistently

demonstrated a familial correlation in adult bodymass index (BMI), at about 0.2 between parents
and offspring,and at about 0.3 between siblings [7,8]. Moustafa and Froguel(2013) [9••] reported
the heritability of human corpulence andadiposity to be between 40 and 70 %. Based on twin
studies,the amount of genetic influence on body fatness and body fatdistribution has previously
been established to be ~70 % forBMI [7,10]. However, the contribution varies according tothe
age of the individual. In childhood, a certain proportion ofthe BMI variance in twins is explained
by shared environmen-tal factors, while in adulthood, it is exclusively the non-
sharedenvironmental experiences. Wardle et al. (2008) confirmed aheritability of 77 % for BMI
and waist circumference (WC) ina UK sample of 5092 twin pairs aged 8–11 years [11]. Themost
interesting finding from this twin study is the relativelylow contribution of the shared-
environment. The shared-environment effect was estimated at just over 10 %. Siblingswould
have been exposed to similar food offers, similar op-tions for television viewing, and physical
activity. They wouldalso have been exposed to the same parent behavior and go tothe same
school. All of this should contribute to a more similarBMI and WC between siblings. Parents
may be the least sur-prised by this result, being aware that children differ despitehaving a similar
upbringing. Blaming parents may be mis-guided. Excessive weight gain in a child may be due to
achild’s genetic susceptibility to an obesogenic environment,and less likely to be the fault of the
parents.Missing HeritabilityDespite the findings that the inter-individual variance in
BMIexplained by genetic factors is between 40 and 70 %, thegenetic variability detected by
molecular genetic research(SNP research) to date explains only around 5 % of inter-individual
BMI variance [12••]. At best, Speliotes et al.(2010) extrapolate that the analysis of 730,000
GWAS datasets might reveal that up to 10 to 15 % of the geneticallyrelated BMI variance could
be explained [8]. Hebebrand etal. (2013) offer possible explanations for the missing herita-bility,
including that heritability is systematicallyoverestimated. This review cannot address all the
reasons,but these are dealt with in greater detail in the article byHebebrand et al.
[12••].Monogenic vs Polygenic ObesityMonogenic obesity refers to rare forms of severe obesity
thatresult from polymorphisms that carry a large effect size on anindividual gene or
chromosomal region. Despite the rarity ofDefining the Difference BetweenNutrigenetics and
NutrigenomicsGenetic variability (nucleotide sequence change)influences how we interact with
our environment.Nutrigenetics describes the influence of gene variantson our ability to interact
with bioactive molecules inthemolecular environment surrounding our cells and theconsequences
of that interaction.In contrast to nutrigenetic interactions where thegene variants act on the
environment, withNutrigenomic interactions, the environment influencesgene expression.
Nutrigenomics is concerned with theinfluence of bioactive molecules interacting with agene,
potentially influencing gene expression, eitherupregulating or downregulating (turning it up
ordown), or activating or silencing (on or off).Nutrigenomic interactions may be direct or
indirect.In a direct interaction, the molecules are of smallmolecular weight, carrier-mediated, and
lipid-soluble.In an indirect interaction, the molecules are larger andhydrophilic. These molecules
interact at the cellsurface.Clinicians are most familiar with the nutrigeneticinteractions available
in commercial tests. This hasresulted in a distorted emphasis on single nucleotidepolymorphisms
(SNPs) and a Bsuperficialînvolve-ment with what the science of nutritional genomicshas to
offer. To comprehend the complex naturebetween diet and genetics on obesity requires an under-
standing of the three pillars of nutritional genomics.These include the following: nutritional
biochemistry,nutrigenetics, and nutrigenomics. Biochemicalprocesses are driven and understood
through nutrition-al biochemistry. It is imperative to understand thesepathways and the
disruption thereof, which contributeto perturbations in health and potentially the develop-ment of
disease. Nutrigenetics provides information ongenetic sequence variants, SNPs, as well as
othervariations such as copy number variants. These may(but not always) alter gene expression
or enzymefunction. By understanding nutrigenomics (nutrientimpact on gene expression), it is
possible to identifynutrient and lifestyle changes that may alter geneexpression. Put together,
these three pillars ofnutritional genomics will empower the practitioner toconstruct targeted and
clinically useful dietary andlifestyle recommendations for weight management. 43 Page 2 of 7
Curr Oncol Rep (2016) 18:43
these monogenic forms of obesity, they have provided greatinsight into our understanding of
several pathways and mech-anisms involved in the development of a more polygenic obe-sity.
Moustafa and Froguel (2013) in their article BFrom obe-sity genetics to the future of
personalized obesity therapy^describe the most common monogenic obesity conditionsand
observed phenotypes [9•• ].Understanding Polygenic ObesityIn this review, we are concerned
only with polygenicobesity which can best be explained by the commondisease—common
variant hypothesis. This proposes thatfrequent alleles of several genes, each with a small ef-fect
on the BMI (or other phenotype), determine anindividual person’s weight by the sum of the
variantspresent [12••].For clinicians, one of the most useful classificationsof genetic obesity is by
Loos and Bouchard [13]. Thisproposes four levels of genetic determination of obesity:genetic
obesity, strong genetic predisposition, slight ge-netic predisposition, and genetically
resistant.&Genetic obesity represents at least 5 % of obesity cases anda large percentage of the
severely obese. Variation in asingle gene causes obesity in spite of the environment.&Strong
genetic predisposition results from a number ofsusceptibility alleles at a number of loci. In a non-
obesogenic environment, individuals would likely beoverweight, but would become obese and
potentially se-verely obese in an obesogenic environment.&Slight genetic predisposition
suggests that in a restrictive(non-obesogenic) environment, individuals will likely benormal
weight or slightly overweight. However, in anobesogenic environment, there is a strong
likelihood thatindividuals will become overweight or obese.&Genetically resistant individuals
remain at normal weightor almost normal weight in a wide range of obesogenicconditions.This
classification is well illustrated by this study byMasuo et al. (2005) [14]. A 24-month weight loss
pro-gram enrolled 154 overweight Japanese men. The dietconsisted of a low calorie, low fat, and
low sodium diet(1600 kcal/day, 55 % CHO, 30 % protein, 15 % fat, 7 gNaCl per day).
Participants performed at least 1 h ofaerobic exercise daily calculated as steps. Complianceto diet
and exercise was considered excellent and con-sistent based on diet and activity records. At the
end ofthe 24 months, the men were grouped into four groupsaccording to their weight loss. All
groups maintainedthe reduced calorie intake and high physical activityover 24 months. The
groups included the following:1. Weight loss maintenance: Successful weight loss
andmaintenance over 24 months.2. Rebound: Lost weight in the first 6 months, but regainedmost
of it over the 24 months.3. Slow weight loss: Weight loss was slower than the firsttwo groups but
the group achieved a successful weightloss at 24 months.4. Weight loss resistance: Almost no
weight was lost, despitecompliance to the diet and exercise program over24 months.Almost a
decade ago, Adamo and Tesson (2007)suggested that identifying individuals responsive
tolifestyle modification to control body mass would beextremely advantageous [15]. Despite
this, mosthealth practitioners have not yet been able to com-prehend and clinically manage the
variable nature ofweight gain and weight loss.Genetic Factors Involved in Obesity
Susceptibilityand Weight RegulationTraditionally, clinical management of obesity has fo-cused
on energy balance, most times ascribing any re-sistance to losing weight as due to excess
calories, in-adequate energy expenditure, or a low metabolic rate.This is clearly a simplistic and
outdated interpretation.If an individual’s susceptibility to obesity and respon-siveness to weight
loss interventions is to be under-stood, then it needs to be addressed at a molecularand metabolic
level, including genetic interactions.Researchers have grouped genes in a number ofways. In a
recent review article by Martinez andMilagro [16••], the first grouping considered
geneticallyregulated processes and mechanisms that contribute tobody weight homeostasis. They
included physical activ-ity, appetite, adipocyte differentiation, insulin signaling,mitochondrial
functions, lipid turnover, thermogenesis,and energy efficiency. They then grouped genes accord-
ing to how they regulate metabolic functions, in whichthere are polymorphisms that have been
related to ge-netically mediated differences to dietary weight loss in-terventions, these include
the following:&Regulating energy intake (e.g., MC3R, MC4R, POMC,LEP, LEPR, FTO)&Lipid
metabolism and adipogenesis (e.g., PLIN1,APOA5, LIPC, FABP2)&Thermogenesis (e.g.,
ADBRs, UCPs)&Adipocytokine synthesis (e.g., ADIPOQ, IL6), as well as,&Transcription
factors (e.g., PPARG, TCF7L2, CLOCK)Curr Oncol Rep (2016) 18:43 Page 3 of 7 43
The length and scope of this review limit the numberof genes and SNPs that can be discussed.
Rather, theintention is to illustrate how applying a three-pillar ap-proach can provide a useful
model to more fully com-prehend the complexity of diet-gene interactions inobesity.Example 1.
Cell Regulation and PPARGThe lipid-sensing PPAR family is both complex and fascinat-ing in
the way it regulates a number of key cellular functions.The name peroxisomal proliferating-
activated receptors pro-vides little clue to the diverse actions of this family of ligand-activated
nuclear transcription factors. Activated by fatty acidsand their derivatives, PPARs closely link
lipid chemistry tometabolic disease and innate immunity [17]. In so doing, theyintegrate various
intra-cellular signaling pathways such thatPPARs effectively contribute to whole-body
homeostasis bymediating regulatory crosstalk between organs and systems.The diversity of
PPAR biochemical functions is appar-ent when considering that, among other actions, it partic-
ipates not only in adipogenesis but also in regulation ofcell survival, osteoblast, skin and gut cell
differentiationand more. It is the PPAR family’s wide-reaching actionsat the biochemical level
that enable it to integrate a num-ber of signaling pathways to coordinate inter-organcrosstalk.
These multiple levels of inter-organ crosstalkimplicate PPARs in carcinogenesis, inflammation,
athero-sclerosis, tissue repair, and immunomodulation [18].Discovered in 1990, early research
into the PPAR familyaccelerated when it was shown that PPAR gamma played akey role in
adipogenesis; it was subsequently described as aBmaster controller of the thrifty gene
response,^tying its func-tion to energy storage, and ultimately to obesity. The develop-ment of
synthetic PPAR gamma ligands displayed insulin-sensitizing effects, which saw
thiazolidinediones released asa new class of pharmaceutical for treatment of type 2 diabetes,a
condition closely associated with excessive adiposity.PPAR Gamma—Relationship to White and
BrownAdipocytesThe synthesis of adipose tissue is dependent on the coordina-tion of numerous
transcription factors and their associated co-activators and co-repressors. PPAR gamma is
considered to beone of the master regulators of adipocyte differentiation in theprocess of
adipogenesis. Mitochondria-dense brown adipo-cyte tissue (BAT) is specialized to enable non-
shivering ther-mogenesis. Here, fatty acids are oxidized to generate heat, aprocess that can both
enhance tolerance to low environmentaltemperature and prevent the storage of excess energy as
fat.Classified as an endocrine organ, white adipose tissue(WAT) has long been considered an
energy storage organ,forming large lipid droplets in white adipocytes in responseto excessive
food-derived energy input. However, the distinc-tion between these two types of adipose tissue is
not quite asclear as first thought. In response to cold exposure or beta-adrenergic stimulation,
brown adipocytes have been detectedin WAT, showing that formation of brown adipocytes may
beinducible by the local environment.PPAR gamma is a key regulator in both WAT and
BAT,with many key genes under PPAR gamma control. Theseinclude genes associated with
lipid transport and metabolism,adipokine production, and insulin signaling. As part of
PPARgamma’s insulin-sensitizing role, it increases synthesis of theadipokine adiponectin in
adipocytes and at the same timedecreases resistin and TNF-alpha; and these effects coordi-nately
regulate insulin sensitivity [19].PPPARs—an Evolutionary Solution to a CellularConundrum?
Lipids are an important fuel in human cells, being a concen-trated source of energy when
Bburntîn oxygen.Mitochondrial involvement in the Bburningôf fatty acidsresults in increased
flux of oxygen in the mitochondria withconsequent generation of superoxide radicals.
Essentially,whenever fat is burned as fuel, the production of reactiveoxygen species (ROS)
increases. This situation has been de-scribed as the Bhypoxia-lipid conundrumîn that
wheneverfat stores are oxidized as fuel, the cell’s redox balance swingsto the oxidative side
[20].PPARs may in effect provide a solution to this conundrumvia several mechanisms: (1)
modulation of mitochondrialuncoupling protein (UCP) expression to reduce the synthesisof
ROS, (2) optimization of forkhead box class O factor(FOXO) activity by the induction of
enzymes that breakdownROS such as MnSOD and catalase [21], and (3) suppressionof the pro-
inflammatory transcription factor NFkB. Figure 1graphically illustrates this important cell
survival relationship[20]. PPARs promote mitochondrial proton gradientuncoupling, reduce
ROS, and increase heat generation, whileensuring safe lipid storage and burning
(reducinglipotoxicity), safe carbohydrate storage, and reducing needfor insulin [22].Clinical
Relevance of PPAR ActivityPPAR gamma activity may be compromised by the presenceof
PPARG polymorphisms. In addition, its activity decreaseswith age, a process that can be slowed
by caloric restriction[23]. Aging is also known to be associated with constitutiveactivity of the
pro-inflammatory transcription factor, NFkB.As a consequence, the protective effects of PPAR
gamma are 43 Page 4 of 7 Curr Oncol Rep (2016) 18:43
likely to diminish with age in all individuals but more soin those who carry particular PPARG
polymorphisms andthose who are overweight or type 2 diabetic; these latterconditions are pro-
inflammatory states. Given the criticalrole of PPAR gamma in protecting the cell against thelipid
catabolism vs redox balance conundrum, solutionswhich can reactivate PPARs may help restore
metabolicbalance.Why Cells Need PPAR Gamma Modulation and NotActivationThe
pharmaceutical PPAR gamma agonists were initiallyhailed as the answer to the developing type
2 diabetes epidem-ic, but the expected benefits were not without associated risks.The effects of
PPAR gamma activation are not all beneficial,so that even though metabolic and immune effects
are gener-ally desirable, prolonged activation in other systems can leadto disturbances in cardiac
and renal status as well as degrada-tion of bone.The pharmaceutical PPAR gamma agonist,
rosiglitazone,exemplifies the dual action of PPAR activators. A 2010study concluded:
Bprescription of rosiglitazone was asso-ciated with an increased risk of stroke, heart failure,
andall-cause mortality, and an increased risk of the compositeof AMI, stroke, heart failure, or all-
cause mortality inpatients 65 years or older^[24]. It is for this reason thatPPAR Bmodulationîs
considered to be a more appropri-ate action than Bactivation.^Pharmaceuticals lack
thespecificity to target a single action, and in the case ofPPAR gamma, activation will result in
adverse as wellas beneficial effects as illustrated in the 2010 findingsdescribed above. In contrast
to pharmaceuticals, dietaryinterventions are typically less potent in their effects, withhuman cells
adapted to such food-derived compounds.Example 2. Thermogenic Processes, ADRB2,and
UCPWe referred earlier to the hypoxia-lipid conundrum in relationto the modulation of
mitochondrial UCP. UCPs are mitochon-drial transporters present in the inner mitochondrial
mem-brane, with UCP-1 uniquely present in brown adipocytes.UCP-1 is activated by free fatty
acids and creates a shuntbetween complexes of the respiratory chain and the
adenosinetriphosphate (ATP)-synthesizing enzyme, ATP synthase.Although physical activity is
the primary mechanism usedby humans for dissipating excess energy, an evolutionary sys-tem of
thermogenesis evolved to protect the body from hypo-thermia; this system is reliant on diverting
energy synthesistowards heat generation when required.When UCP-1 is activated (coupled),
respiration is en-hanced, but when it is uncoupled, oxidation energy is dissi-pated as heat. In this
way, UCP-1 acts as a Bcontrol pointînenergy synthesis. UCP-1 polymorphisms can affect
energyregulation and temperature sensitivity and as such have impli-cations for individuals who
have difficulty in regulating adi-posity and in adapting to a cold environment. Aberrant UCP-
1genes (both hetero- and homozygous) express enzymes oflower activity, resulting in decreased
ability to burn body fatfor heat. Not surprisingly, the thyroid hormone, triiodothyro-nine (T3),
induces the expression of UCP-1 and enhancesmitochondrial biogenesis in human adipocytes
[25].Furthermore, these authors suggest that Bbrown-like adipo-cytes in WAT and skeletal
muscle play a crucial role in theregulation ofbody weight and that understanding of the mech-
anism underlying the increase in UCP-1 expression level inthese organs should, therefore,
provide an approach to man-aging obesity.În adipose tissue, thyroid hormone (TH) reg-ulates
multiple aspects of lipid metabolism, including lipogen-esis, lipolysis, and thermogenesis. TH
treatment inducesUCP-1 expression in brown adipocytes, suggesting a link be-tween lowered
thyroid function and tendency to adiposity.Fig. 1 Transcriptional triad ofsurvival. Adapted from
[20]©2007Nunnetal.Curr Oncol Rep (2016) 18:43 Page 5 of 7 43
How UCP-1 and ADRB2 Are Inter-RelatedThermogenesis by UCP-1 in brown adipocytes is

controlleddirectly by sympathetic nerves principally through the beta-adrenergic action of
norepinephrine. Cold exposure activatesthe sympathetic nervous system, releasing
noradrenalinewhich binds to the surface of adipocytes. This action at theadipocyte surface
promotes the conversion of thyroxine (T4)toT3 by binding to the promoter region of the
deiodinase gene.ConclusionThese examples illustrate that it is not enough to be told oreven to
know what impact a SNP may or may not have onenzyme function and what disease associations
have beenreported in the scientific literature. Nutrigenetics must existin the context of nutritional
biochemistry to provide a deeperunderstanding of the biochemical pathways that have
beenimpacted. An understanding of nutritional biochemistry andnutrigenomics is the key to
developing effective weight man-agement interventions.The three-pillar approach demands that
researchers en-deavor to understand the biochemical environment withinwhich functional gene
variants are situated. And practitionerswill acquire the skills and knowledge to independently
con-struct diet and lifestyle recommendations that surpass the rec-ommendations currently
offered by commercial nutrigenetictests.Compliance with Ethical StandardsConflict of Interest
Yael T. Joffe is the director of Manuka Science, aneducational company that teaches
nutrigenetics and nutrigenomics basedon the ideas expressed in this article.ChristineA. Houghton
isa co-author ofa Manuka Science course thatteaches nutrigenetics and nutrigenomics based on
ideas expressed in thisarticle.Human and Animal Rights and Informed Consent This article
doesnot contain any studies with human or animal subjects performed by anyof the
authors.ReferencesPapers of particular interest, published recently, have beenhighlighted as:•• Of
major importance1. Maury E, Brichard SM. Adipokine dysregulation, adipose
tissueinflammation and metabolic syndrome. Mol Cell Endocrinol.2010;314(1):1–16.2. Bray
MS. Implications of gene-behavior interactions: preventionand intervention for obesity. Obesity
(Silver Spring). 2008;16Suppl 3:S72–8.3. Joffe YT et al. Tumor necrosis factor-alpha gene -308
G/A poly-morphism modulates the relationship between dietary fat intake,serum lipids, and
obesity risk in black South African women. JNutr. 2010;140(5):901–7.4. Joffe YT et al. The -
308 G/A polymorphism of the tumour necrosisfactor-alpha gene modifies the association
between saturated fatintake and serum total cholesterol levels in white South Africanwomen.
Genes Nutr. 2011;6(4):353–9.5. Joffe YT, et al. The tumor necrosis factor-alpha gene -238
G>Apolymorphism, dietary fat intake, obesity risk and serum lipid con-centrations in black and
white South African women. Europeanjournal of clinical nutrition. 2012.6. Stryjecki C, Mutch
DM. Fatty acid-gene interactions, adipokinesand obesity. Eur J Clin Nutr. 2011;65:285–97.7.
Maes HH, Neale MC, Eaves LJ. Genetic and environmental factorsin relative body weight and
human adiposity. Behav Genet.1997;27(4):325–51.8. Speliotes EK et al. Association analyses of
249,796 individualsreveal 18 new loci associated with body mass index. Nat
Genet.2010;42(11):937–48.9.•• Moustafa JSE-S, Froguel P. From obesity genetics to the future
ofpersonalized obesity therapy. Nat Rev Endocrinol. 2013;9(7):402–13. An excellent review
article that documents the differencesbetween monogenic and polygenic obesity. As well as
clearlydescribing the different kinds of genetic studies used, and theircontribution to the
increasing understanding of the relationshipbetween genetics and obesity.10. Schousboe K et al.
Twin study of genetic and environmental influ-ences on adult body size, shape, and composition.
Int J Obes(Lond). 2004;28(1):39–48.11. Wardle J et al. Evidence for a strong genetic influence
on childhoodadiposity despite the force of the obesogenic environment. Am JClin Nutr.
2008;87(2):398–404.12.•• Hebebrand J et al. Molecular genetic aspects of weight
regulation.Deutsch Aerzteblatt Int. 2013;110(19):338. Areviewofthecur-rent molecular genetic
research. Defining monogenic and poly-genic obesity and exploring the discrepancy between the
geneticvariability seen to date in genetic studies and the inter-individual variability of BMI.13.
Loos RJ, Bouchard C. Obesity—is it a genetic disorder? J InternMed. 2003;254(5):401–25.14.
Masuo K et al. Rebound weight gain as associated with high plasmanorepinephrine levels that
are mediated through polymorphisms inthe β2-adrenoceptor. Am J Hypertens.
2005;18(11):1508–16.15. Adamo KB, Tesson F. Genotype-specific weight loss treatment ad-
vice: how close are we? Appl Physiol Nutr Metab. 2007;32(3):351–66.16.•• Martínez JA,
Milagro FI. Genetics of weight loss: a basis for per-sonalized obesity management. Trends Food
Sci Technol.2015;42(2):97–115. A systematic review of nutrigenetic data.The article highlights
how understanding the contribution ofSNPs can impact public health strategies to address
obesity, aswell as contribute to the development of personalized prescrip-tions based on the
individual’s genetic make-up.17. Wahli W, Michalik L. PPARs at the crossroads of lipid
signalingand inflammation. Trends Endocrinol Metab. 2012;23(7):351–63.18. Feige JN et al.
From molecular action to physiological outputs:peroxisome proliferator-activated receptors are
nuclear receptorsat the crossroads of key cellular functions. Prog Lipid Res.2006;45(2):120–
59.19. Koppen A, Kalkhoven E. Brown vs white adipocytes: thePPARgamma coregulator story.
FEBS Lett. 2010;584(15):3250–9. 43 Page 6 of 7 Curr Oncol Rep (2016) 18:43
20. Nunn AV, Bell J, Barter P. The integration of lipid-sensing and anti-inflammatory effects:
how the PPARs play a role in metabolic bal-ance. Nucl Recept. 2007;5(1):1.21. Ponugoti B,
Dong G, Graves DT. Role of forkhead transcriptionfactors in diabetes-induced oxidative stress.
Exp Diabetes Res.2012;2012:939751.22. Nunn AV, Bell J, Barter P. The integration of lipid-
sensing and anti-inflammatory effects: how the PPARs play a role in metabolic bal-ance. Nucl
Recept. 2007;5(1):1.23. Sung B et al. Modulation of PPAR in aging, inflammation, andcalorie
restriction. J Gerontol A Biol Sci Med Sci. 2004;59(10):997–1006.24. Graham DJ et al. Risk of
acute myocardial infarction, stroke, heartfailure, and death in elderly Medicare patients treated
withrosiglitazone or pioglitazone. JAMA. 2010;304(4):411–8.25. Lee JY et al. Triiodothyronine
induces UCP-1 expression and mi-tochondrial biogenesis in human adipocytes. Am J Physiol
CellPhysiol. 2012;302(2):C463–72.Curr Oncol Rep (2016) 18:43 Page 7 of 7 43
Citations (11)
References (24)
... Na obesidade, o controle da necessidade de ingestão alimentar é profundamente afetado por

polimorfismos em genes codificadores de receptores ou de peptídeos sinalizadores periféricos
(como por exemplo, insulina, leptina e adiponectina). Consequentemente, o consumo dietético
total e a saciedade para diversos alimentos podem ser influenciados pelos efeitos destes genes
(FERGUSON, 2006;JOFFE;HOUGHTON, 2016). ...
... Na obesidade, o controle da necessidade de ingestão alimentar é profundamente afetado por
polimorfismos em genes codificadores de receptores ou de peptídeos sinalizadores periféricos
(como por exemplo, insulina, leptina e adiponectina). Consequentemente, o consumo dietético
total e a saciedade para diversos alimentos podem ser influenciados pelos efeitos destes genes
(FERGUSON, 2006;JOFFE;HOUGHTON, 2016). ...
NUTRIGENÔMICA COMO FERRAMENTA PREVENTIVA DE DOENÇAS CRÔNICAS

NÃO TRANSMISSÍVEIS
Article
May 2019
Leucinéia Schmidt
Tais Fatima Soder
Fábia Benetti
ViewShow abstract
... The consolidation of all the networks associated with adiposopathy may allow us to broaden
the clinical perception of the patient with high body fat composition, and take into account its
association with different organ comorbidities, such as hepatic dysfunction [18]. Therefore, in
line with this vision, we propose a pathophysiological model that integrates networks of the main
organokines associated with adiposopathy, beyond BMI, and is referred to as the CLARos'
model (Rosero et. ...
... Simultaneously, IL-15 has been associated with muscular hypertrophy, optimization of
glucose uptake, and to stimulate lipid oxidation in skeletal muscle [22,23]. On the other hand, it
has an important role in lipid metabolism, growth and differentiation of B and T lymphocytes,
natural killer cells, macrophages and monocytes [11][12][13][14][15][16][17][18][19][20][21]
[22][23][24]. Neurotropic factor derived from the brain (BDNF) plays an important role in
learning and memory, as well as in growth and maintenance of neurons and their synapses
[25,26], by acting on adipose tissue to increase its use as an energy source. ...
The Triumvirate of Adiposopathy: A Literature Review and Proposal of the Claros

Pathophysiological Model
Article
Jan 2018
Rosero RJJaramillo AGómez AM
Bruno Geloneze
View
... The openEHR presents a Clinical Knowledge Manager (CKM) -http://www.openehr.org/ckm/.

It is an International clinical-knowledge resource repository that supports international domain
knowledge governance [26], besides being a library of openEHR-archetypes and templates. We
searched the concept name of the scales and core data items in the openEHR to avoid archetype
duplication. ...
OpenEHR Modeling Applied to Eating Disorders in Clinical Practice: OpenEHR-Archetypes in

Eating Disorders
Conference Paper
Jun 2018
Priscila A Maranhão
Gustavo Bacelar
Duarte Gonçalves-Ferreira
Ricardo João Cruz-Correia
ViewShow abstract
... Preservation of an appropriate body weight through diet and exercise training is a key factor
and therefore obesity is considered as a major health hazard (Joffe and Houghton, 2016). In term
of obesity control, it remains dubious what molecular pathways may change the progression of
WAT by differential expression of UCPs and change it to beige adipose tissue to combat obesity
( Linden et al., 2014). ...
Comparative studies on the effects of high-fat diet, endurance training and obesity on Ucp1
expression in male C57BL/6 mice
Article
Full-text available
Jul 2018GENE
Samaneh ShirkhaniSayed Mohammad Marandi
Fatemeh Kazeminasab
Mohammad Hossein Hossein Nasr-Esfahani
ViewShow abstract
... The nutrigenomics nutrition field uses molecular tools to clarify and understand different
responses from nutrient intake by individuals and population groups. 1 It is related to the
influence from dietary factor (bioactive molecules) and gene interactions that potentially change
the gene expression. 2,3 Hence, the human genome sequencing enabled the emergence of the
so-called "personalized nutrition." 4 Hesketh 4 defined personalized nutrition as the ability to
detect thousands of stable genetic differences occurring in humans and their impact on
nutritional sciences. ...
Challenges in Design and Creation of Genetic openEHR-Archetype
Article
Full-text available
Jan 2018Stud Health Tech Informat
Gustavo Bacelar
ViewShow abstract
... The nutrigenomics nutrition field uses molecular tools to clarify and understand different
responses from nutrient intake by individuals and population groups. 1 It is related to the
influence from dietary factor (bioactive molecules) and gene interactions that potentially change
the gene expression. 2,3 Hence, the human genome sequencing enabled the emergence of the
so-called "personalized nutrition." 4 Hesketh 4 defined personalized nutrition as the ability to
detect thousands of stable genetic differences occurring in humans and their impact on
nutritional sciences. ...
Nutrigenomic Information in the openEHR Data Set
Article
Full-text available
Jan 2018
Gustavo Bacelar
ViewShow abstract
... Nutrigenomics is concerned with the influence of bioactive molecules interacting with a gene,
potentially influencing gene expression, either upregulating or downregulating (Joffe and
Houghton, 2016). It also attempts to create a personalized nutrition for every individual,
according to a unique genetic profile ( Bašić et al., 2011). ...
Evaluation of leptin and MMP2 genes methylation in childhood obesity
Article
Full-text available
Feb 2018
Sara El Sayed
Eman KhairyAyman Ragaa Basheer
Samar K Kassim
ViewShow abstract
... It is generally accepted that, of these environmental factors, a primary cause for susceptibility
to obesity is through gene-nutrient interactions. The importance of gene-nutrient interactions in
promoting obesity and other complex metabolic diseases is evidenced by the rapidly emerging
scientific disciplines of nutritional genetics (nutrigenetics) and nutritional genomics
(nutrigenomics) that may provide more effective personalized healthcare [23]. It should be noted
that a number of brief review articles that focus on gene and environment interactions in relation
to obesity have recently been published [22,[24][25][26]. ...
Gene-nutrient interactions and susceptibility to human obesity
Article
Full-text available
Dec 2017GENES NUTR
Joseph Castillo
Robert Orlando
William S. Garver
ViewShow abstract
From Neighborhood to Genome: Three Decades of Nutrition-Related Research from the
Atherosclerosis Risk in Communities Study
Article
Dec 2017
Margaret R SavocaLyn M. SteffenAlain G. BertoniLynne E Wagenknecht
View
Neuroendocrine regulation of energy balance: Implications on the development and surgical

treatment of obesity
Article
Aug 2017Nutr Health
Gisele FariasBárbara Dal Molin NettoSolange Cravo Bettini
Alexandre Coutinho Teixeira de Freitas
ViewShow abstract
Show more
Recommendations
Project
EASYGENEX Trial.
Christine HoughtonJeff S Coombes
Robert G Fassett
We are investigating the gene expression of a range of Nrf2 target genes in resposne to a
sulforaphane-yielding broccoli sprout encapsulated supplement
View project
Project
Clinical Applications of Nutrigenomics
Christine Houghton
View project
Project
Gut Ecology Project
Christine Houghton

Nutrogenomics and Exercise

Uploaded by

Copyright:

Available Formats

You might also like

Nutrogenomics and Exercise

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Nutrogenomics and Exercise

Uploaded by

Copyright:

Available Formats

NUTROGENOMICS &EXERCISE

Published online 2019 Feb 19. doi: 10.3389/fnut.2019.00008

Sport Nutrigenomics: Personalized Nutrition for Athletic Performance

This article has been cited by other articles in PMC.

Keywords: nutrigenomics, nutrigenetics, personalized nutrition, athletic performance, genetic

An external file that holds a picture, illustration, etc.

Object name is fnut-06-00008-g0001.jpg

The nutrigenomics approach to sport nutrition. An athlete is exposed to a food, beverage,

Sport Nutrigenomics Vs. Talent Identification and Exercise Prescription

There is a considerable amount of ongoing research investigating individual variation in response

Genes Associated With Sport Nutrition

Gene (rs number) Function Dietary factor Dietary sources Performance-related

CYP1A2 (rs762551) Encodes CYP1A2 liver enzyme: metabolizes caffeine; identifies

ADORA2A (rs5751876) Regulates myocardial oxygen demand; increases coronary

BCMO1 (rs11645428) Converts provitamin A carotenoids to Vitamin A Vitamin A

MTHFR (rs1801133) Produces the enzyme methylenetetrahydrofolate reductase, which is

TMPRSS6 (rs4820268), TFR2 (rs7385804), TF (rs3811647) Regulate the peptide

Mitigate exercise-induced ROS production (153, 155)

GC (rs2282679) and CYP2R1 (rs10741657) GC encodes vitamin D-binding protein, involved in

PEMT (rs12325817) Involved in endogenous choline synthesis via the hepatic

MTHFD1 (rs2236225) Encodes protein involved in trifunctional enzyme activities related

SFA: cheese, butter, red meat, baked goods

PPARγ2 (rs1801282) Regulates adipocyte differentiation MUFA Macadamia nuts, almond

Sleep is recognized as an essential component of physiological and psychological recovery from,

Deficiencies of certain micronutrients such as vitamin A decrease immune defense against

Anemia-Related Micronutrients: Iron, Folate, and Vitamin B12

Low Iron Status

Vitamin C is a water-soluble antioxidant that aids in the reduction of exercise-induced free-

Macronutrients and Body Composition

Saturated Fat and Polyunsaturated Fat

Conflict of Interest Statement

3. Hietaranta-Luoma HL, Tahvonen R, Iso-Touru T, Puolijoki H, Hopia A. An intervention study

4. Livingstone KM, Celis-Morales C, Navas-Carretero S, San-Cristobal R, Macready AL,

5. Celis-Morales C, Marsaux CF, Livingstone KM, Navas-Carretero S, San-Cristobal R, Fallaize

13. Abrahams M, Frewer L, Bryant E, Stewart-Knox B. Factors determining the integration of

17. Pitsiladis Y, Ferriani I, Geistlinger M, de Hon O, Bosch A, Pigozzi F. A holistic antidoping

25. Pichler I, Minelli C, Sanna S, Tanaka T, Schwienbacher C, Naitza S, et al. . Identification of

27. Garcia M, Martinez-Moreno JM, Reyes-Ortiz A, Suarez Moreno-Arrones L. Garcia AA,

33. Webborn N, Williams A, McNamee M, Bouchard C, Pitsiladis Y, Ahmetov I, et al. . Direct-

52. Begas E, Kouvaras E, Tsakalof A, Papakosta S, Asprodini EK. In vivo evaluation of

53. Ghotbi R, Christensen M, Roh HK, Ingelman-Sundberg M, Aklillu E, Bertilsson L.

54. Djordjevic N, Ghotbi R, Bertilsson L, Jankovic S, Aklillu E. Induction of CYP1A2 by heavy

55. Koonrungsesomboon N, Khatsri R, Wongchompoo P, Teekachunhatean S. The impact of

57. Palatini P, Ceolotto G, Ragazzo F, Dorigatti F, Saladini F, Papparella I, et al. . CYP1A2

64. Graham-Paulson T, Perret C, Goosey-Tolfrey V. Improvements in cycling but not

67. Salinero JJ, Lara B, Ruiz-Vicente D, Areces F, Puente-Torres C, Gallo-Salazar C, et al.

82. Robson-Ansley PJ, Gleeson M, Ansley L. Fatigue management in the preparation of

85. Bodenmann S, Hohoff C, Freitag C, Deckert J, Retey JV, Bachmann V, et al. .

116. Curro M, Di Mauro D, Bruschetta D, D'Amico F, Vecchio M, Trimarchi F, et al. . Influence

131. Pantopoulos K, Porwal SK, Tartakoff A, Devireddy L. Mechanisms of mammalian iron

137. Colombani PC MC. Energie- und Nährstoffaufnahme im Schweizer Spitzensport – eine

140. Petroczi A, Naughton DP, Mazanov J, Holloway A, Bingham J. Performance enhancement

156. Cahill LE, Fontaine-Bisson B, El-Sohemy A. Functional genetic variants of glutathione S-

185. Elsawy G, Abdelrahman O, Hamza A. Effect of choline supplementation on rapid weight

202. Naclerio F, Larumbe-Zabala E. Effects of whey protein alone or as part of a multi-

205. de Luis DA, Aller R, Izaola O, Primo D, Urdiales S, Romero E. Effects of a

Article | PubReader | ePub (beta) | PDF (864K) | Citation

Share on Facebook FacebookShare on Twitter TwitterShare on Google Plus Google+