Current Nutrition Reports

https://doi.org/10.1007/s13668-020-00327-z

DIABETES AND OBESITY (CB CHAN, SECTION EDITOR)

Nutrigenetics/Nutrigenomics, Personalized Nutrition,

and Precision Healthcare
James A. Marcum 1

# Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract
Purpose of Review The purposes of the present review are to examine the emergence of nutrigenetics/nutrigenomics, to analyze
the relationship between nutrigenetics and nutrigenomics, to explore the impact of nutrigenetics/nutrigenomics on healthcare
with respect to noncommunicable diseases, and to discuss the challenges facing the implementation of nutrigenetics/
nutrigenomics within healthcare.
Recent Findings Nutrigenetics/nutrigenomics is certainly a thriving specialty given the sharp increase of publications over the
last two decades. The relationship between nutrigenetics and nutrigenomics is proposed as complementary. The current clinical
and research literature supports the significant impact nutrigenetics/nutrigenomics has on treating and preventing
noncommunicable diseases. Although several challenges face the implementation of nutrigenetics/nutrigenomics into healthcare,
they are not insurmountable.
Summary Nutrigenetics/nutrigenomics plays an important role not only in treating diseases and illnesses but also in promoting
health and wellness through both basic and clinical research; and it is critical for the future of both personalized nutrition and
precision healthcare.

Keywords Cancers . Cardiovascular diseases . Nutrigenetics/nutrigenomics . Obesity . Personalized nutrition . Type 2 diabetes
mellitus

Introduction mellitus, cancers, and cardiovascular diseases. The review

concludes with a discussion of the challenges facing the im-
Since the turn of the twenty-first century, nutrigenetics/ plementation of nutrigenetics/nutrigenomics, especially in
nutrigenomics has become an important specialty for both terms of personalized nutrition and precision healthcare.
clinical research and practice to prevent and treat disease and
illness and to sustain and promote health and wellness [1, 2].
In this review, nutrigenetics/nutrigenomics is introduced and
the role it plays in contemporary healthcare is discussed. To
Emergence of Nutrigenetics/Nutrigenomics
that end, the emergence of both nutrigenetics and
To investigate the emergence of nutrigenetics/nutrigenomics
nutrigenomics is examined in the next section and the rela-
within the healthcare literature, PubMed (https://www.ncbi.
tionship between them is explored in a following section. In a
nlm.nih.gov/pubmed/) was mined as a database, using
subsequent section, the impact of nutrigenetics/nutrigenomics
“nutrigenetics” and “nutrigenomics” as search terms for each
on healthcare delivery is reviewed with respect to the
year between 2000 and 2019. As shown in Fig. 1, the first
noncommunicable diseases of obesity, type 2 diabetes
publications to appear on nutrigenetics or nutrigenomics in
PubMed are in the early 2000s—although there were a few
This article is part of the Topical Collection on Diabetes and Obesity
publications on nutrigenetics prior to 2000. Since then, the
number of annual publications has increased dramatically.
* James A. Marcum
[email protected]
Specifically, from 2005 to 2010, there was an increase from
a little over 20 publications in 2005 to over 180 publications in
1
Institute of Biomedical Studies, Baylor University, Waco, TX 76798, 2010—representing almost an order of magnitude increase in
USA publications within 5 years. Since 2010, the number of
 Curr Nutr Rep

Fig. 1 Annual number of

publications in PubMed for
nutrigenetics and nutrigenomics

publications has continued to increase, surpassing 200 publi- Relationship Between Nutrigenetics
cations per annum in 2015. and Nutrigenomics
Although the use of the terms nutrigenetics and
nutrigenomics within the healthcare literature increased signif- Both nutrigenetics and nutrigenomics are often used inter-
icantly during the first decade of the twenty-first century, the changeably not only within the public literature but also with-
conceptual background, especially for nutrigenetics, was pres- in the professional nutritional and healthcare literature. So,
ent within the biological literature from the twentieth century. what is the relationship between nutrigenetics and
For example, much of the early work in classical genetics was nutrigenomics and why the contraction to nutrigenetics/
on the genetic determination of nutritional requirements within nutrigenomics? The answer to this question reflects the history
a variety of organisms, from unicellular to multicellular organ- of genetics and genomics. Nutrigenetics has its roots within
isms [3]. However, the term nutrigenetics was not introduced classical genetics. And, as Brennan [4] conceived it originally,
into the healthcare literature until 1975. Specifically, Richard nutrigenetics pertains to the interaction of nutritional and ge-
Brennan [4] coined the term nutrigenetics with respect to netic factors that may play a role in disease etiology. Its main
treating hypoglycemia. The term, however, enjoyed only mod- goal is to investigate the impact of genetic variation, particu-
erate success in the literature after its introduction. On the other larly as a single-nucleotide polymorphism (SNP), on an indi-
hand, in 2000, Nancy Fogg-Johnson and Alex Merolli [5] in- vidual’s response to dietary intake, especially in terms of how
troduced the term nutrigenomics into the literature and since its genetic variation influences an individual’s metabolic state
introduction, the term has become common (Fig. 1). [8]. For example, an individual’s response to caffeine varies
Currently, nutrigenetics/nutrigenomics is a well- because of genetic polymorphism in the CYP1A2 gene [9].
established specialty within the healthcare industry. For ex- This gene encodes for an enzyme synthesized in the liver that
ample, the Journal of Nutrigenetics and Nutrigenomics was demethylates caffeine and certain variants of the gene demeth-
launched in 2007 sponsored by the International Society of ylate caffeine more quickly than others [10]. In sum,
Nutrigenetics/Nutrigenomics, which was founded in 2005 and nutrigenetics is concerned with how an individual’s genotypic
holds annual conferences throughout the world. In the inau- composition influences the phenotypic response to dietary
gural issue of the journal, the society’s president stressed the intake.
importance of nutritional genetics and genomics for contem- Nutrigenomics, however, has its roots in the Human
porary healthcare and society, especially in terms of treating Genome Project and especially in the postgenomic era and
noncommunicable diseases [6]. Interestingly, the journal was its high-throughput omics technologies [11]. Its goal is to
renamed Lifestyle Genomics in 2018 to reflect the additional investigate the impact of diet and nutrition on gene expression,
lifestyle factors besides diet, which have an impact on genes in especially through epigenomic (e.g., histone methylation),
terms of promoting health and preventing illness [7•]. transcriptomic (e.g., RNA transcription), proteomic (e.g.,
Curr Nutr Rep

protein synthesis), and metabolomic (e.g., metabolite synthe- global burden for humanity not only in terms of health but also
sis) high-throughput assays [12]. For example, the results in quality of life, especially for the developing world [21]. In
from a metabolomic study using premenopausal women sug- this section, the role of nutrigenetics/nutrigenomics in both the
gest that ingestion of soy isoflavone has a significant impact prevention and potential treatment of obesity, type 2 diabetes
on various metabolic pathways associated with osmolyte fluc- mellitus, cancers, and cardiovascular diseases is reviewed.
tuation and energy metabolism [13]. These metabolic changes According to many healthcare professionals, obesity is an
were even greater after ingesting unconjugated soy isoflavone epidemic [22•, 23]—if not a pandemic [24•]. Obesity is de-
or miso. The results, according to the study’s authors, indicate fined as a body mass index or BMI (kg/m2) of 30 or greater
that the chemical composition of isoflavones present in soy- [25]. A recent study of obesity incidence in almost 200 coun-
based nutrition has a significant impact on an individual’s tries reported that in 2015 over 100 million children and over
metabolism. Finally, the long-term goal of nutrigenomics is 600 million adults were obese, i.e., around 10% of the world’s
to obtain and integrate an individual’s personalized nutritional population [26]. Although there is considerable debate as to its
omics profile that includes also the individual’s microbiome, cause, there is consensus that unhealthful nutrition and phys-
which constitutes the “gutome” [14]. ical inactivity play major roles, especially in terms of an
Finally, I propose that the relationship between “obesogenic” environment [27]. But this environment is only
nutrigenetics and nutrigenomics can be depicted as reciprocal part of the reason for the pandemic—genotype is also thought
and complementary, which thereby answers the second part of to play a role. Within the last several decades, well over 50
the question as to why the contraction of nutrigenetics and candidate genes for obesity, such as the melanocortin-4-
nutrigenomics to nutrigenetics/nutrigenomics. Whereas receptor (MC4R) gene, have been identified through GWAS
nutrigenetics is traditionally concerned with the genetic poly- [28•]. Another important example is the first obesity suscep-
morphisms through identifying SNPs and allied haplotypes, tibility locus identified by GWAS—the fat mass and obesity-
using genome-wide association studies (GWAS), associated (FTO) gene [29]. Certain variants of this gene con-
nutrigenomics focuses on the expression of genes with respect tribute to an increased risk for obesity through changes in an
to diet through high-throughput omics technology. individual’s food preference and intake [30]. Current studies
Consequently, nutrigenetics can inform nutrigenomics of pos- based on nutrigenetics/nutrigenomics are being conducted to
sible candidate genes through the detection of SNPs via determine how best to design personalized nutrition to address
GWAS. With this information in hand, experimental studies the obesity problem [31•, 32].
in nutrigenomics can then be designed using omics assays, Obesity itself is not only a major health problem, but also a
from genomics to metabolomics, to identify the specific comorbid risk factor for other noncommunicable diseases
mechanisms involved in terms of the possible impact diet such as type 2 diabetes mellitus [33]. Although the incidence
can have on gene expression. In short, I propose that through of diabetes mellitus in general is rising, the incidence of type 2
these reciprocal interactions nutrigenetics and nutrigenomics diabetes—which accounts for over 90% of diabetic cases—is
complement one another as the nutrigenetics/nutrigenomics rising at an alarming rate—quadrupling within the last four
specialty to provide a comprehensive picture of an individ- decades [34]. Just as for obesity, the cause of the type 2 dia-
ual’s integrated metabolism, in order to construct a personal- betes pandemic is contested within the healthcare literature;
ized diet to avoid illness and possible health risks, as well as to however, it does parallel the increased incidence of obesity
promote health and longevity [15••, 16]. [35], even though the two noncommunicable diseases share
only a few candidate genes for susceptibility based on GWAS
[36, 37]. Although type 2 diabetes mellitus is multigenetic, a
Noncommunicable Diseases major candidate gene for susceptibility to the disease is the
transcription factor 7-like 2 (TCF7L2) gene, which is involved
Although healthcare has enjoyed enormous success in curing in regulating insulin secretion and sensitivity [38]. Finally,
most infectious and acute diseases, it has failed to cure—or studies based on nutrigenetics/nutrigenomics are providing
even to manage effectively—the majority of noncommunicable insight into the impact of nutrients, like polyunsaturated fats,
diseases, i.e., diseases that are generally not transmissible be- on genes, like TCF7L2 [39, 40]. Unfortunately, the complex-
tween individuals [17]. In fact, the mortality rates for these ity of type 2 diabetes is a major challenge to developing pre-
diseases are on the rise [18]. According to the World Health ventive and therapeutic personalized diets [41, 42].
Organization [19], over 40 million people are currently dying According to the World Health Organization [43], cancer is
each year from these diseases. Noncommunicable diseases are the second leading cause of death globally and is responsible
often chronic in duration and reflect lifestyle choices, such as for around 1 in 6 deaths. The organization also reports that
tobacco and alcohol consumption [20••]. They include obesity, approximately one-third of deaths from cancer are due to a
diabetes mellitus, cancers, and cardiovascular and pulmonary handful of factors, including low fruit and vegetable intake,
diseases, among others. These diseases represent a serious alcohol and tobacco consumption, high BMI, and lack of
 Curr Nutr Rep

exercise. A person’s diet has also been implicated in the risk of cardiovascular diseases—although its rate has been falling over
carcinogenesis [44, 45•]. For example, a literature review pub- the last several decades for older adults [64]. An important risk
lished in the 1980s reported etiological correlations between factor in cardiovascular diseases is thought to be diet [65]. For
breast cancer and several dietary factors ranging from energy example, various studies suggest that diets low in saturated fats
intake to various proteins, carbohydrates, and fats, as well as or high in polyunsaturated fats have lower risk for cardiovas-
to different vitamins and trace minerals and elements [46]. cular diseases such coronary artery disease [66, 67•], although
Moreover, the absence or reduction of certain nutrients within their exact effect is controversial [68]. Nevertheless, contempo-
the diet is also thought to trigger carcinogenesis. For example, rary nutritional guidelines encourage replacing saturated fatty
dietary deficiency in folate may be linked to carcinogenesis, acids with whole grains while avoiding refined sugar and re-
especially colorectal and pancreatic cancers [47, 48]. Folate is placing animal and dairy protein with plant protein, to prevent
an active agent in maintaining DNA integrity through its re- cardiovascular diseases [69]. In sum, cardiovascular diseases
pair, and reduced dietary levels result in genomic instability are polygenetic and reflect the interaction of an individual’s
through epigenetic mechanisms [49]. However, many of the genes, diet, lifestyle, and environment.
factors that are thought to play a role in tumorigenesis are The impact of diet on cardiovascular health is mediated
exogenous carcinogens contaminating food, which can acti- t h r o u gh a c o m p l ex n et w o r k o f g e n es fo r w h i c h
vate oncogenes or inhibit tumor suppressor genes—two im- nutrigenetics/nutrigenomics provides effective means to in-
portant hallmarks of carcinogenesis [50, 51]. vestigate [70]. Many of these genes are involved in lipid me-
Although diet and nutrition are thought to be risk factors in tabolism, such as APOA1, whose gene product constitutes
carcinogenesis, they may also play a role in preventing and around 70% of high-density lipoprotein; APOA5, whose gene
even treating cancer [52, 53]. Analyzing this role is an impor- product is involved in regulating triglycerides levels through
tant goal for research on nutrigenetics/nutrigenomics. For ex- modulating lipoprotein lipase activity; and APOE, whose gene
ample, dietary polyphenols have been suggested to be in- product mediates the binding of lipid complexes to cell recep-
volved in preventing or reversing a variety of cancers, from tors; and, their expression can be modulated through diet [71].
breast cancer to prostate cancer, through epigenetic mecha- For example, recent studies suggest that diets rich in omega-3
nisms [54, 55]. The reason nutrition is thought to be effective polyunsaturated fats, as found in fish oils, can reduce the risk
is that epigenetic changes, such as methylation, are potentially of atherosclerosis by regulating several genes, particularly
reversible [56]. Moreover, studies based on nutrigenomics APOA1, APOA5, and APOE, involved in lipid metabolism
suggest that micronutrients, such as certain vitamins and trace [72]. Although many challenges face the implementation of
minerals, and macronutrients, such as dietary fiber, are effec- nutrigenetics/nutrigenomics to the prevention and treatment of
tive not only in preventing cancer but also for treating it, cardiovascular diseases, these challenges are thought not to be
especially in terms of the hallmarks of cancer, which consti- insurmountable [73].
tute around a half dozen traits of tumor cells such as limitless Finally, the American Heart Association (AHA) issued a
replicative potential to metastasis [57•]. For example, diets scientific statement discussing the role of nutrigenomics in
containing flaxseeds have been shown to assist in the treat- studying the diet-gene-cardiovascular disease connection [74].
ment of breast cancer [58]. The mechanism involves a lignan The article canvasses various omics technologies available for
from flaxseed, which is converted to a substance that binds to conducting nutrigenomics research, from genomics to proteo-
estrogen receptors and thereby reduces cell growth [59]. mics and even to microbiomics. For example, the authors dis-
Interestingly, a recent meta-analysis, which involves mining cuss a study in which a correlation was found between intestinal
data from studies based on nutrigenomics, revealed a signa- microbiota metabolism of L-carnitine, present in red meat, and
ture set of 18 genes that are active in regulating the cell cycle atherosclerosis. The AHA article emphasizes that an important
[60]. This set of genes responds to certain bioactive com- goal of nutrigenomics for cardiovascular research is the formu-
pounds, such as sulforaphane and withaferin A, contained in lation of personalized nutrition for preventing and managing
various diets and available as dietary supplements [61]. cardiovascular diseases. Although the AHA article concludes
Finally, nutrigenomics can be used to develop diets to ame- with a brief discussion of the limitations and challenges facing
liorate side effects often associated with traditional cancer this goal, its authors are optimistic that realizing the goal is not
chemotherapy and radiation therapy [62]. only possible for addressing cardiovascular and other
Cardiovascular diseases are the leading cause of death glob- noncommunicable diseases but also necessary.
ally, among adults aged 35–70 [63]. Cardiovascular diseases
represent a diverse set of diseases and conditions, including
coronary artery disease and atherosclerosis, congestive heart Conclusions
failure, hypertension, stroke, and arrhythmia—to name the
more common diseases. Among these diseases, coronary artery Although nutrigenetics/nutrigenomics hold immense promise
disease is the most prevalent and accounts for most deaths from for preventing and even treating noncommunicable diseases,
Curr Nutr Rep

there are several challenges and limitations facing its imple- nutrition can play a major role in realizing personalized
mentation with respect to both biomedical research and clini- healthcare, especially with respect to living the “good life”
cal practice [75–77]. As the AHA scientific statement stresses, [96, 97••, 98].
there are several technical challenges and limitations particu-
larly in terms of designing and conducting randomized clinical Compliance with Ethical Standards
trials to construct a robust knowledge base to counsel patients
[74]. For example, one of the major limitations to Conflict of Interest Dr. Marcum has nothing to disclose.
nutrigenomic clinical trials is controlling participant’s dietary
Human and Animal Rights and Informed Consent This article does not
intake, although use of specific biomarkers for food intake
contain any studies with human or animal subjects performed by any of
could ameliorate this limitation [78]. Moreover, there are also the authors.
practical problems with respect to standardization, especially
in terms of defining clearly the terms employed in
nutrigenetics/nutrigenomics research and clinical practice References
[79]. For example, the notion of the gene as the unit of hered-
ity has changed dramatically during the postgenomic era from
Papers of particular interest, published recently, have been
simply DNA sequence to including chromosomal architecture
highlighted as:
and non-DNA macromolecules that contribute to epigenetic
• Of importance
regulation [80]. Furthermore, there are a variety of ethical,
•• Of major importance
legal, and social challenges, ranging from security of
nutrigenomic information to developing equitable distribution 1. De Caterina R, Martinez JA, Kohlmeier M, editors. Principles of
of dietary resources, especially to underserved and developing nutrigenetics and nutrigenomics: fundamentals of individualized
nations [81–83]. Finally, there is the challenge of healthcare nutrition. London: Academic Press; 2020.
education, i.e., trying to find room within an already crowded 2. Ferguson LR. Nutrigenomics and nutrigenetics in functional foods
and personalized nutrition. Boca Raton: CRC Press; 2014.
curriculum for training in nutrigenetics/nutrigenomics [84]. 3. Roper JA. Genetic determination of nutritional requirements. Proc
Given these challenges and limitations, there is a concern as Nutr Soc. 1960;19:39–45.
to what to do while nutrigenetics/nutrigenomics is being imple- 4. Brennan RO, Mulligan WC. Nutrigenetics: new concepts for reliev-
mented into the healthcare system [85]. One possible way for- ing hypoglycemia. New York: M. Evans & Co; 1975.
ward is for healthcare professionals to recommend a diet for 5. Fogg-Johnson N, Merolli A. Nutrigenomics: the next wave in nu-
trition research. Nutraceuticals World. 2000;3:86–95.
patients suffering from noncommunicable diseases. A recent 6. Simopoulos AP. Editorial. J Nutrigenet Nutrigenomics. 2008;1:2–
meta-analysis of the Mediterranean diet literature supports the 3.
diet’s general efficacy with respect to noncommunicable dis- 7.• Mutch DM, Zulyniak MA, Rudkowska I, et al. Lifestyle genomics:
eases [86] and particularly for obesity [87], type 2 diabetes addressing the multifactorial nature of personalized health.
Lifestyle Genomics. 2018;11:1–8 In this editorial, the authors
mellitus [88], cancers [89], and cardiovascular diseases [90]. discuss the change from the Journal of Nutrigenetics and
However, many nutritionists are resistant to a “one-size-fits- Nutrigenomics to Lifestyle Genomics. One major contributor
all” approach to diets [91] and strict adherence to the diet can to the change is that lifestyle factors other than diet have a
be challenging [92]. Furthermore, the Mediterranean diet does significant impact on health and disease.
8. Ordovas JM, Mooser V. Nutrigenomics and nutrigenetics. Curr
not substitute for developing the personalized nutrition pro-
Opin Lipidol. 2004;15:101–8.
gram, but it does offer a temporary approach to stemming the 9. Cornelis MC. Coffee intake. Prog Mol Biol Transl Sci. 2012;108:
current increase in noncommunicable diseases. 293–322.
Finally, nutrigenetics/nutrigenomics is a necessary special- 10. Thorn CF, Aklillu E, McDonagh EM, et al. PharmGKB summary:
ty for realizing personalized nutrition [15, 16, 93, 94]. caffeine pathway. Pharmacogenet Genomics. 2012;22:389–95.
11. Carlberg C, Ulven SM, Molnár F, editors. Nutrigenomics. Basel:
Personalized nutrition represents the opportunity for Springer; 2016.
preventing, managing, and treating disease and optimizing 12. Sales NMR, Pelegrini PB, Goersch MC. Nutrigenomics: definitions
health; its implementation into healthcare research and prac- and advances of this new science. J Nutr Metab 2014. http://
tice requires three elements [95••]. The first consists of scien- downloads.hindawi.com/journals/jnme/2014/202759.pdf.
Accessed 12 Jan 2020.
tific and clinical research, especially in terms of randomized
13. Solanky KS, Bailey NJ, Beckwith-Hall BM, et al. Biofluid 1H
clinical trials, to provide a robust knowledge base for NMR-based metabonomic techniques in nutrition research—
informing clinicians how best to advise patients. The next metabolic effects of dietary isoflavones in humans. J Nutr
element is professional education in personalized nutrition Biochem. 2005;16:236–44.
ranging from the educational curriculum to continuing educa- 14. Dimitrov DV. The human gutome: nutrigenomics of the host–
microbiome interactions. OMICS. 2011;15:419–30.
tion. The last element pertains to the formulation of guidelines 15.•• Ordovas JM, Ferguson LR, Tai ES, et al. Personalised nutrition and
for therapeutic counseling in terms of recommendations for health. Br Med J. 2018;361. https://www.bmj.com/content/bmj/
best evidence-informed practice. In sum, personalized 361/bmj.k2173.full.pdf. Accessed 10 Feb 2020. The authors
 Curr Nutr Rep

review the current state of personalized nutrition and its role in 31.• Drabsch T, Holzapfel C. A scientific perspective of personalised
healthcare. Although they acknowledge that personalized nu- gene-based dietary recommendations for weight management.
trition is important for providing quality healthcare, there are Nutrients. 2019;11 https://www.mdpi.com/2072-6643/11/3/617.
several challenges facing its implementation in healthcare. Accessed 28 Dec 2019. The authors discuss the problems
16. Simopoulos AP, Milner JA, editors. Personalized nutrition: trans- associated with “one size fits all” diets. They go on to review
lating nutrigenetic/nutrigenomic research into dietary guidelines. current studies on gene-based personalized nutrition and pro-
Basel: Karger; 2010. pose that human intervention studies are required to provide
17. Hunter DJ, Reddy KS. Noncommunicable diseases. N Engl J Med. the evidence needed for gene-based dietary recommendations.
2013;369:1336–43. 32. Heianza Y, Qi L. Gene-diet interaction and precision nutrition in
18. NCD Countdown 2030 Collaborators. NCD Countdown 2030: obesity. Int J Mol Sci 2017;18. https://www.mdpi.com/1422-0067/
Worldwide trends in non-communicable disease mortality and 18/4/787. Accessed 20 Feb 2020.
progress towards Sustainable Development Goal target 3.4. 33. Khaodhiar L, McCowen KC, Blackburn GL. Obesity and its co-
Lancet. 2018;392:1072–88. morbid conditions. Clin Cornerstone. 1999;2:17–31.
19. World Health Organization. Noncommunicable diseases. 2018. https:// 34. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in
www.who.int/news-room/fact-sheets/detail/noncommunicable- diabetes since 1980: a pooled analysis of 751 population-based
diseases. Accessed 2 Jan 2020. studies with 4 4 million participants. Lancet. 2016;387:1513–30.
20.•• Egger G, Binns A, Rössner S, Sagner M. Lifestyle medicine: life- 35. Al-Goblan AS, Al-Alfi MA, Khan MZ. Mechanism linking diabe-
style, the environment and preventive medicine in health and dis- tes mellitus and obesity. Diabetes Metab Syndr Obes. 2014;7:587–
ease. 3rd ed. London: Academic Press; 2017. A very important 91.
collection of essays on lifestyle medicine. The topics range from 36. Grarup N, Sandholt CH, Hansen T, et al. Genetic susceptibility to
the foundations of lifestyle medicine to its application to chronic type 2 diabetes and obesity: from genome-wide association studies
diseases, as well as to its role in the future of healthcare. to rare variants and beyond. Diabetologia. 2014;57:1528–41.
21. Galabos L, Sturchio JL, Whitehead RC, editors. Noncommunicable 37. Unnikrishnan R, Pradeepa R, Joshi SR, et al. Type 2 diabetes:
diseases in the developing world: addressing gaps in global policy demystifying the global epidemic. Diabetes. 2017;66:1432–42.
and research. Baltimore: The Johns Hopkins University Press; 38. Nguyen-Tu MS, da Silva XG, Leclerc I, et al. Transcription factor-
2014. 7–like 2 (TCF7L2) gene acts downstream of the Lkb1/Stk11 kinase
to control mTOR signaling, β cell growth, and insulin secretion. J
22.• Jaacks LM, Vandevijvere S, Pan A, et al. The obesity transition:
Biol Chem. 2018;293:14178–89.
stages of the global epidemic. Lancet Diabetes Endocrinol. 2019;7:
39. Berná G, Oliveras-López M, Jurado-Ruíz E, et al. Nutrigenetics and
231–40 This is an important article on examining the obesity
nutrigenomics insights into diabetes etiopathogenesis. Nutrients.
transition over the past four decades. The authors propose a
2014;6:5338–69.
four-stage model to account for the transition. Their goal is to
40. Harrington JM, Phillips CM. Nutrigenetics: bridging two worlds to
provide guidance for researchers and policy makers to stem the
understand type 2 diabetes. Curr Diab Rep. 2014;14. https://doi.org/
transition in the future.
10.1007/s11892-014-0477-1 Accessed 20 Dec 2019.
23. Kim R, Lee DH, Subramanian SV. Understanding the obesity ep-
41. Ortega Á, Berná G, Rojas A, et al. Gene-diet interactions in type 2
idemic. Br Med J. 2019;366 https://www.bmj.com/content/366/
diabetes: the chicken and egg debate. Int J Mol Sci 2017; 18. https://
bmj.l4409. Accessed 24 Jan 2020.
www.mdpi.com/1422-0067/18/6/1188. Accessed 12 Dec 2019.
24.• Blüher M. Obesity: global epidemiology and pathogenesis. Nat 42. Zimmet PZ, Magliano DJ, Herman WH, et al. Diabetes: a 21st
Rev Endocrinol. 2019;15:288–98 In this review article, the au- century challenge. Lancet Diabetes Endocrinol. 2014;2:56–64.
thor discusses not only the pandemic nature of global obesity 43. World Health Organization. Cancer. 2018; https://www.who.int/
but also its regional differences. He addresses the challenges news-room/fact-sheets/detail/cancer. Accessed 12 Jan 2020.
facing the translation of our understanding of what causes obe- 44. Elsamanoudy AZ, Neamat-Allah MAM, Mohammad FAH, et al.
sity into actionable treatment and prevention. The role of nutrition related genes and nutrigenetics in understand-
25. World Health Organization. Obesity and overweight. 2018. https:// ing the pathogenesis of cancer. J Microsc Ultrastruct. 2016;4:115–
www.who.int/news-room/fact-sheets/detail/obesity-and- 22.
overweight. Accessed 2 Jan 2020. 45.• Patel A, Pathak Y, Patel J, et al. Role of nutritional factors in path-
26. GBD 2015 Obesity Collaborators. Health effects of overweight and ogenesis of cancer. Food Qual Saf. 2018;2:27–36 The authors
obesity in 195 countries over 25 years. N Engl J Med. 2017;377: discuss the role of nutrients, especially micronutrients, in terms
13–27. of modulating the mechanism of carcinogenesis. They also ex-
27. Townshend T, Lake A. Obesogenic environments: current evidence plore the relationship between these nutrients and genetic ex-
of the built and food environments. Perspect Public Health. pression as it relates to the etiology of cancer.
2017;137:38–44. 46. Rohan TE, Bain CJ. Diet in the etiology of breast cancer. Epidemiol
28.• Goodarzi MO. Genetics of obesity: what genetic association studies Rev. 1987;9:120–45.
have taught us about the biology of obesity and its complications. 47. Chittiboyina S, Chen Z, Chiorean EG, et al. The role of the folate
Lancet Diabetes Endocrinol. 2018;6:223–36 The authors review pathway in pancreatic cancer risk. PLoS One. 2018:13. https://doi.
the more than 300 SNPs identified through GWAS associated org/10.1371/journal.pone.0193298 Accessed 15 Jan 2020.
with obesity. They discuss the importance of these SNPs for 48. Choi SW, Mason JB. Folate and carcinogenesis: an integrated
understanding the complexity of obesity in terms of lifestyle scheme. J Nutr. 2000;130:129–32.
and environmental interactions. 49. Kadayifci FZ, Zheng S, Pan Y-X. Molecular mechanisms underly-
29. Loos RJ, Yeo GS. The bigger picture of FTO—the first GWAS- ing the link between diet and DNA methylation. Int J Mol Sci
identified obesity gene. Nat Rev Endocrinol. 2014;10:51–61. 2018;19. https://www.ncbi.nlm.ni h.gov/pmc/articles/
30. Brunkwall L, Ericson U, Hellstrand S, et al. Genetic variation in the PMC6320837/pdf/ijms-19-04055.pdf. Accessed 30 April 2020.
fat mass and obesity-associated gene (FTO) in association with 50. Hanahan D, Weinberg RA. Hallmarks of cancer: the next genera-
food preferences in healthy adults. Food Nutr Res 2013;57. tion. Cell. 2011;144:646–74.
https://foodandnutritionresearch.net/index.php/fnr/article/view/ 51. Tang PK. Consume, digest, and expire: the risks of domesticated
529/861. Accessed 29 April 2020. carcinogens. Lancet Oncol. 2016;17:24–5.
Curr Nutr Rep

52. Ardekani AM, Jabbari S. Nutrigenomics and cancer. Avicenna J 70. Corella D, Ordovas JM. Nutrigenomics in cardiovascular medicine.
Med Biotechnol. 2009;1:9–17. Circ Cardiovasc Genet. 2009;2:637–51.
53. Nicastro HL, Trujillo EB. Milner JA. Nutrigenomics Cancer Prev 71. Nuno NB, Heuberger R. Nutrigenetic associations with cardiovas-
Curr Nutr Rep. 2012;1:37–43. cular disease. Rev Cardiovasc Med. 2014;15:217–25.
54. Braicu C, Mehterov N, Vladimirov B, et al. Nutrigenomics in can- 72. Merched AJ, Chan L. Nutrigenetics and nutrigenomics of athero-
cer: revisiting the effects of natural compounds. Semin Cancer Biol. sclerosis. Curr Atheroscler Rep 2013;15. https://www.ncbi.nlm.nih.
2017;46:84–106. gov/pmc/articles/PMC4003879/pdf/nihms572659.pdf. Accessed
55. Berghe WV. Epigenetic impact of dietary polyphenols in cancer 29 April 2020.
chemoprevention: lifelong remodeling of our epigenomes. 73. Lovegrove JA, Gitau R. Personalized nutrition for the prevention of
Pharmacol Res. 2012;65:565–76. cardiovascular disease: a future perspective. J Hum Nutr Diet.
56. Marcum JA. The cancer epigenome: a review. J Biotechnol 2008;21:306–16.
Biomed. 2019;2:67–83. 74. Ferguson F, Allayee H, Gerszten RE, et al. Nutrigenomics, the
57.• Irimie AI, Braicu C, Pasca S, et al. Role of key micronutrients from microbiome, and gene-environment interactions: new directions in
nutrigenetic and nutrigenomic perspectives in cancer prevention. cardiovascular disease research, prevention, and treatment: a scien-
Medicina. 2019;55 https://www.mdpi.com/1010-660X/55/6/283. tific statement from the American Heart Association. Circ
Accessed 28 Dec 2019. In this rather comprehensive review, Cardiovasc Genet. 2016;9:291–313.
the authors discuss the various key micronutrients, such as 75. Hurlimann T, Menuz V, Graham J, et al. Risks of nutrigenomics
vitamins, selenium, and dietary fiber, involved in and nutrigenetics? What the scientists say. Genes Nutr. 2014;9.
carcinogenesis and its prevention. Importantly, they frame https://doi.org/10.1007/s12263-013-0370-6 Accessed 10
their discussion in terms of the hallmarks of cancer. March 2020.
58. Calado A, Neves PM, Santos T, et al. The effect of flaxseed in 76. Reddy VS, Palika R, Ismail A, Pullakhandam R, Reddy GB.
breast cancer: a literature review. Front Nutr. 2018;5. https://doi. Nutrigenomics: opportunities & challenges for public health nutri-
org/10.3389/fnut.2018.00004/full Accessed 24 Jan 2020. tion. Indian J Med Res. 2018;148:632–41.
59. De Silva SF, Alcorn J. Flaxseed lignans as important dietary poly- 77. Zeisel SH. A grand challenge for nutrigenomics. Front Genet.
phenols for cancer prevention and treatment: chemistry, pharmaco- 2010;1. https://doi.org/10.3389/fgene.2010.00002/full .
kinetics, and molecular targets. Pharmaceuticals. 2019;12. https:// 78. Mathers JC. Nutrigenomics in the modern era. Proc Nutr Soc.
www.ncbi.nlm.nih.gov/pmc/articles/PMC6630319/pdf/ 2017;76:265–75.
pharmaceuticals-12-00068.pdf. Accessed 30 April 2020. 79. Ravi Subbiah MR. Understanding the nutrigenomic definitions and
60. Martín-Hernández R, Reglero G, Dávalos A. Data mining of concepts at the food–genome junction. OMICS. 2008:12229–35.
nutrigenomics experiments: identification of a cancer protective 80. Portin P, Wilkins A. The evolving definition of the term “gene”.
gene signature. J Funct Foods. 2018;42:380–6. Genetics. 2017;205:1353–64.
61. Royston KJ, Paul B, Nozell S, et al. Withaferin A and sulforaphane 81. Godard B, Hurlimann T. Nutrigenomics for global health: ethical
regulate breast cancer cell cycle progression through epigenetic challenges for underserved populations. Curr Pharmacogenomics
mechanisms. Exp Cell Res. 2018;368:67–74. Person Med. 2009;7:205–14.
62. Kang JX. Nutrigenomics and cancer therapy. J Nutrigenet 82. Ferguson LR, De Caterina R, Görman U, et al. Guide and position
Nutrigenomics. 2013;6:I–II. of the International Society of Nutrigenetics/Nutrigenomics on per-
63. Dagenais GR, Leong DP, Rangarajan S, et al. Variations in com- sonalized nutrition: part 1— fields of precision nutrition. J
mon diseases, hospital admissions, and deaths in middle-aged Nutrigenet Nutrigenomics. 2016;9:12–27.
adults in 21 countries from five continents (PURE): a prospective 83. Kohlmeier M, De Caterina R, Ferguson LR, et al. Guide and posi-
cohort study. Lancet. 2020;395:785–94. tion of the International Society of Nutrigenetics/Nutrigenomics on
64. Wilmot KA, O’Flaherty M, Capewell S, et al. Coronary heart dis- personalized nutrition: part 2—ethics, challenges and endeavors of
ease mortality declines in the United States from 1979 through precision nutrition. J Nutrigenet Nutrigenomics. 2016;9:28–46.
2011: evidence for stagnation in young adults, especially women. 84. Castle D, Ries NM. Ethical, legal and social issues in
Circulation. 2015;132:997–1002. nutrigenomics: the challenges of regulating service delivery and
65. Anand SS, Hawkes C, De Souza RJ, et al. Food consumption and building health professional capacity. Mutat Res. 2007;622:138–
its impact on cardiovascular disease: importance of solutions fo- 43.
cused on the globalized food system: a report from the workshop 85. Pavlidis C, Patrinos GP, Katsila T. Nutrigenomics: a controversy.
convened by the World Heart Federation. J Am Coll Cardiol. Appl Transl Genom. 2015;4:50–3.
2015;66:1590–614. 86. Dinu M, Pagliai G, Casini A, et al. Mediterranean diet and multiple
66.• Brandhorst S, Longo VD. Dietary restrictions and nutrition in the health outcomes: an umbrella review of meta-analyses of observa-
prevention and treatment of cardiovascular disease. Circ Res. tional studies and randomised trials. Eur J Clin Nutr. 2018;72:30–
2019;124:952–65 The authors review the various risk factors 43.
associated with cardiovascular diseases with respect to dietary 87. D’Innocenzo S, Biagi C, Lanari M. Obesity and the Mediterranean
factors. They frame their review in terms of four pillars: basic diet: a review of evidence of the role and sustainability of the
research, epidemiology, clinical studies, and centenarian Mediterranean diet. Nutrients. 2019;11. https://www.mdpi.com/
studies. 2072-6643/11/6/1306. Accessed 12 March 2020.
67. Sacks FM, Lichtenstein AH, Wu JH, et al. Dietary fats and cardio- 88. Esposito K, Maiorino MI, Bellastella G, et al. Mediterranean diet
vascular disease: a presidential advisory from the American Heart for type 2 diabetes: cardiometabolic benefits. Endocrine. 2017;56:
Association. Circulation. 2017;136:e1–e23. 27–32.
68. Lichtenstein AH. Dietary fat and cardiovascular disease: ebb and 89. Mentella MC, Scaldaferri F, Ricci C, et al. Cancer and
flow over the last half century. Adv Nutr. 2019;10:S332–9. Mediterranean diet: a review. Nutrients. 2019;11. https://www.
69. Briggs MA, Petersen KS, Kris-Etherton PM. Saturated fatty acids mdpi.com/2072-6643/11/9/2059. Accessed 29 Feb 2020.
and cardiovascular disease: replacements for saturated fat to reduce 90. Martínez-González MA, Gea A, Ruiz-Canela M. The
cardiovascular risk. Healthcare. 2017;5. https://www.mdpi.com/ Mediterranean diet and cardiovascular health: a critical review.
2227-9032/5/2/29. Accessed 2 March 2020. Circ Res. 2019;124:779–98.
 Curr Nutr Rep

91. Marantz PR. Rethinking dietary guidelines. Crit Rev Food Sci Nutr. 96. Komduur RH, Korthals M, Te Molder H. The good life: living for
2010;50:17–8. health and a life without risks? on a prominent script of
92. Iacoviello L. Perspectives and challenges for adoption of the nutrigenomics. Br J Nutr. 2008;101:307–16.
Mediterranean diet. Eur J Pub Health. 2018;28:261–2. 97.•• Aruoma OI, Hausman-Cohen S, Pizano J, et al. Personalized nutri-
93. Kaput J. Nutrigenomics research for personalized nutrition and tion: translating the science of nutrigenomics into practice. J Am
medicine. Curr Opin Biotechnol. 2008;19:110–20. Coll Nutr. 2019;38:287–301 In this important article from the
94. Palou A. From nutrigenomics to personalised nutrition. Genes Nutr. proceedings of the 2018 American College of Nutrition
2007;2:5–7. Meeting, the authors discuss the translation of nutrigenomics
95.•• Bush CL, Blumberg JB, El-Sohemy A, et al. Toward the definition into personalized clinical practice and the challenges facing it.
of personalized nutrition: a proposal by The American Nutrition 98. Loos RJF. From nutrigenomics to personalizing diets: are we ready
Association. J Am Coll Nutr. 2020;39:5–15 In this important for precision medicine? Am J Clin Nutr. 2019;109:1–2.
article from the proceedings of the 2019 American College of
Nutrition Meeting, the authors propose a standard definition
Publisher’s Note Springer Nature remains neutral with regard to jurisdic-
for personalized nutrition for guiding research, clinical prac-
tional claims in published maps and institutional affiliations.
tice, and healthcare policy formation. They conclude with a
discussion of the challenges facing personalized nutrition in
the twenty-first century.