Nutrigenomics

Definition

Nutrigenomics is comprised of nutritional or dietary factors based on an individual's distinct genetic makeup or genotype. Nutrigenomics is one aspect of personalized medicine.

Purpose

The purpose of nutrigenomics is to tailor diets based on individual genetic determinants to optimize health and prevent disease. Although this science is new, a 2014 study reported that personalized dietary advice based on individual genetic profiles improved eating habits more than typical dietary recommendations for the general population. As more is learned about human gene variants and genetic susceptibilities, researchers hope that personalized nutrition can help reduce or eliminate various diseases and conditions such as obesity, type 2 diabetes, asthma, cardiovascular disease (CVD), and cancer. Another goal of nutrigenomics is to reduce or eliminate racial and ethnic health disparities that result from interactions between specific gene variants and dietary factors.




Researcher developing food with high mineral, vitamin, and protein content. The sample tubes contain solvents used to extract nutrients from the food as part of the process of determining the amount of nutrients they contain.





Researcher developing food with high mineral, vitamin, and protein content. The sample tubes contain solvents used to extract nutrients from the food as part of the process of determining the amount of nutrients they contain.
(BRIAN BELL/Science Source)

Description

Nutrigenomics is an active field of research with ongoing clinical studies. It draws from various scientific disciplines including genetics, molecular biology, bioinformatics, physiology, pathology, nutrition, sociology, and ethics. This science is based on five basic principles:

Nutrigenomics is in contrast to the U.S. Department of Agriculture's MyPlate recommendations and recommended daily allowances (RDAs) of nutrients, which are intended to meet the nutritional requirements of the general population. Nutrigenomics also contrasts with claims that certain foods and supplements are beneficial for everyone, because genetic variations among individuals can result in very different responses to overall diets and specific foods. For example, a 2015 study that tracked blood sugar levels in 800 people over one week found that identical meals are metabolized differently by different people. Nevertheless, nutrigenomics can be applicable to populations, subpopulations, and ethnic groups that share genetic similarities, as well as to individuals.

Nutrigenomics is sometimes called nutritional genomics, nutritional genetics, or nutrigenetics. However, some scientists distinguish between nutrigenomics and nutrigenetics. They define nutrigenomics as the identification of genes involved in physiological responses to diet and genes in which small changes, called polymorphisms, may have significant nutritional consequences. Nutrigenetics is then defined as the study of these individual genetic variations or polymorphisms, their interaction with nutritional factors, and their association with health and disease. Others define nutrigenetics as the study of functional interactions between food and the genome at the molecular, cellular, and organismic levels and the ways in which individuals respond differently to diets depending on their genetic makeup.

Origins

The concept that diet influences health is an ancient one. In 400 BCE, Hippocrates advised physicians: “Leave your drugs in the chemist's pot if you can heal your patient with food.” Known interactions between food and inherited genes, called “inborn errors of metabolism,” have long been treated by manipulating diet. Furthermore, it has also been known that individuals can differ in their requirements for, and tolerance of, specific nutrients. For example, babies require the enzyme lactase to digest lactose sugar in mothers' milk. After weaning, the lactase gene may no longer be expressed, resulting in lactose intolerance. As some populations began raising animals for dairy foods, natural selection favored individuals with forms of the lactase gene that continued to be expressed into adulthood. Lactose intolerance remains common today, and people with lactose intolerance practice nutrigenomics by avoiding dairy products.

Known interactions between food and inherited genes

Genetic condition

Foods to avoid

Phenylketonuria (PKU)

Food containing the amino acid phenylalanine, including high protein foods such as fish, chicken, eggs, milk, cheese, dried beans, nuts, and tofu

Defective aldehyde dehydrogenase enzyme

Alcohol

Galactosemia (lack of a liver enzyme to digest galactose)

Diets which contain no lactose or galactose, including all milk and milk products

Lactose intolerance (shortage of the enzyme lactase)

Milk and milk products

With the revolution in molecular genetics in the late twentieth century, scientists began identifying more genes that interact with dietary components, and by the 1980s, companies were commercializing nutrigenomics. The Human Genome Project of the 1990s, which sequenced all of the DNA in the human genome, jumpstarted the science of nutrigenomics. By the early twenty-first century, scientists were discovering numerous interrelationships between genes, nutrition, and disease.

Single nucleotide polymorphisms (SNPs)

The DNA sequence of the human genome varies by only 0.1% between individuals. However, small variations called SNPs can make a huge difference in disease susceptibility. Some of the differences in individual responses to nutrients are due to SNPs.

LIPID METABOLISM. One of the first applications of nutrigenomics was the examination of differences among individuals and populations in blood levels of lipids—triglycerides and HDL (“good”) and LDL (“bad”) cholesterol—and the effect of high-fat diets on these levels. High levels of HDL cholesterol are associated with a reduced risk for CVD. Dietary changes have a modest beneficial effect on blood lipid levels in the majority of people; however, some people experience no effect, and other people experience the opposite effect from the same dietary modifications. SNPs in genes that are directly or indirectly involved in lipoprotein metabolism may be responsible for these differences. Thus, typical low-fat diet recommendations may actually harm people with certain genotypes.

In women with a particular SNP in the gene encoding apolipoprotein A-1 (APOA1), an enzyme involved in lipid metabolism, high levels of HDL cholesterol are correlated with high consumption of PUFA. This SNP may significantly affect their risk for CVD. In contrast, high consumption of PUFA in women with the more common form of the APOA1 gene results in low levels of HDL cholesterol. This relationship between HDL cholesterol and PUFA is not seen in men. Thus, increased PUFA consumption from foods such as fish, vegetable oils, and nuts could benefit some women, harm other women, and have little effect on men, although this has not been scientifically demonstrated. However, the elucidation of APOA1 gene variants was possible only because of the Framingham Heart Study—a very large, decades-long epidemiological project.

SNPs have other effects on lipid metabolism. People carrying a particular SNP in the gene encoding hepatic lipase respond to high-fat diets with increased HDL cholesterol. People with variations in the gene for apolipoprotein E (APOE), which is involved in cholesterol balance, respond differently to low-fat diets. One variant of the APOE gene is associated with an increased risk for Alzheimer's disease, but only in Caucasians and Japanese. Black Africans with the same variant are not at increased risk.

High blood triglycerides may increase the risk for heart disease and can be a sign of metabolic syndrome (high blood pressure, high blood sugar, and fat accumulation around the waist), which increases the risk for heart disease, diabetes, and stroke. The protein fetuin-A is elevated in obesity and diabetes. A 2017 study of young adult Mexicans reported that a polymorphism in the AHSG gene that encodes fetuin-A was associated with high triglycerides, but only in overweight individuals. Sugar intake was also associated with elevated triglycerides, but primarily in people with one specific genotype, suggesting that their genes made them more sensitive to a high-sugar diet. The results of this study differed from similar studies conducted in other ethnic groups.

MTHFR. One of the best-known examples of a gene-nutrient interaction is the MTHFR gene, which encodes the enzyme methylene tetrahydrofolate reductase. MTHFR regulates folic acid and maintains blood levels of homocysteine. A specific SNP in the MTHFR gene is found in 10% of northern Europeans and 15% of southern Europeans. People with this SNP in both copies of their MTHFR gene have elevated levels of homocysteine in their blood, particularly if their intake of folic acid is low. This condition is associated with CVD. However, it is not clear whether folic acid supplementation could help prevent CVD in these individuals, and there are numerous genes associated with the development of CVD and various dietary nutrients that may interact with these genes.

The MTHFR SNP also is associated with a reduced risk for colon cancer, but only if folic acid intake is normal. Yet, no evidence supports the theory that folic acid supplements or eating foods high in folic acid can help prevent colon cancer. Although high fruit and vegetable intake is thought to be related to decreased cancer risk, this is not due to folic acid.

CAFFEINE METABOLISM. About half of people metabolize caffeine rapidly, whereas the other half metabolize it slowly. The speed with which caffeine is metabolized appears to depend on SNPs in the CYP1A2 gene. Caffeine consumption by slow metabolizers may increase their risk for heart attacks and other health problems, as well as reducing athletic performance.

Alterations in gene expression

SNPs can cause changes in gene-food interactions by changing the way a protein interacts with a metabolite; SNPs can also affect the expression of a gene, causing the gene to produce more or less protein. Chemicals in foods can directly or indirectly affect gene expression. Plant chemicals called phytonutrients can alter cell-signaling pathways that regulate gene expression. Small plant proteins called peptides can also alter the regulation of gene expression. Lunasin is a substance in soy that has been associated with reduced risk for heart disease and several cancers, including prostate cancer. Lunasin appears to increase the expression of genes that monitor DNA damage and suppress proliferation of tumor cells.

Dietary components, such as retinoic acid and zinc, can bind to DNA and affect gene expression. Zinc, which is abundant in red meat and some seafoods, turns on some genes and turns off others. For example, zinc activates genes associated with the production of white blood cells that fight infection. Dietary fatty acids can also directly modify gene expression.

Nutritional factors can act as signaling molecules that interact with complex systems of hundreds of enzymes called kinases. Kinases transmit signals from the environment, including food, to the genome, turning on and off the expression of genes that produce proteins involved in metabolism. Two specific kinase pathways are known to be involved in satiety, insulin signaling, muscle energy reserves, lipid metabolism, and inflammation—processes associated with obesity, type 2 diabetes, and atherosclerosis. Specific phytonutrients are known to affect these kinase pathways.

Epigenetic modifications are changes to DNA that affect gene expression without changing the DNA sequences of genes. One of these modifications is DNA methylation, which attaches small molecules to DNA. During early development, DNA methylation is highly susceptible to nutritional and other environmental influences.

Eating habits

Nutrigenomics appears to also involve eating habits. A 2016 study reported that for girls carrying a particular gene variant, the interaction between the gene and their early socioeconomic environment determined whether they had above-average or below-average fat intake compared with other girls from the same socioeconomic background. In 2017, scientists studying picky eating among preschoolers reported that SNPs in one gene were associated with limited dietary variety, and SNPs in another gene were associated with struggling for control at mealtimes. Both genes may be associated with bitter taste perception. The researchers speculated that variations in other chemosensory genes involved in food odors and appearance might also be associated with eating habits.

Commercial applications

A number of companies offer genetic profiling or genotyping using DNA swabbed from the inside of the cheek. Their DNA analyses, along with responses to a detailed nutrition and lifestyle questionnaire, are used to recommend individualized nutrition for improving health and preventing disease. However, only a limited number of genes are tested for variations that have nutrigenomic implications. These include:

As of 2018, very few consumers were utilizing nutrigenomics. For the majority of people, nutrigenomic diets do not differ significantly from standard diets that include plenty of fruits and vegetables. Clients may be told to get more exercise and avoid alcohol, preservatives, and foods such as processed breads, bacon and sausage, dairy, and junk food. Major food companies are investing heavily in nutrigenomics and the development of new products to meet the demands of personalized diets, and nutrigenomics is probably the wave of the future. As more gene-diet associations are discovered, genetic profiling and nutritional prescriptions are expected to become commonplace. Many scientists believe that nutrigenomics has tremendous potential for improving public health. Technological developments may enable doctors to perform nutrigenomic tests in their offices. Children may be tested at a young age so that diet can be used as preventative medicine. The development of nutrigenomics is expected to revolutionize the dietetics profession, and specific products may become available to meet the health requirements of individuals.

BRAND NAMES. Examples of nutrigenomics companies include embodyDNA and Nutrigenomix. After sending in a sample to the DNA sequencing company Helix, embodyDNA responds in six to eight weeks with “DNA-based insights and weight loss recommendations” reported on the Lose It! weight-loss app. Nutrigenomix uses a panel of 45 genetic markers that predict individual charcteristics such as the ability to lose weight on a low-carbohydrate or lower blood pressure on a low-salt diet, as well as offering a sports performance and injury risk test. Nutrigenomix offers its tests only through healthcare providers.

Precautions

Far more research is needed before nutrigenomic diets become a reality. As of 2018, very few gene-diet interactions had been researched enough to provide adequate information to yield specific useful advice, and even fewer genetic variants could be screened for. Little evidence was available to indicate that nutritional changes made on the recommendations of commercial analysis would reduce an individual's risk of developing a particular disease. Furthermore, the health effects of a personalized diet depend on far more than genotype. Age, physiological conditions including pregnancy, and medical conditions are all important factors. In addition, most healthcare providers are not qualified to interpret nutrigenomic reports and make appropriate recommendations based on them.

A 2016 study reported that people given personalized nutritional recommendations develop healthier habits, such as reducing their red meat and salt intake. It did not matter whether the personalized advice was based solely on analysis of participants' current diets, diet analysis plus physical characteristics (body fat and blood markers), or diet analysis plus physical characteristics plus genotypes of five genes with strong evidence for diet-gene interactions. Thus, personalization, regardless of its basis, appeared to be the significant factor.

Nutrigenomics raises ethical questions, such as whether genetic profiling should remain restricted to wealthy clients or whether it should be available under standard healthcare coverage, which might eventually overtax the healthcare system. Learning of a disease susceptibility also can cause high levels of anxiety and stress in some people. Genetic testing raises privacy concerns; some companies already sell the results of their genetic profiling to other companies. There also are concerns that people with known genetic susceptibilities could be discriminated against in employment or health insurance.

Side effects

Because the science is new and few studies have been done, no side effects have been discovered. As of 2018, however, the nutrigenomics industry was unregulated and had no defined standards. It was unclear whether any future regulation would treat nutrigenomics as medicine or nutrition. Nutrigenomics companies have been accused of making false claims, lacking scientific accountability, and misleading consumers. Some nutrigenomics companies market supplements and other unregulated products that have no scientific basis. This lack of regulation could result in unforeseen problems or side effects.

Interactions

With the exception of a few well-known examples of interactions between specific nutrients and inherited genes, the science of nutrigenomics is in its infancy. Nevertheless, some interactions have been noted between diet and disease. For example, individuals with lactose intolerance avoid milk and milk products to eliminate their symptoms.

In addition to lactose intolerance, other well-known inherited conditions require nutritional adjustments:

However, nutrigenomics is primarily concerned with gene variants that have much weaker, and often much more complex, interactions with dietary factors. Diseases and conditions that are known to have genetic and/or nutritional components are candidates for nutrigenomic studies to determine whether dietary intervention could affect outcomes. Inherited mutations in genes can increase susceptibility to cancer, and the risk of developing cancer may be markedly increased if gene-diet interactions are involved.

Research has revealed that dietary factors can have either a positive or negative effect on the risk of developing cancer:

Diseases that are known to involve interactions between multiple genetic and environmental factors such as diet include:

Differences in genetic makeup or genotype are thought to be factors in the development of:

Nutrient imbalances are believed to be factors in:

KEY TERMS
Apolipoprotein (APO)—
Proteins that combine with lipids to produce lipoproteins; variants of the APOA1 and APOE genes code for lipoproteins that respond differently to different diets.
Bioinformatics—
The science of gathering and analyzing biological data such as genetic codes.
Cardiovascular disease (CVD)—
Disease affecting the heart and blood vessels.
Epigenetic—
Chemical modification of DNA that affects gene expression without changing the DNA sequence of the gene.
Folic acid—
Folate; a B-complex vitamin that is required for the production of red blood cells and other bodily processes.
Genome—
The entire DNA sequence of a cell or organism.
Genotype—
All or a portion of the genetic makeup of an individual or group.
HDL cholesterol—
High-density lipoprotein; “good” cholesterol; lipoprotein in the blood that is primarily protein with small amounts of triglyceride and cholesterol and that helps protect against heart disease.
Kinase—
An enzyme that catalyzes the transfer of phosphate groups between molecules in cell-signaling pathways.
LDL cholesterol—
Low-density lipoprotein; “bad” cholesterol; lipoprotein that has a high proportion of cholesterol; high LDL levels increase the risk of coronary heart disease.
MTHFR—
The gene encoding methylene tetrahy-drofolate reductase; variants in this gene respond differently depending on folic acid intake.
Phytonutrients—
Phytochemicals; micronutrients in plant foods.
Polyunsaturated fatty acids (PUFA)—
Dietary fats that are affected by variations in the APOA1 gene.
Single nucleotide polymorphisms (SNPs)—
Variable nucleotides (letters) within a DNA sequence.
Triglycerides—
Lipids in the blood formed from one glycerol molecule and three fatty acids.
QUESTIONS TO ASK YOUR DOCTOR

Nutrigenomics also has the potential to prevent unnecessary dietary interventions. For example, only about 15% of people with high blood pressure have sodium-sensitive hypertension. For the other 85%, eliminating dietary salt has no effect on blood pressure. Nutrigenomics is addressing why some people can control their hypertension with diet, whereas others require drugs.

See also Blood type diet ; Cancer ; Hypertension ; Macronutrients ; Phytonutrients .

Resources

BOOKS

Bagchi, Debasis, Anand Swaroop, and Manashi Bagchi. Genomics, Proteomics, and Metabolomics in Nutraceuticals and Functional Foods. 2nd ed. Hoboken, NJ: Wiley, 2015.

Barnett, M. P. G., and L. R. Ferguson. “Nutrigenomics: Integrating Genomic Approaches into Nutrition Research.” In Molecular Diagnostics, edited by George P. Patrinos, Wilhelm Ansorge, and Phillip B. Danielson, 305–21. 3rd ed. Boston: Elsevier/Academic, 2017.

Berdanier, Carolyn D., and Lynne Berdanier. Advanced Nutrition: Macronutrients, Micronutrients, and Metabolism. 2nd ed. Boca Raton, FL: CRC/Taylor & Francis, 2015.

Bhargava, Atul, and Shilpi Srivastava. “Nutrigenomics: The Future of Human Health.” In Biotechnology: Recent Trends and Emerging Dimensions, edited by Atul Bhargava and Shilpi Srivastava, 89–104. Boca Raton, FL: Taylor & Francis, 2018.

Brabeck-Letmathe, Peter. Nutrition for a Better Life: A Journey from the Origins of Industrial Food Production to Nutrigenomics. New York: Campus, 2016.

Burdge, Graham, and Karen Lillycrop, editors. Nutrition, Epigenetics, and Health. Hackensack, NJ: World Scientific, 2017.

Pathak, Yashwant, and Ali M. Ardekani. Nutrigenomics and Nutraceuticals: Clinical Relevance and Disease Prevention. Boca Raton, FL: CRC, 2018.

PERIODICALS

Ferguson, Lynnette R. “Nutritional Modulation of Gene Expression: Might This Be of Benefit to Individuals with Crohn's Disease?” Frontiers in Immunology 6 (September 11, 2015): 467. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566049 (accessed May 12, 2018).

Grimaldi, Keith A., et al. “Proposed Guidelines to Evaluate Scientific Validity and Evidence for Genotype-Based Dietary Advice.” Genes & Nutrition 12 (December 15, 2017). https://genesandnutrition.biomedcentral.com/articles/10.1186/s12263-017-0584-0 (accessed May 12, 2018).

Hutchinson, Alex. “The Caffeine Gene: Will the Stimulant Make You Stronger and Faster? Depends on Your DNA.” Globe and Mail (August 22, 2016): L1.

Monteiro, Jacqueline Pontes, Martin Kussman, and Jim Kaput. “The Genomics of Micronutrient Requirements.” Genes & Nutrition 10, no. 4 (May 19, 2015): 19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434349 (accessed May 12, 2018).

Murphy, Kate. “Meal Plans Tailored to DNA.” New York Times (January 12, 2016): D3.

Oberg, Erica, Carina Parikh, Ryan Bradley, et al. “Epigenetics in Clinical Practice: Characterizing Patient and Provider Experiences with MTHFR Polymorphisms and Methylfolate.” Journal of Nutrigenetics and Nutrigenomics 8, no. 3 (2015): 137–50.

Reddy, Sumathi. “Your Health: Testing Your Genes Can Help Find Your Best Diet.” Wall Street Journal (August 23, 2016): D1.

Riscuta, Gabriela. “Nutrigenomics at the Interface of Aging, Lifespan, and Cancer Prevention.” Journal of Nutrition 146, no. 10 (October 1, 2016): 1931–39.

Silveira, Patricia P., Hélène Gaudreau;, Leslie Atkinson, et al. “Genetic Differential Susceptibility to Socioeconomic Status and Childhood Obesogenic Behavior: Why Targeted Prevention May Be the Best Societal Investment.” JAMA Pediatrics 170, no. 4 (2016): 359–64. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2484697 (accessed May 12, 2018).

Ye, Kaixiong, Feng Gao, David Wang, et al. “Dietary Adaptation of FADS Genes in Europe Varied Across Time and Geography.” Nature Ecology & Evolution 1 (May 26, 2017). https://www.nature.com/articles/s41559-017-0167 (accessed January 30, 2018).

WEBSITES

American Association for Clinical Chemistry. “The Universe of Genetic Testing.” Lab Tests Online. https://labtestsonline.org/articles/genetic-testing?start=2 (accessed May 12, 2018).

Cell Press. “‘Healthy’ Foods Differ by Individual.” Science Daily. https://www.sciencedaily.com/releases/2015/11/151119133230.htm (accessed May 12, 2018).

Cornell University. “Healthy Diet? That Depends On Your Genes.” ScienceDaily. https://www.sciencedaily.com/releases/2017/06/170612153554.htm (accessed May 12, 2018).

Janssens, A. Cecile J. W. “Scientific Evidence for Personalized Nutrition: Ethical Implications of Methodological Limitations.” Nutrigenomics. http://www.cecilejanssens.org/nutrigenomics/ (accessed May 12, 2018).

University of Arizona. “Nutrigenomics.” Nutrigenomics. Arizona.edu . https://www.nutrigenomics.arizona.edu/#Intro (accessed May 12, 2018).

University of Illinois College of Agricultural, Consumer, and Environmental Sciences. “Genetics May Put a Person at Risk of High Triglycerides, But Adopting a Healthy Diet Can Help.” ScienceDaily. https://www.sciencedaily.com/releases/2017/10/171024141723.htm (accessed May 12, 2018).

ORGANIZATIONS

American Association for Clinical Chemistry, 900 Seventh St. NW, Ste. 400, Washington, DC, 20001, (202) 857-0717, Fax: (202) 887-5093, (800) 892-1400, 2labtest sonline@aacc.org, https://labtestsonline.org .

Center for Excellence in Nutrigenomics, Department of Veterinary and Biomedical Sciences, College of Agricultural Sciences, Penn State University, 115 Henning Bldg., University Park, PA, 16802, (814) 863-8532, jpv2@psu.edu, http://vbs.psu.edu/research/centers/nutrigenomics .

Institute for the Future, 201 Hamilton Ave., Palo Alto, CA, 94301, (650) 854-6322, Fax: (650) 854-7850, info@iftf.org, http://www.iftf.org .

International Society of Nutrigenetics/Nutrigenomics, Info@NutritionAndGenetics.org, http://www.nutritionandgenetics.org .

Life Sciences Research Organization, Inc., 9650 Rockville Pike, Bethesda, MD, 20814-3998, (301) 634-7030, Fax: (301) 634-7876, LSRO@lsro.org, http://www.lsro.org/home.html .

National Human Genome Research Institute, National Institutes of Health, Bldg. 31, Rm. 4B09, 31 Center Dr., MSC 2152, 9000 Rockville Pike, Bethesda, MD, 20892-2152, (301) 402-0911, Fax: (301) 402-2218, https://www.genome.gov .

Margaret Alic, PhD

  This information is not a tool for self-diagnosis or a substitute for professional care.