“Let food be thy medicine, and medicine be thy food.” – Hippocrates

Nutrition is something we consider to be extremely important in integrative medicine and it’s something I talk about with every patient I meet. One of several tools that I find helpful when thinking about nutrition is nutrigenomics. Nutrigenomics is a relative newcomer in the world of medicine—it is fully embraced by integrative and functional medicine but hasn’t quite made it into the prime time of conventional medicine.

What is nutrigenomics? Nutrigenomics examines the interactions between nutrition and genetics. Specifically, if focuses on how subtle individual genetic variations caused by a single change in the coding sequence of a gene (a single nucleotide polymorphism, or SNP) influence a person’s response to different nutrients, and how those nutrients influence gene expression and function. Nutrigenomics seeks to understand how the food we eat interacts with our genes to create health or to influence susceptibility to disease. Nutrigenomics is especially helpful in a clinical situation when it examines SNPs that have “low penetrance.”

What is a SNP? As described above, a SNP is a single change in the coding of a particular gene. Sometimes the change in the SNP changes how the gene functions and sometimes it doesn’t. BRCA1, for example, is a gene associated with increased risk of many cancers. But BRCA1 itself isn’t a problem—it’s a gene that everyone has. The gene consists of about 110,000 base pairs of DNA. A change in a single base pairs is a SNP. Several thousand BRCA1 SNPs have been identified. Only some of the BRCA1 SNPs lead to increased cancer risk. And SNPs aren’t all bad—some SNPs can have protective effects.

 What is penetrance? Penetrance is a measure of the proportion of individuals who carry a specific gene and express a particular trait—it is the relationship between genotype (“you have the gene”) and phenotype (“you have the thing related to that gene”).1 In some cases, penetrance is complete, meaning that if someone has the gene, they will also have the resulting condition. One example of this is familial adenomatous polyposis, caused by the APC gene. In individuals with a particular APC SNP, colon cancer is inevitable without colectomy.2 Penetrance is not always an absolute, though—it exists along a spectrum. Genes can have high penetrance or low penetrance. An example of a relatively high-penetrance group of gene would be the BRCA genes—BRCA1 and BRCA2 confer a high life time risk of breast cancer, in the range of 50-80%3. An example of a relatively low-penetrance gene would be CYP2D6—some alterations in this gene may slightly increase the risk of lung and liver cancer, thought the risk is <4%.4

Low penetrance SNPs themselves don’t cause a specific condition, but can, under the right circumstances. But it also means that the genes are actionable. That is, if certain circumstances are avoided (by diet and lifestyle modification, for example), the potential negative repercussions of a particular gene might also be avoided (or the potential positive effects of a gene can be amplified).  

From a therapeutic standpoint, nutrigenomics takes advantage of low penetrance SNPs in five key ways:

·      Personalized nutrition – By understanding how specific genes are related to nutrient metabolism and utilization, it’s possible to develop personalized dietary recommendations based on an individual’s genetic makeup.

·      Disease prevention – By understanding how certain dietary components might increase or decrease the risk of developing certain diseases in a particular individual, it’s possible to develop targeted interventions and dietary strategies to reduce risk.

·      Optimizing nutrient utilization – Different individuals process and absorb nutrients differently. By understanding how an individual processes nutrients, diet (and supplementation, if needed) can be modified to ensure maximum benefit.

·      Identifying nutrient-gene interactions – Specific nutrients can influence gene expression, metabolism, and other cellular processes, which can help understand how diet influences health and disease (and why some people do fine with a certain type of food and others don’t).

·      Tailoring therapies – Based on an individual’s particular genetic profile, it is possible to recommend specific dietary changes, supplements, and lifestyle modifications that can support treatment and improve outcomes.

Here are some examples of low-penetrance genes often considered in the context of nutrigenomics:

MTHFR – Methylenetetrahydrofolatereductase. This gene produces an enzyme associated with the methyl cycle and converts homocysteine to methionine. Two major SNPs have been reported that appear to have implications for Alzheimer’s and other forms of dementia, colon cancer, vascular disease, and neural tube defects. 

APoE – Apolipoprotein E. This gene makes a lipoprotein involved in cholesterol metabolism. Two major SNPs have been reported that produce three different proteins. Variations in ApoE can influence cardiovascular disease and dementia risk. One combination of ApoE proteins increases risk of Alzheimer’s by about 11-fold.  

ACE – Angiotensin 1 converting enzyme gene – Several SNPs have been described that have implications for kidney disease, high blood pressure, response to high blood pressure drugs (ACE inhibitors), and athletic performance.

CLOCK – Circadian Locomotor Output Cycles Kaput. This gene is involved in regulating circadian rhythm. Several SNPs have been described that impact insulin resistance and cardiovascular disease.

Nutrigenomics can be used to look at individual SNPs (for example, testing for the most common MTHFR SNPs in a patient). Perhaps more useful, though, is using a systems medicine approach to examine many SNPs and the interactions between SNPs. Advanced nutrigenomic testing does just this, often testing dozens, and even hundreds, of SNPs that are well understood. This allows us to examine complex, big picture processes like inflammation, cellular function, energy expenditure, and detoxification with both precision and breadth. Nutrigenomics isn’t perfect—the field is still in its infancy, after all—but it can be extremely useful.

References

1.         penetrance | Learn Science at Scitable. Accessed August 14, 2023. https://www.nature.com/scitable/definition/penetrance-69/

2.         Yen T, Stanich PP, Axell L, Patel SG. APC-Associated Polyposis Conditions. In: Adam MP, Mirzaa GM, Pagon RA, et al., eds. GeneReviews®. University of Washington, Seattle; 1993. Accessed August 14, 2023. http://www.ncbi.nlm.nih.gov/books/NBK1345/

3.         Wendt C, Margolin S. Identifying breast cancer susceptibility genes – a review of the genetic background in familial breast cancer. Acta Oncol. 2019;58(2):135-146. doi:10.1080/0284186X.2018.1529428

4.         Houlston RS, Tomlinson IPM. Detecting low penetrance genes in cancer: the way ahead. J Med Genet. 2000;37(3):161-167. doi:10.1136/jmg.37.3.161