The Genetic Diet: Nutrigenetics and the Future of Personalized Nutrition

The recent proliferation of direct-to-consumer genetic testing has generated a promising outlook for the future of personalized health regimens, but can you really "eat for your genes"? Well, yes and no. Genes involved in metabolic diseases and dysfunctions give us hints about how a person should approach their nutrition. However, we are still a ways off from implementing "genetic dieting" in real-world/clinical settings [1].

Regardless, "nutrigenetics" and "nutrigenomics" are fascinating fields of nutrition research; the former refers to the role of genetic variation in responses to nutrients, whereas the latter is the study of how nutrients and bioactive food compounds affect a person's gene expression [2]. By focusing on critical metabolic pathways and how gene expression impacts physiological processes, an individual's genome will provide more precise insight into their "optimal diet." Such information would be paramount for truly personalized nutrition counseling in clinical settings, athletics, and fitness.

This article will overview recent advances in nutrigenetics and nutrigenomics and how gene-diet interactions impact health and performance. We'll also discuss why extrinsic variables confound personalized medicine and likely reduce its precision in everyday applications.

Pharmacogenomics and Nutrigenomics: Are they Flawed Prospects of Precision Medicine?

While pharmacogenomics and nutrigenomics are in their infancy, these related sciences are impending breakthroughs in prescribing health advice. As you may have inferred, pharmacogenomics is the study of how genes affect a person's response to drugs.

The human genome project has allowed researchers to deduce which genetic variants are associated with disease risk. Genetic differences may also reliably predict how a person will respond to specific drugs and nutrients, thereby allowing them to prevent and manage health conditions more effectively.

Yet, the debate over the practicality of nutrigenomics and pharmacogenomics remains contentious. Some scientists argue that the emphasis on reductionist approaches to precision medicine contradicts the exceedingly complex nature of human biology — comparing it to the parable of the blind men and the elephant (i.e. one person's subjective truth can be valid while not accounting for the totality of objective truth) [3].

What Do Genetic Tests Tell You About Dietary Response?

Direct-to-consumer genetic testing is burgeoning and will likely continue to flourish in the years ahead. While a rudimentary genetic test can provide some neat information about specific genetic variants you may express, it's not as cut and dry as one might think.

To illustrate the complexity of human genetic variation and its influence on cardiovascular diseases, roughly 60 independent loci — fixed gene regions on chromosomes — contribute to the genetic risk associated with coronary artery disease; each locus contributes only a small effect to the underlying condition [4]. Likewise, upwards of 100 unique loci influence the risk of developing metabolic diseases like type-2 diabetes mellitus.

Things become even more complicated when we consider epistasis and pleiotropy. Pleiotropic genes can have multiple effects on different traits (which may or may not be related)[5]. Sickle cell anemia is one such disease caused by pleiotropy; a single gene mutation can manifest as a mild-to-severe disease from one person to the next [6].

Likewise, an epistatic genetic variant may depend on the presence of other genetic variants. Hence, the complete genetic makeup of the individual is essential to account for the intricacies of our biology. 

Using Genetic Information to Make Smarter Food Choices

Genome-wide association studies make it clear that what we eat (and what our ancestors ate) has profound effects on the human genome [7]. As such, it's pertinent to consider gene-diet interactions and how they could impact gene expression patterns throughout the lifespan.

For example, as cattle domestication occurred 5,000-10,000 years ago, a strong natural selection for lactase gene variants that produced a high amount of lactase occurred in humans of Northern Europe who consumed large quantities of dairy [8]. In regions where dairy consumption was low (e.g. Africa and Asia), much of the population lacked the same alleles and were lactose intolerant. 

Another example is that African Americans are also significantly more likely than European Americans to have a variant in the fatty acid desaturase gene that affects their ability to produce arachidonic acid, a long-chain polyunsaturated fatty acid, from its biological precursor dihomo-γ-linolenic acid [9]. Again, this was likely a result of food availability and dietary habits of ancestral populations in specific world regions. In turn, individuals with this gene variant may be at an increased risk of chronic diseases like cardiovascular disease due to altered nutrient metabolism.

Having an awareness of gene-diet interactions and metabolic tendencies like the above examples could help people choose foods that are "tailored" to their specific needs. But it's also likely that gene-drug interactions would influence gene-diet interactions over the lifespan. And much like pharmacogenomics, nutrigenomics has a long way to go before we can reliably implement it in a clinical setting.

Then there's the issue of the constant "background noise" we're exposed to (e.g. environmental toxins) that may have mutagenic potential as well. As one can imagine, even the most "precise genetic diet" may not pan out in praxis as populations age and adapt to new stressors/extrinsic variables. 

Regardless, nutrigenomics and nutrigenetics are intriguing facets of precision medicine. Future research will give us a better understanding of how critical genes affect health outcomes and what dietary strategies each person should follow based on such findings.