Nutrigenomics: How Genes and Nutrition Interact

THE PROMISE OF nutritional interventions tailored to one’s specific needs has, until recently, been difficult to realize. More than just “eating right for better health,” using nutrition to benefit health through the care and feeding of genes, though still in its infancy, is an exciting field of study seeing exponential growth. It has long been theorized dietary choices have a direct impact on whether genes, or genetic mutations, are turned on or off, although a firm grasp of just how that interaction might play out has been elusive. Still, the evidence of some kind of link between people’s genes and the foods they consume is there.

Familiar examples of genetic interactions include otherwise apparently healthy individuals who consume vast quantities of foods widely known to cause adverse health outcomes with no ill effect. Yet, others who seem to make all the right choices develop disease nonetheless. The question, then, is “Does diet have a direct impact on an individual’s genetic expression, and if so, how does that effect differ from person to person?”

Science’s understanding of diet’s effects on genes has evolved from merely studying individual single nucleotide polymorphisms (SNP) to studying whole genomes.¹ And, it is hoped that as nutrigenomics (how genes, nutrition and the environment interact) evolves, diet-related diseases will be able to be prevented using genetic testing to predict health risks and offer a tailored approach to a person’s diet based on their specific needs and genetic makeup. It is known diet can affect genomic mutations in vivo and in vitro at the base chromosomal level,² but how?

In addition to nutrigenomics, research is focusing on metabolomics, or how the molecular composition of foods and the chemical process of metabolism lead to the potential for gene expressions. The concept is enticing. While genes account for only 5 percent to 10 percent of the risks linked to diet-related diseases,³ SNP biomechanic pathways account for 90 percent of genetic variation. Further, studies assessing genetic risk scores as aggregates of information from multiple SNPs is evolving.⁴ Understanding how to apply nutrigenomics at the individual level may someday enable nutritional interventions aimed at preventing and even reversing DNA damage as opposed to diagnosing and treating disease. This means our understanding of the effects of eating too much or too little of certain nutrients can ultimately have lasting positive impacts on health choices.

Challenges of Personalized Nutrition

Personalized nutrition comes with many challenges, including a lack of general consensus on how to define it and what constitutes it. For instance, personalized nutrition must take into consideration environmental factors such as smoking, pollution, physical activity and the nutritional quality of foods. What makes personalized nutrition personal is that each individual’s nutritional needs differ. What is a “normal” nutrient requirement for one may be completely unhealthy for another. Hence, the challenge of translating large amounts of study data into something meaningful and individualized persists.

To date, there have been few large-scale, long-term, randomized studies evaluating the links between diet and genes, in part because dietary recall is largely observational and difficult to reproduce. Adding to the complexity are genetic variations and environmental considerations that must be factored into the study design, meaning both diet and genotype must be controlled to truly study the effects of diet on chronic disease. Therefore, for the foreseeable future, it is expected observational studies will continue to be the predominant line of human study, which can provide associations but not much in the way of causation.

Even with the strides made in understanding diet and genes, developing exact and appropriate personalized nutrition plans could be elusive until individuals know their own personal genotype. But, the problem lies in provider and patient buy-in to act on the potential benefits of nutrigenomics. A Greek survey showed that although 80.5 percent of nutritionists and doctors reported a willingness to recommend a nutrigenomics analysis, only 17 percent had actually done so.⁵

Some argue the public isn’t ready for personalized nutrition. Yet, others say we now know enough about developing personalized nutrition to benefit patients. For instance, genetic information can be used to create some dietary recommendations, even if it isn’t yet tailored to a point where diet can influence genes.

Food Choices and DNA

In a practical sense, genetic variations are directly related to energy balances, and they play out in a multitude of ways from appetite, food preferences, insulin signaling, inflammation, the formation of fat cells and metabolism. This means a person’s weight and body composition are functions of more than just how many calories they burn in relation to how many calories they consume.⁴

While science has linked genetics and dietary choices for some conditions such as celiac disease and lactose intolerance, this knowledge is just the tip of the iceberg. The interplay of DNA sequence variations of SNPs, ribonucleic acid (RNA) and how dietary choices alter our risk for disease is seen, though not understood, in numerous examples such as the connection between folate and riboflavin, both of which can catalyze a reaction of the methylenetetrahydrofolate reductase (MTHFR) gene. Folate is a substrate for MTHFR, and riboflavin is a cofactor of MTHFR. In some homozygous carriers of the C677T polymorphism, high intake of these two nutrients could cause developmental defects, but also subsequent protection from certain cancers. Additionally, calcium intake may enhance the effects of a diet high in folate, while a diet high in riboflavin may exacerbate the effects of a diet low in folate. This may explain higher cancer rates among those who consume more red meat (high in riboflavin), more alcohol (which deletes folate) and fewer vegetables (high in folate).²

Nutrigenomics has thus far been most widely studied in relation to obesity. For instance, findings such as a link between SNPs and the obesity-associated protein FTO demonstrate high-protein diets result in the loss of more body fat for those with one specific FTO variation, but they have little impact on those without it. And, Mediterranean diets have been found to be most effective in controlling obesity and protecting against type 2 diabetes in groups with one type of SNP of the FTO gene, but not another.⁶

These examples demonstrate that without knowing an individual’s genetic makeup, today’s recommendations of which type of diet to follow is largely based on generalized recommendations. However, as more nutrition-related SNPs are identified, recommendations can become more tailored and more effective, which should increase patient motivation for compliance as the implications of dietary choices become clearer.⁴

The Science of Food

Foods and beverages are also being analyzed in great chemical detail to understand how their micronutrients and bioactive substances impact both gene expression and genome health. With thousands of DNA alterations and damage from environmental factors occurring daily, quick repair of DNA is critical. Diets and lifestyle choices can provide some of the needed repairs. Additionally, it is thought diet may be able to compensate for inherited defects in DNA repair mechanisms and may be able to stabilize the genome from further disrepair once genetic alterations have occurred. Therefore, scientists must look more broadly at how multiple nutritional imbalances impact the genome.²

Foods produced or altered in laboratories have been questioned for their authenticity and health benefits, but what if they were supplemented with the extra dose of whatever vitamin or mineral is largely missing in an individual’s diet? Or, what if food was produced without a substance toxic to one’s system? Would that food be considered the wave of the future?

Food that can be 3D printed is in rapid research and development, and someday, it may be able to solve many of the consumption challenges individuals face. From pureed food for those with chewing challenges to gourmet chocolates for the discerning palate, this newer technology (which today is in its infancy) may hold the key to solving for missing nutritional links, while at the same time reducing food waste. 3D printers, which create foods from substances in powder and oil forms housed in cartridges (that forms a gel when combined with water) may be able to create nutritious foods. And, future generation printers may be able to individualize nutrients to meet consumer needs, offering an entirely new tailored approach.

Of course, the idea of printing food is a lot more challenging than printing plastic. Food ingredients interact with each other differently, layers of ingredients may need to be cooled before the next layer is added, and the number of ingredient cartridges needed to createsomething as simple as a vegetable could bein the millions, making them cost-prohibitive. However, as technology improves, many feel 3D printing can someday be a missing link that marries personalized data and the kitchen.⁷

Preferences Take the Cake

So, what does the future of food look like? From genetically modified organisms (GMO) to non-GMOs to 3D-printed foods, the culinary world is on the cusp of new technologies to enable specific choices that will catalyze specific chemical reactions that can impact our genetic expression and conceivably improve health outcomes. As scientists work to find new techniques for food production and nutritionalenhancements, our understanding of how to use food for specific genetic manipulation will someday intersect.

Of course, until a more complete picture emerges of how diet impacts genes that then impact health, the question remains: “Will people follow that advice?” Humans are finicky eaters, and food-consumption choices are often based on factors and preferences other than nutrition. Tastes are discretionary, but availability, cost and access to foods that can most benefit individuals can, in some cases, be prohibitive.

Still, the future of nutrigenomics holds great promise. As healthcare costs continue to soar and access to care in remote areas continues to be a challenge, patients will one day be able to, with the watchful eye of their providers, make more intentional dietary choices for the better care and feeding of their genes.