Precision Nutrition and You: Nutrigenomic Approaches To Disease And Health

Evan Stevens

We have previously discussed the growing field of nutrigenomics here at Forever Fit Science in the article How Should I Eat. The idea of personalized nutrition was introduced – eating based who you are; how nutrition interacts with your genetic make-up.

The study of these interactions falls under an umbrella term called “nutrigenomics” (or nutrigenetics), and while it is a field still in its infancy, it is rapidly growing and becoming more and more important ass nutrition and lifestyle-related diseases continue to rise. Advances within the field are rapidly adding to our understanding of the role of individuality, specific genetic markers, in the development, treatment, and prevention of chronic disease. Nutrigenomic understanding is the first major step forward we have into the realm of truly personalized healthcare.

Advances in genetic sequencing are giving us a clearer picture of the interactions between genetic and epigenetic (changes to the expression of the gene, not the gene itself) markers and environmental factors – namely diet and exercise. From this growing understanding we are able to now produce customized and personalized treatment therapies; what we call precision medicine. These highly personalized therapies rely on individual differences relating to a person’s genetic profile, gender, microbiome, and environmental factors. Precision nutrition is a part of precision medicine that may aid in the development of nutritional guidelines for an individual rather what we currently use: outdated population-based food guides.

A new article published in the Journal of Nutrigenetics and Nutrigenomics on July 8^th presents an excellent guide for current approaches to nutrition as medicine in certain scenarios.

The Genetic Approach

Using data collected from human genome projects all over the world, the authors have presented a multitude of examples and discussion points relating the association of single nucleotide variants (SNVs) and polymorphisms (SNVs) in disease development through interactions with nutrition. Single changes to a base (the single nucleotide) within a certain gene can lead to alterations in the function of that gene. Sometimes these changes can be the cause of very dangerous diseases such as sickle-cell anemia or cystic fibrosis, but in the realm of nutrition, the interactions are far more minor but over time can contribute to serious chronic disease. Several SNPs have been associated with common chronic diseases that we contribute to poor diet and lifestyle, such as obesity, type 2 diabetes, osteoporosis, non-alcoholic fatty liver disease (NAFLD), and so other metabolic syndrome diseases.

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What is really interesting is that these chronic diseases developed by SNPs can be attributed to certain dietary interactions, such as the intake of specific micro and macronutrients. The article gives a very good example of how these SNPs can result in disease of certain people with certain heritages. They showed that certain individuals of Mexican descent may have an increased risk (above that of other populations) of dyslipidemia and high cholesterol when consuming high amounts of carbohydrates or fats because of SNPs in genes that encode for “sweetness” taste receptors.

An increased risk of CVD and hyper tension were found in heavy coffee drinkers who have a polymorphism in a gene that encodes for certain cytochrome p450 enzymes which are an integral part of the citric acid cycle which move electrons across membranes to generate energy. While the link between coffee and CVD is still somewhat controversial there are multitudes of studies that show that 3 to 5 cups of coffee a day can decrease the risk of CVD and hypertension (like this systematic review in the Journal of Circulation). Similarly, SNPs in the FTO gene, which codes for an enzyme that demethylates DNA (turns genes on or off), can result in either weight loss under high protein diets, or increased insulin levels under low-fat diets.

Approaching nutrition with the individual in mind rather than using general population-based nutrition advice can lead to far more beneficial outcomes for health. By looking at a person’s genes we can cut certain foods out or add in certain foods to improve outcomes.

The Diet Approach and Gene Expression

Looking at a person’s genetic code and creating a diet based off of that is one thing, but using the food itself as a therapy to target specific genes is a very new and exciting prospect as well. Knowing that offering certain food type or certain bioactives (something that creates a response in the body) within certain foods can affect the expression of certain genes can greatly benefit an individual’s health outcomes. We can use food to regulate gene expression, genes which positively or negatively affect our health. For example, Selenium, a trace element in redox reactions, can help reduce the risk of certain types of cancer, such as breast, prostate, liver, lung, colorectal, and fibrosarcomas when selenium is deficient.

Low Selenium decreases the expression of the VHL tumor suppressor gene, which, you guessed it, suppresses the development and growth of tumors. High saturated fatty acids turn off certain genes, or decrease the expression of them, such as the PPARGC1A gene, responsible for encoding Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), which regulates mitochondrial biogenesis (the increase in size and number of mitochondria) and can lead to an increased risk of NAFLD. As well, choline- and folate-deficient diets were associated with altered regulation of genes involved in lipid metabolism, which influence the susceptibility and severity of NAFLD.

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Good foods alter gene expression as well – it is not just deficiencies and poor western diets. Mediterranean diets downregulate the expression of pro-inflammatory proteins, and oxidative stress enzymes after a meal. Energy restricted diets (low caloric intake) paired with supplemented Eicosapentaenoic acid (EPA –omega 3 fatty acid) increased the expression of interleukin 10 (IL10), which is an anti-inflammatory cytokine (cell signaling molecules). Polyphenolic compounds (chemicals in plants that have a host of functions such as protecting the seeds from predators, providing colouration, preventing UV stress, etc.) found in the skins of apples improve the expression of anti-obesity genes while at the same time decreasing the expression of genes linked to increased obesity.

The Epigenetic Approach

The epigenetic approach to precision nutrition is very similar to the dietary approach. Epigenetic effects are changes caused by modifications to gene expression and not the coding of the gene itself. The dietary effects of food on the expression of genes is but one of many epigenetic effects that can induce changes in health outcomes. It often involves the methylation or acetylation (adding methyl or acetyl groups to parts of the genome to usually turn the gene off) of genes and is involved in most biological and physical process.

It is a process that can happen from certain imprinting events, during embryonic development, silencing certain chromosomal sequences (the inactive X chromosome in a female is highly methylated or “turned off”), cellular differentiation, or the development and growth of organs. Research has found that high fat and sugar diets alter the methylation of certain neural pathways that dictate food intake. You eat junk food, it causes your body to turn off some of its satiety pathways, you eat more junk food; you are not only eating crappy food, the crappy food is making you eat more crappy food. And yet people still wonder why obesity is such a problem.

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Deficiencies in micronutrients can cause certain changes to methylation as well. Inadequacies in folate, vitamin A, potassium, Iron, vitamin B, and selenium all lead to huge increases in methylation of tumor suppressor genes and greatly increases the risk of cancer. Lacking these micronutrients turns off key the body’s ability to prevent tumor growth and development. Similarly, deficiencies in vitamin D, chromium, magnesium, and calcium all caused altered methylation to pathways involved in glucose homeostasis, increasing the risk of Type 2 Diabetes, insulin resistance, and inflammatory risk factors.

Yet using a precise nutrition approach we can design specific nutritional interventions to help reverse some of these epigenetic effects which may have a huge impact on individual healthcare. The authors of the article point to the example of the Mediterranean diet and how it caused hypermethylation of pro-inflammatory genes. Apple phenols hypermethylated genes related to obesity. Curcumin not only hypomethylated and acetylated genes that transcribed microRNA that turned on tumor suppressor genes, but also proved to have protective effects against liver injury and heart failure through modifying patterns of DNA methylation of key genes in those pathways.

Take Aways

This whole idea that certain foods and bioactives can be used therapeutically has given rise to the “epigenetic diet” which could be an effective strategy for individualized healthcare. Everything from obesity to longevity to neurological development seems to be able to be modulated by nutritional intervention acting on genes. Studies have even reported that our circadian rhythms can be methylated via a Mediterranean diet which correlates to improved weight loss and lipid homeostasis.

We are now at the point where we are able to start constructing some basic personalized healthcare. Knowing that there are certain genetic markers that we can either look for to see if we have them or knowing that we can alter the ones that we currently have, can dictate how we should eat. Precision nutrition is a key component of this “personalized medicine” ideal and an emerging approach for disease prevention and treatment that takes into account genetic/ epigenetic information, as well as age, gender, physiopathological status and environmental issues, including personal lifestyle.

As our understanding of our own personal genetics improves, we are better able to properly modify and our therapies, treatments, and preventative measures be they from a disease standpoint or improving our standards of living well into old age. Targeted therapies prescribed for an individual may seem like the future but it is now. New companies are sprouting up that offer genetic testing and it is only going to become easier to get this kind of information to better inform us on how to eat.

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