Nutrigenomics and nutrigenetics in whole food nutritional medicine

Townsend Letter for Doctors and Patients, Feb-March, 2007 by Ani K. Hawkinson

Epidemiological studies have repeatedly demonstrated a relationship between diet and disease. (1) However, until now, we have not been able to answer questions such as how foods alter disease risk; who will respond to dietary modification; and to which diet. Why does one intervention work for one person with a given disease, but not for another with the same disease? What foods optimize health--and why? Nutrigenomics and nutrigenetics (nutritional genomics and genetics) have finally begun to unravel answers to these questions.

Nutrigenomics forms the interface between nutrition and physiology. The study of nutrigenomics seeks to understand the effects of diet on health by looking at how genes and bioactive food components interact. Most genes have small sequence differences--polymorphisms--that vary among individuals. Some affect protein function; others influence how proteins interact with various substrates. Single nucleotide polymorphisms (SNPs) are the most common type of variation, and certain ones have now been identified as screening tools for predicting disease risk, such as the E4 allele of the APOE gene for cholesterol homeostasis and Alzheimer's disease. (2) Although SNPs correlate with certain diseases, the actual phenotype that is expressed depends upon a combination of genes and environment. This is where dietary nutrients assume importance: at least some of the variation in response to food components appears to be due to SNPs. (3) This means that it may be possible to mitigate genetic susceptibility to certain conditions with specific nutrients.

Nutrigenomic research is revealing the chemical mechanisms by which various micro- and macronutrients act upon the human genome to alter genetic expression and gene products, both directly and indirectly. This has made it possible to relate different cellular responses to particular nutrients. (4) For example, the intercellular signaling mechanism that stimulates gene expression in the genome involves the activity of the protein kinase family of enzymes. These selectively phosphorylate enzymes, allowing the body to quickly modify cellular function to respond to immediate needs. (5) The adenosine monophosphate kinase (AMPK) and mammalian target of rapamycin kinase (mTOR) pathways are both important in satiety, muscle energy reserves, insulin signaling, lipid metabolism, and inflammation associated with type II diabetes, atherosclerosis, and obesity. (6) Specific phytonutrients that modulate these pathways are epigallocatechin gallate (Camellia sinensis), resveratrol (grapes), and specific isohumulones (Humulus lupulus). (7) Knowing the nutrigenomic impact of a food and variations in genetic polymorphic responses to it allows nutritionists to design optimal diets for different conditions across various (phenotype) populations.

While nutrigenomics studies how genes and foods interact, nutrigenetics identifies how the genetic make-up of a particular individual coordinates his or her response to various dietary nutrients. By identifying and characterizing gene variants associated with differential responses to nutrients, it becomes possible to relate selected nutrients to disease states associated with the polymorphisms. (7) This allows health care providers to identify those who will benefit most from, or be placed at risk by, particular dietary interventions. (8) For example, in the Framingham Heart Study, high levels of high density lipoprotein (HDL), associated with reduced risk for cardiovascular disease, correlated with high polyunsaturated fatty acid (PUFA) consumption in women with the A allele SNP in the Apolipoprotein A1 promoter region. An inverse relationship between PUFA consumption and HDL levels was found in women with the more common G allele. No relationship between HDL levels and PUFA consumption was found in men, regardless of their APOA1 polymorphism. (9) Clearly then, increased PUFA consumption only benefits one group of women. In fact, it harms the other group and does little for men. In this instance, nutrigenetics makes it possible to use diet to modulate risk factors associated with cardiovascular disease according to different APOA1 genetic polymorphisms.

Beyond the prospect of individualizing nutritional recommendations based upon a person's polymorphic genetic profile, nutrigenomic research suggests a simple metaphor for the clinical practice of whole foods nutrition that can be used to help nonscientists truly grasp how foods impact their health: foods do more than provide energy for metabolism. (10) Foods talk to our genes. Genes encode proteins that perform specialized functions in cells. If the food that is "talking" to a gene is not saying what the gene understands, then the resulting protein may be defective. Dysfunctional proteins result in poor cellular function. Poor cellular metabolism leads to increased susceptibility to disease. This "nutrient-gene conversation" is the foundation of health.

Nutrigenetics reveals why and how people respond differently to the same nutrient. Genetic variations determine what kinds of nutrients will be "heard" and how they will be interpreted by genes. Certain foods, in certain individuals, disrupt or alter nutrient-gene communication significantly, resulting in increased risk for various diseases. People respond to dietary interventions according to their unique genetic responses to the nutrients involved. Thus, they respond differently to diet therapies. A lack of response does not mean that a particular therapy is wrong or that a person will not respond to therapy. It simply means that the person in question is not yet eating something that speaks a language his or her genes can understand.