FOOD, MEDICINE, & HEALTH

Nutrigenomics: From Nutrition to Genes
It seems only yesterday that Watson and Crick announced the discovery of circular DNA isolated from Escherichia coli. Since this exciting advancement in the genetics era, new research has attempted to identify the genetic basis and molecular causes of chronic diseases. Recorded history acknowledges that dietary components contribute to cellular replication, growth, and apoptosis, yet the mechanisms remain in a maze in which the paths to healthiness wait to be revealed.

We now welcome an era of nutrigenomics, an exciting new multidisciplinary science that recognizes the potential of common nutrients to act as potent dietary signals that influence the metabolic behavior of cells (Fogg-Johnson and Kaput, 2003). More specifically, it has become clear that certain bioactive constituents of foods may alter gene expression at the cellular level by serving as ligands for transcription-factor receptors, by altering concentrations of substrates or intermediates, or by serving directly as signaling molecules. This awareness has given birth to the notion that foods might be “designed” or modified to directly support health, reduce the risk of diet-related diseases, and lead to individualized nutrition (Kaput and Rodriguez, 2004; German et al., 2004).

Epidemiological and controlled laboratory animal studies have identified types of specific dietary constituents and excess calories as the main culprits inducing or contributing to chronic diseases. Normal variations in genes among humans (i.e., single nucleotide polymorphisms, SNPs) and the difficulties of controlling or assessing what individuals eat confound the analyses of how diet affects health. The complexity is readily apparent when we consider that the human genome contains about 30,000 genes, approximately 3 billion base pairs, and more than 1.5 million SNPs. These numbers illustrate a new dimension to nutrition research.

Published research has demonstrated that mutations in more than 1,000 genes contribute to the development of congenital, chronic, and medically rare diseases. However, it appears that there are few research efforts that examine the role of diets on the activity of those genes. (Ordovas and Corella, 2004). There are several genes associated with familial hypercholesterolemia, an inherited disorder of lipoprotein metabolism, which may be modulated by dietary and environmentally factors. At least 12 mutated genes alter many cellular functions that regulate glucose homeostasis among type 2 diabetics. Lactose intolerance, phenylketonuria, galactosemia, and celiac disease are examples of dynamic gene–nutrient interactions in health and disease through the life span. Obesity, diabetes, osteoporosis, cardiovascular disease, metabolic syndrome, cancers, and Alzheimer’s disease represent a few examples of possible genetic-linked diseases associated with polymorphisms.

Foods represent a complex matrix of nutritional components that can affect thousands of genes, genetic polymorphisms, and gene expression products recognized in this new nutrigenomics arena. As the pharmaceutical industry explores pharmacogenomics to discover drug targets, define drug efficacy, and reduce undesirable side effects in response to individual genetic variations within a human population, it is time for a revolutionary approach in nutrition to understand how foods interact at the cellular level among individual genotypes. Similarly, our study of genomics within an agricultural setting will lead to cultivar selection that could lead to more healthful crops for a significant subset of the population (Watkins et al., 2001).

This understanding of individual genetic variation in humans and in cultivars is critical to further explain differences in nutrient requirements and how we can meet those needs. This, in turn, will lead to the development of “personalized” nutrition that delays the onset of disease and optimizes and maintains human health.

by ROGER CLEMENS, Dr.P.H.
Director, Analytical Research
Professor, Molecular Pharmacology & Toxicology
USC School of Pharmacy, Los Angeles, Calif.
[email protected]

by PETER PRESSMAN, M.D.
Internal Medicine
Geller, Rudnick, Bush & Bamberger
Beverly Hills, Calif.
[email protected]

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