The groundwork for nutritional genomics was laid by researchers like Jose Ordovas, now the director of the Nutrition and Genomics Laboratory at the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University. Ordovas has spent decades studying the correlation between the metabolism of dietary fats and the risk of cardiovascular disease. Perhaps the best-studied diet-gene interaction involves low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol. One of the most interesting findings of recent years concerns HDL and LDL cholesterol and a gene variant, or allele, that regulates their metabolism. Some people who eat a diet high in saturated fat will never see an increase in their “bad” LDL cholesterol, whereas others will see a spike and won’t even benefit from following the universal advice to eat a low-fat diet. It turns out that the differing effects of a high-fat diet depend in part on an allele of a gene involved in the metabolism of “good” HDL cholesterol called the hepatic-lipase gene. Ordovas explains that the remedy for these frustrated dieters is to continue eating a normal amount of fat, but to make a very high percentage of it polyunsaturated.
This kind of targeted advice, which can be dispensed to anyone at the return of a genetic screening, is the great promise of nutritional genomics, and cholesterol is the teasing example that drives businesses and researchers forward. But it is only one needle in a very high haystack. Ordovas was able to identify the curious effect of the hepatic-lipase allele because he had access to data from the Framingham Offspring Study, part of the huge, very well funded, decades-long Framingham Heart Study conducted by NIH’s National Heart, Lung, and Blood Institute.
Walter Willett, a professor of epidemiology and nutrition at the Harvard School of Public Health, conducted a review of the Davis center in his capacity as chairman of its external advisory committee. He told the Davis researchers that new observational studies would be prohibitively expensive to mount, and that the center should devise questionnaires to be incorporated into established long-term health trials and seek to obtain serum or blood samples from subjects to screen for genotype. Already the center has begun several collaborations, one with a long-term asthma trial under way at the University of California, San Francisco, where the researchers will look for connections between diet, genotype, and the disease, and others with studies of prostate cancer and restricted-calorie diets.
The study of diet-gene interactions in heart disease progressed so quickly, not only because that’s where the money was, but because the biomarkers for heart disease, like HDL and LDL cholesterol, are well understood and easy to measure. But the Davis researchers are hoping that the accumulation of genetic information about many populations, combined with the techniques of systems biology and the algorithms Malyj and his colleagues are using, will be able to disclose more-obscure diet-gene interactions.
They have their work cut out for them. Cancer, despite a huge scientific literature and investment in research, illustrates the difficult proposition for nutritional genomics. Markers vary for each kind of cancer, and environmental stimuli might play important roles in the disease’s progress. For cancer, and for cardiovascular and other diseases, the field’s first results are likely to be generalized recommendations for large ethnic groups whose genotypes are relatively well defined and easily studied, and of course for men and women, whose needs for and reactions to nutrients can differ greatly. Despite the number of genetic-screening companies contending to charge hundreds of dollars to devise individual “DNA diets,” the narrowest focus Rodriguez foresees in his lifetime, he says, is at the level of “a middle-aged man of Hispanic descent” like himself. And that, he says, is “close enough.”