More than 2,000 years ago, Hippocrates wrote: "Leave your drugs in the chemist's pot if you can heal the patient with food." Scientists may finally be catching up with the Father of Medicine. One of the newest fields of nutrition science, known as nutritional genomics, is dedicated to understanding the interaction between diet and the genome. The goal is to use food to prevent disease by identifying genetic predispositions for chronic conditions that can be mitigated by the proper dietary intake. Researchers in the field warn that they need to collect much more evidence before nutrigenomic, or nutrigenetic, dieting becomes a reality.
"What we are seeing now is the very, very beginning," says Jose Ordovas at Tufts University, Boston. Ordovas is widely respected by academic and corporate leaders alike as having conducted some of the most elegant gene-diet interaction experiments to date. "Nutrigenomics has established proof of concept, but that's...
MAKING THE SALE
Grimaldi and Genelex cofounder Howard Coleman both point to the
Most people have a cytosine (C) at
The disease-prevention implications of this interaction are less certain. Homocysteine is a key intermediate in methionine metabolism, and researchers have known for years that elevated plasma homocysteine levels are associated with a higher risk of cardiovascular disease (CVD). Whether hyperhomocysteinemia causes CVD, however, or is a consequence of it is unclear.2 "The thing that's missing," says University of Iowa cardiologist Steven Lentz, "is that there is not good evidence yet that treating people with folic acid prevents heart disease. It's an interesting example of a nutrient-genome interaction, but we just don't have enough information yet to be sure that it's clinically useful."
The T allele at base pair 677 has also been associated with a lower risk of colorectal adenomas and colon cancer risk, but only when folate intake is normal, again illustrating a dietary influence on this gene's expression.3 The increased risk of cancer associated with low folate intake is particularly pronounced in individuals older than 60 and is exacerbated by the consumption of moderate levels of alcohol. But again, as with the relationship between
Lentz says that about a dozen ongoing clinical trials are aimed at determining the effectiveness of homocysteine-lowering therapy with folic acid in preventing secondary CVD events (i.e., in people with already-diagnosed disease). Results from these studies aren't available yet, and preliminary findings are inconsistent. Until data demonstrate clinical benefit, Lentz says that he will continue using folic acid intervention only in high-risk cases, such as patients with other, nonhomocysteine-related CVD risk factors. He says that he doesn't rely on
Can your genes tell you how to focus your diet?
The etiology of CVD is vastly more complicated than its association with folic acid,
One of those other genes is apolipoprotein A-1 (
The multitude of epigenetic modifications that coat the genome further complicates the multigenic etiology of chronic disease. Epigenetic modifications are heritable changes in gene expression that have little to do with DNA sequence. Duke University's Randy Jirtle, professor of radiation and oncology, says such changes are key to understanding the relationship between diet and chronic disease. In particular, cystosine methylation, a common epigenetic mechanism, is highly susceptible to dysregulation by nutrients (and other environmental components) during early development.5. Early nutrients is so important in mammals, Jirtle says, that "by the time you go to the doctor and say 'I'm pregnant,' all this is done. So, in reality, you really have to be thinking about your diet and nutrition long before you know you are pregnant." This raises yet another question about the preventative effectiveness of nutrigenomic dieting in adults, unless the dieter is thinking a generation ahead.
Nutrigenomics companies send personalized reports like this one to their clients.
Scientists are not the only experts calling for more data, Among ethicists, "there are concerns that the advice or products the public receives are as efficacious as claimed," says David Castle, University of Guelph, Ontario. Castle is currently serving on an international advisory council for the Ethics and Nutritional Genomics Project Canada. He says that consumers want to know that what they are buying is effective. But if the lack of intervention studies is any indication, efficacy is precisely where nutritional genetics falls short. Consumers are either unaware of this shortcoming or they are pursuing what they know is scientifically premature advice. Coleman says Genelex sells about 50 kits each week, while Grimaldi reveals that Sciona has sold about 10,000 assays in the past year. GeneCare managing director Maritha Kotze estimates that she's prepared about 50 evaluations over the past month and says that service is becoming more popular light of increasing publicity. GeneCare was recently awarded the equivalent about $775,000 (US) for product development from Cape Biotech, a government-sponsored biotechnology development initiative.
Coleman describes his company's clientele as "middle or upper income individuals who either have a personal or family history of chronic disease or weight management issues. They have made a commitment to make health their priority." Katzin says that many of her clients are baby boomers whose parents have had a chronic illness, and they are concerned about their own aging process. Many, she says, have already had complete blood work done and are looking for "more information."
Even the skeptics agree that something about obtaining a personalized set of dietary guidelines, interventional evidence notwithstanding, motivates people to become more conscientious, healthier eaters. Today's personalized plans can't offer the specificity that nutrigenomic dieting may one day provide, but few would argue that "eat more leafy greens" is bad advice. Grimaldi estimates that about 75% of Sciona's customers follow their individualized plans for at least a year. That's impressive, given that only 13% to 15% of UK adults consume the recommended five daily portions of fruits and vegetables.
But better diet adherence pales in comparison to the promise of nutrigenomics. "Wouldn't that be sad," quips Jirtle, "if this is the most important scientific advance we've made?"