News
April 26
Eat a diet low in fat, with plenty of fruits and vegetables, and a lot of fiber - you've heard the universal nutrition recommendations so many times it hurts. But what if eating a low fat diet was the wrong recommendation? What if it was the right recommendation for your roommate, but not for you? Those are the questions Jos?© Ordovas, Director of the Nutrition and Genomics Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA), is working fervently to answer. As a pioneer in the relatively new field virtually unknown five years ago called "nutrigenomics", Ordovas investigates how nutritional recommendations are influenced by what we inherit from our parents - our genes. Ordovas describes nutrigenomics as, "interactions between genes and the environment." His trail-blazing research takes him on non-stop travel across the globe, where he collaborates with more than 70 scientists worldwide. "[By] moving from one country to another, from one ethnic group to another, we capture the global genetic variability in the world population ... but at the same time, we capture the fact that these populations are subject to different environments," he said. Our genes determine such physical characteristics as eye and hair color, and are partially responsible for the reason why some are more prone to developing certain diseases, such as cardiovascular disease, while others are not. Herein lies the foundation of nutrigenomics. For example, low HDL cholesterol - the so-called "good" cholesterol - is a risk factor for the development of cardiovascular disease. To raise HDL cholesterol levels, the American Heart Association (AHA) recommends losing or maintaining a healthy weight, not smoking and getting plenty of physical activity, but specific dietary recommendations are less clear. What's more, an enzyme called "hepatic lipase" is thought to influence HDL cholesterol metabolism. Elevated levels of the enzyme may decrease HDL, while lowered levels may raise HDL. Researchers have discovered a variation - called a polymorphism - in the gene that codes for the hepatic lipase enzyme. This polymorphism is thought to decrease hepatic lipase activity and therefore increase HDL cholesterol levels. But the relationship between the polymorphism and HDL levels may be complicated further by diet. Ordovas and his colleagues investigated how this polymorphism may interact with dietary fat to influence HDL levels in offspring subjects of the Framingham Heart Study. In those subjects consuming less than 30 percent of their calories from fat, the polymorphism was associated with increased HDL cholesterol compared to the normal gene. However, in those subjects consuming 30 percent or more of their calories from fat, the polymorphism was associated with decreased HDL cholesterol compared to the normal gene. This suggests that HDL levels may increase or decrease, depending on both dietary intake and genetic variation. "Different variations of your genes may interact differently with your diet," said Michael Crosier, a doctorate student in Nutritional Biochemistry and Metabolism in the Friedman School. "These interactions can influence the amount of cholesterol levels in your blood. If you have this gene [variant], this could give you a tendency to have a higher cholesterol level." Crosier works with Ordovas on samples from a three-year clinical trial, conducted by Sarah Booth, Scientist I in the Vitamin K Research Laboratory at the HNRCA and associate professor at the Friedman School. The trial is examining vitamin K supplementation and how it affects bone density and vascular calcification, a term used to describe the build up of calcium deposits in blood vessels that may be a predictor of cardiovascular disease. "[Vitamin] K-dependent proteins are found in both bone and vascular smooth muscle cells," Booth said. "The theory is that inadequate vitamin K results in impaired function of these proteins, which ultimately leads to abnormal calcification in the tissues where they function." Crosier is looking at the possible interactions between vitamin K and genetics. "We are looking at the genetics involved in vitamin K metabolism and how it relates to bone density and vascular calcification," Crosier said. "We are hoping that variations in those genes will correlate with variations in bone density and vascular calcification." Toshiko Tanaka, a doctoral student at the Friedman School in the Nutrition and Genomics Laboratory, is working with Ordovas on a project studying taste receptors and eating patterns. "Based on the genotype, people may have different patterns of eating because of the way they taste food," she said. This suggests that nutrigenomics may someday partly explain eating behavior and why some people eat diets rich in fruits and vegetables, while other people prefer diets high in salt and fat. Ordovas and his colleagues have also now identified two different variations of the "perilipin" gene in women enrolled in the Framingham Heart Study, which may be linked with a higher risk of obesity. This gene produces the perilipin protein that regulates the breakdown of fat. Recent research suggests the more perilipin protein produced, the more fat is stored in a cell. The futuristic goal for nutrigenomics is that someday patients will be treated for certain diseases based on their genotype. "The idea is in the future, we know that there are people that respond to diet so well, that they will not have to be exposed to the problems and cost of drugs ... and these people should take seriously dietary advice," Ordovas said. "Then for other people that do not respond to diet, obviously we have to get to them with drugs." However, Ordovas cautions not to "jump the gun" on nutrigenomics. One of the challenges of the field is the need for better studies. Studies conducted so far have been "heavily underpowered in terms of number of subjects" and the Framingham Heart Study only provides a "hint" to answer the questions of nutrient and gene interactions, he said. While larger studies may improve the quality of nutrigenomics research, Ordovas said these studies will likely be observational in nature and may not provide all of the scientific evidence researchers are seeking. According to Ordovas, the key evidence needed involves implementing an intervention study in which subjects' diets are changed. "A clinical trial selecting people based on their genotypes and then providing them with different variations in diet that may wake up the genotypic effect of diet," is what is needed he said. "We put them on a low-fat diet and high-fat diet in a cross-over design and we see if we can reproduce in intervention what we see in observation." If findings from intervention studies provide enough conclusive evidence, using nutrigenomics to personalize dietary recommendations may be a real possibility in the near future. "That is something we see in the range of three to five years," he said. There are already genotyping procedures now available, but Ordovas said he is "uncomfortable" using them to make diet recommendations at the present time. "[At] this point it would be too costly to the society ... and the professionals to translate this to the public do not exist. Health professionals have not been trained," he said. "Now is too early for everybody ... it is too early in terms of knowledge and in terms of transmission of that knowledge." Ordovas does see a future for the use of nutrigenomics in weight control since there is a genetic factor involved in obesity. "You have this [variant], if you [eat] this instead of that, or this plus this, it should work," he said. "It is very risky, because obesity control is very difficult, but we can make our first impact in terms of the population approach." So, what if all Americans did follow the dietary guidelines? Ordovas estimates 80 percent would see a benefit in health. "The remaining people would be the ones that would benefit [from genotyping]." When Tufts students were asked if they would like to know their personal dietary recommendations, responses varied. "I would absolutely want to know," said Kate Rosenbaum, a senior psychology major. Pauline Eveillard, a senior art history major, partly agreed with Rosenbaum. "I would like to have personal dietary recommendations, but it is not a necessity for me," she said. On the contrary, Rachel Young, a senior English major, disagreed. "Trying new things is a part of life, and it's never just one thing that leads to an unhealthy diet. I'd rather just enjoy a little of everything."Erika Nakamoto is a graduate student in nutritional biochemistry and metabolism at the Friedman School. She has a BS from Boston University in health studies.
