Genes Key in How Diet Affects Cholesterol Levels

NEW YORK (Reuters Health) - Anyone who has ever renounced dessert and failed to be rewarded with low cholesterol levels may be able to blame it on genetics, a new study suggests.

The study of 28 pairs of male twins -- one a lean athletic type, the other a bit rounder and sedentary -- found that brothers tended to show the same cholesterol response to high-fat and low-fat diets, even though their exercise habits were starkly different.

Because identical twins share the same genetic makeup, the findings point to the importance of genes in determining how a person's cholesterol levels respond to diet and lifestyle changes, according to the study authors.

It's a well-known phenomenon that some people can eat whatever they want yet stay thin and have normal cholesterol levels, while others send up their cholesterol just by looking at cheesecake. Likewise, some people with high cholesterol can manage the problem by altering their eating habits, while others need medication.

For those who fail to better their cholesterol profile with diet, genes -- rather than a lack of will -- could be the reason, said Paul T. Williams, a researcher at the Lawrence Berkeley National Laboratory in California and the study's lead author.

He and his colleagues report their findings in the July issue of the American Journal of Clinical Nutrition.

For the study, the researchers recruited 28 pairs of male identical twins; in each case, one brother was an avid runner, while the other tended to stay on the couch. The researchers looked at the men's cholesterol responses to each of two 6-week diets -- a high-fat diet where 40 percent of calories came from fat, and a low-fat regimen with 20 percent of calories coming from fat.

The study found a high degree of similarity in how brothers' LDL cholesterol (the "bad" form of cholesterol) responded to the switch from the high-fat diet to the low-fat one. On average, the men's LDL declined on the low-fat diet, but any individual's response seemed to depend largely on genes.

"What's remarkable is that we found such a high correlation" between twin brothers' LDL responses, Williams told Reuters Health. This suggests, he said, that "there's a lot to be found" in the hunt for genes that help regulate cholesterol levels.

Scientists have identified a few genes that appear to be at work, but these cannot explain the wide variance seen in individuals' cholesterol responses to diet changes, Williams and his colleagues note.

In general, low-fat diets tend to lower LDL concentrations, but can also decrease "good" HDL cholesterol and raise triglycerides, another type of blood fat. So cutting dietary fat may not have a net benefit, depending on the individual.

If researchers can uncover the genes that govern cholesterol responses, Williams said, then it may be possible to identify people who are "good candidates" for dietary management of high cholesterol, and those who may need to try medication sooner.

Other research, Williams noted, has shown that a person's response to cholesterol medication may also depend on genes.

SOURCE: American Journal of Clinical Nutrition, July 2005.