December 14, 2000
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Because of certain inherited genetic traits, an extreme low fat/high carbohydrate diet can, for some individuals, actually increase the risk of heart disease, says a scientist with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab).

Slide courtesy of Berkeley HeartLab

Speaking at an international workshop on diet and gene interactions sponsored by the U.S. Department of Agriculture (USDA), Dr. Ronald Krauss, head of the Department of Molecular Medicine in Berkeley Lab’s Life Sciences Division, reported on the recent findings of his research group in which it was shown that in genetically susceptible individuals, an extreme low-fat/high-carbohydrate diet can produce metabolic reactions that cause a change in the cholesterol profile of their blood. An extreme low-fat diet was defined as one in which fat comprised less than 25 percent of the total daily calorie intake.

In these cases, patients with a "pattern A" profile -- meaning the low-density lipoproteins LDLs or the "bad" cholesterol in their blood are predominantly made up of relatively large and more buoyant particles -- will shift to a "pattern B" profile, in which most of the LDLs are smaller, more densely packed. Earlier studies by Krauss and others have already established that the pattern B profile poses a much greater risk of heart disease than the pattern A.

"Tests for these genetically susceptible traits are not widely available," says Krauss. "A clue is if there are elevated levels of triglycerides (another type of blood fat linked to heart disease) and lowered levels of high-density lipoproteins (HDLs or the "good" cholesterol) when a patient goes on a very low-fat/high-carbohydrate diet."

Heart disease remains the number one cause of death and disability in the United States and increasing numbers of Americans, especially those over 50, have turned to diets aimed at lowering LDL cholesterol levels as a means of reducing the risk. While the effects of such dietary changes are beneficial to the population at large, these effects can vary widely among individuals, according to Krauss.

"Studies of dietary effects on LDL cholesterol must take into consideration that LDL is comprised of distinct subclasses that differ in particle size and density, and that there is variation in the distribution of these subclasses among individuals," he says. "Small LDL particles appear to have a great atherogenic potential than large LDL particles by virtue of reduced receptor-mediated clearance, and higher arterial transport, proteoglycan binding, and oxidative susceptibility."

The interaction between diet and genes and how this interaction affects the two LDL subclass patterns may help to explain why there can be so much variability in the effects of low-fat diets on the risk of heart disease. For patients who started out with the pattern B cholesterol profile, the study by Krauss and his research group showed that an extreme low-fat/high-carbohydrate diet can reduce the number of circulating small LDL particles which in turn reduces the risk of heart disease. LDL particles carry cholesterol through the blood stream and deposit it along arterial walls, creating a waxy buildup that can eventually restrict the flow of blood to the heart.

For patients who started out with the pattern A cholesterol profile, however, Krauss and his research group found that an extreme low- fat/high-carbohydrate diet worked to reduce the cholesterol content of the LDL particles circulating in the blood. This depletion in the composition of the LDL particles resulted in a downsizing that in turn led to a conversion from the pattern A to the pattern B profile.

"Studies in families have indicated that LDL subclass patterns are influenced by major genes, and linkage of LDL particle size phenotypes to several candidate genes have been reported," says Krauss. "However, overall heritability of LDL particle sizes is less than 50 percent, consistent with the strong influence of modifying factors on the expression of LDL subclass patterns."

Previously, these modifying factors were listed as age and gender, plus certain metabolic conditions that affect triglyceride levels such as abdominal adiposity and resistance to insulin. To these factors can now be added diet, says Krauss.

Results of the study by Krauss and his collaborators were originally reported in the June 2000 edition of the American Journal of Clinical Nutrition. Krauss’ coauthors on that paper were Darlene Dreon, Harriet Fernstrom, and Paul Williams.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California.

Slide courtesy of Berkeley HeartLab