July 12, 2005
Twins Study Shows Some Have Genetically Low Cholesterol

Some people can eat a lot of fat without much change in cholesterol levels.

BERKELEY, CA Why does it seem like some people can eat all the ice cream they want without increasing their cholesterol or gaining much weight, while others with high cholesterol have to watch their diets like a hawk? Because no matter what their lifestyle, people's genes play an overriding role in their cholesterol response.

So says a new study by researchers at the Department of Energy's Lawrence Berkeley National Laboratory and the Children's Hospital Oakland Research Institute (CHORI), conducted by Paul Williams of Berkeley Lab's Life Sciences Division in collaboration with Robin Rawlings and Patricia Blanche of CHORI and Ronald M. Krauss of CHORI and Berkeley Lab's Genomics Division. They report their findings in the July 8, 2005, issue of the American Journal of Clinical Nutrition.

The investigators analyzed how "bad" cholesterol (low-density lipoprotein, or LDL, cholesterol) responded to diets that were either high or low in fat in 28 pairs of identical male twins one twin a vigorous exerciser, the other a comparative couch potato.

"Although identical twins share exactly the same genes, we chose these twins because they had very different lifestyles," says Williams. "One member of each pair was a regular long-distance runner, someone we contacted through Runner's World magazine or at races around the country. His brother clocked 40 kilometers a week less, at least, if he exercised at all."

For six weeks the twins ate either a high-fat diet (40 percent of its calories from fat) or a low-fat diet (only 20 percent of its calories from fat); then the pairs switched diets for another six weeks. After each six-week period the twins' blood cholesterol levels were tested.

The researchers were interested in learning if blood cholesterol changes due to the different diets would be the same or different in each pair of genetically identical twins, even though their lifestyles were very different. A correlation of zero between the two would mean that their responses to the diets had no relation to each other, while a correlation of 1.0 would mean that their responses were identical.

The researchers found an astounding 0.7 correlation in responses to the change in diet, an incredibly strong similarity in the way each pair of twins responded even though the responses themselves among different pairs of twins differed considerably.

"If one of the twins could eat a high-fat diet without increasing his bad cholesterol, then so could his brother," says Williams. "But if one of the twins' LDL cholesterol shot up when they went on the high-fat diet, his brother's did too."

The correlations showed that the twins had very similar changes in LDL cholesterol because they had the same genes. Some twins had one or more genes that made them very sensitive to the amount of fat in their diets. Other twins had genes that made them insensitive to dietary fat, no matter how much they exercised.

The genes which cause this difference in response to fats will be identified. A more immediate benefit of identifying those genes would come from genetic tests that would tell you whether your cholesterol level is sensitive to your diet. If your cholesterol level is not sensitive to the amount or types of fat you eat then you could stop fighting your desires to eat higher fat foods - at least for the sake of your cholesterol.

A longer term benefit will come from using this knowledge to guide the genetic reengineering of one's cholesterol metabolosm. My guess is that these genes exercise their influence in the liver. For people who have diet-sensitive cholesterol gene therapy could reprogram the liver cells to keep overall cholesterol low and HDL cholesterol high regardless of diet or exercise. Either the existing liver could be reprogrammed or stem cells from your body could be removed, genetically modified, and then grown to create a replacement liver that more optimally regulates cholesterol.

Not everyone who has cholesterol levels that are insensitive to diet have low cholesterol. Some have cholesterol that is stuck at dangerously high levels. Those people who have high cholesterol without much dietary sensitivity for cholesterol levels would derive the greatest benefit from geneticaly reengineered livers. For now the best they can do is take statin drugs.

If you were willing to make the effort and spend some money you could discover with the help of your doctor whether your cholesterol level is diet sensitive. Try different diets with different fat levels and fat types and get a test of your various types of cholesterol after eating each diet. for 6 weeks as these researchers did. If you want to try this then consider putting the ape diet on your list of diets to try. If even the ape diet doesn't lower cholesterol then you might as well enjoy ice cream for breakfast.

Share |      Randall Parker, 2005 July 12 12:36 PM  Aging Diet Studies

Lei said at July 17, 2005 7:00 AM:

Another "duh" result in my opinion. We've known for years that there are genes involved in cholesterol synthesis and processing. What we need now is to figure out the way these genes work together and with lifestyle factors to cause changes in our cholesterol levels. Then we could set about developing gene/protein-targeted drugs that had fewer side effects than statins. Don't know why it's taking so long. Could it be that the pharmas have already invested so much money in statins that they're reluctant to move on?!

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