Fooling Mother Nature Last week I got an e-mail from a friend of mine, Paul, who was very excited to tell me about a recent study he'd seen. There's a good chance you read about it too. Using a synthetic form of the so-called "good cholesterol," high density lipoprotein (HDL), researchers at the Cleveland Clinic apparently reduced arterial plaque in subjects with heart disease. Paul was excited by this study for three reasons. 1) He's
constantly having to listen to me talk about studies I've seen
and was happy to be doing the talking for a change; 2) he tends to have low HDL levels and he's convinced this puts him at high risk of plaque building up in his arteries; and 3) most of the media reports on this study fairly gushed with optimistic excitement, using words like "milestone," and "landmark." I didn't tell Paul this (yet), but, in fact, this study is not a
real milestone, and it's far from a landmark. It does, however,
provide us with a good opportunity to recognize the true role
that HDL plays in the risk of heart disease. And contrary to
what many nutritionists will tell you, it's NOT the result of
saturated fat intake.
"Extremely preliminary" is how Susan K. Bennett (clinical
director of the George Washington University Hospital Women's Heart Program) described the Cleveland Clinic study to the Washington Post. In other words: Let's not get carried away.
Headed up by the Cleveland Clinic, researchers at 10 hospitals around the U.S. recruited 47 patients with acute coronary syndromes. Subjects were split into three groups and received weekly injections of placebo, or injections of the synthetic HDL (called ETC-216) at 15 mg/kg or 45 mg/kg. Using ultrasound techniques, accumulation of arterial plaque was measured at the start of the study, and at the conclusion, five weeks later. The results: On average, plaque increased by a very small
fraction of one percent in the placebo subjects. But among those receiving ETC-216, arterial plaque decreased on average by just over one percent. Apparently no adverse side effects were reported, but for extended use of such a treatment, that has to be a concern. As we've seen many times in the past, there are almost always repercussions for fooling Mother Nature with synthetic agents. So while this outcome is intriguing, is it really a "milestone"?
That would be completely overstating the significance of a brief study using only a small group of patients. If you've been reading the e-Alert for a while, it will come as
no surprise that many research projects are funded by the
manufacturers of the products tested. And that's the case here, with the manufacturer of ETC-216, Esperion Therapeutics, Inc., providing the complete financial backing. Encouraged by the Cleveland Clinic results, Esperion executives say they're now planning a one-year study with "thousands" of patients. If they come up with the same results, and no adverse side effects, then they may actually have a milestone on their hands. That's a big "if." And at least one doctor believes that it's
not going to happen because it would be completely contrary to the way HDL is known to perform.
While researching the Cleveland Clinic study, I found literally
hundreds of Internet sources that had picked up the basic
details of the report and, without questioning, sang the praises of this synthetic HDL "breakthrough." The one refreshing - and thoroughly logical - voice of reason I
was able to find came from Malcolm Kendrick, M.D., a columnist for the web site Red Flags Daily. With a few deft strokes, Dr. Kendrick, explains how HDL recycles cholesterol in the body, and why it simply isn't capable of clearing out arterial plaque. As I've written in previous e-Alerts, body cells use cholesterol to perform several chores that are essential to good health.
When cells break down, they release cholesterol, which HDL
collects and carries to the liver. Many doctors and researchers have theorized that HDL can also collect cholesterol from arterial plaques. Dr. Kendrick points out that HDL is what he calls a "passive, inanimate chemical" that collects free-floating cholesterol, but by its nature is incapable of aggressively extracting cholesterol from plaque. So can Esperion's synthetic HDL manage to do what normal HDL can't? Dr. Kendrick strongly suspects it can't. He adds that if it can he'll eat his hat. And he'll be looking forward (as we will) to the results of further studies. Dr. Kendrick also notes that low HDL is a marker for high levels of very low density lipoproteins (VLDLs). This is significant because raised VLDL is a marker for insulin resistance, which is one of the causes of heart disease. So while HDL levels don't have a direct effect on arterial plaque, low HDL is an important indicator of a potentially dangerous pre-diabetic condition.
According to previous studies, combining regular exercise with a low-carbohydrate diet is a good way to raise HDL levels. And of course this is also the best way to prevent type 2 diabetes. Paul, who's concerned about his low HDL levels, is one of the most devoted exercisers I've ever known. But he's also just as passionately devoted to the mainstream notion that a high-fiber, low-fat diet is the best way to prevent plaque buildup and artery disease. He's got the exercise half of the equation right. I have to think that if he tried changing his dietary views - and his diet - for a few months, he just might solve his HDL problem. But who am I to tell him that? To Your Good Health, Jenny Thompson
Health Sciences Institute Sources:
"Effect of Recombinant ApoA-I Milano on Coronary Atherosclerosis in Patients With Acute Coronary Syndromes" Journal of the American Medical Association, vol. 290, no. 17, 11/5/03, jama.ama-assn.org "Liquid Drano-Like Synthetic "Good Cholesterol" Plaque Buster! It's Science, but Not as We Know it" Malcom Kendrick, M.D., Red Flags Daily, 11/6/03, redflagsweekly.com "Synthetic 'Good' Cholesterol Helps Clear Arteries" Rob Stein, Washington Post, 11/5/03, washingtonpost.com "Researchers: Raising HDL Levels Might Reverse Heart Disease" WBAL TV, 11/4/03, thebalchannel.com "Cholesterol Treats Heart Disease" BBC News, 11/5/03,
news.bbc.co.uk
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