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The HDL Conundrum: What’s Bad about Drugs for Good Cholesterol?

The views expressed are those of the author and are not necessarily those of Scientific American.


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graphic showing normal interior view of artery w/red blood cells and cholesterolAfter federal officials announced on May 26 the halting of a trial probing whether Abbott Laboratories’ formulation of the B vitamin niacin can help prevent heart disease and strokes, scientists and physicians were left with an  immediate follow-on question. Specifically, was this event just another nail in the coffin of the premise on which that trial was based, the so-called HDL Hypothesis?

On the surface, the basic conjecture, the idea that raising high-density lipoprotein cholesterol (HDL-C) can help prevent cardiovascular disease, is well-grounded in science. Studies have shown that people with high levels of HDL experience less heart disease. So that should mean that raising HDL, which shuttles cholesterol from artery walls back to the liver for excretion, should prevent cardiovascular problems as well. In recent years, that notion has become a big maybe, what might be re-titled as the HDL Conundrum.

The AIM-HIGH trial using Abbott’s drug Niaspan in conjunction with a statin that lowers LDL cholesterol—LDL “bad,” HDL “good,” probably a macro in some health reporters’ laptops—showed that the drug worked as billed. It raised HDL, but it didn’t prevent cardiovascular risk any better (actually it may have registered a slightly worse result) than a statin alone. This is not the first hit for the famed good lipid. A Pfizer drug that increased levels of HDL by a different biological mechanism was halted in 2006 because it upped the risks of deaths. Still, Merck is putting big money behind another HDL.

So what’s going on here? Nobody knows for sure, but there are a few ideas kicking around. A review article published in 2010 in the Journal of Lipid Research by a group of scientists from the University of Amsterdam underlined that the HDL hypothesis remains just that, a hypothesis. The scorecard for HDL on a variety of standard measures is mixed. Yes, the epidemiology shows that high HDL is protective. And a series of lab dish studies indicate that HDL has properties that guard against cardiovascular disease, but none of these things have been validated in humans. Animal studies indicate the same, but other blood lipids were changing along with the increase in HDL, possibly muddying the picture. Genetic studies looking at whether HDL is protective remain unconvincing. So what sounds good on paper is sketchy at best, particularly in light of this most recent study. So to quote Stephen Jay Gould when he appeared on The Simpsons: Much more research is needed.

In the meantime, maybe those reporters should think about changing the macros in their computers.

Image: U.S. National Library of Medicine





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  1. 1. ravenrose 5:07 pm 05/27/2011

    Of course as with everything like this, we are very primitive in our classifications and measuring. Possibly (probably) HDL is made up of several things with different effects, just like LDL is. At one time people thought LDL was one thing and it was bad. Of course now we know (and you can have measured with a VAP test) that the small dense LDL particles are dangerous and the large fluffy LDL particles aren’t, and quite possibly might be a good thing… I would venture that perhaps what statins raise and we measure as HDL isn’t the same thing as naturally occurring HDL. And none of this mentions triglycerides which might be the most important of all, possibly because the only good way to lower them is to decrease carbohydrate consumption and people persist in thinking carbohydrates are healthy.

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  2. 2. JamesDavis 7:04 am 05/28/2011

    When Mrs. Bush said, "Just say no to drugs." Maybe she was also talking about legal drugs and you should listen to her and have your bowl of oats with a tablespoon full of almond butter or peanut butter…and don’t forget the fruit. Switch from mineral salt to sea salt and sprinkle some garlic powder over your steak the next time.

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  3. 3. tharter 1:25 pm 05/28/2011

    Or just don’t eat meat and dairy, which overall is rather convincingly linked to improved heath.

    http://www.thechinastudy.com/ is a pretty good book on the subject and explicates some pretty solid science.

    In the end though, all the drugs in the world don’t substitute for good life habits, hew that how we may…

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  4. 4. karagi 10:51 pm 05/28/2011

    Mineral salt is made of 99.9% sodium chloride while sea salt is 98% sodium chloride — almost identical other than sea salt having some trace minerals such as iron, sulfur & magnesium but no iodine while table salt has iodine added which prevents people from suffering from iodine deficiency diseases.

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  5. 5. Ralf123 10:47 pm 05/29/2011

    Raised HDL may just be a byproduct of other metabolic processes. As always, correlation is not causation.
    Just raise your HDL the old fashioned way: With exercise. It’s known to work.

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  6. 6. Ungolythe 1:16 am 05/31/2011

    An ounce of prevention is worth a pound of cure. You make sense in that the real "cure" for the prevalence of heart disease is a better diet and good physical activity can’t be stressed more. In a perfect world we would all eat less meat and more vegetables and fruits and be better off for it. I’m not sure why using sea salt is any healthier then table salt. It does contain minute amounts of iodine and we get more than enough iodized salt elsewhere to not worry about thyroid problems from using it but I think rather than being any healthier it just tastes better in certain applications like on a nice 6oz steak.

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  7. 7. davetrindle 1:08 pm 05/31/2011

    You state, "Or just don’t eat meat and dairy, which overall is rather convincingly linked to improved heath"

    You really can’t conclude this unless you differentiate between meat and dairy-with-hormones, antibiotics, etc. and organic meat and dairy.

    Also, many of the studies more than 5 years old never differentiated saturated fat from trans-fat, rendering these studies equally useless.

    Also you would have to control for genetic and lifestyle differences between meat-eating groups and vegetarians. When was this ever done?

    There’s a lot of bad science in the whole area of saturated fat, cholesterol, and heart disease. This is evidenced by the need to continually re-vamp the model of cause-and-effect. First there was cholesterol, then "good" vs "bad" cholesterol, then "good" & "good" "bad cholesterol vs "bad" bad cholesterol–i.e. those with larger particle size.

    It’s a bad sign when you have to keep changing your model to justify your conclusion. The actual process of atherosclerosis is still (after 60 years of bashing cholesterol) not understood. The old idea of cholesterol "clogging" the pipes turned out to be a joke.

    The drug companies are making billions on this confusion. That’s another bad sign.

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  8. 8. hbeierbeck 7:41 pm 06/2/2011

    Two thoughts occurred to me on reading this article.

    First, blood vessels have to be damaged through chronic inflammation before LDL particles can get in and cause damage. If raising HDL levels doesn’t reduce inflammation or eliminate small dense LDL particles, then there is no reason why it should lower CVD risk.

    Secondly, you can only expect an increase in HDL levels to decrease CVD risk if there is a causal inverse correlation between the two. If this correlation is merely statistical, i.e. if there is some other factor that both raises HDL levels and lowers CVD risk, then again there is no reason why increasing the number of HDL particles should lower CVD risk.

    The article doesn’t address either one of these points.

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  9. 9. bucketofsquid 5:58 pm 06/8/2011

    Carbohydrates are healthy – if you burn every calory you consume of carbs and are maintaining a low body mass via large amounts of cardio exercise every day. An hour or two at the gym every day doesn’t really count as sufficient cardio.

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