“Good” Cholesterol Not So Good After All, New Study Shows

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A study of over a hundred thousand trial participants showed that gene variations which change levels of HDL have no effect on heart attack risk.

The revelation that high-density lipoprotein, or HDL, is the “good cholesterol” has suffered a major blow. A meta-study involving over a hundred thousand participants used two different strategies to see if genetic mutations that increased levels of HDL also decreased risk for heart disease. In both cases the answer was a resounding no. The researchers were shocked when they saw the data. Now it’s their turn to shock HDL proponents and drug companies looking to cash in on the HDL craze.

The study, which was published recently in The Lancet, is causing quite a stir in the field. As Dr. James de Lemos, from the University of Texas Southwestern Medical Center, told the New York Times, “I’d say the HDL hypothesis is on the ropes right now.” Dr. de Lemos was not involved in the study.

So what’s the story here? How is it possible that LDL/HDL dichotomy has propagated so powerfully through conventional wisdom that even the CDC refers to them as “good” and “bad” cholesterols and pharmaceutical companies like Abbot Laboratories are working hard to get in on the HDL cash cow?

Past studies have shown that much of what increases our risk for heart disease, like obesity, lack of exercise, smoking, and insulin resistance, is correlated with low HDL. It was a logical conclusion, then, that by increased HDL levels we could decrease those risks. But correlation doesn’t mean causation, and the takeaway conclusion from the current study is that decreased HDL is simply a sign of increased risk for heart disease but the level of HDL doesn’t actually affect heart disease.

In the most recently published study researchers used genetic, lipoprotein, and heart attack outcome data from some thirty odd studies to see if a genetic mutation known to increase HDL levels decreased the chance of heart attack. They focused on the gene for endothelial lipase. Past research has shown that when endothelial lipase has certain single-nucleotide polymorphisms (SNPs) it leads to increased levels of HDL. Looking at study data from 116,000 participants, they saw that 2.6 percent of them had the SNPs and confirmed that their HDL levels were significantly higher than average. But when they compared the incidence of heart attack between the two groups they found no difference whatsoever.

The second part of the study took a similar approach, but instead of limiting analysis to one gene the researchers looked at 14 gene variants know to affect HDL levels and asked if the variations affected cardiovascular health. Again, the amount of HDL did not affect whether or not a person suffered a heart attack.

But even with such a high sample size, it’s possible that the methodology of the study was somehow flawed. Using low-density lipoprotein (LDL) - the so-called bad cholesterol - as a control, the researchers analyzed gene variants among the participant pool and confirmed that decreased levels of LDL lessened the chance of a heart attack, validating their analysis of the HDL data.

Think twice before you reach for that bottle of HDL-boosting Niacin.

This may come as a shock to many, but another study published last year suggested that HDL was not so “good” after all. The trial tested the effects of niacin, a drug that increases a person’s HDL levels, on over 3,000 patients at risk for heart disease. Because niacin stimulates the production of HDLs they were expected to improve the cardiovascular outlook of these high-risk patients. Two years into the study researchers confirmed that the group’s HDL levels were increased. At three years, however, the study was stopped prematurely due to “lack of efficacy.”

But while the research may be “on the ropes,” not everyone’s throwing in the HDL towel just yet. Dr. Steven Nissen who is the Cleveland Clinic’s chair of cardiovascular medicine and conducts HDL research himself told the New York Times that he is “hopeful,” reasoning that HDL is “complicated.” In 2010 the Cleveland Clinic received a $11.6 million grant to study the benefits of HDL, so it’s easy to see how the current study would indeed “complicate” things.

Cardiovascular disease is the world’s number one killer. Responsible for 30 percent of all deaths globally, it claimed the lives of nearly 16 million people in 2008. The pharmaceutical giants all have their own version of cholesterol-lowering statin: Merck’s Zocor, AstraZeneca’s Crestor, and Pfizer’s Lipitor, which has become the most profitable drug of all time at sales of over $130 billion. It’s no wonder then that companies have been busy trying to reap the rewards of HDL-boosting niacin.

Abbott Laboratories, which offers a version of niacin called Niaspan, responded to the halted trial by saying it might not work for the chronically high-risk, but it remains to be seen if others won’t benefit. But like Dr. Nissen, I suppose Abbott can take momentary solace in the fact that these are, after all, just two studies – albeit one a very large study. But if others begin to confirm the current findings, the “good” in HDL will become “good riddance.”

[image credits: Healthy Living, DoctorSaputo.com, and Benefits of Niacin]
images: Healthy Living, DoctorSaputo.com, and Benefits of Niacin

Peter Murray

Peter Murray was born in Boston in 1973. He earned a PhD in neuroscience at the University of Maryland, Baltimore studying gene expression in the neocortex. Following his dissertation work he spent three years as a post-doctoral fellow at the same university studying brain mechanisms of pain and motor control. He completed a collection of short stories in 2010 and has been writing for Singularity Hub since March 2011.

Discussion — 8 Responses

  • Brent May 20, 2012 on 11:37 am

    What’s shocking is that there still exist medical researchers who believe that cholesterol causes heart disease. Do they not read anyone else’s research? Anyone who has seriously looked at the data knows that there is no causal relationship between cholesterol, which is an essential nutrient used extensively throughout the body, and heart disease. The lipid hypothesis is dead. If you’re interested in this subject, Chris Kresser has written quite a bit about it.


    • AlanX Brent May 20, 2012 on 4:07 pm

      Brent thanks for posting that but I am afraid that only 1 out 100 people will believe it or pay any attention. My own GP, good in other ways, is constantly pushing statin drugs on me and it really annoying. I’m supposed to be terrified because my LDL numbers popped up a bit last test.

      Other links on the subject you might like:


      Chris Masterjohnn does a particularly good job at deconstruction all the nonsense. What I think he is really on to is the fact that it is oxidized LDL that causes the CHD trouble, not normal LDL and not any other form of lipoprotein. People with a lot of oxidized LDL tend to have higher LDL numbers so it appears that is the risk factor when actually it isn’t.

      Of course this “breakthrough” study isn’t going to shed any light on that — it will just convince more people that their cholesterol numbers mean danger and so they will buy lots of dangerous but profitable statin drugs.

  • Joel Mark Collins May 21, 2012 on 2:13 am

    I’m sorry to diss an otherwise informative article, but Niacin isn’t “a drug that increases a person’s HDL levels”. It is an essential vitamin (B3) involved in cell growth, DNA repair and the proper functioning of the adrenal gland. If you don’t consume enough Niacin you die. “Think twice before you reach for that bottle of HDL-boosting Niacin”? Really?

    • Peter Murray Joel Mark Collins May 21, 2012 on 8:49 am

      My bad. My article was in the context of using niacin to raise HDL levels to decrease CVD risk. You’re right, people should still take their vitamins.

  • texasbrian May 21, 2012 on 7:42 am

    The photo above shows inositol hexanicotinate, a form of niacin that does nothing with HDL levels. The therapeutic version of niacin is known as nicotinic acid. You’re doing a story about baseball, and the photo shows a basketball.

    • Peter Murray texasbrian May 21, 2012 on 8:47 am

      Oops. I guess I should read labels more clearly.

      • turtles_allthewaydown Peter Murray May 22, 2012 on 2:01 pm

        Whoa, I need to look at my niacin at home and see which one I’ve been taking for my HDL.
        Although, it now appears that both types are probably unnecessary for me, at least for my heart.

  • turtles_allthewaydown May 22, 2012 on 2:23 pm

    I’m a little bit hesitant to put too much faith into this report until other researchers have had time to dig into it, perhaps duplicate it. But it does seem to back up the study from last year, and it’s a large sample size, so it does seem to have some validity with it.

    I was curious though why they were looking at gene variations, then confirming those people had the expected HDL or LDL levels, and then comparing the results with heart attacks. Why not just look directly at the HDL and LDL levels? There might be diet and exercise factors that also affect HDL and LDL, or are they trying to remove diet & exercise from the cholesterol equation?

    I’m disappointed with my doctor. He’s totally fixated on lowering cholesterol and is ignoring my borderline glucose levels, even though my brother has diabetes, and ignoring my surprisingly low vitamin D levels. I argued with the nurse last week to get those tests added to my blood check, let’s see if they actually did run them. Vitamin D, diabetes, cholesterol – which one would affect my health first?