For decades doctors have been telling patients to get their “bad” LDL cholesterol levels down and to boost their “good” HDL cholesterol. Cardiologists have been prescribing niacin to do both for more than 50 years. Niacin lowers LDL cholesterol levels anywhere from 15 to 40 percent, raises good HDL cholesterol 10 to 20 percent and also brings down triglycerides.

A landmark study published in 1986, the Coronary Drug Project, tracked heart attack victims for 15 years. Men who had been prescribed niacin had substantially fewer repeat heart attacks and 11 percent fewer deaths than men on placebo. In a follow-up analysis, it was revealed that the benefit persisted for many years, even after the men stopped taking niacin.

Now, in a giant flip-flop, doctors are being told to stop routine prescribing of niacin and patients are being told that the risks outweigh the benefits. Two new studies published in the New England Journal of Medicine (July 17, 2014) suggest that even though niacin produced favorable lipid changes (lowering LDL cholesterol and triglycerides and raising HDL cholesterol), it did not produce meaningful improvements in heart attacks, strokes or death. This led to a flurry of headlines in popular media:

“Don’t take niacin for heart health, doctors warn” (Fox News)

“Taking niacin for the heart may pose serious health risks” (CBS News)

“Niacin for high cholesterol carries death risk” (Yahoo News)

“Niacin Won’t Help, May Harm Heart Patients” (AARP Blog)

 

What is the People’s Pharmacy take on the new studies and the scary headlines?

Let’s actually examine the studies a bit more carefully than some of the talking heads have done on the evening news. What has not been clearly stated is that neither of the studies in the New England Journal of Medicine actually compared pure niacin to placebo the way the original Coronary Drug Project did decades ago. Both studies placed all patients on statins before assigning any of them to take either extended-release niacin or a niacin combination drug in addition to the statin.

In the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), patients were prescribed 40 mg of simvastatin (Zocor) during the “run-in phase” of the trial. If this statin didn’t lower their total cholesterol levels below 135 they were also prescribed ezetimibe (Zetia). This treatment led to average LDL cholesterol levels in all patients of 63 before niacin therapy was added to the regimen.

It was only after cholesterol levels were in the basement that niacin was added. But here’s the catch. The study subjects did not get pure niacin. They either received a placebo or a Merck drug called Tredaptive that contained both niacin and an experimental compound called laropiprant. This additional medication was included to reduce facial flushing, a common side effect of niacin.

What They Found:

In patients taking high doses of statin (and possibly Zetia) with very low cholesterol levels, there was no cardiovascular improvement achieved by adding Tredaptive (niacin plus laropiprant). Patients taking 40 mg of statins (and possibly Zetia) together with niacin and laropiprant had more adverse reactions than patients taking statins and ezetimibe alone. Those complications included flushing and other skin reactions, digestive distress, musculoskeletal problems, infections, bleeding disorders and diabetes.

Unanswered Questions:

  • Do statins (and/or ezetimibe) render niacin ineffective or more dangerous? (We are puzzled that the investigators and “experts” have not considered such a possibility.)
  • Did the added laropiprant have any impact on the outcome?
  • How would pure niacin have performed without laropiprant or statins (plus Zetia)?
  • Is it possible that raising HDL cholesterol levels with drugs has no measurable benefit and that only naturally high HDL levels provide heart protection?

The other study, called AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes), also involved patients given 40 mg of simvastatin plus 10 mg of ezetimibe to get LDL cholesterol below 70 mg per deciliter. Once LDL cholesterol levels were reduced dramatically, patients were randomized to as much as 2000 mg of niacin or placebo daily. Again, there was no benefit to adding niacin to the statin therapy.

Seemingly overlooked in the trashing of niacin was the fact that there was no statistically significant difference in overall serious adverse events between patients on simvastatin plus ezetimibe and placebo (32.5% serious adverse events) compared to those on simvastatin, ezetimibe and niacin (34.2%).

BOTTOM LINE:

Neither study published in the New England Journal of Medicine looked at niacin by itself in reducing heart attacks, strokes or death. As far as we can tell no one has considered the possibility that adding statins (and/or ezetimibe) to niacin therapy renders niacin ineffective and/or more more dangerous. Such a drug interaction needs to be ruled out.

It is entirely possible that niacin is not beneficial and carries serious side effects, but these studies involved three or four drugs (depending upon design): simvastatin, ezetimibe, niacin and laropiprant. To conclude that niacin is useless and dangerous from these studies is, in our opinion, somewhat premature. To make that conclusion one would need to repeat the original Coronary Drug Project and randomize people at risk of heart disease to either niacin or placebo and follow them for a long time. That is not likely to happen given that niacin is available generically and there is no incentive for a drug company to conduct such a large and expensive trial.

One Final Note:

Combining ezetimibe (Zetia) with simvastatin (Zocor), as both trials did, may not make much sense. There are no good data suggesting that ezetimibe reduces heart attacks or strokes and improves survival stats. One key study (ENHANCE) did not demonstrate better outcomes when Zetia was added to simvastatin. Why these researchers chose to include ezetimibe in both niacin trials remains a mystery to us. The combination of simvastatin and ezetimibe may also pose special risks. Adding ezetimibe to a high-dose statin regimen may increase the likelihood of side effects such as muscle pain and weakness as well as liver damage.

Niacin should never be a do-it-yourself project. Liver enzyme monitoring is essential, especially with slow-release products. Other side effects that must be considered include blood sugar elevation, digestive distress and bleeding. That said, if you have been taking niacin under medical supervision without complications, do not stop without first checking with your physician. Those scary headlines may be misleading for all the reasons stated above.

For more information about the pros and cons of niacin and other cholesterol-lowering approaches we suggest Best Choices from The People’s Pharmacy. It offers many non-drug alternatives that are likely to be better tolerated than statins, ezetimibe or niacin.

Share your own statin story or niacin experience below.

 

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  1. MR
    Reply

    The enzyme nattokinase seems to be quite good at clearing plaque out of the arteries. Maybe it would be a whole lot better for many people to take nattokinase instead of getting mixed up with prescription drugs, or even niacin. We do need that cholesterol, after all.

  2. C.S.
    Reply

    I take several of the Bs, not just niacin, in megadoses. What none of the vitamin and mineral enthusiasts mention is the need for a modest daily dose of trace minerals to balance out the mix.
    I have no proof that the trace minerals are necessary, but given the soil depletion our veggies grow in, and the poor diet of most animals that are transformed into our meat, it’s probably a good idea to investigate the necessity of adding trace minerals to the mix they tell us to take without ever mentioning what we’re missing.

  3. Martha P.
    Reply

    I have very high cholesterol and statins made me feel weak and with muscular pain in my hips. So my cardiologist prescribed the new slow release niacin. After taking it a week I had an episode of very bad heart arrythmias. I have a pacemaker and I thought it was not working. I almost went to the ER. I took some aspirin and waited it out. After about 2-3 hours my heart calmed down. I went off the niacin and will never take it again.

  4. Kristin
    Reply

    ANY responsible scientist should know that a proper test involves one variable, not several. Ridiculous! I also suspect that the reason they didn’t test the niacin alone was because niacin is not a patented drug and they were being paid by the drug companies.
    One thing that the article did not point out is the difference between regular niacin and flush-free niacin. Flush-free does NOT have the same positive impact on cholesterol in my opinion. By the way, the flushing should disappear after a couple of weeks, and until that time it only lasts 30-60 minutes. Yes, it’s irritating, but put up with it until your body adjusts and then judge whether niacin works for you.

  5. Kristin
    Reply

    It is common, if not universal to initially have ‘Niacin flushes’ when you first start taking it. I itched like crazy, turned bright red, hated it. But after a week the response had mostly disappeared, and after two weeks I had no flushing at all. I suspect you stopped before your body got used to it.

  6. Greg Sava
    Reply

    Thank you Joe and Terry for clearing this up. Whenever a new “finding” is announced warning of the danger of one unpatentable supplement or another, there is almost always something fishy about it. Why isn’t your clarification of these phony studies making headlines!!
    Also, who in their right mind would want to lower cholesterol and LDL below these already dangerously low levels? Maybe those levels were causing the adverse symptoms?

  7. Bob
    Reply

    Your statement “Liver enzyme monitoring is essential, especially with slow-release products” leads me to ask why especially slow-release?
    I’ve being taking the Slo-Niacin for several years (available at Costco), with more years prior to that on regular niacin. No problems. I actually asked my doctor when he was considering Liptor if I could try the niacin and we successfully ramped it up to 500mg 2X day.
    People’s Pharmacy response: We don’t know why slow-release niacin may be riskier, only that that has been reported previously.

  8. Marti V.
    Reply

    While on vacation I felt pretty good despite more than normal activities and lots of changes to diet and sleep. When I came back home, I realized I’d forgotten to pack my niacin. I started taking it again and after a few days started feeling tired and having digestive problems.
    After reading this article I’m going off niacin for a couple of weeks and see if that might be the problem. I have a severe adverse reaction to statins so that’s why I was going the niacin route.
    I think aside from a few basic supplements and my thyroid medication. Eating right and spending limited time in the sun each week are better than supplements, and certainly less expensive.

  9. AES
    Reply

    Hi–I took Slo-Niacin on the recommendation of some medical professionals/doctors that I am friends with. I had MASSIVE flushing that was actually a raised, hot skin rash all over my body, and had to take massive doses of Benadryl to counter these attacks
    This happened 3 times, with once going to the doctor… so I stopped taking it. Please beware this is a very scary reaction. The fact that I was taking it only a few times per week and was taking the slow-release formula does not mean that this will be be tolerated, or even beneficial, to everyone. I’m afraid of taking it because of my severe reactions, which are apparently relatively common.

  10. Carol
    Reply

    I think there’s an error in the wording of the first “unanswered question”. Should it be, “Do statins render *niacin*…?”
    PEOPLE’S PHARMACY RESPONSE:
    Thank you for catching our mistake! We posted that unanswered question at 4:30 am and were a little fuzzy at the time.
    it should have read (and is now corrected):
    Do statins (and/or ezetimibe) render niacin ineffective or more dangerous? (We are puzzled that the investigators and “experts” have not considered such a possibility.)

  11. WJR
    Reply

    I think you have a typo in your first (red ink) question – shouldn’t it read “statins…render NIACIN ineffective”? Good article. I take Vytorin (Zocor/Zetia 40/10) with excellent cholesterol results, but maybe with no improved life expectancy?!
    PEOPLE’S PHARMACY RESPONSE:
    Another alert reader. Thanks for catching our mistake!

  12. cara
    Reply

    I read the article about niacin the other day and laughed. Statins cause some of the same problems niacin does, yet they are pushed by doctors.

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