Niacin: A Natural Treatment for High Cholesterol Not to be Dismissed
Niacin (vitamin B3) was one of the first drugs that was ever used to improve cholesterol levels. It was frequently used with good results before the introduction of statin medications. Now it is common for conventional medical doctors to tell patients to stop taking niacin and take statins instead.
When Statins for High Cholesterol Are Patient Incompatible
In 2019, Lipitor was the most prescribed drug in the United States and is still considered the standard of care for anyone with an LDL over 100. Typical statins (lipid-lowering medications) include Crestor (rosuvastatin), Lipitor (atorvastatin), Zocor (simvastatin), Livalo (ptivistatin), Mevacor (lovastatin), and pravastatin (Pravachol). Statins work by blocking an enzyme called HMGCoA reductase. Unfortunately, this mechanism also blocks the body’s production of coenzyme Q10. About 25% of patients are statin intolerant or do not fill their prescriptions. The most common symptoms I see are tendinitis, muscle pain, joint pain, elevated blood sugar, and cognitive difficulties. Recent studies point to less benefits from statins in the elderly.
In patients who do not tolerate statins well I have had good results with lowering the dose of the statin medication and adding niacin. I sometimes use niacin alone or with a number of other natural molecules and nutraceuticals. Niacin does not come without side effects but when used under guided medical supervision these side effects can be mitigated.
Limitations of Cholesterol Trials
So why are medical doctors telling patients to stop niacin? There have been two studies published in prominent medical journals since 2011. I will tell you why they had serious faults. The Atherothrombosis Intervention and Metabolic Syndrome with Low HDL and High Triglycerides and Impact on Global Health Outcomes Study (AIM-HIGH) published in 2011 and the Heart Protection Study-2 Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) published in 2014 concluded that adding niacin to his statin did not provide any clinical benefit compared to statin alone. It is as if both trials were designed to make niacin look bad. There are major limitations to these two trials. 1, 2, 3.
- Patients were pretreated with statins and both cases had baseline LDLs averaging ~72 mg/dL which is already at target. Yes, that is correct, their LDLs were already averaging low 70s. The biggest changes to risk occur when the patient has high numbers to start with.
- The placebo group received an active placebo (50 g of niacin), and more patients in the placebo group received ezetimibe (Zetia). Zetia is a cholesterol drug I like that blocks cholesterol absorption in the intestine and thus lowering blood levels. So yes, the placebo group got more treatment, making the group receiving the niacin look worse than it should have.
- Subjects were not good candidates for niacin in the first place because they had normal triglycerides, HDL and LDL. The main actions of niacin are lowering LDL, decreasing triglycerides, and increasing HDL. If the patient just has a high LDL I typically will not use niacin.
- The dose of niacin was much smaller than in previous positive studies (2 g vs 3-4 g)
- The placebo group received a higher mean statin dose
- In my view the study was stopped prematurely (only three years)
- Superko HR, Zhao XQ, Hodis HN, Guyton JR. Niacin and heart disease prevention: Engraving its tombstone is a mistake. J Clin Lipidol. 2017 Nov-Dec;11(6):1309-1317.
- Zeman M, Vecka M, Perlík F, Hromádka R, Staňková B, Tvrzická E, Žák A. Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place? Med Sci Monit. 2015 Jul 25;21:2156-62.
- Houston M, Pizzorno J. “Niacin Doesn’t Work and Is Harmful!” Proclaim the Headlines. Yet Another Highly Publicized Questionable Study to Discredit Integrative Medicine. Integr Med (Encinitas). 2014 Oct;13(5):8-11.
HPS2 THRIVE Trial:
- In this study sponsored by Merck, the maker of simvastatin, baseline lipids were not high enough (mean LDL ~63 mg/dL) to substantiate the use of niacin. These patients had even lower levels of LDL than the AIM-HIGH study.
- Subjects were pretreated with statins. So yes, rather than starting off fresh with a statin and niacin together compared to statin alone or compared to niacin alone, these patients had been rolling along on statins already.
- Laropiprant was used with niacin. Laropiprant can counteract the beneficial effects of niacin. Laropiprant has actions that counteract the beneficial effects of niacin as well as possible negative cardiovascular side effects independent of niacin.
- There was no niacin-only group.
- In addition, a disproportionate number of Chinese subjects were included in the study. A genetic predisposition to side effects from niacin with laropiprant may occur in this population.4
In both studies, simvastatin was used, there was no niacin monotherapy group, inclusion criteria have been questioned, and positive results occurred in some subgroups that were not discussed. I do not believe firm conclusions about niacin should be made based on these two studies, especially considering their flaws. This is sad when considering niacin has been shown in other studies to be beneficial in reversing plaque, lowering cholesterol, and reducing risk. The Coronary Drug Project (CDP) the Stockholm Trial, CLAS, HATS, ARBITER-2, ARBITER-6, AFREGS all demonstrated improvements in nonfatal heart attack, plaque regression, and incidence of cardiovascular events.
The Benefits of Natural Treatment for High Cholesterol
It is not just the limitations of these two trials that are important to consider. Niacin has other benefits for the vascular system. Niacin can improve endothelial function and make arteries more resilient by decreasing oxidative stress and inflammation. Some people just cannot handle statins or intestinal cholesterol blockers like Zetia. By the way, I am not against cholesterol drugs. I infrequently use them along with other treatments on my patients.
What is sad is that in the conventional model, patients who cannot tolerate the conventional medications would not be treated at all. The exception is when the patient has good insurance and the PSK 9 inhibitor gets approved. This is an injectable monoclonal antibody that blocks cholesterol production that cost between $500.00 and 1,000 per month.
I also think it is important to compare the benefits and risks of niacin as compared to a statin drug. The best use of niacin may not be when combined with a statin drug. Niacin is appropriate for statin intolerant patients but especially those with low HDL, high triglycerides, lipoprotein a, and elevated small LDL lipoprotein particle number.
Side Effects of Niacin for High Cholesterol
The side effects of niacin depend on the dose, but at 1,000 mg and below, side effects are minimal. The main side effect is increased blood flow to the skin causing skin flushing. This feeling is like a mild sunburn that lasts for a few minutes. If taken with food this typically goes away after a few weeks.
At higher doses side effects can include elevated uric acid, increases in homocysteine, slight increases in blood sugar, and increased liver enzymes when doses get up around 2000 mg a day or when used with a statin.