If youre taking high doses of niacin supplements (vitamin B3) in hopes of preventing heart disease, new results from a large international clinical trial of prescription doses of niacin might give you second thoughts. The study, dubbed HPS2-THRIVE, found no benefit compared to placebo, and raised red flags about potentially serious side effects. A new subanalysis of a similar US niacin trial, AIM-HIGH, was published alongside the findings in the New England Journal of Medicine, confirming the incidence of side effects.
The cumulative data from two major studies suggest no added benefit of adding high dose extended-release niacin in patients treated with statin drugs and increased rates of adverse events, says Alice H. Lichtenstein, DSc, director of Tufts HNRCA Cardiovascular Nutrition Laboratory.
DOUBLE DISAPPOINTING RESULTS: Niacin has long been known to affect blood levels of lipids, raising hopes that by boosting good HDL cholesterol and modestly lowering bad LDL it could combat cardiovascular disease. But the last major trial of niacins effectiveness was conducted in the 1960s, before todays cholesterol-lowering statin medications. The two new trials were designed to test whether niacin could help prevent heart disease and stroke among high-risk patients already treated with statins.
The AIM-HIGH trial, sponsored by the National Institutes of Health, was stopped early because there was no evidence of benefits and continuing was deemed futile. Those disappointing results were published in 2011; the new report focused on side effects, with serious adverse events including infection and bleeding associated with niacin.
The HPS2-THRIVE trial, funded by the drug company Merck, followed 25,673 patients for almost four years. Half got a placebo, while half were randomly assigned to 2,000 milligrams of niacin plus a drug to counter the flushing side effects common with niacin. (Non-prescription niacin supplements range in dose from 100 to 1,000 milligrams.) Now that trial, too, has reported no significant effect on the incidence of major vascular events. That lack of benefit was coupled with greater risk of serious side effects involving the gastrointestinal system, muscle and skeletal system, and skin, as well as infection.
SIDE-EFFECTS CONCERNS: During the preliminary run-in phase of the HPS2-THRIVE trial, side effects caused one-third of volunteers to drop out. Patients given niacin were also 32% more likely to be diagnosed with diabetes, while those in the niacin group already with diabetes suffered 55% more serious problems with disease management. The HPS2-THRIVE trial also reported a 9% greater mortality risk among those taking niacin.
In an editorial accompanying the new results and subanalysis, Donald M. Lloyd-Jones, MD, ScM, of Northwestern University commented, On the basis of the weight of available evidence showing net clinical harm, niacin must be considered to have an unacceptable toxicity profile for the majority of patients, and it should not be used routinely. Although higher HDL cholesterol levels are associated with better outcomes, it is time to face the fact that increasing the HDL cholesterol level in isolation seems unlikely to offer the same benefit.