Niacin For Raising HDL Cholesterol

Niacin. MediaForMedical/UIG/Getty Images

Taking niacin - also known as vitamin B3 - is perhaps the most reliable method currently available for increasing HDL cholesterol levels (“good” cholesterol). However, the use of niacin for this purpose is not simple or straightforward, and in recent years researchers have even questioned whether increasing HDL cholesterol with niacin improves clinical outcomes.

    Niacin and Blood Lipid Levels

    It is important to know that “niacin” actually has two different forms - nicotinic acid and nicotinamide - and of the two only nicotinic acid has an appreciable effect on blood lipids. When nicotinic acid is taken in high doses, typically there is a modest reduction in LDL cholesterol (“bad” cholesterol), but a much more impressive increase in HDL cholesterol - HDL often goes up by as much as 30 - 35%. These changes in lipid levels are not seen with the nicotinamide form of niacin.

    The doses of nicotinic acid needed to effect lipid levels are much higher than the dose needed to prevent vitamin B3 deficiency (which is only 14 - 18 mg per day). Typically, the amount of nicotinic acid required to increase HDL levels is scores of times higher than that - between 1,000 and 3,000 mg per day.

    Side Effects of Niacin

    Taking nicotinic acid in such high doses presents a challenge.

    When taken in its usual, crystalline, rapid-acting form, high-dose nicotinic acid typically produces significant flushing of the skin, often accompanied by itching, tingling and burning, as well as nausea. These symptoms can last from a few minutes to a few hours, and are frequently severe enough that the drug simply cannot be tolerated.

    These flushing-related symptoms can be reduced to some extent by taking aspirin 30 minutes before taking the nicotinic acid. Furthermore, certain sustained-release niacin preparations (described below) can also help minimize these symptoms.

    Other important side effects of high-dose niacin include an increase in blood glucose levels in patients with diabetes or pre-diabetes, an increase in uric acid that may cause acute gout attacks in people who have gout, and a drop in blood pressure in patients taking certain kinds of medicine for hypertension. Liver damage is also possible, especially, unfortunately, with some of the sustained-release forms of nicotinic acid that minimize flushing.

    Niacin Preparations

    Over-the-counter (OTC) niacin: OTC niacin is not FDA-regulated in the United States, so it is often impossible to know for sure what kind of niacin these preparations contain. Most niacin sold as “no-flush” probably contains only nicotinamide (which does not benefit blood lipids), and not nicotinic acid.

    OTC sustained release nicotinic acid preparations reduce the risk of skin flushing, and can increase HDL levels - but some of these preparations have an especially high incidence of liver toxicity and should be avoided. (The OTC preparation Slo-niacin appears to be relatively safe in regard to liver problems, however.)

    Prescription niacin: The prescription drug Niaspan is an FDA regulated, slow-release form of nicotinic acid that minimizes skin flushing and is not associated with increased liver toxicity. Most physicians who ask their patients to take niacin to raise their HDL levels will recommend Niaspan, if the patient can afford it. It is much more expensive than OTC niacin preparations.

    When Do Doctors Prescribe Niacin?

    Niacin - in the form of nicotinic acid - is most often prescribed for patients who have known coronary artery disease (CAD) and who also have low HDL cholesterol levels despite being on statin therapy.

    When crystalline (rapid-acting) nicotinic acid is prescribed, generally the patient starts with 100 mg is three times a day, and the dose is gradually increased to at least 300 - 500 mg three times a day - if the drug is tolerated. When Niaspan (the prescription slow-release formulation) is used, the drug can be taken once per day. Niaspan is started at 1000 mg, and is gradually increased to 2000 mg per day, if tolerated. Higher doses are occasionally necessary to substantially increase HDL levels. Niaspan is said to be tolerated better if taken at bedtime.

    Taking 325mg or 650 mg of aspirin 30 minutes prior to taking nicotinic acid often reduces flushing, and increases a person’s chances of tolerating the drug.

    How Useful Is Niacin?

    The usefulness of nicotinic acid in improving clinicical outcomes is more questionable than it appeared to be just a few years ago. The current consensus is that nicotinic acid is more effective than other non-statin drugs in increasing HDL levels - but its ability to improve cardiovascular outcomes when added to a statin drug is unproven.

    In one randomized clinical trial in patients with CAD (the ARBITER–6 HALTS trial), patients treated with a statin + niacin had better clinical outcomes than patients treated with statin + ezetimibe (Zetia, Vitorin). But in a more recent randomized trial which enrolled similar patients (the AIM-HIGH trial), there was no benefit to adding nicotinic acid to statin therapy. Further, in the AIM-HIGH trial there appeared to be more strokes in the patients randomized to nicotinic acid (though in the final analysis the increase in strokes was not statistically significant). The results of the AIM-HIGH trial have substantially dampened the enthusiasm for nicotinic acid among most physicians.

    In fact, the AIM-HIGH trial has thrown even more cold water on the assumption that increasing HDL is always a good thing to do.

    The Bottom Line

    It is probably reasonable for doctors to consider adding nicotinic acid to statin therapy in patients with CAD whose HDL cholesterol levels remain very low. However, the benefit of doing so must be regarded as unproven. And indeed, the 2013 guidelines on cholesterol from the American Heart Association and the American College of Cardiology do not recommend adding any drugs (including niacin) to statin therapy, in patients who are taking statins.


    Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009; 361:2113.

    AIM-HIGH Investigators, Boden WE, Probstfield JL, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011; 365:2255.

    Continue Reading