Lipid Disorders and Vitamin B3

The common vitamin B3 (niacin) is an accepted medical treatment for high cholesterol. Niacin helps reduce levels of LDL ("bad") cholesterol and triglycerides, while raising levels of HDL ("good") cholesterol.

Niacin also lowers levels of lipoprotein A, another risk factor for atherosclerosis. Long-term use of niacin has been shown to significantly reduce death rates from cardiovascular disease. Niacin appears to be a safe and effective treatment for high cholesterol in people with diabetes as well, and (contrary to previous reports) does not seem to raise blood sugar levels.

Niacin may be prescribed in the form of Niacor and related medications.

Niacin can have a number of favorable effects on serum (blood) lipids--it reduces bad cholesterol, increases good cholesterol, and reduces triglycerides. It probably reduces levels of bad cholesterol by inhibiting cholesterol production in the liver.

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Several well-designed, double-blind, placebo-controlled studies have found that niacin reduced LDL cholesterol by approximately 10% and triglycerides by 25%, and raised HDL cholesterol by 20%-30%.^22-27 Niacin also lowers levels of lipoprotein A—another risk factor for atherosclerosis—by about 35%. Furthermore, long-term use of niacin has been shown to significantly reduce death rates from cardiovascular disease.²⁸

Niacin appears to be a safe and effective treatment for high cholesterol in people with diabetes as well, and (contrary to previous reports) does not seem to raise blood sugar levels.²⁹ Unfortunately, niacin, if taken in sufficient quantities to lower cholesterol, can cause an annoying flushing reaction and occasionally liver inflammation.³⁰ Close medical supervision is essential when using niacin to lower cholesterol.

Combining high-dose niacin with statin drugs (the most effective medications for high cholesterol) further improves lipid profile by raising HDL (“good”) cholesterol.^149-151 Unfortunately, there are real concerns that this combination therapy could cause a potentially fatal condition called rhabdomyolysis.

A growing body of evidence, however, suggests that the risk is relatively slight in individuals with healthy kidneys. Furthermore, even much lower doses of niacin than the usual dose given to improve cholesterol levels (100 mg versus 1,000 mg or more) may provide a similar benefit.¹⁵² At this dose, the risk of rhabdomyolysis should be decreased. Nonetheless, it is not safe to try this combination except under close physician supervision.

When used as therapy for a specific disease, niacin, niacinamide, and inositol hexaniacinate are taken in dosages much higher than nutritional needs, about 1 to 4 g daily. (See Requirements/Sources in the Vitamin B3 article.) Because of the risk of liver inflammation at these doses, medical supervision is essential.

Combining high-dose niacin with statin drugs (the most effective medications for high cholesterol) further improves lipid profile by raising HDL (“good”) cholesterol. There are concerns that this combination therapy could cause a potentially fatal condition called rhabdomyolysis. A growing body of evidence, however, suggests that the risk is relatively slight in individuals with healthy kidneys. Furthermore, even much lower doses of niacin than the usual dose given to improve cholesterol levels (100 mg versus 1,000 mg or more) may provide a similar benefit. At this dose, the risk of rhabdomyolysis should be decreased.

Many people experience an unpleasant flushing sensation and headache when they take niacin. These symptoms can usually be reduced by gradually increasing the dosage over several weeks or by using slow-release niacin. However, slow-release niacin appears to be more likely to cause liver inflammation than other forms. Inositol hexaniacinate may also cause less flushing than plain niacin, and if you take an aspirin along with niacin, the flushing reaction will usually decrease.

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Safety Issues

When taken at a dosage of more than 100 mg daily, niacin frequently causes annoying skin flushing, especially in the face, as well as stomach distress, itching, and headache.⁶⁵ In studies, as many as 43% of individuals taking niacin quit because of unpleasant side effects.⁴⁴

A more dangerous effect of niacin is liver inflammation. Although some reports suggest that it occurs most commonly with slow-release niacin, it can occur with any type of niacin when taken at a daily dose of more than 500 mg (usually 3 g or more). Regular blood tests to evaluate liver function are, therefore, mandatory when using high-dose niacin (or niacinamide or inositol hexaniacinate). This reaction almost always goes away when niacin is stopped. Note: Contrary to claims on some manufacturers' websites, there is no reliable evidence that inositol hexaniacinate is safer than ordinary niacin.

As noted above, a single dose of 2.5 to 5 grams of niacin (used in the vain hope of passing a urine drug test despite the presence of drugs in the system) can cause life-threatening disturbances in body function.⁷⁰ Since this range includes the high-end of the dosage used for treating cholesterol, presumably people who gradually work up to taking several grams of niacin daily can accommodate it in a way that those who take it suddenly cannot.

If you have liver disease, ulcers (presently or in the past), gout, or drink too much alcohol,⁴⁵ do not take high-dose niacin except on medical advice.

While there has been some concern that niacin may raise blood sugar levels in diabetics, the effect appears to be slight, and it carries little, if any, clinical significance.^46,56,71

Combining high-dose niacin with statin drugs (the most effective medications for high cholesterol) further improves cholesterol profile by raising HDL (“good”) cholesterol.^52-54 Unfortunately, there are real concerns that this combination therapy could cause a potentially fatal condition called rhabdomyolysis.

A growing body of evidence, however, suggests that the risk is relatively slight in individuals with healthy kidneys. Furthermore, even much lower doses of niacin than the usual dose given to improve cholesterol levels (100 mg versus 1,000 mg or more) may provide a similar benefit.⁵⁵ At this dose, the risk of rhabdomyolysis should be decreased.

Nonetheless, it is not safe to try this combination except under close physician supervision. Rhabdomyolysis can be fatal.

Another potential drug interaction involves the anticonvulsant drugs carbamazepine and primidone. Niacinamide might increase blood levels of these drugs, possibly requiring reduction in drug dosage.⁵⁰ Do not use this combination except under physician supervision.

The maximum safe dosage of niacin for pregnant or nursing women has been set at 35 mg daily (30 mg if 18 years old or younger).⁵¹

Interactions You Should Know About

If you are taking:

• Cholesterol-lowering drugs in the statin family, niacin might offer potential benefits; however, there are real dangers to this combination. Do not try it except under physician supervision.
• The antituberculosis drug isoniazid (INH): You may need extra niacin.
• Anticonvulsant drugs such as carbamazepine or primidone: Do not take niacinamide except under physician supervision.

If you drink alcohol excessively:

• Do not take niacin except under physician supervision.

22. Illingworth DR, Stein EA, Mitchel YB, et al. Comparative effects of lovastatin and niacin in primary hypercholesterolemia. A prospective trial. Arch Intern Med. 1994;154:1586-1595.
23. Guyton JR, Goldberg AC, Kreisberg RA, et al. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol. 1998;82:737-743.
24. Vega GL, Grundy SM. Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphalipoproteinemia. Arch Intern Med. 1994;154:73-82.
25. Lal SM, Hewett JE, Petroski GF, et al. Effects of nicotinic acid and lovastatin in renal transplant patients: a prospective, randomized, open-label crossover trial. Am J Kidney Dis. 1995;25:616-622.
26. Elam MB, Hunninghake DB, Davis KB, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients With diabetes and peripheral arterial disease. The ADMIT Study: a randomized trial. JAMA. 2000;284:1263-1270.
27. Morgan JM, Capuzzi DM, Guyton JR, et al. Treatment effect of Niaspan, a controlled-release niacin, in patients with hypercholesterolemia: a placebo-controlled trial. J Cardiovasc Pharmacol Ther. 1996;1:195-202.
28. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8:1245-1255.
29. Elam MB, Hunninghake DB, Davis KB, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease. The ADMIT Study: a randomized trial. JAMA. 2000;284:1263-1270.
30. Crouse JR III. New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug. Coron Artery Dis. 1996;7:321-326.
149. Jacobson TA, Amorosa LF. Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. Am J Cardiol. 1994;73:25D-29D.
150. Kashyap ML, Evans R, Simmons PD, et al. New combination niacin/statin formulation shows pronounced effects on major lipoproteins and is well tolerated. J Am Coll Cardiol. 2000;35(suppl A):326.
151. Wolfe ML, Vartanian SF, Ross JL, et al. Safety and effectiveness of Niaspan when added sequentially to a statin for treatment of dyslipidemia. Am J Cardiol. 2001;87:476-479.
152. Wink J, Giacoppe G, King J. Effect of very-low-dose niacin on high-density lipoprotein in patients undergoing long-term statin therapy. Am Heart J. 2002;143:514-518.