Nicotinic Acid: A Review of Its Clinical Use in the Treatment of Lipid Disorders

Abstract

Nicotinic acid (niacin) is a water-soluble vitamin widely used for the treatment of lipid disorders. In pharmacologic doses (1 g or more/day), alone or in combination with other lipid-lowering drugs, nicotinic acid lowers very low-density (VLDL) and low-density lipoprotein (LDL) levels, while concurrently increasing high-density lipoprotein (HDL) levels. It may reduce long-term mortality in patients with known coronary artery disease and may slow or reverse the progression of atherosclerosis. A major consideration against using nicotinic acid is the occurrence of frequent, bothersome, adverse reactions such as cutaneous flushing, skin rash, and gastric upset. Careful dosing titration may, however, minimize these effects. The beneficial effects, taken together with the low cost of nicotinic acid therapy and the relative freedom from serious side effects, have made nicotinic acid the agent of choice for the treatment of many patients with hyperlipidemia.

Nicotinic acid and DP1 blockade: studies in mouse models of atherosclerosis

“…Whereas the effects of nicotinic acid on circulating lipids and lipoprotein particles have been well studied both clinically and in multiple preclinical species ( 1,11,12,27 ), few studies in preclinical species address the potential effect of nicotinic acid on plaque. In an 8 week study of male rabbits on a cholesterol-enriched (2% w/w) diet, the addition of nicotinic acid (0.4% w/w) reduced serum, liver, and aortic cholesterol (by 60%, 77%, and 64%, respectively) compared with a cholesterol diet alone ( 28 ).…”

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triglycerides (TGs) and decreases cardiovascular events in high-risk patients ( 1,2 ). Despite demonstrated effi cacy in cardiovascular disease, nicotinic acid is poorly tolerated and underused in clinical practice, largely due to the adverse effect of fl ushing, i.e., cutaneous vasodilation and attendant discomfort in the face, neck, trunk, and arms ( 2 ).

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Effects of cigarette smoking and its cessation on lipid metabolism and energy expenditure in heavy smokers.

“…Intracellular cycling represents a thermogenic process that is relatively benign in terms of systemic metabolism, the only systemic consequence being release of glycerol. In contrast, extracellular recycling also involves entry ofFFA into the systemic circulation and reesterification in the liver, which will tend to increase hepatic VLDL-triglyceride (TG) production and secondarily alter plasma lipoproteins (35)(36)(37)(38)(39)(40)(41).…”

“…Although it certainly would not be desirable from a general health point of view to administer a lipolysis inhibitor in order to allow people to continue smoking with less atherogenic risk, the question may have practical relevance for use ofnicotine patches. Niacin is believed to increase adipocyte reesterification of FFA and thereby reduce FFA release (38). Ifthis mechanism ofaction ofniacin can be confirmed, it might in principle maintain the net reesterification rate induced by nicotine but redirect it to the adipocyte and away from the liver.…”

“…In several dyslipi-demic conditions, including diabetes (35)(36)(37), increased delivery of FFA to the liver and hepatic reesterification has been proposed to be the cause of increased VLDL triglyceride secretion and secondary alterations in serum lipids. Conversely, the mechanism by which niacin improves lipids in humans is believed to be through inhibition of lipolysis (38)(39)(40). Hepatic reesterification of FFA may therefore link the thermogenic and atherogenic effects of CS.…”