Nicotinic acid: the broad‐spectrum lipid drug. A 50th anniversary review

Abstract

Nicotinic acid has, like the Roman God Janus, two faces. One is the vitamin. The other is the broad-spectrum lipid drug. The Canadian pathologist Rudolf Altschul discovered 50 years ago that nicotinic acid in gram doses lowered plasma levels of cholesterol. From the point of view of treatment of the dyslipidaemias that are risk factors for clinical atherosclerosis nicotinic acid is a miracle drug. It lowers the levels of all atherogenic lipoproteins--VLDL and LDL with subclasses as well as Lp(a)--and in addition it raises more than any other drug the levels of the protective HDL lipoproteins. Trials have shown that treatment with nicotinic acid reduces progression of atherosclerosis, and clinical events and mortality from coronary heart disease. The new combination treatment with statin-lowering LDL and nicotinic acid-raising HDL is reviewed. A basic effect of nicotinic acid is the inhibition of fat-mobilizing lipolysis in adipose tissue leading to a lowering of plasma free fatty acids, which has many metabolic implications which are reviewed. The very recent discovery of a nicotinic acid receptor and the finding that the drug stimulates the expression of the ABCA 1 membrane cholesterol transporter have paved the way for exciting and promising new 50 years in the history of nicotinic acid.

Antagonism of the prostaglandin D 2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans

“…This increase was transient; the plasma PGD 2 returned to near baseline levels at 30 min (data not shown). Administration of aspirin alone at 200 mg͞kg had no effect on plasma PGD 2 , whereas when given 30 min before the administration of NA, it completely blocked the increase in PGD 2 (Fig. 2 A).…”

“…Studies in humans have shown that the plasma concentrations of PGD 2 , PGI 2 , and thromboxane A 2 (TXA 2 ) are elevated by NA treatment (16)(17)(18)(19)(20). Because the magnitude of the reported PGD 2 increase far exceeds those reported for PGI 2 and TXA 2 , we focused on the potential role that PGD 2 might play in NA-induced vasodilation and examined whether one or both of the two PGD 2 receptors, DP1 and DP2, might play a role in vasodilation through use of specific receptor agonists. Administration of BW245C, a high-affinity agonist of human and mouse DP1 that is inactive at DP2 (25,26), caused a dosedependent increase of perfusion in the mouse ear (data not shown).…”

“…aspirin ͉ prostaglandin D2 receptor 1 antagonist ͉ MK-0524 ͉ niacin ͉ flushing N icotinic acid (NA), sometimes called niacin, is a watersoluble B vitamin that has been used to treat dyslipidemia for almost 50 years (1,2). Used in high doses, it reduces plasma low-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a) and increases high-density lipoprotein cholesterol and apolipoprotein A-I (3,4).…”

“…These results led to the hypothesis that PGD 2 generation in the skin drives NA-induced flushing (17). However, because NA treatment also increases other prostanoids (16,(18)(19)(20) [for example, PGI 2 (16), which is also vasodilatory (21)], the prostanoid(s) responsible for flushing in humans remains to be unequivocally determined.…”

Discovery of a Potent Nicotinic Acid Receptor Agonist for the Treatment of Dyslipidemia

“…[1][2][3][4][5][6][7] Studies have demonstrated that nicotinic acid is able to reduce the rate of nonfatal myocardial infarction (MI) and decrease total mortality of patients with a previous history of heart disease. 8,9 In combination with statins, nicotinic acid provided better therapeutic benefit than taking statins alone.…”