MECHANISM OF ACTION
Nicotinic acid in gram doses, but not nicotinamide, lowers serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL) and triglycerides. High-dose nicotinic acid also increases serum levels of high-density lipoprotein cholesterol (HDL-C) and decreases serum levels of lipoprotein (a) [Lp(a)] and apolipoprotein B-100 (Apo B). The mechanism of the antihyperlipidemic action of nicotinic acid is not well understood. It is thought that this effect is mediated, in part, via decreases in the release of free fatty acids from adipose tissue, thereby decreasing the influx of free fatty acids into the liver, the hepatic reesterification of free fatty acids and the rate of production of hepatic very low-density lipoprotein (VLDL). A decrease in the hepatic production of VLDL reduces the level of circulating VLDL available for conversion to LDL. Another hypothesis holds that nicotinic acid directly inhibits hepatic synthesis or secretion of apolipoprotein B-containing lipoproteins. Still another hypothesis holds that nicotinic acid has the potential to cause a generalized inhibition of synthetic function in the liver. This mechanism may be considered a manifestation of nicotinic acid hepatotoxicity resulting in decreased LDL-cholesterol. However, this liver-damaging hypothesis would not explain the HDL-elevating effect of nicotinic acid. The mechanism by which nicotinic acid elevates HDL is unknown.
High dose nicotinic acid has been found to significantly decrease cardiovascular and cerebrovascular events in those with coronary heart disease. It is thought that this effect is due, in part, to nicotinic acid's antihyperlipidemic activity.