CHAPTER 39: Pharmacological Use of Niacin for Lipoprotein Disorders

Niacin administered orally in daily doses between 500 and 3000 mg has been used since 1955 to improve blood lipoprotein levels. Niacin is the most effective currently marketed drug for raising high density lipoprotein cholesterol levels and it lowers levels of triglyceride, low density lipoprotein cholesterol and lipoprotein(a). In 2003 niacin was discovered to interact with a G-protein-coupled receptor, GPR109A, whose natural ligand is β-hydroxybutyrate. While this receptor accounts for anti-lipolysis and for the flushing side effect of niacin, the lipoprotein-modifying effects appear not to depend on GPR109A, but rather on incompletely characterized hepatic effects. Niacin-induced flushing can be surmounted in most patients by pretreatment with aspirin, dosing with food, and reliance on the tachyphylaxis of flushing with regular dosing over weeks to months. Clinical trials evaluating niacin's effect on quantitative measures of atherosclerosis in human have achieved almost uniformly beneficial results, but most trials were small and used niacin in combination with other drugs. One large and five small randomized trials have also suggested benefit for clinical cardiovascular outcomes, but the most recent large randomized trial did not. There are several possible explanations for the discrepancy in clinical event reductions among these trials.