title: Niacin therapy in atherosclerosis.
abstract: OBJECTIVE
  Well designed, randomized, placebo-controlled studies show that niacin prevents cardiovascular disease and death. Unfortunately, early studies and anecdotal evidence have limited its use by promoting the opinion that niacin is intolerable and contraindicated in diabetes. As evidence mounts that treating multiple lipid risk factors decreases cardiovascular risk, the use of niacin in the treatment of atherosclerosis is experiencing somewhat of a renaissance.
  
  
  RESULTS
  Emerging clinical evidence shows that niacin is both safe and effective in diabetes. Niacin beneficially alters lipoprotein subclass distribution and when used in combination with statins, has additional effects on lipoproteins. Niacin selectively and directly inhibits hepatic diacylglycerol acyltransferase 2, but not diacylglycerol acyltransferase 1, thus inhibiting hepatic triglyceride synthesis and very low density lipoprotein secretion. The recent discovery and characterization of a membrane-bound nicotinic acid receptor (HM74) explains niacin's acute inhibition of adipocyte lipolysis, but the role of HM74 in lowering triglycerides is unclear. Niacin possesses antioxidant, antiinflammatory, and other beneficial effects on atherosclerosis unrelated to lipid lowering. Finally, niacin appears to activate nuclear transcription factors such peroxisome proliferator activator receptor gamma, possibly via prostaglandin metabolism.
  
  
  CONCLUSIONS
  New data indicate that niacin alters lipoprotein metabolism in novel ways, and mediates other beneficial nonlipid changes that may be atheroprotective. This information forms the rationale for the use of niacin in combination with agents possessing complementary mechanisms of action (e.g. statins) for cardiovascular risk reduction beyond that observed with monotherapy. Further research into the specific mechanisms of niacin may identify additional targets for future drug development.
authors.affiliation: Endocrinology Section, VA Long Beach Healthcare System, Department of Medicine, University of California, Irvine, California, USA.
authors.forename: C Daniel
authors.initials: CD
authors.lastname: Meyers
authors.forename: Vajinath S
authors.initials: VS
authors.lastname: Kamanna
authors.forename: Moti L
authors.initials: ML
authors.lastname: Kashyap
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004359:Drug Therapy, Combination; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology; D009525:Niacin / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000893:Anti-Inflammatory Agents; D009525:Niacin; D008148:Lovastatin