title: Niacin (nicotinic acid) in non-physiological doses causes hyperhomocysteineaemia in Sprague-Dawley rats.
abstract: Niacin (nicotinic acid) in its non-physiological dose level is known to be an effective lipid-lowering agent; its potential risk as a therapeutic agent, however, has not been critically considered. Since niacin is excreted predominantly as methylated pyridones, requiring methionine as a methyl donor, the present study was undertaken to examine whether metabolism of the amino acid is altered in the presence of large doses of niacin. Male Sprague-Dawley rats were given a nutritionally adequate, semi-synthetic diet containing niacin at a level of either 400 or 1000mg/kg diet (compared to 30mg/kg in the control diet) for up to 3 months. Supplementation with niacin (1,000 mg/kg diet) for 3 months resulted in a significant increase in plasma and urinary total homocysteine levels; this increase was further accentuated in the presence of a high methionine diet. The hyperhomocysteineaemia was accompanied by a significant decrease in plasma concentrations of vitamins B6 and B12, which are cofactors for the metabolism of homocysteine. The homocysteine-raising action of niacin, in particular, has an important toxicological implication, as hyperhomocysteineaemia is considered to be an independent risk factor for arterial occlusive disease. The niacin-associated change in homocysteine status may be an important limiting factor in the use of this vitamin as a lipid-lowering agent.
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada. tbasu@afns.ualberta.ca
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Basu
authors.forename: Neelam
authors.initials: N
authors.lastname: Makhani
authors.forename: Gary
authors.initials: G
authors.lastname: Sedgwick
mesh_terms: D000818:Animals; D019587:Dietary Supplements / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D020138:Hyperhomocysteinemia / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D008099:Liver / Q000254:growth & development; D008297:Male; D008715:Methionine / Q000097:blood; D009525:Niacin / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
chemical_list: D009525:Niacin; D025101:Vitamin B 6; D008715:Methionine; D014805:Vitamin B 12