Volume 87, Issue 2, February (2002), pp. 115-119 © The Author 2002
doi:10.1079/BJN2001486

Medline/PubMed Citation | Related Articles in PubMed | Download to Citation Matcher  

Niacin (nicotinic acid) in non-physiological doses causes hyperhomocysteineaemia in Sprague–Dawley rats

Tapan K.Basu*, Neelam Makhani and Gary Sedgwick
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, T6G 2P5 Canada

 (Received 22 September 2000–Revised 17 July 2001–Accepted 6 August 2001)

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 1000 mg/kg diet (compared to 30 mg/kg in the control diet) for up to 3 months. Supplementation with niacin (1000 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.

Keywords:
Niacin: Homocysteine: Methionine: Cysteine: B-vitamins