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

Published online by Cambridge University Press:  09 March 2007

Tapan K. Basu ,
Neelam Makhani  and
Gary Sedgwick
Tapan K. Basu*
Affiliation:
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, T6G 2P5 Canada
Neelam Makhani
Affiliation:
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, T6G 2P5 Canada
Gary Sedgwick
Affiliation:
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, T6G 2P5 Canada
*
*Corresponding author: Dr Tapan K. Basu, fax +1 780 492 9130, email tbasu@afns.ualberta.ca
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Abstract

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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

NiacinHomocysteineMethionineCysteineB-vitamins
Type
Research Article
Information
British Journal of Nutrition , Volume 87 , Issue 2 , February 2002 , pp. 115 - 119
Copyright
Copyright © The Nutrition Society 2002

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