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

Br J Nutr. 2002 Feb;87(2):115-9. doi: 10.1079/BJN2001486.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Supplements / toxicity
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / chemically induced*
  • Hyperhomocysteinemia / physiopathology
  • Liver / growth & development
  • Male
  • Methionine / blood
  • Niacin / toxicity*
  • Organ Size / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Vitamin B 12 / blood
  • Vitamin B 6 / blood
  • Weight Gain / drug effects


  • Niacin
  • Vitamin B 6
  • Methionine
  • Vitamin B 12