Smoking and plasma homocysteine

Eur Heart J. 2002 Oct;23(20):1580-6. doi: 10.1053/euhj.2002.3172.


Background: Smoking is known to be associated with an increased plasma homocysteine level. Both are associated with an increased risk of cardiovascular disease. B-vitamins modulate plasma homocysteine levels.

Aims: To investigate the relationships between smoking, plasma homocysteine, nutrient levels and risk of cardiovascular disease.

Methods: The European Concerted Action Project case control study of 750 cases and 800 age- and sex-matched controls aged less than 60 years from 19 centres in 10 European countries.

Results: Smokers were at increased risk of vascular disease. This risk was greatly increased in the presence of a raised plasma homocysteine; cigarette smokers with a plasma homocysteine above 12 micromol.l(-1) had a 12-fold increased risk of cardiovascular disease (OR 12.4 95% CI 7.3 to 21.2) compared with non-smokers with a normal plasma homocysteine. In both cases and controls the current smokers had a higher plasma homocysteine level than the never smokers (11.7 micromol.l(-1) vs 10.07 micromol.l(-1), P<0.05 cases; 9.90 micromol.l(-1) vs 9.53 micromol.l(-1)P value non significant controls). Current smokers tended to have lower levels of folate, and vitamin B6 and vitamin B12 than never smokers. The risk of cardiovascular disease associated with smoking was not significantly altered by adjustment for levels of B-vitamins using a conditional regression model (OR for current smoker > 8.19, after adjustment for B6, B12, folate OR 7.09).

Conclusions: This case control study suggests that smokers with high plasma homocysteine are at greatly increased risk of cardiovascular disease and should therefore be offered intensive advice to help them cease smoking. They also have reduced levels of those B-vitamins (folate, vitamin B6 and vitamin B12) that modulate homocysteine metabolism. While this finding may reflect a direct effect of smoking or reduced B-vitamin intake, supplementation of these nutrients may be appropriate in smokers with high homocysteine levels.

Publication types

  • Comment

MeSH terms

  • Adult
  • Cardiovascular Diseases / etiology
  • Case-Control Studies
  • Female
  • Folic Acid / blood
  • Homocysteine / blood*
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Smoking / adverse effects*
  • Vitamin B 12 / blood
  • Vitamin B 6 / blood


  • Homocysteine
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12