Hyperhomocysteinemia, vascular function and atherosclerosis: effects of vitamins

Cardiovasc Drugs Ther. 2002 Sep;16(5):391-9. doi: 10.1023/a:1022130217463.


Homocysteine is a metabolic product of methyl group donation by the amino acid methionine. Moderate elevation of plasma homocysteine (>15 microM) is most commonly caused by B-vitamin deficiencies, especially folic acid, B(6) and B(12). Genetic factors, certain drugs and renal impairment may also contribute. Homocysteine has several potentially deleterious vascular actions. These include increased oxidant stress, impaired endothelial function, stimulation of mitogenesis, and induction of thrombosis. Homocysteine also appears to increase arterial pressure. In humans, experimental induction of hyperhomocysteinemia by methionine loading rapidly causes profound impairment of endothelium-dependent dilatation in both resistance and conduit arteries. This endothelial dysfunction can be reversed by administration of antioxidants. Epidemiological evidence suggests that homocysteine acts as an independent risk factor for atherosclerosis, thrombosis and hypertension. Prospective studies have shown that elevated plasma homocysteine concentrations in the top quintile of the population (>12 microM) increase risk of cardiovascular disease by about 2-fold. There are currently no data available from randomized, controlled trials of the effects of lowering plasma homocysteine on atherothrombotic events. Nonetheless, it would seem appropriate to screen for and treat hyperhomocysteinemia in individuals with progressive or unexplained atherosclerosis. Folic acid and vitamins B(6) and B(12) are the mainstay of therapy. Treatment of moderately elevated plasma homocysteine in patients without atherosclerosis should be deferred until the completion of randomized outcome trials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Arteriosclerosis / drug therapy*
  • Avitaminosis / complications
  • Coronary Disease / drug therapy*
  • Folic Acid Deficiency / complications
  • Homocysteine / adverse effects
  • Homocysteine / metabolism
  • Humans
  • Hyperhomocysteinemia / drug therapy*
  • Hyperhomocysteinemia / etiology
  • Hyperhomocysteinemia / genetics
  • Hypertension / etiology
  • Kidney Failure, Chronic / complications
  • Methionine / adverse effects
  • Methionine / metabolism
  • Risk Factors
  • Thrombosis / etiology
  • Vitamin B 12 Deficiency / complications
  • Vitamin B 6 Deficiency / complications
  • Vitamins / therapeutic use*


  • Vitamins
  • Homocysteine
  • Methionine