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Homocysteine in Health and Disease
- Ian Graham, FRCPI, FCCP
- Royal College of Surgeons in Ireland and Trinity College; Dublin, Ireland (Graham)
Is an elevated plasma homocysteine level bad for you? Homocystinuria, the consequence of a severely elevated plasma homocysteine level of genetic origin, was first described in 1962 (1, 2). Patients with homocystinuria frequently experience thromboembolic events. Thirty years ago, McCully (3) noted that several different metabolic defects were characterized by two common factors: homocystinuria and premature thromboembolic disease. This implied that the elevated plasma levels of homocysteine, rather than any other metabolite, was the cause. With this information, McCully and Wilson evolved the homocysteine theory of arteriosclerosis (4), from which it has been suggested that a moderately elevated plasma homocysteine level may be a cardiovascular risk factor in the general population.
As with plasma cholesterol levels, homocysteine levels may be determined by both genetic and nutritional factors. Genetic causes are mostly defects in the enzymes that control homocysteine metabolism, whereas nutritional causes are deficiencies of folate, vitamin B12, or vitamin B6, all of which affect homocysteine metabolism. Vitamin B6 is a co-factor for the irreversible degradation of homocysteine, and vitamin B12 and folate are both required for the remethylation of homocysteine to methionine.
Subsequent ecological, cross-sectional, case–control, nested case–control, and cohort studies by and large indicate an association between elevated plasma homocysteine level and cardiovascular disease (5-8). However, Danesh and Lewington's meta-analysis (8) indicates that the more rigorous the epidemiologic methods, the weaker the association. It has been suggested that an elevated plasma homocysteine level merely indicates lower socioeconomic status and poor nutrition, or …
