Homocysteine, vitamins and sex.

tHcy predicted vascular disease more strongly in women than in men, while the reverse was true for fasting tHcy. While post-methionine tHcy was higher in men than in women, in line with previous studies, the percentage change was greater in women, possibly reflecting an overdose of methionine with respect to lean tissue mass. Unlike previous studies, the current paper found only slight evidence of a post-menopausal rise in fasting tHcy over and above the age-related rise. However, a much larger effect was observed on post-methionine tHcy levels. Again contradicting earlier studies, the authors found that the relationship between fasting tHcy was stronger in prethan in post-menopausal women. The lower level of tHcy in pre-menopausal women is likely to be due to oestrogen, which may have an up-regulatory effect on the hepatic enzyme betaine:homocysteine methyltransferase, although Verhoef et al. suggest that the observed hormonal effect is mediated chiefly through effects on muscle mass. It has been proposed that the lower levels of tHcy in pre-menopausal women may partially account for the low incidence of vascular disease in this group, while the rise in tHcy seen post-menopause may account for the rise in disease incidence approaching male levels. Mean vitamin levels did not differ between the sexes, and thus failed to account for sex differences in tHcy. Whilst low levels of vitamin B6 constituted a greater risk in women than in men, the reverse was true for folate. The authors suggest that this is due to an increased demand for folate in males, to supply methionine for creatinine formation. The correlation between vitamin B6 and vascular disease was partially independent of tHcy levels, and is suggested to relate to an effect on clotting mechanisms and cholesterol levels. The interaction of homocysteine with known risk factors poses certain questions relating to its status as an independent risk factor for cardiovascular disease. It has been suggested that the ‘homocysteine theory of atherosclerosis’ supplies a unifying mechanism for the action of numerous risk factors. Support for this view comes from experiments in vitro and in animal models showing a direct effect of homocysteine on the vasculature. Other researchers have suggested that elevated homocysteine is an epiphenomenon occurring as a result of vascular damage, with no primary role in disease causation. This view is supported by the body of evidence showing that homozygosity for the See page 1234 for the article to which this Editorial refers