S-adenosylhomocysteine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine are not related to folate, cobalamin and vitamin B6 concentrations

Background: It is unclear whether homocysteine itself is causal in the pathogenesis of cardiovascular disease. Alternatively or additionally, the association between homocysteine and cardiovascular disease may be because of its metabolic precursor, S-adenosylhomocysteine, or of the ratio of S-adenosylmethionine to S-adenosylhomocysteine. Therefore, it is relevant to know how these moieties are interrelated, and whether, as is the case for homocysteine, they are influenced by blood levels of folate, cobalamin or vitamin B₆. Design: We cross-sectionally studied a population-based cohort of 97 Caucasian subjects aged 60-85 years. Concentrations of homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, folate, cobalamin and vitamin B6 were measured in fasting blood samples. Results: In multiple regression analysis, homocysteine was associated with vitamin B12 (per 50 pmol L^-1 increase of cobalamin, change in homocysteine, -0.70 mmol L^-1; 95% CI, -1.30 to-0.10 mmol L^-1) and folate (per 100 nmol L^-1 increase in erythrocyte folate, change in homocysteine, -0.68 mmol L^-1; 95% CI-1.28 to-0.08 mmol L^-1). S-adenosylhomocysteine, S-adenosylmethionine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine were not associated with serum folate, cobalamin or vitamin B6, nor with erythrocyte folate. Furthermore, plasma homocysteine showed a negative correlation with the ratio of S-adenosylmethionine to S-adenosylhomocysteine in plasma (r =-0.27;P < 0.01) but not in erythrocytes. Conclusions: In contrast to homocysteine, the plasma concentrations of S-adenosylhomocysteine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine were not associated with the folate, cobalamin and vitamin B6 concentrations in the present study. If these precursors in part explain why homocysteine is associated with cardiovascular disease, homocysteine-lowering treatment with B vitamins may be less effective than currently expected, at least in an elderly population.