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

Abstract

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.