Effect of folic acid and betaine on fasting and postmethionine-loading plasma homocysteine and methionine levels in chronic haemodialysis patients

Objectives. To study fasting and postmethionine-loading (increment and decr ement) plasma homocysteine levels in end-stage renal disease (ESRD) patient s in relation to B-vitamin status and after folic acid treatment without or with betaine. Design. Plasma total homocysteine (tHcy) and methionine levels were measure d in chronic haemodialysis patients after an overnight fast, and 6 and 24 h after an oral methionine load (0.1 g kg(-1)). The patients were subsequent ly randomized to treatment with folic acid 5 mg daily with or without betai ne 4 g daily, and the loading test was repeated after 12 weeks. The patient s were then re-randomized to treatment with 1 or 5 mg folic acid daily for 40 weeks, after which a third loading test was performed. Setting. Haemodialysis unit of university hospital and centre for haemodial ysis. Subjects. Twenty-nine consecutive maintenance (> 3 months) haemodialysis pa tients, not on folic acid supplementation, 26 of whom completed the study. Results. At baseline, the mean fasting, the 6 h postload and the 6 h postlo ad increment plasma tHcy levels were increased as compared with those in he althy controls (46.8 +/- 6.9 (SEM), 92.8 +/- 9.1 and 46.0 +/- 4.2 mu mol L- 1, respectively) and correlated with serum folate (r = -0.42, P = 0.02; r = -0.61, P = 0.001 and r = -0.54, P = 0.003, respectively), but not with vit amin B-6 or vitamin B-12. At week 12, these variables had all decreased sig nificantly. Betaine did not have additional homocysteine-lowering effects. At week 52, fasting and postload tHcy levels did not differ significantly b etween patients on 1 or 5 mg folic acid daily. Plasma tHcy half-life and pl asma methionine levels after methionine loading were not altered by folic a cid treatment. Conclusions. In chronic haemodialysis patients, fasting as well as postmeth ionine-loading plasma tHcy levels depend on folate status and decrease afte r folic acid therapy. Increased postload homocysteine levels in these patie nts therefore do not necessarily indicate an impaired transsulphuration cap acity only; alternatively, folate may indirectly influence transsulphuratio n. The elucidation of the complex pathogenesis of hyperhomocysteinaemia in chronic renal failure requires further investigation.