Betaine as a Determinant of Postmethionine Load Total Plasma Homocysteine Before and After B-Vitamin Supplementation

Objective—Betaine is a substrate in the betaine–homocysteine methyltransferase reaction, converting homocysteine to methionine. There are only sparse data on plasma betaine as a determinant of the plasma total homocysteine (tHcy) concentration. Methods and Results—Ninety patients undergoing coronary angiography were randomized into 4 groups administered oral: (1) folic acid (0.8 mg), vitamin B12 (0.4 mg), and vitamin B6 (40 mg); (2) folic acid and vitamin B12; (3) vitamin B6 alone; or (4) placebo. Nonfasting blood samples were collected at baseline and 3, 14, and 28 days and 3, 6, and 12 months after treatment start. A 4-hour methionine-loading test (0.1 g/kg) was performed at baseline and after 3 months. At baseline, median (interquartile range) plasma betaine was 36.9 &mgr;mol/L (range: 30.3 to 46.8) and was increased by 15% after methionine loading. The postmethionine load (PML) increase in tHcy was inversely related to plasma betaine (&bgr;=−0.29, P =0.02) and even more strongly to PML betaine (&bgr;=−0.47, P <0.001). After 3 months of intervention, the relation between the PML increase in tHcy and PML betaine was weakened (&bgr;=−0.33, P =0.007). Conclusions—Plasma betaine is a strong determinant of the PML increase in tHcy in subjects not supplemented with B-vitamins.