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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:301.)
© 2004 American Heart Association, Inc.

Vascular Biology

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

Pål I. Holm; Øyvind Bleie; Per M. Ueland; Ernst A. Lien; Helga Refsum; Jan E. Nordrehaug; Ottar Nygård

From Locus for Homocysteine and Related Vitamins (P.I.H., Ø.B., P.M.U., E.A.L., O.N.), Institute of Medicine (Ø.B., J.E.N., O.N.), University of Bergen, Norway, and the Department of Pharmacology (H.R.), University of Oxford, United Kingdom.

Correspondence to Per Magne Ueland, LOCUS for Homocysteine and Related Vitamins, Department of Pharmacology, University of Bergen, N-5021 Bergen, Norway. E-mail per.ueland{at}ikb.uib.no

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 µmol/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 (ß=-0.29, P=0.02) and even more strongly to PML betaine (ß=-0.47, P<0.001). After 3 months of intervention, the relation between the PML increase in tHcy and PML betaine was weakened (ß=-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.

Key Words: betaine • homocysteine • folate • vitamin B12 • vitamin B6

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