Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention

• Published in: The American journal of clinical nutrition Vol. 80; no. 3; pp. 641 - 648
• Main Authors: Bleie, O, Refsum, H, Ueland, P.M, Vollset, S.E, Guttormsen, A.B, Nexo, E, Schneede, J, Nordrehaug, J.E, Nygard, O
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 01.09.2004; American Society for Clinical Nutrition, Inc
• Subjects: Administration, Oral; Adult; Aged; Aged, 80 and over; Analysis of Variance; Biological and medical sciences; Cardiovascular disease; Cardiovascular Diseases - blood; Cardiovascular Diseases - etiology; Cardiovascular Diseases - prevention & control; Cardiovascular Diseases/blood/etiology/prevention & control; Clinical trials; Cystathionine - blood; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Feeding. Feeding behavior; Female; Folic Acid - administration & dosage; Fundamental and applied biological sciences. Psychology; Homocysteine - blood; Humans; Hyperhomocysteinemia - blood; Hyperhomocysteinemia - complications; Hyperhomocysteinemia - drug therapy; Hyperhomocysteinemia/blood/complications/drug therapy; Male; Methionine - administration & dosage; Methionine - metabolism; Methionine/administration & dosage/metabolism; Middle Aged; Norway; Prospective Studies; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin B; Vitamin B 12 - administration & dosage; Vitamin B 6 - administration & dosage; Norway; Human; Methionine; Cardiovascular disease; B-Vitamins; Change; Concentration; methionine loading; Folic acid; Folate; Vascular disease; vitamin B-6; vitamin B-12; Homocystein; Cystathionine; Homocysteine; 80 and over; Administration; Aged; Oral; Combination; Drug Therapy
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/80.3.641

Background: Vitamin B-6 is necessary for the metabolism of homocysteine and is often used in combination with folic acid and vitamin B-12 in clinical trials that investigate whether the lowering of plasma total homocysteine (tHcy) can prevent vascular disease. Objective: We compared the effects of vitamin B-6 with the effects of folic acid and vitamin B-12, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on basal and postmethionine load (PML) tHcy and cystathionine concentrations. Design: Ninety patients with suspected coronary artery disease were randomly assigned to 1 of 4 groups to receive daily oral treatment with 1) 0.8 mg folic acid, 0.4 mg vitamin B-12, and 40 mg vitamin B-6 (group A); 2) 0.8 mg folic acid and 0.4 mg vitamin B-12 (group B); 3) 40 mg vitamin B-6 (group C); or 4) placebo (group D). For the first 2 wk, groups A and B received additional folic acid (5 mg/d). A methionine-loading test was performed at baseline and after 3 mo. Results: Treatment with folic acid and vitamin B-12 caused a rapid and significant lowering of basal (31%) and PML tHcy concentrations (22%), with no effect on cystathionine. Vitamin B-6 did not change basal tHcy and had a significant but limited effect on PML tHcy concentrations. However, vitamin B-6 treatment markedly lowered basal and PML cystathionine by 31% and 42%, respectively. Conclusion: The folic acid and vitamin B-12 combination applied in WENBIT provides rapid, substantial, and long-term tHcy-lowering effects, whereas the effect of vitamin B-6 on tHcy was relatively small and confined to PML tHcy. However, vitamin B-6 treatment caused a marked reduction in plasma cystathionine. Cystathionine could be a useful marker for assessment of the vitamin B-6 effect and should, together with tHcy, be related to clinical outcome in ongoing trials.