Vol. 282, Issue 2, 845-850, 1997

Influence of Oral S-Adenosylmethionine on Plasma 5-Methyltetrahydrofolate, S-Adenosylhomocysteine, Homocysteine and Methionine in Healthy Humans¹

Franziska M. T. Loehrer, Roger Schwab, Christian P. Angst, Walter E. Haefeli and Brian Fowler

University Children's Hospital Basel, Metabolic Unit (F.M.T.L., C.P.A., B.F.) and University Hospital Basel, Division of Clinical Pharmacology, Basel, Switzerland (R.S., W.E.H.)

Elevated plasma homocysteine concentration is an independent risk factor for vascular disease in humans. In addition to nutritional and genetic factors, an interruption of the coordinate regulatory function of S-adenosylmethionine has been proposed to be involved in the occurrence of hyperhomocysteinemia. The effect of oral S-adenosylmethionine on homocysteine metabolism in humans is unknown. We investigated the effect of oral S-adenosylmethionine (400 mg) on plasma levels of 5-methyltetrahydrofolate, which is the active form of folate in the remethylation of homocysteine to methionine, S-adenosylhomocysteine, the demethylated product of S-adenosylmethionine, homocysteine and methionine over 24 hr in 14 healthy subjects. After oral administration, S-adenosylmethionine increased from 38.0 ± 13.4 to 361.8 ± 66.4 nmol/liter (mean ± S.E., P < .001) and returned to base-line values with a half-life of 1.7 ± 0.3 hr. Both S-adenosylhomocysteine and 5-methyltetrahydrofolate showed a significant transient increase (from 29.9 ± 3.7 to 51.7 ± 7.1 nmol/liter, and from 25.1 ± 2.5 to 36.2 ± 3.5 nmol/liter, respectively, P < .001), although homocysteine and methionine did not change over the time of measurement. These changes were not found in subjects without previous S-adenosylmethionine administration. The observed metabolic changes suggest that S-adenosylmethionine, at least in concentrations obtained in this study, does not inhibit 5,10-methylenetetrahydrofolate reductase, the 5-methyltetrahydrofolate forming enzyme. Rather they indicate a positive effect on 5-methyltetrahydrofolate, a key cofactor in homocysteine metabolism, which should be considered in homocysteine lowering strategies for the prevention of vascular disease.