Dietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy human subjects: a double-blind, placebo-controlled, randomized clinical trial

Abstract

Objectives: To determine if exogenous S-adenosyl-l-methionine (AdoMet), a commonly used nutritional supplement, increases the level of plasma homocysteine (Hcy), a potential cardiovascular risk factor, in healthy human subjects.

Design: Double-blind, placebo-controlled, randomized clinical trial.

Setting: Mayo Clinic, Rochester, Minnesota.

Subjects: Fifty-two (52) healthy human volunteers.

Intervention: Subjects received placebo or AdoMet (800 mg per day) for 4 weeks. Hcy levels were measured before and after administration of AdoMet or placebo.

Outcome measures: The primary outcome measure was change in Hcy level. Secondary outcome measures included an interim Hcy determination (at 2 weeks) and changes in levels of high-sensitivity C-reactive protein (hsCRP), lipids, and alanine aminotransferase.

Results: There was no statistically significant change in Hcy between groups. Similarly, no statistically significant differences in change in Hcy or hsCRP levels were observed at 2 or 4 weeks. There was a small but statistically significant increase (p < 0.04) in alanine aminotransferase at week 2 and a statistically significant decrease (p < 0.04) in total cholesterol in the AdoMet group compared with the placebo group.

Conclusions: AdoMet at a daily dose of 800 mg for 4 weeks does not appear to significantly affect Hcy levels in the blood.

Trial registration: ClinicalTrials.gov NCT00284011.

Figures

FIG. 1. (A)

The structure of S-adenosyl-l-methionine (AdoMet). (B) Homocysteine (Hcy) and homocystine. Hcy is a monomer, and homocystine is an Hcy dimer. (C) Metabolic pathways of AdoMet and Hcy. The circled numbers correspond to enzymatic reactions: 1, AdoMet decarboxylase; 2, AdoMet-dependent; MT, methyltransferase; 3, Gly-N-MT; 4, S-adenosyl-l-homocysteine (AdoHcy) hydrolase; 5, cystathione β-synthase; 6, betaine Hcy MT; 7, MTHF reductase; 8, AdoMet synthetase; 9, cystathione γ-lase. The AdoMet, AdoHcy, and Hcy pathway is emphasized in bold. ATP, adenosine triphosphate; Cys, cysteine; DMG, dimethyl-glycine; Gly, glycine; Met, methionine; MS, methyltetrahydrofolate-Hcy MT; MTHF, methyltetrahydrofolate; Pi, inorganic phosphate; PPi, inorganic diphosphate; PLP, pyridoxal phosphate; Sar, sarcosine; THF, tetrahydrofolate.

FIG. 2.

Flow diagram of clinical trial. AdoMet, S-adenosyl-l-methionine; ALT, alanine aminotransferase.