Baylor Research Institute (BRI): Effect of S-adenosylmethionine on Blood Homocysteine

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Effect of S-adenosylmethionine on Blood Homocysteine

PI: Teodoro Bottiglieri
Funding Organization: NIH
Project Start: April 1, 2004
Project End: March 31, 2009

S-adenosylmethionine (AMe), a molecule present in all cells, serves as the methyl-group donor in numerous methyltransferase reactions involving proteins, phospholipids, DNA and catecholamines. Widely available as an over-the counter dietary supplement, it is promoted as a treatment for depression, osteoarthritis and liver disease. Studies indicate that SAMe is not associated with any serious adverse effects. However, because of its role in the methylation cycle and metabolism to homocysteine (Hcy), there is concern that SAMe may influence blood total Hcy(tHcy) concentrations. Furthermore, SAMe is a potent activator of the enzyme cystathionine synthetase, which acts to remove Hcy. The effects of SAMe on Hcy metabolism are not clear, especially in subjects with hyperhomocysteinemia. In these subjects with impaired metabolism of Hcy, oral administration of SAMe may either worsen the hyperhomocysteinemia or aid in the removal of Hcy. Since elevated blood tHcy is a known risk factor for vascular disease, it is important to understand the effect that SAMe supplementation may have on Hcy metabolism. An additional mechanism of vascular toxicity exists with SAMe supplementation through increased methylation of proteins that give rise to asymmetric dimethylarginine (ADMA), a potent inhibitor of nitric oxide synthetase implicated in endothelial dysfunction. We therefore propose a double-blind trial to determine the effect of SAMe on blood tHcy in human subjects with vascular disease and mild to moderate hyperhomocysteinemia (14 pmol/L). The specific aims of the study are: 1) To determine the effect of oral SAMe (1200 mg/day) on plasma tHcy; 2) to determine the effect of oral SAMe with and without supplementation of folate, vitamin B12 and B6 (Foltx ^®), on plasma tHcy; 3) to determine the effect of oral SAMe on plasma levels of ADMA. This study is important to better understand and assess the benefit to risk of SAMe supplementation. The outcome of this trial will provide the basis for future clinical studies of SAMe supplementation.