Site Search     
  A CHR Trial Investigation Outcomes of Exercise Training
  A Pull-Push Strategy for Lymphoma Immunotherapy
  Altered CD8+ T Cell Compartment in SLE Patients
  Biology and Diagnosis of HNPCC
  Center for Lupus Research
  CHAVI Innate Discovery
  Colon Cancer Prevention Program Project
  Consortium to Analyze Tolerogenic Dendritic Cells in Respiratory Syncytial Virus Infection
  Development of Neonatal Oxygen Therapy Information System to Support Oximetry Targets in Newborn Intensive Care Units
Effect of S-adenosylmethionine on Blood Homocysteine
  Functional MR in Ischemic Cardiomyopathy
  Human Dendritic Cells and In Vivo Immunity to Biothreat
  Improving the Efficacy of Dendritic Cell Vaccines
  JC Virus and Tumor Formation in the Human Colon
  New Predictors of SLE Disease Activity
  NIAID Cooperative Center Luminex Facility
  Rural Hospital Collaborative for Excellence Using IT
  Subpopulations of Human Dendritic Cells
  Targeting Langerhans Cells for Therapeutic Vaccination in Breast Cancer
  Transcriptional Signatures for Diagnosis of Different Spectra of Mycobacterium tuberculosis Infection and Characterization of the Immune Response during Latency or Active Disease
  Use of Microarrays to Understand Systemic Arthritis
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.