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Elevated serum S-adenosylhomocysteine in cobalamin-deficient elderly and response to treatment.

AbstractBACKGROUND: S-Adenosylmethionine (SAM)-dependent methylation reactions produce S-adenosylhomocysteine (SAH), the precursor of homocysteine, which has been associated with adverse events when it is elevated. OBJECTIVE: We studied a cohort of elderly with a high prevalence of cobalamin deficiency to determine whether SAH, SAM, or their ratio was abnormal; whether they correlated with other markers of vitamin deficiency; and whether they changed with cobalamin therapy. DESIGN: A convenience sample of elderly attending nutrition centers was enrolled for baseline demographic, biochemical, and nutritional assessments. Methylmalonic acid (MMA), total homocysteine, and other metabolites were measured by using gas chromatography-mass spectrometry. Serum SAM and SAH were measured by using stable-isotope-dilution liquid chromatography-mass spectrometry. Subjects found to have elevated serum MMA were treated with oral cyanocobalamin tablets (1000 microg/d) for 3 mo. Subjects with normal MMA were randomly assigned to 1 of 3 dosage groups: 0, 25, or 100 microg cyanocobalamin/d. RESULTS: The 149 elderly subjects had a mean age of 76.3 y; 81% were female, and 30% were African American. Serum MMA concentrations were elevated in 30% and SAH concentrations were elevated in 64% of the cohort. Those with elevated MMA concentrations had higher SAH and SAM concentrations. High-dose oral cobalamin lowered SAH, MMA, and total homocysteine concentrations significantly, although subjects with creatinine concentrations >109 umol/L had higher posttreatment SAH than did those with lower creatinine. CONCLUSIONS: Elevated serum SAH concentrations are common in elderly and are strongly influenced by both renal status and cobalamin deficiency. These elevated concentrations can be lowered with high-dose oral cobalamin therapy.
AuthorsSally P Stabler, Robert H Allen, Evi T Dolce, Mary Ann Johnson (Affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA. sally.stabler at UCHSC.edu)
JournalThe American journal of clinical nutrition (Am J Clin Nutr) Vol. 84 Issue 6 Pg. 1422-9 (Dec 2006) ISSN: 0002-9165 United States
PMID17158426 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Vitamin B Complex
  • S-Adenosylmethionine
  • Vitamin B 12
  • S-Adenosylhomocysteine
Topics
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Gas Chromatography-Mass Spectrometry (methods)
  • Humans
  • Kidney (metabolism)
  • Linear Models
  • Male
  • Middle Aged
  • Nutrition Assessment
  • S-Adenosylhomocysteine (blood)
  • S-Adenosylmethionine (blood)
  • Treatment Outcome
  • Vitamin B 12 (therapeutic use)
  • Vitamin B 12 Deficiency (blood, drug therapy)
  • Vitamin B Complex (therapeutic use)