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

Abstract

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. 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. 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. 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. 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.