Sulfate could mediate the therapeutic effect of glucosamine sulfate.

Glucosamine sulfate is a controversial osteoarthritis remedy that is presumed to stimulate articular cartilage glycosaminoglycan synthesis by increasing glucosamine concentrations in the joint space. However, this is not plausible because even large oral doses of the product have no effect on serum glucosamine concentrations. We propose instead that sulfate could mediate the clinical benefit attributed to this treatment. Sulfate is required for glycosaminoglycan synthesis, and unlike glucosamine, its serum level can be modified by dietary and other factors. In this study, we tested whether oral glucosamine sulfate increases serum sulfate concentrations and whether the sulfate concentration in the synovial fluid reflects that in the serum. The serum sulfate concentration of 7 normal subjects was 331 +/- 21 micromol/L before ingestion of 1.0 g glucosamine sulfate and 375 +/- 17 micromol/L 3 hours after (P <.05). Serum sulfate concentrations decreased from 325 +/- 19 to 290 +/- 19 micromol/L when the same dose of glucosamine sulfate was ingested with 1.0 g of the analgesic drug acetaminophen, which is largely metabolized by sulfation (P <.05). Unlike glucosamine sulfate, oral sodium sulfate did not significantly increase the serum sulfate concentration. Synovial fluid and serum sulfate concentrations were closely similar when measured in 15 patients undergoing diagnostic needle aspiration of a knee effusion (r =.99, slope =.97, P <.0001). These results do not prove that glucosamine sulfate improves osteoarthritis, but considered with other data, they do provide a plausible biochemical mechanism for its reported beneficial effects. This hypothesis is clinically relevant because it predicts that nonsulfate salts of glucosamine will be ineffective and that renal function, diet, and concurrent acetaminophen therapy could confound clinical trials of this therapy.

Parenteral vitamin B12 reduces hyperhomocysteinemia in end-stage renal disease.

OBJECTIVE: The authors found considerably lower plasma total homocysteine (tHcy) concentrations in patients with end-stage renal disease (ESRD) on maintenance hemodialysis, who routinely received high-dose parenteral vitamin B12, than in comparable patients receiving much higher doses of folic acid but only replacement-dose oral vitamin B12. They therefore sought prospective evidence that high-dose parenterally administered vitamin B12 may partially ameliorate renal failure-associated hyperhomocysteinemia. DESIGN: Open phase 2 clinical trial. SETTING: Outpatient hemodialysis unit. PATIENTS: Fourteen clinically stable patients on maintenance hemodialysis with normal baseline serum vitamin B12 concentrations. INTERVENTION: Three parenteral injections of 1 mg vitamin B12 given at 4-week intervals. OUTCOME MEASURES: Plasma tHcy and serum vitamin B12 concentrations were measured before, during and 7 months after the termination of vitamin B12 therapy. RESULTS: The mean (and standard error) baseline plasma tHcy was 26.5 (1.8) micromol/L. The plasma tHcy value fell successively after each vitamin injection to reach a value of 23.6 (1.6) micromol/L 1 month after the final injection (p < 0.05), while the serum vitamin B12 concentration increased from 471 (42) pmol/L to 890 (74) pmol/L (p < 0.05). Seven months after the final injection, the serum B12 concentration had fallen and tHcy had risen to near their original values. CONCLUSIONS: Three monthly vitamin B12 injections modestly but distinctly reduced tHcy concentrations in hemodialysis patients whose prior vitamin B12 status was normal. Randomized placebo-controlled clinical trials of longer duration and using larger or more frequent parenteral doses are indicated to determine whether administration of this safe and inexpensive vitamin can improve hyperhomocysteinemia in ESRD.