MONZA, Italy—As clinicians await the results from the much-anticipated ancillary arm of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) looking at whether glucosamine hydrochloride and/or chondroitin prevent radiographic progression in osteoarthritis (OA), new research showing that oral glucosamine sulphate is bioavailable in the blood and the joints may help pacify some critics of the supplements. The findings appear in the July issue of Osteoarthritis and Cartilage.¹ Glucosamine sulphate is a dietary supplement approved in Europe for OA.

"Our findings indicate that the drug is available systemically and at the site of action (the joint) at concentrations that are in line with those found to be effective in in vitro models on the putative mechanism of action of the drug, thus supporting the favorable clinical results in OA," report researchers led by Stefano Persiani, PhD, of the Rotta Research Laboratorium/Rottapharm, in Monza, Italy. The crystalline glucosamine sulphate powder used in the study, which is available by prescription in Europe and differs from the glucosamine sold in the United States, was manufactured by Rottapharm.

Synovial fluid, plasma levels tested after oral glucosamine sulphate

Researchers measured the synovial and plasma glucosamine concentrations in 12 patients with OA following oral administration of crystalline glucosamine sulphate at the therapeutic dose of 1500 mg once-daily for 2 weeks. Plasma and synovial fluid were collected simultaneously at baseline and 3 hours after the last dose.

The median endogenous glucosamine concentrations in plasma was 52.0 ng/mL (0.29 µM) and the median endogenous glucosamine concentrations in synovial fluid was 36.5 ng/mL (0.21 µM). Patients' concentrations ranged from 41 ng/mL to 121 ng/mL in the plasma and from <10 ng/mL to 67 ng/mL in the synovial fluid.

Glucosamine sulphate was absorbed and easily detected in blood and synovial fluid of all the study patients after 2 weeks of treatment. The glucosamine concentrations at both sites increased from baseline among all patients. The median posttreatment value was 1282 ng/mL (7.17 µM) in blood and ranged from 600 to 4061 ng/mL (3.35-22.7 µM). The median posttreatment synovial glucosamine concentration was 777 ng/mL (4.34 µM). The glucosamine concentration was significantly lower than in plasma (P = .001), and ranged from 577 to 3248 ng/mL (3.22-18.1 µM). Plasma and synovial glucosamine concentrations were highly correlated and were in the 10 µM range, the study showed.

Study adds to evidence that some forms of oral glucosamine may be bioactive

"This study answers the big important question which is that when you take glucosamine orally, is the concentration enough to cause a physical effect? [T]his study clearly shows that it is," said Jason Theodosakis, MD, of the University of Arizona College of Medicine, in Tucson, and author of Arthritis Cure and Maximizing the Arthritis Cure.
"This study proved biologic plausibility," Dr. Theodosakis told CIAOMed.

Different studies, differing results, new clues?

The original GAIT study showed that glucosamine hydrochloride and chondroitin sulfate alone or in combination did not reduce pain over all in the group of patients with knee OA, although the supplements in combination showed some suggestion of efficacy in the subgroup of patients with moderate-to-severe pain. The study appeared in the February 23 issue of the New England Journal of Medicine² and the preliminary results were reported at the 2005 American College of Rheumatology meeting, in San Diego, California.

GAIT included 1583 patients with symptomatic knee OA who received 1500 mg of glucosamine hydrochloride daily, 1200 mg of chondroitin sulfate daily, 1500 mg glucosamine HCL plus 1200 mg chondroitin sulfate daily, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia.

Results from an ancillary arm of GAIT designed to study the supplements' effects on radiographic disease progression at 1 and 2 years may be released at the upcoming meeting of the American College of Rheumatology, in Boston, this November.

"Additional studies should compare the bioavailability of glucosamine at the site of action after the administration of the prescription glucosamine sulfate formulation used here with that of other glucosamine salts, derivatives, formulations or dose regimens," Persiani et al conclude. "This might provide some clues to explain the observed discrepancies in therapeutic effects."

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