Regulation of Dietary Supplements

The Dietary Supplement Health and Education Act passed by the United States Congress in 1994 permits the marketing of a product claimed to affect the structure or function of the body as a "dietary supplement' without the approval of any government agency, as long as the labeling includes a disclaimer saying that it has not been evaluated by the FDA and the product is not intended to diagnose, treat of prevent any disease. If a question about safety arises, the burden of proof is on the FDA, not the manufacturer.

Mechanism of Action

In vitro, glucosamine stimulates cartilage cells to synthesize glycosaminoglycans and proteoglycans [1]. In animal models, oral glucosamine sulfate has a beneficial effect on inflammation, mechanical arthritis and immunological-reactive arthritis, but much less that of indomethacin (Indocin and others) [2].

Clinical Use

In short-term controlled trials, glucosamine has been reported to be effective in relieving pain and increasing range of motion in patients with osteoarthritis [3]. One four-week double-blind trial in 252 patients with osteoarthritis of the knee found oral glucosamine sulfate 500 mg three times a day more effective than placebo in relieving symptoms [4]. Another four-week double-blind trial in 200 patients with osteoarthritis of the knee found 500 mg of glucosamine sulfate as effective in relieving symptoms as ibuprofen (Motrin and others) 400 mg three times a day from the second week onward [5]. In a double-blind eight week study in 40 patients with osteoarthritis, glucosamine sulfate 500 mg three times a day orally was as effective as ibuprofen 400 mg three times a day in relieving pain after the first two weeks, and by the end of the trial was more effective [6].

In all reports, the drug was generally well tolerated. Gastrointestinal discomfort and nausea have been reported, but the incidence was no higher than with placebo. One Medical Letter consultant in a area where many patients are taking glucosamine has not detected any adverse effects.

Preparations

Glucosamine is available in pharmacies and health food stores as the sulfate, hydrochloride, n-acetyl or chlorhydrate salt and as the destrorotatory isomer. It is sometimes combined with chondroitin sulfate, a glycosaminoglycan that has been reported to maintain viscosity in joints, stimulate cartilage repair mechanisms and inhibit enzymes that break down cartilage [7].

Conclusion

Glucosamine appears to be safe and might be effective for treatment of osteoarthritis, but most published trials of the drug lasted only four to eight weeks and Medical Letter consultants find them unconvincing. As with other "dietary supplements," the purity of the glucosamine products sold in pharmacies, health food stores, and supermarkets in the USA is unknown.

References

1. Basleer C and others. International Journal of Tissue Reaction 14:231, 1992.

2. Setnikar I and others. Antiarthritic effects of glucosamine sulfate studied in animal models. Arzneimittelforschung 41:542, 1991.

3. McCarty MF. The neglect of glucosamine as a treatment for osteoarthriti s: A personal perspective. Medical Hypotheses 42:323, 1994.

4. Noack W and others. Osteoarthritis Cartilage 2:51, 1994.

5. Muller-Fassbender H and others. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage 2:61, 1994.

6. Vas AL. Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthritis of the knee is outpatients. Current Medical Research and Opinion 8: 145, 1982.

7. Pipitone VR. Chondroprotection with chondroitin sulfate. Drugs experimental and Clinical Research 17:3, 1991.