Glucosamine

GLUCOSAMINE

Glucosamine is found in human tissue, is a substrate for the pro-duction of articular cartilage, and serves as a cartilage nutrient. Glucosamine is commercially derived from crabs and other crustaceans. As a dietary supplement, glucosamine is primarily used for pain associated with knee osteoarthritis. Sulfate and hydrochloride forms are available, but recent research has shown the hydrochloride form to be ineffective.

Pharmacologic Effects & Clinical Uses

Endogenous glucosamine is used for the production of gly-cosaminoglycans and other proteoglycans in articular cartilage. In osteoarthritis, the rate of production of new cartilage is exceeded by the rate of degradation of existing cartilage. Supplementation with glucosamine is thought to increase the supply of the neces-sary glycosaminoglycan building blocks, leading to better mainte-nance and strengthening of existing cartilage.

Many clinical trials have been conducted on the effects of both oral and intra-articular administration of glucosamine. Early studies reported significant improvements in overall mobility, range of motion, and strength in patients with osteoarthritis. More recent studies have reported mixed results, with both positive and nega-tive outcomes. One of the largest and well-designed clinical trials, which compared glucosamine, chondroitin sulfate, the combina-tion, celecoxib, and placebo, found no benefit for glucosamine therapy in mild to moderate disease. Unfortunately the investiga-tors studied the glucosamine hydrochloride formulation, which has been shown to be inferior to the sulfate formulation. The formulation of glucosamine appears to play an important role with regard to efficacy. More research is needed to better define the specific patient populations that stand to benefit from glu-cosamine sulfate.

Adverse Effects

Glucosamine sulfate is very well tolerated. In clinical trials, mild diarrhea and nausea were occasionally reported. Cross allergenicity in people with shellfish allergies is a potential concern; however, this is unlikely if the formulation has been properly manufactured and purified.

Drug Interactions & Precautions

Glucosamine sulfate may increase the international normalized ratio (INR) in patients taking warfarin, increasing the risk for bruising and bleeding. The mechanism is not well understood and may be dose-related as increases in INR have occurred when the glucosamine dose was increased. Until more is known, the combi-nation should be avoided or very carefully monitored.

Dosage

The dosage used most often in clinical trials is 500 mg three times daily or 1500 mg once daily. Glucosamine does not have direct analgesic effects, and improvements in function, if any, may not be observed for 1–2 months.