Dietary Outcomes in Osteoarthritis Disease Management

Carol J. Henderson, PhD, RD
Department of Nutrition
Georgia State University 
Atlanta, GA

Glucosamine Sulfate and Chondroitin Sulfate

Glucosamine is an aminomonosaccharide, a component of almost all human tissues, including cartilage. It is the principle component of O- and N-linked glycosaminoglycans, which form the matrix of all connective tissues. Glucosamine sulfate has a relatively low molecular weight and is the sulfate salt of the natural aminomonosaccharide, glucosamine. Glucosamine is commercially available in pharmacies, health food stores, and retail stores and is sold via the Internet. It is most commonly available as the sulfate, HCl, N-acetyl or chlorhydrate salt isomers, which are water-soluble (10). The sulfate and HCl forms differ in their purity, sodium content, bioactive glucosamine, and equivalent dosages. Unlike glucosamine sulfate and HCl forms that are most commonly used in clinical trials, glucosamine does not have active intestinal transport. In some preparations, glucosamine is combined with chondroitin sulfate.

Glucosamine sulfate provides pain relief and improved function in knee OA (11). In a recent 3-year, randomized, placebo-controlled, prospective study by Bruyere et al, 212 patients with knee OA were evaluated to determine the effect of glucosamine and chondroitin on symptom and structure modification in knee OA (12). In patients who had mild OA and were in the highest quartile of baseline mean joint space narrowing, glucosamine was associated with a trend (p=0.10) towards a significant reduction in joint space narrowing (13). The authors reported indistinguishable symptomatic efficacies for both compounds as indicated by two 3-year, double-blinded, controlled studies (14,15).

Chondroitin sulfate occurs naturally in human cartilage, bone, cornea, skin and the arterial wall. Preparations of chondroitin sulfate are derived form bovine and calf cartilage. Careful selection of cattle to avoid herds contaminated with bovine spongiform encephalopathy must be considered. Chondroitin sulfate is a larger and more poorly absorbed; <10% intestinal absorption compared to 90% for glucosamine sulfate (10).

Several small, short-term, 3- to 12-month, randomized placebo controlled clinical trials to evaluate the effects on chondroitin sulfate/placebo or NSAID have demonstrated modest reductions in knee OA pain and improved function (16). Sustained effects have been reported up to 3 months after discontinuation of chondroitin sulfate (17).

Few studies have attempted to evaluate the potential chondroprotective effects of chondroitin sulfate by observing the progression of radiographic changes of OA (18,19). Using a computerized technique to evaluate joint space narrowing, patients were treated with 800 mg chondroitin sulfate/day or with placebo (18). After 1 year, joint space narrowing had decreased significantly in placebo-treated patients but had not changed from the baseline value in the chondroitin sulfate treatment group. In a 3-year trial, hand radiographs of 119 patients with OA were evaluated, of which 34 received chondroitin sulfate 400 mg/day and 85 patients received placebo (19). A significant decrease in the number of patients with new erosive OA was observed in the chondroitin sulfate group compared to the placebo group.

Reports of small, randomized controlled trials have examined the combination of glucosamine and chondroitin sulfate for knee OA pain and low back pain have been reported. It is important to note that these studies treatments were not consistent and included both oral and intravenous glucosamine, glucosamine HCl, and manganese ascorbate. In general studies using chondroitin sulfate combined with other agents (eg, glucosamine sulfate), improved symptoms of OA compared to placebo (9).

Precautions and Possible Side Effects:
There are no known contraindications to glucosamine supplementation. Glucosamine appears safe and has few short-term side effects. Pregnant women, children, and very elderly people should avoid glucosamine since no studies among these specific populations exist. Patients taking blood-thinners should be extremely careful if they take glucosamine combined with chondroitin. Chondroitin is chemically similar to blood-thinning drugs such as heparin, warfarin, and even aspirin, and could cause excessive bleeding. Possible side effects of glucosamine include nausea, diarrhea, heartburn, drowsiness, skin rash, and headache. There has been an unsubstantiated concern that glucosamine derived from the shellfish exoskeletons may cause reactions in people allergic to shellfish. One case study reports the exacerbation of an asthma attack associated with the use of a glucosamine-chondroitin supplement prescribed for OA pain (20). A recent 3-month, randomized, placebo-controlled trial did not demonstrate elevated blood glucose levels associated with glucosamine use (21). Insufficient data exist regarding possible interactions between glucosamine and other dietary supplements.

Recommendations:
Glucosamine sulfate 1500 mg daily in divided doses for patient with symptomatic OA may be considered. Response is slower than NSAIDs. Discontinuation is recommended if there is no documented response after 3 months.

Chondroitin sulfate may be considered in the treatment of pain from OA and may be given in the amount of 1,200 mg/day or 400 mg tid. Efficacy of a single daily dose of 1,200 mg/day does not seem to differ from that of 400 mg given tid.