Glucosamine And Chondroitin – Do They Work For Joint Pain?

Glucosamine is derived from the shells of crabs and oysters, and is widely promoted as a natural substance for the treatment of arthritis and joint pain. Glucosamine is felt to be a precursor of proteoglycans. Proteoglycans are thought to be instrumental in helping cartilage retain water and in promoting formation of an elastic layer, which may improve the functional characteristics of cartilage.

Chondroitin is a product derived from the cartilage of sharks and cows that is promoted for the prevention of arthritis and the treatment of joint pain. Chondroitin is often combined with glucosamine where it is sold in health food stores. Chondroitin stimulates the production of proteoglycans and hyaluronic acid and inhibits proteolytic enzymes, which destroy cartilage. Chondroitin and glucosamine are often given in combination for osteoarthritis.

Most of the earlier studies of glucosamine and chondroitin were performed by manufacturers and were not well controlled (1). A meta-analysis performed in 2000 of studies of glucosamine and chondroitin found that studies funded by supplement manufacturers resulted in more favorable results for the supplement combo than independent studies; few of the manufacturers’ studies were properly controlled. Overall there was a moderate effect for both, and the authors concluded that some degree of efficacy was probable (1).

Only one of the studies reviewed in 2000 reported that patients definitely did not know whether they were being given a supplement or a placebo. In that study, 252 patients with osteoarthritis of the knee were randomly assigned to receive four weeks of glucosamine or placebo. Glucosamine was associated with a drop in pain ratings from 10.6 to 7.5 versus 10.6 to 8.4 in placebo; fifty two percent of glucosamine patients had a clinically significant change as measure by a three-point drop on an index of arthritis severity compared to 37% on placebo. These differences were statistically significant.

More recently several randomized placebo controlled trials have been performed.

In one study 212 patients with osteoarthritis of the knee were assigned to placebo or glucosamine for three years of treatment. Patients on placebo had a greater narrowing of the disk space in the knee compared to glucosamine as measured on X-ray (-.31 mm v -.06 mm). Glucosamine patients had a significant improvement in pain ratings compared to placebo. Glucosamine showed no increase in side effects compared to placebo (2).

In another study 98 males with osteoarthritis of the knee were assigned to glucosamine or placebo for two months of treatment. There was no difference in pain ratings between patients treated with glucosamine (3.3) and placebo (3.5) (3). Glucosamine was also associated with more side effects, including loose stools, nausea, heartburn, and headache.

Another study randomized 202 patients with osteoarthritis of the knee to three years of treatment with glucosamine or placebo. Placebo treated patients had a greater degree of joint space narrowing as measured by X-ray than glucosamine (-.19 mm v +.04 mm). There were statistically significantly greater reductions in glucosamine for measures of pain self ratings (-2 v -1.3) as well as measures of stiffness and function. One randomized placebo controlled study showed efficacy with a glucosamine-chondroitin combination compared to placebo (4).

In 2006 a large well-controlled study assigned 1583 patients with osteoarthritis of the knee to glucosamine, chondroitin, a glucosamine/chondroitin combination, celecoxib, or placebo for six months of treatment. A positive treatment outcome was defined as a 20% change in knee pain severity. Sixty percent of placebo patients responded to treatment compared to 67% of glucosamine/chondroitin patients, a difference that was not statistically significant. Celecoxib had a 70% response that was statistically significantly better than placebo. A subgroup of patients with moderate to severe pain at baseline did significantly better with glucosamine/chondroitin than placebo (79% response v 54%) (5). In summary the glucosamine and chondroitin combination shows some efficacy for treatment of osteoarthritis.

1. McAlindon, T.E., LaValley, M.P., Gulin, J.P., Felson, D.T. Glucosamine and chondroitin for treatment of osteoarthritis: A systematic quality assessment and meta-analysis. Journal of the American Medical Association. 2000;283(11):1469-1475.

2. Reginster, J.-Y., Deroisy, R., Rovati, L.C., Lee, R.L., Lejeune, E., Bruyere, O., Giacovelli, G., Henrotin, Y., Dacre, J.E., Gossett, C. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357:251-256.

3. Rindone, J.P., Hiller, D., Collacott, E., Nordhaugen, N. Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. Western Journal of Medicine. 2000;172(2):91-94.

4. Lefler, C.T., Philippi, A.F., Leffler, S.G. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Military Medicine. 1999;164:85-91.

5. Clegg, D.O., Reda, D.J., Harris, C.L., Klein, M.A., O’Dell, J.R., Hooper, M.M., Bradley, J.D., Bingham, C.O., 3rd, Weisman, M.H., Jackson, C.G., Lane, N.E., Cush, J.J., Moreland, L.W., Schumacher, H.R., Jr., Oddis, C.V., Wolfe, F., Molitor, J.A., Yocum, D.E., Schnitzer, T.J., Furst, D.E., Sawitzke, A.D., Shi, H., Brandt, K.D., Moskowitz, R.W., Williams, H.J. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. New England Journal of Medicine. Feb 23 2006;354(8):795-808.