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Questions from practice: What’s this methylsulfonylmethane?

Question: I usually take glucosamine and chondroitin for arthritis in my knees but I’ve just seen this product, which says it also contains MSM. What is it? Will it help my arthritis? And while I’m here, is the 500mg glucosamine in my tablets enough? There are 1,000mg ones.

(Mona Makela/


MSM (methylsulfonylmethane) is an organic sulphur-containing compound. Cartilage has a high sulphur content and MSM is claimed to be a source of sulphur for the formation of connective tissue, particularly in conditions such as osteoarthritis where there is degeneration of cartilage. However, sulphur is widely available in the diet (especially from proteins). Preliminary evidence from two small trials suggests that MSM, either alone or in combination with glucosamine, could reduce pain and improve physical function in arthritis but larger controlled trials are required to confirm these suggested benefits.


Glucosamine is a natural substance found in mucopolysaccharides, mucoproteins and chitin. It is a basic building block for constituents of articular cartilage, such as glycoprotein, glycolipids, hyaluronic acid, glycosaminoglycans and proteoglycans. It is found in high concentrations in joints where it is important for maintaining the elasticity, strength and resilience of cartilage. Chondroitin sulphate, also a natural substance, is a glycosaminoglycan synthesised by chondrocytes.

Doses of glucosamine used in studies have been 500mg three times a day and for chondroitin 400–1,200mg daily, and these are doses recommended by most manufacturers. Risk assessment supports safety at intakes of up to 2000mg/day of glucosamine. The regimen should suit the individual.

Is there any benefit?

Since 1990, more than 50 studies have examined the effects of oral glucosamine or chondroitin, or both, in osteoarthritis. However, many of these have been short, and many have major design flaws and critical problems with data analysis and interpretation of results.

Double blind placebo controlled trials have demonstrated mixed findings. Measured outcomes, while mostly including pain, differ between trials and include joint space narrowing, knee flexion, stiffness, physical function and analgesic use. Most controlled studies have only involved patients with arthritis of the knee.

About two-thirds of the placebo-controlled trials have shown improvements in pain and stiffness with glucosamine, with joint narrowing occurring to a greater extent in patients in placebo arms. Some of these trials have included chondroitin and provided some evidence of a small synergistic effect.

Several meta-analyses have also been conducted. Some have found glucosamine to be more effective than placebo for reducing pain, improving joint function and reducing disease progression. However, a recent meta-analysis published in the BMJ evaluated the effect of glucosamine, chondroitin, or both on joint pain and radiological progression of disease in osteoarthritis of the hip or knee. Changes in pain and joint space narrowing were all small and insignificant. The authors recommended that health organisations should not cover the costs of these preparations and patients perceiving a benefit should pay for themselves (PJ, 25 September 2010, p328).

Other controlled trials have compared glucosamine with non-steroidal anti-inflammatory drugs such as ibuprofen and piroxicam. Those using pain as an outcome have generally found that glucosamine is as effective as ibuprofen 400mg tds, if not quite as fast to provide relief.

However, the multicentre, double-blind, placebo- and celecoxib-controlled glucosamine/chondroitin arthritis intervention trial (GAIT), which included 1,583 patients with osteoarthritis of the knee, found that glucosamine or chondroitin sulphate, or both, were not significantly better than placebo for the measured outcome, which was reducing knee pain by 20 per cent: the rate of response to glucosamine was 3.9 per cent higher than placebo (P=0.30), the rate of response to chondroitin was 5.3 per cent higher (P=0.17), the rate of response to combined treatment was 6.5 per cent per cent higher (P=0.09) and the rate of response to celecoxib was 10 per cent higher (P=0.008) than placebo.

However, for a subgroup with moderate to severe knee pain at baseline, the rate of response was significantly higher with combined glucosamine and chondroitin therapy than with placebo (79.2 per cent vs 54.3 per cent, P=0.002). This suggests that glucosamine and chondroitin in combination may be effective in patients with moderate to severe pain, but not in patients overall with osteoarthritis of the knee.

Most of the glucosamine products on the market are food supplements. One licensed product (Alateris) is available on prescription for symptomatic relief of mild to moderate osteoarthritis of the knee in adults. This is a 625mg tablet and two tablets are to be taken daily with a review of treatment if there has been no benefit after three months. However, the British National Formulary identifies glucosamine as a product of limited suitability for prescribing and the Scottish Medicines Consortium has advised that it is not recommended for use in NHS Scotland for the above indications.


Side effects reported with glucosamine have included constipation, diarrhoea, heartburn, nausea, drowsiness, headache and rash.
Glucosamine should not be used in pregnancy and breast-feeding due to lack of data. Anyone allergic to shellfish should avoid it. There is some evidence that glucosamine can alter glucose regulation and insulin sensitivity.

Research in humans taking oral supplements is conflicting, but most data in people without diabetes do not suggest a problem. Data in patients with diabetes are more limited and it would seem wise to monitor these people.

•    MSM is claimed to be a source of sulphur for the formation of connective tissue but sulphur is widely available in the diet.
•    Risk assessment supports safety at intakes of up to 2,000mg/day of glucosamine.
•    The British National Formulary identifies glucosamine as a product of limited suitability for prescribing.


Pamela Mason, freelance journalist and author with a special interest in nutrition. Dr Mason is an adviser to the Health Supplements Information Service

Citation: The Pharmaceutical Journal URI: 11074563

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