Methylsulfonylmethane, or MSM, is an organosulfur compound. Most often used as a protagonistic agent to anti-inflammatory prostaglandin action, MSM is frequently found in compounded creams and other topical treatments.

Most research has focused on the potential efficacy of MSM on osteoarthritis in large joints, such as the knee. One of MSM’s chemical properties that make it well-suited to this type of use is its ability to be converted into a solvent that can penetrate dermal layers. 


In research published in 1982, biochemist Robert Herschler meticulously examined MSM for its role in phosphorus supplementation.1 His findings broadened the interest in MSM from applications mainly for arthritis to those that included allergies, gastrointestinal complaints, and mucous membrane inflammation.1

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In 2002, Jacob Stanley brought a great deal of attention to MSM’s use in alternative medicine when he wrote a book detailing more than 18,000 patient experiences with MSM for a wide variety of ailments.2


The mechanism of action of MSM is not clearly understood and may very well act on more than one level at a time. MSM’s ability to penetrate into the intradermal layers is a crucial aspect of its benefit. By being able to penetrate the fat barrier in the skin, MSM can block the signaling process that activates the release of inflammatory cytokines and prostaglandins.3

Other studies support MSM’s action to stabilize cell membranes, which can slow leakage and allow healing time in the absence of the inflammatory compounds.4

Use of MSM can significantly reduce pain and dysfunction in patients with osteoarthritis. In a study of 49 adults with radiographically confirmed severe osteoarthritis of the knee, participants were randomly assigned to receive 12 weeks of either treatment with an oral MSM product or a placebo product.5

Patients were screened for symptoms of pain, stiffness, and altered quality of life at the beginning and end of the trial using the aggravated locomotor function (ALF) test and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Patients in the MSM treatment group experienced statistically significant reductions overall in pain and dysfunction, exceeding a 20% change from baseline to the end of the study. 

A meta-analysis of three trials involving more than 325 patients also found that MSM was effective in the treatment of osteoarthritis of the knee.6 In a summary statement of findings, researchers agreed that the data established an overall reduction in pain with the use of MSM, but emphasized that the three trials identified an average reduction of 6.34 mm on a visual analog scale that requires a minimum change from baseline of 17.5 mm for statistical significance. 

Perhaps the most exciting potential of MSM is in its association with malignant melanoma cells, which have been found to be saturated with the compound.7 As a volatile organic compound, the intense clusters of MSM in these cells gives off an odor. Researchers are exploring the potential of nanotechnology sensors that can “sniff out” the MSM in melanoma long before it is visible. 

Safety, interactions, side effects

To date, there have been no serious side effects with the use of MSM reported in published clinical trials. The most commonly reported adverse effects have been gastrointestinal upset, headache, and fatigue.8 Studies have confirmed, however, that MSM crosses the blood-brain barrier, and it is not recommended for use in pregnant or nursing mothers.9

Cost, how supplied, dose

MSM is chiefly supplied as either powder-filled capsules or in compounded creams with other ingredients such as glucosamine sulfate. Powder-filled 1,000-mg capsules of MSM cost $5 to $10 per 100 capsules, depending on the supplier.

Studies of oral MSM for large-joint osteoarthritis typically used at least 6 g per day, usually in two divided doses. Safety studies have shown no unanticipated adverse reactions at these doses for up to three weeks with tolerability that is similar to topical blends.8


The idea of a compound that is nearly harmless but possibly relieves some of the country’s tremendous burden of osteoarthritis pain is appealing. However, there is still a lack of robust data to determine the true efficacy of MSM in this condition. It is quite possible, however, that future research will find an even bigger role for MSM in cancer detection and treatment.

Sherril Sego, FNP-C, DNP, is a staff clinician at the VA Hospital in Kansas City, Mo., where she practices adult medicine and women’s health. She also teaches at the nursing schools of the University of Missouri and the University of Kansas. 


  1. Herschler RJ. Dietary and pharmaceutical uses of 
methylsulfonylmethane and compositions comprising it. Patent number: US4514421A. Available at 

  2. Jacob SW, Appleton J. MSM the Definitive Guide: The Nutritional Breakthrough for Arthritis, Allergies, and More. Topanga, Calif.: Freedom Press; 2003.

  3. Pagonis TA, Givissis PA, Kritis AC, Christodoulou AC. The effect of methylsulfonylmethane on osteoarthritic large joints and mobility. International Journal of Orthopaedics. 2014;1(1):19-24. Available at 

  4. Hasegawa T, Ueno S, Kumamoto S, Yoshikai Y. Suppressive effect of methylsulfonylmethane (MSM) on type II collagen-induced arthritis in DBA/1J mice. Japanese Pharmacology and Therapeutics. 2004;32(7):421-427. 

  5. Debbi EM, Agar G, Fichman G, et al. Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: A randomized controlled study. BMC Complement Altern Med. 2011;11:50. Available at

  6. Brien S, Prescott P, Lewith G. Meta-analysis of the 
related nutritional supplements dimethyl sulfoxide and methylsulfonylmethane in the treatment of osteoarthritis of the knee. Evid Based Complement Alternat Med. 2011:528403. Available at 

  7. Kwak J, Gallagher M, Ozdener MH, et al. Volatile biomarkers from human melanoma cells. J Chromatogr B Analyt Technol Biomed Life Sci. 2013;931:90-96. 

  8. Bauer BA. Are there any adverse effects from long-term use of MSM for arthritis pain? Mayo Clinic Web site. Published June 6, 2014. Available at

  9. Engelke UF, Tangerman A, Willemsen MA, et al. Dimethyl sulfone in human cerebrospinal fluid and blood plasma confirmed by one-dimensional (1)H and two-dimensional (1)H-(13)C NMR. NMR Biomed. 2005;18(5):331-336.

All electronic documents accessed June 3, 2015.