MSM (methylsulfonylmethane, also called dimethyl sulfone) is a small sulfur-containing molecule. It occurs naturally at low levels in foods and is formed in the body from dimethyl sulfoxide (DMSO). As a supplement it is sold mainly for joint pain and osteoarthritis (OA), often combined with glucosamine and chondroitin, and is also marketed for exercise recovery (Butawan et al., Nutrients 2017).
The most important fact is that the evidence is thin. A handful of small, 12-week trials in knee OA found modest improvements in pain or function. Meta-analyses call the evidence promising but not definitive, and the effects are of unclear clinical importance. Exercise studies are tiny, and none shows that MSM builds muscle or improves performance.
This page summarizes what the clinical trials, reviews and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Organosulfur compound; oxidized metabolite of DMSO |
| Chemistry | C₂H₆O₂S, molecular weight 94.14 g/mol (PubChem) |
| Route | Oral (capsules, tablets, powder); also in topical products |
| Doses used in trials | 1.5–6 g/day in single-ingredient OA trials; 1.5–3 g/day or 50 mg/kg/day in exercise studies |
| Half-life | 12.2 h in rats (Magnuson 2007); no peer-reviewed human value |
| Main studied use | Pain and function in knee osteoarthritis |
| US status | Sold as a dietary supplement; not an FDA-approved drug. One branded MSM (OptiMSM) received an FDA “no questions” letter as a GRAS food ingredient in 2008 (FDA GRN 229) |
| Evidence quality | Small, short trials; several funded by or linked to manufacturers |
What it is
MSM is the fully oxidized form of the sulfur compounds dimethyl sulfide and DMSO (Butawan et al., Nutrients 2017). The review by Butawan and colleagues describes its background:
- It is found in small amounts in fruits, vegetables, grains, beer, coffee, tea and cow’s milk.
- It is also produced in the gut by bacteria and found in normal human blood and urine.
- Commercial MSM is made by oxidizing DMSO with hydrogen peroxide, then purifying it by crystallization or distillation.
- When people take DMSO, roughly 15% is oxidized to MSM.
Researchers began testing MSM in the late 1970s and early 1980s as an odorless relative of DMSO. MSM is often marketed as “organic sulfur” and described as a sulfur donor for building amino acids such as methionine and cysteine. That idea comes mainly from a guinea pig study in which labeled sulfur from MSM appeared in serum proteins. The review notes that this probably depended on gut bacteria. An unpublished human dose study it cites found no dose-related changes in blood sulfate or homocysteine.
The proposed anti-inflammatory mechanism comes from cell-culture work. In cell culture, MSM reduced the activity of NF-κB, a master switch for inflammatory genes, and lowered the expression of the inflammatory enzymes COX-2 and iNOS (Butawan et al., Nutrients 2017). These are laboratory findings. They have not been shown to explain any clinical effect in people.
How it behaves in the body
The best kinetic data come from rats. In male rats given a single oral 500 mg/kg dose of radiolabeled MSM (Magnuson et al., J Agric Food Chem 2007):
| Measure | Result in rats |
|---|---|
| Time to peak blood level | 2.1 h |
| Elimination half-life | 12.2 h |
| Recovered in urine by 120 h | 85.8% of the dose |
| Recovered in feces | 3% |
| Tissue levels at 120 h | None quantifiable |
MSM spread fairly evenly through the body’s tissues, with lower levels in skin and bone. The review cites an unpublished human dose-escalation report suggesting a half-life over 12 hours, but no peer-reviewed human pharmacokinetic study was found (Butawan et al., Nutrients 2017).
MSM crosses into the human brain. Using magnetic resonance spectroscopy (a scanner method that measures chemicals in tissue), researchers detected MSM in the brains of all 7 people taking 1–3 g/day, at 0.42–3.40 mmol/kg (Lin et al., Toxicol Lett 2001). It was not detectable in 25 people not taking it. No adverse clinical or brain-chemistry effects were seen. The finding matters mainly because it can show up as an unexpected signal on brain scans.
Regulatory status
In the US, MSM is sold as a dietary supplement. It is not approved as a drug for any condition.
Separately, Bergstrom Nutrition filed a notice with the FDA in 2007 that its distilled MSM is “generally recognized as safe” (GRAS) for use in foods. The FDA closed the notice in February 2008 with a “no questions” letter (FDA GRN 229). The notified uses were:
- meal supplements, meal replacements, smoothies and thirst-quencher drinks, at up to 4,000 mg/kg of food;
- food bars such as granola and energy bars, at up to 30,000 mg/kg.
A GRAS notice covers use as a food ingredient. It is not an FDA finding that MSM treats arthritis or any other disease.
What the research shows
Knee osteoarthritis: placebo-controlled trials
All of the main trials were small and lasted 12 weeks or less. Outcomes were questionnaires such as WOMAC, a standard knee OA score for pain, stiffness and physical function.
| Trial | n | MSM dose | Duration | Main result vs placebo |
|---|---|---|---|---|
| Usha & Naidu 2004 | 118 | 500 mg three times daily, alone or with glucosamine | 12 weeks | MSM, glucosamine and the combination all improved pain; the combination improved most |
| Kim et al. 2006 | 50 | 3 g twice daily | 12 weeks | Better WOMAC pain and physical function; no difference in stiffness or total score |
| Debbi et al. 2011 | 49 | 1.125 g three times daily | 12 weeks | Better WOMAC function (14.6 mm, 95% CI 4.3–25.0) and total score; WOMAC pain not significant (p = 0.08) |
| Toguchi et al. 2023 | 88 | 2 g/day | 12 weeks | Japanese knee score 8.1 vs 10.9 points (difference −2.8, p = 0.046) in adults with mild knee pain |
The Debbi authors concluded that the improvements were small and that it was not yet clear whether they mattered clinically. The Toguchi trial was supported by Chlorella Industry, which employed three of its four authors (Toguchi et al., Nutrients 2023). In the Debbi trial, the manufacturer donated the MSM and placebo (Debbi et al., BMC Complement Altern Med 2011).
Combined with glucosamine and chondroitin
MSM is often sold in combination products. In an Indonesian trial, 147 people with early knee OA (Kellgren-Lawrence grade I–II) took one of the following once daily for 12 weeks (Lubis et al., Acta Med Indones 2017):
- glucosamine 1,500 mg plus chondroitin sulfate 1,200 mg;
- the same plus MSM 500 mg;
- placebo.
The three-ingredient combination improved WOMAC and pain scores more than the other two arms, and glucosamine-chondroitin alone did not beat placebo. For the wider evidence on the two other ingredients, see the glucosamine and chondroitin page.
Systematic reviews and meta-analyses
| Review | What it included | Conclusion |
|---|---|---|
| Brien et al. 2008 | 2 MSM trials (168 patients, 52 on MSM) plus 4 DMSO trials | MSM trials “positive but not definitive”; optimal dose and long-term safety unknown |
| Brien et al. 2011 | 3 eligible trials (1 MSM, 2 DMSO), 326 patients | Pooled pain reduction 6.34 mm on a visual analogue scale (95% CI −0.49 to 13.17), not statistically significant |
| Liu et al. 2018 | 69 trials of 20 supplements for hand, hip or knee OA | MSM improved short-term pain statistically, but of unclear clinical importance; no supplement had clinically important effects in the long term |
In short, the trials point in a favorable direction, but they are few, small and short. None tested whether MSM changes joint structure in people.
Exercise recovery and performance
Interest in MSM among athletes rests on a few very small studies of muscle soreness and blood markers of muscle damage and oxidative stress.
| Study | Participants | Dose | Exercise | Findings |
|---|---|---|---|---|
| Kalman et al. 2012 | 8 men; no placebo group (1.5 vs 3 g/day) | 1.5 or 3 g/day for 30 days | 18 sets of knee extensions | Trend toward less soreness with 3 g (p = 0.080); higher antioxidant capacity with 3 g; no change in work performed |
| Barmaki et al. 2012 | 18 active men | 50 mg/kg/day for 10 days | 14 km run | Creatine kinase (a muscle damage marker) lower than placebo at 24 h; higher antioxidant capacity |
| Withee et al. 2017 | 22 adults (17 women) | 3 g/day for 23 days | Half-marathon | No statistically significant effect on oxidative stress, muscle damage markers or pain |
| Tennent et al. 2017 | 180 military trainees | 3 g/day for 8 weeks | Basic training | No improvement in knee symptom scores or mood scores at 30 or 60 days |
The largest and longest study, in military trainees, was negative. The half-marathon trial reported pain reductions over 10 mm that did not reach statistical significance, and its first author worked for the MSM manufacturer Bergstrom during the study (Withee et al., JISSN 2017).
“MSM helps build muscle.” No controlled study has measured muscle mass or strength gains with MSM. The only trial above that measured exercise performance found no change in work output (Kalman et al. 2012).
Side effects and risks
General tolerability
In the trials above, MSM was well tolerated at up to 6 g/day for 12–16 weeks:
- Kim et al. reported minor bloating, constipation, indigestion, fatigue, poor concentration, insomnia and headache, at about the same frequency as placebo (as summarized by Debbi et al. 2011).
- The Debbi and Toguchi trials recorded no adverse events (Debbi et al. 2011; Toguchi et al. 2023).
- In a low back pain trial, 6 g/day for 16 weeks did not change blood counts, liver enzymes (ALT, AST), bilirubin, creatinine, weight or blood pressure compared with placebo (Crawford et al., Complement Ther Med 2019).
Long-term safety beyond about four months has not been studied in controlled trials.
Animal toxicity data
In rats, a single 2 g/kg dose and 1.5 g/kg/day for 90 days caused no deaths, organ weight changes or tissue damage (Horváth et al., Food Chem Toxicol 2002). In pregnant rats given up to 1,000 mg/kg/day, there was no maternal or fetal toxicity and no malformations (Magnuson et al., Food Chem Toxicol 2007). These are animal results and do not establish safety in human pregnancy.
Pregnancy and breastfeeding
No studies have tested oral MSM in breastfeeding mothers. The NIH LactMed database notes that MSM is a normal component of blood and breast milk, and judges it unlikely to harm a breastfed infant based on topical use and low toxicity (LactMed). No human pregnancy studies were found.
Alcohol and drug interactions
Online claims that MSM increases sensitivity to alcohol have never been studied (Butawan et al., Nutrients 2017). The clinical trials cited here did not test interactions with medicines.
Key takeaways
- A DMSO relative sold as “organic sulfur.” MSM occurs in foods and in the body, and commercial MSM is made from DMSO.
- Modest, uncertain benefit in knee OA. Small 12-week trials found some improvement in pain or function, but reviews call the evidence not definitive and of unclear clinical importance.
- Weak evidence for exercise recovery. Studies are tiny and mixed, the largest was negative, and none shows gains in muscle or performance.
- Well tolerated in short trials. Doses up to 6 g/day for up to 16 weeks caused only minor stomach complaints, at rates similar to placebo.
- Industry ties are common. Several trials and the main review were funded by, supplied by or co-authored with MSM manufacturers.
Sources
- Butawan M, Benjamin RL, Bloomer RJ. Methylsulfonylmethane: applications and safety of a novel dietary supplement. Nutrients. 2017;9(3):290. PubMed.
- US Food and Drug Administration. GRAS Notice No. 229: Methylsulfonylmethane (Bergstrom Nutrition). Closed February 18, 2008, “FDA has no questions.” FDA.
- National Center for Biotechnology Information. Dimethyl sulfone (methylsulfonylmethane), PubChem CID 6213. PubChem.
- Magnuson BA, Appleton J, Ames GB. Pharmacokinetics and distribution of [35S]methylsulfonylmethane following oral administration to rats. J Agric Food Chem. 2007;55(3):1033–1038. PubMed.
- Lin A, Nguy CH, Shic F, Ross BD. Accumulation of methylsulfonylmethane in the human brain: identification by multinuclear magnetic resonance spectroscopy. Toxicol Lett. 2001;123(2-3):169–177. PubMed.
- Usha PR, Naidu MU. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Investig. 2004;24(6):353–363. PubMed.
- Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2006;14(3):286–294. PubMed.
- 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. PubMed.
- Toguchi A, Noguchi N, Kanno T, Yamada A. Methylsulfonylmethane improves knee quality of life in participants with mild knee pain: a randomized, double-blind, placebo-controlled trial. Nutrients. 2023;15(13):2995. PubMed.
- Lubis AMT, Siagian C, Wonggokusuma E, Marsetyo AF, Setyohadi B. Comparison of glucosamine-chondroitin sulfate with and without methylsulfonylmethane in grade I-II knee osteoarthritis: a double blind randomized controlled trial. Acta Med Indones. 2017;49(2):105–111. PubMed.
- Brien S, Prescott P, Bashir N, Lewith H, Lewith G. Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis. Osteoarthritis Cartilage. 2008;16(11):1277–1288. PubMed.
- 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;2011:528403. PubMed.
- Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2018;52(3):167–175. PubMed.
- Kalman DS, Feldman S, Scheinberg AR, Krieger DR, Bloomer RJ. Influence of methylsulfonylmethane on markers of exercise recovery and performance in healthy men: a pilot study. J Int Soc Sports Nutr. 2012;9(1):46. PubMed.
- Barmaki S, Bohlooli S, Khoshkhahesh F, Nakhostin-Roohi B. Effect of methylsulfonylmethane supplementation on exercise-induced muscle damage and total antioxidant capacity. J Sports Med Phys Fitness. 2012;52(2):170–174. PubMed.
- Withee ED, Tippens KM, Dehen R, Tibbitts D, Hanes D, Zwickey H. Effects of methylsulfonylmethane (MSM) on exercise-induced oxidative stress, muscle damage, and pain following a half-marathon: a double-blind, randomized, placebo-controlled trial. J Int Soc Sports Nutr. 2017;14:24. PubMed.
- Tennent DJ, Hylden CM, Kocher BK, Aden JK, Johnson AE. A randomized controlled trial evaluating methylsulfonylmethane versus placebo to prevent knee pain in military initial entry trainees. US Army Med Dep J. 2017;(3-17):21–25. PubMed.
- Crawford P, Crawford A, Nielson F, Lystrup R. Methylsulfonylmethane for treatment of low back pain: a safety analysis of a randomized, controlled trial. Complement Ther Med. 2019;45:85–88. PubMed.
- Horváth K, Noker PE, Somfai-Relle S, Glávits R, Financsek I, Schauss AG. Toxicity of methylsulfonylmethane in rats. Food Chem Toxicol. 2002;40(10):1459–1462. PubMed.
- Magnuson BA, Appleton J, Ryan B, Matulka RA. Oral developmental toxicity study of methylsulfonylmethane in rats. Food Chem Toxicol. 2007;45(6):977–984. PubMed.
- Drugs and Lactation Database (LactMed). Dimethyl sulfone. National Institute of Child Health and Human Development; updated February 15, 2025. NCBI Bookshelf.