Methylsulfonylmethane (MSM) is an organosulfur compound with the formula (CH3)2SO2. It is also known by several other names including methyl sulfone and dimethyl sulfone (DMSO2).[2] This colorless solid features the sulfonyl functional group and is considered relatively inert chemically. It occurs naturally in some primitive plants, is present in small amounts in many foods and beverages, and is marketed as a dietary supplement. It is sometimes used as a cutting agent for illicitly manufactured methamphetamine.[3] It is also commonly found in the atmosphere above marine areas, where it is used as a carbon source by the airborne bacteria Afipia.[4]

IUPAC name
dimethyl sulfone
Preferred IUPAC name
Other names
methyl sulfone
3D model (JSmol)
ECHA InfoCard 100.000.605
RTECS number
  • PB2785000
Molar mass 94.13 g·mol−1
Appearance White crystalline solid
Density 1.45 g/cm3
Melting point 109 °C (228 °F; 382 K)
Boiling point 248[1] °C (478 °F; 521 K)
Safety data sheet External MSDS
S-phrases (outdated) S22 S24/25
NFPA 704 (fire diamond)
Flash point 143 °C (289 °F; 416 K)
Related compounds
Related compounds
dimethyl sulfide
dimethyl sulfate
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Structure and chemical properties

MSM and the corresponding sulfoxide, dimethyl sulfoxide ((CH3)2SO, or DMSO), have different physical properties. MSM is a white crystalline solid at room temperature (m.p. = 109 °C) whereas DMSO is typically a liquid (m.p. = 19 °C). The sulfoxide is a highly polar aprotic solvent and is miscible with water; it is also an excellent ligand. MSM is less reactive than DMSO because the S-atom of the sulfone is already in its highest oxidation state (VI). Indeed, oxidation of the sulfoxide produces the sulfone, both under laboratory conditions and metabolically.[5]

Use as a solvent

Because of its polarity and thermal stability, MSM is used industrially as a high-temperature solvent for both inorganic and organic substances. It is used as a medium in organic synthesis. For example, displacement of aryl chlorides by potassium fluoride can be usefully conducted in molten MSM.[6] With a pKa of 31, it can be deprotonated with sodium amide, and the conjugate base is an effective nucleophile.

Pharmacology and toxicity

The LD50 of MSM is greater than 17.5 grams per kilogram of body weight. In rats, no adverse events were observed after daily doses of 2 g MSM per kg of body weight. In a 90-day follow-up study, rats received daily MSM doses of 1.5 g/kg, and no changes were observed in terms of symptoms, blood chemistry or gross pathology.[7]

Nuclear magnetic resonance (NMR) studies have demonstrated that oral doses of MSM are absorbed into the blood and cross the blood/brain barrier.[8][9] An NMR study has also found detectable levels of MSM normally present in the blood and cerebrospinal fluid, suggesting that it derives from dietary sources, intestinal bacterial metabolism, and the body's endogenous methanethiol metabolism.[10]

Published clinical trials of MSM did not report any serious side effects, but there are no peer-reviewed data on the effects of its long-term use in humans.

Medical and dietary use

Although no medical uses for MSM have been approved by any government, a variety of health benefits have been claimed and studied. Stanley W. Jacob reported having administered MSM to over 18,000 patients with a variety of ailments;[11] he co-authored a book promoting MSM with a variety of claims, including a utility as a natural source of "biologically active sulfur,"[12] suggesting that people are deficient in such forms of sulfur in their dietary intake. There is no Dietary Reference Intake (DRI) or Daily Value established for sulfur and sufficient dietary sources are readily available in onions, garlic and cruciferous vegetables and in protein-containing foods, including nuts, seeds, milk and eggs (whites and yolks).[13]

The claims for the need for sulfur supplementation originate with Robert Herschler, a biochemist who patented "Dietary and pharmaceutical uses of methylsulfonylmethane and compositions comprising it" in 1982; he claimed that MSM was useful in stress, mucous-membrane inflammation, allergies and gastrointestinal conditions.[14]

Moreover, in cases involving topical therapeutics, the role of MSM as an active agent, per se, versus its having a role in promoting skin permeation (in manner, akin to its solvent relative DMSO) must be characterized/controlled.[15] The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has anti-inflammatory effects.[16] The spectrum of biological effects of dimethyl sulfoxide (DMSO) and MSM differ, but those of DMSO may be mediated, at least in part, by MSM.[17]

FDA action

In July 2007 a manufacturer of MSM submitted a notification to the U.S. FDA claiming generally recognized as safe (GRAS) status. GRAS status is for safety, and has no evaluation of efficacy. The FDA responded in February 2008 with a letter of non-objection, functionally designating OptiMSM, the branded form of MSM, as GRAS. The designation allows MSM to be added to meal supplement and meal replacement foods, fruit smoothie-type drinks, fruit-flavored thirst quencher-type beverages, and food bars such as granola bars and energy-type bars.[18]

Evidence from clinical trials

Small-scale studies of possible treatments with MSM have been conducted on both animals and humans. These studies of MSM have suggested some benefits, particularly for treatment of oxidative stress and osteoarthritis, but evidence for other uses is lacking. Natural Medicines Comprehensive Database contains a continually updated list of health-related MSM studies.[19]


A South Korean study focussing on the role of MSM affecting growth factors associated with breast cancer identifies MSM to have multiple targets, both in vitro and in vivo, including STAT3, STAT5b, IGF-1R and VEGF, confirming the ability of MSM to suppress tumor initiation, growth and metastasis in a dose dependent manner. The expression of triple negative hormone receptors is also down regulated by MSM. In a xenograft model the mice showed inhibited tumor cell migration and suppressed tumor growth in a dose dependent manner when receiving MSM as part of their drinking water at nul, three or five percent MSM weight over volume. The authors strongly recommend MSM as a trial drug for treating breast cancers because of its multi-targeting mechanism.[20]


Extensive research in animal models indicates MSM has a very low toxicity when administered both orally and topically.[21][22][23]

In clinical trials, several studies reported minimal or absence of side effects after 12 weeks of dosing. Reported side effects from these studies included mild gastrointestinal issues, fatigue, and headache, although they did not appear to differ from placebo.[24][25] A more recent 26-week study on large joint osteoarthritis observed no adverse events or abnormal changes in lab monitoring when taking 6 grams MSM per day.[26] MSM is considered 'Possibly Safe' at therapeutic doses, although further research is still needed to assess its safety for long-term use.[19][27]


A review of two small randomized controlled trials of methylsulfonylmethane in osteoarthritis (OA) knee pain relief[24][28] "reported significant improvement in pain outcomes in the treatment group compared to comparator treatments; however, methodological issues and concerns over optimal dosage and treatment period were highlighted." The two trials included 168 people, of whom 52 received MSM, either 1.5 g/day or 6.0 g/day. The review authors stated: "No definitive conclusion can currently be drawn" and there is "no definitive evidence that MSM is superior to placebo in the treatment of mild to moderate osteoarthritis of the knee.[29]

Subsequent to the 2008 review there have been two more clinical trials :

  • One was a double-blind, randomized, placebo controlled trial with 49 participants taking 1.125 g of MSM or placebo three times daily for 12 weeks. The results showed a significant decrease in WOMAC physical function and total WOMAC scores, as well as improvement in VAS pain scores. The effect size of MSM supplementation was slightly lower than that of NSAID use as reported in other clinical trials. The authors wrote "longer-term trials may yield additional and greater improvements."[25]
  • The second used 6.0 g/day versus placebo for 26 weeks. Subjects were evaluated through the WOMAC questionnaire, SF-36 Quality of Life survey, and Global Assessments for OA symptoms from both patients and physicians. WOMAC results showed significant improvements in all areas for the MSM group. The MSM group also showed a strong trend towards changes in disease status. Careful lab monitoring of health indicators showed no side effects of MSM supplementation and no adverse events were reported.[26]
Synergism of methylsulfonylmethane and glucosamine
  • There are findings from Indian researchers that show an improvement of symptoms like pain, inflammation and swelling in patients by a combined intake of MSM and glucosamine.[30]

Oxidative stress and inflammation

Multiple human and animal trials indicate MSM may reduce oxidative stress and inflammation. In one small human trial, MSM has been shown to protect muscles from damage by reducing the amount of oxidative stress damage incurred through exercise.[31][32] In a second small trial the total antioxidant capacity was significantly increased after taking MSM.[33] Studies in animals indicate a hepatoprotective effect of MSM against several toxins including acetaminophen, paraquat, and carbon tetrachloride.[34][35][36][37] Animal models of experimental colitis and pulmonary hypertension indicate a protective effect as well.[38][39]


  1. Gaylord Chemical Company, LLC
  2. "Various Names for MSM" (PDF). Archived from the original (PDF) on July 11, 2011. Retrieved June 8, 2009.
  3. "Information Bulletin: Crystal Methamphetamine". Retrieved 20 January 2018.
  4. DeLeon-Rodriguez N, Lathem TL, Rodriguez-R LM, Barazesh JM, Anderson BE, Beyersdorf AJ, Ziemba LD, Bergin M, Nenes A, Konstantinidis KT (February 2013). "Microbiome of the upper troposphere: species composition and prevalence, effects of tropical storms, and atmospheric implications". Proceedings of the National Academy of Sciences of the United States of America. 110 (7): 2575–80. Bibcode:2013PNAS..110.2575D. doi:10.1073/pnas.1212089110. PMC 3574924. PMID 23359712. This group [Afipia] is commonly found in aquatic environments and is known to use dimethyl sulfone (DMSO2) as a sole carbon source. DMSO2 represents an intermediate of the oxidation of dimethyl sulfide (DMS), which is commonly found in the marine atmosphere(page 5 of 6, quote slightly edited).
  5. He X, Slupsky CM (December 2014). "Metabolic fingerprint of dimethyl sulfone (DMSO2) in microbial-mammalian co-metabolism". Journal of Proteome Research. 13 (12): 5281–92. doi:10.1021/pr500629t. PMID 25245235.
  6. Hareau G, Kocienski P (2001). "Dimethyl Sulfone". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rd371. ISBN 978-0471936237.
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  30. Usha PR, Naidu MU (2004). "Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis". Clinical Drug Investigation. 24 (6): 353–63. doi:10.2165/00044011-200424060-00005. PMID 17516722.
  31. Barmaki S, Bohlooli S, Khoshkhahesh F, Nakhostin-Roohi B (April 2012). "Effect of methylsulfonylmethane supplementation on exercise - Induced muscle damage and total antioxidant capacity". The Journal of Sports Medicine and Physical Fitness. 52 (2): 170–4. PMID 22525653.
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