Methylsulfonylmethane 945206 221305776 2008-06-23T23:10:46Z JNF Tveit 2132725 {{Chembox new | Name = Methylsulfonylmethane | ImageFileL1 = Me2SO2.png | ImageSizeL1 = 100px | ImageNameL1 = Methylsulfonylmethane | ImageFileR1 = Dimethylsulfone-3D-vdW.png | ImageSizeR1 = 100px | ImageNameR1 = Dimethylsulfone | IUPACName = dimethyl sulfone | OtherNames = methyl sulfone<br />methylsulfonylmethane<br />sulfonylbismethane<br />DMSO<sub>2</sub> | Section1 = {{Chembox Identifiers | SMILES = CS(C)(=O)=O | CASNo = 67-71-0 | RTECS = PB2785000 }} | Section2 = {{Chembox Properties | Formula = C<sub>2</sub>H<sub>6</sub>O<sub>2</sub>S | MolarMass = 94.13 g/mol | Appearance = white crystalline solid | Density = 1.45 g/mL g/cm<sup>3</sup>, ? | Solubility = miscible | MeltingPt = 109 °C (382 K) | BoilingPt = 238 °C (511 K) | Viscosity = }} | Section7 = {{Chembox Hazards | ExternalMSDS = [http://www.cise.columbia.edu/clean/msds/dimethylsulfoxide.pdf External MSDS] | MainHazards = | NFPA-H = 1 | NFPA-F = 1 | NFPA-R = | FlashPt = 143 °C | RPhrases = | SPhrases = 24/25 }} | Section8 = {{Chembox Related | Function = [[sulfone]]s | OtherFunctn = | OtherCpds = [[Dimethyl sulfoxide|DMSO]]<br />[[dimethyl sulfide]]<br />[[sulfolane]] }} }} '''Methylsulfonylmethane''' (MSM, or dimethylsulfone) is an [[organosulfur compound]] with the [[chemical formula|formula]] (CH<sub>3</sub>)<sub>2</sub>SO<sub>2</sub>. This colourless solid features the [[sulfone]] [[functional group]] and is considered relatively inert chemically. It occurs naturally in some primitive plants and is present in small amounts in many foods and beverages and it is marketed as a [[dietary supplement]], although its benefits are disputed. ==Structure and chemical properties== MSM is structurally related to [[dimethyl sulfoxide]] (DMSO), but the behavior of these two species is different. DMSO is a highly polar solvent and an excellent ligand, with water-like dissolving properties whereas MSM is relatively less polar and less reactive. ==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.<ref>Georges Hareau and Philip Kocienski, "Dimethyl Sulfone" in Encyclopedia of Reagents for Organic Synthesis 2001 John Wiley & Sons. DOI: 10.1002/047084289X.rd371</ref> With a pK<sub>a</sub> of 31, it can be deprotonated with [[sodium amide]], and the conjugate base is an effective [[nucleophile]]. ==Effects on health== MSM is promoted as a natural source of sulfur by the supplement and health food industry, suggesting that people are deficient in sulfur intake. However, protein in the diet is an abundant source of sulfur, which is contained in the [[amino acids]] [[methionine]] and [[cysteine]]. The efficacy of MSM has been questioned. Clinical research on the medical use of the chemical is limited to a few pilot studies that have suggested beneficial effects.{{Fact|date=October 2007}} MSM is sold as a [[dietary supplement]] that is marketed with a variety of claims and is commonly used (often in combination with [[glucosamine]] and/or [[chondroitin]]) for helping to treat or prevent [[osteoarthritis]]. U.S. Retail sales of MSM as a single ingredient in dietary supplements amounted to $115 million in 2003. The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has [[anti-inflammatory]] effects (Morton ''et al.'' 1986; Childs, 1994; Murav'ev ''et al.'', 1991). Any health effects of dimethyl sulfoxide (DMSO) may be mediated, at least in part, by MSM (Williams et al, 1966; Kocsis et al, 1975). [[Stanley W. Jacob]], M.D., of the [[Oregon Health and Science University]], claims to have used MSM to treat over 18,000 patients with a variety of ailments (Jacob & Appleton, 2003). MSM is the primary [[metabolite]] of DMSO in humans. ===Evidence from clinical trials=== Clinical evidence for the usefulness of MSM is limited to animal studies and four published clinical studies in humans. These pilot studies of MSM have suggested some benefits, particularly for treatment of osteoarthritis. Further studies would be needed to test the usefulness of the chemical as a medical therapy. * '''Osteoarthritis''': After several reports that MSM helped arthritis in [[animal model]]s, a [[double-blind]], [[placebo|placebo-controlled]] study suggested that 1500 mg per day MSM (alone or in combination with glucosamine sulfate) was helpful in relieving symptoms of knee [[osteoarthritis]] (Usha and Naidu 2004). Kim ''et al.'' then conducted a double-blind clinical trial of MSM for treatment of patients with osteoarthritis of the knee. Twenty-five patients took 6 g/day MSM and 25 patients took a placebo for 12 weeks. Ten patients did not complete the study, and [[intention to treat analysis]] was performed. Patients who took MSM had significantly reduced pain and improved physical functioning, without major adverse events (Kim et al). No evidence of a more general anti-inflammatory effect was found, as there were no significant changes in two measures of systemic inflammation: [[C-reactive protein]] level and [[erythrocyte sedimentation rate]]. The authors cautioned that this short pilot study did not address the long-term safety and usefulness of MSM, but suggested that physicians should consider its use for certain osteoarthritis patients, and that long-term studies should be conducted (Kim ''et al.'' 2006). * '''Seasonal Allergic Rhinitis''': Barrager ''et al.'' evaluated the efficacy of MSM for [[hayfever]] (Barrager et al, 2002). Twenty-five subjects consumed 2,600 mg of MSM per day for 30 days, and a significant improvement in symptoms was observed compared to those taking a placebo. However, the study was not [[double-blind|blinded]]. Also, no significant changes were observed in two indicators of inflammation ([[C-reactive protein]] and [[immunoglobulin E]] levels). The authors suggest that MSM is safe for short-term use and recommend that a larger, double-blind study be performed to establish its usefulness in treating symptoms of seasonal allergic rhinitis. * '''Interstitial cystitis''': In 1978, the FDA approved [[dimethyl sulfoxide]] (DMSO) for instillation into the bladder as a treatment for interstitial cystitis. Since DMSO is metabolized to MSM by the body, it is possible that MSM is the active ingredient in DMSO treatments (Childs 1994). * '''Snoring''': Blum & Blum conducted a randomized, double-blind, placebo controlled clinical trial of an MSM-containing throat spray for snoring (Blum & Blum, 2004). ===Pharmacology and toxicity=== The [[LD50]] (dose at which 50% of test subjects are killed) 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 (Horvath ''et al.'', 2002). [[Nuclear magnetic resonance]] (NMR) studies have demonstrated that oral doses of MSM are absorbed into the blood and cross the [[blood-brain barrier]] (Rose ''et al.'', 2000; Lin ''et al.'', 2001). 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 (Engelke ''et al.'', 2005). The published clinical trials of MSM did not report any serious side-effects of treatment, but there are no peer-reviewed data on the effects of long-term use in humans. ==Miscellaneous== According to U.S. law enforcement officials, MSM is used to dilute [[methamphetamine]] in the [[illegal drug trade]]. [http://www.whitehousedrugpolicy.gov/publications/drugfact/pulsechk/nov02/meth.html] ==References== <references /> *Barrager E, Veltmann JR, Schauss AG, Schiller RN. A multi-centered, open label trial on the safety and efficacy of methylsulfonylmethane in the treatment of seasonal allergic rhinitis. ''J Altern Complement Med'' 2002;8:167–74. PMID 12006124 * Blum JM, Blum RI. The effect of methylsulfonylmethane (MSM) in the control of snoring. ''Integrative Medicine'' 2004;3(6)24-30. *Childs SJ. Dimethyl sulfone (DMSO2) in the treatment of interstitial cystitis. ''Urol Clin North Am'' 1994;21:85–8. PMID 8284850 *Engelke UF, Tangerman A, Willemsen MA, Moskau D, Loss S, Mudd SH, Wevers RA. 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 Aug;18(5):331-6. PMID 15996001 *Horváth K, Noker PE, Somfai-Relle S, ''et al.'' Toxicity of methylsulfonylmethane in rats. ''Food Chem Toxicol'' 2002;40:1459–62. PMID 12387309 *Jacob SW, Appleton J. ''MSM-The Definitive Guide'' (Topanga, Freedom Press, 2003) ISBN 1-893910-21-0 * 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):286–94. PMID 16309928 *King CJ. ''Separation Processes'', 2nd ed. New York, McGraw-Hill, 1980. ISBN 0-07-034612-7 *Kocsis JJ, Harkaway S, Snyder R. Biological effects of the metabolites of dimethyl sulfoxide. ''Ann N Y Acad Sci'' 1975;243:104–9. PMID 1055534 *Lin A, Nguy CH, Shic F, Ross BD. Accumulation of methylsulfonylmethane in the human brain: identification by multinuclear magnetic resonance spectroscopy. ''Toxicol Lett'' 2001;123:169–77. PMID 11641045 *Morton JI, Siegel BV. Effects of oral dimethyl sulfoxide and dimethyl sulfone on murine autoimmune lymphoproliferative disease. ''Proc Soc Exp Biol Med'' 1986;183:227–30. PMID 3489943 *Murav'ev IuV, Venikova MS, Pleskovskaia GN, ''et al.'' [Effect of dimethyl sulfoxide and dimethyl sulfone on a destructive process in the joints of mice with spontaneous arthritis]. ''Patol Fiziol Eksp Ter'' 1991;(2):37–9 [in Russian]. PMID 1881708 *Pearson TW, Dawson HJ, Lackey HB. Natural occurring levels of dimethyl sulfoxide in selected fruits, vegetables, grains and beverages. ''J Agric Food Chem'' 1981;29:1019–21. PMID 7309994 *Pfiffner JJ, North HB. Dimethyl sulfone: A constituent of the adrenal gland. ''J Biol Chem'' 1940;134:781–2. [http://www.jbc.org/cgi/reprint/134/2/781 PDF online]. *Rose SE, Chalk JB, Galloway GJ, Doddrell DM. Detection of dimethyl sulfone in the human brain by ''in vivo'' proton magnetic resonance spectroscopy. ''Magn Reson Imaging'' 2000;18:95–8. PMID 10642107 *Usha PR, Naidu MUR. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. ''Clin Drug Invest'' 2004;24(6):353–63. *Williams KIH, Burstein SH, Layne DS. Dimethyl sulfone: isolation from cows’ milk. ''Proc Soc Exp Biol Med'' 1966;122:865–6. PMID 5918965 *Williams KIH, Burstein SH, Layne. Metabolism of dimethyl sulfide, dimethyl sulfoxide, and dimethyl sulfone in the rabbit. ''Arch Biochem Biophys'' 1966;117:84–7. PMID 5971744 ==External links== * [http://www.quackwatch.org/01QuackeryRelatedTopics/DSH/msm.html Quackwatch opinion about Methylsulfonylmethane (MSM)] -- expresses negative view of research published prior to April 2001 [[Category:Dietary supplements]] [[Category:Solvents]] [[Category:Sulfones]] [[cs:Methylsulfonylmethan]] [[da:Metylsufonylmetan]] [[de:Dimethylsulfon]] [[fi:Metyylisulfonyylimetaani]]