Methylsulfonylmethane

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Methylsulfonylmethane
Methylsulfonylmethane Dimethylsulfone
Identifiers
CAS number 67-71-0 YesY
PubChem 6213
ChemSpider 5978 YesY
UNII 9H4PO4Z4FT YesY
KEGG C11142 YesY
ChEBI CHEBI:9349 YesY
ChEMBL CHEMBL25028 YesY
RTECS number PB2785000
Jmol-3D images Image 1
Properties
Molecular formula C2H6O2S
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 238 °C (460 °F; 511 K)
Hazards
MSDS External MSDS
S-phrases S22 S24/25
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oil Health code 1: Exposure would cause irritation but only minor residual injury. E.g., turpentine Reactivity (yellow): no hazard code Special hazards (white): no codeNFPA 704 four-colored diamond
Flash point 143 °C (289 °F; 416 K)
Related compounds
Related compounds DMSO
dimethyl sulfide
dimethyl sulfate
sulfolane
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

Methylsulfonylmethane (MSM) is an organosulfur compound with the formula (CH3)2SO2. It is also known by several other names including DMSO2, methyl sulfone, and dimethyl sulfone.[1] 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 also commonly found in the atmosphere above marine areas, where it is used as a carbon source by the airborne bacteria Afipia,[2] and is found distinctively in human melanoma cells.[3]


Structure and chemical properties[edit]

MSM and the corresponding sulfoxide dimethyl sulfoxide ((CH3)2SO, DMSO) have different physical properties. MSM is a white crystalline solid at STP (m.p. = 109 °C) whereas DMSO is a liquid under standard conditions. 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.

Use as a solvent[edit]

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.[4] With a pKa of 31, it can be deprotonated with sodium amide, and the conjugate base is an effective nucleophile.

Pharmacology and toxicity[edit]

The LD50 (dose at which 50% of test subjects are killed by the high dosage) 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.[5]

Nuclear magnetic resonance (NMR) studies have demonstrated that oral doses of MSM are absorbed into the blood and cross the blood–brain barrier.[6][7] 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.[8]

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[edit]

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;[9] he co-authored a book promoting MSM with a variety of claims, including a utility as a natural source of "biologically active sulfur,"[10] 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).[11]

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.[12]

MSM is sold as a dietary supplement and marketed with a variety of claims, often in combination with glucosamine and/or chondroitin for helping to treat or prevent osteoarthritis. According to one review, "The benefits claimed [for MSM] far exceed the number of scientific studies. It is hard to build a strong case for its use other than for treating arthritis problems."[13]

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.[14] The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has anti-inflammatory effects.[15] 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.[16]

Herschler's patent documents, and much of the alternative medical literature supporting MSM use, claim that "the average diet is deficient in methylsulfonylmethane because it is readily lost during conventional food processing, such as frying, dehydrating, dilution with synthetic fillers and other poorly nutritional additives, cooking, radiation or pasteurizing, and long-term storage".

FDA enforcement action[edit]

In October 2000, the United States Food and Drug Administration warned one MSM promoter, Karl Loren, to cease and desist from making therapeutic claims for MSM, as the marketing of drugs without the approval of the FDA is illegal.[17]

Evidence from clinical trials[edit]

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 osteoarthritis. An extensive list of MSM and DSMO peer reviewed studies is included in S. Parcelli's article "Sulfur in Human Nutrition and Applications in Medicine", Parcell, S., Alternative Medicine Review, 2002; 7(1):22-44. [18]

Osteoarthritis[edit]

A review by S. Brien, P. Prescott, N. Bashir, H. Lewith, and G. Lewith of the two small randomized controlled trials of methylsulfonylmethane in osteoarthritis knee pain relief[19][20] "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."[21]

The two trials included 168 people, of whom 52 received the drug. The review authors state: "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."[21] While one of the two studies suggests that taking MSM for 12 weeks or less may be safe, "further research is needed to assess its safety for long-term use."[22] Side effects of MSM ingestion include stomach upset, diarrhoea, and headache.[22] In the absence of studies into dosage, longer-term safety, and definitive efficacy trials, MSM must be considered experimental and should not be self-administered or prescribed outside clinical trials.[22]

After several reports that MSM helped arthritis in animal models, one study by P.R. Usha et al. had suggested that 1.5 g per day MSM (alone or in combination with glucosamine sulfate) was helpful in relieving symptoms of knee osteoarthritis.[20]

Kim et al. conducted a second 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 reported reduced pain and improved physical function, but no evidence was found of a more general anti-inflammatory effect; there were no significant changes in two measures of systemic inflammation: C-reactive protein level and erythrocyte sedimentation rate.[19]

Interstitial cystitis[edit]

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.[23]

Other conditions[edit]

Barrager et al. evaluated the efficacy of MSM for hay fever.[24] Fifty-five subjects consumed 2.6 g of MSM per day for 30 days. This study was not blinded and did not include controls; while an improvement in symptoms was observed compared to initial baseline, no significant changes were observed in two indicators of inflammation (C-reactive protein and immunoglobulin E levels).

Blum & Blum also conducted a double-blind, placebo-controlled clinical trial of an MSM-containing throat spray to reduce snoring.[25]

Marker for melanoma[edit]

In 2013, the Monell Chemical Senses Center in Philadelphia, United States, found that melanoma cells could be identified by a unique odor signature.[26] Besides differences in isoamyl alcohol and isolvaleric acid, melanoma cells produced dimethyldi- and trisulphide compounds not found in non-cancerous cells.[27] A nanotechnology-based sensor was developed for this purpose which detects dimethyl sulfone.[3]

Notes[edit]

  1. ^ "Various Names for MSM". Retrieved June 8, 2009. 
  2. ^ Natasha DeLeon-Rodriguez, others (full list) (December 19, 2012 (received for review July 15, 2012)). "Microbiome of the upper troposphere: Species composition and prevalence, effects of tropical storms, and atmospheric implications". Retrieved March 1, 2014. "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).
  3. ^ a b "Sniffing for Cancer". Institute for Electrical and Electronic Engineers. 20 Dec 2013. 
  4. ^ Hareau, Georges; Kocienski, Philip (2001). "Dimethyl Sulfone". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rd371. ISBN 0471936235. 
  5. ^ Horváth, K; Noker, PE; Somfai-Relle, S; Glávits, R; Financsek, I; Schauss, AG (2002). "Toxicity of methylsulfonylmethane in rats". Food and chemical toxicology 40 (10): 1459–62. doi:10.1016/S0278-6915(02)00086-8. PMID 12387309. 
  6. ^ Rose, SE; Chalk, JB; Galloway, GJ; Doddrell, DM (2000). "Detection of dimethyl sulfone in the human brain by in vivo proton magnetic resonance spectroscopy". Magnetic resonance imaging 18 (1): 95–8. doi:10.1016/S0730-725X(99)00110-1. PMID 10642107. 
  7. ^ Lin, A; Nguy, CH; Shic, F; Ross, BD (2001). "Accumulation of methylsulfonylmethane in the human brain: Identification by multinuclear magnetic resonance spectroscopy". Toxicology letters 123 (2–3): 169–77. doi:10.1016/S0378-4274(01)00396-4. PMID 11641045. 
  8. ^ Engelke, UF; Tangerman, A; Willemsen, MA; Moskau, D; Loss, S; Mudd, SH; Wevers, RA (2005). "Dimethyl sulfone in human cerebrospinal fluid and blood plasma confirmed by one-dimensional (1)H and two-dimensional (1)H-(13)C NMR". NMR in biomedicine 18 (5): 331–6. doi:10.1002/nbm.966. PMID 15996001. 
  9. ^ Jacob, Stanley (2003). MSM the Definitive Guide: Nutritional Breakthrough for Arthritis, Allergies and More. Freedom Press. ISBN 978-1-893910-22-5. 
  10. ^ Stanley Jacob, R.M. Lawrence, M. Zucker (1999). The Miracle of MSM: The Natural Solution for Pain. New York: Penguin-Putnam. 
  11. ^ Kerry L. Lang, RD (17 June 2001). "Methylsulfonylmethane (MSM)". Quackwatch. Retrieved 2011-03-12. 
  12. ^ R.J. Herschler, "Dietary and pharmaceutical uses of methylsulfonylmethane and compositions comprising it", U.S. Patent 4,514,421. April 30, 1985. Accessed 2011-03-12.
  13. ^ "Pharmacists review the effectiveness, benefits and side effects of MSM". 
  14. ^ Shanmugam, Srinivasan; Baskaran, Rengarajan; Nagayya-Sriraman, Santhoshkumar; et al. 2009. The Effect of Methylsulfonylmethane on Hair Growth Promotion of Magnesium Ascorbyl Phosphate for the Treatment of Alopecia, Biomol. Therapeut. 17(3):241-248. [DOI: 10.4062/biomolther.2009.17.3.241]
  15. ^ Morton, JI; Siegel, BV (1986). "Effects of oral dimethyl sulfoxide and dimethyl sulfone on murine autoimmune lymphoproliferative disease". Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine 183 (2): 227–30. doi:10.3181/00379727-183-42409. PMID 3489943. 
  16. ^ Kocsis, JJ; Harkaway, S; Snyder, R (1975). "Biological effects of the metabolites of dimethyl sulfoxide". Annals of the New York Academy of Sciences 243: 104–9. doi:10.1111/j.1749-6632.1975.tb25349.x. PMID 1055534. 
  17. ^ Warning letter to Karl Loren, Vibrant Life/B&B International", FDA Center for Food Safety and Applied Nutrition, 20 October 2000
  18. ^ Parcell, S (2002). "Sulfur in human nutrition and applications in medicine". Altern Med Rev 7 (1): 22–44. PMID 11896744. 
  19. ^ a b Kim, LS; Axelrod, LJ; Howard, P; Buratovich, N; Waters, RF (2006). "Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: A pilot clinical trial". Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society 14 (3): 286–94. doi:10.1016/j.joca.2005.10.003. PMID 16309928. 
  20. ^ a b 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. 
  21. ^ a b Brien, S; Prescott, P; Bashir, N; Lewith, H; Lewith, G (2008). "Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis". Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society 16 (11): 1277–88. doi:10.1016/j.joca.2008.03.002. PMID 18417375. 
  22. ^ a b c Brent A. Bauer, M.D., "MSM for arthritis pain: Is it safe?", Expert Answers, Mayo Clinic, July 9, 2009. Accessed 2011-03-11.
  23. ^ Childs, SJ (1994). "Dimethyl sulfone (DMSO2) in the treatment of interstitial cystitis". The Urologic clinics of North America 21 (1): 85–8. PMID 8284850. 
  24. ^ Barrager, E; Veltmann, JR; Schauss, AG; Schiller, RN (2002). "A multicentered, open-label trial on the safety and efficacy of methylsulfonylmethane in the treatment of seasonal allergic rhinitis". Journal of alternative and complementary medicine 8 (2): 167–73. doi:10.1089/107555302317371451. PMID 12006124. 
  25. ^ Blum JM, Blum RI. The effect of methylsulfonylmethane (MSM) in the control of snoring. Integrative Medicine 2004;3(6)24-30
  26. ^ "Monell-Led Research Identifies Scent of Melanoma". Monell Chemical Senses Center. 13 June 2013. 
  27. ^ "Nanotechnology Sensor Detects Melanoma". LC GC Chromatography Online. 26 Jul 2013. 

External links[edit]