Methylsulfonylmethane

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Methylsulfonylmethane
Methylsulfonylmethane
Dimethylsulfone
Names
IUPAC name
dimethyl sulfone
Preferred IUPAC name
(methanesulfonyl)methane
Other names
methyl sulfone
methylsulfonylmethane
sulfonylbismethane
DMSO2
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.605
KEGG
RTECS number PB2785000
UNII
Properties
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 248[1] °C (478 °F; 521 K)
Hazards
Safety data sheet External MSDS
S-phrases (outdated) S22 S24/25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 oilHealth code 1: Exposure would cause irritation but only minor residual injury. E.g., turpentineReactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogenSpecial hazards (white): no codeNFPA 704 four-colored diamond
1
1
0
Flash point 143 °C (289 °F; 416 K)
Related compounds
Related compounds
DMSO
dimethyl sulfide
dimethyl sulfate
sulfolane
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

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]

Structure and chemical properties[edit]

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[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.[6] 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 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[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;[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[edit]

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[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 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]

Safety[edit]

Extensive research in animal models indicates MSM has a very low toxicity when administered both orally and topically.[20][21][22]

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.[23][24] 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.[25] MSM is considered 'Possibly Safe' at therapeutic doses, although further research is still needed to assess its safety for long-term use.[19][26]

Osteoarthritis[edit]

A review of two small randomized controlled trials of methylsulfonylmethane in osteoarthritis (OA) knee pain relief[23][27] "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.[28]

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."[24]
  • 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.[25]

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.[29]

Oxidative stress and inflammation[edit]

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.[30][31] In a second small trial the total antioxidant capacity was significantly increased after taking MSM.[32] Studies in animals indicate a hepatoprotective effect of MSM against several toxins including acetaminophen, paraquat, and carbon tetrachloride.[33][34][35][36] Animal models of experimental colitis and pulmonary hypertension indicate a protective effect as well.[37][38]

Notes[edit]

  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". www.justice.gov. 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 0471936235.
  7. ^ Horváth K, Noker PE, Somfai-Relle S, Glávits R, Financsek I, Schauss AG (October 2002). "Toxicity of methylsulfonylmethane in rats". Food and Chemical Toxicology. 40 (10): 1459–62. doi:10.1016/S0278-6915(02)00086-8. PMID 12387309.
  8. ^ Rose SE, Chalk JB, Galloway GJ, Doddrell DM (January 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.
  9. ^ Lin A, Nguy CH, Shic F, Ross BD (September 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.
  10. ^ Engelke UF, Tangerman A, Willemsen MA, Moskau D, Loss S, Mudd SH, Wevers RA (August 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.
  11. ^ Jacob S (2003). MSM the Definitive Guide: Nutritional Breakthrough for Arthritis, Allergies and More. Freedom Press. ISBN 978-1-893910-22-5.[page needed]
  12. ^ Jacob S, Lawrence RM, Zucker M (1999). The Miracle of MSM: The Natural Solution for Pain. New York: Penguin-Putnam.
  13. ^ Lang KL (17 June 2001). "Methylsulfonylmethane (MSM)". Quackwatch. Retrieved 2011-03-12.
  14. ^ US granted 4514421, Herschler RJ, "Dietary and pharmaceutical uses of methylsulfonylmethane and compositions comprising it", issued 30 April 1985 
  15. ^ Shanmugam S, Baskaran R, Nagayya-Sriraman S, Yong C, Choi H, Woo J, Yoo B (31 July 2009). "The Effect of Methylsulfonylmethane on Hair Growth Promotion of Magnesium Ascorbyl Phosphate for the Treatment of Alopecia". Biomolecules and Therapeutics. 17 (3): 241–248. doi:10.4062/biomolther.2009.17.3.241.
  16. ^ Morton JI, Siegel BV (November 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.
  17. ^ Kocsis JJ, Harkaway S, Snyder R (January 1975). "Biological effects of the metabolites of dimethyl sulfoxide". Annals of the New York Academy of Sciences. 243: 104–9. Bibcode:1975NYASA.243..104K. doi:10.1111/j.1749-6632.1975.tb25349.x. PMID 1055534.
  18. ^ "Agency Response Letter GRAS Notice No. GRN 000229". fda.gov. 2008.
  19. ^ a b "MSM Monograph". Natural Medicines Comprehensive Database. Therapeutic Research Faculty. Retrieved 14 July 2015.
  20. ^ Schoenig G (1968). Acute oral toxicity of sample No. 751, dimethyl sulfone 1 BT No. A6409. Northbrook, Illinois: Industrial BIO-TEST Laboratories, Inc.
  21. ^ Kababick JP (1999). Ocular and Dermal Irritation Assay for OptiMSM Brand of Methylsulfonylmethane. Grants Pass, Oregon: Flora Research Laboratories.
  22. ^ Takiyama K, Konishi F, Nakashima Y, Mumamoto C (2010). "Single and 13-week Repeated Oral Dose Toxicity Study of Methylsulfonylmethane in Mice". Oyo Yakuri Pharmacometrics. 79: 23–30.
  23. ^ a b Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF (March 2006). "Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial". Osteoarthritis and Cartilage. 14 (3): 286–94. doi:10.1016/j.joca.2005.10.003. PMID 16309928.
  24. ^ a b Debbi EM, Agar G, Fichman G, Ziv YB, Kardosh R, Halperin N, Elbaz A, Beer Y, Debi R (June 2011). "Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study". BMC Complementary and Alternative Medicine. 11: 50. doi:10.1186/1472-6882-11-50. PMC 3141601. PMID 21708034.
  25. ^ a b Pagonis TA (2014). "The Effect of Methylsulfonylmethane on Osteoarthritic Large Joints and Mobility". International Journal of Orthopaedics. 1 (1): 19–24. doi:10.6051/j.issn.2311-5106.2014.01.7.
  26. ^ Bauer BA (6 June 2014). "MSM for arthritis pain: Is it safe?". Expert Answers. Mayo Clinic. Retrieved 14 July 2015.
  27. ^ 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.
  28. ^ Brien S, Prescott P, Bashir N, Lewith H, Lewith G (November 2008). "Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis". Osteoarthritis and Cartilage. 16 (11): 1277–88. doi:10.1016/j.joca.2008.03.002. PMID 18417375.
  29. ^ 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. PMID 17516722.
  30. ^ 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.
  31. ^ Nakhostin-Roohi B, Barmaki S, Khoshkhahesh F, Bohlooli S (October 2011). "Effect of chronic supplementation with methylsulfonylmethane on oxidative stress following acute exercise in untrained healthy men". The Journal of Pharmacy and Pharmacology. 63 (10): 1290–4. doi:10.1111/j.2042-7158.2011.01314.x. PMID 21899544.
  32. ^ Nakhostin-Roohi B, Niknam Z, Vaezi N, Mohammadi S, Bohlooli S (2013). "Effect of single dose administration of methylsulfonylmethane on oxidative stress following acute exhaustive exercise". Iranian Journal of Pharmaceutical Research. 12 (4): 845–53. PMC 3920715. PMID 24523764.
  33. ^ Bohlooli S, Mohammadi S, Amirshahrokhi K, Mirzanejad-Asl H, Yosefi M, Mohammadi-Nei A, Chinifroush MM (August 2013). "Effect of Methylsulfonylmethane Pretreatment on Aceta-minophen Induced Hepatotoxicity in Rats". Iranian Journal of Basic Medical Sciences. 16 (8): 896–900. PMC 3786100. PMID 24106592.
  34. ^ Amirshahrokhi K, Bohlooli S (October 2013). "Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice". Inflammation. 36 (5): 1111–21. doi:10.1007/s10753-013-9645-8. PMID 23595869.
  35. ^ Kamel R, El Morsy EM (September 2013). "Hepatoprotective effect of methylsulfonylmethane against carbon tetrachloride-induced acute liver injury in rats". Archives of Pharmacal Research. 36 (9): 1140–8. doi:10.1007/s12272-013-0110-x. PMID 23591777.
  36. ^ Disilvestro RA, Disilvestro DJ, Disilvestro DJ (2008). "Methylsulfonylmethane (MSM) Intake in Mice Produces Elevated Liver Glutathione and Partially Protects Against Carbon Tetrachloride-Induced Liver Injury". FASEB J. 22 (1): 445–8.
  37. ^ Amirshahrokhi K, Bohlooli S, Chinifroush MM (June 2011). "The effect of methylsulfonylmethane on the experimental colitis in the rat". Toxicology and Applied Pharmacology. 253 (3): 197–202. doi:10.1016/j.taap.2011.03.017. PMID 21463646.
  38. ^ Mohammadi S, Najafi M, Hamzeiy H, Maleki-Dizaji N, Pezeshkian M, Sadeghi-Bazargani H, Darabi M, Mostafalou S, Bohlooli S, Garjani A (2012). "Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress in monocrotaline-induced pulmonary hypertensive rats". Advances in Pharmacological Sciences. 2012: 507278. doi:10.1155/2012/507278. PMC 3478703. PMID 23118745.