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m →‎Structure and chemical properties: - removed reference to STP: both DMSO and MSM are solids at STP, whilst DMSO is liquid at warm room temps
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==Structure and chemical properties==
==Structure and chemical properties==
MSM and the corresponding sulfoxide, [[dimethyl sulfoxide]] ((CH<sub>3</sub>)<sub>2</sub>SO, or [[DMSO]]), have different physical properties. MSM is a white crystalline solid at [[Standard Temperature and Pressure|STP]] (m.p. = 109&nbsp;°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.
MSM and the corresponding sulfoxide, [[dimethyl sulfoxide]] ((CH<sub>3</sub>)<sub>2</sub>SO, or [[DMSO]]), have different physical properties. MSM is a white crystalline solid at room temperature (m.p. = 109&nbsp;°C) whereas DMSO is typically a liquid (m.p. = 19&nbsp;°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.


==Use as a solvent==
==Use as a solvent==

Revision as of 11:28, 18 October 2017

Methylsulfonylmethane
Methylsulfonylmethane
Methylsulfonylmethane
Dimethylsulfone
Dimethylsulfone
Names
IUPAC name
dimethyl sulfone
Preferred IUPAC name
methanesulfonylmethane
Other names
methyl sulfone
methylsulfonylmethane
sulfonylbismethane
DMSO2
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.605 Edit this at Wikidata
KEGG
RTECS number
  • PB2785000
UNII
  • InChI=1S/C2H6O2S/c1-5(2,3)4/h1-2H3 checkY
    Key: HHVIBTZHLRERCL-UHFFFAOYSA-N checkY
  • InChI=1/C2H6O2S/c1-5(2,3)4/h1-2H3
    Key: HHVIBTZHLRERCL-UHFFFAOYAG
  • [O-][S++]([O-])(C)C
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
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
1
0
Flash point 143 °C (289 °F; 416 K)
Safety data sheet (SDS) External MSDS
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).
checkY verify (what is checkY☒N ?)

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.[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 also commonly found in the atmosphere above marine areas, where it is used as a carbon source by the airborne bacteria Afipia,[3] and is found distinctively in human melanoma cells.[4]

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.

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.[5] 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.[6]

Nuclear magnetic resonance (NMR) studies have demonstrated that oral doses of MSM are absorbed into the blood and cross the blood/brain barrier.[7][8] 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.[9]

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;[10] he co-authored a book promoting MSM with a variety of claims, including a utility as a natural source of "biologically active sulfur,"[11] 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).[12]

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.[13]

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.[14] 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."[15]. Further, this review points out that even in arthritis, MSM has been used in combination with glucosamine and chondroitin, so that it is hard to determine which agents are responsible for clinical benefit.

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.[16] The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has anti-inflammatory effects.[17] 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.[18]

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.[19]

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.[20]

Safety

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.[20][27]

Osteoarthritis

A review of two small randomized controlled trials of methylsulfonylmethane in osteoarthritis 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," and "the relative safety of MSM, especially when compared to serious risks associated with current OA drugs, makes it a compelling supplement for further research to determine long-term effects, safety, and dosage."[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]

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.[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]

Other conditions

Barrager evaluated the efficacy of MSM for hay fever.[39] 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). A double-blind, placebo-controlled clinical trial of an MSM-containing throat spray to reduce snoring reported a severity decrease of 28% in the placebo group and 54% for the treated group. The difference was statistically significant.[40]

Notes

  1. ^ Gaylord Chemical Company, LLC
  2. ^ "Various Names for MSM" (PDF). Retrieved June 8, 2009.
  3. ^ Natasha DeLeon-Rodriguez, others (full list) (19 December 2012). "Microbiome of the upper troposphere: Species composition and prevalence, effects of tropical storms, and atmospheric implications". Proceedings of the National Academy of Sciences. 110: 2575–2580. doi:10.1073/pnas.1212089110. Retrieved 1 March 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 {{cite journal}}: |author= has generic name (help); External link in |author= (help)CS1 maint: numeric names: authors list (link)(page 5 of 6, quote slightly edited).
  4. ^ "Sniffing for Cancer". Institute for Electrical and Electronic Engineers. 20 Dec 2013. Retrieved March 5, 2017.
  5. ^ Hareau, Georges; Kocienski, Philip (2001), "Dimethyl Sulfone", Encyclopedia of Reagents for Organic Synthesis, doi:10.1002/047084289X.rd371, ISBN 0471936235
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ Jacob, Stanley (2003). MSM the Definitive Guide: Nutritional Breakthrough for Arthritis, Allergies and More. Freedom Press. ISBN 978-1-893910-22-5.
  11. ^ Stanley Jacob; R.M. Lawrence; M. Zucker (1999). The Miracle of MSM: The Natural Solution for Pain. New York: Penguin-Putnam.
  12. ^ Kerry L. Lang, RD (17 June 2001). "Methylsulfonylmethane (MSM)". Quackwatch. Retrieved 2011-03-12.
  13. ^ 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.
  14. ^ "MSM (Methylsulfonylmethane)".
  15. ^ "Pharmacists review the effectiveness, benefits and side effects of MSM".
  16. ^ Shanmugam, Srinivasan; Baskaran, Rengarajan; Nagayya-Sriraman, Santhoshkumar; Yong, Chul-Soon; Choi, Han-Gon; Woo, Jong-Soo; Yoo, Bong-Kyu (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.
  17. ^ 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.
  18. ^ 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. Bibcode:1975NYASA.243..104K. doi:10.1111/j.1749-6632.1975.tb25349.x. PMID 1055534.
  19. ^ "Agency Response Letter GRAS Notice No. GRN 000229". fda.gov. 2008.
  20. ^ a b "MSM Monograph". Natural Medicines Comprehensive Database. Therapeutic Research Faculty. Retrieved 14 July 2015.
  21. ^ Schoenig, G (1968). Acute oral toxicity of sample No. 751, dimethyl sulfone 1 BT No. A6409. Northbrook, Illinois: Industrial BIO-TEST Laboratories, Inc.
  22. ^ Kababick, JP (1999). Ocular and Dermal Irritation Assay for OptiMSM Brand of Methylsulfonylmethane. Grants Pass, Oregon: Flora Research Laboratories.
  23. ^ 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.
  24. ^ 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.
  25. ^ a b Debbi, EM (2011). "Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study". BMC Complement Altern Med. 11 (50): 50. doi:10.1186/1472-6882-11-50. PMC 3141601. PMID 21708034.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  26. ^ a b Pagonis, TA (2014). "The Effect of Methylsulfonylmethane on Osteoarthritic Large Joints and Mobility". Int J Orthopaedics. 1 (1).
  27. ^ Brent A. Bauer, M.D., "MSM for arthritis pain: Is it safe?", Expert Answers, Mayo Clinic, June 6, 2014. Accessed 2015-07-14.
  28. ^ 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.
  29. ^ 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.
  30. ^ Barmaki, S; Bohlooli, S; Khoshkhahesh, F; Nakhostin-Roohi, B (2012). "Effect of methylsulfonylmethane supplementation on exercise-induced muscle damage and total antioxidant capacity". J Sport Med Phys Fit. 52: 170–174.
  31. ^ Nakhostic-Roohi, B; Barmaki, S; Khoshkhahesh, F; Bohlooli, S (2011). "Effects of chronic supplementation with methylsulfonylmethane on oxidative stress following acute exercise in untrained healthy men". J Pharm Pharmacol. 63 (10): 1290–1294. doi:10.1111/j.2042-7158.2011.01314.x.
  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". Iran J Pharm Res. 12 (4): 845–853.
  33. ^ Bohlooli, S; Mohammadi, S; Amirshahrokhi, K (2013). "Effect of methylsulfonylmethane pretreatment on acetaminophen induced hepatotoxicity in rats". Iran J Basic Med Sci. 16 (8): 896–900. PMC 3786100. PMID 24106592.
  34. ^ Amirshahrokhi, K; Bohlooli, S (2013). "Effect of methylsulfonylmethane on paraquate-induced acute lung and liver injury in mice". Inflammation. 36 (5): 1111–1121. doi:10.1007/s10753-013-9645-8.
  35. ^ Kamel, R; El Morsy, EM (2013). "Hepatoprotective effect of methylsulfonylmethane against carbon tetrachloride-induced acute liver injury in rats". Arch Pharm Res. 36 (9): 1140–1148. doi:10.1007/s12272-013-0110-x.
  36. ^ Disilvestro, Robert A; Disilvestro, David J; Disilvestro, Daniel J (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 (2011). "The effect of methylsulfonylmethane on the experimental colitis in the rat". Toxicol Appl Pharmacol. 253 (3): 197–202. doi:10.1016/j.taap.2011.03.017. PMID 21463646.
  38. ^ Mohammadi, S; Najafi, M; Hamzeiy, H (2012). "Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress in monocrotaline-induced pulmonary hypertensive rats". Adv Pharmacol Sci. 2012.
  39. ^ 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.
  40. ^ Blum, JM; Blum, RI (2004). "The effect of methylsulfonylmethane (MSM) in the control of snoring". Integrative Medicine. 3 (6): 24–30.
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