Methylsulfonylmethane

Methylsulfonylmethane
IUPAC name dimethyl sulfone
Preferred IUPAC name methanesulfonylmethane
Other names methyl sulfone methylsulfonylmethane sulfonylbismethane DMSO2
Identifiers
CAS number	67-71-0 Y
PubChem	6213
ChemSpider	5978 Y
UNII	9H4PO4Z4FT Y
KEGG	C11142 Y
ChEBI	CHEBI:9349 Y
ChEMBL	CHEMBL25028 Y
RTECS number	PB2785000
Jmol-3D images	Image 1
SMILES O=S(=O)(C)C
InChI InChI=1S/C2H6O2S/c1-5(2,3)4/h1-2H3 Y Key: HHVIBTZHLRERCL-UHFFFAOYSA-N Y InChI=1/C2H6O2S/c1-5(2,3)4/h1-2H3 Key: HHVIBTZHLRERCL-UHFFFAOYAG
Properties
Molecular formula	C2H6O2S
Molar mass	94.13 g/mol
Appearance	White crystalline solid
Density	1.45 g/cm3
Melting point	109 °C, 382 K, 228 °F
Boiling point	238 °C, 511 K, 460 °F
Hazards
MSDS	External MSDS
S-phrases	S22 S24/25
NFPA 704	1 1 0
Flash point	143 °C
Related compounds
Related compounds	DMSO dimethyl sulfide dimethyl sulfate sulfolane
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
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 and is present in small amounts in many foods and beverages and it is marketed as a dietary supplement.

Structure and chemical properties

MSM is structurally related to dimethyl sulfoxide (DMSO), but the behavior of these two is different. DMSO is a highly polar solvent and an excellent ligand, with water-like dissolving properties whereas MSM is less polar and less reactive. MSM is also a metabolite of DMSO.

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.^[2] With a pK_a of 31, it can be deprotonated with sodium amide, and the conjugate base is an effective nucleophile.

Effects on health

Stanley W. Jacob reported having administered MSM to over 18,000 patients with a variety of ailments;^[3] he co-authored a book promoting MSM with a variety of claims, including its supposed utility as a natural source of "biologically active sulfur,"^[4] 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 sulphur; it is readily available in onions, garlic and cruciferous vegetables and in protein-containing foods, including nuts, seeds, milk and eggs.^[5]

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.^[6] Registered dietitian Kerry Lang on quackwatch disparages this claim, pointing out:^[5]

Herschler's patent documents 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.' This statement is absurd, because the amount of sulfur in protein foods is not affected by processing. Since Americans tend to consume more protein than they need, 'sulfur deficiency' is very unlikely and would not occur without obvious evidence of severe malnutrition. If it could occur, the remedy would be to eat adequate protein, not to supplement with MSM.

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."^[7] The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has anti-inflammatory effects.^[8] 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.^[9]

FDA enforcement action

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.^[10]

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 osteoarthritis.

Osteoarthritis

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^[11][12] "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."^[13]

The two trials included only 168 people, of whom 52 actually received the drug, so the review authors are careful to 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."^[13] 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."^[14] Side effects of MSM ingestion include stomach upset, diarrhoea and headache.^[14] 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.^[14]

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.^[12] The Usha clinical trial, however, was outsourced to India and conducted by researchers with little prior experience in clinical trials; tests were described without associated data, while some results were unsupported by the data that was shown. K.S. Jayaraman has warned that such outsourcing of clinical trials can be "rash" and "risky," citing deficient ethics committees as well as an unethical approach to patient recruitment.^[15]

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.^[11] Not counting an unpublished, no-control group trial by Lawrence, these two articles are the only clinical-trial support for MSM for osteoarthritis.

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.^[16]

Other conditions

Barrager et al. evaluated the efficacy of MSM for hay fever.^[17] Fifty-five subjects consumed 2.6 g of MSM per day for 30 days. This study was not blinded; while an improvement in symptoms was observed compared to those taking a placebo, 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.^[18]

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.^[19]

Nuclear magnetic resonance (NMR) studies have demonstrated that oral doses of MSM are absorbed into the blood and cross the blood-brain barrier.^[20][21] 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.^[22]

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.

Notes

1. ^ Various Names for MSM Retrieved June 8, 2009.
2. ^ Georges Hareau and Philip Kocienski, "Dimethyl Sulfone" in Encyclopedia of Reagents for Organic Synthesis 2001 John Wiley & Sons. DOI: 10.1002/047084289X.rd371
3. ^ Stanley Jacob, MSM the Definitive Guide: Nutritional Breakthrough for Arthritis, Allergies and More. Freedom Press, 2003. ISBN 9781893910225
4. ^ Stanley Jacob, R.M. Lawrence, M. Zucker, "The Miracle of MSM: The Natural Solution for Pain." New York: Penguin-Putnam, 1999.
5. ^ ^{a b} Kerry L. Lang, RD, "Methylsulfonylmethane (MSM)", Quackwatch, 17 June 2001. Accessed 2011-03-12.
6. ^ 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.
7. ^ "Pharmacists review the effectiveness, benefits and side effects of MSM". http://www.natural-remedies-review.com/msm.html. 
8. ^ 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
9. ^ 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
10. ^ Warning letter to Karl Loren, Vibrant Life/B&B International", FDA Center for Food Safety and Applied Nutrition, 20 October 2000
11. ^ ^{a b} 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 and Cartilage. 2006;14(3):286–94. PMID 16309928
12. ^ ^{a b} Usha PR, et al. "Double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis." Clinical Drug Investigation. 2004;24:353-63.
13. ^ ^{a b} Brien S, et al., "Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis", Osteoarthritis and Cartilage. 2008;16:1277e.
14. ^ ^{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.
15. ^ Jayaraman K.S., "Outsourcing clinical trials to India rash and risky, critics warn". Nat Med 2004;10:440.
16. ^ Childs SJ. Dimethyl sulfone (DMSO2) in the treatment of interstitial cystitis. Urol Clin North Am 1994;21:85–8. PMID 8284850
17. ^ 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
18. ^ Blum JM, Blum RI. The effect of methylsulfonylmethane (MSM) in the control of snoring. Integrative Medicine 2004;3(6)24-30
19. ^ Horváth K, Noker PE, Somfai-Relle S, et al. Toxicity of methylsulfonylmethane in rats. Food Chem Toxicol 2002;40:1459–62. PMID 12387309
20. ^ 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
21. ^ 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
22. ^ 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

External links

• Quackwatch opinion about Methylsulfonylmethane (MSM) -- clinical dietician skeptical of MSM's marketing claims