Methylsulfonylmethane: Difference between revisions

| Watchedfields = changed

| verifiedrevid = 443307912

| Name = Dimethyl sulfone

| ImageFile1_Ref = {{chemboximage|correct|??}}

| ImageFile1 = Me2SO2.png

| = Methylsulfonylmethane

| = Dimethylsulfone-3D-vdW.png

| ImageName2 = Dimethylsulfone

| PIN = (Methanesulfonyl)methane

| OtherNames = methyl sulfone<br />methylsulfonylmethane<br />sulfonylbismethane<br />DMSO₂

| Section1 = {{Chembox Identifiers

|CASNo = 67-71-0

|CASNo_Ref = {{cascite|correct|CAS}}

|Abbreviations = MSM

|Beilstein = 1737717

| = {{|correct|}}

|ChEBI = 9349

|ChEMBL_Ref = {{ebicite|correct|EBI}}

|ChEMBL = 25028

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|ChemSpiderID = 5978

|EC_number = 200-665-9

|Gmelin = 130437

|PubChem = 6213

| = {{|correct|}}

| =

|InChI = 1/C2H6O2S/c1-5(2,3)4/h1-2H3

|InChIKey = HHVIBTZHLRERCL-UHFFFAOYAG

|RTECS = PB2785000

|UNII_Ref = {{fdacite|correct|FDA}}

|UNII = 9H4PO4Z4FT

| = {{|correct|}}

|StdInChI = 1S/C2H6O2S/c1-5(2,3)4/h1-2H3

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = HHVIBTZHLRERCL-UHFFFAOYSA-N

|SMILES = [O-][S++]([O-])(C)C

}}

| Section2 = {{Chembox Properties

|C=2 | H=6 | O=2 | S=1

|Appearance = White crystalline solid

|Density = 1.45 g/cm³

|MeltingPtC = 109

|BoilingPtC = 248<ref>Gaylord Chemical Company, LLC</ref>

}}

| Section3 = {{Chembox Hazards

|ExternalSDS = [https://web.archive.org/web/20070609155852/http://www.cise.columbia.edu/clean/msds/dimethylsulfoxide.pdf External MSDS]

|NFPA-H = 1

|NFPA-F = 1

|NFPA-R =

| = 143

|Hazards_ref=<ref>{{cite web |title=Dimethyl sulfone |url=https://pubchem.ncbi.nlm.nih.gov/compound/6213#section=Safety-and-Hazards |website=pubchem.ncbi.nlm.nih.gov |language=en}}</ref>

| = {{}}

|GHSSignalWord = Warning

|HPhrases = {{H-phrases|319}}

|PPhrases = {{P-phrases|264|280|305+351+338|337+313}}

|LD50 = 5g/kg (oral, rat) <ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/Dimethyl-sulfone#section=Toxicity|title = Dimethyl sulfone}}</ref>

}}

| Section4 = {{Chembox Related

|OtherCompounds = [[Dimethyl sulfoxide|DMSO]]<br />[[dimethyl sulfide]]<br />[[dimethyl sulfate]]<br />[[sulfolane]]

}}

'''Dimethyl sulfone''' ('''DMSO₂''') is an [[organosulfur compound]] with the [[chemical formula|formula]] (CH₃)₂SO₂. It is also known by several other names including '''methyl sulfone''' and (especially in alternative medicine) '''methylsulfonylmethane''' ('''MSM''').<ref>{{cite web|url= http://www.gaylordchemical.com/bulletins/Bulletin301B/Bulletin301B.pdf|title= Various Names for MSM|access-date= June 8, 2009|url-status= dead|archive-url= https://web.archive.org/web/20110711080324/http://www.gaylordchemical.com/bulletins/Bulletin301B/Bulletin301B.pdf|archive-date= July 11, 2011}}</ref> This colorless solid features the [[sulfonyl]] [[functional group]] and is the simplest of the sulfones. It is relatively inert chemically and is able to resist decomposition at elevated temperatures. It occurs naturally in some primitive plants, is present in small amounts in many foods and beverages, and is marketed (under the MSM name) as a [[dietary supplement]]. It is sometimes used as a [[cutting agent]] for illicitly manufactured [[methamphetamine]].<ref>{{Cite web|url=https://www.justice.gov/archive/ndic/pubs1/1837/1837t.htm|title=Information Bulletin: Crystal Methamphetamine|website=www.justice.gov|access-date= 20 January 2018 }}</ref> It is also commonly found in the atmosphere above marine areas, where it is used as a carbon source by the airborne bacteria ''[[Afipia]]''.<ref>{{cite journal | vauthors = DeLeon-Rodriguez N, Lathem TL, Rodriguez-R LM, Barazesh JM, Anderson BE, Beyersdorf AJ, Ziemba LD, Bergin M, Nenes A, Konstantinidis KT | title = Microbiome of the upper troposphere: species composition and prevalence, effects of tropical storms, and atmospheric implications | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 7 | pages = 2575–80 | date = February 2013 | pmid = 23359712 | pmc = 3574924 | doi = 10.1073/pnas.1212089110 | quote = 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 | bibcode = 2013PNAS..110.2575D | doi-access = free }}(page 5 of 6, quote slightly edited).</ref> Oxidation of [[dimethyl sulfoxide]] produces the sulfone, both under laboratory conditions and metabolically.<ref name="pmid25245235">{{cite journal | vauthors = He X, Slupsky CM | title = Metabolic fingerprint of dimethyl sulfone (DMSO2) in microbial-mammalian co-metabolism | journal = Journal of Proteome Research | volume = 13 | issue = 12 | pages = 5281–92 | date = December 2014 | pmid = 25245235 | doi = 10.1021/pr500629t | url = http://www.escholarship.org/uc/item/7w78k2pt }}</ref>

Because of its polarity and thermal stability, used industrially as a high-temperature [[solvent]]. For example, displacement of aryl chlorides by [[potassium fluoride]] conducted in .<ref> Dimethyl Sulfone Encyclopedia of Reagents for Organic Synthesis 2001 </>

With a pK_a of 31, the sulfone can be deprotonated with [[sodium amide]]. The conjugate base has been used as a [[nucleophile]].

==Pharmacology and toxicity==

[[Nuclear magnetic resonance]] (NMR) studies have demonstrated that oral doses of MSM are absorbed into the blood and cross the [[blood–brain barrier|blood/brain barrier]].<ref>{{cite journal | vauthors = Rose SE, Chalk JB, Galloway GJ, Doddrell DM | title = Detection of dimethyl sulfone in the human brain by in vivo proton magnetic resonance spectroscopy | journal = Magnetic Resonance Imaging | volume = 18 | issue = 1 | pages = 95–8 | date = January 2000 | pmid = 10642107 | doi = 10.1016/S0730-725X(99)00110-1 }}</ref><ref>{{cite journal | vauthors = Lin A, Nguy CH, Shic F, Ross BD | title = Accumulation of methylsulfonylmethane in the human brain: identification by multinuclear magnetic resonance spectroscopy | journal = Toxicology Letters | volume = 123 | issue = 2–3 | pages = 169–77 | date = September 2001 | pmid = 11641045 | doi = 10.1016/S0378-4274(01)00396-4 }}</ref> 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.<ref>{{cite journal | vauthors = Engelke UF, Tangerman A, Willemsen MA, Moskau D, Loss S, Mudd SH, Wevers RA | title = Dimethyl sulfone in human cerebrospinal fluid and blood plasma confirmed by one-dimensional (1)H and two-dimensional (1)H-(13)C NMR | journal = NMR in Biomedicine | volume = 18 | issue = 5 | pages = 331–6 | date = August 2005 | pmid = 15996001 | doi = 10.1002/nbm.966 | s2cid = 34324509 }}</ref>

==Medical and dietary use==

Although no medical uses for MSM have been approved, 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;<ref name="jacob1">{{Cite book |first=Stanley |last=Jacob | name-list-style = vanc |title=MSM the Definitive Guide: Nutritional Breakthrough for Arthritis, Allergies and More |publisher=Freedom Press |year=2003 |isbn=978-1-893910-22-5}}{{page needed|date=June 2018}}</ref> he co-authored a book promoting MSM with a variety of claims, including a utility as a natural source of "biologically active [[sulfur]],"<ref name="jacob2">{{Cite book | vauthors = Jacob S, Lawrence RM, Zucker M |title=The Miracle of MSM: The Natural Solution for Pain |location=New York |publisher=Penguin-Putnam |year=1999}}</ref> 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 but notable dietary sources include [[cruciferous vegetables]], [[garlic]], [[onions]], [[asafoetida]], [[legumes]], [[nut (food)|nut]]s, [[seeds]], [[plant milk]], [[animal milk]] and [[egg as food|eggs]] (whites and yolks).<ref name="lang">{{cite web | first = Kerry L. | last = Lang | name-list-style = vanc | url = http://www.quackwatch.org/01QuackeryRelatedTopics/DSH/msm.html |title=Methylsulfonylmethane (MSM) |work=Quackwatch |date=17 June 2001 |access-date=2011-03-12}}</ref>

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.<ref name="herschler">{{cite patent |country= US |number= 4514421 |status= granted |title= Dietary and pharmaceutical uses of methylsulfonylmethane and compositions comprising it |pubdate= |gdate= 30 April 1985 |fdate= |pridate= |inventor= Herschler RJ |assign1= }}</ref>

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.<ref>{{cite journal |last1=Shanmugam |first1=Srinivasan |last2=Baskaran |first2=Rengarajan |last3=Nagayya-Sriraman |first3=Santhoshkumar |last4=Yong |first4=Chul-Soon |last5=Choi |first5=Han-Gon |last6=Woo |first6=Jong-Soo |last7=Yoo |first7=Bong-Kyu | name-list-style = vanc |title=The Effect of Methylsulfonylmethane on Hair Growth Promotion of Magnesium Ascorbyl Phosphate for the Treatment of Alopecia |journal= Biomolecules and Therapeutics|date=31 July 2009 |volume=17 |issue=3 |pages=241–248 |doi=10.4062/biomolther.2009.17.3.241|doi-access=free }}</ref>

The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has [[anti-inflammatory]] effects.<ref>{{cite journal | vauthors = Morton JI, Siegel BV | s2cid = 23242700 | title = Effects of oral dimethyl sulfoxide and dimethyl sulfone on murine autoimmune lymphoproliferative disease | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 183 | issue = 2 | pages = 227–30 | date = November 1986 | pmid = 3489943 | doi = 10.3181/00379727-183-42409 }}</ref>

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.<ref>{{cite journal | vauthors = Kocsis JJ, Harkaway S, Snyder R | title = Biological effects of the metabolites of dimethyl sulfoxide | journal = Annals of the New York Academy of Sciences | volume = 243 | issue = 1 | pages = 104–9 | date = January 1975 | pmid = 1055534 | doi = 10.1111/j.1749-6632.1975.tb25349.x | bibcode = 1975NYASA.243..104K | s2cid = 45625081 }}</ref>

== 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.<ref>{{cite web |url=https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm153891.htm |title=Agency Response Letter GRAS Notice No. GRN 000229 |work=fda.gov |year=2008}}</ref>

==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.

======

A South Korean study focussing on the role of MSM affecting [[growth factor]]s associated with breast cancer identifies MSM to have multiple targets, both [[in vitro]] and [[in vivo]], including [[STAT3]], [[STAT protein|STAT5b]], [[Insulin-like growth factor 1 receptor|IGF-1R]] and [[Vascular endothelial growth factor|VEGF]], confirming the ability of MSM to suppress tumor initiation, growth and metastasis in a dose dependent manner. The expression of triple negative hormone receptors is also down regulated by MSM. In a xenograft model the mice showed inhibited tumor cell migration and suppressed tumor growth in a dose dependent manner when receiving MSM as part of their drinking water at nul, three or five percent MSM weight over volume. The authors strongly recommend MSM as a trial drug for treating breast cancers because of its multi-targeting mechanism.<ref>{{Cite journal|last1=Lim|first1=Eun Joung|last2=Hong|first2=Dae Young|last3=Park|first3=Jin Hee|last4=Joung|first4=Youn Hee|last5=Darvin|first5=Pramod|last6=Kim|first6=Sang Yoon|last7=Na|first7=Yoon Mi|last8=Hwang|first8=Tae Sook|last9=Ye|first9=Sang-Kyu|last10=Moon|first10=Eon-Soo|last11=Cho|first11=Byung Wook|date=2012|title=Methylsulfonylmethane suppresses breast cancer growth by down-regulating STAT3 and STAT5b pathways|journal=PLOS ONE|volume=7|issue=4|pages=e33361|doi=10.1371/journal.pone.0033361|issn=1932-6203|pmc=3317666|pmid=22485142|bibcode=2012PLoSO...733361L|doi-access=free}}</ref>

====HDL cholesterol====

A small 2021 Randomized Controlled Trial on cardiometabolic markers found a possible relationship between a daily dose of 3 g of MSM and [[high-density lipoprotein]] (HDL) levels on overweight and obese people. The MSM group demonstrated higher HDL levels after 16 weeks (51.8 ± 2.8&nbsp;mg/dL) when compared to the baseline (44.9 ± 3.7&nbsp;mg/dL) and also versus the placebo group (42.7 ± 2.5&nbsp;mg/dL at baseline vs 48.0 ± 4.9&nbsp;mg/DL at 16 weeks). Other markers (inflammation, fasting glucose, resting heart rate, etc.) showed no significant changes between baseline and 16 weeks on either the placebo or the MSM groups with the exception of [[C-reactive protein]] levels, which were higher on the placebo group than on the MSM group at baseline and continued to increase up to the 16 weeks mark while showing a very slight decrease on the MSM group. However, the authors state they cannot explain why CRP levels were higher on the placebo group nor whether MSM may play a stabilizing role on CRP. The authors also state more and larger studies are required to establish the relationship between MSM and HDL.<ref>{{Cite journal|last1=Miller|first1=Lindsey|last2=Thompson|first2=Kari|last3=Pavlenco|first3=Carolina|last4=Mettu|first4=Vijaya Saradhi|last5=Haverkamp|first5=Hans|last6=Skaufel|first6=Samantha|last7=Basit|first7=Abdul|last8=Prasad|first8=Bhagwat|last9=Larsen|first9=Julie|date=October 2021|title=The Effect of Daily Methylsulfonylmethane (MSM) Consumption on High-Density Lipoprotein Cholesterol in Healthy Overweight and Obese Adults: A Randomized Controlled Trial|journal=Nutrients|language=en|volume=13|issue=10|pages=3620|doi=10.3390/nu13103620|pmc=8540167|pmid=34684621|doi-access=free}}</ref>

====Safety====

The {{LD50}} of MSM is greater than 17.5&nbsp;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.<ref>{{cite journal | vauthors = Horváth K, Noker PE, Somfai-Relle S, Glávits R, Financsek I, Schauss AG | title = Toxicity of methylsulfonylmethane in rats | journal = Food and Chemical Toxicology | volume = 40 | issue = 10 | pages = 1459–62 | date = October 2002 | pmid = 12387309 | doi = 10.1016/S0278-6915(02)00086-8 }}</ref>

Extensive research in animal models indicates MSM has a very low toxicity when administered both orally and topically.<ref>{{cite book | vauthors = Schoenig G |title=Acute oral toxicity of sample No. 751, dimethyl sulfone 1 BT No. A6409 |date=1968 |publisher=Industrial BIO-TEST Laboratories, Inc. |location=Northbrook, Illinois}}</ref><ref name=Ocular>{{cite book | vauthors = Kababick JP |title=Ocular and Dermal Irritation Assay for OptiMSM Brand of Methylsulfonylmethane |date=1999 |publisher=Flora Research Laboratories |location=Grants Pass, Oregon}}</ref><ref name=Takiyama>{{cite journal | vauthors = Takiyama K, Konishi F, Nakashima Y, Mumamoto C |title=Single and 13-week Repeated Oral Dose Toxicity Study of Methylsulfonylmethane in Mice |journal=Oyo Yakuri Pharmacometrics |date=2010 |volume=79 |pages=23–30}}</ref>

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.<ref name=kim /><ref name=debbi /> A more recent 26-week study on large joint osteoarthritis observed no adverse events or abnormal changes in lab monitoring when taking 6&nbsp;grams MSM per day.<ref name=pagonis /> MSM is considered 'Possibly Safe' at therapeutic doses, although further research is still needed to assess its safety for long-term use.<ref name=NMCD /><ref name="Bauer">{{cite web | first = Brent A. | last = Bauer | name-list-style = vanc | url = http://www.mayoclinic.com/health/msm/AN00560 | title = MSM for arthritis pain: Is it safe? | work = Expert Answers | publisher = Mayo Clinic | date = 6 June 2014 | access-date = 14 July 2015 }}</ref>

====Osteoarthritis====

A review of two small [[randomized controlled trial]]s of methylsulfonylmethane in [[osteoarthritis]] (OA) knee pain relief<ref name="kim">{{cite journal | vauthors = Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF | title = Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial | journal = Osteoarthritis and Cartilage | volume = 14 | issue = 3 | pages = 286–94 | date = March 2006 | pmid = 16309928 | doi = 10.1016/j.joca.2005.10.003 | doi-access = free }}</ref><ref name="usha">{{cite journal | vauthors = Usha PR, Naidu MU | s2cid = 22184720 | title = Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis | journal = Clinical Drug Investigation | volume = 24 | issue = 6 | pages = 353–63 | year = 2004 | pmid = 17516722 | doi = 10.2165/00044011-200424060-00005 }}</ref> "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."<ref name="review">{{cite journal | vauthors = Brien S, Prescott P, Bashir N, Lewith H, Lewith G | title = Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis | journal = Osteoarthritis and Cartilage | volume = 16 | issue = 11 | pages = 1277–88 | date = November 2008 | pmid = 18417375 | doi = 10.1016/j.joca.2008.03.002 | doi-access = free }}</ref>

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&nbsp;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 [[Visual analogue scale|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."<ref name="debbi">{{cite journal | vauthors = Debbi EM, Agar G, Fichman G, Ziv YB, Kardosh R, Halperin N, Elbaz A, Beer Y, Debi R | title = Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study | journal = BMC Complementary and Alternative Medicine | volume = 11 | pages = 50 | date = June 2011 | pmid = 21708034 | pmc = 3141601 | doi = 10.1186/1472-6882-11-50 | doi-access = free }}</ref>

* 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.<ref name="pagonis">{{cite journal |year=2014 |last1=Pagonis |first1=Thomas A | name-list-style = vanc |title=The Effect of Methylsulfonylmethane on Osteoarthritic Large Joints and Mobility |volume=1 |issue=1 |pages=19–24 |journal=International Journal of Orthopaedics |doi=10.6051/j.issn.2311-5106.2014.01.7 |doi-broken-date=1 November 2024 |url=http://www.ghrnet.org/index.php/ijo/article/view/745/862}}</ref>{{pred |date=July 2024}}

====Synergism of methylsulfonylmethane and glucosamine and chondroitin====

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]].<ref name="usha"/> Two other studies investigated the effects of MSM in combination with glucosamine and [[chondroitin]] (GC) on joint function. In the first study, the GC+MSM group saw significant benefits sooner than the GC group. This suggests that the addition of MSM reduces the time to benefit.<ref name="ARTRA">{{cite journal |last1=Alekseeva |first1=L.I. |last2=Sharapova |first2=E.P. |last3=Kashevarova |first3=N.G. |last4=Taskina |first4=E.A. |last5=Anikin |first5=S.G. |last6=Korotkova |first6=T.A. |last7=Pyanykh |first7=S.E. |title=Use of ARTRA MSM FORTE in patients with knee osteoarthritis: Results of a randomized open-label comparative study of the efficacy and tolerability of the drug |journal=Therapeutic Archive |date=2015 |volume=87 |issue=12 |pages=49–54 |doi=10.17116/terarkh2015871249-54 |pmid=26978418}}</ref> In another, the GC+MSM group saw significant improvements in both WOMAC and VAS pain scores when compared to both the placebo group and GC group. This suggests that the addition of MSM increases the magnitude of benefits.<ref name="LubisGCM">{{cite journal |last1=Lubis |first1=Andri M T |last2=Siagian |first2=Carles |last3=Wonggokusuma |first3=Erick |last4=Marsetyo |first4=Aldo F |last5=Setyohadi |first5=Bambang |title=Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial. |journal=Acta Medica Indonesiana |date=2017 |volume=49 |issue=2 |pages=105–111 |pmid=28790224 |url=http://www.actamedindones.org/index.php/ijim/article/view/168/pdf |access-date=10 April 2020}}</ref>

====Skin, hair, nails====

The first scientific investigation of MSM for skin health was published in 2015. The [[Randomized controlled trial|RCT]] used a 3g per day dose and included only 20 women. Results showed significant improvements in the number and severity of facial wrinkles, firmness, tone and texture.<ref>{{Cite journal|last1=Anthonavage|first1=Michael|last2=Benjamin|first2=Rod|last3=Withee|first3=Eric|date=2015|title=Effects of oral supplementation with methylsulfonylmethane on skin health and wrinkle reduction|url=https://www.naturalmedicinejournal.com/journal/2015-11/effects-oral-supplementation-methylsulfonylmethane-skin-health-and-wrinkle-reduction|journal=Natural Medicine Journal|volume=7|issue=11|pages=1–21}}</ref> Another study evaluated doses of 1g and 3g and showed improvements in wrinkles, firmness, and hydration at both dose levels in 20 persons.<ref>{{Cite journal|last1=Muizzuddin|first1=Neelam|last2=Benjamin|first2=Rodney|date=2020-02-21|title=Beauty from within: Oral administration of a sulfur-containing supplement methylsulfonylmethane improves signs of skin ageing|journal=International Journal for Vitamin and Nutrition Research|volume=92 |issue=3–4 |language=en|pages=182–191|doi=10.1024/0300-9831/a000643|pmid=32083522|s2cid=211232166|issn=0300-9831|doi-access=free}}</ref> The same author published a study on MSM for hair and nails from the same clinical trial. The results showed improvements in hair shine, volume, and appearance, and nail shine and appearance.<ref>{{Cite journal|last1=Muizzuddin|first1=Neelam|last2=Benjamin|first2=Rodney|date=2019|title=Beneficial Effects of a Sulfur-Containing Supplement on Hair and Nail Condition|url=https://www.naturalmedicinejournal.com/journal/2019-11/beneficial-effects-sulfur-containing-supplement-hair-and-nail-condition|journal=Natural Medicine Journal|volume=11|issue=11|pages=1–8}}</ref> An Italian study evaluated the effects of a nutraceutical composed of MSM, [[hyaluronic acid]], and [[Carnosine|L-carnosine]]. The results from RCT showed broad improvements in facial skin hydration and elasticity, as well as decreased sebaceous secretions.<ref>{{Cite journal|last1=Guaitolini|first1=Ennio|last2=Cavezzi|first2=Attilio|last3=Cocchi|first3=Stefania|last4=Colucci|first4=Roberto|last5=Urso|first5=Simone Ugo|last6=Quinzi|first6=Valentina|date=2019|title=Randomized, Placebo-controlled Study of a Nutraceutical Based on Hyaluronic Acid, L-carnosine, and Methylsulfonylmethane in Facial Skin Aesthetics and Well-being|journal=The Journal of Clinical and Aesthetic Dermatology|volume=12|issue=4|pages=40–45|issn=1941-2789|pmc=6508480|pmid=31119010}}</ref>

====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.<ref name=barmaki>{{cite journal | vauthors = Barmaki S, Bohlooli S, Khoshkhahesh F, Nakhostin-Roohi B | title = Effect of methylsulfonylmethane supplementation on exercise - Induced muscle damage and total antioxidant capacity | journal = The Journal of Sports Medicine and Physical Fitness | volume = 52 | issue = 2 | pages = 170–4 | date = April 2012 | pmid = 22525653 | url = http://www.minervamedica.it/index2.t?show=R40Y2012N02A0170 }}</ref><ref name=nakroo>{{cite journal | vauthors = Nakhostin-Roohi B, Barmaki S, Khoshkhahesh F, Bohlooli S | title = Effect of chronic supplementation with methylsulfonylmethane on oxidative stress following acute exercise in untrained healthy men | journal = The Journal of Pharmacy and Pharmacology | volume = 63 | issue = 10 | pages = 1290–4 | date = October 2011 | pmid = 21899544 | doi = 10.1111/j.2042-7158.2011.01314.x | s2cid = 25474694 | url = http://eprints.arums.ac.ir/2588/1/chronic.pdf }}</ref> In a second small trial the total antioxidant capacity was significantly increased after taking MSM.<ref name=naksingle>{{cite journal | vauthors = Nakhostin-Roohi B, Niknam Z, Vaezi N, Mohammadi S, Bohlooli S | title = Effect of single dose administration of methylsulfonylmethane on oxidative stress following acute exhaustive exercise | journal = Iranian Journal of Pharmaceutical Research | volume = 12 | issue = 4 | pages = 845–53 | year = 2013 | pmid = 24523764 | pmc = 3920715 }}</ref> Studies in animals indicate a hepatoprotective effect of MSM against several toxins including [[acetaminophen]], [[paraquat]], and [[carbon tetrachloride]].<ref name=bohlooli>{{cite journal | vauthors = Bohlooli S, Mohammadi S, Amirshahrokhi K, Mirzanejad-Asl H, Yosefi M, Mohammadi-Nei A, Chinifroush MM | title = Effect of Methylsulfonylmethane Pretreatment on Aceta-minophen Induced Hepatotoxicity in Rats | journal = Iranian Journal of Basic Medical Sciences | volume = 16 | issue = 8 | pages = 896–900 | date = August 2013 | pmid = 24106592 | pmc = 3786100 }}</ref><ref name=paraquat>{{cite journal | vauthors = Amirshahrokhi K, Bohlooli S | s2cid = 2209805 | title = Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice | journal = Inflammation | volume = 36 | issue = 5 | pages = 1111–21 | date = October 2013 | pmid = 23595869 | doi = 10.1007/s10753-013-9645-8 }}</ref><ref name=kamel>{{cite journal | vauthors = Kamel R, El Morsy EM | s2cid = 27990171 | title = Hepatoprotective effect of methylsulfonylmethane against carbon tetrachloride-induced acute liver injury in rats | journal = Archives of Pharmacal Research | volume = 36 | issue = 9 | pages = 1140–8 | date = September 2013 | pmid = 23591777 | doi = 10.1007/s12272-013-0110-x }}</ref><ref name=disilv>{{cite journal |last1=Disilvestro |first1=Robert A |last2=Disilvestro |first2=David J |last3=Disilvestro |first3=Daniel J | name-list-style = vanc |title=Methylsulfonylmethane (MSM) Intake in Mice Produces Elevated Liver Glutathione and Partially Protects Against Carbon Tetrachloride-Induced Liver Injury |journal=FASEB J. |date=2008 |volume=22 |issue=1 |pages=445–8|doi=10.1096/fasebj.22.1_supplement.445.8 |doi-access=free |s2cid=84049802 }}</ref> Animal models of experimental colitis and pulmonary hypertension indicate a protective effect as well.<ref name=expcolitis>{{cite journal | vauthors = Amirshahrokhi K, Bohlooli S, Chinifroush MM | title = The effect of methylsulfonylmethane on the experimental colitis in the rat | journal = Toxicology and Applied Pharmacology | volume = 253 | issue = 3 | pages = 197–202 | date = June 2011 | pmid = 21463646 | doi = 10.1016/j.taap.2011.03.017 | bibcode = 2011ToxAP.253..197A }}</ref><ref name=pulmhyp>{{cite journal | vauthors = Mohammadi S, Najafi M, Hamzeiy H, Maleki-Dizaji N, Pezeshkian M, Sadeghi-Bazargani H, Darabi M, Mostafalou S, Bohlooli S, Garjani A | title = Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress in monocrotaline-induced pulmonary hypertensive rats | journal = Advances in Pharmacological Sciences | volume = 2012 | pages = 1–6 | year = 2012 | pmid = 23118745 | pmc = 3478703 | doi = 10.1155/2012/507278 | doi-access = free }}</ref>

====Allergies and immunity====

Two studies have evaluated the effects of MSM on allergic rhinitis. A 2004 multi-centered, open-label clinical trial found that MSM reduced both upper and lower respiratory symptoms associated with seasonal [[allergic rhinitis]] (SAR), and increased energy levels. It found no significant changes in [[Immunoglobulin E|IgE]] levels, although the duration of the study was not likely long enough to see changes.<ref>{{Cite journal|last1=Barrager|first1=Eleanor|last2=Veltmann|first2=Joseph R.|last3=Schauss|first3=Alexander G.|last4=Schiller|first4=Rebecca N.|date=2002|title=A Multicentered, Open-Label Trial on the Safety and Efficacy of Methylsulfonylmethane in the Treatment of Seasonal Allergic Rhinitis|journal=The Journal of Alternative and Complementary Medicine|language=en|volume=8|issue=2|pages=167–173|doi=10.1089/107555302317371451|pmid=12006124|issn=1075-5535}}</ref> An RCT evaluated three doses of MSM and found that a 3g daily dose was most effective compared to 1g or 6g per day. Daily use at 3g decreased allergy-associated symptoms, including itchy eyes, itchy nose, watery eyes, [[rhinorrhea]], sneezing, and nasal obstruction. The 3g dose also improved [[peak nasal inspiratory flow]] (PNIF) indicating improved breathing. The study also evaluated an acute 12g dose and found significant improvements in all symptoms except itching eyes and sneezing, but not for PNIF.<ref>{{Cite journal|last1=Hewlings|first1=Susan|last2=Kalman|first2=Douglas S|date=2018-11-29|title=Evaluating the Impacts of Methylsulfonylmethane on Allergic Rhinitis After a Standard Allergen Challenge: Randomized Double-Blind Exploratory Study|journal=JMIR Research Protocols|language=en|volume=7|issue=11|pages=e11139|doi=10.2196/11139|issn=1929-0748|pmc=6293242|pmid=30497995 |doi-access=free }}</ref>

MSM has been shown to improve immune function markers. RCT found that in blood samples taken after bouts of exhaustive exercise, there was a reduced response to an infectious stimulus in the placebo group, but the MSM group maintained a robust response, indicating that MSM protected against stress-induced [[immunosuppression]]. The authors postulate that MSM’s anti-inflammatory properties reduce the overstimulation of inflammatory cells during exercise, thus conserving their ability to respond to infections threats.<ref>{{Cite journal|last1=van der Merwe|first1=Mariè|last2=Bloomer|first2=Richard J.|date=2016|title=The Influence of Methylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise|journal=Journal of Sports Medicine|language=en|volume=2016|pages=7498359|doi=10.1155/2016/7498359|issn=2356-7651|pmc=5097813|pmid=27844051|doi-access=free}}</ref> This is supported by ''in vitro'' research showing MSM inhibits over-activation of white blood cells and has an anti-[[Apoptosis|apoptotic]] effect.<ref>{{Cite journal|last1=Kim|first1=Yoon Hee|last2=Kim|first2=Dae Hwan|last3=Lim|first3=Hwan|last4=Baek|first4=Doo-Yeon|last5=Shin|first5=Hyun-Kyung|last6=Kim|first6=Jin-Kyung|date=2009|title=The anti-inflammatory effects of methylsulfonylmethane on lipopolysaccharide-induced inflammatory responses in murine macrophages|journal=Biological & Pharmaceutical Bulletin|volume=32|issue=4|pages=651–656|doi=10.1248/bpb.32.651|issn=0918-6158|pmid=19336900|doi-access=free}}</ref><ref>{{Cite journal|last1=Karabay|first1=Arzu Z.|last2=Aktan|first2=Fugen|last3=Sunguroğlu|first3=Asuman|last4=Buyukbingol|first4=Zeliha|s2cid=29105910|date=2014|title=Methylsulfonylmethane modulates apoptosis of LPS/IFN-γ-activated RAW 264.7 macrophage-like cells by targeting p53, Bax, Bcl-2, cytochrome c and PARP proteins|journal=Immunopharmacology and Immunotoxicology|language=en|volume=36|issue=6|pages=379–389|doi=10.3109/08923973.2014.956752|pmid=25211405|issn=0892-3973}}</ref>

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[[Category:Food additives]]

[[Category:Methyl compounds]]