Methylsulfonylmethane (MSM) is an
organosulfur compound
Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature abounds with organosulfur compounds—sulfu ...
with the
formula
In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwee ...
(CH
3)
2SO
2. It is also known by several other names including methyl sulfone and dimethyl sulfone (DMSO
2). This colorless solid features the
sulfonyl
In organosulfur chemistry, a sulfonyl group can refer either to a functional group found primarily in sulfones, or to a substituent obtained from a sulfonic acid by the removal of the hydroxyl group, similarly to acyl groups. Sulfonyl groups c ...
functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...
and is the simplest of the sulfones. It is considered 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 as a
dietary supplement
A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
. It is sometimes used as a cutting agent for illicitly manufactured
methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...
. It is also commonly found in the atmosphere above marine areas, where it is used as a carbon source by the airborne bacteria ''
Afipia
''Afipia'' is a genus of bacteria in the Nitrobacteraceae family.
Phylogeny
The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN). The phylogeny is based on whole-genome analysis.
Ref ...
''. Oxidation of
dimethyl sulfoxide
Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds a ...
produces the sulfone, both under laboratory conditions and metabolically.
Use as a solvent
Because of its polarity and thermal stability, MSM has been used industrially as a high-temperature
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
. For example, displacement of aryl chlorides by
potassium fluoride
Potassium fluoride is the chemical compound with the formula KF. After hydrogen fluoride, KF is the primary source of the fluoride ion for applications in manufacturing and in chemistry. It is an alkali halide and occurs naturally as the rare m ...
has been conducted in molten MSM.
With a pK
a of 31, MSM can be deprotonated with
sodium amide
Sodium amide, commonly called sodamide (systematic name sodium azanide), is the inorganic compound with the formula . It is a salt composed of the sodium cation and the azanide anion. This solid, which is dangerously reactive toward water, is white ...
. The conjugate base has been used as a
nucleophile
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
.
Pharmacology and toxicity
Nuclear magnetic resonance
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with a ...
(NMR) studies have demonstrated that oral doses of MSM are absorbed into the blood and cross the
blood/brain barrier. An NMR study has also found detectable levels of MSM normally present in the blood and
cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
, suggesting that it derives from dietary sources, intestinal bacterial metabolism, and the body's endogenous
methanethiol
Methanethiol (also known as methyl mercaptan) is an organosulfur compound with the chemical formula . It is a colorless gas with a distinctive putrid smell. It is a natural substance found in the blood, brain and feces of animals (including hum ...
metabolism.
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;
he co-authored a book promoting MSM with a variety of claims, including a utility as a natural source of "biologically active
sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
,"
suggesting that people are deficient in such forms of sulfur in their dietary intake. There is no
Dietary Reference Intake
The Dietary Reference Intake (DRI) is a system of nutrition recommendations from the National Academy of Medicine (NAM) of the National Academies (United States). It was introduced in 1997 in order to broaden the existing guidelines known as Reco ...
(DRI) or Daily Value established for sulfur but notable dietary sources include
cruciferous vegetables
Cruciferous vegetables are vegetables of the family Brassicaceae (also called Cruciferae) with many genera, species, and cultivars being raised for food production such as cauliflower, cabbage, kale, garden cress, bok choy, broccoli, Brussels spr ...
,
garlic
Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
,
onions
An onion (''Allium cepa'' L., from Latin ''cepa'' meaning "onion"), also known as the bulb onion or common onion, is a vegetable that is the most widely cultivated species of the genus ''Allium''. The shallot is a botanical variety of the onion ...
,
asafoetida
Asafoetida (; also spelled asafetida)
is the dried latex ( gum oleoresin) exuded from the rhizome or tap root of several species of ''Ferula'', perennial herbs growing tall. They are part of the celery family, Umbelliferae. Asafoetida is thou ...
,
legumes
A legume () is a plant in the family Fabaceae (or Leguminosae), or the fruit or seed of such a plant. When used as a dry grain, the seed is also called a pulse. Legumes are grown agriculturally, primarily for human consumption, for livestock fo ...
,
nut
Nut often refers to:
* Nut (fruit), fruit composed of a hard shell and a seed, or a collective noun for dry and edible fruits or seeds
* Nut (hardware), fastener used with a bolt
Nut or Nuts may also refer to:
Arts, entertainment, and media Co ...
s,
seeds
A seed is an embryonic plant enclosed in a protective outer covering, along with a food reserve. The formation of the seed is a part of the process of reproduction in seed plants, the spermatophytes, including the gymnosperm and angiosperm pl ...
,
plant milk
Plant milk is a plant beverage with a color resembling that of milk. Plant milks are non-dairy beverages made from a water-based plant extract for flavoring and aroma. Plant milks are consumed as alternatives to milk, and often provide a crea ...
,
animal milk
Milk is a white liquid food produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals (including breastfed human infants) before they are able to digest solid food. Immune factors and immune-modulati ...
and
eggs
Humans and human ancestors have scavenged and eaten animal eggs for millions of years. Humans in Southeast Asia had domesticated chickens and harvested their eggs for food by 1,500 BCE. The most widely consumed eggs are those of fowl, especial ...
(whites and yolks).
The claims for the need for sulfur supplementation originate with Robert Herschler, a
biochemist
Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and Cell (biology), cell parts. The word "biochemist" is a portmanteau of ...
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.
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.
The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...
effects.
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.
U.S. 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.
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.
Cancer
A South Korean study focussing on the role of MSM affecting
growth factor
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...
s associated with breast cancer identifies MSM to have multiple targets, both
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
and
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
, including
STAT3
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family.
Function
STAT3 is a member of the STAT protein family. In respons ...
,
STAT5b,
IGF-1R
The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 ( IGF-1) and by a related hormone called IGF-2. ...
and
VEGF
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...
, 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.
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
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are ty ...
(HDL) levels on overweight and obese people. The MSM group demonstrated higher HDL levels after 16 weeks (51.8 ± 2.8 mg/dL) when compared to the baseline (44.9 ± 3.7 mg/dL) and also versus the placebo group (42.7 ± 2.5 mg/dL at baseline vs 48.0 ± 4.9 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
C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 ...
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.
Safety
The 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.
Extensive research in animal models indicates MSM has a very low toxicity when administered both orally and topically.
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.
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.
MSM is considered 'Possibly Safe' at therapeutic doses, although further research is still needed to assess its safety for long-term use.
Osteoarthritis
A review of two small
randomized controlled trial
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...
s of methylsulfonylmethane in
osteoarthritis
Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
(OA) knee pain relief
"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."
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
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and h ...
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
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
use as reported in other clinical trials. The authors wrote "longer-term trials may yield additional and greater improvements."
* The second used 6.0 g/day versus placebo for 26 weeks. Subjects were evaluated through the WOMAC questionnaire,
SF-36
The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status and an abbreviated variant of it, the SF-6D, is commonly used in health economics as a variable in the quality-adjus ...
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.
=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
Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of two polysaccharides, chitosan and chitin. Glucosamine is one of the most ...
.
Two other studies investigated the effects of MSM in combination with glucosamine and
chondroitin
A chondroitin is a chondrin derivative.
Types include:
* Chondroitin sulfate
* Dermatan sulfate
Chondroitin as a supplement is now commonly used (often in combination with glucosamine) in treating the joint disease of osteoarthritis. In contrast ...
(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.
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.
=Skin, hair, nails
=
The first scientific investigation of MSM for skin health was published in 2015. The
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. Another study evaluated doses of 1g and 3g and showed improvements in wrinkles, firmness, and hydration at both dose levels in 20 persons. 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. An Italian study evaluated the effects of a nutraceutical composed of MSM,
hyaluronic acid
Hyaluronic acid (; abbreviated HA; conjugate base hyaluronate), also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans ...
, and
L-carnosine. The results from RCT showed broad improvements in facial skin hydration and elasticity, as well as decreased sebaceous secretions.
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.
In a second small trial the total antioxidant capacity was significantly increased after taking MSM.
Studies in animals indicate a hepatoprotective effect of MSM against several toxins including
acetaminophen,
paraquat, and
carbon tetrachloride
Carbon tetrachloride, also known by many other names (such as tetrachloromethane, also IUPAC nomenclature of inorganic chemistry, recognised by the IUPAC, carbon tet in the cleaning industry, Halon-104 in firefighting, and Refrigerant-10 in HVAC ...
.
Animal models of experimental colitis and pulmonary hypertension indicate a protective effect as well.
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
Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, i ...
(SAR), and increased energy levels. It found no significant changes in
IgE
Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (ε chain) and two light chains, with the ε c ...
levels, although the duration of the study was not likely long enough to see changes. 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
Rhinorrhea, rhinorrhoea, or informally runny nose is the free discharge of a thin mucus fluid from the nose; it is a common condition. It is a common symptom of allergies ( hay fever) or certain viral infections, such as the common cold or COVID- ...
, 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.
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
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
. 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. This is supported by ''in vitro'' research showing MSM inhibits over-activation of white blood cells and has an anti-
apoptotic
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes incl ...
effect.
Notes
{{Authority control
Dietary supplements
Experimental medical treatments
Solvents
Sulfones
Food additives