Methylsulfonylmethane
Encyclopedia
Methylsulfonylmethane is an organosulfur compound with the formula
(CH3)2SO2. It is also known by several other names including DMSO2, methyl sulfone, and dimethyl sulfone. 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
.
(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.
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. With a pKa of 31, it can be deprotonated with sodium amide
, and the conjugate base is an effective nucleophile
.
," 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.
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. Registered dietitian
Kerry Lang on quackwatch
disparages this claim, pointing out:
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."
The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has anti-inflammatory
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.
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.
s of methylsulfonylmethane in osteoarthritis
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 the drug. 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." 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." Side effects of MSM ingestion include stomach upset, diarrhoea and headache. 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.
After several reports that MSM helped arthritis in animal model
s, 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.
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
.
(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.
. 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.
Nuclear magnetic resonance
(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
, suggesting that it derives from dietary sources, intestinal bacterial metabolism, and the body's endogenous methanethiol
metabolism.
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.
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....
(CH3)2SO2. It is also known by several other names including DMSO2, methyl sulfone, and dimethyl sulfone. This colorless solid features the sulfonyl
Sulfonyl
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...
functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
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
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
.
Structure and chemical properties
MSM is structurally related to dimethyl sulfoxideDimethyl sulfoxide
Dimethyl sulfoxide is an organosulfur compound with the formula 2SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water...
(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
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
of DMSO.
Use as a solvent
Because of its polarity and thermal stability, MSM is used industrially as a high-temperature solventSolvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
for both inorganic and organic substances. It is used as a medium in organic synthesis
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
. For example, displacement of aryl chlorides by potassium fluoride
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 metal halide and occurs naturally as the rare mineral carobbiite...
can be usefully conducted in molten MSM. With a pKa of 31, it can be deprotonated with sodium amide
Sodium amide
Sodium amide, commonly called sodamide, is the chemical compound with the formula NaNH2. This solid, which is dangerously reactive toward water, is white when pure, but commercial samples are typically gray due to the presence of small quantities of metallic iron from the manufacturing process...
, and the conjugate base is an effective nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...
.
Effects on health
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 its supposed utility as a natural source of "biologically active sulfurSulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
," 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.
The claims for the need for sulfur supplementation originate with Robert Herschler, a biochemist
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
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. Registered dietitian
Dietitian
Dietitians supervise the preparation and service of food, develop modified diets, participate in research, and educate individuals and groups on good nutritional habits. The goals of dietitians are to provide medical nutritional intervention, and to obtain, safely prepare, serve and advise on...
Kerry Lang on quackwatch
Quackwatch
Quackwatch is an American non-profit organization founded by Stephen Barrett with the stated aim being to "combat health-related frauds, myths, fads, fallacies, and misconduct" and with a primary focus on providing "quackery-related information that is difficult or impossible to get elsewhere."...
disparages this claim, pointing out:
MSM is sold as a dietary supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
and marketed with a variety of claims, often in combination with glucosamine
Glucosamine
Glucosamine is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of the polysaccharides chitosan and chitin, which compose the exoskeletons of crustaceans and other arthropods, cell walls in fungi and...
and/or chondroitin
Chondroitin
Chondroitin is a chondrin derivative.Types include:* Chondroitin sulfate* Dermatan sulfate...
for helping to treat or prevent osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
. 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."
The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has anti-inflammatory
Anti-inflammatory
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
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.
FDA enforcement action
In October 2000, the United States Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
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.
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 trialRandomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
s of methylsulfonylmethane in osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
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 the drug. 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." 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." Side effects of MSM ingestion include stomach upset, diarrhoea and headache. 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.
After several reports that MSM helped arthritis in animal model
Animal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...
s, 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.
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
Intention to treat analysis
In epidemiology, an intention to treat analysis is an analysis based on the initial treatment intent, not on the treatment eventually administered. ITT analysis is intended to avoid various misleading artifacts that can arise in intervention research...
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
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
level and erythrocyte sedimentation rate
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
.
Interstitial cystitis
In 1978, the FDA approved dimethyl sulfoxideDimethyl sulfoxide
Dimethyl sulfoxide is an organosulfur compound with the formula 2SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water...
(DMSO) for instillation into the bladder as a treatment for interstitial cystitis
Interstitial cystitis
Interstitial cystitis or bladder pain syndrome is a chronic, oftentimes severely debilitating disease of the urinary bladder...
. Since DMSO is metabolized to MSM by the body, it is possible that MSM is the active ingredient in DMSO treatments.
Other conditions
Barrager et al. evaluated the efficacy of MSM for hay feverHay Fever
Hay Fever is a comic play written by Noël Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss. Laura Hope Crews played the role in New York...
. Fifty-five subjects consumed 2.6 g of MSM per day for 30 days. This study was not blinded
Double-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....
; 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
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
and immunoglobulin E
Immunoglobulin E
Immunoglobulin E is a class of antibody that has been found only in mammals. IgE is a monomeric antibody with 4 Ig-like domains...
levels).
Blum & Blum also conducted a double-blind, placebo-controlled clinical trial of an MSM-containing throat spray to reduce snoring.
Pharmacology and toxicity
The (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.Nuclear magnetic resonance
Nuclear magnetic resonance
Nuclear magnetic resonance is a physical phenomenon in which magnetic nuclei in a magnetic field absorb and re-emit electromagnetic radiation...
(NMR) studies have demonstrated that oral doses of MSM are absorbed into the blood and cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. An NMR study has also found detectable levels of MSM normally present in the blood and cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
, suggesting that it derives from dietary sources, intestinal bacterial metabolism, and the body's endogenous methanethiol
Methanethiol
Methanethiol is a colorless gas with a smell like rotten cabbage. It is a natural substance found in the blood and brain of humans and other animal as well as plant tissues. It is disposed of through animal feces. It occurs naturally in certain foods, such as some nuts and cheese...
metabolism.
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.
External links
- Quackwatch opinion about Methylsulfonylmethane (MSM) -- clinical dietician skeptical of MSM's marketing claims