Methylsulfonylmethane (MSM) is a naturally occurring sulfur compound present in small amounts in many foods and beverages.

MSM is marketed as a dietary supplement. However, the claims of proof of its beneficial effects are disputed and published research on the compound's effects is considered thin.

MSM is also known as dimethyl sulfone, or DMSO₂, a name that reflects its close metabolic relationship to dimethyl sulfoxide (DMSO). MSM is the primary metabolite of DMSO in humans, and it shares some of its parent compound’s properties. According to law enforcement officials [1], MSM is also used to dilute methamphetamine in the illegal drug trade in the United States.

Sulfur in the environment

The enormous biomass of the oceans (i.e., algae and phytoplankton) release sulfur compounds—mainly dimethyl sulfide (DMS)— into the troposphere as they undergo decomposition. The highly volatile DMS is converted by ozone and ultraviolet light into DMSO and MSM. DMSO and MSM, both water-soluble compounds, are taken up into clouds and return to the earth in rainfall. They are then absorbed into the root systems of plants and concentrated.

DMSO and MSM are widely distributed in nature. Both compounds are found in selected fruits, vegetables, grains, and beverages. Milk is the most abundant known source of dietary MSM, containing between 3.3 parts per million (ppm) to 8.2 ppm. Other dietary sources of MSM include coffee, tomatoes, tea, Swiss chard, beer, corn, and alfalfa. Trace amounts of MSM have also been detected in asparagus, beets, cabbage, cucumber, oats, apples, and raspberry. MSM is found naturally in human biological tissue in small concentrations (0.7 to 1.1 parts per million).

Sulfur in the human body

The sulfur-bearing amino acids, cysteine and methionine, are the most abundant dietary sources of sulfur. MSM is also a source of dietary sulfur, containing approximately 34% sulfur by weight. Sulfur is the fourth most abundant mineral in the body, after calcium, phosphorus, and potassium. A 154-pound human body contains approximately 200 grams of elemental sulfur, slightly less than 1% of the total body weight. The sulfur component of MSM has been shown to be taken up by sulfur-containing amino acids in the body.

Sulfur is a major component of connective tissues, of amino acids, and of vitamins required for various enzyme reactions (i.e., coenzymes). In connective tissue, sulfur is found in glycosaminoglycans, chondroitin sulfate, dermatan sulfate, hyaluronic acid, and ground substance. It is most abundant skin and cartilage. Sulfur helps maintain the structure of intracellular proteins by forming cross-linkages through disulfide bonds. Sulfur is a constituent of the antioxidant glutathione, which has widespread activity in the human body, particularly inside of cells. Sulfur is part of coenzyme A, a key cofactor in various metabolic pathways; throughout the body, sulfhydryl groups are required for energy metabolism, and for the synthesis of fatty acids, enzymes hormones, receptors, and many other vital cellular components.

Claims of beneficial effects

MSM has been purported to have anti-inflammatory and anti-cancer properties and to inhibit prostacyclin (PGI2) synthesis in cultured cells of the endothelium, an action that is believed to combat atherosclerosis. The therapeutic action of dimethyl sulfoxide (DMSO) may be mediated, at least in part, by MSM. MSM may also be a methyl group donor and thereby lower homocysteine. (disputed — see talk page)

Animal studies

In an experimental model of spontaneous arthritis in mice, oral MSM decreased joint degeneration. In a mouse rheumatoid arthritis model, oral MSM decreased proliferation of the synovium, inflammation and auto[antibody] titers. A similar regimen in experimental lupus erythematosus in mice showed a reduced antinuclear antibodies and reduced incidence of anemia, while protecting against kidney damage. Oral MSM also modified immune responses, reducing arthritis deformities and swelling induced by collagen injections in mice, indicating a potential role for MSM in treating rheumatoid arthritis. Several animal studies suggest a role for MSM in the prevention of breast cancer and colon cancer. (disputed — see talk page)

Human studies

Stanley W. Jacob, M.D., F.A.C.S. of the Oregon Health & Science University claims to have treated over 18,000 patients with MSM. Dr. Jacob claims to have successfully treated with MSM include osteoarthritis, rheumatoid arthritis, chronic pain syndromes, repetitive stress injuries (e.g., carpal tunnel syndrome, tendinitis, bursitis), scleroderma, lupus erythematosus, interstitial cystitis, fibromyalgia, myasthenia gravis, asthma, hayfever, snoring and many lesser-known clinical entities. (disputed — see talk page)

Arthritis: A randomized controlled trial found that 6 grams per day of MSM reduced pain of osteoarthritis of the knee, and also improved ability to perform activities of daily living. That same study found that MSM reduced elevated serum homocysteine, a risk factor for ischaemic heart disease and stroke. In another double-blind study of MSM for osteoarthritis, patients with knee osteoarthritis received either 1,500 mg MSM, 1,500 mg glucosamine sulfate, 1,500 mg each of MSM and glucosamine sulfate, or placebo; significant decreases in the Lequesne Index were reported with MSM, glucosamine sulfate and their combination. (disputed — see talk page)

Seasonal Allergic Rhinitis: Most people think of MSM as supplement strictly for joint health. (disputed — see talk page) However, the first clinical study of oral MSM to be published in a peer-reviewed medical journal evaluated the efficacy of MSM, not for arthritis, but for hayfever. Fifty subjects completed the open-label study. Participants consumed 2,600 mg of MSM (OptiMSM, Cardinal Nutrition, Vancouver, WA) orally per day for 30 days. A Seasonal Allergy Symptom Questionnaire (SASQ) was used to evaluate clinical respiratory symptoms and energy levels at baseline and on days 7, 14, 21 and 30. Immune and inflammatory reactions were measured by plasma IgE and C-reactive protein at baseline and on day 30. Day 7 upper and total respiratory symptoms were reduced significantly from baseline. Lower respiratory symptoms were significantly improved from baseline by week 3. All respiratory improvements were maintained through the 30-day visit. Energy levels increased significantly by day 14; this increase continued through day-30.

Interstitial cystitis: In 1978, the FDA approved a 50-percent dilution of MSM for instillation into the bladder as a treatment for interstitial cystitis. ([2], citing [3].) Stacy J. Childs, M.D., then of the University of Alabama-Tuscaloosa and now practicing in Cheyenne, Wyoming, published a case series describing the successful intravesicular use of MSM use among interstitial cystitis patients who had not been helped by standard medical treatments. The report was published in 1994 in the Urologic Clinics of North America.

Toxicity

Clinical experience indicates that MSM may be used for prolonged periods without serious toxicity. According to Dr. Jacob, for more than two decades, thousands of people came to the DMSO Clinic at the Oregon Health & Science University (OHSU) and received upwards of 100 grams per day of MSM without serious side effects. In total, Dr. Jacob claims to have treated some 18,000 patients with MSM. (disputed — see talk page)

MSM appears to have no significant acute toxicity in laboratory tests. The LD50 (dose at which 50% of test subject are killed) of MSM is so large that the concept loses significant meaning. The LD50 of MSM is considered to be > 17.5 grams per kilogram of body weight. In the first and only toxicity study of MSM to be published in a peer-reviewed scientific journal, both the acute and subchronic oral toxicity of MSM in rats were studied; no adverse effects, clinical signs of toxicity, or mortalities were observed at doses of 2 grams/kilogram body weight per day. In a 90-day follow-up study rats received daily oral doses of 1.5 g/kg of MSM. The animals were assessed by hematology, clinical chemistry, clinical symptom observation and gross pathology. No deaths occurred, and no changes related to the administration of MSM were noted in any of the parameters examined. (disputed — see talk page)

Dose

MSM supplement manufacturers typically suggest doses for use as a dietary supplement ranging from 2 to 10 grams per day. Higher amounts appear to be safe, although some people do experience loose stool or abdominal discomfort when too much is taken at once. (disputed — see talk page)

Manufacturing and purity

After the reaction phase (DMSO + Hydrogen Peroxide yields MSM + water), MSM must be stripped of water and purified. There are two methods of purification currently used in commercial production of MSM as a dietary supplement: crystallization and distillation. The comparative advantages and disadvantages of these methods can be stated as follows: Distillation produces a product of superior purity, but it is more expensive and therefore fewer manufacturers invest in it; crystallization yields product with varying degrees of purity, but it is a more cost-effective method of production and is thus preferred by manufacturers making cheaper MSM.

Purity of MSM separated by crystallization is dependent upon the purity of the solvent and the raw materials used in manufacturing, and on the industrial hygiene procedures employed at the plant. As crystals grow in solution, they naturally form pockets, called occlusions, which entrap solvent within the crystal structure. Contaminants may therefore be present in crystallized MSM. This is a concern when MSM is manufactured in countries where water pollution is problematic, like China.

Distillation uses boiling point differentials to purify the MSM mixture. First, water is vaporized; then MSM is separated from “low boilers” (i.e., components with low boiling temperatures). Further distillation yields the pure MSM product. Components with high boiling temperatures (e.g., heavy metals, salts) remain in the bottom of the distillation vessel and are removed as waste. Distillation yields a product of excellent purity. The product is quite dry (typically < 0.05% moisture) when distilled properly, so fewer moisture-related problems occur, such as product degradation and microbial contamination. The less water present in a product, the less water quality is a concern. Heavy metals, which are removed from the still bottoms, cannot be removed by crystallization. Because potential contaminants have unique boiling points that are different from that of MSM, they are all removed by distillation. Purity of distilled MSM is, therefore, not dependent on water quality.

Many brands of MSM claim to be 99.9% pure, but that figure can be misleading. Purity is usually assessed in these cases using high resolution gas-liquid chromatography (HRGC), but this technique only measures volatile purity. Contaminants in the MSM that cannot be volatilized (e.g., heavy metals) would not show up on this test result. So unless other purity tests are performed, that figure is meaningless. The answers to the purity question, unfortunately, do not appear on the supplement label. It requires contacting the manufacturer and requesting data from the Certificate of Analysis on the raw material

One such test is melting point. The presence of contaminants changes the melting point of MSM, either by raising or lowering it. MSM should melt at 109.5 degrees Celsius, give or take one degree. It is a narrow range, as it should be, and the one degree leeway is really only given to account for lab-to-lab differences in equipment calibration. Variations in melting point more than a degree up or down are indicative of the presence of contaminants; specifically, non-volatile contaminants like heavy metals.

MSM should also be free of residual DMSO, a raw material used in its manufacture. DMSO is regulated as a drug in the United States.

MSM should also be tested for microbiological contaminants and heavy metals. Because MSM is taken in gram dosages, lead content should as low as analytical laboratory detection methods permit (0.01 parts per million).