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Methylsulfonylmethane (MSM)

Common Name(s): DMSO2, Methylsulfonylmethane, MSM

Clinical Overview

Use

MSM is commonly used for osteoarthritis, but may also benefit in alleviating GI upset, musculoskeletal pain, and allergies; boosting the immune system; and fighting microbial infections. Clinical trials are needed to verify these potential uses.

Dosing

MSM commonly is given as 2 to 6 g/day in 2 to 3 divided doses for arthritis and other joint conditions.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation in humans is lacking.

Interactions

None well documented.

Adverse Reactions

No conclusive data on adverse reactions with MSM have been reported, although suspected MSM-induced acute angle closure has been reported in 1 case study.

Toxicology

No toxicity was noted in animal studies.

Source

MSM is found in green plants such as Equisetum arvense, certain algae, fruits, vegetables, and grains. Other sources include the adrenal cortex of cattle, human and bovine milk, and urine. MSM is also found in human cerebral spinal fluid and plasma at 0 to 25 mcmol/L concentrations.1 MSM is naturally occurring in fresh foods; however, it is destroyed with only moderate food processing, such as heating or dehydration.2

History

Most research on MSM involves animal studies. MSM has been suggested for use as a food supplement and is available in the United States as a dietary supplement under the Dietary Supplement Health and Education Act.

Chemistry

MSM is a normal oxidation product of dimethyl sulfoxide (DMSO). Unlike DMSO, MSM is odor free and is a dietary factor. MSM has been referred to as "crystalline DMSO."3 MSM provides a dietary source of sulfur for methionine.2 MSM's medicinal properties are theorized to be similar to DMSO, without the odor and skin irritation complications.4

Uses and Pharmacology

The sulfur content of MSM can be used by the body to maintain normal connective tissues. MSM has also exhibited possible anti-inflammatory, antiatherosclerotic, and chemopreventative activities along with free radical scavenging.5, 6, 7 MSM has been reported to alleviate allergies, arthritis, GI upset, musculoskeletal pain, and to boost the immune system. It also possesses antimicrobial effects against organisms such as Giardia lamblia, Trichomonas vaginalis, and some fungi. The suggested mechanism is that MSM may bind to surface receptor sites, blocking the interaction of parasite and host.

Osteoarthritis

There are a limited number of clinical trials in osteoarthritis to guide the use of MSM, support its efficacy, and describe adverse effects.

A randomized, double-blind, parallel, placebo-controlled study compared oral MSM with glucosamine and the combination of the 2 in 118 patients with mild to moderate osteoarthritis for a minimum of 6 months.4 For 12 weeks, patients received either placebo (n = 28), MSM 500 mg 3 times daily (n = 30), glucosamine 500 mg 3 times daily (n = 30), or 500 mg each of MSM and glucosamine 3 times daily (n = 30). The primary outcome was the reduction of pain intensity assessed by a visual analogue scale (VAS). Pain, swelling, and joint mobility were also scored on a 0 to 3 scale, with 3 as the most severe. The primary outcome was not reported; however, all groups except for placebo experienced statistically significant improvements in pain and swelling. The combination of glucosamine and methylsulfonylmethane showed statistically significant decreases in pain and swelling compared with either single treatment alone.

A 12-week pilot, randomized, double-blind, placebo-controlled clinical trial (n = 40) was conducted in patients with knee osteoarthritis, classified by American College of Rheumatology (ACR) criteria as functional class I, II, or III, for at least 3 months. Participants received 3 g of oral MSM micropill (OptiMSM) twice daily (increasing to this dose over 1 week) or placebo.8 The primary end points were the composite subscales in the Western Ontario and McMaster University Osteoarthritis Index VAS on pain, stiffness, physical function, and aggregated total symptoms (0 = no pain, 100 = worst pain). After 12 weeks, there was a statistically significantly higher decrease in pain (−14.6 for MSM group and −7.3 for placebo group, P = 0.041) and for physical function impairment (−15.7 for MSM group and −8.8 for placebo group, P = 0.045).

A trial (n = 89) on the effects of the oral combination product AR7, which includes sternum collagen II, methylsulfonylmethane, cetyl myristoleate, lipase, vitamin C, and bromelain, was conducted in osteoarthritis.9 A decrease in the percentage of patients reported to have pain, stiffness, and tenderness in the treatment group was found after 3 months.

A randomized, double-blind, placebo-controlled, 6-month trial (n = 60) evaluated the benefit of methylsulfonylmethane 5 g/day plus boswellic acids 7.2 mg/day for knee OA diagnosed by ACR criteria, with grade 3 Kellgren andLawrenceradiographic staging. Pain assessed by VAS was significantly worse in the treatment group compared with placebo at 2 months, and no significant difference between groups was seen at 6 months. Joint function assessed by Lequesne index was not significantly different between groups at either 2 or 6 months. The treatment group had significant reductions in anti-inflammatory drug use compared with baseline at 2 and 6 months, and these differences were also significantly lower than the placebo group.19

Cancer

Tumor onset in colon cancer–induced rats was markedly delayed in animals receiving MSM supplementation versus controls, suggesting a chemopreventative effect.10 Four percent receiving MSM had a similar delaying effect on rat mammary breast cancer.11

Diabetes

MSM showed no effect in preventing diabetes when tested in spontaneously diabetic mice compared with DMSO or dimethylsulfide.12

Rosacea

Topical MSM showed benefit in combination with silymarin to treat rosacea in 46 patients.13 A statistically significant decrease in erythema, papules, and itch intensity occurred. MSM was theorized to be beneficial in rosacea due to strong photoprotective action along with antioxidant effects and desensitization of the skin to potential allergens.

Exercise muscle injury

A small, randomized, placebo-controlled study (n = 18) evaluated the effectiveness of MSM on exercise-induced muscle damage. Healthy volunteers were randomized to receive 50 mg/kg of MSM in 200 mL of water or placebo daily for 10 days. Blood samples were drawn at baseline, and following supplementation and a 14 km run. The group receiving MSM had significant reductions in serum bilirubin and creatine kinase levels following exercise compared with placebo, and total antioxidant capacity was significantly higher in the MSM group compared with placebo.20

Ichthyosis

There is 1 case study of a patient with unrelieved ichthyosis treated unsuccessfully with a variety of topical agents.14 After treatment with an over-the counter skin care product olivamine, a product that combines amino acids, vitamins, antioxidants, MSM, and water-resistant silicones with surfactant-free phospholipid cleansers, the patient was completely clear of thickened scales and itching after 4 weeks.

Veterinarian Uses

A 10-day course of MSM also has been evaluated in 13 horses with chronic obstructive pulmonary disease, and no changes occurred in parameters, such as lung sounds, respiratory rate, heart rate, temperature, nasal discharge, or arterial blood gas.15 However, MSM exerted some protective effects on oxidative and inflammatory exercise-induced injury in 24 jumping horses when given daily for 6 weeks before and during competition.16

Dosing

MSM commonly is given as 2 to 6 g/day in 2 to 3 divided doses for arthritis and other joint conditions. A study evaluating benefits for exercised-induced muscle injury administered 50 mg/kg daily.20

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. The first report evaluating developmental toxicity of MSM in a mammalian model was published in 2007.17 Pregnant Sprague-Dawley rats were given MSM up to 1,000 mg/kg/day orally for 14 days during gestation. No evidence of maternal toxicity was observed, nor any significant increases in the incidence of fetal anomaly.

Interactions

DIs checked May 2018None well documented.

Adverse Reactions

When orally administered MSM was given to rats at 5 to 7 times the maximum recommended dose in humans, no adverse events or mortality were observed after 90 days.18 In one study, similar rates of adverse effects were seen in the MSM and placebo groups.8 Possible adverse events included bloating, constipation, decline in concentration, fatigue, headache, indigestion, and insomnia.

Bilateral acute angle closure (AAC) was reported in a 35-year-old woman 1 week after starting multiple dietary supplements. She presented with bilateral AAC, choroidal effusion, and ciliary body edema similar to that seen with sulfa-based drugs. Her medical history was positive for systemic lupus erythematosus treated with prednisone, azathioprine, and hydroxychloroquine for the past year. Additionally, she was also taking multiple nutritional supplements (eg, Hera Cortin E, silymarin, Bicarb-Balance, potassium, Ortho-Biotic). One week prior to ocular symptom onset, she had begun 3 more supplements: D3-50 Cholecalciferol, Cortrex, and Basic Detox Nutrients. The latter product contained MSM, which was the only constituent with a sulfonyl moiety, and was therefore the suspected cause of the adverse event. Complete symptom resolution occurred within 4 days of discontinuing the most recently added 3 supplements.21

Toxicology

No important toxicity was noted in animal studies.10, 11, 18

References

1. Engelke UF, Tangerman A, Willemsen MA, et al. Dimethyl sulfone in human cerebrospinal fluid and blood plasma confirmed by one-dimensional (1)H and two-dimensional (1)H-(13)C NMR. NMR Biomed. 2005;18(5):331-336.15996001
2. Richmond VL. Incorporation of methylsulfonylmethane sulfur into guinea pig serum proteins. Life Sci. 1986;39(3):263-268.3736326
3. Bertken R. "Crystalline DMSO": DMSO2. Arthritis Rheum. 1983;26(5):693-694.6847737
4. Usha PR, Naidu MU. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Investig. 2004;24(6):353-363.17516722
5. Ebisuzaki K. Aspirin and methylsulfonylmethane (MSM): a search for common mechanisms, with implications for cancer prevention. Anticancer Res. 2003;23(1A):453-458.12680248
6. Alam SS, Layman DL. Dimethyl sulfoxide inhibition of prostacyclin production in cultured aortic endothelial cells. Ann N Y Acad Sci. 1983;411:318-320.6410965
7. Beilke MA, Collins-Lech C, Sohnle PG. Effects of dimethyl sulfoxide on the oxidative function of human neutrophils. J Lab Clin Med. 1987;110(1):91-96.3598341
8. Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF. Efficacy of methysulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2006;14(3):286-294.16309928
9. Xie Q, Shi R, Xu G, Cheng L, Shao L, Rao J. Effects of AR7 joint complex on arthralgia for patients with osteoarthritis: results of a three-month study in Shanghai, China. Nutr J. 2008;7:31.18954461
10. O'Dwyer P, McCabe DP, Sickle-Santanello BJ, Woltering EA, Clausen K, Martin EW Jr. Use of polar solvents in chemoprevention of 1,2-dimethylhydrazine-induced colon cancer. Cancer. 1988;62(5):944-948.3409175
11. McCabe D, O'Dwyer P, Sickle-Santanello B, Woltering E, Abou-Issa H, James A. Polar solvents in the chemoprevention of dimethylbenzanthracene-induced rat mammary cancer. Arch Surg. 1986;121(12):1455-1459.3098207
12. Klandorf H, Chirra AR, DeGruccio A, Girman DJ. Dimethyl sulfoxide modulation of diabetes onset in NOD mice. Diabetes. 1989;38(2):194-197.2914623
13. Berardesca E, Cameli N, Cavallotti C, Levy JL, Piérard GE, de Paoli Ambrosi G. Combined effects of silymarin and methylsulfonylmethane in the management of rosacea: clinical and instrumental evaluations. J Cosmet Dermatol. 2008;7(1):8-14.18254805
14. Fleck CA. Managing ichthyosis: a case study. Ostomy Wound Manage. 2006;52(4):82-86, 88, 90.16636365
15. Traub-Dargatz JL, McKinnon AO, Thrall MA, et al. Evaluation of clinical signs of disease, bronchoalveolar and tracheal wash analysis, and arterial blood gas tensions in 13 horses with chronic obstructive pulmonary disease treated with prednisone, methyl sulfonmethane, and clenbuterol hydrochloride. Am J Vet Res. 1992;53(10):1908-1916.1456540
16. Marañón G, Muñoz-Escassi B, Manley W, et al. The effect of methyl sulphonyl methane supplementation on biomarkers of oxidative stress in sport horses following jumping exercise. Acta Vet Scand. 2008;50:45.18992134
17. Magnuson BA, Appleton J, Ryan B, Matulka RA. Oral developmental toxicity study of methylsulfonylmethane in rats. Food Chem Toxicol. 2007;45(6):977-984.17258373
18. Horváth K, Noker PE, Somfai-Relle S, Glávits R, Financsek I, Schauss AG. Toxicity of methylfulfonylmethane in rats. Food Chem Toxicol. 2002;40(10):1459-1462.12387309
19. Notarnicola A, Tafuri S, Fusaro L, Moretti L, Pesce V, Moretti B. The "MESACA" study: methylsulfonylmethane and boswellic acids in the treatment of gonarthrosis. Adv Ther. 2011;28(10):894-906.2198678010.1007/s12325-011-0068-3
20. Barmaki S, Bohlooli S, Khoshkhahesh F, Nakhostin-Roohi B. Effect of methylsulfonylmethane supplementation on exercise - Induced muscle damage and total antioxidant capacity. J Sports Med Phys Fitness. 2012;52(2):170-174.22525653
21. Hwang JC, Khine KT, Lee JC, Boyer DS, Francis BA. Methyl-sulfonyl-methane (MSM)-induced acute angle closure. J Glaucoma. 2015;24:e28-e30.24240884

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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