MSM (Methylsulfonylmethane) for Inflammation and Joint Health

TL;DR

MSM (methylsulfonylmethane) is a sulfur-containing compound that may help reduce inflammation by lowering cytokines such as TNF-α, IL-1, and IL-6 and by supporting antioxidant defenses like glutathione. These effects may help calm inflammatory processes involved in joint pain, oxidative stress, and tissue damage. While much of the research is experimental, the mechanisms suggest MSM may support overall inflammatory balance and connective tissue health.

What Is MSM?

MSM, or methylsulfonylmethane, is an odorless, white, crystalline, water-soluble compound and an oxidation product of dimethylsulfoxide (DMSO). It is also referred to as crystalline DMSO or dimethyl sulfone [1,2]. MSM is a small molecule with the ability to penetrate membranes and distribute widely throughout the body.

MSM for Inflammation

MSM has been shown to inhibit NF-κB and downregulate inflammatory cytokines such as TNF-α, IL-1, and IL-6 [3-7]. It may also have an indirect inhibitory effect on mast cell-mediated inflammation [8,9]. By reducing inflammatory cytokines and vasodilating agents, the flux and recruitment of immune cells to sites of local inflammation may be reduced [8,9]. MSM was also patented as an anti-inflammatory substance [10-12].

The antioxidant effects of MSM were first noticed in the 1980s, when neutrophil-stimulated production of reactive oxygen species (ROS) was suppressed in vitro [13]. MSM has also been shown to help restore the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio toward normal [25].

Animal studies using MSM as the primary treatment for experimentally induced injuries caused by toxic chemicals have shown reductions in malondialdehyde, glutathione disulfide, and myeloperoxidase, along with increases in glutathione and superoxide dismutase [25-29].

MSM and Joint Health

Because of its anti-inflammatory properties, MSM is commonly used for arthritis. Animal studies have shown reductions in cytokine production and, in some cases, lower CRP when MSM is used in combination with glucosamine [14-16]. Inflammatory cytokines such as TNF-α and IL-6 are implicated in cartilage destruction, and in vitro studies suggest MSM may help protect cartilage through this mechanism [7,17,18]. In animal models, MSM supplementation has reduced cartilage surface degeneration and improved joint findings [19,20].

Human studies have also been done. These studies are non-invasive and rely on questionnaires and joint function to measure results. Clinical trials suggest MSM may be effective in reducing pain, as indicated by the VAS pain scale and WOMAC pain subscale [21-24]. Improvements in physical function have also been reported [21-24].

MSM has also been studied in combination with other ingredients. In one double-blind, placebo-controlled study, the combination of MSM with glucosamine and chondroitin sulfate produced results where glucosamine and chondroitin sulfate alone did not [30]. In another study involving low back pain, subjects undergoing conventional physical therapy along with a glucosamine complex containing MSM reported improvements in quality of life [31].

MSM as a Source of Sulfur

MSM has long been thought of as a sulfur donor for sulfur-containing compounds such as methionine, cysteine, homocysteine, taurine, and many others. Guinea pigs fed radiolabeled MSM incorporated labeled sulfur into serum proteins containing methionine and cysteine [32].

Sulfur-containing amino acids can be used to increase synthesis of S-adenosylmethionine (SAMe), glutathione (GSH), taurine, and N-acetylcysteine (NAC). This may help explain why MSM and other sulfur compounds have been explored in a wide range of conditions [36].

Muscle Pain After Exercise

Microtrauma and inflammation can lead to muscle pain after exercise. Because MSM can reduce oxidative stress, lower inflammation, and deliver sulfur to connective tissue, studies have shown that supplementation may reduce pain and muscle damage following exercise [33-35].

Seasonal Allergies

MSM has also been studied as an anti-inflammatory compound in seasonal allergies. In one study, 2.6 g/day of MSM was given for 30 days. Supplementation improved upper and total respiratory symptoms, as well as lower respiratory symptoms, by the third week, and these improvements were maintained throughout the study [37].

Skin

Dr. Herschler’s initial patent included MSM’s use for healthy skin. Its role as a sulfur donor to keratin may help explain this effect [2]. A lotion containing EDTA and MSM improved burn sites on rats when applied every eight hours [38]. Human studies also suggest value for skin health [39,40], and a combination of silymarin and MSM proved useful in managing rosacea symptoms [41].

Cancer

MSM has also been studied for anticancer effects. In vitro studies have shown suppression of various cancer cell lines, including breast [42-46], esophagus, stomach, and liver [47,48], bladder [49], and skin cancers [50,51]. Additional laboratory studies suggest MSM may influence cancer cells to resemble non-cancerous cells more closely [52-54].

Final Thoughts

MSM is a sulfur-containing compound with anti-inflammatory and antioxidant effects that has been studied in a wide range of conditions. Much of the research is experimental, but the physiology is interesting. It appears to reduce inflammatory signaling, improve antioxidant status, and provide sulfur for compounds involved in tissue repair, detoxification, and cellular protection.

Selected References

[1] Freedom Press; 2003. Msm-the Definitive Guide: A Comprehensive Review of the Science and Therapeutics of Methylsulfonylmethane.

[2] U.S. Patent. August 30, 1979. Methylsulfonylmethane and Methods of Use.

[3] PLoS One. 2016;11:e0159891. Methylsulfonylmethane inhibits RANKL-induced osteoclastogenesis in BMMs by suppressing NF-κB and STAT3 activities.

[4] Biol Pharm Bull. 2009;32:651-656. The anti-inflammatory effects of methylsulfonylmethane on lipopolysaccharide-induced inflammatory responses in murine macrophages.

[5] Cytokine. 2015;71:223-231. Methylsulfonylmethane inhibits NLRP3 inflammasome activation.

[6] Osteoarthritis Cartilage. 2007;15:C123. The effect of distilled methylsulfonylmethane (MSM) on human chondrocytes in vitro.

[7] Biol Pharm Bull. 2009;32:651-656. The anti-inflammatory effects of methylsulfonylmethane on lipopolysaccharide-induced inflammatory responses in murine macrophages.

[8] Curr Vasc Pharmacol. 2012;10:4-18. The role of nitric oxide on endothelial function.

[9] Clin Exp Immunol. 2002;129:4-10. A regulator of mast cell activation and mast cell-mediated inflammation.

[10] U.S. Patent. July 26, 1989. Use of Methylsulfonylmethane to Relieve Pain and Relieve Pain and Nocturnal Cramps and to Reduce Stress-Induced Deaths in Animals.

[11] U.S. Patent. June 26, 1986. Dietary Products and Uses Comprising Methylsulfonylmethane.

[12] U.S. Patent. September 14, 1982. Dietary and Pharmaceutical Uses of Methylsulfonylmethane and Compositions Comprising It.

[13] J Lab Clin Med. 1987;110:91-96. Effects of dimethyl sulfoxide on the oxidative function of human neutrophils.

[14] Jpn Pharmacol Ther. 2004;32:421-428. Suppressive effect of methylsulfonylmethane (MSM) on type II collagen-induced arthritis in DBA/1J mice.

[15] FASEB J. 2008;22:1094.3. Assessment of methylsulfonylmethane (MSM) on the development of osteoarthritis (OA): An animal study.

[16] Toxicol Ind Health. 2013;29:187-201. The effectiveness of echinacea extract or composite glucosamine, chondroitin and methyl sulfonyl methane supplements on acute and chronic rheumatoid arthritis rat model.

[17] Cytokine. 2015;71:223-231. Methylsulfonylmethane inhibits NLRP3 inflammasome activation.

[18] Osteoarthritis Cartilage. 2007;15:C123. The effect of distilled methylsulfonylmethane (MSM) on human chondrocytes in vitro.

[19] J Bone Miner Metab. 2013;31:16-25. Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model.

[20] PLoS One. 2015;10:e0141565. Methyl sulfone blocked multiple hypoxia- and non-hypoxia-induced metastatic targets in breast cancer cells and melanoma cells.

[21] BMC Complement Altern Med. 2011;11:50. Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: A randomized controlled study.

[22] Osteoarthritis Cartilage. 2007;15:C231. The role of MSM in knee osteoarthritis: A double blind, randomized, prospective study.