MSM is an organosulfur compound that occurs naturally in some plants and animals. MSM is a product of the sulfur cycle — a cycle through which sulfur moves between the air, ground, and living things. Through this process MSM is eventually absorbed into the soil, where it can be taken up by plants and therefore is found in fruit, vegetables, and grains. MSM can also be manufactured by oxidizing another organosulfur compound, dimethyl sulfoxide (DMSO). There is no difference structurally between manufactured and naturally-occurring MSM, and the manufactured products are equally safe and make it much easier to reach the recommended dose.^[5]

MSM is primarily used in osteoarthritis. While studies show it can improve pain and function in people with osteoarthritis of the knee, the benefits are small and often clinically insignificant.^{[1][6][7][8][9]} Taking MSM might also benefit osteoarthritis in other joints, including the lumbar spine, the ankle, and the shoulder. It might also improve joint pain in people who do not have arthritis. However, the evidence is not conclusive, and more well-designed controlled trials are needed to confirm these findings.^[10][5][11]

MSM is on the FDA’s list of generally recognized as safe (GRAS) substances.^[5] However, there is very limited safety data, with most research to date being done on animals. Minor adverse events, such as gastrointestinal upset, skin rash, and allergies have been reported. In one animal study, these adverse effects were first noted at around 17 times the maximum recommended dosage. No changes to kidney or liver function have been noted with MSM use up to 6 grams per day.^[1][12][13] In a study done on rats, MSM was found to be safe during pregnancy, but this is not yet confirmed in human studies,^[14] and while the use of MSM during breast feeding is thought to be safe, there is little evidence to support this.^[15]

MSM works through several different mechanisms. MSM inhibits the proinflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, leading to lower levels of inflammatory cytokines including interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α). The inhibition of the NF-κB pathway may also inhibit cyclooxygenase-2 (COX2), an enzyme that plays a role in inflammation.^[5] The reduction in COX2 and the inhibition of inflammatory cytokines can also have antioxidant effects, as they regulate the generation of reactive oxygen species. MSM (and other sulfur-containing compounds) also regulates immune function, potentially inhibiting interleukin-6 and modulating cell death in certain types of cancer cells. MSM may also promote cartilage and bone health by stimulating signal molecules that promote osteogenesis (the formation/development of bone) and cartilage differentiation. These effects have been demonstrated in in vitro studies and in animal studies, and more research is needed to clarify the mechanisms through which MSM works in humans.^[5][11]