Methylsulfonylmethane

Common Name(s): DMSO2, Methylsulfonylmethane, MSM

Medically reviewed by Drugs.com. Last updated on Feb 20, 2024.

Clinical Overview

Use

Limited data from a few small placebo-controlled clinical trials provide some evidence for the short-term use of MSM for pain and swelling associated with osteoarthritis.

Dosing

MSM dosages ranging from 1.5 to 6 g/day in 2 to 3 divided doses (treatment durations up to 12 weeks) have been studied for management of symptoms associated with osteoarthritis.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

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

Interactions

None well documented.

Adverse Reactions

Mild GI reactions have been reported with MSM. A suspected but unconfirmed case of MSM-induced acute angle closure has been reported.

Toxicology

No data.

Source

MSM, a naturally occurring organosulfur molecule, is found in green plants such as Equisetum arvense and in 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 cerebrospinal fluid and plasma at concentrations of 0 to 25 mcmol/L.(Al Laham 2019, Engelke 2005) MSM is naturally occurring in fresh foods; however, it is destroyed with only moderate food processing, such as heating or dehydration.(Richmond 1986)

History

In the late 1970s, researchers began experimenting with the odorless MSM in search of similar therapeutic uses to dimethyl sulfoxide (DMSO). In 1981, Dr. Robert Herschler was granted a United States utility patent for the use of MSM to smooth and soften skin, to strengthen nails, or as a blood diluent. Subsequent patents claimed MSM relieves stress, relieves pain, is effective in parasitic infections, increases energy, boosts metabolism, enhances circulation, and improves wound healing, though there is little supporting scientific evidence. The literature suggests that MSM may have clinical applications for arthritis and other inflammatory disorders such as interstitial cystitis, allergic rhinitis, and acute exercise-induced inflammation. MSM research has expanded since early patents, and one MSM product (OptiMSM [Bergstrom Nutrition]) was granted generally recognized as safe (GRAS) status by the Food and Drug Administration in 2007; use of MSM remained largely unchanged from 2002 to 2012. MSM use appears to be on the rise, based on MSM sales data.(Butawan 2017)

Chemistry

MSM is a normal oxidation product of DMSO. MSM's medicinal properties are theorized to be similar to DMSO, without the odor and skin irritation complications.(Usha 2004) Unlike DMSO, MSM (sometimes referred to as "crystalline DMSO") is a dietary factor(Bertken 1983) and is a dietary source of sulfur for methionine.(Richmond 1986)

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, chemopreventive, antiparasitic, and free radical scavenging activities.(Alam 1983, Beilke 1987, Butawan 2017, Ebisuzaki 2003) It has been reported to alleviate allergies, arthritis, GI upset, and musculoskeletal pain, and to boost the immune system.(Butawan 2017)

Anti-inflammatory effects

Animal and in vitro data

Anti-inflammatory effects, specifically on enhancement of CD34+ stem cell activity, were examined in a mouse model of induced pancreatitis. Three MSM doses (100, 250, or 500 mg/kg) were administered via intraperitoneal injection. Multiple markers of inflammation were decreased in the pancreas and lungs, with significance noted primarily in the largest dose group. Anti-inflammatory mechanisms included reduction of H₂S and interleukin 1beta levels in the target tissues, reduced nuclear factor kappa B (NF-KB) activation, and increased localization of CD34+ cells.(Velusamy 2018)

In an in vitro study of THP-1 cells treated with natural sulfur compounds, MSM reduced high glucose–induced inflammation through multiple signaling pathways, including by reduced activation of NF-KB.(Jo 2020)

Cancer

Animal and in vitro data

Tumor onset in rats with induced colon cancer was markedly delayed in animals receiving MSM supplementation versus controls, suggesting a chemopreventive effect.(O'Dwyer 1988) Rats receiving MSM 4% showed a similar delaying effect on mammary breast cancer.(McCabe 1986) In an endometrial cancer cell line, MSM demonstrated apoptosis induction when used alone and increased the apoptotic and DNA-damaging effects of doxorubicin when used in combination.(Kowalska 2020)

Diabetes

Animal data

Compared with DMSO or dimethylsulfide, MSM showed no effect in preventing diabetes when tested in spontaneously diabetic mice.(Klandorf 1989)

Exercise-induced muscle injury

Animal data

MSM daily for 6 weeks (given before and during competition) exerted some protective effects on oxidative and inflammatory exercise-induced injury in 24 jumping horses.(Marañón 2008)

Clinical data

A small, randomized, placebo-controlled study (N=18) evaluated the effectiveness of MSM on exercise-induced muscle damage. Healthy volunteers were randomized to receive MSM 50 mg/kg/day in 200 mL of water or placebo for 10 days. Blood samples were drawn at baseline, and then following supplementation and a 14 km run. The group receiving MSM showed reductions in serum bilirubin and creatine kinase levels and higher total antioxidant capacity following exercise compared with placebo.(Barmaki 2012) In contrast, a small double-blind, randomized, placebo-controlled study that investigated the effects of MSM on exercise-induced muscle damage and pain in 24 healthy half-marathon runners showed no differences in oxidative or muscle damage outcomes following MSM 3 g/day administered for 3 weeks prior to the day of the race.(Withee 2017)

Osteoarthritis

Clinical data

A limited number of clinical trials in patients with osteoarthritis provide guidance on the use of MSM, as well as information regarding adverse effects.

A randomized, double-blind, parallel, placebo-controlled study evaluated use of oral MSM, alone and in combination with glucosamine (salt form not specified), in 118 patients with mild to moderate osteoarthritis (minimum duration of symptoms, 6 months). For 12 weeks, patients received 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 reduction in pain intensity assessed by a visual analog scale (VAS). Pain, swelling, and joint mobility were also scored on a 4-point scale (0=no restriction in joint movement; 3=most severe). Glucosamine alone significantly decreased mean pain intensity (from 58±11 mm at baseline to 54±10 mm, 48±11 mm, 42±10 mm, and 39±11 mm at the end of 2, 4, 8, and 12 weeks, respectively); MSM alone also decreased pain intensity (from 57±9 mm at baseline to 53±10 mm, 51±10 mm, 46±12 mm, and 38±10 mm, respectively). The decrease in mean pain intensity was much higher with the combination therapy group (from 56±12 mm at baseline to 50±9 mm, 44±11 mm, 41±10 mm, and 36±9 mm after 2, 4, 8, and 12 weeks, respectively) compared to placebo or MSM alone. Results data were also reported for swelling index, with significant decreases observed with glucosamine or MSM alone and a greater decrease observed with combination therapy (P<0.05 vs glucosamine and MSM alone). During the 12-week treatment, glucosamine, MSM, and combination therapy were well tolerated; except for mild GI discomfort, no patient experienced any serious adverse effect. The main adverse event was diarrhea, occurring in greater than 5% of patients and being more common in the glucosamine group.(Usha 2004)

In a 12-week pilot, randomized, double-blind, placebo-controlled trial in patients with knee osteoarthritis (American College of Rheumatology [ACR] functional class I, II, or III) and regular arthritis pain (arthritis pain most days) for at least 3 months (N=40), participants received oral MSM (OptiMSM micropill) 3 g twice daily or placebo; a 1-week stepwise approach to the full MSM dose was used, with 2 g/day in 2 divided doses administered for 3 days, then 4 g/day for 4 days, followed by 6 g/day starting at week 2. After 12 weeks, statistically significant improvements in VAS scores were observed for pain (−14.6 for MSM group and −7.3 for placebo group; P=0.041) and physical function impairment (−15.7 for MSM group and −8.8 for placebo group; P=0.045). Incidences of GI and other adverse effects included bloating, constipation, indigestion, fatigue, concentration issues, insomnia, and headache. These symptoms were minor, without complications, and did not interfere with daily activity or require treatment. Patients in the MSM and placebo groups reported symptoms at comparable frequencies.(Kim 2006)

Pain

Clinical data

In a randomized, double-blind, parallel, placebo-controlled study in patients with mild to moderate osteoarthritis (N=118), administration of MSM 500 mg 3 times daily for 12 weeks improved pain and swelling. However, the combination of glucosamine and MSM showed greater decreases in pain and swelling compared with either agent alone.(Usha 2004)

A small double-blind, randomized, placebo-controlled study investigated the effects of MSM on exercise-induced muscle damage and pain in 24 healthy half-marathon runners. Administration of MSM 3 g/day for 3 weeks prior to a race resulted in clinically, but not statistically, significant reductions in muscle pain compared with placebo at 15 minutes, 90 minutes, and 1 day after the race. Results were similar for joint pain at the 1-day postrace follow-up. No differences were observed in oxidative or muscle damage outcomes. Mild GI effects (n=2) and insomnia (n=1) were reported in the MSM group.(Withee 2017)

Skin aging

Clinical data

MSM 1 or 3 g/day for 4 months improved signs of skin aging in 63 subjects. Outcome measures included skin elasticity, moisturization, expert visual grading on a VAS scale, and subject self-assessment.(Muizzuddin 2020)

Ulcerative colitis

Animal data

In a rat model of induced ulcerative colitis, MSM 1,000 mg/kg for 6 days significantly decreased the weight/length ratio of the colon, while body weight was increased.(Al Laham 2019)

Dosing

MSM dosages of 1.5 to 6 g/day in 2 to 3 divided doses (treatment durations up to 12 weeks) have been studied for management of symptoms associated with osteoarthritis.(Kim 2006, Usha 2004)

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. In a developmental toxicity study, 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 increases in the incidence of fetal anomaly.(Magnuson 2007)

Interactions

None 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.(Horváth 2002) In one clinical study, similar rates of adverse effects were seen in the MSM and placebo groups; adverse events included bloating, constipation, decline in concentration, fatigue, headache, indigestion, and insomnia.(Kim 2006) Mild GI effects have been reported in healthy volunteers taking MSM.(Withee 2017)

The safety of MSM was investigated in adults 18 to 65 years of age with osteoarthritis and at least a 12-week history of low back pain in a double-blind, randomized, placebo-controlled trial (N=100). After a 2-week washout period of muscle relaxer or pain medications, MSM 6 g/day or placebo was administered as an adjunct to naproxen for 16 weeks. No difference was found between MSM and placebo with regards to physiological (eg, blood pressure, weight) or laboratory (eg, white blood cell count [WBC], hemoglobin, platelets, glucose, creatinine, total bilirubin, ALT, AST) values.(Crawford 2019)

Bilateral acute angle closure was reported in a 35-year-old woman 1 week after starting multiple dietary supplements. The patient presented with bilateral acute angle closure, choroidal effusion, and ciliary body edema similar to that observed with sulfa-based drugs. Her medical history was positive for systemic lupus erythematosus treated with prednisone, azathioprine, and hydroxychloroquine for the past year. Additionally, the patient was taking multiple nutritional supplements (eg, Herba 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 therefore suspected as the cause of the adverse event. Complete symptom resolution occurred within 4 days of discontinuing the most recently added 3 supplements.(Hwang 2015)

Toxicology

No important toxicity has been noted in studies.(Crawford 2019, Horváth 2002, McCabe 1986, O'Dwyer 1988)

References

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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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