INGREDIENTS & RESEARCH

MSM

BACKGROUND

Ingredient Type: Substance to supplement the diet 

Also Known As: Dimethyl Sulfone, Dimethylsulfon, Crystalline DMSO, Dimethyl Sulfone MSM, DMSO2, Methyl Sulfone, Methylsulfonylmethane, Methyl Sulfonyl Methane, Methyl Sulphonyl Methane, MSM, Sulfonyl Sulfur (1,2)

MSM is an easy to absorb bioavailable form of sulfur that naturally occurs in fruits, vegetables, grains, green plants, animals, and humans. It is also present in other foods like beer, port wine, coffee, tea, and cow’s milk. Although MSM is found in nature, it can also be produced in the laboratory (1,2,3).  MSM is well absorbed in humans taking less than an hour in duration.

In 1950s-1970s, MSM was studied for its antioxidant and anti-inflammatory properties (1), anticholinesterase activity, membrane penetrability, and capability to stimulate histamine release from mast cells. In 1981, Dr. Herschler in the United States studied it for its ability to smooth and soften skin, soften nails, and act as a blood diluent.  In 1999, MSM became famous due to the publication of the book entitled The Miracle of MSM the Natural Solution for Pain (4). Finally, in 2007, the Food and Drug Administration granted MSM the “Generally Recognized As Safe” status (5).

 

TRADITIONAL USES

Although there are no known traditional uses of MSM, sulfur, one of its base elements, has been used for thousands of years.  The ancient Chinese used sulfur as an ingredient in gunpowder.  In the Victorian period, people used sulfur mixed with syrup as a laxative and a tonic for children.  During the 1800s, people often went to hot springs rich in sulfur to help with various ailments (6).

 

WHAT DOES SCIENCE TELL US?

  MSM Might Have Antioxidation Properties:

In a randomized, double-blind, placebo-controlled study, sixteen subjects (healthy, young, untrained men) were divided into two groups and were given either MSM (prepared in water as 100 mg/ kg body weight) or placebo (water) before a 45-min run on a treadmill (at 75% VO2max). While there was no significant difference in the plasma GSH (reduced Glutathione) between the groups, post-assessment determined via markers of oxidative stress showed,

  • A lowered serum protein carbonyl (PC) in the MSM group two and twenty-four hours after the run
  • A higher plasma total antioxidant capacity (TAC) in the MSM group twenty-hour hours after the run
  • A significantly low serum level of uric acid and bilirubin in the MSM group after immediately after the run

The results of this study confirmed that a single MSM dose of oral supplementation indeed lowers the oxidative stress induced by exercise in the studied subjects (healthy untrained young men) (7).

In another randomized, double-blind, placebo-controlled study, eighteen subjects (untrained men) were divided into two groups and given a supplementation of MSM (50 mg/kg) or placebo for a duration of ten days. The assessment included an 8.7 mile run following a measurement of oxidative stress markers. Post-assessment results showed that the supplementation of MSM maintained oxidative stress markers, such as protein carbonyl (PC), serum malondialdehyde (MDA), plasma oxidized glutathione (GSSG), at low levels.

In addition, the study results showed that in the MSM group the plasma level of GSH and the ratio of GSH/GSSG were significantly higher. The results of the study indicate that MSM supplementation alleviates the previously mentioned oxidative stress markers (which are naturally increased by exercise) in the studied subjects (8).

  MSM Possibly Reduces Inflammation:

A single study was retrieved on the effect of MSM on inflammation; this renders the existing evidence insufficient. Regardless, the existing evidence suggests that MSM is effective in reducing inflammation following exercise in physically active subjects.

MSM has been tested for its known anti-inflammatory properties in physically active men in a double-blind, placebo-controlled study. Forty subjects were divided into two groups and either given 3 g/day of MSM or placebo (rice flour) for a duration of twenty-eight days prior to performing exercises (100 repetitions of eccentric knee extension). The following results were determined as a result of the MSM supplementation:

  • A decrease in IL-1β induction as a result of lipopolysaccharide stimulation of whole blood after MSM supplementation (while there was no effect on IL-6, TNF-α, or IL-8)
  • A strong release of IL-6 and TNF-α while there was a reduction in response to lipopolysaccharide in the placebo
  • A decrease (although small) in resting levels of pro-inflammatory cytokines
  • An acute increase in IL-10 (post exercise)

The study concluded MSM’s ability to dampen the release of inflammatory molecules in response to exercise (9).

  MSM Possibly Supports Healthy Skin by Reducing Lines and Wrinkles:

Only one study has been conducted on MSM’s effectiveness in reducing skin’s lines and wrinkles. Additional studies have found MSM to be beneficial in improving skin quality and texture, however, in these studies MSM was not studied in isolation, but with other components (10,11,12). Thus, it would be prudent to note that other components may have played a significant role in the same outcome and MSM’s contribution cannot be fully determined. 

In a primary double-blind, placebo-controlled, randomized study, twenty female subjects were divided into two groups and received either 3 g/day of MSM or placebo for a duration of over sixteen weeks. Post-assessment in weeks eight and sixteen showed MSM’s capability in regulating the genomic expression of the essential skin genes that prevent aging; in addition, the study found:

  • Statistically significant improvements in crow’s feet (Eighth week: P=0.024; Sixteenth week: P=0.002) and skin firmness (Sixteenth week: P=0.004) both from the mean baseline; and in comparison, with placebo for firmness (Eighth week: P=0.046) and for crow’s feet at week eight and sixteen (P=0.090)
  • Statistically significant improvements in tone (Eighth week: P=0.032; Sixteenth week: P=0.031) and texture of the skin (Eighth week: P=0.040; Sixteenth week: P<0.001)  
  • Statistically significant improvements in wrinkle (crow’s feet) total count (P=0.042), average length (P=0.032), severity (P<0.001), deep line counts (P=0.036)
  • Statistically significant improvements in wrinkle (global) total count (P=0.012), length (P=0.019), and average severity (P=0.024)

The study results indicated MSM’s effectiveness in benefiting skin health as it relates to reducing wrinkles and fine lines (12).

  MSM Might Decrease Muscle Soreness:

The most recent study on MSM’s impact in attenuating exercise-induced oxidative stress, muscle soreness, and muscle function includes a double-blind, placebo-controlled study where forty subjects (physically active men) were divided into two groups and either given 3g/day of MSM or placebo for a duration of twenty-eight days. The study followed with exercises (ten sets of ten repetitions of eccentric knee extension exercise). Post-assessment showed unaffected oxidative stress biomarkers; MSM attenuated muscle soreness by approximately 15-20% leading to a rapid recovery of isometric quadriceps force. The results of the study did not show a significant difference and concluded that a supplement of MSM for four weeks protects muscles force production and soreness to a certain degree (13).

In another randomized clinical trial, twenty-four subjects (moderately exercise-trained men; 25.5±5.6 yrs) were divided into two groups and given either 3 gm/d of MSM or placebo for a duration of fourteen days (with a 17-day washout between). Post-assessment which included three tests (baseline, no product and the second and third following fourteen-day supplementation with MSM and placebo) including various exercises, the results showed significantly less pain and discomfort in the MSM group (p=0.012) and a significant change in IL-6 (p = 0.006).  The study concluded MSM’s effectiveness in alleviating post-exercise discomfort or pain (14).

The alleviating effect of MSM on muscle soreness is further supported by another study. In a double-blind randomized study, eight subjects (healthy, moderately exercise-trained, exercising <150 minutes per week;27.1 ± 6.9 yrs old) were divided into two groups and given either 1.5 grams per day or 3.0 grams per day of MSM for a duration of thirty days (28 days before and 2 days following exercise). Subjects performed exercised to induce muscle damage. Post-measurement noted the following:

  • A trend in reduced muscle soreness for the 3g MSM group in comparison with the 1.5 gr MSM group (p = 0.080)
  • A decrease in fatigue with 3.0 grams (p = 0.073); for both dosages combined (p = 0.087)
  • A significant decrease (p = 0.007) in TEAC (blood antioxidant status measured by glutathione and Trolox Equivalent Antioxidant Capacity) after the exercise for the 3.0 gr of MSM group

The study concluded MSM effectiveness in increasing the antioxidant status of the body and improving exercise recovery including a reduction in muscle soreness when supplemented with 3 grams per day, but a larger sample of subjects and additional measurements are needed to confirm these findings (15).

  MSM Might Support Healthy Joints:

The most recent study includes a randomized, double-blind, placebo-controlled study where one hundred subjects (with hip and/or knee osteoarthritis) were divided into two groups and given either 6g/day of MSM or placebo for a duration of twenty-six weeks. Post-assessment results showed:

  • Significant decreases (P < 0.05) in all Western Ontario and McMaster University Osteoarthritis Index Visual Analogue Scale (WOMAC) subscales
  • Significant improvement (P < 0.05) in daily activities as measured by SF-36 (overall health-related quality of life)

The study concluded MSM’s effectiveness in improving all physical symptoms in patients with hip and/or knee osteoarthritis (16).

In another randomized, double-blind, placebo-controlled design where fifty subjects (men and women; 40-76 years of age; with knee osteoarthritis pain) were divided into two groups and given either 6g/day of MSM or placebo for a duration of twelve weeks. Post-assessment results showed a significant decrease (P<0.05) in pain and physical function impairment as measured via the Western Ontario and McMaster University Osteoarthritis Index visual analogue scale (WOMAC) in the MSM group (in comparison with placebo) and a significant improvement (P<0.05) in performing activities of daily living SF-36 (overall health-related quality of life) in the MSM group (in comparison with placebo).  The study concluded MSM’s ability to improve symptoms of pain and physical function in the studied subjects (17).

In a prospective, randomized, double-blind, controlled study, forty-nine subjects (men and women; 45-90; mean 68 ± SD 7.3 years of age with knee osteoarthritis; obese, overweight) were divided into two groups and given either 1.125 grams MSM three times daily (a total of 3.375 a day) or placebo for a duration of twelve weeks. Post-assessment results showed,

  • Significant differences in physical function (p = 0.04) between groups as measured by the Western Ontario and McMaster University Osteoarthritis Index visual analogue scale (WOMAC) Index for pain
  • Significant differences (p = 0.03) in the total WOMAC score
  • A significant difference (p = 0.05) in pain as measured by the visual-analogue-scale (VAS) between the groups while no difference was found in the pain and stiffness as measured via WOMAC

The study concluded MSM effectiveness in improving pain and physical function when taken in the studied dosage for twelve weeks. Due to the small magnitude of improvement, additional clinical trials should be considered. It is important to note variability in the results, thus presenting a challenge in making statistically difference effect on treating symptoms of osteoarthritis (18).

In a randomized, double-blind, parallel, placebo-controlled study, one hundred eighteen subjects (with mild to moderate osteoarthritis) were divided into three groups and given either 500mg/day of Glucosamine, 500mg/day of MSM or their combination for a duration of twelve weeks. Post-assessment results showed:

  • A significant decrease in the pain index for the MSM group (from 1.53 +/- 0.51 to 0.74 +/- 0.65)
  • An even more significant decrease in the mean pain index for the combination group (p < 0.001)
  • A significant decrease in the mean swelling index for both individually, but even greater decrease for the combination group (p < 0.05)
  • A statistically significant decrease in the Lequesne index

The study concluded that glucosamine and MSM, individually and when paired, produce an analgesic and anti-inflammatory effect in osteoarthritis. The study notes the greater efficacy in the combination of the two for reducing pain and swelling. The pair is also able to improve the functional ability of joints better than standalone. All in all, the pair has been concluded to provide a rapid improvement in the studied subjects (19).

A meta-analysis in which two related nutritional supplements dimethyl sulfoxide and methylsulfonylmethane in the treatment of osteoarthritis of the knee were analyzed. The analysis included randomized or quasi-randomized controlled trials, and specifically three RCTs, two DMSO and one MSM with a total of three hundred twenty-six subjects. The results of the meta-analysis indicated statistically significant (but not clinically relevant) reduction in pain compared with placebo (two studies) and a non-significant reduction of pain on the visual analogue scale.  The meta-analysis concluded DMSO and MSM’s ineffectiveness in reducing pain when treating subjects with osteoarthritis of the knee (20).

In a 2008 systematic review, DMSO and MSM evaluated six studies in which six hundred eighty-one subjects with osteoarthritis of the knee participated (DMSO, 297 on active treatment; MSM, 168 with 52 on active treatment). The results showed a significant improvement in pain outcomes in the two DMSO trials and both MSM trials in comparison with placebo.  The review noted that the MSM trials were more rigorous albeit more evidence is needed to confirm the positive results of MSM treating mild to moderate OA of the knee osteoarthritis (21).

  MSM Possibly Decreases Pollen Induced Allergies:

Only one study has been identified on the effect of MSM in decreasing pollen-induced allergies and nasal congestion; as such, the evidence is inadequate.

In a multicentered, open-label trial, fifty subjects were given 2,600 mg of MSM orally per day for a duration of thirty days. Post-assessment results showed,

  • A significant reduction in upper (p < 0.01) and total (p < 0.005) respiratory symptoms on day 7 in comparison with the baseline
  • A significant improvement (p < 0.001) in the lower respiratory symptoms in comparison with the baseline by week three
  • A significant increase (p < 0.0001) in energy levels by day fourteen and continuing through the thirtieth day

Moreover, efficacy was maintained at the end of the trial (the thirtieth day). The study concluded that although the results obtained are promising, larger, randomized, double-blind, placebo-controlled study would be worth conducting to confirm MSM’s effectiveness in reducing respiratory symptoms associated with allergies (22,23).

 

SAFETY

MSM is considered a Generally Recognized As Safe (GRAS) approved substance. MSM is likely safe and well tolerated by most people when taken up to four grams daily (1). A dosage of six grams a day has also been studied and proven to be safe (17).  Per FDA, the safe dosage at which MSM can be administered should be under 4845.6 mg/day (5).

  • MSM should not be given to children due to the limited research in children (24)
  • Because there isn’t enough evidence for the safety of MSM in pregnancy and breastfeeding, it is best to avoid taking it until further research is available (22,25)

Interactions:

  • No known interactions

Side-Effects:

  • A study reported MSM’s potential in causing acute angle closure (AAC) (26)
  • Nausea, diarrhea, bloating, headache, fatigue, insomnia, and difficulty concentrating, constipation, indigestion, fatigue has been reported, however, these were minor and were reported in placebo (17,22)
  • Gastrointestinal side-effects were observed when MSM was administered alone and when paired with glucosamine (22,27)
  • A rare incidence of pruritus was also noted (22)

 

REFERENCES

  1. Butawan M, Benjamin R, Bloomer R. Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients. 2017;9(3):290. doi:10.3390/nu9030290.
  2. Methylsulfonylmethane: MedlinePlus Supplements. Medlineplusgov. 2017. https://medlineplus.gov/druginfo/natural/522.html. Accessed April 5, 2018.
  3. Magnuson B, Appleton J, Ames G. Pharmacokinetics and Distribution of [35S]Methylsulfonylmethane following Oral Administration to Rats. J Agric Food Chem. 2007;55(3):1033-1038. doi:10.1021/jf0621469.
  4. Jacob S, Lawrence RM, Zucker M. The Miracle of MSM: The Natural Solution for Pain. New York: Penguin-Putnam, 1999.
  5. Borzelleca J.F., Sipes I.G., Wallace K.B.  Dossier in Support of the Generally Recognized as Safe (GRAS) Status of Optimism (Methylsulfonylmethane; MSM) as a Food Ingredient. Food and Drug Administration; Vero Beach, FL, USA: 2007.
  6. Sulfur. The Environmental Literacy Council. https://enviroliteracy.org/special-features/its-element-ary/sulfur/  Accessed June 13, 2018.
  7. Nakhostin-Roohi B, Niknam Z, Vaezi N, Mohammadi S, Bohlooli S. Effect of single dose administration of methylsulfonylmethane on oxidative stress following acute exhaustive exercise. Iran J Pharm Res2013;12(4):845-53.
  8. Nakhostin-Roohi B, Barmaki S, Khoshkhahesh F, Bohlooli S. Effect of chronic supplementation with methylsulfonylmethane on oxidative stress following acute exercise in untrained healthy men. Journal of Pharmacy and Pharmacology. 2011;63(10):1290-1294. doi:10.1111/j.2042-7158.2011.01314.x.
  9. Van der Merwe M, Bloomer R. The Influence of Methylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise. Journal of Sports Medicine. 2016; 2016:1-9. doi:10.1155/2016/7498359.
  10. Berardesca E, Cameli N, Cavallotti C, Levy J, Piérard G, de Paoli Ambrosi G. Combined effects of silymarin and methylsulfonylmethane in the management of rosacea: clinical and instrumental evaluation. J Cosmet Dermatol. 2008;7(1):8-14. doi:10.1111/j.1473-2165.2008.00355.x.
  11. Berardesca E, Cameli N, Primavera G, Carrera M. Clinical and instrumental evaluation of skin improvement after treatment with a new 50% pyruvic acid peel. Dermatol Surg. 2006 Apr; 32(4):526-31. doi:10.1111/j.1524-4725.2006.32106.x
  12. Anthonavage M, Benjamin R, Withee E. Effects of Oral Supplementation With Methylsulfonylmethane on Skin Health and Wrinkle Reduction. Natural Medicine Journal2015;7(11).
  13. Melcher D, Lee S, Peel S, Paquette M, Bloomer R. Effects of methylsulfonylmethane supplementation on oxidative stress, muscle soreness, and performance variables following eccentric exercise. A Journal on Internal Medicine and Pharmacology2017;176(5):271-83.
  14. Kalman D, Feldman S, Samson A, Krieger D. A Randomized Double Blind Placebo Controlled Evaluation of MSM for Exercise Induced Discomfort/Pain. The FASEB Journal2013;27(1).
  15. Kalman D, Feldman S, Scheinberg A, Krieger D, Bloomer R. Influence of methylsulfonylmethane on markers of exercise recovery and performance in healthy men: a pilot study. J Int Soc Sports Nutr. 2012;9(1):46. doi:10.1186/1550-2783-9-46.
  16. Pagonis T.A, Givissis P.A, Kritis A.C, Christodoulou A.C. The effect of methylsulfonylmethane on osteoarthritic large joints and mobility. Int. J. Orthop2014;1:19–24
  17. Kim L, Axelrod L, Howard P, Buratovich N, Waters R. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthr Cartil. 2006;14(3):286-294. doi:10.1016/j.joca.2005.10.003.
  18. Debbi E, Agar G, Fichman G et al. Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study. BMC Complement Altern Med. 2011;11(1). doi:10.1186/1472-6882-11-50.
  19. Debi R, Fichman G, Ziv Y.B, Kardosh R, Debbi E, Halperin N, Agar G. The role of msm in knee osteoarthritis: A double blind, randomized, prospective study. Osteoarthr. Cartil. 2007;15:C231. doi:10.1016/S1063-4584(07)62057-3.
  20. Brien S, Prescott P, Lewith G. Meta-Analysis of the Related Nutritional Supplements Dimethyl Sulfoxide and Methylsulfonylmethane in the Treatment of Osteoarthritis of the Knee. Evidence-Based Complementary and Alternative Medicine. 2011;2011:1-12. doi:10.1093/ecam/nep045.
  21. Brien S, Prescott P, Bashir N, Lewith H, Lewith G. Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis. Osteoarthr Cartil. 2008;16(11):1277-1288. doi:10.1016/j.joca.2008.03.002.
  22. Barrager E, Veltmann J, Schauss A, Schiller R. A Multicentered, Open-Label Trial on the Safety and Efficacy of Methylsulfonylmethane in the Treatment of Seasonal Allergic Rhinitis. The Journal of Alternative and Complementary Medicine. 2002;8(2):167-173. doi:10.1089/107555302317371451.
  23. Barrager E, Schauss A. Methylsulfonylmethane as a Treatment for Seasonal Allergic Rhinitis: Additional Data on Pollen Counts and Symptom Questionnaire. The Journal of Alternative and Complementary Medicine. 2003;9(1):15-16. doi:10.1089/107555303321222874.
  24. Glucosamine: Bottom Line Monograph. Assessing the research on this popular supplement. Natural Medicine Journal2011;3(5).
  25. Lin A, Nguy C, Shic F, Ross B. Accumulation of methylsulfonylmethane in the human brain: identification by multinuclear magnetic resonance spectroscopy. Toxicol Lett2001;123(2-3):169-77.
  26. Hwang JC, Khine KT, Lee JC, Boyer DS, Francis BA. Methyl-sulfonyl-methane (MSM)-induced acute angle closure. J Glaucoma. 2015 Apr-May;24(4):e28-30. doi:10.1097/IJG.0000000000000027.
  27. Usha P, Naidu M. Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis. Clin Drug Investig2004;24(6):353-63.

See the MedlinePlus entry for methylsulfonylmethane, the Examine.com entry for methylsulfonylmethane, the WebMD entry for MSM (methylsulfonylmethane), the Michigan Medicine Health Library entry for methylsulfonylmethane, or the RXList entry for MSM (methylsulfonylmethane) for more information.