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MSM Research Papers

A review of the major research conducted on MSM. If you have research that you'd like to see published here, please contact the MSM Guide Advisory Authority.

MSM: Research, Studies, Clinical Trials

MSM has been studied extensively on humans and animals in a wide variety of investigations. Several of these published papers research MSM's effect on reducing pain associated with osteoarthritis, its anti-inflammatory activity, and its safety .

Due to copyright limitations, we cannot reprint these papers. However, we can provide abstracts and links to PubMed or other resources where you can get more information.

If you have any research you would like to submit for consideration, please email the MSM Guide Advisory Authority.

Human Clinical Trials | Animal studies | In vitro, Experimental
Metabolism & Kinetics | Chemical | Toxicity

Human Clinical Trials

Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF. Efficacy of methylsulfonyl-methane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis and Cartilage 2006;14:286-94.
Southwest College Research Institute, Southwest College of Naturopathic Medicine & Health Sciences, Tempe, AZ, USA. [Abstract on PubMed]

In 2004, Kim et al conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the effects of distilled MSM on mild to moderate osteoarthritis of the knee. Participants received 3,000 mg twice daily of either placebo or MSM (OptiMSM, Bergstrom Nutrition, Vancouver, WA)) for 12 weeks. Patients were evaluated using standardized clinical efficacy scales as well as for several secondary endpoints, adverse events, and clinical laboratory markers. Compared to placebo, those taking MSM had statistically significant reductions in pain and in difficulty performing activities of daily living. Statistically significant reductions in serum homocysteine (a risk factor for cardiovascular disease) and urinary malondialdehyde (a marker of oxidative stress) were also observed. There were no significant adverse events in the study.

Engelke UF, Tangerman A, Willemsen MA, et al. Dimethyl sulfone [MSM] in human cerebrospinal fluid and blood plasma confirmed by one-dimensional (1)H and two-dimensional (1)H-(13)C NMR. NMR Bio Med 2005;18:33l-6.
Radboud University Nijmegen Medical Centre, Laboratory of Pediatrics and Neurology, L-6500 HB Nijmegen, The Netherlands. [Abstract on PubMed]

(1)H-NMR spectroscopy at 500 MHz was used to confirm that a previously unidentified singlet resonance at 3.14 ppm in the spectra of cerebrospinal fluid and plasma samples corresponds to dimethyl sulfone (DMSO(2)). A triple resonance inverse cryogenic NMR probe, with pre-amplifier and the RF-coils cooled to low temperature, was used to obtain an (1)H-(13)C HSQC spectrum of CSF containing 8 microM (753 ng/ml) DMSO(2). The (1)H-(13)C correlation signal for DMSO(2) was assigned by comparison with the spectrum from an authentic reference sample. In plasma and CSF from healthy controls, the concentration of DMSO(2) ranged between 0 and 25 micromol/l. The concentration of DMSO(2) in plasma from three of four patients with severe methionine adenosyltransferase I/III (MAT I/III) deficiency was about twice the maximum observed for controls. Thus, DMSO(2) occurs as a regular metabolite at low micromolar concentrations in cerebrospinal fluid and plasma. It derives from dietary sources, from intestinal bacterial metabolism and from human endogenous methanethiol metabolism. Copyright (c) 2005 John Wiley & Sons, Ltd.

Barrager E, Veltmann JR, Schauss AG, Schiller RN. A multi-centered, open label trial on the safety and efficacy of methylsulfonylmethane in the treatment of seasonal allergic rhinitis. J Altern Complement Med 2002;8:167-74.

In a open-label study of 55 patients with seasonal allergic rhinitis (SAR; hayfever), MSM at 2600mg/day significantly reduced upper and total respiratory symptoms within 7 days; lower respiratory symptoms were significantly improved from baseline by week 3. No significant changes were observed in plasma IgE or histamine levels. Few side effects were associated with the use of MSM and no patient dropped out of the study due to adverse reactions. Energy levels increased significantly by day 14. The results suggest that MSM may be an efficacious in reducing symptoms associated with SAR.

Blum JM, Blum RI. The effect of methylsulfonylmethane (MSM) in the control of snoring. Integrative Medicine 2004;3(6)24-30.

Childs SJ. Dimethyl sulfone (DMSO2) in the treatment of interstitial cystitis. Urol Clin North Am 1994;21:85-8.

Dr. Childs presents six case studies on the use of intravesicular MSM for interstitial cystitis in patients who were refractory to previous therapy.

Lawrence RM. Methylsulfonylmethane (M.S.M.) A double-blind study of its use in degenerative arthritis. Int J Anti-Aging Med 1998;1(1):50 [abstract].

In this abstract, Lawrence presented data on a "preliminary study" in which patients suffering from degenerative arthritis were treated with either 2,250 mg per day of MSM (Adaptin, no manufacturer specified) or placebo for an unspecified length of time. Sixteen patients were reportedly enrolled in the study. Eight received MSM and six received placebo. The author does not indicate what treatment, if any, was administered to the two remaining patients. Lawrence reported "a better than 80 percent control of pain within six weeks of beginning the study." The title of the abstract indicates that a double-blind protocol was followed.

Usha PR, Naidu MUR. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Invest 2004; 24:353-63.

Randomized, double-blind trial comparing MSM, glucosamine, both, or placebo for osteoarthritis of the knee. Approximately 30 patients per group. Dose was 1,500 mg per day for 12 weeks. The efficacy parameters studied were the pain index, the swelling index, visual analogue scale pain intensity, 15m walking time, the Lequesne index, and consumption of rescue medicine. There were statistically significant decreases in pain with Glu and with MSM respectively. The combination treatment resulted in a more significant decrease in the mean pain index than either treatment alone. Conclusion: Glu, MSM and their combination produced an analgesic and anti-inflammatory effect in osteoarthritis. Combination therapy showed better efficacy in reducing pain and swelling and in improving the functional ability of joints than the individual agents.

Vidyasagar S, Mukhyaprana P, Shashikiran U,et al. Efficacy and Tolerability of glucosamine chondroitin sulphate - methyl sulfonyl methane (MSM) in osteoarthritis of knee in Indian patients. Iran J Pharmacol Ther 2004;3:61-5.

Isolation; presence in nature, in animals and humans

Pearson TW, Dawson HJ, Lackey HB. Natural occurring levels of dimethyl sulfoxide in selected fruits, vegetables, grains and beverages. J Agric Food Chem 1981; 29:1019-21.

Performed at Crown-Zellerbach, this study documents the presence of MSM (DMSO2; Me2SO2) in asparagus, alfalfa, beets, cabbage, corn, cucumber, oats, swiss chard, tomatoes, apples, raspberry, beer, coffee, milk and tea.

Pfiffner JJ, North HB. Dimethyl sulfone: A constituent of the adrenal gland. J Biol Chem 1940;134:781-2.

From the research labs of Parke-Davis, one of the earliest isolations of dimethyl sulfone (1940). Originally isolated from cattle blood, this study found MSM in fresh beef glands.

Williams KIH, Burstein SH, Layne DS. Dimethyl sulfone: isolation from cows' milk. Proc Soc Exp Biol Med 1966;122:865-6.

Supported in part by the National Institute of Arthritis and Metabolic Diseases and performed at the Worcester Foundation for Experimental Biology, this study isolated MSM from cow's milk and noted that urinary excretion of MSM approximated 5-10mg/24 hours in humans.

Williams KIH, Burstein SH, Layne DS. Dimethyl Sulfone:  Isolation from human urine. Arch Biochem Biophys 1966;113:251-2.

MSM is isolated in human urine. In samples from 4 women and 4 men, the rate of excretion varied from 4mg to 11mg. The authors speculate that the MSM excreted may be derived from dietary sources or a product of the metabolism of sulfur containing amino acids.

Williams KIH, Burstein SH, Layne. Metabolism of dimethyl sulfide, dimethyl sulfoxide, and dimethyl sulfone in the rabbit. Arch Biochem Biophys 1966;117:84-7.

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Animal Studies

David Amiel, PhD; Robert M Healey, BS, MBA and Yasushi Oshima, MD, PhD, Assessment of methylsulfonylmethane (MSM) on the development of osteoarthritis (OA): An animal study FASEB J. 2008 22:1094.3.

This study examined the effects of ultra pure methylsulfonylmethane (OptiMSM) on osteoarthritis of the knee. A prior study showed that while OptiMSM is clinically effective, the mechanism remained enigmatic. In this study, the right knee ACL was transected (ACLT) in mature NZW rabbits (n=10) (2). Five weeks after ACLT an MSM constant delivery system to the joint was created by implanting an Alzet osmotic pump. Controls received no other treatment. Animals were sacrificed 9 wks postop, and OA grading of the femoral surface was performed: Grade-I (G-1): intact surface; Grade-II (G-II): minimal fibrillation; Grade-III (G-III): overt fibrillation; and Grade-IV (G-IV): erosion of articular cartilage surface (2). Results showed 2 G-III and 1 G-IV (avg 3.3) in control. The MSM-treated group showed 1 G-I, 3 G-II, 1 G-III, and 2 G-IV (avg 2.6). Expression of type II collagen and aggrecan showed no difference between control and MSM, yet expression of TNF-a in both cartilage and synovial tissue was decreased by MSM (p<0.01). MSM preserved the articular cartilage surface during OA development and reduced inflammation (i.e. TNF-a) in both cartilage and synovium.

Robert A DiSilvestro, David J DiSilvestro, and Daniel J DiSilvestro, Methylsulfonylmethane (MSM) Intake in Mice Produces Elevated Liver Glutathione and Partially Protects Against Carbon Tetrachloride-Induced Liver Injury FASEB J. 2008 22:445.8.

MSM's antioxidant actions have been proposed based mostly on indirect evidence. For example, antioxidant actions in vivo of a related compound, DMSO, may be produced by MSM formed in vivo from DMSO. Thus, a study was done in mice to determine whether oral intake of OptiMSM could affect tissue levels of an internal sulfur-containing antioxidant, glutathione, and resistance to chemically-induced oxidant stress. MSM administration (5 weeks, 80 mg/100 ml drinking water) produced a statistically significant increase in liver glutathione (mean increase of 78%). A similar effect was not seen in lung or skeletal muscle. In addition, MSM partially inhibited liver injury after injection of carbon tetrachloride, which induces liver oxidant stress (injury evaluation based on blood indexes of hepatic injury). These results indicate the need for further testing for MSM antioxidant actions in vivo, and to explore the mechanism of elevated glutathione.

Magnuson, B.A., Appleton, J., Ryan, B., Matulka, R.A., Oral Developmental Toxicity Study of Methylsulfonylmethane in Rats, Food and Chemical Toxicology (2006), doi: 10.1016/j.fct.2006.12.003

The objective of these studies was to determine the developmental toxicity potential of MSM when administered orally to pregnant rats during the period of major organogenesis and histogenesis. In a preliminary dose-finding study, distilled MSM microprill (i.e., microspherical pellets of MSM) was administered by oral gavage at dose levels of 0 (vehicle control), 50, 250, 500, and 1000 mg/kg/day to 8-9 sperm-positive female Sprague-Dawley rats/group/day on gestation days 6 through 20. No evidence of maternal or fetal toxicity was observed. For the definitive developmental study, four groups of 24-25 timed-bred primiparous female rats were administered 0, 50, 500, or 1000 mg MSM/kg/day via gavage on gestation days 6 through 20. Maternal feed consumption, body weight, body weight gain, uterus weight and corrected body weight/body weight gain were unaffected by treatment. No evidence of maternal toxicity, and no significant differences in litter viability, litter size, or litter body weight were detected. Fetal evaluations failed to show any biologically significant increase in the incidence of anomalies in the MSM treated groups, and no malformations were seen in any of the fetuses. No evidence of fetal mortality, alterations to growth, or structural alterations were observed in the fetuses of dams administered 50 to 1000 mg/kg/day. Therefore, under the conditions of this study, the no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity was 1000 mg/kg/day.

Magnuson, B.A., Appleton, J., Ames, B.A., Pharmacokinetics and Distribution of [35S]Methylsulfonylmethane following Oral Administration to Rats, Journal of Agricultural and Food Chemistry (2006)

The objective of this study was to evaluate the pharmacokinetic profile and distribution of radiolabeled MSM in rats. Male Sprague-Dawley rats were administered a single oral dose of [35S]MSM (500 mg/kg), and blood levels of radioactivity were determined at different time points for up to 48 h. Tissue levels of radioactivity at 48 and 120 h and urine and fecal radioactivity levels were measured at different time points for up to 120 h following [35S]MSM administration to rats. Oral [35S]MSM was rapidly and efficiently absorbed with a mean tmax of 2.1 h, Cmax of 622 µg equiv/mL, and AUC0-inf of 15124 h.µg equiv/mL. The t1/2 was 12.2 h. Soft tissue distribution of radioactivity indicated a fairly homogeneous distribution throughout the body with relatively lower concentrations in skin and bone. Approximately 85.8% of the dose was recovered in the urine after 120 h, whereas only 3% was found in the feces. No quantifiable levels of radioactivity were found in any tissues after 120 h, indicating complete elimination of [35S]MSM. The results of this study suggest that [35S]MSM is rapidly absorbed, well distributed, and completely excreted from the body.

Richmond VL. Incorporation of methylsulfonylmethane sulfur into guinea pig serum proteins. Life Sci 1986;39:263-8.

Wang M-Y, Anderson G, Nowicki D. Preventive effect of methylsulfonylmethane (MSM) at the induction stage of mammary carcinogenesis induced by DMBA in female SD rats. Proc Am Assoc Cancer Res 2003; 44(8):787 [Abstract #3445].

Wang M-Y, Anderson GL, Nowicki D. Synergistic effect of Tahitian Noni Juice (TNJ) and methylsulfonylmethane (MSM) on mammary breast cancer prevention at the initiation stage of chemical carcinogenesis induced by DMBA in female Sprague-Dawley (SD) rats. Cancer Epidemiol Biomarkers Prev 2003;12:1354S.

Carlson, RP [study director]. Bergstrom Nutrition rat carrageenan air pouch model No. 1. White Eagle Toxicology Laboratories [Unpublished: data on file]. (Sponsored by Bergstrom Nutrition).

Anti-inflammatory actions of MSM observed in an experimental rat study in 2001. MSM compared to indomethacin in a rat carrageenan air pouch model. The objective of the study was to determine whether MSM inhibited leukocyte influx and edema in an acute inflammation model. MSM was administered orally (300 or 1,000 mg/kg for three days) to male CD Charles River rats, in which inflammation was produced with injections of carrageenan.  Oral MSM at 1,000mg/kg, administered for two days prior and up to two hours prior to carrageenan injections inhibited the total number of leukocytes migrating into the pouch at four hours by 26%. The 300mg/kg dose inhibited leukocyte infiltration by 18%. These results did not reach statistical significance, possibly due to the small number of animals studied, or because the anti-inflammatory effects of MSM are more likely to be demonstrated in a chronic inflammation model.

Gerhards E, Gibian H. The metabolism of dimethyl sulfoxide and its metabolic effects in man and animals. Ann N Y Acad Sci 1967;141:65-76.

Metabolism of DMSO, including its oxidation to MSM, in the human. Key factoid: 15% of ingested DMSO is rapidly oxidized to DMSO2 (MSM) in vivo, by hepatic microsomes in the presence of NADPH2 and molecular oxygen.

Hasegawa T, Kumamoto S, Ueno S, Yoshikai Y. Suppressive effect of methylsulfonylmethane (MSM) on Type-II collagen-induced arthritis in SBA/1J mice. Jpn Pharmacol Ther 2004;32:421-7.

Oral administration of MSM (OptiMSM, Bergstrom Nutrition, Vancouver, WA) modified immune responses in DBA/1J mice. Arthritic deformation and swelling induced by type II collagen injections (an animal model of rheumatoid arthritis) were significantly diminished in mice drinking MSM compared to controls. Abnormal white blood cell proliferation in lymph nodes was also reduced in mice drinking MSM.

Hasegawa T, Ueno S, Kumamoto S. Anti-inflammatory effect of methylsulfonylmethane (MSM) in mice Jpn Pharmacol Ther 2005;33:1217-23.

Researchers investigated three aspects of the anti-inflammatory activity of OptiMSM: skin damage caused by ultraviolet (UV) light exposure, skin inflammation, and itching.  Mice models were used in these experiments: UV-irradiated hairless mice for skin damage, ovalbumin-immunized mice for inflammatory skin reaction, and mice injected under the skin with histamine for scratching behavior. Application of topical MSM suppressed the skin inflammation caused by UV radiation, improved weight gain, and prevented a rise in sialic acid. Oral MSM (2.5% ad libitum) had suppression the immediate-phase swelling reaction induced by ovalbumin injections. Lastly, scratching behavior was considerably less in mice that were allowed to drink 2.5% MSM solution starting one week prior to the histamine injections.

Klandorf H, Chirra AR, DeGruccio A, Girman DJ. Dimethyl sulfoxide modulation of diabetes onset in NOD mice. Diabetes 1989;38:194-7.

Dimethyl sulfoxide (DMSO) modulation of diabetes onset in NOD mice. Authors sought to determine whether the intake of DMSO or its derivatives MSM and dimethyl sulfide (DMS) could prevent the expression of autoimmune diabetes in the spontaneously diabetic NOD mouse. DMSO (2.5%) markedly increased the rate at which the animals expressed overt diabetes. MSM had no effect. DMS reduced the incidence and rate of diabetes onset.

McCabe DP, O'Dwyer PJ, Sickle-Santanello BJ, et al. Polar solvents in the chemoprevention of dimethylbenzanthracene-induced rat mammary cancer. Arch Surg 1986;121:1455-9.

Authors used 5% DMSO, 1% and 4% MSM, 0.3% N-methylformamide (NMF), and retinol acetate in the chemoprevention of rat mammary breast cancer. Tumor incidence was not statistically affected. Time to appearance (latency period) of both tumors and cancers were prolonged by NMF, DMSO, and 4% MSM. No group exhibited toxic reactions or significant weight loss.

Moore RD, Morton JI. Diminished inflammatory joint disease in MRL/1pr mice ingesting dimethylsulfoxide (DMSO) or methylsulfonylmethane (MSM). Federation of American Societies for Experimental Biology 69th Annual Meeting, Anaheim, California, April 21-26, 1985:Abstract 692.

The MRL/1pr strain of mice had been identified as a model for the spontaneous development of rheumatoid arthritis-like joint lesions. Knee joint examination revealed proliferation of synovial lining cells in all control animals and in only 71% of the MSM-treated mice. The degree of proliferation was less marked in the experimental group. 95% of the control animals had an synovial inflammation, compared with only 50% of the MSM-treated animals. The degree of inflammation was also judged to be less severe in the MSM-treated group. Pannus formation was present in 50% of controls but only in 14% of MSM-treated mice. The decreases in inflammatory joint disease observed with MSM treatment in this study are consistent with previously reported decreases in autoantibody titers and abnormal T cell proliferation in similar animals; moreover, they are consistent with the clinical effects of MSM we have seen in RA patients at Dr. Jacob's clinic at Oregon Health & Science University (OHSU).

Morton JI, Siegel BV. Effects of oral dimethyl sulfoxide and dimethyl sulfone on murine autoimmune lymphoproliferative disease. Proc Soc Exp Biol Med 1986;183:227-30.

At a dose of 6-8 gm/kg/day, MSM demonstrated "significant protection against the development of murine autoimmune lymphoproliferative disease….(there were) no signs of toxicity…possible mechanisms of protection are discussed." Mouse model.

Morton JI, Moore RD. Lupus nephritis and deaths are diminished in B/W mice drinking 3% water solutions of dimethyl sulfoxide (DMSO) or dimethyl sulfone (DMSO2). J Leukocyte Biol 1986;40:322.

Lupus nephritis and deaths are diminished by MSM. Lupus-prone B/W hybrid mice were fed 3% solutions of either DMSO or MSM, or water (control group), from the age of one month. After 6 to 8 months, strong plasma antinuclear antibody (ANA) responses were observed in 46% of those drinking water, 6% of those drinking the DMSO solution, and 14% of those drinking the MSM solution. At 7 months of age, 30% of the control and none of the DMSO- or MSM-fed females had died. Anemia, as determined by hematocrit, was less severe in the DMSO and MSM groups, compared with the control group. In the control mice, 25 to 36% of the glomeruli showed severe renal damage, with extensive deposition of extracellular material; distortion of tuft, with compression and distention of basement membranes; obliteration of capillary lumens; and decreased cellularity. Only 3 to 5% of DMSO glomeruli, and 7 to 17% of MSM glomeruli showed this degree of change. Other B/W females were started on DMSO or MSM treatment at 7 months of age, when disease was well developed. After three months, only 14% of the controls were alive, compared with 78% of those treated with DMSO and 62% of those treated with MSM. The mechanisms of these protective effects are not known, but the authors of the study speculated that diminished disease may have resulted from decreased ANA formation, or diminished deposition or enhanced clearance of immune complexes.

Murav'ev IuV, Venikova MS, Pleskovskaia GN, et al. [Effect of dimethyl sulfoxide and dimethyl sulfone on a destructive process in the joints of mice with spontaneous arthritis]. Patol Fiziol Eksp Ter 1991 Mar-Apr;(2):37–9[in Russian].

O'Dwyer PJ, McCabe DP, Sickle-Santanello BJ, et al. Use of polar solvents in chemoprevention of 1,2-dimethylhydrazine-induced colon cancer. Cancer 1988;62:944–8.

Researchers at Ohio State demonstrate that MSM significantly reduces the latent period to tumor onset in DMH-induced colon cancer in rats. No weight loss or toxicity was observed.

Pratt SE, Clarke AF, Riddolls L, McKee S. A study of the absorption of methylsulfonylmethane in horses. Proc 17th Equine Nutr Physiol Soc:141-2.

Researchers found that a substantial amount of MSM (OptiMSM, Bergstrom Nutrition, Vancouver, WA) is absorbed through the intestinal tract and retained. Six horses were used in the study after adapting to a diet of hay and grain fed twice daily for two weeks. Horses remained on this diet throughout the trial. They had free access to water, and their temperature, and heart and respiratory rates were monitored daily. Feces and urine were collected twice daily throughout the trial. On days 0, 5, and 9, blood and synovial fluids were also obtained. However, the researchers were not able to obtain sufficient amounts of synovial fluid from some of the horses, and this prevented statistical analysis of the synovial fluid results. On days 1 to 5, four of the horses were given 18,500 kBq of radiolabeled OptiMSM each. The required volume (0.83 ml) was measured and applied to a piece of bread. Molasses was then added to increase palatability, and the mixture was fed to each horse. The control horses received only bread and molasses. On days 6 to 9, 20 grams of "cold" MSM was given to the four treatment horses. Radiolabeled sulfur was detected in both urine and feces by day 1, with peak excretion around day 5. By day 9, there were decreased levels of radioactivity in both the urine and feces. Additional samples from the four treatment horses revealed no presence of radiolabeled sulfur (S-35) in the feces or urine approximately one month after completion of the trial. This trial, and an initial trial using one catheterized mare found that 55% of the S-35 was absorbed by the horse. Although statistical analysis of the synovial fluid samples could not be performed, the authors stated that their data suggested some S-35 was present in the synovial fluid. There was no effect of radiolabeled MSM (35MSM) on any variable in the hematology reports.

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;53:1908–16.

Authors evaluated the efficacy of 3 treatments for chronic obstructive pulmonary disease in horses: prednisone (400 mg/horse, PO, daily; n = 7), MSM (10 g/horse, PO, q 12 h; n = 6), and clenbuterol hydrochloride (0.4 mg/horse, PO, q 12 h; n = 7). A fourth group acted as controls (n = 6) and was not treated. The treatment period lasted 10 days. Each horse was a member of 2 different groups for 10 days, separated by an 18-day interval of no treatment. Changes in lung sounds, respiratory effort, degree of anal movement, nasal discharge, temperature, respiratory rate, or heart rate were not significant. Changes in arterial blood gas tensions, tracheal wash or bronchoalveolar lavage cytologic findings, or phagocyte function were not significant. All horses were tachypneic and most were tachycardic. The median value for PaO2 was below normal for all horses. All tracheal wash and most bronchoalveolar lavage cytologic findings represented a suppurative response. Negative linear correlation was observed between PaO2 and degree of respiratory effort in these horses (e.g., as PaO2 decreased, the degree of respiratory effort increased).

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In vitro, Experimental

Oshima Y, Theodosakis J, Amiel D. The Effect Of Distilled Methylsulfonylmethane (MSM) on Human Chondrocytes in vitro. 2007 World Congress on Osteoarthritis, Ft. Lauderdale, Florida; Osteoarthritis and Cartilage 2007;15:213.

This investigation, conducted in the laboratory of cartilage biology expert David Amiel, PhD, from the Department of Orthopedics at the University of California , San Diego , assessed the impact of OptiMSM(R) on inflammation and degradation markers of human knee joint cartilage. Human (cadaver-derived) knee joints, displaying varying degrees of osteoarthritis, were cultured with varying concentrations of OptiMSM. Extracts were then obtained from the cultures and gene expression testing was performed. Positive trends indicated OptiMSM incubation of cartilage cells derived from humans with moderate severity osteoarthritis reduced the activation of genes coding for the manufacture of pro-inflammatory cytokines. This study also found in the same grade of osteoarthritic joint-derived cartilage cells a positive trend in reducing the activation of genes coding for the manufacture of enzymes that promote the breakdown and "digestion" of cartilage--matrix metalloproteases, or MMPs. The authors suggested that these basic research findings lend themselves to explaining, in part, how OptiMSM may support joint health and functionality.

Alam SS, Layman DL. Dimethyl sulfoxide inhibition of prostacyclin production in cultured aortic endothelial cells. Ann N Y Acad Sci 1983;411:318-20.

Dimethyl sulfoxide inhibition of prostacyclin production in cultured aortic endothelial cells. They also studied MSM. MSM inhibited PGI2 synthesis by cultured aortic endothelial cells by 50%. Suggests anti-inflammatory mechanism with potential cardiovascular applications.

Beilke MA, Collins-Lech C, Sohnle PG. Effects of dimethylsulfoxide on the oxidative function of human neutrophils. J Lab Clin Med 1987;110:91-6.

Effects of DMSO (and MSM) on the oxidative function of human neutrophils. In 1987, Beilke and colleagues published the results of in vitro experiments testing the ability of DMSO and MSM to interfere with the production of oxidants by stimulated human neutrophils.  Both DMSO and MSM significantly suppressed the production of superoxide, hydrogen peroxide, and hypochlorous acid by human neutrophils stimulated with either phorbol myristate or opsonized zymosan. Neither DMSO nor MSM reduced the viability of the stimulated neutrophils. The authors suggest that this inhibition of the oxidative function of human neutrophils could provide an explanation for these compounds' enhancement of the microbiocidal activity of neutrophils, and for their observed anti-inflammatory effects.

Ebisuzaki K. Aspirin and methylsulfonylmethane (MSM): a search for common mechanisms, with implications for cancer prevention. Anticancer Res 2003;23:453-8.

Layman DL. Growth inhibitory effects of dimethyl sulfoxide and dimethyl sulfone on vascular smooth muscle and endothelial cells in vitro. In Vitro Cell Development Biol 1987;23:422-8.

The growth of bovine aortic smooth muscle and endothelial cells was studied after exposure to dimethyl sulfoxide (DMSO) or its major metabolite, dimethyl sulfone (DMSO2, MSM). Both compounds caused a dose-dependent inhibition of cell growth as determined by [3H]thymidine incorporation and by counting the number of cells with time of exposure in culture. MSM was a more potent inhibitor of cell growth than DMSO and its growth inhibition was less reversible than that produced by DMSO. Implications for the prevention of atherosclerosis.

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Metabolism & Kinetics

Hucker HB, Hoffman EA. A new method for assay of radioactive dimethyl sulfoxide and its metabolite, dimethyl sulfone. Experientia 1966;22:855-6.

Merck researchers articulate and develop an assay method for radiolabeled MSM.

Hucker HB, Miller JK, Hochberg A, et al. Studies on the absorption, excretion and metabolism of dimethylsulfoxide (DMSO) in man. J Pharmacol Exp Ther 1967;155:309-317.

Key findings: Humans and animals both metabolize DMSO to MSM in a similar fashion. Striking difference in the rates of excretion of DMSO and MSM: Excretion of oral DMSO was complete after 120 hours, whereas MSM excretion was much more prolonged, lasting 480 hours or more. Gerhards reported similar findings, but did not follow excretion past 96 hours.

Kocsis JJ, Harkaway S, Snyder R. Biological effects of the metabolites of dimethyl sulfoxide. Ann N Y Acad Sci 1975;243:104-9.

Key findings: MSM protects against the adverse effects of anticholinesterase agents. Also observed tranquilizing or sedative effects due to decreased motor activity following intrapedal injection, but not oral supplementation, of MSM. Evidence of substantial similarities in actions of DMSO and MSM.

Layman DL, Jacob SW. The absorption, metabolism and excretion of dimethyl sulfoxide by rhesus monkeys. Life Sci 1985;37:2431-7.

Absorption, distribution, metabolism and excretion of DMSO and MSM in rhesus monkeys.

Martin W. [Natural occurrence of DMSO and DMSO2 in the human organism.] In: Jacob SW, Kappel JE, eds. DMSO International DMSO Workshop, Hannover, Germany, September 19, 1987. San Francisco: W. Zuckschwerdt Verlag, 1987, 71–7.

Human plasma naturally contains both DMSO and MSM in small but significant concentrations. Although it is assumed that the presence of these agents in human plasma is the result of absorption from foodstuffs, some authors have proposed a model of DMSO (and hence, MSM) synthesis within the human organism. The authors examined blood samples from 100 volunteers and determined the naturally occurring levels of DMSO in human plasma to be between 20 and 40 ng/mL (which is equivalent to 20 to 40 parts per billion). The concentrations of MSM found in human plasma were far greater, between 700 and 1,100 ng/mL (0.7 to 1.1 ppm).

Otsuki S, Qian W, Ishihara A, Kabe T. Elucidation of dimethylsulfone metabolism in rat using a 35S radioisotope tracer method. Nutr Res 2002; 22:313–22.

Ruzicka L, Goldberg MW, Meister H. [Isolation of dimethylsulfone from bovine blood]. Acta Chimica Helvetica 1940; 23:559-61 [in German].

First isolation of MSM from bovine blood.

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Chemical

Sowada R. [Preparation, properties and uses of dimethylsulfone]. Zeitschrift fur Chemie 1968; 8(10):361-76 [in German].

Comprehensive study of the chemistry of dimethyl sulfone

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Toxicity

Cecil KM, Lin A, Ross BD, Egelhoff JC. Methylsulfonylmethane observed by in vivo proton magnetic resonance spectroscopy in a 5-year-old child with developmental disorder: effects of dietary supplementation. J Comput Assist Tomogr 2002;26:818-20.

Proton magnetic resonance spectroscopy (MRS) revealed a distinct resonance at 3.15 ppm in the brain of a 5-year-old male diagnosed with autism. The resonance assignment is attributable to ingestion of methylsulfonylmethane (MSM) as a dietary supplement. Glucosamine with MSM is marketed as a source of dietary sulfur and treatment of joint pain. Recognition of this chemical on brain proton MRS as an exogenous compound is necessary to avoid confusion as a pathologic metabolite of pediatric metabolic disease.

Horváth K, Noker PE, Somfai-Relle S, et al. Toxicity of methylsulfonylmethane in rats. Food Chem Toxicol 2002; 40:1459-62.

The first and only toxicology study of MSM (OptiMSM, Bergstrom Nutrition, Vancouver, WA) to be published in a peer-reviewed journal. Published in the Journal of Food & Chemical Toxicology. GLP-compliant. No adverse effects were noted in either acute or subchronic (90) studies at dose levels of 2 g/kg in the acute phase and 1.5 g/kg in the subchronic phase. Toxicology, lab, gross pathology, histology were all negative.

Goldstein P, Magnano L, Rojo J. Effects of dimethyl sulfone (DMSO2) on early gametogenesis in Caenorhabditis elegans: ultrastructural aberrations and loss of synaptonemal complexes from pachytene nuclei. Reprod Toxicol 1992;6:149-59.

Concern has been raised based on the results of this in vitro study, which found meiosis was interrupted in early gametogenesis in the nematode Caenorhabditis elegans (C. elegans is a small (about 1 millimeter), primitive worm that shares certain essential biological characteristics with humans (e.g., it produces sperm and eggs, reproduces, has a nervous system, etc.). Its short lifespan, rapid development, and easy cultivation under controlled conditions make it a favorite of research scientists as a model for toxicologic assays. When it was grown in concentrations of MSM exceeding 1%. Increasing concentrations of MSM impaired the fecundity and viability of treated worms. This study is actually attempting to suggest the possibility of a teratogenic effect. However, more definitive research has shown no teratogenic effects or developmental toxicity.

Lin A, Nguy CH, Shic F, Ross BD. Accumulation of methylsulfonylmethane in the human brain: identification by multinuclear magnetic resonance spectroscopy. Toxicol Lett 2001;123:169-77.

In vivo magnetic resonance spectroscopy (MRS) was used to detect and quantify MSM in the brains of four patients with memory loss and in three normal volunteers all of who had ingested MSM at the recommended doses of 1-3 g daily. MSM was detected in all subjects at concentrations of 0.42-3.40 mmole/kg brain and was equally distributed between gray and white matter. MSM was undetectable in drug-naive normal subjects (N=25), patients screened for 'toxic exposure' (N=50) or patients examined with 1H MRS for the diagnosis of probable Alzheimer Disease (N=520) between 1991 and 2001. No adverse clinical or neurochemical effects were observed. Appearance of MSM in significant concentrations in the human brain indicates ready transfer across the intact blood-brain barrier.

Hixson O. Acute intragastric toxicity (LD-50). Dimethyl sulfone (methylsulfonylmethane, MSM). Laboratory of Vitamin Technology, Inc., Chicago, Illinois, August 21, 1958.

Study to assess acute intragastric toxicity of MSM. LD50 could not be established because even the maximum dose of 20g/kg failed to kill any of the animals (n = 10); no adverse effects were noted (the maximum recommended dose in humans approximates 300mg/kg).

Rose SE, Chalk JB, Galloway GJ, Doddrell DM. Detection of dimethyl sulfone in the human brain by in vivo proton magnetic resonance spectroscopy. Magn Reson Imaging 2000;18:95-8.

Schoenig G. Acute oral toxicity of sample No. 751, dimethyl sulfone 1 BT No. A6409. Industrial BIO-TEST Laboratories, Inc., Northbrook, Illinois, September 19, 1968.

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