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.

(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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.