The Effect of Methylsulfonylmethane on Osteoarthritic Large Joints and Mobility.
Pagonis TA, Givissis PA, Kritis AC, Christodoulou AC.Int J Orthop. 2014;1(1):19-24.
AIM: Methylsulfonylmethane (MSM) is a non-pharmacologic nutrition supplement used against osteoarthritis (OA). Objective: Delineate the effect of MSM on osteoarthritic joints and mobility. MATERIALS AND METHODS: Randomized, double-blind, placebo-controlled trial including 100 patients, with hip and/or knee OA stratified in an intervention and a placebo group. Intervention: MSM 6 gr per day or placebo for 26 weeks. Outcomes measured were the Western Ontario and McMaster University Osteoarthritis Index visual analogue scale (WOMAC), patient and physician assessments and SF-36 (overall health-related quality of life). RESULTS: Compared to placebo the MSM group presented significant decreases in all subscales of WOMAC (P < 0.05) with improved performance of daily living activities on the SF-36 evaluation (P < 0.05). Patient and Physician assessments exhibited favorable effects on the MSM group CONCLUSION: MSM improved all physical symptoms in the WOMAC scale during the short intervention without any adverse events.
Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study.
Debbi EM, Agar G, Fichman G, et al.BMC Complement Altern Med. 2011;11(1):50.
BACKGROUND: Patients with osteoarthritis (OA) take a variety of health supplements in an attempt to reduce pain and improve function. The aim of this study was to determine the efficacy of methylsulfonylmethane (MSM) in treating patients with knee OA.
METHODS: This study was a prospective, randomized, double-blind, controlled clinical trial. Forty nine men and women 45-90 (mean 68 ± SD 7.3) years of age with knee OA according to the American College of Rheumatology clinical criteria for OA of the knee and with radiographic confirmed knee OA were enrolled in the study and randomly assigned into 2 groups: One received MSM in doses of 1.125 grams 3 times daily for 12 weeks and the other received a placebo in the same dosing frequency. The primary outcomes were the WOMAC Osteoarthritis Index for pain, stiffness and physical function, the Aggregated Locomotor Function (ALF) test that evaluates each patient's physical function, the SF-36 quality of life health survey and the visual-analogue-scale (VAS) for pain. The secondary outcomes were Knee Society Clinical Rating System for Knee Score (KSKS) and Function Score (KSFS). Patients were assessed at baseline, 6 weeks and 12 weeks. All continuous variables were tested by the Kolmogorov-Smirnov test for Normal distribution. Changes within the groups and differences between the groups were calculated by repeated measures of analysis (ANOVA) with one nested variable.
RESULTS: There were significant differences between treatment groups over time in WOMAC physical function (14.6 mm [CI: 4.3, 25.0]; p = 0.04) and in WOMAC total score (15.0 mm [CI: 5.1, 24.9]; p = 0.03). Treatment groups did not differ significantly in WOMAC pain (12.4 mm [CI: 0.0, 24.8]); p = 0.08) or WOMAC stiffness (27.2 mm [CI: 8.2, 46.2]; p = 0.08). There was a non-significant difference in SF-36 total score between treatment groups (11.6 [CI: 1.0, 22.1]; p = 0.54). A significant difference was found between groups in VAS for pain (0.7 s [CI: -0.9, 2.4]; p = 0.05). Secondary outcomes showed non-significant differences between the two groups.
CONCLUSIONS: Patients with OA of the knee taking MSM for 12 weeks showed an improvement in pain and physical function. These improvements, however, are small and it is yet to be determined if they are of clinical significance.
The Effect Of Distilled Methylsulfonylmethane (MSM) on Human Chondrocytes in vitro.
Oshima Y, Amiel D, Theodosakis J.Osteoarthr Cartil. 2007;15:213.
Purpose: Osteoarthritis (OA) is a joint disease characterized by a degenerative change of articular cartilage and underlying subchondral bone and often accompanied by inflammation. MSM, a dietary supplement composed of about 34% sulfur and self-affirmed as GRAS (generally recognized as safe) in the U.S., is most utilized for treating OA. A recent study by Kim et. al., OA & Cart, 2006, showed clinical effectiveness of MSM supplementation at 3 gm BID x 12 weeks compared to placebo. The objective of our study was to examine the effect of MSM at varying concentrations on cultured human healthy and osteoarthritic chondrocytes in vitro with a focus on catabolic and anabolic markers.
Methods: Human cartilage tissues were obtained from 22 knees, 72 hrs postmortem from donors with different grades of OA. We used the Outerbridge classification (Grades I - IV), Grade I for intact surface; Grade II for minimal fibrillation; Grade III for overt fibrillation; and Grade IV for erosion of the articular cartilage surface. Following gross assessment of the donor knees, the following knees were studied for Grade I (n=6) (aged 23-38); Grade II (n=9) (aged 50-77); for Grade III (n=5) (aged 32-70); and Grade IV (n=2) (aged 70-93). Cartilage tissues were harvested from femoral condyles and tibial plateaus, the matrix was dissolved with collagenase; the chondrocytes were then cultured for 2 weeks in culture media without MSM. After reaching confluence, 2 x 105 chondrocyte cells in 10 ml culture medium with varying concentrations of MSM (0, 1, 3, 6, 12, and 60 μg/ml) were cultured in 100 mm (in-diameter) plates at 37 °C in 5% CO2 for 3 days. The concentrations were estimated to correspond to human, oral dosing at between 0 and 30 grams of MSM per day. mRNA expression of various markers by RT-PCR including: TNF-alpha, IL-1, MMP-1, MMP-3, and MMP-13 was also determined for each OA grade and each concentration of MSM or control. Anabolic pathways examined included proteoglycan synthesis (by a pulse chase analysis of 35SO4 incorporation) and chondrocyte mRNA expressions of Type-II collagen and aggrecan. A one-way ANOVA was performed to establish the level of statistical significance. Results: In Grade II OA chondrocytes treated with MSM at the concentration of 12 μg/ml, there was a strong trend for MSM to reduce the mRNA expression of inflammatory markers: TNF-alpha (-33%, p=0.08) and IL-1 (-29%, p=0.08) when compared to lower concentrations of MSM and control. These results did not apply for OA chondrocytes of Grade III or IV. MSM did not show an increase in proteoglycan synthesis in cultured chondrocytes or an increase of cartilage matrix production in normal and osteoarthritic chondrocytes at the mRNA level.
Conclusion: MSM might have an ability to protect articular cartilage in early OA by reducing expression of inflammatory cytokines, i.e. TNF-alpha & IL-1. The effective concentration of 12 μg/ml MSM correlates with the dosage used in a recent clinical trial. MSM did not elicit an anabolic response in this study.
Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial.
Kim, LS; Axelrod, LJ; Howard, P; Buratovich N.Osteoarthr Cartil. 2006;14:286-294.
OBJECTIVE: Osteoarthritis (OA) is the most common form of arthritis and the second most common cause of long-term disability among middle-aged and older adults in the United States. Methylsulfonylmethane (MSM) is a popular dietary supplement used as a single agent and in combination with other nutrients, and purported to be beneficial for arthritis. However, there is paucity of evidence to support the use of MSM.
METHODS: A randomized, double-blind, placebo-controlled trial was conducted. Fifty men and women, 40-76 years of age with knee OA pain were enrolled in an outpatient medical center. Intervention was MSM 3g or placebo twice a day for 12 weeks (6g/day total). Outcomes included the Western Ontario and McMaster University Osteoarthritis Index visual analogue scale (WOMAC), patient and physician global assessments (disease status, response to therapy), and SF-36 (overall health-related quality of life).
RESULTS: Compared to placebo, MSM produced significant decreases in WOMAC pain and physical function impairment (P<0.05). No notable changes were found in WOMAC stiffness and aggregated total symptoms scores. MSM also produced improvement in performing activities of daily living when compared to placebo on the SF-36 evaluation (P<0.05).
CONCLUSION: MSM (3g twice a day) improved symptoms of pain and physical function during the short intervention without major adverse events. The benefits and safety of MSM in managing OA and long-term use cannot be confirmed from this pilot trial, but its potential clinical application is examined. Underlying mechanisms of action and need for further investigation of MSM are discussed.
Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis.
Usha PR, Naidu MUR.Clin Drug Investig. 2004;24(6):353-363.
OBJECTIVE: Glucosamine, classified as a slow-acting drug in osteoarthritis (SADOA), is an efficacious chondroprotective agent. Methylsulfonylmethane (MSM), the isoxidised form of dimethyl-sulfoxide (DSMO), is an effective natural analgesic and anti-inflammatory agent. The aim of this study was to compare the efficacy and safety of oral glucosamine (Glu), methylsulfonylmethane (MSM), their combination and placebo in osteoarthritis of the knee.
PATIENTS AND DESIGN: A total of 118 patients of either sex with mild to moderate osteoarthritis were included in the study and randomised to receive either Glu 500mg, MSM 500mg, Glu and MSM or placebo capsules three times daily for 12 weeks. Patients were evaluated at 0 (before drug administration), 2, 4, 8 and 12 weeks post-treatment for efficacy and safety. 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.
RESULTS: Glu, MSM and their combination significantly improved signs and symptoms of osteoarthritis compared with placebo. There was a statistically significant decrease in mean (+/- SD) pain index from 1.74 +/- 0.47 at baseline to 0.65 +/- 0.71 at week 12 with Glu (p < 0.001). MSM significantly decreased the mean pain index from 1.53 +/- 0.51 to 0.74 +/- 0.65, and combination treatment resulted in a more significant decrease in the mean pain index (1.7 +/- 0.47 to 0.36 +/- 0.33; p < 0.001). After 12 weeks, the mean swelling index significantly decreased with Glu and MSM, while the decrease in swelling index with combination therapy was greater (1.43 +/- 0.63 to 0.14 +/- 0.35; p < 0.05) after 12 weeks. The combination produced a statistically significant decrease in the Lequesne index. All treatments were well tolerated.
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. All the treatments were well tolerated. The onset of analgesic and anti-inflammatory activity was found to be more rapid with the combination than with Glu. It can be concluded that the combination of MSM with Glu provides better and more rapid improvement in patients with osteoarthritis.
Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model.
Ezaki J, Hashimoto M, Hosokawa Y, Ishimi Y. J Bone Miner Metab. 2013;31(1):16-25.
Methylsulfonylmethane (MSM), which is one of the popular ingredients of so-called health foods in Japan, is expected to relieve inflammation in arthritis and allergies. However, there is no scientific evidence to confirm the efficacy and safety of MSM in detail. In this study, we examined the effects of MSM on cartilage formation in growing rats (G) and cartilage degradation in STR/Ort mice (A), an accepted human osteoarthritis (OA) model. For cartilage formation study, 6-week-old growing male Wister rats were assigned to four groups to receive a control or MSM-containing diet. To examine the efficacy of MSM on the cartilage of OA model mouse, 10-week-old male STR/OrtCrlj mice were assigned to three groups to receive a control or MSM-containing diet. The dosages used were amounts equal to the recommended supplements for humans [0.06 g/kg body weight (BW)/day: MSM1G and MSM1A], 10 fold higher (0.6 g/kg BW/day: MSM10G and MSM10A), and 100 fold higher (6 g/kg BW/day: MSM100G). Intake of MSM for 4 weeks did not affect cartilage formation in the knee joint in growing rats. Body, liver, and spleen weight in the MSM100G group were significantly lower than those in the control group. Intake of MSM for 13 weeks decreased degeneration of the cartilage at the joint surface in the knee joints in STR/Ort mice in a dose-dependent manner.These results suggest that appropriate intake of MSM is possibly effective in OA model mice; however, intake of large amounts of MSM induced atrophy of several organs.
Suppressive Effect of MSM on Type II collagen-induced Arthritis in SBA/1J Mice.
Hasegawa T, Ueno S, Kumamoto S, Yoshikai Y. Jpn Pharmacol Ther. 2004;32(7):421-427.
Background: Methylsulfonylmethane (MSM) is a natural constituent of the environment found in plants, cow’s milk and urine of both bovines and humans. It has been reported that MSM was efficacious in the reduction of symptoms associated with seasonal allergic rhinitis, and protected from the development of murine autoimmune lymphoproliferative symptoms in MRL/lpr mice and the destructive changes in the joints of MRL/Mn/lnr female mice with spontaneous arthritis. In this study, we investigated the effect of MSM on type II collagen-induced murine arthritis as an animal model of rheumatoid arthritis. Methods: Murine arthritis was induced as follows. Male DBA/1J mice were injected intradermally at the base of the tail with 200 μg of the type II collagen. Three weeks after primary immunization, the mice were boosted in the same way. Male DBA/1J mice were placed on a continuous treatment regimen with 2.5% MSM in the drinking water, ad libitum, commencing at one week before primary immunization of the type II collagen. The clinical severity of arthritis (deformation and swelling) was scored based on the appearance of each paw which was graded scale. Results: The arthritic score (deformation) and swelling score increased gradually from two weeks up to eight weeks after the type II collagen immunization. On the other hand, the arthritic score in the MSM drinking mice was significantly lower than that in control mice. The total number of leukocytes in inguinal lymph nodes was significantly smaller in the MSM drinking mice than that in control mice. Flowcytometry revealed that the number of B220+ cells in the lymph nodes was significantly smaller in the MSM drinking mice than that in control mice. Notably, expression level of IL-12 p40 mRNA was reduced in spleen of the MSM drinking mice as compared with control mice Conclusion: These results suggested that MSM administration was able to modify the immune responses to the type II collagen, resulting in protection of the development of arthritis of type II collagen induced arthritis in DBA/1J mice.
Effect of DMSO and MSM on a destructive process in the joints of mice with spontaneous arthritis.
Muravyev I, Venikova M, Pleskovskaia G, Riazantseva T, Sigidin I. Patol Fiziol Eksp Ter. 1991;2:37-39.
The authors used the blind method for evaluation of the morphological picture of the joints and the level of circulating immune complexes to study the effect of prolonged oral administration of dimethyl sulfoxide (DMSO) and its main metabolite dimethyl sulfone (MSM) on the development of spontaneous arthritis in 36 Mrl/Mn/lnr female mice. It was found that DMSO and MSM lessen the destructive changes in the joints, while DMSO also inhibits the manifestation of immune disorders, i.e. producs a “basal” effect on the course of spontaneous chronic arthritis in experimental animals.
Diminished Inflammatory Joint Disease in MRL/1pr Mice Ingesting DMSO or MSM.
Moore R, Morton J.FASEB 1985;530:p692
MRL/lpr strain mice have been identified as a model for the spontaneous development of rheumatoid arthritis-like joint lesions. Anecdotal information has suggested that topical application of DMSO may alleviate the manifestations of rheumatoid arthritis in the human. In the present study, a 3% solution of DMSO or its in vivo oxidation product, MSM, was administered in the drinking water, ad libitum from two months until 4-to 5-months of age. Knee joints from 18 water-drinking, 28 DMSO-treated, and 14 MSM-treated mice were examined. Focal degeneration of articular cartilage was present in 50% of the controls, 14% of the DMSO-treated, and none of the MSM-treated mice. Although proliferation of synovial lining cells was present in all control animals, 82% of DMSO-treated and 71% of MSM treated mice, it was less marked in the experimental groups. 95% of control animals had an inflammatory reaction in the synovial tissues, compared to 46% of the DMSO-treated and 50% of the MSM mice; though less severe in the treated animals. Pannus formation was present in 50% of the controls, 43% of DMSO-treated and 14% of the MSM-treated mice. Pannus was usually minimal in the experimental animals. This decrease in inflammatory joint disease in DMSO- and MSM-treated MRL/lpr mice may be associated with previously described decreases in autoantibody titers and abnormal T-cell proliferation in similar animals.