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Animal Studies

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.

The effect of methyl sulphonyl methane supplementation on biomarkers of oxidative stress in sport horses following jumping exercise.
Marañón G, Muñoz-escassi B, Manley W, et al.

Acta Vet Scand. 2008;50(45).

Background: Exercise induces changes in several organs and tissues, and this process might be due to oxidative damage caused by free radicals and inflammatory mediators. Methyl Sulphonyl Methane, better known as MSM, is a naturally occurring sulphur compound with well-known antioxidant properties. On the other hand, Vitamin C is important in limiting free radical damage in the aqueous phase of the cell, and cellular vitamin C status may be linked to the mechanisms involved in quenching cellular reactive oxygen species. The aim of this study was to determine if supplementation with MSM and vitamin C could alleviate exercise-induced oxidative stress in horses undergoing jumping competition.
Methods: Twenty four jumping horses involved in competition were used. Horses were given the following three treatment diets: control (without supplementation), MSM 8 mg/kg, and combined supplements (MSM 8 mg/kg + Vit-C 5 mg/kg). EDTA blood samples were collected before exercise, upon arrived to the schooling area (control), and each week after last show. Nitric oxide, carbon monoxide, lipid hydroperoxides and the antioxidant enzymes, glutathione peroxidase, glutathione transferase and glutathione reductase, plasma levels were determined.
Results: Competition induced a significant increase in lipid peroxidation, nitric oxide and carbon monoxide. By contrary, reduced glutathione as well as antioxidant enzyme activities, were decreased. MSM administration significantly ameliorated all these exercise-related changes, and this effect was potentiated by Vit C reaching values in some of the parameters similar to those found before competition.
Conclusion: These results suggest that jumping exercise could induce harmful effects on horses, probably due to an increase in oxidative damage and proinflammatory molecules. In addition, we have demonstrated that MSM could exert some protective effect on oxidative and inflammatory exercise-induced injury.

Anti-inflammatory Effect of Methylsulfonylmethane (MSM) in Mice.
Hasegawa T, Ueno S, Kumamoto S, Publishers LS.

Jpn Pharmacol Ther. 2005;33(12).

In this study, we systematically investigated the effect of Methylsulfonylmethane (MSM) on anti-inflammatory properties in mice. The mice models used in our experiments were UVB-irradiated hairless mice for skin damage, ovalbumin-immunized mice for inflammatory cutaneous reaction, and mice injected intradermally with histamine for scratching behavior. We examined MSM's protective effect against skin damage induced by ultraviolet irradiation in hairless mice. The irradiated hairless mice were exposed to UVB (290-320nm) four times a week for 3 weeks, eliciting inflammation of the back skin. It was concluded that the application of MSM ointment helped alleviate the inflammation of the back skin. Next, we examined the effect of MSM administration on the immediate-phase reaction or the late phase reaction in ovalbumin-injected mice. MSM administration suppressed the immediate swelling reaction but not the late-phase reaction in ovalbumin-injected mice. The intradermal injection of histamine induced both scratching behavior and an increase in vascular permeability in ICR mice. Next, we examined the effect of MSM administration on scratching behavior after the intradermal injection of histamine in ICR mice. It was concluded that MSM administration significantly inhibited the scratching behavior caused by histamine. The mechanism underlying the inhibitory effect of scratching behavior by MSM administration remained unclear. However, at least the action of inhibitory scratching behavior is involved with anti-histamine action.

Effects of Oral Dimethyl Sulfoxide and Dimethyl Sulfone on Murine Autoimmune Lymphoproliferative Disease.
Morton JI, Siegel BV.

Proc Soc Exp Biol Med. 1986;183:227-230.

The results from several studies examining the effects of DMSO on autoimmune phenomena have been inconclusive, possibly because of differences in experimental models, treatment regimens and doses employed. In the present investigation, autoimmune strain MRL/lpr, C3H/lpr, and male BXSB mice were placed on a continuous treatment regimen with 3% DMSO or 3% DMSO2 in the drinking water, ad libitum, commencing at 1 to 2 months of age, before spontaneous disease development could be detected. This represented doses of 8-10 g/kg/day of DMSO and 6-8 g/kg/day of DMSO2. Both compounds were observed to extend the mean life span of MRL/lpr mice from 5 1/2 months to over 10 months of age. All strains showed decreased antinuclear antibody responses and significant diminution of lymphadenopathy, splenomegaly, and anemia development. Serum IgG levels and spleen IgM antibody plaque formation, however, did not differ from control values. There was no indication of involvement of systemic immunosuppressive or antiproliferative effects, and treated animals were observed to remain healthy and vigorous with no signs of toxicity. These results demonstrate that high doses of both DMSO and its major in vivo metabolite, DMSO2, provide significant protection against the development of murine autoimmune lymphoproliferative disease. Possible mechanisms of protection are discussed.

Comparison of the Therapeutic Actions of Taurine, Methylsulfonylmethane and Silymarin Against Acetaminophen-Induced Neuro- and Hepato-Toxicity in Rat.
Radwan OK, Shehata AM.

J Biomed Pharm Res. 2016;5(3):10-17.

To evaluate the hepatocurative effects of taurine (TAU) and methylsulfonylmethane (MSM) in acetaminophens- induced neuro- and hepato- toxicity in albino rats. Silymarin (SLN) was used as reference drug.
Methods: A total of 40 albino rats were assigned into five groups of 8 rats in each group. Rats was administered a single daily dose of acetaminophen (APAP, 500 mg/kg body weight, p.o) for 14 days. Acetaminophen treated rats were divided into four groups, the positive control group, taurine treated group, MSM treated group and silymarin treated group. The Acetaminophen- intoxicated animals were treated with the tested drugs for two weeks. A group of untreated animals served as negative control.
Results: There was significant (P<0.05) increase in levels of liver marker enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the actaminophen- treated rats, compared to the normal control. Moreover, acetaminophen induced oxidative stress in both liver and brain tissues in terms of increased MDA, GSSG and NO contents and decreased GSH; and caused oxidative DNA damage in terms of elevation of 8-hydroxy-2-deoxyguanine (8-OHdG). In brain, acetaminophen (APAP) moderately disturbed the normal levels of DA, NE and serotonin. Both silymarin, taurine and MSM normalized the serum activities of liver marker enzymes (ALT and AST) and restored the normal redox status and ameliorated acetaminophen induced DNA- oxidative damage in liver. In addition, both silymarin, taurine and MSM restored the normal redox status and the normal levels of brain monoamines (DA, NE and 5-HT) and ameliorated acetaminophen induced DNA- oxidative damage in brain. The efficiency of neuro- and hepatocurative effect was SLN> TAU > MSM. Conclusion: the study shows that taurine, silymarin and MSM possess significant neuro- and hepato-curative attribute due to their antioxidant properties.

Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice.
Amirshahrokhi K, Bohlooli S.

Inflammation. 2013;36(5):1111-1121.

Methylsulfonylmethane (MSM) is a natural organosulfur compound that exhibits antioxidative and anti-inflammatory effects. This study was carried out to investigate the effect of MSM on paraquat (PQ)-induced acute lung and liver injury in mice. A single dose of PQ (50 mg/kg, i.p.) induced acute lung and liver toxicity. Mice were treated with MSM (500 mg/kg/day, i.p.) for 5 days. At the end of the experiment, animals were euthanized, and lung and liver tissues were collected for histological and biochemical analysis. Tissue samples were used to determine malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and tumor necrosis factor-α (TNF-α) levels. Blood samples were used to measure plasma alanine transaminase (ALT), γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Histological examination indicated that MSM decreased lung and liver damage caused by PQ. Biochemical results showed that MSM treatment significantly reduced tissue levels of MDA, MPO, and TNF-α, while increased the levels of SOD, CAT, and GSH compared with PQ group. MSM treatment also significantly reduced plasma levels of ALT, GGT, and ALP. These findings suggest that MSM as a natural product attenuates PQ-induced pulmonary and hepatic oxidative injury.

Effect of methylsulfonylmethane pretreatment on acetaminophen induced hepatotoxicity in rats.
Bohlooli S, Mohammadi S, Amirshahrokhi K, et al.

Iran J Basic Med Sci. 2013;16(8):896-900.

Objective(s): Methylsulfonylmethane (MSM) is a sulfur-containing compound found in a wide range of human foods including fruits, vegetables, grains and beverages. In this study the effect of MSM pretreatment on acetaminophen induced liver damage was investigated.
Materials and Methods: Male Sprague Dawley rats were pretreated with 100 mg/kg MSM for one week. On day seven rats were received acetaminophen (850 mg/kg, intraperitoneal). Twenty-four hours later, blood samples were taken to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Tissue samples of liver were also taken for the determination of the levels of malondialdehyde (MDA); total glutathione (GSH), superoxide dismutase (SOD), and myeloperoxidase (MPO) activity together with histopathological observations.
Results: High dose of acetaminophen administration caused a significant decrease in the GSH level of the liver tissue, which was accompanied with a decrease in SOD activity and increases in tissue MDA level and MPO activity. Serum ALT, AST levels were also found elevated in the acetaminophen-treated group. Pretreatment with MSM for one week was significantly attenuated all of these biochemical indices.
Conclusion: Our findings suggest that MSM pretreatment could alleviate hepatic injury induced by acetaminophen intoxication, may be through its sulfur donating and antioxidant effects.

Hepatoprotective effect of methylsulfonylmethane against carbon tetrachloride-induced acute liver injury in rats.
Kamel R, El Morsy EM.

Arch Pharm Res. 2013;36(9):1140-1148.

This study evaluated the effect of methylsulfonylmethane (MSM) on carbon tetrachloride (CCl₄)-induced acute liver injury in rats. A single injection of CCl₄ (2 ml/kg, i.p.) increased serum aminotransferases (ALT and AST) activities. In addition, CCl₄ treatment led to elevation of hepatic malondialdehyde (MDA) content as well as decrease in superoxide dismutase (SOD) and catalase (CAT) activities. Furthermore, cytochrome P450 2E1 (CYP2E1) content was suppressed while proinflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels increased in liver tissue after CCl4 administration. We showed that acute CCl₄-induced damage was accompanied by a rise in Bax/Bcl₂ ratio indicating apoptosis. Pre-treatment with MSM (400 mg/kg) inhibited the increases of serum ALT and AST activities, decreased hepatic MDA, TNF-α, IL-6 and Bax/Bcl₂ ratio compared to CCl₄ treated group. On the other hand, MSM raised SOD and CAT activities as well as CYP2E1 level in liver tissues. The present study shows that MSM possesses a hepatoprotective effect against CCl₄-induced liver injury in rats. This protective effect might be through its antioxidant, anti-inflammatory and antiapoptotic properties.

Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress in monocrotaline-induced pulmonary hypertensive rats.
Mohammadi S, Najafi M, Hamzeiy H, et al.

Adv Pharmacol Sci. 2012;2012:507278.

Methylsulfonylmethane (MSM) is naturally occurring organic sulfur that is known as a potent antioxidant/anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on hemodynamics functions and oxidative stress in rats with monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). Wistar rats were randomly assigned to 38-days treatment. MSM was administered to rats at 100, 200, and 400 mg/kg/day doses 10 days before a single dose of 60 mg/kg, IP, MCT. Hemodynamics of ventricles were determined by Powerlab AD instrument. Blood samples were obtained to evaluate changes in the antioxidative system including activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) and malondialdehyde (MDA). Improvements in cardiopulmonary hemodynamics were observed in the MSM-treated pulmonary arterial hypertensive rats, with a significant reduction in right ventricular systolic pressure (RSVP) and an increase in the mean arterial pressure (MAP). The values of CAT, SOD, GSH-px activities, and GSH were significantly lower in MCT-induced PAH (P < 0.01), but they were recovered to control levels of MSM-treated groups. Our present results suggest that long-term administration of the MSM attenuates MCT-induced PAH in rats through modulation of oxidative stress and antioxidant defense.

The effect of methylsulfonylmethane on the experimental colitis in the rat.
Amirshahrokhi K, Bohlooli S, Chinifroush MM.

Toxicol Appl Pharmacol. 2011;253(3):197-202.

Methylsulfonylmethane (MSM), naturally occurring in green plants, fruits and vegetables, has been shown to exert anti-inflammatory and antioxidant effects. MSM is an organosulfur compound and a normal oxidative metabolite of dimethyl sulfoxide. This study was carried out to investigate the effect of MSM in a rat model of experimental colitis. Colitis was induced by intracolonic instillation of 1 ml of 5% of acetic acid. Rats were treated with MSM (400 mg/kg/day, orally) for 4 days. Animals were euthanized and distal colon evaluated histologically and biochemically. Tissue samples were used to measurement of malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), glutathione (GSH) and proinflammatory cytokine (TNF-α and IL-1β) levels. Results showed that MSM decreased macroscopic and microscopic colonic damage scores caused by administration of acetic acid. MSM treatment also significantly reduced colonic levels of MDA, MPO and IL-1β, while increased the levels of GSH and CAT compared with acetic acid-induced colitis group. It seems that MSM as a natural product may have a protective effect in an experimental ulcerative colitis.

Methylsulfonylmethane (MSM) Intake in Mice Produces Elevated Liver Glutathione and Partially Protects Against Carbon Tetrachloride-Induced Liver Injury.
Disilvestro RA, Disilvestro DJ, Disilvestro DJ.

FASEB J. 2008;22(1):0-1.

Methylsulfonylmethane (MSM) is a organic molecule present in small amounts in a number of foods and sold as a dietary supplement. 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 MSM (OptiMSM®, Bergstrom Nutrition) 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. This work was supported in part by an unrestricted research gift from Bergstrom Nutrition.

Single and 13-week Repeated Oral Dose Toxicity Study of Methylsulfonylmethane in Mice.
Takiyama K, Konishi F, Nakashima Y, Mumamoto C.

Oyo Yakuri Pharmacometrics. 2010;79((1/2)):23-30.

Abstract: Methylsulfonylmethane is a type of organic sulfur compound found in minute amounts in foods, such as milk, vegetables, and fruits (Pearson et al., 1981) and it is approximately 34% of sulfur in composition. Next to calcium, phosphorus, and potassium, sulfur is the fourth most abundant mineral found in the body and it has been confirmed by research in guinea pigs that the sulfur in MSM is incorporated into the sulfur-containing amino acids, cysteine and methionine (Richmond, 1986). Recent studies report that MSM has a mitigating effect on arthritis (Hasegawa et al., 2004), an anti-inflammatory effect (Hasegawa et al., 2005), and an anti-allergy effect (Barrager et al., 2002) however, it has been brought to attention that the amount of MSM contained in food is minute because available MSM becomes damaged during processing and cooking (Steely, 1994), thus it is necessary to replace it with supplements in order to expect functionality of MSM. Furthermore, as a functional food in Japan, the target daily intake amount has been determined as 3g and it is equivalent to 0.06g/kg-BW estimating that a human’s weight is 50kg. It has been substantiated in toxicity tests with rats that there is no indication of any toxicity when administering 2.0g/kg-BW in a single dose as well as administering 1.5g/kg-BW daily, for 90 days (Horvath et al., 2002). Furthermore, 1.5g/kg-BW, the amount used for the 90-day repetitive dose test, is equivalent to the 25 times more than the target daily intake amount. In order to confirm safety with a dose that is higher than what Horvath et al. reports, single dose and 13-week repetitive administration toxicity tests of MSM were conducted.

Pharmacokinetics and Distribution of [35S] Methylsulfonylmethane following Oral Administration to Rats.
Magnuson BA, Appleton J, Ames GB.

J Agric Food Chem. 2007;55:1033-1038.

Methylsulfonylmethane (MSM) is a sulfur-containing compound found in a wide range of human foods including fruits, vegetables, grains, and beverages. More recently, it has been marketed as a dietary supplement worldwide. 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 48h. Tissue levels of radioactivity at 48 and 120h and urine and fecal radioactivity levels were measured at different time points for up to 120h following [35S]MSM administration to rats. Oral [35S]MSM was rapidly and efficiently absorbed with a mean tmax of 2.1h, Cmax of 622 µg equiv/mL, and AUC0-inf of 15124 h•μg equiv/mL. The t1/2 was 12.2h. 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 120h, whereas only 3% was found in the feces. No quantifiable levels of radioactivity were found in any tissues after 120h, 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.

Oral developmental toxicity study of methylsulfonylmethane in rats.
Magnuson BA, Appleton J, Ryan B, Matulka RA.

Food Chem Toxicol. 2007;45:977-984.

Methylsulfonylmethane (MSM) is a metabolite of dimethyl sulfoxide, and occurs naturally at low levels in many foods. MSM has received wide attention as a dietary supplement to promote joint health. 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 6-20. 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 6-20. 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 50-1000 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.

Preventive effect of Methylsulfonymethane (MSM) at the induction stage of mammary carcinogenesis induced by DMBA in female SD rats.
Wang Y, Anderson GL, Nowicki D.

Proc Am Assoc Cancer Res. 2003;44:787.

ABSTRACT: Methylsulfonylmethane (MSM) is a sulfur donor compound occurring in nature and has been found in plants, milk, and urine of bovines and humans. MSM is a normal oxidation product of dimethylsulfoxide (DMSO). Sulfur is the sixth most abundant macro mineral in breast milk and the third most abundant mineral in the human body based upon percentage of total body weight and is an essential element for the structure of every living cell. MSM possess a broad range of health benefits including analgesic, anti-inflammatory, anti-allergy, while enhancing immune function by providing nutritionally essential organic sulfur and methyl groups. A scientific study has reported that 35S-labeled MSM was incorporated into essential sulfur-containing amino acids such as methionine and cysteine of guinea pig serum protein; thus MSM may provide a source of sulfur for essential sulfur-containing amino acids in animal and humans. Although the medicinal values of MSM have been studied, the cancer preventative effect of MSM remains unclear. In this study, the cancer preventative effect of MSM at the initiation state of multiple stage chemical carcinogenesis was investigated on a mammary breast carcinogenic animal model induced by DMBA in female SD rats. Forty-five female SD rats were divided onto three groups: age-matched control, DMBA, and DMBA+5%MSM. The experiment was started at the 35th postnatal day with water being given to the aged-matched control groups and the DMBA group and 5% MSM suppled to the MSM+DMBA group. DMBA (25mg/kg) was administered by mouth at the 50th postnatal day in the DMBA and DMBA+MSM groups. Five percent MSM was continuously supplied for an additional 90 days after DMBA administration. All animals were sacrificed at the 9th month after DMBA treatment to examine the pathological changes in the mammary glands by light microscopy. Compared to the age-matched control group, the DMBA treated group showd a variety of lesions, including epithelial hyperplasia (12.5%), benign tumors (25%), and carcinomas in-situ (25%). No benign tumor or carcinoma was observed in the MSM+DMBA and age-matched control group, which only showed normal histology or mild hyperplasia. Our preliminary results indicated that MSM may prevent mammary breast cancer at the initiation stage of chemical carcinogenesis. The mechanisms for this need further study.

Toxicity of methylsulfonylmethane in rats.
Horvath K, Noker PE, Somfai-Relle S, Glavits R, Financsek I, Schauss AG.

Food Chem Toxicol. 2002;40:1459-1462.

Methylsulfonylmethane (MSM) is a popular dietary supplement used in a variety of conditions including pain, inflammation, allergies, arthritis, parasitic infections and the maintenance of normal keratin levels in hair, skin and nails. Despite its popularity, there is little published toxicology data on MSM. The objective of this study was to evaluate the acute and subchronic toxicity of MSM in rats at a dose five to seven times the maximum recommended dose in humans. MSM administered in a single gavage dose of 2 g/kg resulted in no adverse events or mortality. MSM administered as a daily dose of 1.5 g/kg for 90 days by gavage resulted in no adverse events or mortality. Necropsy did not reveal any gross pathological lesions or changes in organ weights. Renal histology of treated animals was normal. It is concluded that MSM is well tolerated in rats at an acute dose of 2 g/kg and at a subacute chronic dose of 1.5 g/kg.

Incorporation of methylsulfonylmethane sulfur into guinea pig serum proteins.
Richmond VL.

Life Sci. 1986;39:263-268.

Methionine, an essential amino acid, and cysteine are the major sulfur-containing amino acids in the body and both are thought to be synthesized predominantly in plants and micro-organisms. Methylsulfonylmethane (MSM) is a natural constituent of the environment in which it is found in plants, in milk and urine of both bovines and humans, is a normal oxidation product of dimethyl sulfoxide (DMSO) also in the natural environment and may be part of the natural global sulfur cycle. To determine whether sulfur from methylsulfonylmethane (MSM) is incorporated into sulfur amino acids, I fed 35S-MSM to guinea pigs. 35S was incorporated into peptidyl methionine and cysteine of guinea pig serum proteins. The specific activity of 35S-methionine was 30% greater than for 35S-cysteine, suggesting a precursor-product relationship. Total specific activity of serum proteins was increased by only 30% with a 100% increase of administered 35S-MSM, suggesting a limiting step in synthesis. Approximately 1% of the radioactivity was recovered in serum proteins, none in the feces and most was excreted in the urine. Microorganisms of intestinal lumen may be responsible for the incorporation of the 35S of MSM into sulfur amino acids. MSM may provide a source of sulfur for essential animal methionine by mechanisms not yet elucidated in either animals or micro-organisms.

Acute Oral Toxicity of Dimethyl Sulfone.
Schoenig G.

Report: Industrial Bio-Test Laboratories, Inc.: 1968.

An acute oral toxicity study was conducted on Sample No. 751, dimethyl sulfone, employing albino rats as test animals. The acute oral median lethal dose (LD50) was found to be ≥ 17020 mg/kg. The test material was administered in the form of a 25.0% (w/v) aqueous solution; however, the LD50 value is expressed in terms of actual Sample No. 751 received.

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Privacy Overview

This website uses cookies to improve your experience while you navigate through the website. Out of these, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may affect your browsing experience.
Necessary
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Necessary cookies are absolutely essential for the website to function properly. These cookies ensure basic functionalities and security features of the website, anonymously.
CookieDurationDescription
cookielawinfo-checkbox-analytics11 monthsThis cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Analytics".
cookielawinfo-checkbox-functional11 monthsThe cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional".
cookielawinfo-checkbox-necessary11 monthsThis cookie is set by GDPR Cookie Consent plugin. The cookies is used to store the user consent for the cookies in the category "Necessary".
cookielawinfo-checkbox-others11 monthsThis cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Other.
cookielawinfo-checkbox-performance11 monthsThis cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Performance".
viewed_cookie_policy11 monthsThe cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies. It does not store any personal data.
Functional
Functional cookies help to perform certain functionalities like sharing the content of the website on social media platforms, collect feedbacks, and other third-party features.
Performance
Performance cookies are used to understand and analyze the key performance indexes of the website which helps in delivering a better user experience for the visitors.
Analytics
Analytical cookies are used to understand how visitors interact with the website. These cookies help provide information on metrics the number of visitors, bounce rate, traffic source, etc.
Advertisement
Advertisement cookies are used to provide visitors with relevant ads and marketing campaigns. These cookies track visitors across websites and collect information to provide customized ads.
Others
Other uncategorized cookies are those that are being analyzed and have not been classified into a category as yet.
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