A collection of technical documents for customers wishing to understand more of the science behind our products.

Written by:  Dr Tom Shurlock for and on behalf of GWF Nutrition Limited.

Copyright GWF Nutrition Limited January 2019 - Not for reproduction.

MSM is a source of sulphur, which helps to form cross links with other molecules that maintain the strength and integrity of connective tissues. It is also essential for the manufacture of collagen. It does, however, have properties, including interactions with the inflammatory cycle, oxidation and immunomodulation.

 

Natural synthesis of MSM begins with the uptake of sulphate to produce dimethylsulfoniopropionate (DMSP) by algae, phytoplankton, and other marine microorganisms DMSP is cleaved to form dimethyl sulphoxide (DMSO), the parent molecule of MSM. MSO & MSM is released into the atmosphere and absorbed into the soil, where it is taken up by plants; MSM is widely found in fruit, vegetable and cereal crops. Plants use MSM as a sulphur source. Levels found are generally low, and nature/biochemically identical products can be synthesised to supplement natural sources.

 

Unlike many phytochemicals, both DMSO and MSM are rapidly absorbed, the former being reduced to MSM in the liver, although data suggests it has a fairly rapid turnover in the body; up to 75% can be found in the urine of rats after 24 hours; it can also be found in faeces, saliva, milk and other bodily secretions. It is believed to be absorbed by passive mechanisms; it is easily soluble in water and, due to its covalent bonding and mild ligand property, can pass directly across cell membranes and the blood-brain barrier. MSM has a greater ability to deliver sulphur than other sources due to a greater efficiency of absorption. Data also shows that MSM can be delivered to all tissues and has a rapid rate of accumulation. Although the half life of MSM is measured in hours, data shows that accumulation is rapid. This allows MSM to function in all areas, across a range of characteristics.

 

Sulphur tends, in biological systems, to form disulphide bonds, once called sulphur bridges. Sulphur links two molecules, either between identical molecules (such as cystine links giving structure to hair strands, and skin) or asymmetrical molecules. This lends tensile strength to connective tissue, especially collagens, and mucopolysaccharides. MSM can achieve this through sulphur donation.

 

Sulphur donation

Although animal biochemistry cannot synthesise methionine, there is evidence that microbial MSM can be converted to the sulphur amino acids; however, MSM can spare the donation by methionine/cysteine, as in the case of intestinal mucus production. MSM donates sulphur to 3-phosphoadenosine 5-phosphosulfate (PAPS), a central sulphur donor. More specifically, MSM contributes to the sulphation and detoxification of acetaminophen and the sulphation of cartilage proteoglycans. As such, supporting synthesis of GAGs and chondroitin sulphate, MSM supports the actions of glucosamine and chondroitin in the manufacture of collagen.

 

Inflammatory processes

MSM operates through the inhibition of the proinflammatory nuclear factor kappa beta (NF- 𝜅𝛽) signalling pathway and attenuation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, resulting in decreased release of the proinflammatory cytokines such as interleukins IL-1𝛽, IL-6, and IL-8. It has been shown to help reduce baseline levels of pro-inflammatory cytokines, especially after exercise. In addition, it reduces the inflammatory markers of TNF-α. MSM can also diminish the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) through suppression of NF-κβ; thus lessening the production of vasodilating agents such as nitric oxide (NO) and prostanoids . NO not only modulates vascular tone but also regulates mast cell activation ; therefore, MSM may indirectly have an inhibitory role on mast cell mediation of inflammation. With the reduction in cytokines and vasodilating agents, flux and recruitment of immune cells to sites of local inflammation are inhibited. Reduction of NOS and COX impact on reactive oxygen species (ROS).

 

Oxidation

Suppression of ROS by MSM is thought to act at mitochondrial level. Reducing COX & NOS reduces superoxide and nitric oxide; reduction of pro-inflammatory cytokines also reduces ROS. MSM increases the levels of glutathione (GSH), catalase (CAT) and prostaglandin E2 (PGE2); MSM acts through reduction of oxidative enzymes, support of antioxidative markers and free radical scavenging.

 

Immunomodulation

Alongside the effects of the interaction of the inflammatory cycle and oxidation on the immune response, which are well documented, involving the activation of macrophages and cytokine release, sulphur products are known to have immunomodulatory actions. MSM, through its actions on No helps reduce apoptosis of macrophages.

 

The above actions give MSM a versatility that can help support a number of mechanisms; these can then manifest in a number of physiological systems where it can maintain a favourable anabolism/catabolism balance.

 

Bone formation

Bone equilibrium is a balance between osteoblast and osteoclast genesis. RANKL induced osteoclastogenesis, by increasing osteoclasts, increases the rate of bone resorption. RANKL is the ligand responsible for NF- 𝜅𝛽. MSM has been shown to inhibit this marker. At the same time, MSM influences growth hormone mediated regulation of osteoblasts.

 

Joint Integrity

Obviously, one factor in joint physiology is the integrity of bone; MSM does appear to have an active role in maintaining homeostasis. MSM can also act in other ways.

Through inflammation & oxidation, causative factors initiate a sequence of events that impact on collagen homeostasis, resulting in cartilage damage (see collagen article on Knowledge Base).

MSM (Methylsulfonylmethane)

January 2019

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info@gwfnutrition.com

 

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By direct interaction with superoxide, and mitigating inflammatory cytokines and IGF, both oxidative stress and MMP generation is reduced, and collagen integrity is improved.

Additionally, MSM support of glucosamine & chondroitin, and sulphur donation into proteoglycans aids collagen synthesis; chondroitin is a component of collagen, so MSM acts through two pathways.

 

Various

Beyond the role of MAM in bone and joint physiology, it also impacts in other areas. Its involvement with cytokines and oxidative enzymes means it has similar impacts to other botanicals; it has been implicated in pain relief, both joint and muscular pain. There is also evidence that MSM aids recovery from oxidative damage during exercise.

There is evidence that MSM has beneficial effects on multiple metabolic dysfunctions, including hyperglycemia, hyperinsulinemia, insulin resistance, and inflammation, can ameliorate seasonal allergic conditions, skin quality and texture and may even have a role in supporting cancer treatments.

References

 

Bohlooli, S.; Mohammadi, S.; Amirshahrokhi, K.; Mirzanejad-Asl, H.; Yosefi, M.; Mohammadi-Nei, A.; Chinifroush, M.M. Effect of Methylsulfonylmethane Pretreatment on Aceta-minophen Induced Hepatotoxicity in Rats. Iran J. Basic Med. Sci. 2013, 16, 896–900.

 

Butawan MN, Benjamin RL, Bloomer RJ. Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients 2017, 9, 290-311.

 

Ines, Park SY, Chung M, Ju JH, Kang MC, Gaspar JM,  Seo JA, Macedo MP, Soo  PK, Mantzoros C, Lee SH, Kim YB.  Methylsulfonylmethane (MSM), an organosulfur compound, is effective against obesity-induced metabolic disorders   in mice, Metabolism (2016), doi: 10.1016/j.metabol.2016.07.007

 

Joung YH, Darvin P, Kang DY, Nipin SP, Byun HJ, Lee CH, Lee HK, Yang YM. Methylsulfonylmethane Inhibits RANKLInduced Osteoclastogenesis in BMMs by Suppressing NF-κB and STAT3 Activities. PLOS ONE | DOI:10.1371/journal.pone.0159891 July 22, 2016

 

Joung YH, Lim EJ, Darvin P, Chung SC, Jang JW, Park JD, Lee HK, Kim HS, Park T, Yang YM. MSM Enhances GH Signaling via the Jak2/STAT5b Pathway in Osteoblast-Like Cells and Osteoblast Differentiation through the Activation of STAT5b in MSCs. PLOS ONE | www.plosone.org 1 October 2012 | Volume 7 | Issue 10 | e47477

 

Lubis AMT, Siagian C, Wonggokusuma E, Marsetyo AF, Setyohadi B. Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial. Acta Medica Indonesiana, Vol 49, Iss 2 (2017)

Otsuki, S.; Qian, W.; Ishihara, A.; Kabe, T. Elucidation of dimethylsulfone metabolism in rat using a 35S-radioisotope tracer method. Nutr. Res. 2002, 22, 313–322.

Pecora, F.; Gualeni, B.; Forlino, A.; Superti-Furga, A.; Tenni, R.; Cetta, G.; Rossi, A. In vivo contribution of amino acid sulfur to cartilage proteoglycan sulfation. Biochem. J. 2006, 398, 509–514. 

Usha PR, Naidu MU. Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis. Clin Drug Investig. 2004;24(6):353-63

 

van derMerwe M, Bloomer RJ. The Influence of  methylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise. Journal of Sports Medicine Volume 2016, Article ID 7498359,

 

Withee ED, Tippens KM, Dehen R, Tibbitts D, Hanes D, Zwickey H. Effects of Methylsulfonylmethane (MSM) on exercise-induced oxidative stress, muscle damage, and pain following a halfmarathon: a double-blind, randomized, placebo-controlled trial. Journal of the International Society of Sports Nutrition (2017) 14:24-35.

 

Wong T, Bloomer RJ, Benjamin RL, Buddington RK.  Small Intestinal Absorption of

Methylsulfonylmethane (MSM) and Accumulation  of the Sulfur Moiety in Selected Tissues of Mice. Nutrients 2018, 10, 19-28

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