Research and References

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Methylsulfonylmethane (MSM), a sulfur-donor, will increase intracellular inorganic sulfate levels and contribute to the sulfation of glycosaminoglycans in the glycocalyx, therefore exhibiting antimicrobial and immune modulating properties 1-3. A well-sulfated, intact epithelial and endothelial glycocalyx, contribute to pathogen evasion and barrier functions, the regulation of inflammation, vascular permeability and tone, coagulation, the mediation of shear stress 4, 5, lipid metabolism 6, 7, immune modulation and leukocyte adhesion8-10, as well as protection against oxidative stress4. Therefore, any changes in the degree of sulfation due to reduced availability of inorganic sulfate, are associated with a wide range of pathophysiological consequences, such as capillary leak syndrome and consequent oedema formation11, accelerated inflammation, hypercoagulation, platelet hyperaggregation, and loss of vascular responsiveness 5, 6.

Furthermore, as a source of organic sulfur, MSM will increase the synthesis of other sulfur amino acids and glutathione 12, apart from inorganic sulfate 2, 3. It was shown that MSM attenuated paraquat-induced pulmonary and hepatic injury in mice, confirmed by the reduction of inflammatory markers and the increase in superoxide dismutase, glutathione, and catalase levels in lung and liver tissues12. Several research studies demonstrated that MSM inhibits lipopolysaccharide-induced release of oxidative stress biomarkers, such as nitric oxide and prostaglandin E2 in macrophages, through downregulation of NF-κB signaling 13, 14. It has been established that MSM potentially inhibits the translocation of the p65 subunit of NF-κB to the nucleus, thereby minimising downstream events associated with local and systemic inflammation 15-17.  Indeed, it has been demonstrated that supplementation with MSM will minimise the expression of many pro-inflammatory cytokines 12, 15, 17.  MSM attenuated experimental colitis by reducing IL-1b levels and protected against hepatic liver injury by decreasing TNFα and IL-6 levels 12, 18. In another study, MSM significantly mitigated lung and pancreatic histopathological changes, decreased serum amylase and myeloperoxidase activity, and inhibited caerulein-induced IL-1b expression 16. The availability of inorganic sulfate for glycosaminoglycan sulfation has been associated with the development of many inflammatory diseases19, such as atherosclerosis, stroke, sepsis, diabetes mellitus and related renal diseases, cardiovascular diseases, hypertension, obesity, pulmonary diseases, and various cancers4, 8, 20-27. MSM suppresses hepatic tumour development through activation of apoptosis and breast cancer growth by down-regulating STAT3 and STAT5b pathways 14, 28.

MSM is entirely safe and effective, taken at daily dosages of up to 4 g to prevent and treat inflammatory diseases1.

References:

1. Butawan M, Benjamin R, Bloomer R. Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement.
Nutrients. 2017;9(3):290. doi:10.3390/nu9030290
2. Nimni ME, Han B, Cordoba F. Are we getting enough sulfur in our diet?N utr Metab (Lond). Nov 2007;4:24.
doi:10.1186/1743-7075-4-24
3. Amadi B, Fagbemi AO, Kelly P, et al. Reduced production of sulfated glycosaminoglycans occurs in Zambian children
with kwashiorkor but not marasmus. Am J Clin Nutr. 2009;89(2):592-600. doi:10.3945/ajcn.2008.27092
4. Aldecoa C, Llau JV, Nuvials X, Artigas A. Role of albumin in the preservation of endothelial glycocalyx integrity and the
microcirculation: a review. Annals of Intensive Care. Jun 22 2020;10(85):1-12. doi:10.1186/s13613-020-00697-1
5. Meli I. Assessing the role of albumin in the formation of the endothelial glycocalyx layer using a microfluidic in vitro
model. University of Bern; 2019. https://www.cvrc.unibe.ch/e286839/e780601/20190201_MasterThesisIvoMeli.pdf
6. Kolarova H, Ambruzova B, Sindlerova LS, Klinke A, Kubala L. Modulation of endothelial glycocalyx structure under
inflammatory conditions. Mediators Inflamm. 2014;2014694312. doi:10.1155/2014/694312
7. Stopschinski BE, Holmes BB, Miller GM, et al. Specific glycosaminoglycan chain length and sulfation patterns are
required for cell uptake of tau versus α-synuclein and β-amyloid aggregates. J Biol Chem. 2018;293(27):10826-10840.
doi:10.1074/jbc.ra117.000378
8. Hayden MR. Endothelial activation and dysfunction in metabolic syndrome, type 2 diabetes and coronavirus disease
2019. J Int Med Res. Jul 2020;48(7)0300060520939746. doi:10.1177/0300060520939746
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doi:10.1111/jth.14371
10. Martin L, Koczera P, Zechendorf E, Schuerholz T. The endothelial glycocalyx: New diagnostic and therapeutic
approaches in sepsis. Biomed Res Int. 2016;20163758278. doi:10.1155/2016/3758278
11. Arokiasamy S, King R, Boulaghrasse H, et al. Heparanase-dependent remodeling of initial lymphatic glycocalyx

regulates tissue-fluid drainage during acute inflammation in vivo. Front Immunol. 2019;10:2316.
doi:10.3389/fimmu.2019.02316
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Inflammation. Oct 2013;36(5):1111-1121. doi:10.1007/s10753-013-9645-8
13. Mohammadi S NM, Hamzeiy H, Maleki-Dizaji N, Pezeshkian M, Sadeghi-Bazargani H, Darabi M, Mostafalou S,
Bohlooli S, Garjani A. Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress in
monocrotaline-induced pulmonary hypertensive rats. . Adv Pharmacol Sci. 2012;2012:507278.
doi:10.1155/2012/507278
14. Kim YH, Kim DH, Lim H, Baek D-Y, Shin H-K, Kim J-K. The Anti-inflammatory Effects of Methylsulfonylmethane on
Lipopolysaccharide-Induced Inflammatory Responses in Murine Macrophages. Biol Pharm Bull. 2009;32(4):651-656.
doi:10.1248/bpb.32.651
15. Kalman DS, Feldman S, Scheinberg AR, Krieger DR, Bloomer RJ. Influence of methylsulfonylmethane on markers of
exercise recovery and performance in healthy men: a pilot study. J Int Soc Sports Nutr. Sep 27 2012;946.
doi:10.1186/1550-2783-9-46
16. Velusamy RK, Tamizhselvi R. Protective effect of methylsulfonylmethane in caerulein-induced acute pancreatitis and
associated lung injury in mice. J Pharm Pharmacol. Sep 2018;70(9):1188-1199. doi:10.1111/jphp.12946
17. van der Merwe M, Bloomer RJ. The Influence of Methylsulfonylmethane on Inflammation-Associated Cytokine Release
before and following Strenuous Exercise. Journal of sports medicine (Hindawi Publishing Corporation). 2016
2016;2016:7498359-7498359.
18. Sousa-Lima I, Park SY, Chung M, et al. Methylsulfonylmethane (MSM), an organosulfur compound, is effective against
obesity-induced metabolic disorders in mice. Metab Clin Exp. Oct 2016;65(10):1508-1521.
doi:10.1016/j.metabol.2016.07.007
19. Martin, David, Michael. Oxidation of heparan sulphate by hypochlorite: role of N-chloro derivatives and dichloraminedependent
fragmentation. Biochem J. 2005;391(1):125-134. doi:10.1042/bj20050630
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of hyaluronan and hyaluronidases. Arterioscler Thromb Vasc Biol. Jul 2018;38(7):1427-1439.
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derivatives. Molecules. Jan 2020;25(2)390. doi:10.3390/molecules25020390
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visualization. Pflug Arch Eur J Physiol. Jun 2007;454(3):345-359. doi:10.1007/s00424-007-0212-8
24. Hayden MR. Type 2 diabetes mellitus increases the risk of late-onset Alzheimer’s disease: Ultrastructural remodeling
of the neurovascular unit and diabetic gliopathy. Brain Sciences. 2019;9(10):262. doi:10.3390/brainsci9100262
25. Nadanaka S, Purunomo E, Takeda N, Tamura J, Kitagawa H. Heparan sulfate containing unsubstituted glucosamine
residues: Biosynthesis and heparanase inhibitory activity. Glycobiology. Nov 2014;24(11):1206-1206.
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diabetes progression in humans. PLoS One. Feb 7 2018;13(2)e0191360. doi:10.1371/journal.pone.0191360
28. Lim EJ, Hong DY, Park JH, et al. Methylsulfonylmethane Suppresses Breast Cancer Growth by Down-Regulating
STAT3 and STAT5b Pathways. PLoS One. 2012;7(4):e33361. doi:10.1371/journal.pone.0033361