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Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model

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Abstract

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.

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Abbreviations

MSM:

Methylsulfonylmethane

OA:

Osteoarthritis

DMSO2 :

Dimethyl sulfone

DMSO:

Dimethyl sulfoxide

PGI2 :

Prostacyclin

BW:

Body weight

BMD:

Bone mineral density

DXA:

Dual energy X-ray absorptiometry

CV:

Coefficient of variation

TC:

Total cholesterol

TG:

Triglyceride

ANCOVA:

Analysis of covariance

References

  1. Pearson TW, Dawson HJ, Lackey HB (1981) Natural occurring levels of dimethyl sulfoxide in selected fruits, vegetables, grains, and beverages. J Agric Food Chem 29:1089–1091

    Article  PubMed  CAS  Google Scholar 

  2. Williams KI, Burstein SH, Layne DS (1966) Dimethyl sulfone: isolation from human urine. Arch Biochem Biophys 113:251–252

    Article  PubMed  CAS  Google Scholar 

  3. Parcell S (2002) Sulfur in human nutrition and applications in medicine. Altern Med Rev 7:22–44

    PubMed  Google Scholar 

  4. (2003) Natural Medicines Comprehensive Database, 5th edn. Therapeutic Research Faculty

  5. Rose SE, Chalk JB, Galloway GJ, Doddrell DM (2000) Detection of dimethyl sulfone in the human brain by in vivo proton magnetic resonance spectroscopy. Magn Reson Imaging 18:95–98

    Article  PubMed  CAS  Google Scholar 

  6. Lin A, Nguy CH, Shic F, Ross BD (2001) Accumulation of methylsulfonylmethane in the human brain: identification by multinuclear magnetic resonance spectroscopy. Toxicol Lett 123:169–177

    Article  PubMed  CAS  Google Scholar 

  7. Cecil KM, Lin A, Ross BD, Egelhoff JC (2002) Methylsulfonylmethane observed by in vivo proton magnetic resonance spectroscopy in a 5-year-old child with developmental disorder: effects of dietary supplementation. J Comput Assist Tomogr 26:818–820

    Article  PubMed  Google Scholar 

  8. Engelke UF, Tangerman A, Willemsen MA, Moskau D, Loss S, Mudd SH, Wevers RA (2005) Dimethyl sulfone in human cerebrospinal fluid and blood plasma confirmed by one-dimensional (1)H and two-dimensional (1)H-(13)C NMR. NMR Biomed 18:331–336

    Article  PubMed  CAS  Google Scholar 

  9. McCabe D, O’Dwyer P, Sickle-Santanello B, Woltering E, Abou-Issa H, James A (1986) Polar solvents in the chemoprevention of dimethylbenzanthracene-induced rat mammary cancer. Arch Surg 121:1455–1459

    Article  PubMed  CAS  Google Scholar 

  10. O’Dwyer PJ, McCabe DP, Sickle-Santanello BJ, Woltering EA, Clausen K, Martin EW Jr (1988) Use of polar solvents in chemoprevention of 1, 2-dimethylhydrazine-induced colon cancer. Cancer (Phila) 62:944–948

    Article  Google Scholar 

  11. Ebisuzaki K (1988) Aspirin and methylsulfonylmethane (MSM): a search for common mechanisms, with implications for cancer prevention. Anticancer Res 23:453–458

    Google Scholar 

  12. Alam SS, Layman DL (1983) Dimethyl sulfoxide inhibition of prostacyclin production in cultured aortic endothelial cells. Ann N Y Acad Sci 411:318–320

    Article  PubMed  CAS  Google Scholar 

  13. Beilke MA, Collins-Lech C, Sohnle PG (1987) Effects of dimethyl sulfoxide on the oxidative function of human neutrophils. J Lab Clin Med 110:91–96

    PubMed  CAS  Google Scholar 

  14. Layman DL (1987) Growth inhibitory effects of dimethyl sulfoxide and dimethyl sulfone on vascular smooth muscle and endothelial cells in vitro. In Vitro Cell Dev Biol 23:422–428

    Article  PubMed  CAS  Google Scholar 

  15. Morton JI, Siegel BV (1986) Effects of oral dimethyl sulfoxide and dimethyl sulfone on murine autoimmune lymphoproliferative disease. Proc Soc Exp Biol Med 183:227–230

    PubMed  CAS  Google Scholar 

  16. Barrager E, Veltmann JR Jr, Schauss AG, Schiller RN (2002) A multicentered, open-label trial on the safety and efficacy of methylsulfonylmethane in the treatment of seasonal allergic rhinitis. J Altern Complement Med 8:167–173

    Article  PubMed  Google Scholar 

  17. Akesson K (1999) Osteoarthritis and degenerative spine pathologies. In: Seibel MJ, Robins SP, Bilezikian JP (eds) Dynamics of bone and cartilage metabolism. Academic Press, London, pp 637–648

    Google Scholar 

  18. Rizzo R, Grandolfo M, Godeas C, Jones KW, Vittur F (1995) Calcium, sulfur, and zinc distribution in normal and arthritic articular equine cartilage: a synchrotron radiation-induced X-ray emission (SRIXE) study. J Exp Zool 273:82–86

    Article  PubMed  CAS  Google Scholar 

  19. Murav’ev IuV, Venikova MS, Pleskovskaia GN, Riazantseva TA, IaA Sigidin (1991) Effect of dimethyl sulfoxide and dimethyl sulfone on a destructive process in the joints of mice with spontaneous arthritis. Patol Fiziol Eksp Ter 2:37–39

    PubMed  Google Scholar 

  20. Hasegawa T, Ueno S, Kumamoto S, Yoshikai Y (2004) Suppressive effect of methylsulfonylmethane (MSM) on type II collagen-induced arthritis in DBA/1 J mice (in Japanese). Yakuri To Chiryo (Jpn Pharmacol Ther) 32:421–427

    CAS  Google Scholar 

  21. Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951

    PubMed  CAS  Google Scholar 

  22. Miyaura C, Onoe Y, Inada M, Maki K, Ikuta K, Ito M, Suda T (1997) Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: similarity to estrogen deficiency. Proc Natl Acad Sci USA 94:9360–9365

    Article  PubMed  CAS  Google Scholar 

  23. Gimblet EG, Marney AF, Bonsnes RW (1967) Determination of calcium and magnesium in serum, urine, diet, and stool by atomic absorption spectrophotometry. Clin Chem 13:204–214

    PubMed  CAS  Google Scholar 

  24. Mankin HJ, Dorfman H, Lippiello L, Zarins A (1971) Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 53:523–537

    PubMed  CAS  Google Scholar 

  25. McAlindon TE, LaValley MP, Gulin JP, Felson DT (2000) Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 283:1469–1475

    Article  PubMed  CAS  Google Scholar 

  26. Usha PR, Naidu MUR (2004) Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Invest 24:353–363

    Article  CAS  Google Scholar 

  27. Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF (2006) Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthr Cartil 14:286–294

    Article  PubMed  CAS  Google Scholar 

  28. Brien S, Prescott P, Bashir N, Lewith H, Lewith G (2008) Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis. Osteoarthr Cartil 16:1277–1288

    Article  PubMed  CAS  Google Scholar 

  29. Brien S, Prescott P, Lewith G (2009) Meta-analysis of the related nutritional supplements dimethyl sulfoxide and methylsulfonylmethane in the treatment of osteoarthritis of the knee. Evid Based Complement Alternat Med 2011(528403):12

    Google Scholar 

  30. Debbi EM, Agar G, Fichman G, Ziv YB, Kardosh R, Halperin N, Elbaz A, Beer Y, Debi R (2011) Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study. BMC Complement Alternat Med 11:50

    Article  CAS  Google Scholar 

  31. Mason RM, Chambers MG, Flannelly J, Gaffen JD, Dudhia J, Bayliss MT (2001) The STR/ort mouse and its use as a model of osteoarthritis. Osteoarthr Cartil 9:85–91

    Article  PubMed  CAS  Google Scholar 

  32. Richmond VL (1986) Incorporation of methylsulfonylmethane sulfur into guinea pig serum proteins. Life Sci 39:263–268

    Article  PubMed  CAS  Google Scholar 

  33. Horvath K, Noker PE, Somfai-Relle S, Glavits R, Financsek I, Schauss AG (2002) Toxicity of methylsulfonylmethane in rats. Food Chem Toxicol 40:1459–1462

    Article  PubMed  CAS  Google Scholar 

  34. Magnuson BA, Appleton J, Ryan B, Matulka RA (2007) Oral developmental toxicity study of methylsulfonylmethane in rats. Food Chem Toxicol 45:977–984

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are grateful to Dr. Kazuhiko Yamada (Kagawa Nutrition University) for helpful discussion and Dr. Hisashi Murayama (Kureha Chemical Industry) for their assistance with the histomorphological analyses. This study was supported by a Grant of the National Institute of Health and Nutrition.

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All authors have no conflicts of interest to declare.

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Correspondence to Yoshiko Ishimi.

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Ezaki, J., Hashimoto, M., Hosokawa, Y. et al. Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model. J Bone Miner Metab 31, 16–25 (2013). https://doi.org/10.1007/s00774-012-0378-9

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  • DOI: https://doi.org/10.1007/s00774-012-0378-9

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