Comprehensive Guide to Methylsulfonyl Methane (MSM)

Methylsulfonyl Methane (MSM)Dr. James Meschino DC, MS, ND
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General Features
MSM is a naturally occurring sulfur compound, which first arose from a complex series of reactions in the surface waters of the ocean, according our present scientific understanding. 1 One of the products of oceanic phytoplankton production is the compound DMS (dimethylsulfide). DMS is a volatile liquid that easily finds its way into the upper layers of the atmosphere, where it becomes oxidized (photochemically) to form a variety of sulfur compounds, including MSM and DMSO (dimethylsulfoxide). 2 Rain of marine origin is the dominant carrier of atmospheric MSM, which provides much of the sulfur used to make biologically important sulfur –containing nutrients that we derive from plant and animal foods.
MSM’s hexavalent sulfur atom is abstracted by living organisms and is primarily used for the biochemical synthesis of many divalent sulfur-containing products. When MSM is broken apart by plants and animals, a portion of the sulfur is used to synthesize sulfur-containing amino acids (methionine and cystine) and another portion is used directly to produce many other biologically important organo-sulfur molecules (e.g., isothiocyanates, allicin, allyl propyl disulfide, diallyl disulfide). 3 Yet, many foods contain unadulterated MSM in its native form that has been absorbed from the soil by plants and passed up the food chain. As such, MSM in its native form is a common nutrient found in small amounts in grains, green vegetables, fish, meat and cow’s milk. 4,5 In this native form MSM is well absorbed and shows up in human urine with an excretion rate ranging from 4–11mg per day. 6 Maintenance levels of MSM in humans has been shown to be as low as 0.5–1.0 mg/kg of body weight per day. 7 Thus, a person weighing 70 kg would require 35–70 mg per day of MSM, which primarily acts as a sulfur donor to repair and restore damaged covalent disulfide bonds and the sulfhydral groups of many enzymes. 8 In this capacity, MSM is considered to be an integral part of maintaining the structural integrity of connective tissues, cartilage, nails, skin, hair, and certain enzymes, hormones, and immunoglobulins. 3
From a therapeutic standpoint, MSM supplementation, at levels that exceed those attainable from food alone, is emerging as a significant intervention in the treatment and prevention of a number of common conditions. Thus, many holistically minded practitioners are showing a high level of interest in MSM supplementation for use as a preventive and therapeutic agent. In regards to stability, MSM is very volatile and considerable amounts are destroyed during modern day food processing.
From a historical perspective it has been argued that MSM is a chemical that has been present on earth for a very long time. During the development of higher life forms on this planet three nutrients were always present: water, sodium chloride and MSM. As such, MSM has been shown to be a factor in the diets of our ancestors, which serves to strengthen the notion that MSM may be an overlooked and vital nutrient that is required for health maintenance.
Clinical Application and Mechanism of Action
1. Arthritis and Inflammatory Conditions Of The Musculoskeletal System
For many years the compound DMSO (dimethylsulfoxide) has been used as a topical agent in veterinary medicine due to its well established anti-inflammatory and analgesic properties. 9 DMSO has also been used by athletes for topical treatment of sports-related injuries involving inflammation of muscles, tendons, ligaments and bursitis problems. 10 Unfortunately, toxicity studies using DMSO revealed that it causes damage to the lens of the eye in animal studies, which was shown to be reversible upon DMSO with drawl. Although this effect has not been demonstrated in humans, The Food and Drug Administration (FDA) was reluctant to approve its use as a
therapeutic compound for humans. However, in 1978, DMSO was approved by the FDA for its use as an effective treatment for interstitial cystitis. 11, 12
An additional drawback to the use of DMSO is the strong garlic-breath one is left with after its application. This occurs due to the fact that the body metabolizes much of DMSO to DMS. 10 Approximately 15% of DMSO is metabolized by the body into MSM, which does not produce the garlic-breath effect generated by DMS. 13 Unlike DMSO, MSM can be taken orally for therapeutic purposes. It is very soluble in water and is readily absorbed from the GI tract. 1,14,15,16
Animal studies have demonstrated that MSM has potent anti-inflammatory properties and can help to halt the further destruction of joint cartilage in osteoarthritis. These studies also revealed an improvement in joint mobility. 17,18,27
More recently, a number of human trials have been undertaken to establish the efficacy of MSM in musculoskeletal disorders. Drs. Jacob and Lawrence have conducted controlled studies using MSM in cases of arthritis. Dr. Jacob compared MSM to the over-the-counter, nonsteroidal anti-inflammatory drug, Motrin. Subjects in both groups reported the same degree of pain relief after one month of follow up. 19 Dr. Lawrence compared MSM to a placebo in a double-blind study. Results demonstrated that pain relief was significantly greater in patients given the MSM. Eighty-two percent of the patients given the MSM reported significant pain reduction versus 18% in the placebo group. 20 Both Drs. Jacob and Lawrence indicate that efficacy of MSM is further enhanced by combining it with glucosamine sulfate. 19 Both of these clinicians also use MSM supplementation in the treatment of back pain. For the treatment of a broad spectrum of pain and inflammatory conditions (non-migraine headache, fibromyalgia, tendonitis, carpal-tunnel syndrome) the authors cite figures of up to 70% of patients reporting marked relief of symptoms when MSM was added to the treatment regime. Other conditions that may benefit from MSM supplementation include rheumatoid arthritis, lupus, scleroderma and interstitial cystitis. 19 Dr. Jacobs has used MSM in the treatment of more than 18,000 patients suffering from osteoarthritis and a variety of autoimmune diseases, including rheumatoid arthritis. It is generally accepted that MSM acts to support the structural integrity of joint cartilage, provides an anti-inflammatory effect to some degree and may have mild analgesic properties as well. The combination of these effects is thought to account for the results seen in clinical studies involving arthritic patients and patients presenting with other musculoskeletal and inflammatory conditions.
2. Scleroderma
When applied topically, MSM may also reduce scarring and provide benefit for people with scleroderma—a disorder that involves hardening of the skin as one clinical aspect.19
3. Interstitial Cystitis
Based on the proven benefit of DMSO in the cases, preliminary research has been undertaken with MSM. It appears that MSM may also be of useful in the treatment of interstitial cystitis, but further investigation is necessary to substantiate this application
Dosage and Standardized Grade
When administered as a single treatment agent a dose as low as 250 mg per day has been shown to be effective. Other studies have used doses as high as 2,000-6,000 mg per day. As indicated by Drs Jacob and Lawrence, it is likely best to use MSM in conjunction with glucosamine sulfate, and possibly other natural anti-inflammatory agents, to assist in the management of arthritis and other musculoskeletal disorders
Adverse Side Effects and Toxicity
There are naturally occurring concentrations of MSM in the human system of approximately 0.2–0.25 ppm, presumably originating from food. 22 The LD-50 in rats has been determined in excess of 20g/kg BM/d, indicating that MSM is an extremely non-toxic compound. 23 Other animal studies of toxicity have provided similar evidence, reporting no or very low toxicity at extremely high doses. 23 In humans, MSM has been established as a safe supplement. At high doses (2-8 gms per day), some gastric upset or diarrhea may occur

Drug-Nutrient Interactions
There are no well-known drug-nutrient interactions at this time in regards to MSM supplementation

Other Frontiers Of MSM Research Include Cancer Prevention In animal studies MSM supplementation has been shown to prevent and delay the development of colon and breast cancer in rats treated with known chemical carcinogens. 13, 28 This effect may be due to its ability to support methionine levels (helping to prevent hypomethylation of DNA, which results in fragile chromosomal linkages leading to mutations) or related more to its anti-proliferative action. 29,30 How this applies to humans at this time is not known.
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the developing fetus and there is generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other than a prenatal supplement. Any supplementation practices beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium and the treatment of preeclampsia.)

References: Pregnancy and Lactation
1. Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.
2. Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and Company Inc. 1998.
3. The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
4. Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine. Institute of Applied Complementary Medicine Inc. 1997.
References
1. Lovelock, J.E. Atmospheric dimethyl sulphide and the natural sulphur cycle. Nature1972;237:453-453
2. Hucker, H.B., et al. Studies on the absorption, excretion and metabolism of dimethyl sulfoxide (DMSO) in man. J Pharmacol Exp Ther 1967;155(2):309-317
3. Herschler, R.J. MSM: The Scientific Rationale For Nutritional Sulfur – A summary of writings and conversations with R.J. Herschler
4. Williams, K.I.H., et al. Dimethyl sulfone: isolation from cows’ milk. Proc Soc Exp Biol Med 1966;122:865
5. Pearson, T.W. Natural occurring levels of dimethyl sulfoxide in selected fruits, vegetables, grains, and beverages. J Agr Food Chem 1981;29:1089
6. Williams, K.I.H. Dimethyl sulfone: Isolation from human urine. Arch Biochem Biophys 1966;113:251-252
7. Herschler, R.J. 1986. MSM: A nutrient for the horse. Equ Vet Data;7:268-269
8. Herschler, R. Use of Methylsulfonylmethane to enhance the diet of an animal. 1991, United States Patent 5,071,878
9. Metcalf, J. MSM – A dietary derivative of DMSO. Equine Vet Data 1983;3(5):174-175
10. Cronin, J.R. Methylsulfonylmethane. Nutraceutical of the Century.
11. Rubin, L.F. Barnett, K.C. Ocular effects of oral and dermal application of dimethyl sulfoxide in animals. Ann NY Acad Sci 1967;141:333-345
12. National Academy of Sciences Research Council. Dimethyl sulfoxide as a therapeutic agent: Report of the ad hoc committee on dimethyl sulfoxide. New York: National Academy of Sciences 1973
13. Challem, J. Sulfur Power, Natural Way Publications, 1998Feb28
14. Richmond, V.L. Incorporation of methylsulfonylmethane sulfur into guinea pig serum proteins. Life Sci 1986;39:263-8
15. Richmond, V.A. Incorporation of methylsulfonylmethane sulfur into methionine and cysteine of guinea pig serum protein. Am J Clin Nutrition;43(6):Abs 42
16. Richmond, V.A. Incorporation of methylsulfonylmethane sulfur into guinea pig serum proteins. Life Sciences 1986;39:263-8
17. Hanson, R.R. DVM, DACVS. Will medicine keep your horse sound? 1996, The Horse, April issue:38-40
18. Repine, J.E., Fox, R.B., Berger, E.M. Effect of dimethyl sulfoxide on the bactericidal function of polymorphonuclear leukocytes. Ann NY Acad Sci 1983;411:11-13
19. Jacob, S.W., Lawrence, R.M., Zucker, M. The Miracle of MDM: The Natural Solution for Pain. New York. G.P. Putman’s Sons 1999
20. Lawrence, R.M. Methylsulfonylmethane (MSM): A double-blind study of its use in Degenerative Arthritis. Int J Anti-Aging Medicine 1998;1(1):50
21. MSM Herbal Advisor, www.herbaladvisor.com 2001
22. Jacob, S.W., Herschler, R. Introductory Remarks: Dimethyl sulfoxide after twenty years. Ann NY Acad Sci 1983;411:13-17
23. Metcalf, J.W. MSM status report. Eq Vet Data 1986;7:332-4
24. Deichman, W.B. Gerards, H.W. (eds.) Toxicology of Drugs and Chemicals. (ed.) New York:Academic Press 1969
25. Challem, Jack. The Power of MSM: Let’s Live (magazine) 2001January
26. 2000 Healthnotes, Inc;Sulfur. www.healthnotes.com
27. Moore, R.D., Morton, J.I. Diminished inflammatory joint disease in MRL/1pr mice ingesting dimethyl sulfoxide (DMSO) or dimethylsulfone (MSM). Federation of American Societies for Experimental Biology, 69th Annual Meeting 1985 April:p.692
28. Layman, D. Growth inhibitory effects of dimethyl sulfoxide and dimethyl sulfone on vascular smooth muscle and endothelial cells in vitro. In Vitro Cell Develop Biol 1987;23(6):422-8
29. Richmond, V.I. Incorporation of methylsulfonylmethane sulfur into guinea pig serum proteins. Life Sci 1986;39:263-8
30. Morton, J.I., Siegel, B.V. Effects of oral dimethyl sulfoxide and dimethyl sulfone on marine autoimmune lymphoproliferative disease. Proc Soc Exp Biol Med 1986;183:227-30