MSM health benefits
April 14, 2012
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MSM Reviews
Methylsulfonylmethane (MSM) [dimethyl sulfone (DMSO2) and methyl sulfone] is an organic sulfur-containing
compound that occurs naturally in vegetables, grains, animals as well as human body. [A2] MSM is the oxidized form
of dimethyl-sulfoxide (DSMO); it is considered as an effective natural analgesic and anti-inflammatory agent by some
researchers. [2] MSM (methylsulfonylmethane) has been promoted to have many benefits, and to treat osteoarthritis,
pain, inflammation, allergies, and the maintenance of normal keratin levels in hair, skin and nails for years. Until now,
scientific evidence for supporting most of these claims is still insufficient, only a few studies about MSM benefits are

Other Names: OptiMSM"

MSM Biological Effects
A study has demonstrated that MSM crosses the blood-brain barrier in significant concentrations after oral dosing.
Further, MSM distributed evenly throughout the brain. [A1] An in vitro study further demonstrates the anti-
inflammatory and anti-oxidative activities on hydrogen peroxide, superoxide and hypochlorous acid. [A3]

MSM Benefits

OptiMSM' may be used as a supplemental source of MSM', at levels up to 4000 ppm in meal supplement and meal
replacement foods, h i t smoothie-type drinks, and fruit-flavored thirst quencher-type beverages, and up to 30,000
ppm in food bars, such as granola bars and energytype bars, provided that food standards of identity do not preclude
such use MSM Potential Benefits on Allergy. (GRN 000229)

A study of 50 subjects demonstrates dose of 2600 mg of MSM reduced allergy symptoms in 7 days. [A4] Two studies
of rats in the demonstrated a significant reduction in the time to tumor onset in rats treated with MSM. [A5, A6] MSM
may also benefit subjects suffered from autoimmune disease, as a rat study demonstrated that treatment of DMSO or
DMSO2 led to significant diminishment of lymphoid organ enlargement. [A7]

MSM Potential Benefits on Osteoarthritis
In May of 2009, Brien S and co-workers from Aldermoor Health Centre, UK, concluded that MSM has no significant
effect in the reduction of pain in the treatment of osteoarthritis from a review of several studies. [3] But, in another
study of 55 people suffered from knee osteoarthritis, researchers from Southwest College Research Institute found
dose of 3 g of MSM twice a day benefited the users, with a significant decreases in pain and physical function
impairment as evidence. [1] Further, Debbi EM and co-workers from Assaf Harofeh Medical Center, Israel, also found
MSM supplementation is useful on osteoarthritis of the knee - an improvement in pain and physical function. The
treated group took MSM in doses of 1.125 grams 3 times a day for 12 weeks.

In addition, the users may gain better MSM benefits (if any) if MSM is combined with glucosamine. Indian researchers
compared the efficacy and safety of oral glucosamine (500 mg), methylsulfonylmethane (MSM; 500 mg), and their
combination with a placebo three times daily in treating osteoarthritis of the knee for 12 weeks. They found that MSM
significantly decreased a pain index, and the combination resulted in a more significant decrease in the mean pain
index. The combination therapy also worked very well in the swelling index. They concluded that glucosamine, MSM
and their combination produced an analgesic and anti-inflammatory effect in osteoarthritis. Combination therapy might
offer better benefits to people suffered from osteoarthritis as they showed better efficacy in reducing pain and swelling
and in improving the functional ability of joints than the individual agents. [C2]

MSM Potential Benefits on Patients at risk of certain types of cancers

In a study of human breast cancer cells, MSM effectively regulated multiple targets including STAT3/VEGF and
STAT5b/IGF-1R. These are the major molecules involved in tumor development, progression, and metastasis. [C1] In
another study, MSM showed cytotoxic effect on gastrointestinal cancer cell lines by apoptosis and cell cycle arrest.

MSM Potential Benefits on Animals suffered from colitis
In a study, colitis was induced by intracolonic instillation of 1 ml of 5% of acetic acid. Rats were treated with MSM
(dosage: 400 mg/kg/day, orally) for 4 days. MSM decreased macroscopic and microscopic colonic damage scores
caused by administration of acetic acid. MSM treatment also significantly reduced colonic levels of malondialdehyde,
myeloperoxidase and proinflammatory cytokine IL-1β. [C4]

MSM + EDTA may benefits animals suffered from edema.
The effect of topical application of a lotion containing MSM+EDTA was studied in a double blind, placebo controlled
clinical trial. In phase 1, patients having swelling in the lower extremities were randomly distributed to receive the
MSM+EDTA lotion or a placebo alone. In the second phase, patients were given MSM as placebo followed by
MSM+EDTA lotion for 2 weeks. The circumference of calf, ankle and foot for both legs were observed to decline
significantly after 2 weeks of application of the lotion/ but not placebo. However, application of MSM alone increased
the swelling. [C5]


A Copy of Agency Response Letter for Using MSM as GRAS:

Agency Response Letter GRAS Notice No. GRN 000229
CFSAN/Office of Food Additive Safety
February 18, 2008

George A. Burdock, Ph.D.
Burdock Group
801 N. Orange Ave. Suite 710
Orlando, FL 32801

Re: GRAS Notice No. GRN 000229

Dear Dr. Burdock:

The Food and Drug Administration (FDA) is responding to the notice, dated July 11, 2007, that you submitted on
behalf of Bergstrom Nutrition in accordance with the agency’s proposed regulation, proposed 21 CFR 170.36 (62 FR
18938; April 17, 1997; Substances Generally Recognized as Safe (GRAS); the GRAS proposal). FDA received the
notice on July 17, 2007, filed it on July 25, 2007, and designated it as GRAS Notice No. GRN 000229.

The subject of the notice is methylsulfonylmethane (MSM). The notice informs FDA of the view of Bergstrom Nutrition
that MSM is GRAS, through scientific procedures, for use as an ingredient in meal supplement and meal replacement
foods, fruit smoothie-type drinks, and fruit-flavored thirst quencher-type beverages at levels up to 4,000 milligrams
per kilogram (mg/kg) and in food bars such as granola bars and energy-type bars at levels up to 30,000 mg/kg
provided that food standards of identity do not preclude such use.

As part of its notice, Bergstrom Nutrition includes the report of a panel of individuals (Bergstrom Nutrition’s GRAS
panel) who evaluated the data and information that are the basis for Bergstrom Nutrition’s GRAS determination.
Bergstrom Nutrition considers the members of its GRAS panel to be qualified by scientific training and experience to
evaluate the safety of substances added to food. Bergstrom Nutrition’s GRAS panel evaluated the starting materials,
method of manufacture, product specifications, supporting analytical data, intended use levels in specified foods,
consumption estimates for all intended uses and estimates of dietary exposure, as well as published and unpublished
studies. Based on this review, Bergstrom Nutrition’s GRAS panel concluded that the intended uses of MSM are GRAS.

Bergstrom Nutrition provides information about the identity, composition, and method of manufacturer of MSM. MSM is
a white, odorless, slightly bitter tasting crystalline substance; it is readily soluble in water. Bergstrom describes MSM
as a metabolite of dimethyl sulfoxide (DMSO), which is also the starting material for the manufacture of MSM. To
manufacture MSM, DMSO is treated with hydrogen peroxide, followed by a four-stage distillation purification process
to remove impurities. After distillation, the molten product is processed into microprills (microspherical pellets of MSM)
in a prilling chamber. Bergstrom Nutrition provides specifications for food-grade MSM, including specifications for lead,
arsenic, aluminum, mercury, and cadmium.

Bergstrom Nutrition provides information about the intended use of, and estimates the daily intake of, MSM. Bergstrom
intends MSM for use as an ingredient in various foods, noting that the use of MSM is self-limiting in foods due to its
bitter taste at high levels. Bergstrom Nutrition notes that MSM is currently used as a dietary supplement
(approximately 17 milligrams per kilogram body weight per day (mg/kg bw/d; based on a 60 kilogram person) and
includes this intake in its estimate of the daily intake for MSM. The notifier estimates the daily intake for all uses
(conventional food + dietary supplement) to be approximately 49 mg/kg bw/d and approximately 81 mg/kg bw/d at the
mean and 90th percentile level of intake, respectively.

Bergstrom Nutrition discusses the metabolic fate of, and toxicology studies conducted on, MSM. MSM is rapidly
absorbed, with a half-life of approximately 12 hours as calculated from published rat studies. Published studies have
shown that MSM and its metabolites are excreted mainly via urine and, there is no accumulation of MSM by the body.

To support the safe use of MSM in foods, Bergstrom Nutrition summarizes several published toxicological studies
conducted in rodents under acute, subacute, and subchronic periods of exposure via the oral route of administration.
The notifier concurs with the published results that the no observed adverse effect level in rats consuming MSM for 90
days is 1500 mg/kg bw/d and that the no observed adverse effect level in a teratology study is 1000 mg/kg bw/d.
Bergstrom Nutrition also describes a published study in which arthritic mice consumed 3.75 g/kg bw/d for 12 weeks in
their drinking water, concurring with the study authors conclusions that there were no adverse effects in the mice.
Bergstrom Nutrition describes several studies in humans that report that MSM is well tolerated when consumed at
levels up to 100 mg/kg bw/d.
Potential Labeling Issues

Under section 403(a) of the Federal Food, Drug, and Cosmetic Act (FFDCA), a food is misbranded if its labeling is
false or misleading in any particular. Section 403(r) of the FFDCA lays out the statutory framework for a health claim.
In describing the intended use of MSM and in describing the information that Bergstrom Nutrition relies on to conclude
that MSM is GRAS under the conditions of its intended use, Bergstrom Nutrition raises a potential issue under these
labeling provisions of the FFDCA. If products that contain MSM bear any claims on the label or in labeling, such claims
are the purview of the Office of Nutrition, Labeling, and Dietary Supplements (ONLDS) in the Center for Food Safety
and Applied Nutrition. The Office of Food Additive Safety neither consulted with ONLDS on this labeling issue nor
evaluated the information in the notice to determine whether it would support any claims made about MSM on the
label or in labeling.


Based on the information provided by Bergstrom Nutrition, as well as other information available to FDA, the agency
has no questions at this time regarding Bergstrom Nutrition’s conclusion that MSM is GRAS under the intended
conditions of use. The agency has not, however, made its own determination regarding the GRAS status of the
subject use of MSM. As always, it is the continuing responsibility of Bergstrom Nutrition to ensure that food ingredients
that the firm markets are safe, and are otherwise in compliance with all applicable legal and regulatory requirements.

In accordance with proposed 21 CFR 170.36(f), a copy of the text of this letter responding to GRN 000229, as well as
a copy of the information in this notice that conforms to the information in the proposed GRAS exemption claim
(proposed 21 CFR 170.36(c)(1)), is available for public review and copying on the homepage of the Office of Food
Additive Safety (on the Internet at


Laura M. Tarantino, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
[1] Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis
pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2006 Mar;14(3):286-94. Epub 2005 Nov 23. [2] 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. [3] Brien S,
Prescott P, Lewith G. Meta-analysis of the Related Nutritional Supplements Dimethyl Sulfoxide and
Methylsulfonylmethane in the Treatment of Osteoarthritis of the Knee. Evid Based Complement Alternat Med. 2009
May 27. [A1] Lin A, Nguy CH, Shic F, Ross BD. Accumulation  of methylsulfonylmethane in the human brain:
identification by multinuclear magnetic resonance spectroscopy. Toxicol Lett 2001;123:169-177. [A2]
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dimethyl sulfoxide on the oxidative function of human neutrophils. J Lab Clin Med 1987;110:91-96. [A4] Barrager E,
Veltmann JR Jr, Schauss AG, Schiller RN. A multicentered, open-label trial on the safety and efficacy of
methylsulfonylmethane in the treatment of seasonal allergic rhinitis. J Altern Complement Med 2002;8:167-173. [A5] O’
Dwyer PJ, McCabe DP, Sickle-Santanello BJ, et al. Use of polar solvents in chemoprevention of 1,2-
dimethylhydrazineinduced colon cancer. Cancer 1988;62:944- 948. [A6] McCabe D, O’Dwyer P, Sickle-Santanello B,
et al. Polar solvents in the chemoprevention of dimethylbenzanthracene-induced rat mammary cancer. Arch Surg
1986;121:1455-1459. [A7] Morton JI, Siegel BV. Effects of oral dimethyl sulfoxide and dimethyl sulfone on murine
autoimmune lymphoproliferative disease. Proc Soc Exp Biol Med 1986:183:227-230.

[C1] Lim EJ et al, Methylsulfonylmethane Suppresses Breast Cancer Growth by Down-Regulating STAT3 and STAT5b
Pathways. PLoS One. 2012;7(4):e33361. [C2] Debbi EM, et al, Efficacy of methylsulfonylmethane supplementation on
osteoarthritis of the knee: a randomized controlled study. BMC Complement Altern Med. 2011 Jun 27;11:50.  [C3]
Jafari N, et al, Cytotoxicity of Methylsulfonylmethane on Gastrointestinal (AGS, HepG2, and KEYSE-30) Cancer Cell
Lines. J Gastrointest Cancer. 2011 May 28. [C4] Amirshahrokhi K et al, The effect of methylsulfonylmethane on the
experimental colitis in the rat. Toxicol Appl Pharmacol. 2011 Jun 15;253(3):197-202. [C5] Tripathi R et al, Effect of
topical application of methylsulfonylmethane (MSM), EDTA on pitting edema and oxidative stress in a double blind,
placebo-controlled study. Cell Mol Biol (Noisy-le-grand). 2011 Feb 12;57(1):62-9.