MSM is one of the most popular ingredients of supplements for joints and recovery. It is marketed as 'organic sulfur', but what is actually known about this molecule? The editorial team explains what methylsulfonylmethane is, how it behaves in the body and which mechanisms of action have confirmation.
What MSM is
Methylsulfonylmethane, or dimethyl sulfone (MSM), is a simple organic sulfur compound with the formula (CH₃)₂SO₂. At room temperature it is a white crystalline powder without a pronounced odor, highly soluble in water. The molecule consists of a sulfur atom, two oxygen atoms and two methyl groups.
MSM is a product of the oxidation of dimethyl sulfoxide (DMSO) - a solvent known in medicine and chemistry. In fact, interest in MSM arose precisely from studies of DMSO: scientists noticed that part of DMSO in the body converts into dimethyl sulfone, and began to study it as a separate substance without the characteristic garlic odor of DMSO.
In nature MSM is present in small amounts in some plants, milk, coffee, tea and other products, as well as in human plasma and urine. However, these amounts are very small, so supplements are produced synthetically - most often by oxidizing DMSO with hydrogen peroxide followed by purification (distillation or crystallization).
By mass, sulfur makes up about a third of the MSM molecule (about 34%). This is why it is often positioned as a 'source of organic sulfur', although in a real diet the main source of sulfur remains proteins with methionine and cysteine.
How MSM behaves in the body
MSM is a small water-soluble molecule that is quickly absorbed in the gastrointestinal tract. In a study with labeled sulfur (Magnuson et al., 2007) in rats, the substance quickly appeared in the blood, distributed throughout the tissues and was excreted mainly in the urine, without signs of significant accumulation.
In humans MSM is also detectable in blood and urine after intake, and in individual works - even in cerebrospinal fluid and the brain, which indicates the ability to cross histohematic barriers. The clinical significance of this fact has not yet been established.
Part of the sulfur from MSM, according to animal studies, may be incorporated into sulfur-containing amino acids. However, how important this pathway is for a human with sufficient protein intake is unknown. Therefore the claim that 'MSM closes a sulfur deficiency' should be treated with caution.
The pharmacokinetic data in humans are quite modest, and standardized parameters (half-life, bioavailability) are not present in guidelines. That is precisely why the intake regimens in studies are usually simple - one or two doses per day over several weeks.
Mechanisms of action: what is known
The review by Butawan, Benjamin and Bloomer (2017) summarized three main directions used to explain the effects of MSM. The first is anti-inflammatory: in cell models MSM suppressed the activation of the transcription factor NF-κB, which regulates the expression of pro-inflammatory cytokines and enzymes.
The second direction is antioxidant. Studies reported changes in markers of oxidative stress and glutathione status with MSM. The mechanism is probably indirect: the molecule itself is not a powerful 'trap' for free radicals, but it may influence the regulation of the body's own antioxidant systems.
The third direction is participation in sulfur metabolism as a 'building block' for the synthesis of sulfur-containing compounds of connective tissue. This is the most popular explanation in marketing, but it is the least supported by direct studies in humans.
Most mechanistic data were obtained in vitro or in animals, at doses that cannot always be compared with human ones. Therefore the mechanisms should be regarded as hypotheses that explain the observed clinical results, rather than as a proven chain of events.
What MSM is used for
Most studies of MSM concern osteoarthritis of the knee joint. In a pilot RCT by Kim and colleagues (2006), 6 g of MSM per day over 12 weeks reduced pain and improved function compared with placebo; similar results were obtained by Debbi and colleagues (2011). The effect was moderate, and the studies small.
In the sports context MSM was studied as a means for recovery after exertion: muscle pain, markers of muscle damage and oxidative stress were assessed. The results are heterogeneous, and we examine them in more detail in a separate article on the evidence base.
MSM was also studied in seasonal allergic rhinitis, in dermatology (often in combinations with other substances) and as a component of products for hair and nails. These directions have an even weaker evidence base.
The table below summarizes the main areas of application with the editorial team's assessment of the quality of the evidence.
| Area | What was studied | Assessment of evidence |
|---|---|---|
| Osteoarthritis of the knee joint | Pain, function (WOMAC) | Several small RCTs, moderate effect |
| Recovery after exertion | Pain, damage markers, OS | Small studies, heterogeneous results |
| Allergic rhinitis | Symptoms | Isolated works |
| Skin, hair, nails | Cosmetic indicators | Weak, often combinations |
Safety and regulatory status
MSM is considered a substance with low toxicity. In studies on rats (Horváth et al., 2002; Magnuson et al., 2007) even very high doses did not cause serious toxic or teratogenic effects. In clinical works in humans, side effects were rare and mild.
Most often described are digestive complaints (bloating, discomfort, loosening of stools), headache, and sometimes skin reactions. They usually pass after reducing the dose or discontinuing the supplement.
In the USA a separate commercial MSM product received GRAS status ('generally recognized as safe') on the basis of data submitted to the FDA. However, this status concerns use as an ingredient in food products and does not mean confirmation of medicinal properties.
There are insufficient data on pregnancy, breastfeeding and long-term intake beyond a few months in humans. People with chronic diseases and those taking anticoagulants or other ongoing medications should discuss intake with a doctor.
- Low acute toxicity in animals.
- Mild and infrequent side effects in human studies.
- Limited data for special population groups.
Editorial conclusions
MSM is a simple sulfur-containing molecule that is quickly absorbed and excreted from the body. Its effects are associated with an anti-inflammatory action through NF-κB, an effect on antioxidant balance and sulfur metabolism.
The best-studied application is pain in osteoarthritis of the knee joint, where small RCTs showed moderate benefit. Data on sports recovery are encouraging but ambiguous.
The safety profile of MSM is favorable, but it is not a medicinal product and does not replace the diagnosis and treatment of joint diseases.
Our articles 'The benefits of MSM for athletes: the evidence base', 'How to take MSM' and 'Side effects of MSM' will help you continue the topic.
References
- Butawan M, Benjamin RL, Bloomer RJ. Methylsulfonylmethane: applications and safety of a novel dietary supplement. Nutrients. 2017;9(3):290.
- Magnuson BA, Appleton J, Ames GB. Pharmacokinetics and distribution of [35S]methylsulfonylmethane following oral administration to rats. J Agric Food Chem. 2007;55(3):1033–1038.
- Kim LS, Axelrod LJ, Howard P, et al. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2006;14(3):286–294.
- Debbi EM, Agar G, Fichman G, et al. Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study. BMC Complement Altern Med. 2011;11:50.
- Horváth K, Noker PE, Somfai-Relle S, et al. Toxicity of methylsulfonylmethane in rats. Food Chem Toxicol. 2002;40(10):1459–1462.
- Magnuson BA, Appleton J, Ryan B, Matulka RA. Oral developmental toxicity study of methylsulfonylmethane in rats. Food Chem Toxicol. 2007;45(6):977–984.
- van der Merwe M, Bloomer RJ. The influence of methylsulfonylmethane on inflammation-associated cytokine release before and following strenuous exercise. J Sports Med (Hindawi). 2016;2016:7498359.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
