MSM Side Effects: Is Methylsulfonylmethane Safe to Take Daily?

Written by the Nuvirox Research Team

Short answer: MSM appears well tolerated at commonly used doses, but "well tolerated" rests on small, short trials. Methylsulfonylmethane (MSM) trials in knee pain have reported few or no side effects at 2 to 6 grams a day for up to 12 weeks, and the ingredient holds GRAS (Generally Recognized As Safe) status in the US. What we don't have is long-term human data, solid information on drug interactions, or any pregnancy safety data in humans. The side effects people mention most, such as stomach upset, headache and trouble sleeping, come mainly from user reports rather than controlled studies.

What is MSM, and why is it considered low-risk?

MSM is a small sulfur-containing compound. It occurs naturally at low levels in many foods and is also a breakdown product of DMSO (dimethyl sulfoxide). Supplement MSM is manufactured, usually by oxidizing DMSO and purifying the result by crystallization or distillation. A 2017 review in Nutrients noted that manufactured MSM has no detectable structural or safety differences from the naturally produced molecule.

Its low-risk reputation comes from three sources: animal toxicology, a formal US safety review, and human trials. Rat studies summarized in that review found no adverse effects at doses as high as 1.5 g/kg per day for 90 days. One MSM product received GRAS status in 2007, and under that notification MSM is considered safe at intakes under 4,845.6 mg per day. If you want the background on why people take MSM in the first place, see our explainer on what MSM does for joint pain.

What side effects does MSM cause?

Controlled trials have reported very few. The 2017 review summarized MSM as "well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects." The complaints most often attributed to MSM in consumer references are digestive (bloating, loose stools, upset stomach), headache, fatigue and sleep disturbance, but these have not separated clearly from placebo in the published trials.

One rare but notable event has been published: a 2015 case report described a 35-year-old woman who developed acute angle-closure (a sudden pressure rise in both eyes) one week after starting several supplements, one of which contained MSM. The authors suspected MSM because of its sulfonyl structure, which resembles certain sulfa drugs known to cause the same reaction. Her eyes recovered fully after she stopped the supplements. A single case can't prove cause, but sudden eye pain, blurred vision or halos around lights after starting any new supplement warrant urgent care.

What human studies actually show

Kim et al., 2006. In this randomized, double-blind, placebo-controlled pilot trial, 50 adults aged 40 to 76 with knee osteoarthritis pain took 3 g of MSM or placebo twice daily (6 g/day) for 12 weeks. The authors reported improvements in pain and physical function "without major adverse events." They were also candid that the "benefits and safety of MSM in managing OA and long-term use cannot be confirmed from this pilot trial."

Debbi et al., 2011. Forty-nine adults aged 45 to 90 with knee osteoarthritis took 1.125 g of MSM three times daily or placebo for 12 weeks. According to the full paper, none of the patients reported side effects or symptoms they hadn't experienced before the study, in either group. The only dropout was a placebo-group participant who left after a snakebite. The authors themselves described the complete absence of side effects as surprising.

Toguchi et al., 2023. In a Japanese randomized, double-blind, placebo-controlled trial, 88 healthy adults with mild knee pain took 2 g/day of MSM (ten 200 mg tablets) or placebo for 12 weeks. Safety was assessed through physical examinations, urine tests, blood tests and interviews, and the investigators reported no health problems and no adverse events.

The limiting finding. Every one of these trials enrolled fewer than 100 people and ran 12 weeks. That is enough to show MSM isn't commonly harmful in the short term, but far too small to detect uncommon reactions like the angle-closure case above, or effects that only emerge over months to years. The 2017 review also points out there have been no studies on MSM and alcohol, despite many anecdotal reports of increased alcohol sensitivity.

What users report (anecdotal)

User reviews and forum threads add texture that trials can't, but they come with heavy caveats: no placebo comparison, no dose standardization, and many people take MSM alongside other supplements. Read this section as a list of things people notice, not as evidence that MSM causes them.

• Digestive upset. The most common complaint, usually loose stools or stomach discomfort, sometimes at higher doses.
• Sleep changes. A few users suspect MSM contributed to insomnia, and some switch to morning dosing.
• Headache. Reported occasionally, typically mild and early on.
• Alcohol sensitivity. A recurring forum claim that drinking feels stronger or worse while taking MSM. As noted above, this has never been studied.
• No side effects. A large share of reviewers report nothing at all, which fits the trial data.

When MSM may not be the right choice

MSM's clean short-term record doesn't extend to every situation. These are the honest gaps:

• Pregnancy and breastfeeding. A rat developmental study found no maternal or fetal toxicity up to 1,000 mg/kg per day, but there are no human pregnancy data. Most clinicians would advise avoiding it.
• Medications. No drug interactions are well documented, but that partly reflects how little has been studied. People on blood thinners, multiple prescriptions, or medications with a narrow safety margin should check with a pharmacist.
• Sulfa-drug reactions or narrow-angle glaucoma risk. Given the published case, people with a history of drug-induced angle closure should discuss MSM with an eye doctor first.

See a doctor if joint pain comes with redness, warmth, marked swelling, fever or follows an injury, and seek urgent care for sudden eye pain or vision changes, hives, facial swelling or difficulty breathing after starting MSM.

How to take MSM to minimize side effects

The trial doses give a practical frame. Two to roughly 3.4 grams a day, taken in divided doses, is the range where trials reported no adverse events, and the GRAS notification sets a safe intake under about 4.8 grams. The 6 g/day dose in Kim 2006 was also tolerated, but it sits above that GRAS level.

• Start low (around 1 g/day) and increase over one to two weeks if you tolerate it.
• Split the daily amount into two or three doses and take them with meals, as the trials did.
• Take it earlier in the day if you notice any effect on sleep.
• Allow around 12 weeks to judge whether it is helping, since that is the trial window.

MSM is frequently paired with other joint ingredients. If you're weighing it alongside chondroitin, our review of chondroitin's side effects covers that ingredient's safety record, and our look at bromelain and MSM together for joint pain covers the evidence for that particular pairing.

Frequently asked questions

Can MSM cause diarrhea?

Loose stools are among the most common complaints in user reports, usually at higher single doses. Controlled trials didn't show a clear difference from placebo, but splitting the dose and taking it with food is a sensible first step if it happens to you.

Does MSM keep you awake at night?

Some users report sleep disturbance, and switching to morning dosing is a common workaround. This hasn't been tested in a controlled study, so it's best described as a possible individual reaction rather than an established effect.

Is MSM safe if I'm allergic to sulfa drugs?

MSM is not a sulfonamide antibiotic, and a sulfa allergy is not the same thing as a reaction to dietary sulfur. That said, the one published eye case was linked to MSM's sulfonyl structure, so people with a history of serious sulfa-drug reactions should ask their doctor or pharmacist before trying it.

Can you take MSM every day long term?

Daily use for up to 12 weeks is well supported by trial data. Beyond that, the evidence is mostly absence of reported problems rather than formal long-term studies, so periodic check-ins with your clinician are reasonable.

Is it safe to drink alcohol while taking MSM?

Nobody knows for certain. Forum reports describe heightened alcohol sensitivity, and a 2017 review noted that no study has examined MSM and alcohol. Moderation and paying attention to how you feel are the cautious approach.

The bottom line

MSM has a reassuring short-term safety record: animal toxicology is clean, the US GRAS notification covers intakes up to about 4.8 grams a day, and small 12-week trials at 2 to 6 grams reported few or no adverse events. The fair reading is that MSM is low-risk for most healthy adults, not that it is proven safe for everyone indefinitely. Long-term data, interaction studies and pregnancy data are missing, and one rare eye reaction has been reported. Start low, take it with food, and loop in your clinician if you take medications or have a relevant health history.

References

1. Butawan M, Benjamin RL, Bloomer RJ. Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients. 2017;9(3):290. DOI: 10.3390/nu9030290. PMID: 28300758. PMCID: PMC5372953
2. 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;14(3):286-94. DOI: 10.1016/j.joca.2005.10.003. PMID: 16309928
3. 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. DOI: 10.1186/1472-6882-11-50. PMID: 21708034. PMCID: PMC3141601
4. Toguchi A, Noguchi N, Kanno T, Yamada A. Methylsulfonylmethane Improves Knee Quality of Life in Participants with Mild Knee Pain: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2023;15(13):2995. DOI: 10.3390/nu15132995. PMID: 37447322. PMCID: PMC10346176
5. Hwang JC, Khine KT, Lee JC, Boyer DS, Francis BA. Methyl-sulfonyl-methane (MSM)-induced acute angle closure. J Glaucoma. 2015;24(4):e28-30. DOI: 10.1097/IJG.0000000000000027. PMID: 24240884
6. Magnuson BA, Appleton J, Ryan B, Matulka RA. Oral developmental toxicity study of methylsulfonylmethane in rats. Food Chem Toxicol. 2007;45(6):977-84. DOI: 10.1016/j.fct.2006.12.003. PMID: 17258373

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This article is for informational purposes only and is not a substitute for professional medical advice.