MSM

• Joint health
• Anti-inflammatory
• Antioxidant support
• Connective tissue health

• Skin health
• Allergy relief
• Hair and nail strength
• Immune modulation
• Detoxification support
• Exercise recovery

Methylsulfonylmethane (MSM) exerts its biological effects through multiple interconnected mechanisms. As a source of bioavailable sulfur, MSM provides a critical element for maintaining the structural integrity of connective tissues by supporting the formation of disulfide bonds in proteins like collagen and keratin. These bonds are essential for proper tissue structure in joints, skin, hair, and nails. MSM’s anti-inflammatory properties stem from its ability to inhibit nuclear factor kappa B (NF-κB) translocation to the nucleus, thereby reducing the expression of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6).

It also decreases the production of prostaglandin E2 (PGE2) by inhibiting cyclooxygenase-2 (COX-2) expression. Additionally, MSM blocks the migration of leukocytes across endothelial barriers by interfering with cell surface adhesion molecules, reducing inflammatory cell infiltration into tissues. MSM’s antioxidant effects operate both directly and indirectly. It acts as a direct free radical scavenger and enhances the body’s endogenous antioxidant defenses by increasing levels of glutathione and the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase.

This helps neutralize reactive oxygen species (ROS) that contribute to oxidative stress and tissue damage. In cartilage, MSM appears to protect chondrocytes from oxidative damage and may stimulate the production of glycosaminoglycans and other extracellular matrix components, potentially supporting cartilage regeneration. MSM modulates immune function by regulating B and T cell activity and reducing immunoglobulin production in hypersensitivity reactions, which may explain its benefits for allergic conditions. It also enhances cell membrane permeability, potentially improving nutrient absorption and cellular detoxification processes.

In the context of exercise and muscle recovery, MSM reduces exercise-induced oxidative stress and muscle damage, decreasing markers like creatine kinase and lactate dehydrogenase while improving antioxidant capacity. For skin health, MSM influences the expression of genes involved in inflammation, cell differentiation, and extracellular matrix production. It may enhance cross-linking in collagen fibers, improving skin elasticity and reducing signs of aging. MSM also appears to have mild antimicrobial properties and may help regulate the gut microbiome composition, though these mechanisms are less well-established.

At the molecular level, MSM may influence cellular signaling pathways beyond NF-κB, including mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT) proteins, affecting cellular responses to stress and inflammatory stimuli.

Typical dosage ranges from 1,000-6,000 mg (1-6 g) per day, divided into 2-3 doses. Most clinical studies have used doses between 1.5-6 g daily. For general health maintenance, 1,000-3,000 mg daily is commonly recommended.

Methylsulfonylmethane (MSM) is generally well-absorbed in the gastrointestinal tract, with an estimated bioavailability of 70-90% when taken orally. It is rapidly absorbed in the small intestine and distributed throughout the body, with peak plasma concentrations typically occurring within 2-4 hours after ingestion.

Taking with vitamin C may enhance absorption and efficacy due to synergistic antioxidant effects, Consuming with a meal containing some fat may improve absorption, Liposomal formulations can increase bioavailability by protecting MSM from degradation in the digestive tract, Micronized MSM powder provides greater surface area for absorption, Distilled MSM (such as OptiMSM®) offers higher purity and potentially better absorption than synthetic forms, Liquid MSM formulations may be absorbed more rapidly than capsules or tablets, Dividing the daily dose into 2-3 smaller doses throughout the day may maintain more consistent blood levels, Combining with bioperine (black pepper extract) may enhance absorption through inhibition of enzymes that metabolize MSM, Topical application can provide localized effects for joint and skin conditions, bypassing gastrointestinal absorption

MSM is best taken with meals to minimize potential gastrointestinal discomfort and possibly enhance absorption. For joint conditions, dividing the daily dose into 2-3 administrations (morning, afternoon, and evening) may help maintain more consistent blood levels throughout the day. When using MSM for exercise recovery, taking a dose approximately 30-60 minutes before exercise and another dose post-exercise may be beneficial, though research on optimal timing is limited. For sleep-related benefits, some users report taking a portion of their daily dose in the evening.

For allergies, consistent daily dosing is more important than specific timing, though maintaining regular administration throughout the day may provide more consistent symptom relief. When using MSM for skin conditions, both oral supplementation and topical application may be combined for enhanced effects. If gastrointestinal sensitivity occurs, starting with a lower dose and gradually increasing over 1-2 weeks may improve tolerance. MSM does not appear to interact significantly with most medications, but as a general precaution, separating MSM intake from medication administration by 2 hours may be advisable.

• Mild gastrointestinal discomfort (most common)
• Bloating or gas
• Diarrhea (particularly at higher doses)
• Headache (infrequent)
• Fatigue (rare)
• Difficulty sleeping (rare)
• Mild allergic reactions (rare)
• Nausea (typically with doses >6g/day)
• Increased thirst or urination
• Temporary worsening of allergy symptoms (initial reaction in some individuals)

• Known hypersensitivity to MSM or sulfur compounds
• Pregnancy and lactation (due to insufficient safety data)
• Scheduled for surgery within two weeks (theoretical concern due to potential blood-thinning effects)
• Severe liver or kidney disease (use with caution due to limited research)
• Children under 12 years (insufficient safety data)
• Individuals taking high doses of blood-thinning medications (theoretical concern, though clinical significance is unclear)

• Blood thinners (theoretical concern, though clinical evidence of significant interaction is limited)
• NSAID medications (may have additive effects, potentially allowing for reduced NSAID dosage)
• Alcohol (may increase risk of gastrointestinal side effects)
• Chemotherapy drugs (insufficient research; consult oncologist before use during cancer treatment)
• Diabetes medications (MSM may affect blood sugar levels in some individuals)
• Antihypertensive medications (theoretical interaction based on MSM’s potential mild effect on blood pressure)

No official upper limit has been established for MSM. Clinical studies have used doses up to 6,000 mg (6 g) per day for extended periods without serious adverse effects. Some practitioners recommend not exceeding 8,000-10,000 mg daily without medical supervision. Toxicity studies in animals have shown MSM to be extremely safe, with an LD50 (median lethal dose) greater than 17 g/kg body weight in rats, equivalent to over 1,000 g for an average human.

Most side effects are mild and dose-dependent, typically resolving with reduced dosage. Starting with lower doses (e.g., 1,000-2,000 mg daily) and gradually increasing can help minimize gastrointestinal discomfort.

In the United States, methylsulfonylmethane (MSM) is regulated as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA) of 1994. As a dietary supplement, MSM does not require pre-market approval from the FDA, but manufacturers must ensure the product is safe and that any claims made are not misleading. The FDA has not approved any specific health claims for MSM. Manufacturers are limited to making structure/function claims (e.g., ‘supports joint health’) rather than disease claims (e.g., ‘treats arthritis’).

MSM has self-affirmed GRAS (Generally Recognized as Safe) status for certain food applications, though this is not the same as FDA GRAS designation. The FDA requires that supplement labels for MSM include standard supplement facts and appropriate disclaimers. MSM is subject to FDA’s current Good Manufacturing Practices (cGMP) regulations for dietary supplements.

Eu: In the European Union, MSM is regulated as a food supplement under Directive 2002/46/EC. It is legally sold throughout the EU, though regulations regarding claims vary by country. The European Food Safety Authority (EFSA) has not approved any health claims for MSM under the Nutrition and Health Claims Regulation. In some EU countries, MSM may also be classified as a ‘borderline substance’ that could be considered either a food supplement or a medical product depending on presentation and claims. Novel Food authorization is not required for MSM as it has a history of consumption before May 1997.

Canada: Health Canada regulates MSM as a Natural Health Product (NHP). It has been issued a Natural Product Number (NPN) and is approved for use in helping to relieve joint pain associated with osteoarthritis. Health Canada allows specific claims for MSM related to joint health and osteoarthritis when certain conditions are met regarding dosage and formulation. MSM must comply with Canadian quality standards and Good Manufacturing Practices for Natural Health Products.

Australia: The Therapeutic Goods Administration (TGA) regulates MSM as a listed complementary medicine. It is included in the Australian Register of Therapeutic Goods (ARTG) and can be legally sold with appropriate listing. The TGA permits limited claims related to joint health and anti-inflammatory effects when supported by evidence. MSM products must comply with the quality and safety standards established by the TGA.

Japan: In Japan, MSM is regulated as a non-drug food product and can be sold as a food supplement. It is not approved as a Food for Specified Health Uses (FOSHU), which would allow specific health claims. The Japanese Ministry of Health, Labour and Welfare permits its sale with general structure/function claims but not disease-specific claims.

China: The China Food and Drug Administration (CFDA) regulates MSM primarily as a food ingredient/supplement. It is not currently included in the list of approved direct food additives. For use in health food products making specific claims, manufacturers must obtain Health Food Approval from the CFDA, which requires substantial safety and efficacy data.

Low to moderate. MSM is generally one of the more affordable supplements, particularly when compared to other joint health supplements like glucosamine, chondroitin, or collagen.

Generic MSM powder: $0.10-0.30 per day (at 3g daily dose). Standard MSM capsules/tablets: $0.15-0.40 per day (at 3g daily dose). Premium distilled MSM (e.g., OptiMSM®): $0.30-0.60 per day (at 3g daily dose). MSM in combination joint formulas: $0.50-1.00 per day (typically includes other ingredients). Topical MSM creams/lotions: $0.50-2.00 per application, depending on concentration and additional ingredients.

When evaluating the cost-effectiveness of MSM supplementation, several factors should be considered beyond the simple price per gram. For joint health applications, MSM offers good value compared to many alternatives, providing significant benefits at a relatively low cost. Clinical studies showing efficacy for osteoarthritis have typically used doses of 3-6g daily, which remains affordable even with premium forms of MSM. The form and quality of MSM significantly impact both price and value.

Distilled MSM (such as OptiMSM®) commands a premium price but offers higher purity (typically 99.9%) and potentially better results than lower-grade crystallized MSM. For many users, this quality difference justifies the additional cost. Powder forms generally provide the best value in terms of cost per gram, though they require measuring and may have a slightly bitter taste. Capsules and tablets offer convenience but typically cost 20-40% more than equivalent powder.

For those seeking joint health benefits, combination products containing MSM along with glucosamine, chondroitin, or other synergistic ingredients may provide better overall value than MSM alone, despite the higher price point. These formulations leverage the synergistic effects between ingredients, potentially enhancing outcomes. The cost-benefit ratio is particularly favorable for MSM when compared to pharmaceutical anti-inflammatory medications, as MSM typically has fewer side effects and may reduce the need for these medications in some individuals. This could result in significant cost savings over time, especially when considering the potential costs associated with managing side effects from long-term NSAID use.

For athletes and active individuals using MSM for exercise recovery, the relatively low cost compared to many sports supplements makes it an economical addition to a supplement regimen. For skin, hair, and nail applications, the value proposition is less clear, as results are more variable and may take longer to manifest. However, given the moderate cost, many users find the potential benefits worth the investment. Finally, considering the multiple potential benefits of MSM across different body systems (joints, skin, allergies, etc.), the overall value may be greater than what’s apparent when focusing on a single application.

Pure methylsulfonylmethane (MSM) is remarkably stable, with a typical shelf life of 3-5 years when properly stored in its crystalline form. Capsules, tablets, and other formulations generally have a shelf life of 2-3 years, depending on additional ingredients and packaging. Liquid formulations typically have a shorter shelf life of 1-2 years once opened.

Store in a cool, dry place away from direct sunlight and excessive heat. While refrigeration is not necessary for crystalline MSM or capsules, it may extend shelf life. Keep containers tightly sealed to prevent moisture absorption, as MSM is somewhat hygroscopic (attracts water). MSM is stable under normal storage conditions and does not require special handling.

For liquid formulations, refrigeration after opening may help maintain freshness and prevent microbial growth. Avoid storing near strong-smelling substances, as MSM may absorb odors over time. MSM is generally stable through temperature fluctuations, but consistent storage conditions are ideal for maximum shelf life.

Prolonged exposure to high humidity (may cause clumping due to MSM’s hygroscopic nature), Extreme heat (temperatures consistently above 40°C/104°F may accelerate degradation), Contamination with metals or other catalytic impurities, Microbial contamination (particularly in liquid formulations), Exposure to strong oxidizing agents, Prolonged exposure to direct sunlight (UV radiation), Chemical reactions with certain additives in formulations, Improper sealing allowing moisture ingress, Exposure to strong acids or bases (can accelerate decomposition)

Synthesis Methods

Natural Sources

Quality Considerations

Unlike many traditional supplements with centuries of historical use, methylsulfonylmethane (MSM) has a relatively short history as a dietary supplement. MSM was first identified as a natural compound in the 1800s, but its potential health benefits weren’t explored until much later. The modern history of MSM as a therapeutic agent begins with its chemical precursor, dimethyl sulfoxide (DMSO). In the 1960s, Dr.

Stanley Jacob at the University of Oregon Medical School began researching DMSO for its potential medical applications, particularly for inflammation and pain relief. DMSO gained popularity for its apparent therapeutic effects but faced regulatory challenges due to safety concerns. Researchers subsequently discovered that DMSO naturally converts to MSM in the body and that MSM shares some of DMSO’s beneficial properties with fewer side effects. By the 1980s, scientists had identified MSM as a natural component of many foods and the human body, though in very small amounts.

Dr. Jacob, along with Dr. Robert Herschler, began investigating MSM specifically in the early 1980s. They found that while DMSO had a distinctive odor and potential side effects, MSM was odorless and appeared to have a superior safety profile while retaining many of the beneficial properties.

Their early research suggested potential benefits for pain, inflammation, allergies, and detoxification. The first patents related to MSM’s therapeutic use were filed in the early 1980s, and small-scale production of MSM as a dietary supplement began around this time. However, MSM remained relatively obscure until the 1990s, when it began gaining popularity in alternative health circles. The publication of the book ‘The Miracle of MSM: The Natural Solution for Pain’ by Dr.

Stanley Jacob, Dr. Ronald Lawrence, and Martin Zucker in 1999 significantly increased public awareness of MSM. This book, along with growing interest in natural approaches to joint health, helped establish MSM as a popular supplement for arthritis and other inflammatory conditions. Commercial production expanded significantly in the late 1990s and early 2000s as manufacturing processes improved and consumer demand increased.

The development of distilled MSM (such as OptiMSM®) in the early 2000s provided a higher-purity option that further enhanced MSM’s reputation and adoption. Scientific research on MSM has accelerated since the early 2000s, with numerous clinical trials investigating its effects on osteoarthritis, exercise recovery, allergies, and other conditions. Today, MSM is widely available as a dietary supplement in various forms and is often included in joint health formulations, often alongside glucosamine and chondroitin. It has evolved from an obscure sulfur compound to a mainstream supplement with a growing body of scientific evidence supporting specific applications.

Butawan M, Benjamin RL, Bloomer RJ. Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients. 2017;9(3):290., 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. 2011;2011:528403., Ahn H, Kim J, Lee MJ, Kim YJ, Cho YW, Lee GS. Methylsulfonylmethane inhibits NLRP3 inflammasome activation. Cytokine. 2015;71(2):223-231., Ezaki J, Hashimoto M, Hosokawa Y, Ishimi Y. Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model. J Bone Miner Metab. 2013;31(1):16-25., Lubis AMT, Siagian C, Wonggokusuma E, Marsetyo AF, Setyohadi B. Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial. Acta Med Indones. 2017;49(2):105-111.

Effects of MSM on Biomarkers of Oxidative Stress and Inflammation in Healthy Adults, Methylsulfonylmethane for Treatment of Knee Osteoarthritis: A Multi-Center Trial, Efficacy of MSM in Combination with Glucosamine and Chondroitin for Joint Health, MSM Supplementation for Exercise-Induced Muscle Damage in Athletes, Topical MSM for Inflammatory Skin Conditions: A Randomized Controlled Trial