Methylsulfonylmethane - Gnc Detox Drink

Methylsulfonylmethane (MSM) is an organosulfur compound with the formula (CH₃)₂SO₂. It is also known by several other names including DMSO₂, methyl sulfone, and dimethyl sulfone. This colorless solid features the sulfonyl functional group and is considered relatively inert chemically. It occurs naturally in some primitive plants, is present in small amounts in many foods and beverages, and is marketed as a dietary supplement. It is also commonly found in the atmosphere above marine areas, where it is used as a carbon source by the airborne bacteria Afipia, and is found distinctively in human melanoma cells.

Structure and chemical properties

MSM and the corresponding sulfoxide dimethyl sulfoxide ((CH₃)₂SO, DMSO) have different physical properties. MSM is a white crystalline solid at STP (m.p. = 109 °C) whereas DMSO is a liquid under standard conditions. The sulfoxide is a highly polar aprotic solvent and is miscible with water; it is also an excellent ligand. MSM is less reactive than DMSO because the S-atom of the sulfone is already in its highest oxidation state (VI). Indeed, oxidation of the sulfoxide produces the sulfone, both under laboratory conditions and metabolically.

Use as a solvent

Because of its polarity and thermal stability, MSM is used industrially as a high-temperature solvent for both inorganic and organic substances. It is used as a medium in organic synthesis. For example, displacement of aryl chlorides by potassium fluoride can be usefully conducted in molten MSM. With a pK_a of 31, it can be deprotonated with sodium amide, and the conjugate base is an effective nucleophile.

Pharmacology and toxicity

The LD₅₀ of MSM is greater than 17.5 grams per kilogram of body weight. In rats, no adverse events were observed after daily doses of 2 g MSM per kg of body weight. In a 90-day follow-up study, rats received daily MSM doses of 1.5 g/kg, and no changes were observed in terms of symptoms, blood chemistry or gross pathology.

Nuclear magnetic resonance (NMR) studies have demonstrated that oral doses of MSM are absorbed into the blood and cross the blood/brain barrier. An NMR study has also found detectable levels of MSM normally present in the blood and cerebrospinal fluid, suggesting that it derives from dietary sources, intestinal bacterial metabolism, and the body's endogenous methanethiol metabolism.

Published clinical trials of MSM did not report any serious side effects, but there are no peer-reviewed data on the effects of its long-term use in humans.

Medical and dietary use

Although no medical uses for MSM have been approved by any government, a variety of health benefits have been claimed and studied. Stanley W. Jacob reported having administered MSM to over 18,000 patients with a variety of ailments; he co-authored a book promoting MSM with a variety of claims, including a utility as a natural source of "biologically active sulfur," suggesting that people are deficient in such forms of sulfur in their dietary intake. There is no Dietary Reference Intake (DRI) or Daily Value established for sulfur and sufficient dietary sources are readily available in onions, garlic and cruciferous vegetables and in protein-containing foods, including nuts, seeds, milk and eggs (whites and yolks).

The claims for the need for sulfur supplementation originate with Robert Herschler, a biochemist who patented "Dietary and pharmaceutical uses of methylsulfonylmethane and compositions comprising it" in 1982; he claimed that MSM was useful in stress, mucous-membrane inflammation, allergies and gastrointestinal conditions.

MSM is sold as a dietary supplement and marketed with a variety of claims, often in combination with glucosamine and/or chondroitin for helping to treat or prevent osteoarthritis. According to one review, "The benefits claimed [for MSM] far exceed the number of scientific studies. It is hard to build a strong case for its use other than for treating arthritis problems."

Moreover, in cases involving topical therapeutics, the role of MSM as an active agent, per se, versus its having a role in promoting skin permeation (in manner, akin to its solvent relative DMSO) must be characterized/controlled. The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has anti-inflammatory effects. The spectrum of biological effects of dimethyl sulfoxide (DMSO) and MSM differ, but those of DMSO may be mediated, at least in part, by MSM.

Herschler's patent documents, and much of the alternative medical literature supporting MSM use, claim that "the average diet is deficient in methylsulfonylmethane because it is readily lost during conventional food processing, such as frying, dehydrating, dilution with synthetic fillers and other poorly nutritional additives, cooking, radiation or pasteurizing, and long-term storage".

FDA action

In 2008 Bergstrom Nutrition, a U.S. manufacturer of MSM, submitted a notification to the FDA claiming generally recognized as safe (GRAS) status. The FDA responded with a letter of non-objection, functionally designating OptiMSM, the branded form of MSM manufactured by Bergstrom Nutrition, as GRAS. The designation allows MSM to be added to meal supplement and meal replacement foods, fruit smoothie-type drinks, fruit-flavored thirst quencher-type beverages, and food bars such as granola bars and energy-type bars.

Evidence from clinical trials

Small-scale studies of possible treatments with MSM have been conducted on both animals and humans. These studies of MSM have suggested some benefits, particularly for treatment of oxidative stress and osteoarthritis, but evidence for other uses is lacking. Natural Medicines Comprehensive Database contains a continually updated list of health-related MSM studies.

Safety

Extensive research in animal models indicates MSM has a very low toxicity when administered both orally and topically. In clinical trials, several studies reported minimal or absence of side effects after 12 weeks of dosing. Reported side effects from these studies included mild gastrointestinal issues, fatigue, and headache, although they did not appear to differ from placebo. A more recent 26 week study on large joint osteoarthritis observed no adverse events or abnormal changes in lab monitoring when taking 6 grams MSM per day. MSM is considered 'Possibly Safe' at therapeutic doses, although further research is still needed to assess its safety for long-term use.

Osteoarthritis

A review by Brien et al of two small randomized controlled trials of methylsulfonylmethane in osteoarthritis knee pain relief "reported significant improvement in pain outcomes in the treatment group compared to comparator treatments; however, methodological issues and concerns over optimal dosage and treatment period were highlighted." The two trials included 168 people, of whom 52 received MSM. The review authors state: "No definitive conclusion can currently be drawn" and there is "no definitive evidence that MSM is superior to placebo in the treatment of mild to moderate osteoarthritis of the knee.

After several reports that MSM helped arthritis in animal models, one study by P.R. Usha et al. had suggested that 1.5 g per day MSM (alone or in combination with glucosamine sulfate) was helpful in relieving symptoms of knee osteoarthritis.

Kim et al. conducted a second clinical trial of MSM for treatment of patients with osteoarthritis of the knee. Twenty-five patients took 6 g/day MSM and 25 patients took a placebo for 12 weeks. Ten patients did not complete the study, and intention to treat analysis was performed. Patients who took MSM reported reduced pain and improved physical function, but no evidence was found of a more general anti-inflammatory effect; there were no significant changes in two measures of systemic inflammation: C-reactive protein level and erythrocyte sedimentation rate.

Debbi et al. conducted a double-blind, randomized controlled trial with 49 participants taking 1.125 g of MSM or placebo three times daily for 12 weeks. The results showed a significant decrease in WOMAC physical function and total WOMAC scores, as well as improvement in VAS pain scores. The effect size of MSM supplementation was slightly lower than that of NSAID use, and its clinical significance needs to be better determined. The authors note however, that "longer-term trials may yield additional and greater improvements", and "the relative safety of MSM, especially when compared to serious risks associated with current OA drugs, makes it a compelling supplement for further research to determine long-term effects, safety, and dosage."

Pagonis et al. built on previous studies by expanding the number of study participants to 100, and lengthening the intervention to 26 weeks. In this randomized-controlled trial, participants took 6 g of MSM or placebo per day for 26 weeks, and were evaluated through the WOMAC questionnaire, SF-36 Quality of Life survey, and Global Assessments for OA symptoms from both patients and physicians. WOMAC results showed significant improvements in all areas for the MSM group. The MSM group also showed a strong trend towards changes in disease status. Careful lab monitoring of health indicators showed no side effects of MSM supplementation and no adverse events were reported.

Oxidative stress and inflammation

Multiple human and animal trials indicate MSM may reduce oxidative stress and inflammation, although it is not a direct antioxidant. In human studies, MSM has been shown to protect muscles from damage by reducing the amount of oxidative stress damage incurred through exercise. The total antioxidant capacity was significantly increased after taking MSM. Studies in animals indicate a hepatoprotective effect of MSM against several toxins including acetaminophen, paraquat, and carbon tetrachloride. Animal models of experimental colitis and pulmonary hypertension indicate a protective effect as well.

Other conditions

Barrager et al. evaluated the efficacy of MSM for hay fever. Fifty-five subjects consumed 2.6 g of MSM per day for 30 days. This study was not blinded and did not include controls; while an improvement in symptoms was observed compared to initial baseline, no significant changes were observed in two indicators of inflammation (C-reactive protein and immunoglobulin E levels).

Blum & Blum also conducted a double-blind, placebo-controlled clinical trial of an MSM-containing throat spray to reduce snoring.

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