After James Coburn won an Oscar for Best Supporting Actor this year, he credited the supplement MSM for helping him overcome the pain and disability of rheumatoid arthritis. MSM, he said in many interviews, made it possible for him to work.

MSM (which stands for methylsulfonylmethane), was already selling briskly, and with added publicity from Coburn, sales have boomed. Hundreds of vendors market it for a range of ailments including pain and/or inflammation from rheumatoid arthritis (RA), osteoarthritis (OA), fibromyalgia and gout; and to correct constipation, relieve allergies, control stomach acidity and - believe it or not - stop snoring.

However, there’s not much on which to base these claims: There are numerous testimonials, but little hard scientific data on MSM’s safety or benefits. “How can we say if it’s safe or not - much less, if it works?” asks David Pisetsky, MD, chief of rheumatology at Duke University Medical Center and an arthritis researcher. “We just don’t know enough about it.”

Stanley Jacob, MD, the doctor who developed MSM, acknowledges that the “arthritis cure” claims are over-hyped. While Dr. Jacob stands by the many benefits of MSM, he is quick to point out that it’s not a “cure.”

“I don’t know of a single disease that MSM cures. We are not curing arthritis - I want that understood,” says Dr. Jacob. He says MSM’s major benefit for those with OA and RA is pain relief: It hasn’t been shown to repair or preserve cartilage or to modify or stop progression or joint destruction caused by autoimmune types of arthritis, and its effects last only as long as the supplement is taken.

Some rheumatologists are suspicious of MSM because of its relationship to DMSO - a substance that has stirred controversy since the 1960s. MSM is a sulfur compound plentiful in fresh fruits and vegetables, milk, fish and grains, but quickly destroyed when foods are processed. Vendors say MSM boosts sulfur levels; they also say it is a “natural” product, but the supplement being sold is actually a chemical compound made from DMSO.

What’s the real story on MSM? We had to look at the history of DMSO to find some answers.

The Mother Compound
DMSO (which stands for dimethyl sulfoxide) is a versatile compound with many uses and a checkered past.

It is both a prescription drug and an industrial solvent. It’s formed as a byproduct of wood pulp processing; its use is determined by the quality: You will find industrial-grade DMSO in paint thinner and antifreeze, and medical-grade DMSO in many medical laboratories. Its industrial usefulness comes from its remarkable solvent qualities, and much of its medical value from its ability to transport other substances through cell membranes. It is also reported to have anti-inflammatory and antioxidant properties.

Medical-grade DMSO is safe, and is widely used in medical processes. DMSO is the chemical used to protect human tissue (such as bone marrow, stem cells and embryos) when frozen for storage. It’s also an FDA-approved prescription drug (called Rimso) given by catheter for interstitial cystitis, a painful bladder condition.

Dr. Jacob says thousands of scientific papers have been published about DMSO’s chemistry, including test tube, animal and human studies. Some have shown DMSO can relieve muscle and joint pain; reduce inflammation; soften collagen to relieve scleroderma symptoms; help heal skin ulcers caused by diabetes and scleroderma; and relieve blood vessel constrictions common to Raynaud’s phenomenon. Other research has suggested it may help prevent brain damage after stroke or head injuries. And it appears to have few side effects, even at very high dosages.

DMSO is approved for use in many other countries for arthritis and related conditions. In fact, a new drug, combining DMSO with the nonsteroidal anti-inflammatory drug (NSAID) diclofenac is being considered by the FDA for approval as a prescription topical NSAID (see “A Stronger Topical NSAID”).

So why the controversy?

DMSO: Why the Controversy?
The controversial history of DMSO begins with Dr. Jacob, a Harvard-trained surgeon with an endowed chair at Oregon Health Sciences University (OHSU), where he has a special clinic for the use of DMSO.

In the early 1960s, Dr. Jacob headed the organ transplant program at OHSU and was looking for a substance to preserve organs being stored for transplant when he stumbled across DMSO. Further research uncovered DMSO’s medical uses, and it was soon being hailed as a wonder drug.

But in the mid-’60s, DMSO fell out of favor with the FDA during its testing phase when an animal study, using high doses, showed changes in the lens of the eye. (There have, however, been no reports of problems with eyes of participants in human studies.)

DMSO’s ability as a solvent to transport molecules across cell membranes was also a potential problem. It meant that when used topically DMSO could carry anything - including toxins - straight through the skin and directly into the body.

DMSO also has a harmless but unpleasant side effect: Taken internally or even used externally, it causes a bad taste in the mouth and makes those who use it smell like garlic or oysters.

And so medical-grade DMSO faded from the consumer marketplace. Its reputation was further sullied as reports of bad reactions from arthritis patients who had used industrial-grade products bought at roadside stands or gas stations came to light.

Nonetheless, DMSO was approved in 1978 as the prescription drug Rimso for interstitial cystitis. Because medical-grade DMSO is an approved prescription drug (although only for one use), it can’t legally be sold over the counter or as a dietary supplement. Therefore, most of the DMSO people have been trying for the past 30 years has been the same quality used in industrial solvents - in other words, unfit for human use - and doctors have been rightly suspicious of these products.

Enter MSM
Meanwhile, as Dr. Jacob and other researchers at OHSU continued to study DMSO, they found that 15 percent of DMSO was broken down into another sulfur compound in the human body. The compound, which they called MSM, had many of the helpful qualities of DMSO, with some distinct advantages: It lacked the distinctive oyster-garlic smell; it didn’t have the sullied history of DMSO; and it could be sold directly to consumers as a dietary supplement.

But it also lacked research: Unlike DMSO, which has many published studies and evidence of safety, there was little scientific evidence for or against MSM. Animal studies found MSM eased RA-like symptoms in mice, and it prolonged life for mice with a condition similar to lupus nephritis.

But even now, there are no scientifically accepted human studies, and what works in animals doesn’t always work in humans. Dr. Jacob and others have conducted human studies that they say show MSM relieves the pain of OA and other conditions. However, these studies are not published in peer-reviewed medical journals, and there is a potential conflict of interest: Dr. Jacob also serves as medical director for a company that produces and sells MSM.

Dr. Jacob contends MSM does not need research because the DMSO studies can be applied to this breakdown product. He also says MSM is safe, citing animal toxicology studies from manufacturers.

What Rheumatologists Say
The rheumatologists we interviewed consider MSM an unproven remedy. So far, MSM shows most promise as a pain reliever. As for DMSO, rheumatologists don’t know much about the scientific evidence and were skeptical, and patients said they don’t like the oyster-garlic smell.

A handful of rheumatologists are cautiously recommending MSM. Kenneth Nyman, MD, a rheumatologist and internal medicine specialist in Tarzana, Calif., recommends MSM for OA and for pain, but not as a substitute for prescription arthritis drugs. “My patients with aggressive RA need aggressive treatment with proven disease-modifying drugs,” he says. “I use MSM in conjunction with those drugs.” (Dr. Nyman has no financial involvement in MSM.)

But some physicians are concerned that MSM may interfere with other drugs and cause complications. “MSM is a real mystery,” says Ronenn Roubenoff, MD, a rheumatologist and nutritional expert at Tufts University/ New England Medical School. Sulfur compounds, like those in MSM, are “very active in the body and can have powerful effects,” he says. “We really don’t know what the effects will be over time,” he says.

“MSM is worth clinical trials,” says Dr. Roubenoff. “We need to keep an open mind, and not just reject things out of hand. But we also shouldn’t give up the scientific method just because there is a lot of hype about a product. It needs to be tested.”

Bottom line: MSM may be safe, but there is no convincing scientific evidence it helps arthritis. And DMSO may help with a number of arthritis-related conditions, but it is not safe for consumers to use products available on the open market.

Good Advice: MSM and DMSO
DMSO and MSM are both taken several ways: orally; applied externally as lotions or gels; given intravenously and injected.

• If you decide to experiment with these substances, be sure to tell your doctor and ask your doctor to monitor you for any adverse effects with regular blood, kidney and liver function tests.
• Don’t stop taking disease-modifying medication if you have RA or another autoimmune disease.
• Consult your doctor if you are taking heparin or other blood-thinners, including herbs and aspirin, because both substances may have some blood thinning effects.

Good Advice: MSM

• Buy MSM only from an established company that you can be sure will stand by its products - and be wary of companies making “miracle” and other hyped claims.
• Start with a low dosage of 500 milligrams (mg) or less twice a day and gradually increase the amount until you notice some effect. Most sources suggest 1,000 mg (1 gram) twice a day. MSM is most often taken in capsules or dissolved in a liquid.
• Be patient. But if you don’t see any difference after two months, you may never - and it may not be worth continuing to expose yourself to unknown risks.
• Tell your doctor if you get diarrhea, stomach upsets or mild cramps; these side effects are common, especially at higher doses. Lowering the dose may stop these symptoms.

Good Advice: DMSO

• Don’t buy DMSO on your own: Ask your doctor to find a medical-grade source. Almost all DMSO available to the public is industrial grade - including most veterinary DMSO and products sold in health food stores and on the Internet - and may not be safe for medical use.
• Do not try DMSO without a doctor’s help. It’s a powerful transdermal agent, which means it can carry anything that touches it through your skin and into your body.
• If you have a reaction, stop using the product and see your doctor. Some people may have an allergic reaction, skin irritation or itching from DMSO applied externally.
• Be aware DMSO has been known to cause bad breath or a bad taste in the mouth (like garlic or oysters) among those who use it, whether it’s taken orally or applied to the skin.

Judith Horstman, author of The Arthritis Foundation’s Guide to Alternative Therapies (Arthritis Foundation, 1999), is a contributing editor to Arthritis Today. She writes regularly about alternative and complementary therapies.

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A Stronger Topical NSAID?

Why not get the pain medicine right to the joint that hurts - and avoid unwanted systemic side effects from pills? Soon, there may be a drug available in the United States to do just that.

A Canadian company has applied for FDA approval for what would be the first prescription topical NSAID to be marketed in the United States.

Called Pennsaid (for penetrating NSAID), the drug uses the penetrating properties of DMSO as a vehicle to carry the prescription nonsteroidal anti-inflammatory drug (NSAID) diclofenac through the skin to joint, says Peter Block, corporate communications director for Dimethaid, the Ontario-based company seeking to market the drug.

(Over-the-counter salicylate, or aspirin-like, creams are already available. Dimethaid says this prescription drug uses a stronger NSAID, and that the DMSO will make it penetrate deeper.)