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S-adenosylmethionine is a nutritional supplement that has its origins in Europe. Experience there with conditions such as osteoarthritis, fibromyalgia, and even depression demonstrated encouraging results plus a surprisingly lack of significant side-effects. People particularly like SAM-e supplements because they don't have the gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) or the sexual dysfunction, dry mouth and nausea associated with antidepressant drugs.

It takes about a week for SAM-e to start working, which is slower than NSAIDs but about twice as fast as most antidepressant drugs.

So far, SAM-e has shown few signs of drug interaction so it can be taken along with most, if not all, prescription drugs

European physicians have been studying and using SAM-e for more than two decades as a treatment for both osteoarthritis as well as depression. There are numerous European studies, including controlled clinical trials demonstrating it relieves osteoarthritis pain as well as NSAIDs.

SAM-e is a compound that occurs naturally in living cells, and is an integral ingredient in a process called methylation that is involved in more than 100 complex biochemical reactions in the human body.

SAM-e contributes to the building blocks for cartilage, and aids in making glutathione, which the liver uses to remove toxins such as alcohol.

Human beings usually make all the SAM-e they need. But the level of SAM-e decreases as people age, and levels are low in those who are depressed, or who have deficiencies of B vitamins or methionine. Good dietary habits and B vitamin supplementation are helpful but they may not be enough if a person's SAM-e levels are low.

SAM-e supplements can raise levels of this compound. And while scientists don't know for certain how taking SAM-e supplements works, it does relieve OA pain and some fibromyalgia symptoms.

A number of European clinical trials have shown SAM-e performs as well as NSAIDs in terms of pain relief for osteoarthritis.

In one U.S. study of SAM-e for osteoarthritis, it appeared only to work for those with mild OA. Two groups of men were given SAM-e for about a month, first in daily injections and then 600 milligrams (mg) per day in pills.

Those with milder OA showed significantly less overall pain than the group taking a placebo as early as two weeks into the study. However, a group that was made up of older men with more severe OA did not benefit from SAM-e, says John Bradley, MD, of the University of Indiana, lead author on the 1994 study.

"For milder osteoarthritis symptoms, it may be useful, but it needs more study," Dr. Bradley says.

Roland W. Moskowitz, MD, of University Hospitals in Cleveland, Ohio adds, " There's no solid scientific evidence to show SAM-e modifies joint disease."

A number of doctors are suggesting SAM-e to their patients with fibromyalgia, because tricyclic antidepressant drugs in small doses are often used to ease fibromyalgia symptoms. In full therapeutic doses they can also help relieve the depression that frequently accompanies chronic fibromyalgia.

There are mixed results in studies of SAM-e for fibromyalgia. In one small European study of fibromyalgia and SAM-e, 200-mg daily injections reduced the number of tender points and improved mood in patients with fibromyalgia. In another, those taking 800 mg of SAM-e in pill form had less pain, fatigue and morning stiffness than patients taking placebo, but no effect on tender points. A third study showed no benefit.

Mixed opinions from physicians also exist. Some find SAM-e very effective while others don't believe it's all that useful for fibromyalgia.

What are the potential drawbacks? Although it has been used for 20 years, there are no controlled, long-term studies to show what effects might occur in people who take SAM-e for years, as they would for either osteoarthritis or fibromyalgia.

Few rheumatologists know enough about SAM-e or its research to be able to give advice to patients. And the most effective dosage isn't known: Dosages ranging between 200 and 1,600 mg per day of SAM-e were used in studies.

SAM-e is certainly not a cure: You have to take it chronically to get the effects, and it's not cheap; SAM-e costs approximately $60 to $230 per month, depending on the amount taken. It is not covered by insurance.

And, as with all supplements, lack of regulatory supervision means that there is no guarantee that consumers are getting active ingredients in the products they buy.

However, most physicians agree SAM-e is safe for short term usage.

If you decide you would like to try SAM-e for OA or fibromyalgia, here are some tips:

• Remember to tell your physician you are going to try SAM-e, especially if you are taking prescription drugs.

• Don't stop any prescribed drugs without checking with your doctor: It can be harmful to stop some medications abruptly.

• Try to choose a stabilized product. Look for SAM-e butanedisulfonate on the label. SAM-e loses potency easily, so it has to be carefully packaged in airtight, light-proof containers. Also, tablets should be coated to dissolve in your intestines, not your stomach, or you'll not get the proper absorption.

• Do not take more than 1,600 mg per day of SAM-e. For OA pain, some doctors suggest starting with 800 mg per day, taken in two doses. If you see an improvement in pain or mood symptoms in two weeks, reduce the dosage to 400 mg. But if you don't see any change, you may want to increase the dosage and try for another two weeks.

• Consider taking B vitamins ' 800 mg of folic acid and 1,000 mg of B12 a day ' along with SAM-e, because these vitamins help your body utilize SAM-e.

• See a doctor about side effects you experience. He or she may advise you to stop taking SAM-e or lower your dosage. Side effects are rare, but some people may get a rash or nausea. Nausea may be eased by taking SAM-e with food.

• Keep up your regular routine of exercise, and maintain a healthy weight to ease pressure on your joints.