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Herb Information
Name: SAMe (S-Adenosylmethionine)
Biological Name: S-Adenosylmethionine
Other Names: S-Adenosylmethionine, SAM, Ademetionine
Parts Used:
Active Compounds: S-adenosylmethionine is derived from two chemicals: methionine, a sulfur-containing amino acid; and adenosine triphosphate (ATP), the body's main energy molecule.

SAMe was discovered in Italy in 1952. It was first investigated as a treatment for depression. It was accidentally noted to improve arthritis symptoms—a kind of positive "side effect." SAMe is presently classed with glucosamine and chondroitin as a potential "chondroprotective" agent, one that can go beyond treating symptoms to actually slowing the progression of arthritis. This has not yet been proven.

SAMe is also sometimes used by Italian physicians in the first weeks of conventional treatment for depression, because it is thought to act more quickly than certain antidepressant drugs.

Remedies For

Principal Uses

· Osteoarthritis, Depression

Other Uses

· Liver Disease, Fibromyalgia

There is growing evidence suggesting that SAMe is an effective treatment for osteoarthritis. However, the supplements glucosamine and chondroitin are much less expensive and just as well documented.

Several small studies also suggest that SAMe can be helpful for depression.

This supplement may be helpful for certain liver conditions such as the jaundice of pregnancy and Gilbert's syndrome.

SAMe may also help fibromyalgia.

New evidence suggests that SAMe might help medications for Parkinson's disease work better and with fewer side effects.

Scientific Evidence of Effectiveness:


Several good scientific evidence supports the use of SAMe to treat osteoarthritis. Double-blind studies involving a total of more than a thousand participants suggest that SAMe is about as effective as standard anti-inflammatory drugs.

A double-blind placebo-controlled Italian study tracked 732 people taking SAMe, naproxen (a standard anti-inflammatory drug), or placebo. After 4 weeks, participants taking SAMe or naproxen showed about the same level of benefit as compared with those in the placebo group.

However, it should be noted that the dosage of naproxen used in this study was definitely on the low side, only 750 mg daily. This is about half the amount most people would use for arthritis. If a normal dosage of naproxen had been used, the therapeutic effect would probably have been greater, and the drug might have proven more effective. Therefore, this study alone does not prove that SAMe is as effective as conventional treatment when taken in proper doses.

Another double-blind study compared SAMe with a full dosage of the anti-inflammatory drug, piroxicam. A total of 45 individuals were followed for 84 days. The two treatments proved equally effective. However, the SAMe-treated individuals maintained their improvement long after the treatment was stopped, whereas those on piroxicam quickly started to hurt again. 

Other studies showed that oral SAMe has equivalent benefits to various doses of indomethacin, ibuprofen, and naproxen.


In the human body, SAM-e works as a methyl donor, which affects more than 30 different chemical reactions, including certain mood-enhancing brain chemicals like seratonin.  The exact mechanism in which SAMe works is not yet know. There are many possible theories on how this may be working. A 1999 article in Newsweek stated, "Whatever the mechanism, there is little question that SAMe can help fight depression."

SAMe's antidepressant activity was first reported in 1976. Since then, several small double-blind studies involving a total of about 175 individuals have found oral SAMe to be an effective treatment for depression. Some of these studies compared SAMe with placebo, while others used a control group given another antidepressant drug. 

In the last two decades, 40 clinical studies have been published with about 1400 patients.  Although the number of patients is small, the results have been consistent.  In 1994, a psychiatrist in Rome compiled results from a dozen controlled trials and concluded that SAM-e's effectiveness in treating depression "is superior [to] that of placebo and comparable to that of standard... antidepressants."

 Some research suggests that SAM-e may work faster than conventional antidepressants, which often take several weeks to become effective.  Researchers from the University of California, Irvine studied eighteen patients hospitalized for depression in 1988. In this study, intravenous SAM-e was compared to oral imipramine (Tofranil), a commonly prescribed antidepressant.  By the end of the second week, 66% of the patients on SAM-e had improved by at least 50%, while improvement was reported by only 22% of the imipramine group.

In another small study at UCI, severely depressed patients were given either SAM-e or desipramine (a pharmaceutical antidepressant) for four-weeks.  The SAM-e recipients showed a slightly higher response rate (62%) compared to those on desipramine (50%).

Studies conducted thus far seem to indicate that SAM-e may be as effective as traditional antidepressants. However, research has revealed fewer side effects, particularly as compared to the older drugs (tricyclics and MAO inhibitors) commonly used before the availability of SSRIs like Prozac and Zoloft.  Reported side effects of SAM-e have included mild stomach upset and headache, although frequently these symptoms go away after a couple of weeks. 

Caution: Those with bipolar disorder (commonly called manic depression) should avoid SAM-e because it can induce mania in people with the disorder.


Few studies have been conducted specifically with Fibromyalgia patients. One study of 47 Fibromyalgia patients demonstrated a significant reduction in tender points.  In this study, patients were treated with daily intramuscular injections of 200mg of SAM-e, in addition to taking 400mg orally.



A typical full dosage of SAMe is 400 mg taken 3 to 4 times per day. Take it for a few weeks and then try reducing the dosage. As little as 200 mg twice daily may be sufficient to keep you feeling better once the full dosage has "broken through" the symptoms.

Some people develop mild stomach distress if they start full dosages of SAMe at once. To get around this, start low and work up to the full dosage gradually.

SAMe appears to be quite safe, based on the results from both human and animal studies. The most common side effect is mild digestive distress. 

Like other substances with antidepressant activity, SAMe might trigger a manic episode in those with bipolar disease (manic-depressive illness).

Safety in young children, pregnant or nursing women, or those with severe liver or kidney disease has not been established.

There may be risks involved in combining SAMe with standard antidepressants. Consult your doctor before combining SAMe with any antidepressant medication.

Drug Interactions

If you are taking:

Standard antidepressants: Do not take SAMe except on a physician's advice.

Medications for manic-depressive disease: Do not take SAMe except on a physician's advice.

Drugs that are "excreted by conjugation": It is possible that use of SAMe may require you to increase your medication dose. Ask your pharmacist for advice.

Levodopa for Parkinson's disease: SAMe might help it work better.

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