What is SAM-e and How does it work?

SAM-e is a stable, bio-available form of S-Adenosyl-Methionine.  S-Adenosyl-Methionine was first discovered in 1953 by an Italian researcher named G. L. Cantoni. It is formed in the body from amino acid methionine and adenosine triphosphate (ATP) in a reaction catalyzed by methionine adenosyl-transferase. The supplement SAMe is a synthetic form of a compound formed naturally in the body, the energy-producing compound found in all cells in the body. SAMe is believed to work by being a methyl group donor in many reactions in the body.

Why Do People Use SAMe

Depression

How, exactly, might taking extra SAMe improve a person's mood? Researchers have identified several possibilities. Normal brain function involves the passage of chemical messengers between cells. SAMe may enhance the impact of mood-boosting messengers such as serotonin and dopamine—either by regulating their breakdown or by speeding production of the receptor molecules they latch on to. SAMe may also make existing receptors more responsive. These molecules float in the outer membranes of brain cells like swimmers treading water in a pool. If the membranes get thick and glutinous, due to age or other assaults, the receptors lose their ability to move and change in response to chemical signals. By methylating fats called phospholipids, SAMe keeps the membranes fluid and the receptors mobile.

 Whatever the mechanism, there is little question that SAMe can help fight depression. Since the 1970s, researchers have published 40 clinical studies involving roughly 1,400 patients. And though the studies are small by FDA standards, the findings are remarkably consistent. In 1994 Dr. Giorgio Bressa, a psychiatrist at the University Cattolica Sacro Cuore in Rome, pooled results from a dozen controlled trials and found that "the efficacy of SAMe in treating depressive syndromes... is superior to that of a placebo and comparable to that of standard antidepressants."

 This isn't the first natural substance to show promise as a mood booster. Small studies suggest that St. John's wort can ease low-grade melancholy, but SAMe has been tested against far more serious disorders. In one of several small U.S. studies, researchers at the University of California, Irvine, gave 17 severely depressed patients a four-week course of SAMe (1,600 mg daily) or desipramine, a well-established antidepressant. The SAMe recipients enjoyed a slightly higher response rate (62 percent) than the folks on desipramine (50 percent).

Osteoarthritis

There have been a number of studies on the effectiveness of SAMe in the treatment of osteoarthritis. SAMe appears to diminish osteoarthritis pain as effectively as non-steroidal anti-inflammatory medication. It appears to be well-tolerated.

In dozens of European trials involving thousands of patients, it has performed as well as traditional treatments for arthritis and major depression. Research suggests it can also ease normally intractable liver conditions. SAMe doesn't seem to cause adverse effects, even at high doses. And doctors have prescribed it successfully for two decades in the 14 countries where it has been approved as a drug.

If the world needs a better antidepressant, it could also use a better arthritis remedy. Nearly a third of the 40 million Americans with chronic joint pain use drugs like aspirin and ibuprofen. In arthritis-strength doses, these so-called NSAIDs, or nonsteroidal anti-inflammatory drugs, can have devastating gastric side effects. Some 103,000 Americans are hospitalized annually for NSAID- induced ulcers, and 16,500 die. Even when NSAIDs don't destroy the digestive tract, they may ultimately worsen people's joint problems, for they slow the production of collagen and proteoglycans, the tissues that make cartilage an effective shock absorber.

Could SAMe provide an alternative? In a dozen clinical trials involving more than 22,000 patients, researchers have found SAMe as effective as pharmaceutical treatments for pain and inflammation. But unlike the NSAIDs, SAMe shows no sign of damaging the digestive tract. And instead of speeding the breakdown of cartilage, SAMe may help restore it. You'll recall that after giving up its methyl group, SAMe becomes homocysteine, which can be broken down to form glutathione (the antioxidant) or remethylated to form methionine (the precursor to SAMe). As luck would have it, the reactions that produce glutathione also yield molecules called sulfate groups, which help generate those joint-sparing proteoglycans.

What does this mean for patients? The Arthritis Foundation, a mainstream advocacy group, recently said its medical experts were satisfied that SAMe "provides pain relief" but not that it "contributes to joint health." The evidence that SAMe can repair cartilage is admittedly preliminary, but it's intriguing. When German researchers gave 21 patients either SAMe or a placebo for three months, using MRI scans to monitor the cartilage in their hands, the SAMe recipients showed measurable improvements.

Liver disease

Some evidence suggests that SAMe may help people with liver disease. Preliminary research suggests it may help to normalize liver enzyme levels and help with cholestasis (blockage of the bile ducts). SAMe may have other benefits as well. SAMe has also been found to prevent or reverse liver damage caused by certain drugs.

Other Uses for SAMe

SAMe is also used for psychiatric illnesses, infertility, premenstrual disorders and musculoskeletal disorders, among others. Some evidence is available for the use of SAMe for intrahepatic cholestasis of pregnancy although additional study is needed in this area. Anti-inflammatory and analgesic (pain relieving) activity has also been attributed to SAMe.