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 S-Adenosyl-methionine (SAMe) 
The following is one in an ongoing series of columns entitled Natural Medicine Research by . View all columns in series
Ray Sahelian It seems that every year several new supplements are introduced to the over the counter market. It becomes difficult to separate the ones that are effective from those that do no live up to their promise. A relatively new supplement is S-adenosyl-methionine, known simply as SAMe. SAMe, a compound made from the amino acid methionine, has been available by prescription in Europe for many years but has been available over the counter in the US only since about 1996. Dr. Ascanio Polimeni, a physician in Rome, Italy, says, "SAMe is a wonderful supplement. Some doctors prescribe it in Europe as therapy for depression, chronic fatigue syndrome, arthritis, and fibromyalgia."

Studies have shown that SAMe influences the formation of brain chemicals and helping the preservation of glutathione, an important antioxidant. Furthermore, SAMe is involved in the formation of myelin, the white sheath that surrounds nerve cells. Most individuals who take SAMe notice an increase in concentration, energy, alertness, and wellbeing.

SAMe is one of those versatile nutrients that plays a role in a number of clinical conditions. Dr. Bottiglieri, from Baylor Research Institute, in Dallas, Texas, says, "SAMe is required in numerous methylation reactions involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The synthesis of SAMe is intimately linked with folate and vitamin B12 metabolism, and deficiencies of both these vitamins have been found to reduce central nervous system SAMe concentrations. Both folate and vitamin B12 deficiency may cause similar neurological and psychiatric disturbances including depression, dementia, and peripheral neuropathy." The influence of SAM on depression has been tested in numerous studies. One, in particular, was done in the Unites States. Back in 1994, researchers at the University of California, Irvine Medical Center, did a double-blind randomized trial involving a total of twenty-six patients. They compared oral SAM with oral desipramine (a pharmaceutical antidepressant). At the end of the four-week trial, 62 percent of the patients treated with SAMe and 50 percent of the patients treated with desipramine had significantly improved.

A major drawback to the use of SAM is that it is a difficult-to-produce natural substance with high manufacturing and packaging costs. The retail price of SAM is close to a dollar per 200 mg pill. The suggested dose of SAM in the therapy of depression ranges from 100 to 400 mg a day. There are other nutrients that work is a similar fashion to SAMe, particularly dimethylglycine, trimethylglycine, and some of the B vitamins. In fact, B12 and folate help the body produce SAMe.

Caution and side effects
SAM has been available in Europe by prescription for many years. Dr. Ascanio Polimeni, M.D., has extensive clinical experience with this nutrient. He says, "SAMe is a wonderful supplement. I have not found it to have any toxic effects even when it's used for many months or years although high dosages, such as 400 mg or more, can cause dry mouth, nausea, restlessness, and insomnia."

SAM has a good potential in becoming a useful therapeutic agent for depression and possibly age related cognitive decline. Long-term studies are needed with SAMe before making widespread recommendations for its use. However, short-term studies thus far on humans have found it to be safe and effective.

For the initial therapy of depression, my first choice is still St. John's wort. However, some physicians are now incorporating the addition of 200 mg of SAMe to the daily regimen of patients with depression if St. John's wort, by itself, is not effective.

There are several nutrients that have a similar function to SAMe, including betaine (also known as trimethylglycine, TMG) and some of the B vitamins such as B6, folic acid, and B12. Those who take TMG, B12, and folic acid supplements would require a lower dose of SAMe since their effects would be complimentary.

Bottiglieri, T., Hyland, K., and E.H. Reynolds. The clinical potential of S-adenosylmethionine in brain mapping, cerebrovascular hemodynamics, and immune factors. Ann. N.Y. Acad. Sci. 17;777:399-403, 1994.
Bell, K.M., Potkin, S.G., Carreon, D., and L. Plon. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta. Neurol.Scand. Suppl;154:15-8, 1994.

Ray Sahelian, M.D., is the bestselling author of books on Kava, Creatine, 5-HTP, Melatonin, DHEA, Glucosamine, Pregnenolone, Saw Palmetto, and CoQ10. New books include The Common Cold Cure and The Stevia Cookbook. See his web site for the latest updates on natural therapies, herbs, hormones, and supplements.
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 About The Author
Ray Sahelian, M.D., is a popular and respected physician who has been seen on numerous television programs including NBC Today, Dateline NBC, and CNN, and quoted by countless major magazines such as Newsweek He......moreRay Sahelian MD
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