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.

Availability
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."

Recommendations
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.