How SAMe works
Unlike other methyl donors where the research is scarce, there have been a number of studies with SAMe. These studies have shown that SAMe influences brain chemicals by helping to convert norepinephrine to epinephrine and serotonin to melatonin; helping make creatine, an important energy reservoir in muscle tissue; 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 and it can improve brain cell membrane fluidity, thus potentially enhancing the function of receptors.

SAMe therapy for depression
Because of its role in the making of neurotransmitters, SAMe has been tested in the therapy of depression. A number of studies have been published, mostly in Europe, evaluating this nutrient’s role in mood disorders. Back in 1994, Dr. Bressa, from the University Cattolica Sacro Cuore School of Medicine, in Rome, Italy conducted a meta-analysis of the studies on SAMe. A meta-analysis is a statistical pooling of already published research papers. Dr. Bressa concludes, "The efficacy of SAMe in treating depressive syndromes and disorders is superior to that of placebo and comparable to that of standard tricyclic antidepressant."

SAMe and Arthritis
SAMe helps support the incorporation of sulfate groups into proteoglycans which help maintain cartilage and protect joints. Some studies have suggested that SAMe possesses anti-inflammatory and tissue-healing properties that may help protect the health of joints, and perhaps may lessen pain. It is quite possible that SAMe may be useful for people with osteoarthritis, although more research needs to be done in this area. Do not exceed 50 mg a day for long term use.

SAMe Caution and side effects
High doses can lead to anxiety and restlessness, and even insomnia. Long term side effects are currently not known. The effects seem to be additive over several days of use, hence dosage may need to be reduced with time. Some do well on even 50 or 100 mg (one quarter or one half of a 200 mg pill) per day. SAMe may induce a manic swing in those with bipolar disorder.

Q. I took SAMe 400mg a day for 2 years and now have had acute anxiety attacks. Since I didn't have any side effects for the first two years, I still didn't attribute the anxiety attack to the SAMe and thought I was developing generalized anxiety disorder. After several small attacks over the months, I had a huge panic attack 10 months after the first one. I finally figured from reading your info on SAMe that it might be the culprit. I stopped and have been getting better ever since. My symptoms were dizziness and vertigo, tingling, numbness in extremities followed by panic, racing heart and high blood pressure, lasting three or more hours. During the first attack I was extremely nauseas. Thank you.
   A. SAMe is a powerful supplement. In low dosages in can help with depression, but higher amounts cause insomnia, anxiety and can lead to panic attacks.