Within the past year, SAMe (short for S-adenosylmethionine and pronounced "sammy") has become a hot commodity on the shelves in health food and drug stores. SAMe is a substance that occurs naturally in the human body, especially in the liver or brain. Deficiencies in either folic acid or vitamin B₁₂ affect the amount of SAMe in your body. SAMe is also available as a dietary supplement, and it appears to be effective for treating depression and osteoarthritis. In Europe, physicians have been writing SAMe prescriptions for at least 30 years. It was introduced in the U.S. in the spring of 1999 as an over-the-counter supplement.

Numerous studies in the U.S. and other countries show that SAMe is effective for relieving the symptoms of depression and osteoarthritis. Studies dating back to the early 1970s show SAMe to be at least as effective for reducing symptoms of depression. It has been found to be at least as effective as tricyclic antidepressants and acts more quickly: While standard antidepressants sometimes take up to four weeks to start working, people taking SAMe may feel its effects after one week. SAMe is also remarkably free of side effects even after years of use. The two side effects that have been reported are mild anxiety and upper gastrointestinal symptoms.

SAMe has also been shown to be just as effective as standard medication, such as ibuprofen and naproxen, for treating osteoarthritis. It does work more slowly than these medications, however. SAMe reduces the inflammation and pain associated with osteoarthritis. It may also protect cartilage and relieve the depression that often accompanies osteoarthritis.

If you are considering taking SAMe for depression or osteoarthritis, talk with your doctor. Your doctor should know about all the supplements you take. People who have bipolar disorder (manic depression) may not respond well to SAMe. Experts also do not recommend taking SAMe if you are currently taking an antidepressant.

Typical doses of SAMe for depression are 200 mg/day to 800 mg twice a day. For osteoarthritis, the recommended dose is a total of 400 mg to 1,200 mg/day, taken divided into two or three doses. Higher doses within this range may increase the therapeutic effects with no increased side effects. Be sure to take SAMe on an empty stomach. Choose tablets with an enteric coating, which improves absorption. You can expect to pay about $2.50 to $4.50 per a 400 mg pill for the supplement.

Agnoli A, Andreoli V, Casacchia M, Cerbo R. Effect of S-adenosyl-l-methionine (SAMe) upon depressive symptoms. J Psychiatr Res. 1976;13:43–54.

Baldessarini RJ. Neuropharmacology of S-adenosyl-l-methionine. Am J Med. 1987;83(suppl 5A):95–103.

Bell KM, Potkin SG, Carreon LP. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand. 1994;154(suppl):15–18.

Bottiglieri T, Godfrey P, Flynn T, Carney MWP, Toone BK, Reynolds EH. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. Neurology. 1990;53:1096–1098.

Bottiglieri T, Hyland K. S-adenosylmethionine levels in psychiatric and neurological disorders: a review. Acta Neurol Scand. 1994;154(suppl):19–26.

Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs. 1994;48(2):137–152.

Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand. 1994;154(suppl):7–14.

Carney MWP, Toone BK, Reynolds EH. S-adenosylmethionine and affective disorder. Am J Med. 1987;83(suppl 5A):104–106.

Di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Am J Med. 1987;83(suppl 5A):60–65.

Domljan Z, Vrhovac B, Dürrigl T, Pucar I. A double-blind trial of ademetionine vs naproxen in activated gonarthrosis. Int J Clin Pharmacol Ther. 1989;27:329–333.

Fava M, Giannelli A, Rapisarda V, Patralia A, Guaraldi GP. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-l-methionine. Psychiatry Res. 1995;56:295–297.

Fazio C, Andreoli V, Agnoli A, Casacchia M, Cerbo R. Therapeutic effects and mechanism of action of S-adenosyl-L-methionine (SAM) in depressive syndromes. [In Italian]. Minerva Med. 1973;64(29):1515–1529.

Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S- adenosylmethionine and clomipramine. Am J Psychiatry. 1993;150(3):522.

König B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med. 1987;83(suppl 5A):89–94.

Maccagno A, di Giorgio EE, Caston O, Sagasta CL. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. Am J Med. 1987;83(suppl 5A):72–77.

Müller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in treatment of osteoarthritis. Am J Med. 1987;83(suppl 5A):81–83.

Rosenbaum JF, Fava M, Falk WE et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand. 1990;81:432–436.

Schumacher HR. Osteoarthritis: the clinical picture, pathogenesis, and management with studies on a new therapeutic agent, S-adenosylmethionine. Am J Med. 1987;83(suppl 5A):1–4.

Stramentinoli G. Pharmacologic aspects of S-adenosylmethionine. Am J Med. 1987;83(suppl 5A):35–42.

Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med. 1987;83(suppl 5A):78–80.