SAMe: The Evidence

Brain Cleaner / Gentle Mood Elevator

Molecular biologists think glutathione might be one of the first signs of life ever created. They think this because they've made soups of the kind of stuff they think was present in ancient seas, zapped it with man-made lightning bolts, and watched organic molecules form all by themselves. Glutathione is one of the first.

Glutathione is the body's natural garbage collector. It detoxifies just about any poison it meets, and it's also a powerful antioxidant.

The body makes glutathione from SAMe. It can also turn SAMe into serotonin, the calming, parasympathetic neurotransmitter that helps us have fun in small doses and sleep in larger ones. Dopamine, the motivating, euphoric, falling-in-love neurotransmitter, can also be made from SAMe as can norepinephrine, the stay-alert and stay-awake one.

An abundant literature documents SAMe's utility in depression1,2,3,4 in large part because of the serotonin-boosting effect.5,6 It augments the effects of common antidepressant medications (the SSRIs)7 helping patients achieve desired outcomes with smaller doses. SAMe is a methyl donor, one of a class of catalysts that help switch molecules back and forth between their different forms and roles. Methionine, an amino acid, does much the same job and is sometimes cheaper. Both are available at better health food stores.

While it's supplying raw material for this rich mix of neuro-active chemicals, SAMe is also helping clear used neurotransmitters from the brain, converting them into a form that can be easily excreted by the kidneys and keeping the mind clear. It increases the fluidity of cell membranes, allowing more efficient transport of nutrients into and waste out of the cell. Dosages usually range from 200-800 mg./day. Of course, in order to obtain maximum benefit from an advanced nutrient like SAMe, it's important to ensure the brain is also supplied with adequate B vitamins, fully-chelated trace minerals and essential fatty acids (omega-3 and omega-6 oils, in a 2:1 ratio.) Find out more about these foundation nutrients here.

Adequate pyridoxine (B6), cyanocobalamin (B12) and folic acid are required for methionine and SAMe's metabolism. Since serotonin function is so variable a subset of about 5% of the population may be comprised of vulnerable individuals may experience manic states when taking methionine or SAMe.8

Don't take SAMe with l-Tyrosine, or with prescription drugs, without medical supervision. Some researchers believe SAMe may act in part similarly to MAO inhibitors, which slow down the rate at which the body breaks down the same neurotransmitters whose concentration is increased by l-Tyrosine. Without supervision it's not a good idea to make more of a substance important to the body at the same time as you slow down the body's ability to break that substance down - too much can build up and that can have bad consequences.


 1. Williams, A.L. 2005. S-adenosylmethionine (SAMe) as treatment for depression: a systematic review. Clinical and Investigative Medicine. 28(3):132-139.

 2. Mischoulon, D., Fava, M. 2002. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. American Journal of Clinical Nutrition. 76(5):1158S-1161S.

 3. Papakostas, G.I., et al. 2003. S-adenosyl-methionine in depression: a comprehensive review of the literature. Current Psychiatry Reports. 5(6):460-466.

 4. Freeman, M.P., et al. 2004. Selected integrative medicine treatments for depression: considerations for women. Journal of the American Women's Medical Association. 59(3):216-224.

 5. Otero-Losada, M.E., Rubio, M.C. 1989. Acute changes in 5-HT metabolism after S-adenosyl-L-methionine administration. General Pharmacology. 20(4):403-406.

 6. Curcio, M. et al. 1978. Effect of S-adenosyl-L-methionine on serotonin metabolism in rat brain. Progress in Neuropsychopharmacology. 2(1):65-71.

 7. Alpert, J.E., et al. 2004. S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine. Journal of Clinical Psychopharmacology. 24(6):661-664.

 8. Goren, J.L., et al. 2004. Bioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humans. Pharmacotherapy. 24(11):1501-1507.