SAMe may look peculiar in print, but it’s pronounced “sammy” so it sounds familiar, like a person’s name. Newsweek magazine took advantage of that coincidence in its March 1999 article “The ‘Sammy’ Solution.”1 At the time the article was written, SAMe was about to hit the shelves of American health-food stores. Little was known about the compound in the United States, although it had been available by prescription for several years in much of Europe.2

Neither a drug nor an herb, SAMe—also known as SAM-e and SAME—is a synthetic version of a naturally occurring coenzyme.3 S-adenosylmethionine (SAM) is involved in numerous metabolic pathways in its role as a methyl-group donor. SAM is largely derived from normal dietary intake of methionine, but the compound is also created by the methylation of homocysteine.2

SAM is primarily produced in the liver from the essential amino acid methionine and adenosine triphosphate, the energy-producing compound found in all human cells. SAM is required for cellular growth and repair and for the biosynthesis of key hormones and neurotransmitters, such as dopamine and serotonin, that affect mood and cognitive function.3

Mechanism of action
Since its introduction to the United States, SAMe has catapulted to popularity for its potential in treating many conditions, especially depression. But it has other applications too.

Osteoarthritis patients have shown significant improvement from the use of supplemental SAMe, supposedly because of its ability to jump-start cellular repair and as an anti-inflammatory agent. Some trials have found SAMe comparable to nonsteroidal anti-inflammatory drugs (NSAIDs) in its ability to relieve pain, stiffness, and swelling and improve range of motion.  Fibromyalgia patients have reported similar experiences.4,5

 Additionally, SAMe’s role as a methyl-group donor is essential in the metabolic formation of sulfate groups, which are ultimately used as key pieces in the body’s manufacture and repair of cartilage.1 These tissue-repair functions may help SAMe relieve certain cirrhotic liver conditions, such as cholestasis, while normalizing enzyme levels within the liver.4

Experts theorize that SAMe works as an antidepressant through a methylation process in the brain leading to greater availability of the dopaminergic neurochemicals and a subsequent boost in mood.6 These chemicals are the “feel good” compounds in the brain and the apparent controllers of our moods and sense of well-being. Vitamin B12 and folic acid are necessary precursors to the methyl-donor process, and researchers are exploring a link between certain mental illnesses and an endogenous deficiency in these vitamins and SAMe.2

Meanwhile, Ivan Goldberg, MD, conducted a MEDLINE search to find 25 international trials that show the efficacy of SAMe in treating depression and arthritis.7 Perhaps the most conclusive data yet published is a meta-analysis of randomized, double-blind studies that compared SAMe with either placebo or tricyclic antidepressants.2

Each research project met stringent criteria for inclusion in this meta-analysis: All participants had to be diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders. SAMe dosage had to be at least 200 mg/day parenterally or 1,600 mg/day orally for at least 12 weeks. Efficacy had to be assessed before and after treatment on the Hamilton Depression Rating Scale, and the data had to be analyzed according to intention-to-treat principles. Overall, the data for some 400 patients showed the response rate for SAMe was superior to the rates for tricyclic antidepressants or placebo.2

Safety and side effects
Therapeutic dosages of SAMe range from 400 to 1,600 mg/day in divided doses, reaching peak absorption in three to five hours. For best results, SAMe should be taken with water on an empty stomach.3 Morning dosing takes advantage of SAMe’s energizing qualities and avoids the insomnia an evening dose might induce. Patients who experience heartburn or nausea after taking a tablet might try drinking more water.4
Because of the potential for serotonin syndrome, anyone taking selective serotonin reuptake inhibitors should not use SAMe. People who have been diagnosed with Parkinson’s disease should avoid it as well.3

SAMe has been linked to mania and hypomania, so health-care providers should supervise patients with psychiatric conditions, such as bipolar or anxiety disorders. The supplement is not recommended for women who are pregnant or lactating or for children.4

Caution people beginning SAMe therapy to be patient. Results may not be apparent for a month, particularly for osteoarthritis.3 Common side effects include nausea and other GI distress. Headache, anxiety, and skin rash have been reported. Lower blood sugar, dry mouth, increased urination, and bloody stools may also occur.3,4

Cost and how supplied
SAMe is usually sold in capsules as a dietary supplement, but it’s also available in enteric-coated tablets for better GI absorption.

Brand names include Admethionine, Adomet, Samyr,  and Gumbaral.3

Prices vary widely; a month’s supply typically costs between $35 and $50.

SAMe appears to be a legitimate player in the antidepressant field of nutraceuticals, although it is not without side effects or cost issues.
For patients who have not had success with current prescription drugs or those who want more controllable access to their therapy,  SAMe is a safe, viable alternative. Patients opting for SAMe should be warned, as with all other supplements, that it is still a medication: It should be taken with caution and its effects monitored by a health-care provider.

1. Underwood A. The ‘Sammy’ solution. Newsweek. March 29, 1999:65.

2. Benjamin SD. SAM-e: For depression and more? Patient Care for the Nurse Practitioner. March 2000; 22-26.

3. Wikipedia. S-Adenosyl_methionine.  Available at  Accessed
July 10, 2008.
4. About. Alternative Medicine:SAMe. Available at Accessed July 10, 2008.

5. University of Maryland Medical Center. S-adenosyl-methionine (SAMe). Available at
/s-adenosylmethionine-000324.htm.  Accessed July 10, 2008.

6. Skidmore-Roth L. Mosby’s Handbook of Herbs & Natural Supplements. 3rd ed. St. Louis, Mo.: Elsevier Mosby; 2006:913.

7. Goldberg I. S-adenosyl-L-methionine as an antidepressant: results of a Medline search. [Dr. Ivan’s Depression Central Web site], available at Accessed July 10, 2008.