SAMe (S-adenosylmethionine)

What Is It?

Health Benefits
Dosage Information

Guidelines for Use

General Interaction

Possible Side Effects



Evidence Based Rating Scale 



What Is It?

SAMe (pronounced "sammy") is short for S-adenosylmethionine, a molecule that the body continually produces to fuel numerous vital body functions. Discovered in 1952, the popularity of SAMe has soared recently with talk of its ability to ease depression as effectively as prescription antidepressants. (Proponents say SAMe also works faster than antidepressants and with virtually no side effects.)

Long prescribed by European doctors for both arthritis and depression, SAMe recently became available in the United States as an over-the-counter supplement. It is also emerging as an effective therapy for arthritis, fibromyalgia, certain liver disorders, and possibly even Alzheimer's disease.

Health Benefits

The body manufactures SAMe from methionine, an amino acid found in protein-rich foods, and adenosine triphosphate (ATP), an energy-producing compound found in all the body's cells. The SAMe molecule then donates a piece of itself (a methyl group) to body tissues and organs, providing a critical link in methylation, a chemical reaction that occurs billions of times a second throughout the body. In giving up a part of itself, SAMe promotes cell growth and repair.

SAMe also contributes to the formation of key compounds in the brain, including the neurotransmitter dopamine and the mood-enhancer serotonin. In addition, it helps to maintain desirable levels of glutathione, a major antioxidant that protects cells against damage from oxygen molecules called free radicals. Taken as a supplement, SAMe compensates for any deficiencies and encourages the body to run efficiently.

Specifically, SAMe may help to:

·  Relieve depression and stress-related blues.  In randomized controlled trials SAMe appears to work as well as the frequently prescribed tricyclic antidepressants (imipramine, amitriptyline, desipramine) in easing depression (1,2). Just as importantly, it works faster, often starting to improve mood within a week. This contrasts significantly with standard antidepressants, whose effects can take several weeks to become apparent. In a University of California study of 17 severely depressed adults, 62% of the participants who took SAMe for four weeks (1,600 mg daily) showed significant improvements in symptoms, compared to 50% of those who used desipramine (a conventional antidepressant) (3). Unlike many prescription antidepressants, which often cause unpleasant side effects such as as drowsiness, dry mouth, and constipation, SAMe appears to cause few if any side effects. SAMe may also be a good choice for women who take oral contraceptives and would like to try a herbal supplement to treat depression. SAMe has not been demonstrated to adversely effect the efficacy of oral contraceptives, as has St. John’s Wort.

·  Treat chronic fatigue syndrome (CFS).
Like conventional antidepressants used to treat chronic fatigue, SAMe appears to benefit CFS sufferers by countering depression. It alters the brain's response to pain and improves the quality of badly needed sleep. As a result, both chronic fatigue syndrome and a condition with which it's commonly confused--chronic fatigue syndrome-fibromylagia (CFS-FM)--are likely to respond to SAMe. CFS-FM, which is actually more common than CFS, appears to be a physical response to chronic stress and depression.

·  Lessen arthritis-related pain and inflammation. The eventual breakdown of SAMe in the body yields substances that help to keep the gel-like cartilage that cushions joints intact (4). In the common degenerative joint disease osteoarthritis, cartilage wears down over time. Studies in thousands of osteoarthritis sufferers have demonstrated that SAMe can be as effective at increasing joint mobility and reducing swelling and pain as such NSAIDs (nonsteroidal anti-inflammatories) as ibuprofen and aspirin (5,6,7). Moreover, SAMe doesn't pose the risk of stomach bleeding or kidney damage that are serious risks with NSAIDs. Recent studies also show that SAMe is also as effective as COX-2 inhibitors such as Celebrex, for the management of osteoarthritis (8). It also doesn't wear down joints, damage cartilage, or block the pain signals that could signal a worsening condition. Although it's not exactly clear how SAMe works for arthritis, very preliminary but intriguing animal studies actually point to a role in repairing cartilage and lubricating joints, properties that may well extend to humans. Clearly more research is needed.

·  Control back pain. SAMe may improve back pain when taken for several weeks, a function of its ability to reduce swelling and pain. The theory is that SAMe takes part in the repair and restoration of spinal discs, cartilage, and the articulating surfaces of joints. Obviously, this takes time. So if you're using SAMe for back pain, don't expect the immediate symptom relief that you get with NSAIDs such as Motrin or COX-2 inhibitors such as Celebrex (8).

·  Reduce fibromyalgia symptoms. SAMe may minimize certain complications of this often debilitating disorder, such as muscle pain, depression, and fatigue. The 44 fibromylagia sufferers in a Danish study who took 800 mg of SAMe daily for six weeks reported some relief from morning stiffness and muscle aches (9). They also noted an improvement in mood. The results from other studies have been mixed, however. For example, a 1997 study to test the effectiveness of intraveneously administered SAMe for fibromylagia failed to show significant benefits. However, given that no single therapy for fibromyalgia is uniformly satisfactory, a trial of SAMe for this often puzzling condition is certainly reasonable.

·  Treat hepatitis and other liver disorders. By producing the extremely powerful antioxidant glutathione, which enhances the liver's ability to clear out toxins, SAMe promotes efficient liver function. Research indicates that SAMe may benefit liver function impaired by alcohol-induced cirrhosis, drug toxicity, hepatitis, and cholestasis (10-13).

·  Protect against Alzheimer's and age-related brain disorders. Preliminary research indicates that SAMe levels are very low in individuals suffering from Alzheimer's disease. In one study of elderly individuals with problems related to alertness and cognition, improvements in such areas as memory, mood, and ability to carry out everyday activities of life occured upon administration of a regimen of oral, intravenous, and intramuscular SAMe. Additional research is now underway to determine what role supplemental SAMe might play in antioxidant production and in disorders of the aging brain. SAMe may also be a good choice of drug for the elderly to fight depression, as SAMe has few known side effects or interactions with other drugs.

Note: SAMe has also been found to be useful for a number of other disorders. For information on these additional ailments, see our Dosage Recommendations Chart for SAMe.


  • tablet

Dosage Information

Special tips:

for enteric-coated SAMe; it's more readily absorbed by the body in this form and remains chemically stable for much longer (the coating protects it from exposure to air).

·  To avoid a toxic buildup of homocysteine molecules (which are formed when SAMe breaks down) be sure to take a high-quality vitamin B complex supplement along with SAMe. These vitamins help metabolize homocysteine, which in high concentrations poses the risk for various health problems including heart attack and stroke. A standard recommendation is to take 100 mg of a B complex once a day, regardless of the SAMe dose.

·  If you're particularly sensitive to medications, start out with half the recommended daily dosage and work up to the full amount after a week.

·  For depression, arthritis, fibromylagia, and liver disorders: Take 400 mg of SAMe twice a day. If symptoms fail to improve after three weeks, try increasing your dose to 400 mg three times a day. On the other hand, if symptoms lessen with 400 mg twice a day, you can try to lower the dose to 200 mg twice a day.

Be sure to check out our Dosage Recommendations Chart, which has therapeutic dosages for specific ailments at a glance.

Guidelines for Use

·  SAMe is best absorbed on an empty stomach, so try to take it about one hour before or two hours after meals. If nausea or heartburn develop, take it with plenty of water.

·  To prevent insomnia, don't take SAMe late in the day. Most people report a mild energy boost with the supplement.

·  SAMe can safely be combined with other natural antidepressants such as St. John's wort, as well as most conventional antidepressants.

·  Purchase SAMe from a reliable company whose quality standards you trust. If improperly handled, the raw material used to make SAMe can deteriorate rapidly, making these costly supplements weak or even inactive. Look for "pharmaceutical grade" products and opt for a more stable form called "butanedisulfonate" rather than "tosylate."

General Interaction

·  Don't take SAMe with MAO inhibitor antidepressants.

Note: For information on interactions with specific generic drugs, see our WholeHealthMD Drug/Nutrient Interactions Chart.

Possible Side Effects

·  SAMe seems to be free of significant side effects, even when taken for long periods of time.

·  In rare cases, daily doses of 400 mg or higher may cause mild stomach upset, dry mouth, and insomnia.

·  At extremely high doses, the supplement may cause diarrhea and heartburn.


·  If you suffer from moderate to severe depression, don't take SAMe without consulting your doctor first. This precaution is particularly important if you have a bipolar disorder because SAMe could trigger or exacerbate mania (the "up" phase) in such cases (14).

·  If you're taking prescription antidepressants, don't discontinue them or reduce your dosage without consulting your doctor.

·  SAMe should lift depression relatively quickly. If you don't notice a significant improvement after four weeks, see your doctor. You may need a different category of antidepressant.

·  If you are taking any other prescription medications check with your doctor before starting any new supplement. There have been very few clinical trials to determine what interactions can occur with SAMe.


Note: If taking SAMe for moderate to severe depression, please contact your physician if you do not notice any improvements in 2-3 weeks. Your physician can help rule out other organic causes for your condition that may or may not respond to supplementation. See the WholeHelathMD Healing Center on Depression for more information.




1. Pancheri P, Scapicchio P, Chiaie RD. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Int J Neuropsychopharmacol. 2002;5(4):287-94.

2. Delle Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr. 2002;76(5):1172S-6S.

3. Bell KM, Potkin SG, Carreon D, Plon L. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl.


4. Konig H, Stahl H, Sieper J, Wolf KJ. Magnetic resonance tomography of finger polyarthritis: morphology and cartilage

signals after ademetionine therapy. Aktuelle Radiol. 1995;5(1):36-40.

5. Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med. 1987;83(5A):81-3.

6. Sander O. Review: S-adenosylmethionine treats osteoarthritis as effectively as nonsteroidal anti-inflammatory drugs with fewer adverse effects. ACP J Club. 2003;138(1):21.

7. Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract. 2002;51(5):425-30.

8. Najm WI, Reinsch S, Hoehler F, Tobis JS, Harvey PW. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. BMC Musculoskelet Disord. 2004;5(1):6.

9. Volkmann H, Norregaard J, Jacobsen S, Danneskiold-Samsoe B, Knoke G, Nehrdich D. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia. Scand J Rheumatol. 1997;26(3):206-11.

10. Mato JM, Camara J, Fernandez de Paz J, Caballeria L, Coll S, Caballero A,

Garcia-Buey L, Beltran J, Benita V, Caballeria J, Sola R, Moreno-Otero R, Barrao F, Martin-Duce A, Correa JA, Pares A, Barrao E, Garcia-Magaz I, Puerta JL, Moreno J, Boissard G, Ortiz P, Rodes J. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized,

placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999;30(6):1081-9.

11. Diaz Belmont A, Dominguez Henkel R, Uribe Ancira F.

Parenteral S-adenosylmethionine compared to placebos in the treatment of alcoholic liver diseases. An Med Interna. 1996;13(1):

Date Published: 09/08/2005
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