S-Adenosylmethionine (SAMe)


SAMe is a metabolite of the essential amino acid methionine. It is a cofactor in three important biochemical pathways and consequently, SAMe is synthesized in cells throughout the body. Because of the important biochemical reactions that it regulates, studies are reporting that SAMe is beneficial for a wide variety of health and medical conditions.

Dosage Info

Dosage Range

200-1,600mg daily.

Most Common Dosage

400mg daily.

Dosage Forms

Tablets, capsules, and intravenous solution.

Adult RDI

None established

Adult ODA

None established


  • : None established

Interactions and Depletions



Active Forms

S-adenosylmethionine (SAMe)


SAMe is readily absorbed from the gastrointestinal tract.

Toxicities & Precautions


SAMe has no reported toxicity.

Side Effects

A few minor side effects have been occasionally reported, which include dry mouth, nausea, (1) and restlessness.

Functions in the Body

Methylation Reactions

SAMe functions as a methyl donor for the synthesis of nucleic acids (DNA and RNA), proteins, phospholipids, catecholamines, and various other neurotransmitters.


SAMe is the precursor in the sulfur metabolic pathways for the synthesis of cysteine, glutathione, and taurine.


SAMe is also necessary for the synthesis of a group of compounds collectively referred to as polyamines, which are spermidine, puescine, and spermine. These polyamines are essential for cellular growth and differentiation, gene expression, protein phosphorylation, neuron regeneration, and the repair of DNA.

Antioxidant production

Because SAMe is necessary for the synthesis of glutathione, which is an antioxidant, it plays a role in protecting the body from free radical-induced aging damage.


Glutathione is important for detoxification in the liver. Glutathione depletion is usually found in individuals with liver malfunction. SAMe supplementation promotes the synthesis of glutathione, which improves liver function and detoxification.

Healthy Cellular Membranes

The ratio between phosphatidyl choline (PC) and cholesterol in cellular membranes determines their relative flexibility or stiffness; PC promotes flexibility whereas cholesterol promotes stiffness. Since SAMe is an important facilitator of phosphatidyl choline synthesis, it plays a role in promoting more pliant cellular membranes. Stiffer cell membranes are not able to transmit cellular signals as effectively and it is more difficult for neuropeptides and other messenger molecules to fit into receptor sites when cellular membranes are stiff.

Neuron Protective

Protects against neuronal death caused by lack of oxygen (anoxia). It regenerates nerves and provokes remyelination of nerve fibers.

Liver Protection

Protects the liver against alcohol, drugs, and cytokines. It protects against cholestasis (bile impairment or blockage). It may protect against chronic active hepatitis. It protects against liver damage caused by MAO inhibitors and anticonvulsants. It reverses hyperbilirubinemia. Supplementation of SAMe in cancer patients during chemotherapy treatment significantly reduced liver toxicity levels. (2)

Clinical Applications

Alzheimer's Disease

Low levels of SAMe were found in Alzheimer’s patients and researchers think supplementation may improve cognitive function and reduce depression which are some of the symptoms associated with this disease. (3) , (4)


SAMe has been found to be a safe and effective natural anti-depressant agent as an alternative to prescription durgs. (5)

Inflammatory Bowel

Low concentrations of SAMe were found in patients with severe inflammatory bowel disease. (6)


Studies have indicated that SAMe may be effective in reducing inflammation and pain in patients suffering from osteoarthritis. (7) , (8)


In a double-blind trial, patients who received 800mg of SAMe daily for 6 weeks several reported improvements in fatigue, pain, morning stiffness, and mood. (9) In another study, fibromyalgia patients treated with SAMe improved in both levels of depression and number of trigger points, prompting the authors of the study to state that SAMe seems to be an effective and safe therapy in the management of fibromyalgia. (10) , (11) , (12) , (13) , (14)


SAMe, which is only produced in the body during the day, is necessary for the synthesis of melatonin at night because it promotes the function of the enzyme that converts serotonin to melatonin. (15)

Intrahepatic Cholestasis

Reported to be reversed in women on 800mg of SAMe daily. (16)

Liver Disease

Patients with cirrhosis and a variety of other chronic liver problems responded well when administered 30mg SAMe, 6 times daily for 30 days, and the improvements continued to be maintained 30 days after the end of therapy. (17) , (18) , (19)

Cardiovascular Disease

Researchers have indicated that SAMe may control homocysteine levels in the body, which are a significant risk factor for cardiovascular diseases. (20) , (21)

Symptoms and Causes of Deficiency

Normally our bodies produce SAMe from the amino acid methionine. Since vitamin B12 and folic acid are necessary for the synthesis of SAMe, a deficiency of these vitamins can lead to a depletion of SAMe.

Dietary Sources

SAMe does not occur in foods to any appreciable degree.


  1. View Abstract: Di Rocco A, et al. S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trial. Mov Disord. Nov2000;15(6):1225-9.
  2. View Abstract: Santini D, Vincenzi B, Massacesi C, et al. S-adenosylmethionine (AdoMet) supplementation for treatment of chemotherapy-induced liver injury. Anticancer Res. Nov2003;23(6D):5173-9.
  3. View Abstract: Bottiglieri T, et al. Cerebrospinal Fluid S-adenosylmethionine in Depression and Dementia: Effects of Treatment with Parenteral and Oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry.(Eng). Dec1990;53(12):1096-98.
  4. Fontanari D, et al. Effects of S-adenosyl-L-methionine on Cognitive and Vigilance Functions in the Elderly. Curr Ther Res Clin Exp.(USA). 1994;55(6):682-689.
  5. View Abstract: Bressa GM, et al. S-adenosyl-l-methionine (SAMe) as Antidepressant: Meta-analysis of Clinical Studies. Acta Neurol Scand Suppl. 1994;154:7-14.
  6. View Abstract: Schmedes A, Nielsen JN, Hey H, Brandslund I. Low S-adenosylmethionine concentrations found in patients with severe inflammatory bowel disease. Clin Chem Lab Med. 2004;42(6):648-53.
  7. View Abstract: Konig B. A Long-term (two years) Clinical Trial with S-adenosylmethionine for the Treatment of Osteoarthritis. Am J Med. Nov1987;83(5A):89-94.
  8. View Abstract: 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. Feb2004;5(1):6.
  9. View Abstract: Jacobsen S, et al. Oral S-adenosylmethionine in Primary Fibromyalgia. Double-blind Clinical Evaluation. Scand J Rheumatol. 1991;20(4):294-302.
  10. View Abstract: Tavoni A, et al. Evaluation of S-adenosylmethionine in Primary Fibromyalgia. A Double-blind Crossover Study. Am J Med. Nov1987;83(5A):107-10.
  11. View Abstract: Tavoni A, et al. Evaluation of S-adenosylmethionine in Primary Fibromyalgia. A Double-blind Crossover Study. Am J Med. Nov1987;83(5A):107-10.
  12. Ianniello A, et al. S-adenosyl-L-methionine in Sjogren's Syndrome and Fibromyalgia. Curr Ther Res Clin Exp.(USA). 1994;55(6):699-706.
  13. Grasetto M, et al. Primary Fibromyalgia is Responsive to S-adenosyl-L-methionine. Curr Ther Res Clin Exp.(USA). 1994;55(7):797-806.
  14. Di Benedetto P, Iona LG, Zidarich V. Clinical Evaluation of S-adenosyl-L-methionine Versus Transcutaneous Electrical Nerve Stimulation in Primary Fibromyalgia. Curr Ther Res. Feb1993;53(2):222.
  15. View Abstract: Sitaram BR, et al. Nyctohemeral Rhythm in the Levels of S-adenosylmethionine in the Rat Pineal Gland and Its Relationship to Melatonin Biosynthesis. J Neurochem. Oct1995;65(4):1887-94.
  16. View Abstract: Frezza M, Pozzato G, et al. Reversal of Inrahepatic Cholestasis of Pregnancy in Women after High Dose S-adenosyl-L-methionine Administration. Hepatol. 1984;4(2):274-78.
  17. View Abstract: Mato JM, et al. S-adenosylmethionine in Alcoholic Liver Cirrhosis: A Randomized, Placebo-controlled, Double-blind, Multicenter Clinical Trial. J Hepatol. Jun1999;30(6):1081-89.
  18. View Abstract: Chawla RK, et al. Biochemistry of Pharmacology of S-adenosyl-L-methionine and Rationale for Its Use in Liver Disease. Drugs. 1990;40(Sup. 3):98-110.
  19. View Abstract: Friedel HA, et al. S-Adenosyl-L-methionine. A review of Its Pharmacological Properties and Therapeutic Potential in Liver Dysfunction and Affective Disorders in Relation to Its Physiological Role in Cell Metabolism. Drugs. 1989;38(3):389-416.
  20. View Abstract: Loehrer FM, et al. Low Whole-blood S-adenosylmethionine and Correlation Between 5-methyltetrahydrofolate and Homocysteine in Coronary Artery Disease. Arterioscler Thromb Vasc Biol. Jun1996;16(6):727-33.
  21. View Abstract: Becker A, Henry RM, Kostense PJ, et al. Plasma homocysteine and S-adenosylmethionine in erythrocytes as determinants of carotid intima-media thickness: different effects in diabetic and non-diabetic individuals. The Hoorn Study. Atherosclerosis. Aug2003;169(2):323-30.