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SAMe (S-adenosyl-L-methionine)

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Also listed as: S-adenosyl-L-methionine
Related terms
Background
Evidencetable
Tradition
Dosing
Safety
Interactions
Attribution
Bibliography

Related Terms
  • Ademetionin, ademetionine, adenosylmethionine, Ade-SD4, AdoMet, Geptral (Russian), Gumbaral (German), Heptral (Russian), S-adenosine-L-methionine, S-adenosyl-L-methionine 1,4-butanedisulfonate, s-adenosyl-L-methionine 1,4-butanedisulphonate (stable salt form), S-adenosylmethionine, S-adenozilmetionin, SAM, SAM-e, SAMe tosylate disulfate, SAMe-butanedisulphonate, Sammy, Samyr®, sulfo-adenosil-L-metionina (Spanish), sulfo-adenosyl-L-methionine sulfate-p-toluensulfonate (stable salt form), sulfoadenosilmethionina (Italian), sulfo-adenosyl-methionine.
  • Selected combination products: GNC Triflex with SAM-e (chondroitin, glucosamine, MSM, SAM-e).

Background
  • SAMe is made in the body from a reaction between methionine, which is an essential amino acid, and adenosine triphosphate, a molecule that carries energy. SAMe is involved in many different reactions in the body.
  • SAMe has been used to treat psychiatric illnesses, infertility, liver problems, premenstrual disorders, and musculoskeletal conditions.
  • SAMe has been widely studied for osteoarthritis and depression. There is evidence that SAMe may help reduce the pain of osteoarthritis.
  • Some evidence is available for the use of SAMe for depression, fibromyalgia, and bile flow problems during pregnancy. SAMe has also been studied for its potential anti-inflammatory and pain-relieving effects. However, higher-quality studies are needed before conclusions can be made.

Evidence Table

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *


SAMe has been widely studied for the treatment of osteoarthritis. There is evidence that SAMe may reduce the pain of osteoarthritis and may be well tolerated. Results suggest that SAMe may be more effective than placebo and as effective as anti-inflammatory drugs.
B


Early evidence suggests that SAMe may benefit adults with ADHD. Higher-quality studies are needed before conclusions can be made.

C


Some evidence suggests that SAMe may treat symptoms linked to bile flow problems. However, information is still limited. SAMe has been studied during feeding through the vein for the treatment of bile flow problems. Higher-quality research is needed in this area.

C


Firm conclusions are lacking on the use of SAMe for bile flow problems during pregnancy. Early research suggests that SAMe may lack benefit over placebo in treating symptoms of the condition. In the available studies, SAMe appears to be well tolerated in mothers or newborns. Information on the use of SAMe before the third trimester is lacking.

C


SAMe has been widely studied for use in depression and bipolar disorder. However, high-quality studies are lacking. Some available evidence suggests that SAMe may be more effective than placebo. Most trials comparing SAMe to antidepressants are short-term only (less than three weeks). It is known that antidepressants require at least 4-6 weeks to show full effectiveness. Trials lasting for six weeks suggest a lack of significant effect of SAMe. High-quality research that compares SAMe to other antidepressants and lasts at least six weeks is needed. Firm conclusions are lacking at this time.

C


Fibromyalgia is known to cause chronic pain and depressive symptoms. SAMe has been studied for the relief of these symptoms. Evidence is mixed with regard to possible benefits of SAMe. More research is needed before firm conclusions can be made.

C


Early evidence suggests that SAMe may benefit people who have liver disease. The use of nutrition supplements, such as SAMe, has been studied for liver disease. High-quality clinical trials are needed before conclusions can be made.

C


Early research suggests that SAMe may improve cognitive problems associated with various genetic disorders. SAMe has also been studied for nervous system disorders related to genetic disorders, such as Lesch-Nyhan syndrome (a condition that affects the breakdown of purines, natural compounds in the body). More high-quality research is needed to form conclusions.

C


Early research suggests that SAMe may treat some symptoms of schizophrenia. These include aggression, quality of life, and depression. However, SAMe may cause irritability. More research is needed in this area.

C


Early human research suggests that a combination treatment involving SAMe may protect the liver in people with sepsis. More studies are needed to determine the effects of SAMe alone.

C


Early human research suggests that SAMe may benefit sexual function. Further research is needed in order to make a firm conclusion

C


Supplementing with SAMe has been suggested as a way to help smokers quit. Early study has found a lack of effectiveness. Higher-quality research is needed to make conclusions.

C
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)


Tradition / Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

  • Acetaminophen toxicity, adjustment disorder, aging, alcoholism, Alzheimer's disease, antioxidant, anxiety, bursitis (inflammation between joints and muscles), cirrhosis (scarring of the liver), dementia, gastritis (inflammation of stomach lining), Gilbert's syndrome (high levels of bilirubin, a toxic substance), head injury, hearing loss, heart disease, high cholesterol, infertility, lead toxicity, liver inflammation, liver toxicity (caused by drugs or toxins), memory, metabolic abnormalities, migraine, multiple sclerosis, pain from nerve disorders, pancreatitis (pancreas inflammation), Parkinson's disease, premenstrual dysphoric disorder (PMDD, severe depression before menstruation), premenstrual syndrome (PMS), psychiatric illness, rheumatoid arthritis, seizures, Sjögren's syndrome (dry eyes and mouth), spinal cord injury, systemic sclerosis (autoimmune disease of skin and blood vessels), tendonitis (tendon inflammation).

Dosing

Adults (18 years and older):

  • For ADHD, 400 milligram SAMe tablets have been taken by mouth three times daily, then increased to a maximum of 800 milligrams three times daily, for four weeks.
  • For bile flow improvement (general), 1,600 milligrams of SAMe have been taken by mouth daily for two weeks. A dose of 1,000 milligrams has been injected into the vein daily for four weeks.
  • For bile flow improvement in pregnancy, the following doses of SAMe have been taken by mouth: 500 milligrams of Transmetil® twice daily for 14 days, followed by 500 milligrams of SAMe twice daily until or after delivery; 600 milligrams of Samyr®, taken alone or with beta-mimetics daily; and 500 milligrams twice daily. The following doses of SAMe have been injected: 1,000 milligrams into the muscle daily until delivery; 200-800 milligrams into the vein daily for 20 days; 800 milligrams into the vein daily in two divided doses until delivery; and 800 milligrams into the vein over three hours for 20 days. A dose of 800 milligrams of disulfate-p-toluene sulfonate stable salt has been injected into the vein daily.
  • For depression, the following doses of SAMe have been taken by mouth or given through feeding into the vein as 200-1,600 milligrams, 1-2 times daily for two days up to eight weeks. The following doses of SAMe have been injected into the vein or muscle: 45-800 milligrams daily or every other day for 3-30 days. The following combination doses of SAMe have been used: 400 milligrams of SAMe injected into the vein for six days, followed by 1,000 milligrams taken by mouth as a single dose; or 200 milligrams injected into the muscle once daily along with 400 milligrams taken by mouth twice daily for six days, followed by 400 milligrams of SAMe taken by mouth three times daily for one day, for a total of four weeks.
  • For fibromyalgia (chronic muscle pain), 200-400 milligrams of SAMe have been injected into the vein daily. A dose of 200 milligrams injected into the muscle daily has been used with 200 milligrams taken by mouth twice daily.
  • For liver disease (general), 400-1,500 milligrams of SAMe has been taken by mouth 1-2 times daily for 1-24 months in the form of Samyr®. A dose of 600 milligrams of SAMe in 250 milliliters of saline has been injected in the vein for three days, followed by 400 milligrams of SAMe taken by mouth three times daily for another 30 days. The following doses of SAMe have been injected into the vein: a single dose containing 50 milligrams; 50-800 milligrams daily for 15-17; 800 milligrams, followed by 1,600 milligrams; 250 milligrams as a slow bolus drip every 12 hours for 30 days in 500 milliliters of 5 percent levulose; 500 milligrams in 250 milliliters of sugar solution daily; and 15 milligrams four times daily for 30 days. The following doses of SAMe have been injected into the muscle: 50-800 milligrams daily for up to 30 days, and 15 milligrams four times daily for 30 days. A dose of 200 milligrams of SAMe has been injected into the vein daily for 15 days, then injected into the muscle for 15 days.
  • For osteoarthritis, 200-400 milligrams of SAMe has been taken by mouth 2-6 times daily for 3-12 weeks. A dose of 400 milligrams of SAMe has been injected into the vein daily for five days, followed by 200 milligrams taken by mouth three times daily for 23 days. A dose of 60 milligrams of SAMe has been injected into the muscle for 7-14 days.
  • For schizophrenia, 400 milligrams of SAMe has been taken by mouth daily for the first week in divided doses, followed by 800 milligrams of SAMe in divided doses daily for the next seven weeks.
  • For sexual function, 400 milligrams of SAMe has been taken by mouth twice daily for the first two weeks, then increased to two 400 milligram SAMe pills twice daily for the remainder of six weeks.
  • For smoking, 400-800 milligrams of SAMe has been taken by mouth twice daily for eight weeks.

Children (younger than 18 years):

  • For liver inflammation, 75 milligrams (in children younger than 13) or 150 milligrams of SAMe (for children 13 or older) have been taken by mouth daily for 35 days. A dose of 100 milligrams of SAMe has been injected into the vein daily for 15 days, followed by 100 milligrams injected into the muscle for 15 days.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in people with known allergy or sensitivity to SAMe.
  • Changes in concentration and memory, dizziness, flushing, heart palpitations, nausea, and skin redness have been reported.

Side Effects and Warnings

  • SAMe is likely safe when taken by mouth in doses of 400-600 milligrams daily for up to two years or 800-1,600 milligrams daily for up to 42 days. SAMe is likely safe when injected into the vein in daily doses of up to 800 milligrams for up to 21 days.
  • SAMe may cause agitation, anorexia, anxiety, bloating, bloody stool, blurry vision, changes in blood levels of SAMe, changes in heart rate or heart palpitations, confusion, constipation, a crawling feeling on the skin, decreased appetite, diarrhea, difficulty breathing or shortness of breath, dizziness, drowsiness, dry mouth, fatigue, a feeling of weakness, frequent or delayed urination, gas, hair loss, headache, heartburn, high levels of liver enzymes, hostility, increased saliva, increased sweating, increased thirst, irritability, itchy ear, jitteriness, joint and back pain, low energy, mood changes, nausea, nervousness, night sweats, numbness or pain at injection site, restlessness, sexual dysfunction, skin itching, skin rashes, sleep problems, stomach pain, suicide attempts or ideation, swelling, tremors, vein inflammation, vivid dreams, vomiting, and weight loss.
  • SAMe may affect the risk of bleeding. Caution is advised in people with bleeding disorders or taking drugs that may affect the risk of bleeding. Dosing adjustments may be necessary.
  • SAMe may lower blood sugar levels. Caution is advised in people with diabetes or low blood sugar, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood sugar levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.
  • SAMe may increase blood pressure. Caution is advised in people with high blood pressure or in those taking drugs or herbs and supplements that affect blood pressure.
  • Use cautiously in people who have abnormal heart rhythms, anxiety or anxiety disorders, depression, headache, insomnia, Parkinson's disease, and stomach disorders.
  • Use cautiously in people who take levodopa and phosphodiesterase inhibitors.
  • Use cautiously in women in their third trimester of pregnancy. SAMe should only be used during pregnancy if the benefits clearly outweigh the risks.
  • Avoid in people who have bipolar disorder or known allergy or sensitivity to SAMe.
  • Avoid in breastfeeding women and women in their first trimester of pregnancy.
  • Note: There is a lack of information on the use of SAMe in children, elderly people, pregnant women in a trimester other than the third trimester, or during breastfeeding.

Pregnancy and Breastfeeding

  • There is a lack of scientific evidence on the use of SAMe during pregnancy or breastfeeding. Use cautiously in women in their third trimester of pregnancy. SAMe should only be used during pregnancy if the benefits clearly outweigh the risks. Avoid in breastfeeding women and women in their first trimester of pregnancy.

Interactions

Interactions with Drugs

  • SAMe may affect bleeding risk when taken with drugs that may affect bleeding risk. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin®) or heparin, antiplatelet drugs such as clopidogrel (Plavix®), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).
  • SAMe may increase blood pressure. Caution is advised in people taking drugs that affect blood pressure.
  • SAMe may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be altered in the blood, and may cause altered effects or potentially serious adverse reactions. People using any medications should check the package insert, and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
  • SAMe may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. People taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
  • SAMe may also interact with agents that affect blood vessel width, agents that harm the liver, agents that increase urination, agents that prevent or treat abnormal heart rhythms, alcohol, anti-anxiety agents, anticancer agents, antidepressants (MAOIs, SSRIs, TCAs), anti-inflammatory agents, antipsychotic agents, cholesterol-lowering agents, clomipramine, ear agents, estrogens, eye agents, genitourinary agents, heart agents, hormonal agents, impotence agents, levodopa, methotrexate, nervous system agents, pain relievers, phosphodiesterase inhibitors, skin agents, stomach and intestine agents, and tolcapone

Interactions with Herbs and Dietary Supplements

  • SAMe may affect bleeding risk when taken with herbs and supplements that are believed to affect bleeding risk. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.
  • SAMe may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of other herbs or supplements may be altered in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.
  • SAMe may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.
  • SAMe may affect blood pressure. Caution is advised in people taking herbs or supplements that affect blood pressure.
  • SAMe may also interact with anti-anxiety herbs and supplements, anticancer herbs and supplements, antidepressants (MAOIs and SSRIs), anti-inflammatory herbs and supplements, antioxidants, antipsychotic herbs and supplements, cholesterol-lowering herbs and supplements, choline, docosahexaenoic acid (DHA), folic acid, genitourinary herbs and supplements, herbs and supplements that affect blood vessel width, herbs and supplements that harm the liver, herbs and supplements that increase urination, herbs and supplements that prevent or treat abnormal heart rhythms, herbs and supplements that treat ear disorders, herbs and supplements that treat eye disorders, herbs and supplements that treat heart disorders, herbs and supplements that treat impotence, herbs and supplements that treat nervous system disorders, herbs and supplements that treat skin disorders, herbs and supplements that treat stomach and intestine disorders, hormonal herbs and supplements, methionine, minerals, pain relievers, phytoestrogens, and vitamins (including B6 and B12).

Attribution
  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Chitiva H, Audivert F, and Alvarez C. Suicide attempt by self-burning associated with ingestion of S-adenosylmethionine: a review of the literature and case report. J.Nerv.Ment.Dis. 2012;200(1):99-101.
  2. Dording CM, Mischoulon D, Shyu I, et al. SAMe and sexual functioning. Eur.Psychiatry 2012;27(6):451-454.
  3. Furujo M, Kinoshita M, Nagao M, et al. Methionine adenosyltransferase I/III deficiency: neurological manifestations and relevance of S-adenosylmethionine. Mol.Genet.Metab 2012;107(3):253-256.
  4. Green T, Steingart L, Frisch A, et al. The feasibility and safety of S-adenosyl-L-methionine (SAMe) for the treatment of neuropsychiatric symptoms in 22q11.2 deletion syndrome: a double-blind placebo-controlled trial. J.Neural Transm. 2012;119(11):1417-1423.
  5. Huidobro C, Fernandez AF, and Fraga MF. The role of genetics in the establishment and maintenance of the epigenome. Cell Mol.Life Sci. 2013;70(9):1543-1573.
  6. Kharbanda KK. Methionine metabolic pathway in alcoholic liver injury. Curr.Opin.Clin.Nutr.Metab Care 2013;16(1):89-95.
  7. Kharbanda KK, Bardag-Gorce F, Barve S, et al. Impact of altered methylation in cytokine signaling and proteasome function in alcohol and viral-mediated diseases. Alcohol Clin.Exp.Res. 2013;37(1):1-7.
  8. Levkovitz Y, Alpert JE, Brintz CE, et al. Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder. Eur.Psychiatry 2012;27(7):518-521.
  9. Liu XZ, Xie D, Yuan HJ, et al. Hearing loss and PRPS1 mutations: Wide spectrum of phenotypes and potential therapy. Int.J.Audiol. 2013;52(1):23-28.
  10. Mischoulon D, Alpert JE, Arning E, et al. Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder. J.Clin.Psychiatry 2012;73(6):843-848.
  11. Nierenberg AA, Kansky C, Brennan BP, et al. Mitochondrial modulators for bipolar disorder: a pathophysiologically informed paradigm for new drug development. Aust.N.Z.J.Psychiatry 2013;47(1):26-42.
  12. Shafqat N, Muniz JR, Pilka ES, et al. Insight into S-adenosylmethionine biosynthesis from the crystal structures of the human methionine adenosyltransferase catalytic and regulatory subunits. Biochem.J. 5-15-2013;452(1):27-36.
  13. Shilov VV, Shikalova IA, Vasil'ev SA, et al. [Correction of metabolic disorders during treatment of alcohol-induced liver injuries in patients with acute alcoholic intoxication]. Klin.Med.(Mosk) 2013;91(2):45-48.
  14. Sood A, Prasad K, Croghan IT, et al. S-adenosyl-L-methionine (SAMe) for smoking abstinence: a randomized clinical trial. J.Altern.Complement Med. 2012;18(9):854-859.
  15. Wang J, Wu Z, Li D, et al. Nutrition, epigenetics, and metabolic syndrome. Antioxid.Redox.Signal. 7-15-2012;17(2):282-301.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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