Natural Standard® Patient Monograph, Copyright © 2014 (www.naturalstandard.com). All Rights Reserved. Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

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.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older):

To treat attention-deficit hyperactivity disorder (ADHD), 400-milligram tablets of SAMe have been taken by mouth three times daily and then increased to a maximum of 800 milligrams three times daily for four weeks.

To treat bile flow problems, 1,600 milligrams of SAMe has been taken by mouth daily for two weeks. A dose of 1,000 milligrams has been injected into the vein (IV) daily for four weeks.

To treat bile flow problems in pregnancy, 500 milligrams of Transmetil® has been given by slow infusion twice daily for 14 days, followed by 500 milligrams of SAMe taken by mouth twice daily until or after delivery. A dose of 600 milligrams of Samyr® has been taken by mouth alone. A dose of 1,800 milligrams of Samyr® has been taken by mouth together with beta-mimetics daily. A dose of 500 milligrams has been taken by mouth twice daily. Doses of SAMe that have been given include: 1,000 milligrams injected into the muscle daily until delivery, 200 or 800 milligrams given through IV daily for 20 days; 800 milligrams given through IV daily in two divided doses until delivery; 800 milligrams given through IV; and 800 milligrams given through IV over three hours for 20 days. A dose of 800 milligrams of disulfate-p-toluene sulfonate stable salt (BioResearch, S.p.A, Milan, Italy) has been given through IV daily.

To treat depression, daily doses of 800-1,600 milligrams of SAMe by mouth for up to six weeks are most common. Daily doses of 200-1,600 milligrams have been taken by mouth or given through tube feeding. Doses of SAMe have been given through IV or injected into the muscle, ranging from 200 to 400 milligrams daily for up to eight weeks. A dose of 200 milligrams of SAMe has been taken by mouth twice daily for two days, followed by 1,000 milligrams daily for nine days, followed by 1,200 milligrams daily for nine days, followed by 1,600 milligrams daily to day 42. Doses of 1,000-1,600 milligrams have been taken by mouth daily for 15 days to six weeks. Doses of 150-400 milligrams given through IV daily for 3-4 weeks are most common. A dose of 400 milligrams of s-adenosyl-L-methionine 1,4-butanedisulphonate stable salt (Knoll Farmaceutici S.p.A., Liscate, Milan, Italy) has been injected into the muscle daily. Doses of 75-200 milligrams of SAMe have been injected into the muscle for 14-30 days. Doses of 200-400 milligrams of SAMe per 250 milliliters of saline have been given ithrough IV during the first three days of treatment, followed by 400 milligrams of SAMe daily on days 4-14. Doses of 45 milligrams or 150 milligrams of SAMe have been injected into the muscle for 1-2 weeks. Bolus injections of 200 milligrams of SAMe have been given once daily in the morning for 14 days. Doses of 200-1,600 milligrams of SAMe daily have been taken by mouth or given with tube feeding. Doses of SAMe that have been given include 200-400 milligrams daily of injectable formulas or 800-1,600 milligrams taken by mouth daily with meals and typically in divided doses, for up to eight weeks. Doses of 200-800 milligrams of SAMe have been given through IV daily or every other day for 2-3 weeks. A dose of 200 milligrams of SAMe has been injected into the muscle daily for 3-4 weeks, as has 15 milligrams three times daily for 15 days, or 150 milligrams daily for 15 days. Doses of 800-1,600 milligrams of SAMe have been taken by mouth daily. Doses of 150-400 milligrams have been given through IV or injected into the muscle daily. A dose of 400 milligrams of SAMe has been injected into the muscle daily for 28 days.

To treat depression caused by opiate use, 400 milligrams of SAMe has been given through an IV for six days, followed by 1,000 milligrams of SAMe taken by mouth once daily for one day or 200 milligrams of SAMe injected into the muscle once daily and 400 milligrams SAMe 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.

To treat fibromyalgia, 400 milligrams has been taken by mouth twice daily. A dose of 200 milligrams has been injected into the muscle daily, plus 200 milligrams taken by mouth twice daily. Doses of 200-400 milligrams have been given through IV daily. A dose of 200 milligrams has been injected into the muscle daily with 200 milligrams of SAMe taken by mouth twice daily.

To treat general liver disease, 400-1,200 milligrams of SAMe has been taken by mouth daily for up to 24 weeks. A dose of 200 milligrams of Samyr® has been taken by mouth twice daily for six months. Doses ranging from 1,200 to 1,500 milligrams daily have been taken by mouth for 1-24 months. A dose of 600 milligrams of SAMe in 250 milliliters of saline has been injected into the muscle for three days, followed by 400 milligrams of SAMe taken by mouth three times daily for an additional 30 days. Doses of 200-800 milligrams of SAMe have been used daily for up to 15 days. A dose of 100 milligrams of SAMe has been injected into the muscle daily for 30 days. A single dose containing 50 milligrams of SAMe, 50-100 milligrams of SAMe daily, or 15 milligrams of SAMe have been given through IV or injected into the muscle four times daily for 30 days. A dose of 200 milligrams of SAMe has been injected into the muscle daily for 30 days. Doses of 200-800 milligrams have been given through IV daily for 15-17 days. A dose of 800 milligrams of SAMe has been given through IV daily for 17 days. A dose of 800 milligrams has been given through IV, followed by 1,600 milligrams given through IV. A dose of 600 milligrams of SAMe in 250 milliliters of saline has been given through IV for three days, followed by 400 milligrams of SAMe by mouth three times daily for an additional 30 days.

To treat osteoarthritis, 600mg-1,200 milligrams of SAMe has been taken by mouth daily in 1-3 divided doses for 10-84 days. A five-milliliter bolus containing 400 milligrams of SAMe has been given through IV daily for five days, followed by 200 milligrams of SAMe taken by mouth three times daily for 23 days. SAMe has been taken by mouth for 3-12 weeks in doses ranging from 200 milligrams 3-6 times daily to 400 milligrams 2-6 times daily; in some cases, 400 milligrams of SAMe has been given through IV once daily for the first five days, followed by SAMe taken by mouth. A dose of 60 milligrams of SAMe has been injected into the muscle for 7-14 days. SAMe has typically been taken by mouth for 3-12 weeks in doses ranging from 200 milligrams 3-6 times daily to 400 milligrams 2-6 times daily; however, 400 milligrams of SAMe has been given through IV once daily for five days before switching to a formula taken by mouth.

To treat 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 week.

To treat cirrhosis (liver disease in which there is bile duct inflammation), 50-100 milligrams of SAMe has been given through IV or injected into the muscle in 1-4 divided doses or as a single treatment for up to 30 days.

To treat fatty liver disease, 250 milligrams of SAMe has been given through a slow bolus drip every 12 hours for 30 days in 500 milliliters of five-percent levulose.

To treat hepatitis (swelling and inflammation of the liver), 200 milligrams of SAMe has been given through IV daily for 15 days, followed by SAMe injected into the muscle for 15 days. A dose of 500 milligrams of SAMe has been given through IV in 250 milliliters of glucose solution daily until recovery.

Children (younger than 18 years):

To treat hepatitis, 75 milligrams of SAMe has been taken by mouth daily for 35 days in children under 13 years of age. A dose of 150 milligrams of SAMe has been taken by mouth daily for 35 days in children over 13 years of age. A dose of 100 milligrams of SAMe has been given through IV daily for 15 days, followed by SAMe injected into the muscle for 15 days.

Evidence

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.

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 against this use (it may not work)
F
Strong scientific evidence against this use (it likely does not work)

Grading rationale

Evidence gradeCondition to which grade level applies
B

Osteoarthritis

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. Doses have ranged from 600 to 1,200 milligrams taken by mouth daily, but the optimal dose still needs to be determined.
C

Attention-deficit hyperactivity disorder (ADHD)

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

Bile flow improvement

Some evidence suggests that SAMe may treat symptoms linked to bile flow problems. However, information is still limited. A report has been published on the use of SAMe during tube feeding for the treatment of bile flow problems. Higher-quality research is needed in this area.
C

Bile flow improvement (pregnancy)

Conclusions are unable to be made on the use of SAMe for bile flow problems during pregnancy. One trial suggests that SAMe may be no better than placebo in treating symptoms of the condition. In the available studies, SAMe appears to have been well tolerated and lacking side effects on mothers or newborns. Common doses range from 500 milligrams taken by mouth twice daily to 800 milligrams through an intravenous (IV) tube daily. Information on the use of SAMe before the third trimester is still lacking.
C

Depression

SAMe has been widely studied for use in depression. 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. One trial was conducted over six weeks and suggested that SAMe may not be as effective as antidepressants. Higher-quality research that compares SAMe to other antidepressants and is conducted for at least six weeks is needed. Firm conclusions are lacking at this time.
C

Fibromyalgia (chronic muscle pain)

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

Liver disease (general)

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

Schizophrenia

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.

Uses based on tradition or theory

The below uses are based on tradition or scientific theories. 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.

Acetaminophen toxicity, adjustment disorder, aging, alcoholism, Alzheimer's disease, antioxidant, anxiety, bursitis (inflammation between joints and muscles), cirrhosis (primary biliary, inflammation of bile ducts), dementia, gastritis (inflammation of stomach lining), Gilbert's syndrome (high levels of bilirubin, a toxic substance), head injury, heart disease, hepatitis, hepatitis (in children), high cholesterol, infertility, lead toxicity, liver toxicity (caused by drugs or toxins), male sterility, memory, metabolic abnormalities, migraine, multiple sclerosis, nerve pain, nervous system disorders, pancreatitis (pancreas inflammation), Parkinson's disease, postpartum depression, premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), psychiatric illness, rheumatoid arthritis, seizures, Sjögren's syndrome (dry eyes and mouth), spinal cord injury, stroke, systemic sclerosis (autoimmune disease of skin and blood vessels), tendonitis (tendon inflammation).

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 affect 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 increased in the blood and may cause increased 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 may affect the nervous system, agents that may be toxic to the liver, agents that may treat psychiatric disorders, alcohol, antidepressants (monoamine oxidase inhibitors [MAOIs] and selective serotonin reuptake inhibitors [SSRIs]), anti-inflammatory agents, cholesterol-lowering agents, clomipramine, ear agents, estrogens, eye agents, levodopa, methotrexate, pain relievers, skin agents, stomach agents, tolcapone, and tricyclic antidepressant drugs (TCAs).

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 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 alcohol, antidepressants (monoamine oxidase inhibitors [MAOIs] and selective serotonin reuptake inhibitors [SSRIs]), anti-inflammatory herbs and supplements, antioxidants, cholesterol-lowering herbs and supplements, choline, docosahexaenoic acid (DHA), folic acid, herbs and supplements that may affect the nervous system, herbs and supplements that may be toxic to the liver, herbs and supplements that may treat psychiatric disorders, hormonal herbs and supplements, methionine, minerals, pain relievers, stomach agents, vitamins, vitamin B6, and vitamin B12.

Methodology

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

Monograph methodology

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® (Italian), sulfo-adenosil-L-metionina (Spanish), sulfo-adenosyl-L-methionine sulfate-p-toluensulfonate (stable salt form), sulfoadenosilmethionina, sulfo-adenosyl-methionine.

Selected combination products: GNC Triflex with SAM-e (chondroitin, glucosamine, MSM, SAM-e).

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 if allergic or sensitive to S-adenosyl-L-methionine (SAMe). There have been reports of dizziness, heart palpitations, memory and concentration problems, nausea, and skin flushing and redness.

Side Effects and Warnings

SAMe has been found to be generally well tolerated. Common side effects include anxiety and skin rashes. Some studies report that significant side effects related to SAMe given through tube feeding are lacking in general.

SAMe is likely safe when taken by mouth in doses of 400-600 milligrams daily for up to two years; when taken by mouth at doses of 800-1,600 milligrams daily for up to 42 days; and when given through IV in doses up to 800 milligrams daily for up to 21 days.

SAMe is possibly safe when used during the third trimester of pregnancy in doses of 800 milligrams given through IV daily for short periods of time (less than four weeks). Use cautiously in pregnant women. SAMe should only be used in pregnancy if the benefits clearly outweigh the risks. More safety information is needed on the use of SAMe during pregnancy other than the third trimester, during breastfeeding, and in children and the elderly.

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 affect blood pressure. Caution is advised in people with high blood pressure or those taking drugs or herbs and supplements that affect blood pressure.

Use cautiously in people who have anxiety disorders, bipolar disorder, and depression.

Avoid if allergic or sensitive to SAMe. There have been reports of dizziness, heart palpitations, memory and concentration problems, nausea, and skin flushing and redness.

Avoid in people who have bipolar disorder. SAMe has been linked to mood changes in people with and without a history of bipolar disorder.

SAMe may also cause abscess (buildup of pus) at the injection site, abnormal heart rhythm, agitation, aggression, anorexia, bloating, bloody stool, blurry vision, changes in urination, changes in weight, congestion, constipation, a crawling feeling on the skin, decreased appetite, diarrhea, difficulty breathing, drowsiness, dry mouth, fatigue, a feeling of weakness, gas, hair loss, headache, heartburn, high levels of liver enzymes, hives, increased saliva, increased suicide risk, increased sweating, increased thirst, irritability, itchy ear, jitteriness, low energy, nervousness, night sweats, numbness or pain at injection site, queasiness, restlessness, serotonin syndrome (drug reaction), shakiness, shortness of breath, skin itching, sleep problems, soft stools, stomach pain, vein inflammation, and vomiting.

Pregnancy and Breastfeeding

There is a lack of scientific evidence on the use of SAMe during the first and second trimesters of pregnancy or during breastfeeding. SAMe has been used in the third trimester for the treatment of bile flow problems, with a lack of side effects in mothers or babies. However, all studies were short-term (less than four weeks). Information on long-term safety is still needed.

Selected references

  1. Ackermann R, Semmler A, Maurer GD, et al. Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites. J.Neurooncol. 2010;97(3):425-427.
  2. Adams JB, Audhya T, McDonough-Means S, et al. Effect of a vitamin/mineral supplement on children and adults with autism. BMC.Pediatr. 2011;11:111.
  3. Chan A, Remington R, Kotyla E, et al. A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia. J.Nutr.Health Aging 2010;14(3):224-230.
  4. 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.
  5. da Costa KA, Sanders LM, Fischer LM, et al. Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans. Am.J.Clin.Nutr. 2011;93(5):968-974.
  6. De Silva V, El-Metwally A, Ernst E, et al. Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology.(Oxford) 2011;50(5):911-920.
  7. De Silva V, El-Metwally A, Ernst E, et al. Evidence for the efficacy of complementary and alternative medicines in the management of fibromyalgia: a systematic review. Rheumatology.(Oxford) 2010;49(6):1063-1068.
  8. Feld JJ, Modi AA, El-Diwany R, et al. S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders. Gastroenterology 2011;140(3):830-839.
  9. Gerards M, Sluiter W, van den Bosch BJ, et al. Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome. J.Med.Genet. 2010;47(8):507-512.
  10. Grubbs R, Vugrek O, Deisch J, et al. S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal hydrops and fatal outcomes. J.Inherit.Metab Dis. 2010;33(6):705-713.
  11. Lamers Y, Coats B, Ralat M, et aI. Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women. J.Nutr. 2011;141(5):835-842.
  12. Papakostas GI, Mischoulon D, Shyu I, et al. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am.J.Psychiatry 2010;167(8):942-948.
  13. Pizzolo F, Blom HJ, Choi SW, et al. Folic acid effects on s-adenosylmethionine, s-adenosylhomocysteine, and DNA methylation in patients with intermediate hyperhomocysteinemia. J.Am.Coll.Nutr. 2011;30(1):11-18.
  14. Sarris J. Clinical depression: an evidence-based integrative complementary medicine treatment model. Altern.Ther.Health Med. 2011;17(4):26-37.
  15. Shin W, Yan J, Abratte CM, et al. Choline intake exceeding current dietary recommendations preserves markers of cellular methylation in a genetic subgroup of folate-compromised men. J.Nutr. 2010;140(5):975-980.

This evidence-based monograph was prepared by The Natural Standard Research Collaboration

www.naturalstandard.com