Original Article: http://www.mayoclinic.com/health/same/NS_patient-same
Natural Standard® Patient Monograph, Copyright © 2013 (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.
SAMe was first discovered in 1953 by a researcher named Cantoni. It is formed in the body from methionine and adenosine triphosphate in a reaction catalyzed by methionine adenosyltransferase. SAMe functions as a primary methyl group donor in a variety of reactions in the body. After donating a methyl group, SAMe is converted to S-adenosyl-homocysteine.
SAMe is used for psychiatric illnesses, infertility, liver concerns, premenstrual disorders and musculoskeletal disorders, among others.
SAMe has been studied extensively in the treatment of osteoarthritis and depression. Many trials provide evidence that SAMe reduces the pain associated with osteoarthritis and is well tolerated in this patient population. Some evidence is available for the use of SAMe for intrahepatic cholestasis of pregnancy although additional study is needed in this area. Anti-inflammatory and analgesic (pain relieving) activity has also been attributed to SAMe.
Future well-designed clinical trials are required in the areas of depression, fibromyalgia and liver cholestasis before a strong recommendation can be made in these areas.
Ademetionin, ademetionine, adenosylmethionine, Ade-SD4, AdoMet, Geptral (Russian), Gumbaral (German), Heptral (Russian), S-adenosylmethionine, SAM-e, Sammy, Samyr (Italian), sulfoadenosilmethionina (Italian), sulfo-adenosil-L-metionina (Spanish), sulfo-adenosyl-L-methionine sulfate-p-toluensulfonate (stable salt form), sulfo-adenosyl-methionine.
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.
OsteoarthritisSAMe has been studied extensively in the treatment of osteoarthritis. SAMe reduces the pain associated with osteoarthritis and is well tolerated in this patient population. Although an optimal dose has yet to be determined, SAMe appears as effective as the non-steroidal anti-inflammatory drugs (NSAIDS). Additional study is warranted to confirm these findings.
Attention deficit hyperactivity disorder (ADHD)Preliminary evidence from an open trial suggests that SAMe may be of benefit for adults with ADHD. More study is needed in this area.
Cholestasis (pregnancy)Curently, there is insufficient available evidence to recommend for or against the use of SAMe for cholestasis (build up of bile in the liver) in pregnant women. It is important to note that there is no information on the use of SAMe prior to the third trimester.
Cholestasis (non-pregnant)SAMe may be beneficial for pruritus (severe itching) and serum bilirubin levels associated with cholestasis associated with non-pregnancy. However, additional study is needed.
DepressionSAMe has been studied for use in depression for many decades, however, currently available trials are inconclusive.
FibromyalgiaSince fibromyalgia is characterized by chronic pain and depressive symptoms, there is an increased interest in studying SAMe for this indication. Current available evidence, however, does not appear to show any benefit of SAMe over placebo in reducing the number of tender points and in alleviating depression. Additional study is needed to confirm these findings.
Liver disease (general)Preliminary evidence suggests that SAMe may normalize levels of liver enzymes in individuals with liver disease. Additional study is needed in this area.
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)
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 metabolism (hepatic cirrhosis), adjustment disorder, aging, alcoholism, Alzheimer's disease, anxiety, bilirubin and polyphyrin metabolism disorders, bursitis, cirrhosis (primary biliary), dementia, bipolar disorder, drug/toxin induced hepatotoxicity (liver damage), gastritis (hemorrhagic), Gilbert's syndrome, heart disease, hepatitis, high cholesterol, infertility, intrahepatic cholestasis (oral-contraceptive-induced), intrahepatic cholestasis (total parenteral nutrition-induced), ischemic stroke, lead toxicity, male sterility, migraine, multiple sclerosis, pancreatitis, myelopathy (spinal cord injury), Parkinson's disease, post-concussive syndrome, postpartum depression, premenstrual syndrome, premenstrual dysphoric disorder, psychiatric illness, rheumatoid arthritis, seizures, Sjogren's syndrome, systemic sclerosis, tendonitis.
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):
Both oral (taken by mouth) and intravenous (injection) preparations of SAMe have been studied in clinical trials with some evidence of benefit for certain conditions. SAMe appears effective for osteoarthritis, and 600-1,200 milligrams has been taken daily in 1-3 divided doses for 10-84 days. Up to 1,600 milligrams has been taken for up to two weeks for the treatment of cholestasis. For depression, 800-1,600 milligrams daily was the most commonly used dosage range in clinical studies, for up to six weeks. For fibromyalgia, 400 milligrams twice daily has been used. For intrahepatic cholestasis of pregnancy, 500 milligrams given twice daily has been used. For general liver disease, 600-1,200 milligrams daily has also been used.
As an injection into the muscle, the most common dose for SAMe is 200-400 milligrams for 2-4 weeks. Both S-adenosyl-L-methionine 1,4-butanedisulphonate stable salt and disulfate-p-toluenesulfonate stable salt have been studied as injections. 500mg SAMe twice daily has also been delivered in a slow running infusion for twelve days followed by oral administration of 500mg twice daily. Injections should only be given under the supervision of a qualified healthcare professional, including a pharmacist.
Children (younger than 18 years):
There is no proven safe or effective dose for SAMe in children.
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.
Avoid in individuals with a known allergy or hypersensitivity to S-adenosyl-L-methionine. Flushing, erythema (reddening of the skin), palpitation, dizziness, and nausea (symptoms of an anaphylactic reaction) have been reported.
Side Effects and Warnings
SAMe has been well tolerated in the majority of clinical trials conducted. The most common adverse effects reported are gastrointestinal in nature with nausea being the most frequently reported. Skin rashes have also been reported. Anxiety and hypomania have been reported mainly in trials that have included patients with bipolar disorder. The use of SAMe has not been adequately studied in the pediatric and elderly population, in pregnancy other than the third trimester, or during breastfeeding.
When given as an injection, diluted SAMe has caused superficial phlebitis (inflammation of a vein) and tachycardia (increased heart rate), increased perspiration, transient pain at the injection site, arm soreness, flushing, erythema (reddening of the skin), palpitation, dizziness, nausea, pruritus (itching), urticaria ("hives"), and epigastric pain.
SAMe may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.
When taken by mouth or by injection, SAMe may cause a hot sensation and itchiness of the ear, nausea, vomiting, dry mouth, heartburn, blood in the stool, anorexia, mild diarrhea, stomachaches, slight constipation, increased thirst, increased salivation, urinary frequency, intolerable bowel symptoms, gas, and decreased appetite. Anxiety, insomnia, hypomania, hostility, insomnia, elevated mood, psychoactivation, headache, suicidal ideation, hyperactivity, a reduced need for sleep, and bursts of energy have also been reported.
Pregnancy and Breastfeeding
SAMe crosses the placenta. SAMe is not recommended in the first trimester or during breastfeeding due to a lack of available scientific evidence. However, SAMe has been used in the third trimester for the treatment of intrahepatic cholestasis with no reported adverse effects in the pregnant women or their newborn babies. A single study of SAMe included women in second trimester with no adverse effects noted. Use cautiously in women in their third trimester of pregnancy; SAMe should only be used in pregnancy if the benefits clearly outweigh the risks.
This patient information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
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