S-Adenosylmethionine (SAMe)

Covers SAMe for treatment of depression, Alzheimer's Disease and fibromyalgia. Learn about the usage, dosage, side-effects of SAMe.

Covers SAMe, a natural treatment of depression, Alzheimer's Disease, and fibromyalgia. Learn about the usage, dosage, side-effects of SAMe.


S-Adenosylmethionine (SAMe) is a naturally occurring compound that is involved in many biochemical processes in the body. SAMe plays a role in the immune system, maintains cell membranes, and helps produce and break down brain chemicals such as serotonin, melatonin, and dopamine as well as vitamin B12. SAMe also participates in the making of genetic material, known as DNA, and cartilage. Low amounts of folate (vitamin B9) in the body may lead to reduced levels of SAMe.

Numerous scientific studies indicate that SAMe may be useful in the treatment of depression, osteoarthritis, fibromyalgia, and liver disorders. Although it has been available in Europe by prescription for a number of years, SAMe was only recently introduced as a dietary supplement in the United States.


SAM-e Uses

SAMe offers a variety of potential therapeutic uses, primarily in the treatment of the health conditions listed below. It is important to note that SAMe has not been tested carefully over long periods of time. For this reason, it is not yet known whether using SAMe for an extended length of time (months or years) is safe.


SAM-e for depression
Preliminary research suggests that SAMe is more effective than placebo in treating mild to moderate depression and is just as effective as anti-depressant medications without the side affects frequently associated with the medications (headaches, sleeplessness and sexual dysfunction). Plus, antidepressants tend to take six to eight weeks to begin working, while SAMe seems to begin much more quickly than that.

More research regarding the safety and effectiveness of SAMe, especially for longer periods of time, is needed. It is not clear exactly how SAMe works to relieve depression, so it is best to avoid using SAMe together with other antidepressants. In addition, given the serious nature of this mood disorder, professional help should be sought for symptoms of depression before taking SAMe or any substance.

Laboratory and animal studies suggest that SAMe may reduce pain and inflammation in the joints as well as promote cartilage repair, but researchers are not clear about how or why this works. Clinical trials with people (although generally small in size and of short duration) have also shown favorable results for SAMe when used to relieve osteoarthritis symptoms. In several short-term studies (ranging from 4 to 12 weeks), SAMe supplements were as effective as NSAIDs (nonsteroidal anti-inflammatory drugs) in adults with knee, hip, or spine osteoarthritis. SAMe was equivalent to the medications in diminishing morning stiffness, decreasing pain, reducing swelling, improving range of motion, and increasing walking pace. Several of the studies also suggest that SAMe has fewer side effects than NSAIDs.

From studies comparing SAMe to placebo, this supplement seems to improve pain, fatigue, morning stiffness, and mood in those with fibromyalgia.

Liver Disease
Results of several animal studies suggest that SAMe may be beneficial in treating various liver disorders, particularly liver damage caused by excessive alcohol consumption. Animal studies also suggest that SAMe may protect the liver from damage after acetaminophen overdose (a pain-relieving medication purchased without a prescription). A study of 123 men and women with alcoholic liver cirrhosis (liver failure) found that SAMe treatment for 2 years may improve survival rates and delay the need for liver transplants more effectively than placebo. Although the results of this study are encouraging, more clinical trials are needed to determine whether SAMe is safe and effective for the prevention and/or treatment of liver disease.

SAM-e for Alzheimer's Disease
Studies suggest that people with Alzheimer's Disease (AD) have low levels of SAMe in the brain and that supplementation can actually increase those levels. While it has been reported that some individuals with AD have improved cognitive function from SAMe supplementation, well-designed research studies are needed to determine whether this supplement is truly safe and effective for people with the disease.

Although it is premature to tell if these are safe or appropriate uses for SAMe, some early research has looked at the relationship between SAMe and Parkinson's disease, migraine headaches, Sjogrens disorder (which causes pain in connective tissue), attention deficit/hyperactivity disorder (ADHD) in adults, and vascular disorders such as heart disease.

SAMe levels may be low in people with Parkinson's and heart disease. However, experiments in rats have indicated that SAMe supplements may actually cause Parkinson's disease in these animals.

Given SAMe's structure, some have raised concern about the potential for SAMe to increase homocysteine levels. (Homocysteine has been shown to contribute to the development of plaques in the blood vessels). However, early information suggests that SAMe may actually lower homocysteine. Research is needed to know whether taking SAMe supplements may reduce homocysteine and reduce one's chances of getting heart disease.

A preliminary study of 124 migraine sufferers suggests that SAMe may decrease the frequency, intensity, and duration of headaches as well as lead to an improved sense of well being and use of fewer pain killers.


Dietary Sources for SAM-e

SAMe is not found in food. It is produced by the body from ATP and the amino acid methionine. (ATP serves as the cell's major energy source and drives a number of biological processes including muscle contraction and the production of protein).


Available Forms of SAM-e

  • S-adenosylmethionine butanedisulfonate
  • S-adenosylmethionine disulfate ditosylate
  • S-adenosylmethionine disulfate tosylate
  • S-adenosylmethionine tosylate

It is important to purchase enteric-coated tablets packaged in foil or foil blister packs. SAMe should be stored in a cool, dry place, but not refrigerated. Tablets should be kept in the blister pack until the time of ingestion.


How to Take SAM-e

Starting with a low dose (for example 200 mg per day) and increasing slowly helps avoid upset to the digestive system.

It is important to note that many of the studies evaluating SAMe for the conditions mentioned have tested injectable, not oral, forms of SAMe. Therefore, the reliability and effectiveness of oral SAMe is not entirely clear. Look for enteric-coated tablets as these are more stable and may be more dependable in terms of the amount of SAMe in the pill.



There are no known scientific reports on the pediatric use of SAMe. Therefore, it is not currently recommended for children.


Recommended doses of SAMe vary depending on the health condition being treated. The following list provides guidelines for the most common uses:

  • depression: The majority of studies have used between 800 and 1,600 mg of SAMe per day for depression. The daily dosage is typically split between morning and afternoon.
  • Osteoarthritis: A dosage of 600 mg (200 mg three times per day) for the first two weeks and then 400 mg (200 mg twice per day) for another 22 weeks has shown improvement in symptoms of osteoarthritis. Another study demonstrated improvement using 1,200 mg (400 mg three times per day) for 30 days.
  • Fibromyalgia: A dosage of 800 mg per day for six weeks was shown to improve symptoms.
  • Alcoholic liver disease: 800-1,200 mg per day orally in divided doses for six months enhances liver function. For liver disease, SAMe should be administered with the supervision of a qualified health care provider. This is because SAMe is administered intravenously.



Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable healthcare provider.

The safety of SAMe has not been fully assessed in children or women who are pregnant or nursing. For this reason, these groups of people should avoid SAMe. Side effects may include dry mouth, nausea, flatulence, diarrhea, headache, anxiety, a feeling of elation, restlessness, and insomnia. For this reason, SAMe should not be taken at night.

People with bipolar disorder (manic-depression) should not take SAMe since it may worsen manic episodes. SAMe should not be combined with different antidepressants without first consulting a health care provider.

People taking SAMe should supplement its use with a multivitamin that contains folic acid and vitamins B12 and B6.


Possible Interactions

If you are currently being treated with any of the following medications, you should not use SAMe without first talking to your healthcare provider.

SAM-e and antidepressant medications
There have been reports of SAMe interacting with antidepressant medications and increasing the potential for side effects including headache, irregular or accelerated heart rate, anxiety, and restlessness. On the other hand, because it often takes up to six or eight weeks for antidepressant medications to start working, SAMe has been used with certain drugs to relieve symptoms more quickly. Consult your healthcare provider before using SAMe if you are taking any medications for depression.


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APA Reference
Staff, H. (2008, December 21). S-Adenosylmethionine (SAMe), HealthyPlace. Retrieved on 2024, June 22 from

Last Updated: May 8, 2019

Medically reviewed by Harry Croft, MD

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