Herbs & Supplements:
SAMe (S-Adenosylmethionine)

Supplement Forms / Alternate Names
  • S-Adenosylmethionine, SAM, Ademetionine
Principal Proposed Uses
  • Osteoarthritis, Depression
Other Proposed Uses
  • Liver Disease, Fibromyalgia, Parkinson's Disease, Protection Against Ulcers Caused by Alcohol

S-adenosylmethionine is quite a mouthful; the abbreviation SAMe is easier to say. Its chemical structure and name are derived from two materials you may have heard about already: methionine, a sulfur-containing amino acid; and adenosine triphosphate (ATP), the body's main energy molecule.

SAMe was discovered in Italy in 1952. It was first investigated as a treatment for depression, but along the way it was accidentally noted to improve arthritis symptoms—a kind of positive "side effect." SAMe is presently classed with glucosamine and chondroitin as a potential "chondroprotective" agent, one that can go beyond treating symptoms to actually slowing the progression of arthritis. However, this exciting possibility has not yet been proven.

Unfortunately, SAMe is an extraordinarily expensive supplement at present. Full dosages can easily cost more than $200 per month.

Sources

The body makes all the SAMe it needs, so there is no dietary requirement. However, deficiencies in methionine, folate, or vitamin B₁₂ can reduce SAMe levels. SAMe is not found in appreciable quantities in foods, so it must be taken as a supplement.

It's been suggested that the supplement TMG might indirectly increase SAMe levels and provide similar benefits, but this effect has not been proven.

Therapeutic Dosages

A typical full dosage of SAMe is 400 mg taken 3 to 4 times per day. If this dosage works for you, take it for a few weeks and then try reducing the dosage. As little as 200 mg twice daily may suffice to keep you feeling better once the full dosage has "broken through" the symptoms.

However, some people develop mild stomach distress if they start full dosages of SAMe at once. To get around this, you may need to start low and work up to the full dosage gradually.

Recently, SAMe has come on the U.S. market at a recommended dosage of 200 mg twice daily. This dosage labeling makes SAMe appear more affordable (if you're only taking 400 mg per day, you'll spend only about a third or a fourth of what you'd pay for the proper dosage), but it is unlikely that SAMe will actually work when taken at such a low dosage.

Therapeutic Uses

A substantial amount of evidence suggests that SAMe can be an effective treatment for osteoarthritis, the "wear and tear" type of arthritis that many people develop as they get older.¹ However, the supplements glucosamine and chondroitin are much less expensive and just as well documented.

Several small studies suggest that SAMe can be helpful for depression.²

This supplement may also be helpful for certain liver conditions such as liver cirrhosis, pregnancy-related jaundice, and Gilbert's syndrome.^3–10 Additionally, SAMe may help the painful muscle condition known as fibromyalgia.^11,12

SAMe might be helpful for individuals with Parkinson's disease. It has been found to reduce the depression so commonly associated with the disease.¹³ In addition, the drug levodopa, used for Parkinson's disease, depletes the body of SAMe.^14,15 This suggests that taking extra SAMe might be helpful. However, it is also possible that SAMe could interfere with the effect of levodopa, requiring an increase in dosage.

Preliminary evidence suggests that SAMe can protect the stomach against damage caused by alcohol.¹⁶

What Is the Scientific Evidence for SAMe (S-Adenosylmethionine)?

Although there have been many studies of SAMe, a substantial percentage of them involved intravenous use of the supplement instead of the oral form.

Osteoarthritis

A substantial body of scientific evidence supports the use of SAMe to treat osteoarthritis.¹⁷ Double-blind studies involving a total of more than a thousand participants suggest that SAMe is about as effective as standard anti-inflammatory drugs. In addition, animal evidence suggests that SAMe may help protect cartilage from damage.^18,19

For example, a double-blind placebo-controlled Italian study tracked 732 people taking SAMe, naproxen (a standard anti-inflammatory drug), or placebo.²⁰ After 4 weeks, participants taking SAMe or naproxen showed about the same level of benefit as compared with those in the placebo group.

Another double-blind study compared SAMe with the anti-inflammatory drug piroxicam.²¹ A total of 45 individuals were followed for 84 days. The two treatments proved equally effective. However, the SAMe-treated individuals maintained their improvement long after the treatment was stopped, whereas those on piroxicam quickly started to hurt again. Similarly long-lasting results have been seen with glucosamine and chondroitin. This pattern of response suggests that these treatments are somehow making a deeper impact on osteoarthritis than simply relieving symptoms. However, while we have direct evidence that glucosamine and chondroitin can slow the progression of osteoarthritis, we do not know for sure that SAMe offers the same benefit.

In other double-blind studies, oral SAMe has also shown equivalent benefits to various doses of indomethacin, ibuprofen, and naproxen.^22,23,24

Depression

The evidence for SAMe as an antidepressant is provocative but far from definitive.

Several double-blind placebo-controlled studies have found SAMe effective in relieving depression, but they were all small and poorly reported, and many used an injected form of the supplement.^25,26 Furthermore, the most recent trial, a double-blind placebo-controlled study of 133 depressed patients, failed to find intravenous SAMe more effective than placebo. Researchers resorted to questionable statistical manipulation of the data to show benefit.²⁷

A recent 6-week double-blind trial of 281 individuals with mild depression compared oral SAMe to imipramine.²⁸ The results showed that the two treatments were about equally effective.

Other small studies have also compared the benefits of oral or intravenous SAMe to those of tricyclic antidepressants and have found generally equivalent results, although, again, poor reporting and inadequacies of study design (such as too limited a treatment interval) mar the meaningfulness of the outcomes.^29–34

Liver Disease

A 2-year double-blind placebo-controlled study of 117 individuals with alcoholic liver cirrhosis found that treatment with SAMe reduced mortality or need for a liver transplant in those with less advanced disease, but not in the group as a whole.³⁵ Other studies showed benefits in a variety of other liver conditions, including liver toxicity caused by oral contraceptives, pregnancy-related jaundice, and Gilbert's syndrome.^36–42

Fibromyalgia

Four double-blind trials have studied the use of SAMe for fibromyalgia,^43–46 three of them finding it to be helpful. Unfortunately, most of these studies gave SAMe either intravenously or as an injection into the muscles, sometimes in combination with oral doses. When you inject a medication, the effects can be quite different than when you take it orally. For that reason, these studies are of questionable relevance.

However, the one double-blind study that used only oral SAMe did find positive results.⁴⁷ In this trial, 44 people with fibromyalgia took 800 mg of SAMe or placebo for 6 weeks. Compared to the group taking placebo, those taking SAMe had improvements in disease activity, pain at rest, fatigue, and morning stiffness, and in one measurement of mood. In other respects, such as the amount of tenderness in their tender points, the group taking SAMe did no better than those taking the placebo.

It isn't clear whether SAMe is helping fibromyalgia through its antidepressant effects, or by some other mechanism.

Parkinson's Disease

Evidence suggests that levodopa (the drug used to treat Parkinson's disease) can reduce brain levels of SAMe.^48,49,50 This depletion may contribute to the side effects of levodopa treatment, as well as the depression sometimes seen with Parkinson's disease. One study found that SAMe taken orally improved depression without changing the effectiveness of levodopa.⁵¹ However, it is also possible that over time taking extra SAMe could interfere with levodopa's effectiveness (see Safety Issues).

Safety Issues

SAMe appears to be quite safe, according to both human and animal studies.^52–56 The most common side effect is mild digestive distress. However, SAMe does not actually damage the stomach.⁵⁷

Like other substances with antidepressant activity, SAMe might trigger a manic episode in those with bipolar disease (manic-depressive illness).^58,59,60

Safety in young children, pregnant or nursing women, or those with severe liver or kidney disease has not been established.

SAMe might interfere with the action of the Parkinson's drug levodopa.⁶¹ In addition, there may also be risks involved in combining SAMe with standard antidepressants.⁶² For this reason, you shouldn't try either combination except under physician supervision.

Interactions You Should Know About

If you are taking

• Standard antidepressants, including MAO inhibitors, SSRIs, and tricyclics: Do not take SAMe except on a physician's advice.
• Levodopa for Parkinson's disease: SAMe might help relieve the side effects of this drug. However, it might also reduce its effectiveness over time.

Last reviewed March 2002 by Medical Review Board

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