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S-adenosylmethionine is quite a mouthful; the abbreviation SAMe (pronounced samm-ee) 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 symptomsa
kind of positive side effect.
Unfortunately, SAMe is an extraordinarily expensive supplement at present. Full dosages
can easily cost more than $200 per month.
The body makes all the SAMe it needs, so there is no dietary requirement. However,
deficiencies in methionine, folate, or vitamin B
12
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 trimethylglycine (TMG) might indirectly increase
SAMe levels and provide similar benefits, but this effect has not been proven.
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 US 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.
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.
A moderate amount of evidence suggests that SAMe might be helpful for depression.
Weak and inconsistent evidence hints that SAMe might be helpful for a variety of liver
conditions such as cirrhosis, chronic viral hepatitis, pregnancy-related jaundice, and
Gilbert's syndrome.
SAMe may help the painful muscle condition known as fibromyalgia.
SAMe has undergone some investigation as a possible supportive treatment for
Parkinson's disease. One study suggests that it may reduce the depression so commonly
associated with the disease. In addition, the drug levodopa, used for Parkinson's
disease, depletes the body of SAMe. This suggests that taking extra SAMe might be
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helpful. However, it is also possible that SAMe could interfere with the effect of levodopa,
requiring an increase in dosage.
Highly preliminary evidence suggests that SAMe can protect the stomach against damage
caused by alcohol.
Osteoarthritis
A substantial body of scientific evidence supports the use of SAMe to treat
osteoarthritis. Double-blind studies involving a total of more than 1,000 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.
For example, a double-blind, placebo-controlled Italian study tracked 732 people taking
SAMe, naproxen (a standard anti-inflammatory drug), or placebo. After 4 weeks,
participants taking SAMe or naproxen showed about the same level of benefit as compared
to each other, and a superior level of benefit as compared to those in the placebo group.
A more recent double-blind study compared SAMe to celecoxib (Celebrex), a member of the
newest class of non-steroidal anti-inflammatory drugs. Celecoxib produced more rapid
effects than SAMe, but over time SAMe appeared to catch up. However, the lack of a
placebo group makes these results less than fully reliable.
Another double-blind study compared SAMe with the anti-inflammatory drug piroxicam. 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 some direct
evidence that glucosamine and chondroitin can slow the progression of osteoarthritis, the
evidence regarding SAMe is more hypothetical.
In other double-blind studies, oral SAMe has shown equivalent benefits to various doses of
indomethacin, ibuprofen, and naproxen.
Depression
The evidence for SAMe for the treatment of depression is provocative but far from
definitive. Several double-blind, placebo-controlled studies have found SAMe effective in
relieving depression, but most were small and poorly reported, and many used an injected
form of the supplement. Furthermore, 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.
Other trials compared SAMe to standard antidepressants rather than to placebo. The best
of these was a 6-week, double-blind trial of 281 people with mild depression that compared
oral SAMe to imipramine. The results indicated that the two treatments were about
equally effective. However, the absence of a placebo group makes this study less than fully
definitive.
Other studies have also compared the benefits of oral or intravenous SAMe to those of
tricyclic antidepressants and have also found generally equivalent results; however, again,
poor reporting and inadequacies of study design (such as too limited a treatment interval)
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mar the meaningfulness of the reported outcomes.
Researchers have also studied the effectiveness of oral SAMe in combination with
antidepressants. Seventy-three patients with treatment-resistant major depression were
randomized to take SAMe (800 mg twice daily) or a placebo. Both groups continued to
take their selective serotonin reuptake inhibitor (SSRI). Adding SAMe to the treatment
increased the rate at which patients responded to their antidepressant medication.
Fibromyalgia TOP
Four double-blind trials have studied the use of SAMe for fibromyalgia, three of them
finding it to be helpful. Unfortunately, most of these studies used SAMe given 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.
Nonetheless, the one double-blind study that used only oral SAMe did find positive
results. 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 TOP
Evidence suggests that levodopa (the drug used to treat Parkinson's disease) can reduce
brain levels of SAMe. 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. However, it is also possible that over time taking extra SAMe could interfere
with levodopa's effectiveness. (See Safety Issues.)
SAMe appears to be quite safe, according to both human and animal studies. The most
common side effect is mild digestive distress. However, SAMe does not actually damage
the stomach.
Like other substances with antidepressant activity, SAMe might trigger a manic episode in
those with bipolar disease (manic-depressive illness).
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. In addition, there
may also be risks involved in combining SAMe with standard antidepressants. For this
reason, you shouldn't try either combination except under physician supervision.
If you are taking:
Standard antidepressants, including MAO inhibitors, SSRIs, and tricyclics: Do not take
SAMe except on a physician's advice.
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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 August 2013 by EBSCO CAM Review Board
Last Updated: 8/22/2013
This content is reviewed regularly and is updated when new and relevant evidence is made available.
This information is neither intended nor implied to be a substitute for professional medical advice. Always
seek the advice of your physician or other qualified health provider prior to starting any new treatment or
with questions regarding a medical condition.
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