SAMe (S-adenosyl-methionine) for osteoarthritis

We’ve discussed SAMe’s use as an anti-depressant on this Blog, as well as its potential to support liver health. But over the past twenty years there has also been much research into SAMe to counter osteoarthritis pain. In a number of trials in Europe and in the US, SAMe has equalled the effect of nonsteroidal anti-inflammatory drugs (NSAIDS) like ibuprofen in decreasing pain and improving function. Furthermore, it is better tolerated than NSAIDS, which cause clinical concern about side effects especially when taken at high doses over long periods of time.

Here’s one drawback to SAMe for osteoarthritis: trials have shown this supplement to have a slower onset of action than NSAIDs–an initial starting use of about 4 weeks is needed for full effectivesness. In the meantime, some patients may continue to take NSAIDS, gradually reducing the dose.

See the NYBC description of SAMe for additional information, including our recommendation to take adequate B-complex along with this supplement.

For further reading and references on SAMe for osteoarthritis, we recommend Natural Products: A Case-Based Approach for Health Professionals (American Pharmacists’ Assoc., Washington, DC: 2006), pp. 37-49

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SAM-e (S-adenosyl-L-methionine) for liver disease

Here’s an excerpt from the New York Buyers’ Club guide to using nutritional supplements in the management of liver disease. This entry deals with SAMe, which you’ll also find discussed on this Blog for its use as an anti-depressant. (SAMe is currently the subject of a multi-year National Institutes of Health study of depression at Massachusetts General and Butler Hospitals.)

See also the NYBC entry on SAMe, which explains why it may be a good idea to use this supplement together with vitamins B6, B12, folic acid and, possibly, betaine (TMG).

 S-adenosyl-L-methionine (SAMe). SAMe is an amino acid which helps in the manufacture of the “master antioxidant” glutathione in the liver. It appears to help cell membranes function normally, and assists the liver with detoxification (removal of toxins such as ethanol and pesticides from the system). SAMe can help to normalize bile secretion by the liver, a process commonly affected in chronic liver diseases. Interestingly, in several European studies of people living with hepatitis B or C, it has also been shown to help reduce jaundice, fatigue, and chronic skin irritation and itching, while also lowering liver enzymes and bilirubin levels. Dosages of SAMe in these studies were either 800 mg given intravenously or 800 to 1,600 mg given orally. No significant side effects were reported in any of the studies with SAMe in chronic liver disease.


As SAMe’s mechanism of action in the liver has become better understood by researchers, it’s been used to treat people with alcohol-induced damage to the liver. Basically, SAMe raises levels of the key antioxidant glutathione, which acts in the body to eliminate toxins such as ethanol and other poisons. In this way, SAMe can address cirrhosis and hepatitis stemming from alcohol abuse.

Other recent investigations have suggested that SAMe may play a role in preventing liver cancer, since it seems to have the ability to induce the death of cancerous liver cells. See, for example: Pascale RM, Simile MM, De Miglio MR, Feo F. Chemoprevention of hepatocarcinogenesis: S-adenosyl-L-methionine. Alcohol. 2002 Jul;27(3):193-8.

SAM-e (S-Adenosylmethionine): an anti-depressant with added benefits

We’ve reported on the NIH-funded trial of antidepressants SAM-e (a dietary supplement) and Lexapro (a prescription drug) currently underway at Massachusetts General Hospital and Butler Hospital (see under “SAM-e” on this Blog).

Recently one of our NYBC associates drew our attention to an interview from a few years back with Richard Brown, M.D., clinical psychiatry professor at Columbia University with a long-time interest in depression treatments. Dr. Brown has had experience using SAM-e to treat depression in people with HIV, and notes that the added benefits of this dietary supplement for joint and liver health may make it a very good option for treatment over the longer term.

See also the NYBC entry on SAM-e.



Used in tandem with conventional antidepressants, SAM-e also enhances their effectiveness. A study published in Psychiatry Research comparing 40 depression sufferers taking imipramine, half of whom were also given 400 mg of SAM-e a day, found a significant difference between the two treatments. “The SAM-e group was much better in four days,” says Brown. And compared with other pharmaceutical antidepressants, SAM-e also has fewer nasty side effects.

Despite its benefits, SAM-e is not entirely foolproof. Bipolar disorder sufferers should avoid SAM-e as it can induce mania, and some people experience mild gastrointestinal problems, occasional headaches or heart palpitations. Still, SAM-e doesn’t cause the weight gain or sexual dysfunction associated with prescription antidepressants—a huge plus, says Brown, since about 30% of patients stop taking standard antidepressants before improvements can occur. “More people will get better on SAM-e because they won’t drop out because of the side effects,” he explains.

And SAM-e has other unusual bonuses. For starters, research suggests it alleviates arthritis and may even regenerate lost cartilage, and animal studies have found that it restores memory—a promising discovery for Alzheimer’s patients. SAM-e may even benefit the liver: Brown’s own study of 20 HIV patients with depression found that both their mood and liver function improved tremendously—a connection he attributes to SAM-e’s ability to boost levels of glutathione. An antioxidant, glutathione is generated in the liver, and is crucial for immune function and often lacking in HIV patients.

With so much going for it, Brown believes there’s no reason not to use SAM-e. “Eighty percent of people with depression have to be on medication for a lot of their adult lives,” says Brown. “I’d rather give them something that does good things in their bodies as they get older.”

Citation: Psychology Today Magazine, Mar/Apr 2001 – Last Reviewed 14 Dec 2006

Arthritis Supplements reviewed in the journal “American Family Physician”

Our local paper, The New York Times, has just brought us a piece on “Making Sense of Arthritis Supplements” in its Jan. 21, 2008 issue.  It’s motivated by a recent medical journal review, and has already attracted a long string of reader comments.
No surprise, given that arthritis is the leading condition for which Americans use alternative therapies, including dietary supplements. At this point there has been a lot of scientific research on supplements for osteoarthritis; the review in the journal “American Family Physician,” which is the starting point for the NYT piece,  attempts to help people sort through the studies and come to some conclusions about what the best bets are.
Some of our own thoughts on the topic:
Glucosamine sulfate is the acknowledged front-runner, both for symptom relief and on account of evidence that it may have disease-modifying effects. Especially when side effects of ibuprofen or prescription medications cause concern, there’s reason to think about glucosamine sulfate as an alternative.
In 2005, results were made available for the NIH-sponsored “Glucosamine-Chondroitin Arthritis Intervention Trial” (GAIT), which looked at almost 1600 US patients with moderate-to-severe knee osteoarthritis pain. In the glucosamine-chondroitin combination group, 79.2% had pain relief, as opposed to 69.4% in the celecoxib (tradename you might know: Celebrex) group. The competition to interpret this trial to favor supplements or prescription drugs still rages pretty fiercely–see the comment from Dr Jason Theodosakis following the NYT review. (He was on oversight committee of the GAIT study, and is a well-known proponent of glucosamine.)
There is another supplement, more expensive than glucosamine, that has been extensively researched for osteoarthritis: SAM-e (S-Adenosyl-methionine). Below we simply reproduce the abstract of a frequently-cited review of this supplement, with Conclusion highlighted. (BTW, the caution raised in the NYT review about the stability of this product on the shelf is a point well taken.)
Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis
Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM.
University of Maryland, School of Nursing, Baltimore, MD.
OBJECTIVE: We assessed the efficacy of S-adenosylmethionine (SAMe), a dietary supplement now available in the Unites States, compared with that of placebo or nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of osteoarthritis (OA). STUDY DESIGN: This was a meta-analysis of randomized controlled trials. DATA SOURCES: We identified randomized controlled trials of SAMe versus placebo or NSAIDS for the treatment of OA through computerized database searches and reference lists. OUTCOMES MEASURED: The outcomes considered were pain, functional limitation, and adverse effects. RESULTS: Eleven studies that met the inclusion criteria were weighted on the basis of precision and were combined for each outcome variable. When compared with placebo, SAMe is more effective in reducing functional limitation in patients with OA (effect size [ES] =.31; 95% confidence interval [CI],.099-.520), but not in reducing pain (ES =.22; 95% CI, -.247 to.693). This result, however, is based on only 2 studies. SAMe seems to be comparable with NSAIDs (pain: ES =.12; 95% CI, -.029 to.273; functional limitation: ES =.025; 95% CI, -.127 to.176). However, those treated with SAMe were less likely to report adverse effects than those receiving NSAIDs. CONCLUSIONS: SAMe appears to be as effective as NSAIDs in reducing pain and improving functional limitation in patients with OA without the adverse effects often associated with NSAID therapies.
Citation: J Fam Pract. 2002 May;51(5):425-30.