Original Research

Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis

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A meta-analysis




OBJECTIVE: We assessed the efficacy of S-adenosylmethionine (SAMe), a dietary supplement now available in the United 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], .098 - .519), 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.

  • S-adenosylmethionine (SAMe) is as effective as NSAIDs in offering pain relief and improving functional limitation with less risk of side effects.
  • When compared with placebo, SAMe improved functional limitations of osteoarthritis, but there was no improvement in pain.
  • The tolerability of SAMe was similar to that of placebo and greater than that of NSAIDs.

One alternative therapy for osteoarthritis (OA) is Sadenosylmethionine (SAMe), a naturally occurring sulphur-containing physiologic compound synthesized from amino acid L-methionine and adenosine triphosphate (ATP).1,2 Although scientists are not certain how it works to control pain, SAMe plays a key role in 3 major pathways: transmethylation, transsulfuration, and aminopropylation.2 SAMe was introduced in the United States in 1999 as a dietary supplement to promote joint health, mobility, and joint comfort. On the basis of a 1987 review of 12 clinical studies involving more than 20,000 patients, SAMe has been touted as “the prototype of a new class of safe drugs for the treatment of osteoarthritis.”3 However, the majority of the patients in those studies (97%) were enrolled in a single open field trial.

Although systematic reviews have demonstrated the benefit of other alternative strategies for OA, such as glucosamine and chondroitin,4,5 there has been no systematic review of SAMe for OA. Because individual studies of SAMe vary in their sample sizes and report conflicting results, we conducted a meta-analysis to assess the efficacy of SAMe for OA as compared with that of placebo or NSAIDs. We also examined whether study quality, drug dosage, or length of treatment is associated with the effect, and we identified needs for future research.


Literature search and data sources

We conducted computerized searches using the term “arthritis” and all synonyms for SAMe: “S-Adenosylmethionine,” “Ademetionine,” “S-adenosyl-L-methionine,” “Adenosyl-l-methionine,” “Samyr,” “Gumbaral,” “Sammy,” and “SAM-e.” Results were then combined into the optimally sensitive search strategy for retrieving all clinical trials.6,7 All languages were included. Our database search included MEDLINE (1966- September 2000), EMBASE (1987-2000), CAMPAIN (Complementary and Alternative Medicine and Pain), Science Citation Index, International Pharmaceutical Abstracts, The Cochrane Complementary Medicine Field Registry, National Institutes of Health Office of Dietary Supplements Database, and Micromedix. We also hand searched the 3 journals with the highest impact factors for rheumatology (Arthritis and Rheumatism, British Journal of Rheumatology, and Journal of Rheumatology, 1985-1999),8 English-language journals from which we had already retrieved articles, and complementary medicine journals (inception to 1999). In addition, we examined bibliographies from retrieved articles, books, and Web sites related to SAMe and contacted manufacturers of SAMe for previously unidentified research studies.

Inclusion criteria

Criteria for inclusion were established a priori. Studies had to include a sample of patients with a diagnosis of OA; be a randomized controlled trial; compare SAMe with placebo or NSAID; and report data for at least 1 of the outcome variables: pain, functional limitation, and adverse effects. Two raters independently screened studies to determine whether they met the inclusion criteria and agreed in their assessments.

Quality assessment and data extraction

Two raters independently rated study quality of the English studies using the 5-point Jadad scale9 that assesses random allocation, double-blinding, and the reporting of withdrawals and dropouts. An additional rating item concerned concealed allocation. Only 1 of the 2 raters assessed the quality of the 4 non-English articles. Two reviewers also independently extracted descriptive information and outcomes that reflected pain, functional impairment, and adverse effects. Any differences in ratings and data extraction were discussed and a consensus was reached.


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