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

Limitations

Potential limitations must also be noted in our analysis. First, in 6 of the studies, the SAMe dosage of 1200 mg per day exceeded the dosing recommendations for SAMe. These recommendations include 800 mg per day for 2 weeks followed by 400 mg per day as a maintenance dose, or to increase from 200 mg per day to 1200 mg per day over a 19-day period followed by 400 mg per day thereafter.³⁵ Dosage was not related to the ES, however, in studies comparing SAMe with NSAIDs. Second, most studies used a short intervention (28 to 30 days). It may be that NSAIDs are more effective in the long run, that a longer treatment period is needed for patients to realize the effect of SAMe, or that there are more adverse side effects with SAMe over time. It is not yet clear how effective SAMe is over time. Those studies that did have an intervention longer than 30 days^18,22 did not compare SAMe with ibuprofen. In general, concomitant medications for treatment of OA were not permitted, but 3 studies^24-26 failed to provide this information. Finally, most of the studies looked at OA of the knee and/or hip, so generalizability of the results to other locations of OA is limited. Although we included subgroup analyses by location of OA, statistical power for subgroup analysis was low because of the smaller number of subjects for whom data were available.

Conclusions

Although SAMe appears to offer pain relief and improve functional limitations associated with OA without the side effects of NSAIDs, it must be remembered that SAMe is not considered a drug in the United States and is therefore not subject to federal regulations. (In contrast, Samyr is a prescription drug in Italy and is available in 200 mg and 400 mg doses.) Recent testing by ConsumerLab.com of over-the-counter brands of SAMe in the United States found, on average, that for 6 of the 13 brands tested, less than half the amount of SAMe stated on the label was actually present.³⁶ Patients who use SAMe in the United States may fail to experience relief because of this dose inconsistency.

We offer several suggestions for further research. First, the long-term effectiveness of SAMe for the treatment of OA has not been investigated in a randomized controlled trial. Since OA is the most prevalent form of arthritis, the long-term effectiveness of SAMe should be assessed in this manner. Second, given that SAMe has been shown to decrease depression,¹ it seems prudent to use multivariate techniques to examine both depression and OA outcomes (pain and functional limitation) to determine whether the effect of SAMe is directly on the joint or indirectly mediated through depression. Perhaps in the short term SAMe does decrease pain through decreasing depressive symptoms, but in the long term the effectiveness related to pain may diminish. Third, whether SAMe treats the symptoms of the disease or alters the course of the disease by increasing the production of new cartilage, as suggested by animal models, has not been investigated. Finally, can use of SAMe enhance the effectiveness of other nonpharmacologic modalities? These questions should all be investigated before we can make a determination about the efficacy and safety of SAMe for the treatment of OA.

Acknowledgments

This research was supported by grant #5-P50-AT00084-02 from the National Center for Complementary and Alternative Medicine, National Institutes of Health.