Effects of S-Adenosylmethionine on Cognition in Animals and Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: There is increasing evidence that supplementation of S-adenosylmethionine (SAM) can improve cognitive function in animals and humans, although the outcomes are not always inconsistent. Objective: We conducted a systematic review and meta-analysis to evaluate the correlation between SAM supplementation and improved cognitive function. Methods: We searched studies in the PubMed, Cochrane Library, Embase, Web of Science, and Clinical Trials databases from January 1, 2002 to January 1, 2022. Risk of bias was assessed using the Cochrane risk of bias 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation risk of bias (animal studies) tools; and evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. STATA software was employed to perform meta-analysis, and the random-effects models was used to evaluate the standardized mean difference with 95% confidence intervals. Results: Out of the 2,375 studies screened, 30 studies met the inclusion criteria. Meta-analyses of animal (p = 0.213) and human (p = 0.047) studies showed that there were no significant differences between the SAM supplementation and control groups. The results of the subgroup analyses showed that the animals aged <= 8 weeks (p = 0.027) and the intervention duration >8 weeks (p = 0.009) were significantly different compared to the controls. Additionally, the Morriswater maze test (p = 0.005) used to assess the cognitive level of the animals revealed that SAM could enhance spatial learning and memory in animals. Conclusion: SAM supplementation showed no significant improvement in cognition. Therefore, further studies are needed to assess the effectiveness of SAM supplementation.