The effect of L-carnitine on inflammatory mediators: a systematic review and meta-analysis of randomized clinical trials Abstract Aim and background Reducing inflammation by nutritional supplements may help to reduce the risk of many chronic diseases. Our aim in this meta-analysis was to determine the effect of L-carnitine on inflammatory mediators including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Methods Our systematic search to find relevant randomized clinical trials (RCTs) was performed up to October 2018 using ISI Web of Science, Google Scholar, PubMed/Medline, and SCOPUS. In this meta-analysis, the weighted mean differences (WMD) with standard errors (SE) were used to pool the data. WMD was calculated by subtracting change-from-baseline mean values in the control group from change-from-baseline mean values in the intervention group in each study. To identify heterogeneity among studies, the I2 statistic was employed. The protocol was registered with PROSPERO (No. CRD42019116695). Results Thirteen articles were included in our systematic review and meta-analysis. The results of the meta-analysis indicated that L-carnitine supplementation was significantly associated with lower levels of CRP in comparison to controls (WMD = −1.23 mg/L; 95% CI: −1.73, −0.72 mg/dL; P < 0.0001). Also, a slight but statistically significant decrease was observed in IL-6 and TNF-α levels (WMD = −0.85 pg/dL; 95% CI: −1.38, −0.32 pg/dL; P = 0.002 and WMD = −0.37 pg/dL; 95% CI: −0.68, −0.06 pg/dL; P = 0.018, respectively). Conclusion Our results indicate that L-carnitine reduced inflammatory mediators, especially in studies with a duration of more than 12 weeks. Further studies with different doses and intervention durations and separately in men and women are necessary.