Associations between the use of red yeast rice preparations and adverse health outcomes:An umbrella review of meta-analyses of randomized controlled trials

Background:Red yeast rice(RYR),a natural lipid-lowering agent,is widely used in clinical practice.However,the existing meta-analyses concerning the safety of RYR preparations have yielded inconsistent results,and the credibility of the evidence has not been quantified.Objective:This study was designed to evaluate the existing evidence and offer a comprehensive understanding of the associations between the use of RYR preparations and various adverse health outcomes.Search strategy:Seven literature databases were searched from inception to May 5,2023,using medical subject headings and free-text terms(e.g.,“red yeast rice,”“Xuezhikang,”and“Zhibitai”).Inclusion criteria:Meta-analyses that investigated and quantitatively estimated associations between the use of RYR preparations and adverse health outcomes were included in this study.Data extraction and analysis:Two researchers independently extracted data using a standardized data collection table;any disagreements were resolved by consulting a third researcher.Based on the participant,intervention,comparator and outcome(PICO)framework in each eligible meta-analysis,a series of unique associations between the use of RYR preparations and adverse health outcomes were determined.The associations’effect estimates were re-evaluated using random-effect models.Results:Fifteen meta-analyses,comprising 186(164 unique)randomized controlled trials,were identified.Based on A Mea Surement Tool to Assess Systematic Reviews version 2,3(20%)and 12(80%)of these meta-analyses had low and critically low confidence,respectively.A total of 61 unique associations between the use of RYR preparations and adverse health outcomes were extracted from eligible metaanalyses.Based on the random-effect models,10(16.4%)associations indicated a significant protective effect of RYR preparations against adverse health outcomes,while 5(8.2%)indicated an increased risk of adverse health outcomes related to uric acid,alanine transaminase and aspartate transaminase levels.The other 46(75.4%)associations showed no significant difference between the use of RYR preparations and control treatments.Regarding the credibility of the evidence,21(34.4%),34(55.7%)and 6(9.8%)associations showed moderate,low and very low credibility,respectively.Conclusion:The evidence examined in this study suggests that RYR preparations are safe;however,the credibility of the evidence was not high.Further high-quality evidence is required.