Association between non-nutritive sweetener consumption and liver enzyme levels in adults: a systematic review and meta-analysis of randomized clinical trials

Abstract Context The use of non-nutritive sweeteners (NNSs) is dramatically increasing in food commodities, and their effects on biochemical parameters have been the subject of great controversy. Liver enzymes as markers of liver injury may be helpful measures of non-alcoholic fatty liver disease (NAFLD), but the outcomes of randomized controlled trials (RCTs) suggest their associations with NNSs are contentious. Objective The current study was designed to provide a GRADE-assessed systematic review and meta-analysis of RCTs studying the consequences of NNS consumption on ALT, AST, and GGT concentrations (ie, the 3 main liver enzymes in adults). Data Sources Scopus, PubMed, and EMBASE were searched for relevant studies up to April 2021, with no time and language limitations. Data Extraction Two independent researchers extracted information from qualified studies, and a third researcher rechecked it. Data Analysis Of 3212 studies, 10 studies that enrolled a total of 854 volunteers were included. A random-effects or fixed-effects model was utilized to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Heterogeneity between studies was evaluated using Cochran’s Q test and quantified using the I2 statistic. The pooled results demonstrated that, compared with control groups, NNS intake led to nonsignificant reductions in ALT (WMD: −.78, 95% CI: –2.14, .57, P = .25) and GGT (WMD: –.21, 95% CI: –1.46, 1.04, P = .74). Also, a small nonsignificant increasing effect on AST level was found (WMD: .02, 95% CI: –1.26, 1.30, P = .97). NNS significantly reduced AST levels in type 2 diabetes patients when subgroup analyses were performed. Also, in trials with ≥24-week intervention or studies that utilized stevioside for intervention, a significant reducing effect on ALT level was observed. Conclusion The results of this study showed that NNS intake has no significant effect on liver enzyme levels in adults. Systematic Review Registration PROSPERO registration no. CRD42021250067.