Ellagic acid as a potential therapeutic agent in metabolic syndrome: A systematic review and meta-analysis of glycemic control markers and kidney function tests in animal and clinical studies.

Metabolic syndrome comprises a cluster of abnormal metabolic markers, including hyperglycemia, insulin resistance, hypertension, obesity, and dyslipidemia, that increase the risk of diabetes mellitus, cardiovascular diseases, and associated complications. Prolonged hyperglycemia results in microvascular complications such as nephropathy, while other abnormal metabolic markers contribute to progressive kidney dysfunction. Ellagic acid (EA) exhibits antihyperglycemia and nephroprotective effects. This study evaluated the effects of EA on glycemic control markers and kidney function tests in animal and human models with abnormal metabolic markers and preobesity. Comprehensive searches were conducted in Embase, Scopus, PubMed, and the Cochrane Library. Data were synthesized using meta-analysis, and risk of bias was assessed using SYRCLE's tool for animal studies and the Risk of Bias 2 tool for human studies. The certainty of evidence in human studies was evaluated using the GRADE approach. Meta-analysis revealed that EA significantly reduced blood glucose concentration (standardized mean differences = -4.03; 95% confidence intervals = -5.02 to -3.04; P < .0001) and improved insulin resistance by lowering homeostatic model assessment of insulin resistance (standardized mean differences = -2.48, 95% confidence intervals =-3.21 to -1.76, P < .0001) in animal studies. However, EA did not significantly affect glucose concentration, insulin, and homeostatic model assessment of insulin resistance in human studies. EA significantly decreased blood urea nitrogen and creatinine in animal studies. Overall, findings from animal studies suggest that EA may have therapeutic potential for improving glycemic control and mitigating kidney complications in metabolic syndrome. However, the absence of significant effects in humans highlights the need for high-quality clinical trials to determine its translational potential.