(Poly)phenol metabotypes and cardiometabolic health: a systematic review

Background: Inter-individual differences in gut microbial metabolism of dietary (poly)phenols may influence cardiometabolic outcomes, though their clinical relevance remains unclear. Objective: This systematic review examined associations between (poly)phenol metabotypes and cardiometabolic health. Methods: A comprehensive search of seven databases up to March 2025 included randomized controlled trials (RCTs) and observational studies investigating equol, O-desmethylangolensin (ODMA), and urolithin metabotypes (PROSPERO: CRD42020196149). Results: Thirty-three RCTs and 12 observational studies were included. Equol producers (EPs) showed lipid-lowering effects in 9 RCTs and favorable lipid profiles in 3 observational studies, while 11 RCTs and 3 studies found no differences. One RCT and 2 observational studies on ODMA producers reported inconsistent lipid outcomes. One RCT showed lipid-lowering effects for urolithin metabotype B (UM-B), while 2 observational studies linked UM-B to higher lipids vs UM-A. For blood pressure (BP), 2 RCTs and 1 study reported reductions in EPs, while 7 RCTs and 2 studies found no effects. EPs improved endothelial function in 4 RCTs, but not in 6, while no differences between metabotypes were observed in 2 studies. Conclusion: Evidence for the role of (poly)phenol metabotypes in cardiometabolic health is inconclusive. Further clinical studies with standardized metabotype classification and outcome measures are needed.