Biomarkers of (poly)phenol intake: a systematic review

(Poly)phenols in plant-based foods contribute to the prevention of non-communicable diseases, yet defining their optimal intake remains challenging. Biomarkers provide a more objective alternative to self-reported dietary assessments, but their validation is essential. This review systematically summarizes and critically evaluates validated (poly)phenol biomarkers to inform future research. A systematic search of three databases identified studies published from 1995 to January 2025 that quantified (poly)phenol intake biomarkers in biofluids using validated analytical methods and provided evidence of specificity and dose-response. Biomarker validity was assessed based on plausibility/specificity, dose-response, time-response, robustness, reliability, stability, analytical performance, and reproducibility. Five multi-metabolite panels were identified across eight studies: genistein + daidzein or the sum of isoflavone aglycones and metabolites (isoflavone intake), hydroxytyrosol and its phase II metabolites (hydroxytyrosol intake), structurally related (-)-epicatechin metabolites (SREM) ((-)-epicatechin intake), and phase II metabolites of 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (PgVLM) (flavan-3-ol intake). The most extensively validated biomarkers, SREM and PgVLM in 24-h urine, met five validation criteria. However, challenges remain, including limited specificity, short half-lives, inter-individual variability, and a lack of authentic chemical standards. Further research is needed to enhance biomarker validity for precise dietary intake assessment in epidemiological studies.