Table 2.

Translational relevance of representative polyphenols in disease contexts.

Disease context	Representative polyphenols	Candidate biomarkers	Clinical or human evidence	Pharmacokinetic considerations	Long-term safety profile
Cardiometabolic disorders	Curcumin, quercetin, resveratrol, EGCG	hs-CRP, IL-6, TNF-α, oxidative stress markers, lipid profile, glucose metabolism, AMPK/SIRT1-related markers	Human studies suggest potential improvements in inflammatory and metabolic biomarkers (3, 107), although effects vary across populations and formulations	Low parent-compound bioavailability; extensive glucuronidation and sulfation; formulation strongly affects exposure	Generally well tolerated at dietary or moderate supplemental doses; high-dose supplementation may cause gastrointestinal symptoms or interact with medications
Neurological and aging-related disorders	Curcumin, EGCG, resveratrol, urolithin A	Oxidative stress markers, inflammatory cytokines, mitochondrial function markers, neurotrophic factors, autophagy/mitophagy markers	Clinical evidence remains limited and heterogeneous; some human studies report changes in inflammatory or cognitive-related biomarkers (108)	Blood–brain barrier penetration and tissue exposure remain major barriers; metabolites may differ from parent compounds	Long-term efficacy and safety require further evaluation, especially for high-dose or nanoformulated preparations
Inflammatory diseases	Quercetin, curcumin, EGCG, luteolin	NF-κB-related cytokines, CRP, IL-1β, IL-6, TNF-α, immune-cell activation markers	Human biomarker studies support anti-inflammatory potential (109), but disease-specific clinical evidence is variable	Bioactive metabolites and local deconjugation may determine tissue-level activity	Usually safe at dietary levels; caution is needed for concentrated extracts and combined use with anti-inflammatory drugs
Cancer-related contexts	Curcumin, EGCG, resveratrol, genistein	Nrf2 status, ROS burden, apoptosis markers, proliferation markers, inflammatory tumor microenvironment markers	Most evidence remains preclinical (110–112); clinical studies are limited and often focus on tolerability or biomarker modulation rather than survival outcomes	Achievable tumor exposure is uncertain; formulation and tumor microenvironment may influence efficacy	Safety depends on dose, cancer type, treatment combination, and hormone-sensitive status; potential drug interactions should be considered
Metabolic flexibility and precision nutrition	Resveratrol, quercetin, urolithin A, EGCG	Metabolomic profile, microbiome-derived metabolites, insulin sensitivity, lipid metabolites, mitochondrial markers	Emerging human evidence suggests high inter-individual variability in response, partly related to metabolism and microbiome composition (113)	Microbiome-dependent metabolite production may determine responder status	Long-term personalized use requires monitoring of dose, supplement quality, medication interactions, and individual metabolic background