Dietary Phytochemicals as Natural Modulators of Carcinogen Metabolism: A Comprehensive Review

Abstract

The paper shows that dietary phytochemicals influence carcinogen metabolism by rebalancing activation and detoxification metabolism by increasing phase II detoxification and rebalancing phase I carcinogen activation. These effects can reduce adduct burden and mutational risk. The background notes bioactive classes-polyphenols, isothiocyanates, organosulfurs, terpenoids, and alkaloids-show to affect CYP450 isoforms as well as GSTs, UGTs, NQO1 and sulfotransferasing enzymes, and down-regulate reactive oxygen species and inflammation. The aim is to systematically chart compound-enzyme interactions and quantify directionality of responses across tissues and generally assess human relevance through controlled feeding, nutkinetic modelling and real-world diet patterns. The results will comprise a matrix of connections between individual phytochemicals (e.g., sulforaphane, curcumin, resveratrol, EGCG, quercetin) and prioritized nodes in the metabolome, conditions of modulation that are protective vs. those that may be adverse, and factors that influence efficacy (dose, food matrix, microbiome metabolism, genetic polymorphisms). The review additionally assesses the formulation strategies to increase bioavailability and deduce rules of combination of phytochemicals with the standard risk-reduction guidelines. It foresees delivering a translational roadmap of biomarker-directed nutrition intervention trials applying adductomics and metabolomic endpoints ultimately to help support diet-based interventions as feasible, low-risk chemoprevention.