New Advances and Current Trends in Bioavailability of Coffee and Coffee By-Product Constituents and Their Metabolites: A Review

Coffee is one of the most widely consumed beverages worldwide, yet understanding how its bioactive compounds are absorbed and exert health effects remains incomplete. The objective and scope of this review is to critically summarize current advances in coffee bioavailability research, identify major limitations, and highlight emerging research trends. Recent research has advanced in three core areas. First, genetic stratification has moved the field beyond one-size-fits-all approaches by genotyping for key polymorphisms to explain inter-individual variability. Second, advanced metabolomics, including targeted and untargeted LC-MS/MS and multi-omics integration, has provided comprehensive views of phenolic absorption and bioavailability. Third, rigorous intervention designs, including randomized crossover trials and large prospective cohorts with detailed exposure assessment, have improved causal inference. Despite these advances, major limitations persist. Many studies lack sufficient statistical power to detect gene-treatment interactions. The clinical relevance of discovered metabolites is often not established. Observational cohorts remain susceptible to residual confounding, and the field lacks a standardized food matrix for cross-study comparisons. Key strategies to improve the bioavailability of coffee and its by-products were proposed, including novel delivery systems for coffee phytochemicals, human clinical trials involving encapsulated coffee bioactive compounds, and exploring coffee by-products as novel bioactive sources.