Selected food-processing by-products as sources of natural antioxidants: Bridging composition, bioavailability, food applications, and regulatory translation

Selected food-processing by-products have emerged as promising sources of natural antioxidants that can contribute to food preservation, ingredient valorization, and circular bioeconomy strategies. Despite extensive reports detailing their phenolic composition and in vitro antioxidant activity, important gaps remain in translating these properties into biological efficacy, food-matrix performance, and industrial acceptance. This scoping review synthesizes evidence published between 2023 and 2025 ( n = 55 studies) regarding the phytochemical composition, bioaccessibility, bioavailability, in vivo efficacy, food-matrix performance, and safety considerations of antioxidant compounds derived primarily from grape pomace, pomegranate peel, mango peel, and coffee co-products, while also incorporating complementary evidence from other selected food-processing residues. Pomegranate peel and grape pomace frequently exhibit high phenolic concentrations, whereas mango peel and coffee co-products provide complementary antioxidant profiles associated with mangiferin, chlorogenic acids, and melanoidins. However, compositional richness alone does not necessarily predict biological relevance or technological performance, since digestion, metabolism, food-matrix interactions, and processing conditions strongly influence functional outcomes. Evidence derived from INFOGEST-based digestion models and intestinal absorption systems indicates that bioaccessibility commonly ranges from approximately 19% to 46%, whereas the systemic bioavailability of high-molecular-weight phenolic compounds, such as punicalagins and proanthocyanidins, generally remains below 15% due to limited intestinal absorption and extensive microbial and metabolic transformation. In many cases, biological activity is associated with the formation of secondary metabolites, including urolithins, generated through colonic biotransformation. Available animal and limited human studies report moderate reductions in malondialdehyde (−9% to −21%) and increases in endogenous antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), typically ranging from 15% to 35%. Despite encouraging technological and preclinical findings, substantial translational challenges remain. Variability in raw-material composition, lack of extraction standardization, inconsistent reporting units, limited dose-response evidence, scarce clinical studies, and evolving approval requirements continue to hinder industrial implementation. Although toxicological data are generally favorable when contaminants are controlled, and batch standardization is applied, few studies align with EFSA and FDA frameworks for novel ingredients. A coordinated framework linking phytochemical characterization, digestion models, pharmacokinetic assessment, food-matrix validation, and safety evaluation is essential to enable safe and scalable industrial adoption. By integrating chemical, biological, technological, and regulatory perspectives, this review provides a translational roadmap for developing standardized, scientifically validated natural antioxidant ingredients from food-processing by-products.