Bioactive Peptides and Polyphenols as Next-Generation Nutraceuticals: Mechanisms, Bioavailability, and Clinical Prospects

Abstract

Bioactive peptides and polyphenols are compounds found in food that have complementary molecular actions that could participate in the prevention or in the complementary treatment of chronic pathologies. The peptides derived from the proteins in dairy, marine, egg, plant, and meat products can alter the activity of angiotensin-converting enzyme, redox homeostasis, glucose metabolism, immune signalling, and satiety, while polyphenols are known to regulate antioxidant-response pathways, inflammatory mediators, cellular metabolism, vascular function, and gut microbial ecology. They have been limited in their translation to effective nutraceuticals, however, due to inconsistent compositions, gastrointestinal degradation, restricted intestinal permeability, fast metabolism, unknown tissue exposure, and inconsistent clinical trials. This critical integration of evidence brings together sources, structure–activity relationships, production, molecular mechanisms, pharmacokinetics, formulation technologies, clinical applications, safety and regulation information in the context of this narrative review. Literature was retrieved from PubMed/MEDLINE, Scopus, Web of Science and Google Scholar by employing various combinations of the keywords bioactive peptides, polyphenols, nutraceuticals, bioavailability, nanoencapsulation, mechanisms and clinical trials. There is current evidence for biologically plausible effects on antioxidant, anti-inflammatory, cardiometabolic, neuroprotective, and microbiota-mediated effects, but results in purified systems or animal models do not necessarily translate to human exposures.
Apparent bioavailability and stability may be improved by encapsulation, lipid-based carriers, protein–polysaccharide complexes, cyclodextrins, and co-delivery systems, but there is limited comparative human data. Future developments should focus on chemically standardized preparations, validation of dose-response biomarkers, dose-ranging studies, interaction testing and sufficiently sized studies based on diet, microbiome, metabolic phenotype and medication use. Bioactive peptides and polyphenols are next-generation nutraceutical ingredients, but with clinically credible products, there needs to be a change from general antioxidant claims to evidence that is specifically linked to the mechanism, formulated to a specific product, and compliant with regulatory standards.