Food-derived bioactive peptides as functional ingredients for cardiometabolic health: Mechanistic insights, clinical translation, challenges, and future perspectives

Food-derived bioactive peptides (BAPs) are promising functional ingredients for cardiometabolic health, yet none has been approved as a therapeutic agent, and authorized health claims remain limited. This review analyzes this translational gap and provides a mechanistic roadmap for developing food-derived BAPs as evidence-based interventions for cardiometabolic health. Preclinical evidence suggests that BAPs can engage multiple pathways, including renin-angiotensin system, vasorelaxation, nuclear factor erythroid 2-related factor 2 (Nrf2)-associated antioxidant mechanism, nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK)- related anti-inflammatory signaling, and gut-incretin axis, with the gut microbiota driving individual responses. Distinctively, each mechanism is graded separately based on biological effect, pathway engagement, and causal necessity to derive a confidence tier. Based on the evidence reviewed, no mechanism has achieved the highest confidence tier, and evidence jointly establishing target-tissue exposure, pathway engagement, and causal mediation remains insufficient. Effective translation will require pharmacokinetic characterization, microbiome-stratified and sex-inclusive trials, and adequately powered studies with definitive cardiometabolic endpoints.