Food-Derived Antihypertensive Peptides: Mechanisms, Multi-Methodological Approaches, Bioavailability, and Functional Food Applications.

This systematic review was conducted and reported according to the PRISMA 2020 statement to synthesize evidence published between January 2020 and January 2025 on food-derived antihypertensive peptides, with emphasis on mechanisms of action, molecular stability, bioavailability, and functional food applications. PubMed, Scopus, and Web of Science were searched using combined terms related to bioactive or ACE-inhibitory peptides, stability or bioavailability, and alternative protein sources. Original peer-reviewed studies in English evaluating antihypertensive or ACE-inhibitory peptides from plant, marine, insect, fungal, dairy, or terrestrial animal matrices were considered eligible when they reported experimental evidence on activity, stability, transport, or in vivo efficacy. Three reviewers independently screened records and extracted data. A total of 177 studies were included. Plant and marine matrices accounted for approximately 72% of the evidence base, with a strong focus on low-molecular-weight peptides (<3 kDa) and multistage validation pipelines integrating in silico screening, in vitro enzymatic assays, Caco-2 transport models, ex vivo assays, and spontaneously hypertensive rat studies. Overall, the evidence supports the antihypertensive potential of selected food-derived peptides, particularly through ACE inhibition and related vascular mechanisms. Encapsulation and advanced delivery approaches improved peptide stability and bioavailability in several studies. Food-derived antihypertensive peptides represent promising candidates for functional foods and nutraceuticals; however, greater methodological standardization, formal risk-of-bias assessment in primary studies, and well-designed human trials remain necessary to strengthen translation into practice.