Collagen Absorption: Mechanisms, Bioavailability, and Clinical Applications

Abstract

The increasing use of oral collagen peptides has intensified efforts to determine how ingested peptide fragments produce measurable biological and clinical effects. Despite significant progress, the pathways connecting intestinal uptake, systemic peptide availability, and tissue-specific activity remain unexplored. This review critically evaluates the metabolic fate of collagen-derived peptides and integrates evidence from gastrointestinal digestion, epithelial transport, systemic circulation, molecular regulation, and clinical investigation. Currently, Particular attention is given to hydroxyproline-containing sequences, particularly prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly). Their systemic availability suggests that oral collagen may exert its effects through mechanisms involving these peptides in regulating extracellular matrix dynamics, fibroblast function, collagen biosynthesis, inflammatory signaling, and redox homeostasis. Clinical evidence is comparatively robust for selected skin-aging outcomes, whereas findings in osteoarthritis, bone health, and exercise-related connective tissue recovery suggest promising but context-dependent benefits. Nevertheless, substantial heterogeneity in collagen source, peptide composition, manufacturing processes, dosing regimens, and clinical endpoints constrain cross-study comparability and precludes definitive therapeutic recommendations. Future studies should integrate peptide-resolved characterization, pharmacokinetic-pharmacodynamic profiling that validates the biomarkers, and precision nutrition strategies to directly link systemic peptide exposure with molecular response and clinical outcomes.