Enhanced digestion and absorption kinetics of ultra–low molecular weight collagen containing di- and tripeptides: evidence from human and cell models

Background Collagen hydrolysates differ in molecular weight distribution and composition, which may influence gastrointestinal absorption and epithelial transport. Objective The objective of this study is to compare the digestion and absorption kinetics of an ultra-low molecular weight collagen with >45% di- and tripeptides (LMWCP; 500 Da) and a standard collagen hydrolysate (CP; 2,000–3,000 Da) using a Caco-2 cell model and an exploratory human study. Materials and methods A Caco-2 cell Transwell model was used to assess the apical-to-basolateral appearance of collagen-derived free amino acids over 240 minutes after in vitro digestion of the test products. Product characterization included quantification of free amino acids and selected hydroxyproline-containing di- and tripeptides. In parallel, an exploratory single-blind, parallel-group human study in 15 healthy male participants measured postprandial plasma free amino acid kinetics at 0, 15, 30, 120, and 240 minutes after ingestion of LMWCP, CP, or placebo. Results In both models, LMWCP showed faster early-phase kinetics than CP. In the Caco-2 model, collagen-derived amino acids appeared in the basolateral compartment within the first minutes and were highest during the first 30 minutes with LMWCP. In the human study, plasma glycine and proline/hydroxyproline peaked earlier after LMWCP group (30 minutes) compared to CP group (120 minutes). Conclusion Across both in vitro and in vivo models, ultra-low-molecular-weight collagen (LMWCP; 500 Da), with more than 45% di- and tripeptides, exhibited faster early-phase absorption kinetics, thereby enhancing early-phase bioavailability. Collagen-derived amino acids appeared across the epithelial layer within minutes and reached plasma peaks earlier, compared to a standard collagen hydrolysate. These findings suggest that LMWCP exhibits distinct, accelerated absorption kinetics compared to conventional collagen hydrolysates.