Aug 2026· PeerJ· Vol 14, pp. e21398· 0 citations· 30 references
Medicine
TL;DR
Across both in vitro and in vivo models, ultra-low molecular weight collagen (LMWCP), with more than 45% di- and tripeptides, exhibited faster early-phase absorption kinetics, thereby enhancing early-phase bioavailability.
Abstract
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.
Calcium (Ca), primarily consumed through diet, is essential for skeletal health and various other biological functions in humans. While the mechanisms of Ca absorption are well understood, little is known about the role of food structure properties in Ca release kinetics into the GIT, which may have important implications in Ca uptake. Therefore, the aim of this study was to investigate calcium release kinetics from whey protein matrices with varying structures during gastrointestinal digestion. Whey protein structures (liquid: storage modulus G' = 0.18 Pa at 1 Hz; soft gel: 1791 Pa; hard gel: 4103 Pa) with 8% (w/w) protein and an equal Ca concentration (25 mM CaCl2) were subjected to dynamic in vitro gastric digestion using the Human Gastric Simulator, followed by intestinal digestion of emptied chyme fractions using a static model. Results revealed that the release of both soluble and ionic Ca from whey protein gels was significantly delayed, compared with their liquid counterpart. Slower Ca release patterns from protein gels in the gastric phase led to the release of a higher soluble Ca content in the intestinal phase, especially at early stages of digestion. These findings demonstrated that the physical structure of whey protein gels modulates soluble Ca release rates into the gastrointestinal environment. Further research is required to understand the implications of calcium release modulation in absorption efficiency.
Xinya Wang, Aiqian Ye, Harjinder Singh et al.· Food & Function· 0 citations
Lactopontin (L-OPN), a milk-derived active protein vital for the growth of infants and young children, was studied for the calcium absorption-promoting activity and mechanism of its gastrointestinal digestive products. An in vitro dynamic infant digestive system simulated L-OPN digestion; the products were separated via desalting, ultrafiltration and HPLC to screen high calcium-chelating peptides. MS analysis revealed dominant low-molecular-weight peptides with acidic amino acids and serine phosphorylation. Molecular docking identified four high-affinity peptides: SELS(+79.97)KELTPK, KLS(+79.97)QEFH, HSDESDEVDF, PTDIPTIA, with Glu and Asp as key Ca2+-binding residues. In the Caco-2 model, their calcium transport rose by 83.55%, 95.44%, 71.53% and 81.62% vs. CaCl2 group, with lower intracellular calcium retention (accelerated Ca2+ efflux). MS confirmed KLS(+79.97)QEFH's intact intestinal absorption via stable calcium-chelating structure. This study clarifies L-OPN peptide's core calcium absorption mechanism, providing a scientific basis for understanding L-OPN's biological role and developing infant nutritional products.
Xuanxiang Zhao, Ruibiao Hu, Wenjun Cao et al.· Food Chemistry· 0 citations
Fish bone-derived calcium may offer an alternative to conventional supplements, but the contribution of specific peptides to calcium bioavailability has not been clearly defined. This study aimed to valorize an underutilized silver sillago bone by identifying novel calcium-binding peptides using de novo LC-MS/MS, molecular dynamic simulation, and Caco-2 monolayer transport assay. Bio‑calcium from silver sillago was prepared through enzymatic hydrolysis, defatting, bleaching, and grinding, then characterized by X-ray diffraction and FTIR spectroscopy. Caco-2 monolayer transport was used for the bioavailability assay. Peptides released after simulated gastrointestinal digestion were analyzed using LC-MS/MS, and calcium-binding potential was assessed through 100 ns molecular dynamics simulations. XRD confirmed the presence of crystalline hydroxyapatite with peaks at 2θ = 26°-32°, while FTIR identified characteristic Amide I-III and phosphate vibration bands. Among the 20 most abundant peptides, we report three novel peptides from silver sillago (SW4, SW16, and SW17) that demonstrated the strongest calcium-binding potential, with Ca2+-peptide distances <0.35 nm, ≥1.2 close Ca2+ ions, and ≥ 25 atomic contacts per frame. SW4 exhibited the shortest mean distance (0.29 nm), highest Ca2+ proximity (1.76 ions), and ~ 28 contacts/frame. In vitro Caco-2 monolayer transport assay showed that bio‑calcium achieved a calcium absorption rate of 28.63 ± 3.88%, comparable to that of calcium carbonate (27.67 ± 3.81%). These results suggest that collagen-derived peptides in silver sillago bone may contribute to calcium retention and transport in this in vitro model, but their specific roles in cellular uptake and relevance in vivo remain to be established.
J. Saetang, Panatda Khrueakaew, Thaiyawat Haewphet et al.· International Journal of Bio...· 0 citations
Simple Summary Collagen is the main structural protein of skin, bone, tendon, and cartilage, and it was long viewed only as a building material. When collagen is broken into small fragments—during digestion or in collagen supplements—some fragments are absorbed into the blood and act as signals that influence the body well beyond the tissues they came from. This review, the first of two parts, examines what these small collagen fragments are, how efficiently animals absorb them, and which cell-surface sensors and internal pathways they switch on. The evidence comes from laboratory experiments, animal studies, and clinical trials, and we are careful throughout to separate firm clinical findings from early laboratory observations. The strongest current evidence supports specific collagen fragments for relieving joint disease in dogs and horses. We also describe a newly recognised link between collagen fragments, gut bacteria, and bile that may explain effects on metabolism and the liver. The main message for practice is that collagen supplements are biologically active compounds whose effects differ between species, so the dose and the expected benefit should be judged species by species rather than assumed from one animal to another.
Porcine tracheal cartilage, an underutilized Type II collagen-rich by-product, was systematically evaluated as a source of angiotensin I-converting enzyme (ACE) inhibitory, dipeptidyl peptidase-IV (DPP-IV) inhibitory, and antioxidant peptides. Neutrase at 4 h outperformed Papain in generating ACE-inhibitory and antioxidant peptides. The <3 kDa ultrafiltration fraction, enriched in small hydrophobic peptides, exhibited the highest bioactivities. LC-MS/MS identified eight sequences (870–1565 Da). Chemical synthesis confirmed LGLGADMFHR as the most potent ACE inhibitor (IC50 = 0.52 mM), QGLPGPGAVAEYT as the lead DPP-IV inhibitor (IC50 = 1.84 mM), and LGFGADRAGPQ as the strongest antioxidant (5.64 mM Trolox equivalents). Molecular docking revealed LGLGADMFHR binding through Zn2+ coordination and hydrogen bonds with Cys352, Glu376, and Asp453. Standardised INFOGEST gastrointestinal digestion progressively enhanced ACE inhibition and antioxidant activities while DPP-IV inhibition declined, establishing porcine tracheal cartilage as a viable source of gastrointestinally stable cardiovascular bioactive peptides.
R. Purba, Suchanya Sinsranoi, P. Laosam et al.· Food Chemistry: X· 0 citations