As part of an active lifestyle, many consumers choose collagen-enriched diets to support healthy aging, skin beauty or overall mobility and fitness. While beneficial effects of standard molecular weight (SMW) collagen hydrolysate food supplements have long been supported by scientific data, recent studies on its mode of action reveal a central role of small bioactive col lagen di- or tripeptides. Highly efficient low molecular weight (LMW) collagen hydrolysate with a favorable peptide profile, quick uptake, and high bioavailability appears to be the next generation food supplement.
Collagen hydrolysates are produced from animal tissues in a multi-step process that involves gela tinization and subsequent enzymatic hydrolysis of native collagen, yielding peptides with an average molecular weight of approximately 3 kDa (SMW).
Tailored enzymatic digestion with collagenase during this process preserves the collagen-specific sequence Gly-Pro-Hyp (GPH) and yields a LMW hydrolysate that is enriched with this bioactive tripeptide that exerts beneficial effects in various tissues, including skin, muscles, joints or bones.1,2,3
This short review provides a brief overview of recent findings regarding uptake, bioavailability, mode-of-action, and efficacy profile of bioactive peptides in LMW collagen hydrolysates.
Uptake & bioavailability
A study on rats with radioactively marked Carbon (14C) as tracer could map LMW collagen in muscles, joints, bones and cartilage where it remains while disappearing in plasma and organs.4 Radioactivity is retained at a high level in the skin until 14 days after administration (70% of the level observed at 6 h). Human trials focussing on GPH have found that after ingestion, the tripeptide is very efficiently absorbed, rapidly transported into the blood and detectable in a dose-dependent manner in plasma and skin.2,5 In the skin GPH is further hydrolyzed to the bioactive dipeptide Pro-Hyp (PH).
While SMW collagen is degraded in the gastroin- testinal tract but not readily cleaved into bioactive peptides, GPH and PH enriched in LMW collagen easily cross the intestinal barrier into the blood stream via the peptide transporter PEPT1 and remain intact over the entire gastrointestinal pathway.(1,4,5)
The method of collagen hydrolysate preparation apparently influences the peptide profile in the blood stream.(2,5)
Target tissues and mode of action
Several physiological activities of metabolized collagen di- and tripeptides have been described:
Cardiovascular system: In vivo studies found that collagen tripeptides inhibit thrombosis, decrease the number of macrophages in atherosclerotic plaques and can reduce blood pressure.6,7,8
Joints & Bones: One of the most established be nefits of collagen hydrolysate is the promotion of joint and bone health and regeneration (reviewed by Moskowitz).9 The specific effect of bioactive colla gen peptides has been shown, e.g. by Watanabe-Ka miyama et al. who demonstrated that an oral admi nistration for 20 weeks improves bone composition with an increase in organic substance.4 Collagen tripeptides have also been shown to reduce inflammation and stimulate cartilage formation and bone healing.(10,11,12)
Skin: The support of skin health by collagen food supplementation is well documented in the litera ture (reviewed by Sibilla et al.).13 Regarding bioactive collagen di- and tripeptides there appears to be a triple mode of action:
Induction of collagen expression via the p38 MAPK pathway,14 providing free amino acids as building blocks for the formation of collagen and elastin fibers, and acting as ligands for fibroblast receptors, stimu lating growth, the production of new collagen and hyaluronic acid synthesis.2,15,16,17,18 In clinical studies, collagen tripeptides could impro- ve skin elasticity and hydration and were effective in wrinkle reduction and the promotion of wound healing (reviewed by Choi).18 The efficacy of a collagen hydrolysate appears to be proportional to its concentration of bioactive peptides.
Until now, all manufacturers of hydrolyzed collagen have focused on optimizing the organoleptic charac teristics of the supplement, achieving the best smell and taste in standard molecular weights.
Viscofan has developed a LMW collagen hydrolysate taking into account all scientific insights and focus sing on the desired effects – even though the supple ment has undesirable organoleptic characteristics (bitterness/acidity) that can be masked using availa ble technologies or different pharmaceutical forms.
SMW collagen hydrolysate is an evi dence-based oral health food supplement. The current body of literature supports that its bene ficial effects are mostly mediated by metabolized bioactive collagen tri- or dipeptides, in particular GPH or PH. LMW collagen hydrolysate with a high concentration of these characteristic peptides has major advantages over SMW products, including quicker and more efficient peptide uptake, higher bioavailability, as well as enhanced stability and efficacy, especially in the skin.
1 Sontakke S B et al., 2016, Orally Available Collagen Tripeptide: Enzymatic Stability, Intestinal Permeability, and Absorption of Gly-Pro-Hyp and Pro-Hyp; J Agric Food Chem., 64:7127−7133
2 Yazaki M et al., 2017, Oral Ingestion of Collagen Hydrolysate Leads to the Transportation of Highly Concentrated Gly-Pro-Hyp and Its Hydrolyzed Form of Pro-Hyp into the Bloodstream and Skin; J Agric Food Chem, 65:2315−2322
3 Choi S Y et al., 2014, Effects of collagen tripeptide supplement on skin pro- perties: a prospective, randomized, controlled study; J Cosmet Laser Ther, 16: 132−137
4 Watanabe-Kamiyama M et al., 2010, Absorption and effectiveness of orally administered low molecular weight collagen hydrolysate in rats; J Agric Food Chem, 58(2):835-841
5 Yamamoto S et al., 2015, Absorption and plasma kinetics of collagen tripep- tide after peroral or intraperitoneal administration in rats; Biosci Biotechnol, Biochem, 79:2026−2033
6 Hongdong S et al., 2022, Tripeptide Hyp-Asp-Gly from collagen peptides in- hibited platelet activation via regulation of PI3K/Akt-MAPK/ERK1/2 signaling pathway; https://doi.org/10.1111/1750-3841.16215
7 Ichimura T et al., 2009, Antihypertensive effect of enzymatic hydrolysate of collagen and Gly-Pro in spontaneously hypertensive rats; Biosci Biotechnol Biochem, 73:2317–2319
8 Tang L et al., 2015, Effects of oral administration of tripeptides derived from type I collagen (collagen tripeptide) on atherosclerosis development in hy- percholesterolemic rabbits; J Biosci Bioeng, 119: 558–563
9 Moskowitz R W, 2000; Role of collagen hydrolysate in bone and joint disea- se; Seminars in arthritis and rheumatism, Vol. 30(2):87-99. WB Saunders
10 Kouguchi T et al., 2012, Chicken collagen hydrolysate-derived peptides in- hibit tumor necrosis factor-α-induced inflammatory response in endothelial cells; Food Sci Technol Res, 18:667–671
11 Nakatani S et al., 2009, Chondroprotective effect of the bioactive peptide prolyl–hydroxyproline in mouse articular cartilage in vitro and in vivo; Os- teoarthritis Cartilage, 17:1620–1627
12 Hata S et al., 2008, Effect of oral administration of high advanced-collagen tripeptide (HACP) on bone healing process in rat; J Hard Tissue Biol, 17:17–22
13 Sibilla S et al., 2015, An overview of the beneficial effects of hydrolysed col- lagen as a nutraceutical on skin properties: Scientific background and clinical studies; The Open Nutraceuticals Journal, 8:29-42
14 Morikiri Y et al., 2018, The collagen-derived compound collagen tripep- tide induces collagen expression and extends lifespan via a conserved p38 mitogen-activated protein kinase cascade; Biochem Biophys Res Comm, 505 (4):1168-1173
15 Yasutaka S et al., 2009, Effect of Prolyl-hydroxyproline (Pro-Hyp), a Food-Derived Collagen Peptide in Human Blood, on Growth of Fibroblasts from Mouse Skin; J Agric Food Chem, 57:444–449
16 Ohara H et al., 2010, Collagen-derived dipeptide, proline–hydroxyproline stimulates cell proliferation and hyaluronic acidsynthesis in cultured human dermal fibroblasts; J Dermatol, 37: 330–338
17 Sato K et al., 2020, Collagen-Derived Di-Peptide, Prolylhydroxyproline (Pro-Hyp): A New Low Molecular Weight Growth-Initiating Factor for Specific Fibroblasts Associated With Wound Healing; Frontiers in Cell and Develop- mental Biology, 8:548975
18 Choi S Y et al., 2014, Effects of collagen tripeptide supplement on skin properties: a prospective, randomized, controlled study; J Cosmet Laser Ther, 16:132−137
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