Blood kinetics of collagen tripeptide containing collagen in human
Numerous reports exist on the absorbability of general collagen peptide (CP) after oral ingestion. Collagen tripeptide (CTP)-containing collagen is believed to be absorbed more efficiently because CTP is in tripeptide form and is absorbed directly through the small intestine.
In this page, we discuss the comparison of the plasma absorption of Gly-Pro-Hyp (GPHyp) and its metabolite Pro-Hyp (PHyp) after CP and CTP-containing collagen ingestion. GPHyp rarely appears after general CP ingestion but is a major component of CTP. PHyp is widely known as the main metabolite after CP ingestion.
Blood kinetics after the oral administration of CP or CTP-containing collagen in humans
1) Methods
We prepared porcine-derived CTP-containing collagen (Mw: 600 Da) and CP (Mw: 5,000) as test foods. Four healthy men participated in this ingestion test with at least a 2-week washout period between each administration. The subjects ingested 80 mg/kg body weight of a test food dissolved in water after a 16 h fasting period. Blood samples were withdrawn from the subjects’ forearms before and 5, 15, 30, 60, 120, and 240 min after ingestion. Then, the blood samples were centrifuged to obtain the plasma. GPHyp and PHyp in the plasma samples were subsequently analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The changes in the plasma levels and area under the curve (AUC) were calculated from the obtained data. An ingestion test with the tripeptide-rich fraction of the CTP-containing peptide was also performed.
2) Results
We report the results of the change in GPHyp plasma levels after the ingestion of the two test foods. GPHyp appeared in the blood 5 min after CTP-containing collagen ingestion. Subsequently, its plasma level rapidly increased and reached peak plasma concentration in 30–60 min. However, in CP ingestion, GPHyp plasma levels remained very low throughout the measurement period. AUC in CTP-containing collagen ingestion was approximately 39 times higher than that in CP ingestion.
Next, we discuss the change in PHyp plasma levels. PHyp appeared 5 min after CTP-containing collagen ingestion. Then, the plasma level rapidly increased and reached Tmax in 60 min. Consequently, PHyp gradually decreased but remained in the blood even at 240 min after CTP-containing collagen ingestion. AUC in CTP-containing collagen ingestion was approximately 8 times higher than that in CP ingestion.
Gly-Pro-Hyp、Pro-Hypの経時変化
3) Discussion
CTP-containing collagen was superior to general CP in terms of functional tripeptide/dipeptide absorbability and its high absorption provides reliable functionality.
4) Additional information
As shown in the Table below, various functional peptides appeared in the blood after the ingestion of CTP-containing collagen.
Table: Physiological activity of collagen-derived metabolite peptides.
| Peptides | Physiological activity |
|---|---|
| Gly-Pro-Hyp | Promotes collagen1-4) and hyaluronic acid production5), affects platelet aggregation6),and inhibits dipeptidylpeptidase-Ⅳ activity7) |
| Gly-Pro-Ala | Promotes nerve cell differentiation8) and alleviates intestinal damage9) |
| Gly-Pro | Hypotensive action10) |
| Pro-Hyp | Promotes proliferation of cultured fibroblasts11-12) and production of collagen13) and hyaluronic acid14) |
| Hyp-Gly | Suppresses osteoclast activation15) and promotes differentiation of osteoblasts16) and myoblasts17) |
| Leu-Hyp | Promotes collagen production18) |
| Ala-Hyp | Inhibits angiotensin-I-converting enzyme20-21), promotes collagen production 18) and cultured fibroblast proliferation11) |
| References: | |
| 1) |  Min, Geng. "Collagen hydrolysate Gly-Pro-Hyp on osteoblastic proliferation and differentiation of MC3T3-E1 cells." Journal of Clinical and Nursing Research 1.3 (2017) |
| 2) | Lee, Hyun-Jun, et al. "Orally administered collagen peptide protects against UVB-induced skin aging through the absorption of dipeptide forms, Gly-Pro and Pro-Hyp." Bioscience, Biotechnology, and Biochemistry 83.6 (2019): 1146-1156. |
| 3) | Tang, L., et al. "Effect of collagen tripeptide of Type I collagen on midration, proliferation and collagen synthesis of human aortic smooth muscle cells." J Kanazawa Med Univ 34 (2009): 93-100. |
| 4) | Tsuruoka, Naoki, et al. "Promotion by collagen tripeptide of type I collagen gene expression in human osteoblastic cells and fracture healing of rat femur." Bioscience, biotechnology, and biochemistry 71.11 (2007): 2680-2687. |
| 5) | Okawa, Tomoko, et al. "Oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model." Journal of Dermatological Science 66.2 (2012): 136-143. |
| 6) | Postlethwaite, A. E., J. M. Seyer, and A. H. Kang. "Induction of fibroblast chemotaxis by type I, II and III collagens and collagen degradation peptides." Proc. Natl. Acad. Sci. USA 75 (1978): 871. Postlethwaite, A. E. "Snyderman. R. and Kang, AH." J. Exp. Med 144 (1976): 118. |
| 7) | Hatanaka, Tadashi, Kayoko Kawakami, and Misugi Uraji. "Inhibitory effect of collagen-derived tripeptides on dipeptidylpeptidase-Ⅳ activity." Journal of enzyme inhibition and medicinal chemistry 29.6 (2014): 823-828. |
| 8) | 特願2009-272229神経細胞分化促進剤 |
| 9) | Deng, Zhao, et al. "Gly-pro-ala peptide and FGSHF3 exert protective effects in DON-induced toxicity and intestinal damage via decreasing oxidative stress." Food Research International 139 (2021): 109840. |
| 10) | Ichimura, Toshiaki, et al. "Antihypertensive effect of enzymatic hydrolysate of collagen and Gly-Pro in spontaneously hypertensive rats." Bioscience, biotechnology, and biochemistry 73.10 (2009): 2317-2319. |
| 11) | Ohara, Hiroki, et al. "Collagen‐derived dipeptide, proline‐hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts." The Journal of dermatology 37.4 (2010): 330-338. |
| 12) | Shigemura, Yasutaka, et al. "Effect of prolyl-hydroxyproline (Pro-Hyp), a food-derived collagen peptide in human blood, on growth of fibroblasts from mouse skin." Journal of agricultural and food chemistry 57.2 (2009): 444-449. |
| 13) | Lee, Hyun-Jun, et al. "Orally administered collagen peptide protects against UVB-induced skin aging through the absorption of dipeptide forms, Gly-Pro and Pro-Hyp." Bioscience, Biotechnology, and Biochemistry 83.6 (2019): 1146-1156. |
| 14) | Ohara, Hiroki, et al. "Collagen‐derived dipeptide, proline‐hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts." The Journal of dermatology 37.4 (2010): 330-338. |
| 15) | Mano, H., Nakatani, S., Sekiguchi, Y., Shimizu, J., Sugihara, F.,Haketa, Y., and Wada, M., Abstr. 27th Annu. Meet. Jpn. Soc. Bone Miner. Res., p. 227, 2009 Shigemura et al. Food Chemistry129(2011) |
| 16) | Kimira, Yoshifumi, et al. "Collagen-derived dipeptide prolyl-hydroxyproline promotes differentiation of MC3T3-E1 osteoblastic cells." Biochemical and biophysical research communications 453.3 (2014): 498-501. |
| 17) | Kitakaze, Tomoya, et al. "The collagen derived dipeptide hydroxyprolyl-glycine promotes C2C12 myoblast differentiation and myotube hypertrophy." Biochemical and biophysical research communications 478.3 (2016): 1292-1297. |
| 18) | 特許第4995155号 生体コラーゲン合成促進剤並びに生体コラーゲン合成促進用飲食品、化粧品及び医薬部外品 |
| 20) | 岩井浩二, et al. "鶏コラーゲン加水分解物摂取後のヒト血中ペプチドの動態と ACE 阻害作用." 日本食品科学工学会誌 56.6 (2009): 326-330. |
| 21) | Oshima, Genichiro, Hirokazu Shimabukuro, and Kinzo Nagasawa. "Peptide inhibitors of angiotensin I-converting enzyme in digests of gelatin by bacterial collagenase." Biochimica et Biophysica Acta (BBA)-Enzymology 566.1 (1979): 128-137. |
