Type-II Collagen
•Last Updated: September 28 2022
Type II collagen (CII) is a protein and component of joint cartilage. Oral ingestion of CII in its undenatured form may reduce autoimmunity to the body's own CII, resulting in less joint inflammation in instances of osteoarthritis and rheumatism.
Type-II Collagen is most often used for
Last Updated: September 28 2022
Type II collagen (CII) is a peptide and a major component of joint cartilage. When taken as a supplement, CII is usually in one of two forms: undenatured or hydrolyzed. Undenatured collagen has been minimally processed at a low temperature to keep its peptides mostly intact. Hydrolyzed CII has been processed with a higher degree of heat, acid, and enzymes, resulting in the breakdown of peptides from larger forms into smaller ones.
The primary benefit of undenatured CII appears to be improvement in joint pain, mainly in the context of osteoarthritis and rheumatoid arthritis. Hydrolyzed CII (also known as CII hydrolysate) may improve skin health/appearance and reduce joint pain.
By and large, CII seems fairly safe. One potential concern is that collagen (in dosages of around 10 grams per day) has been shown to increase oxalate levels in urine, likely because collagen consists of approximately 10% hydroxyproline, and a major metabolite of hydroxyproline is oxalate. As a result, higher doses of CII could increase the risk of oxalate-based kidney stones in susceptible individuals.
Undenatured CII has been proposed to improve joint pain through an effect on the immune system. More specifically, CII peptides are thought to induce the formation of regulatory T cells (Tregs) in areas of the gut known as Preyer’s patches. These Tregs can enter circulation, where they produce anti-inflammatory compounds (e.g., IL-10), which in theory can inhibit inflammation and tissue damage in joints.
The hydrolysis of type II collagen seems to result in the breakdown of the most immunologically active peptides, meaning that the effect of hydrolyzed collagen on joints may not act via this mechanism. However, in higher doses, hydrolyzed CII might improve joint pain by supplying the amino acids used to repair the damaged tissue.
Note that Type-II Collagen is also known as:
- CII
- Hydrolyzed collagen
- Solubilized collagen
- Gelatin
- Collagen
- Shark gelatin
Type-II Collagen should not be confused with:
- Colostrum (different protein with a similar name)
The dose of CII taken depends on whether it is denatured (hydrolyzed) or undenatured. For skin and joint health, the daily dose of hydrolyzed collagen is around 10 grams per day. For treatment of osteoarthritis and rheumatoid arthritis, undenatured collagen is taken at a much lower daily dose (often around 40 milligrams), and while it doesn't need to be taken at any particular time of the day, it may be ideal to take it on an empty stomach before breakfast.
CII should not be taken as a protein supplement because it has a lackluster amino acid profile.
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1.^Nomura Y1, Oohashi K, Watanabe M, Kasugai SIncrease in bone mineral density through oral administration of shark gelatin to ovariectomized ratsNutrition.(2005 Nov-Dec)
2.^Oesser S1, Adam M, Babel W, Seifert JOral administration of (14)C labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL)J Nutr.(1999 Oct)
3.^Asghar A, Henrickson RLChemical, biochemical, functional, and nutritional characteristics of collagen in food systemsAdv Food Res.(1982)
5.^NEUMAN REThe amino acid composition of gelatins, collagens and elastins from different sourcesArch Biochem.(1949 Dec)
6.^Wu J1, Fujioka M, Sugimoto K, Mu G, Ishimi YAssessment of effectiveness of oral administration of collagen peptide on bone metabolism in growing and mature ratsJ Bone Miner Metab.(2004)
7.^Zhu P1, Li XY, Wang HK, Jia JF, Zheng ZH, Ding J, Fan CMOral administration of type-II collagen peptide 250-270 suppresses specific cellular and humoral immune response in collagen-induced arthritisClin Immunol.(2007 Jan)
8.^Kakoi C1, Udo H, Matsukawa T, Ohnuki KCollagen peptides enhance hippocampal neurogenesis and reduce anxiety related behavior in miceBiomed Res.(2012)
10.^Oral Administration of Shark Type II Collagen Suppresses Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Rats.()
11.^Di Cesare Mannelli L, Micheli L, Zanardelli M, Ghelardini CLow dose native type II collagen prevents pain in a rat osteoarthritis modelBMC Musculoskelet Disord.(2013 Aug 1)
12.^Lugo JP, Saiyed ZM, Lau FC, Molina JP, Pakdaman MN, Shamie AN, Udani JK1Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteersJ Int Soc Sports Nutr.(2013 Oct 24)
13.^Crowley DC1, Lau FC, Sharma P, Evans M, Guthrie N, Bagchi M, Bagchi D, Dey DK, Raychaudhuri SPSafety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trialInt J Med Sci.(2009 Oct 9)
14.^Wright NT, Humphrey JDDenaturation of collagen via heating: an irreversible rate processAnnu Rev Biomed Eng.(2002)
15.^Marone PA1, Lau FC, Gupta RC, Bagchi M, Bagchi DSafety and toxicological evaluation of undenatured type II collagenToxicol Mech Methods.(2010 May)
16.^Moskowitz RWRole of collagen hydrolysate in bone and joint diseaseSemin Arthritis Rheum.(2000 Oct)
17.^Khiari Z1, Ndagijimana M1, Betti M2Low molecular weight bioactive peptides derived from the enzymatic hydrolysis of collagen after isoelectric solubilization/precipitation process of turkey by-productsPoult Sci.(2014 Jun 15)
18.^A randomized controlled trial on the efficacy and safety of a food ingredient, collagen hydrolysate, for improving joint comfort.()
20.^Eyre DR, McDevitt CA, Billingham ME, Muir HBiosynthesis of collagen and other matrix proteins by articular cartilage in experimental osteoarthrosisBiochem J.(1980 Jun 15)
21.^Bagchi D1, Misner B, Bagchi M, Kothari SC, Downs BW, Fafard RD, Preuss HGEffects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic explorationInt J Clin Pharmacol Res.(2002)
22.^Tong T1, Zhao W, Wu YQ, Chang Y, Wang QT, Zhang LL, Wei WChicken type II collagen induced immune balance of main subtype of helper T cells in mesenteric lymph node lymphocytes in rats with collagen-induced arthritisInflamm Res.(2010 May)
23.^McDole JR1, Wheeler LW, McDonald KG, Wang B, Konjufca V, Knoop KA, Newberry RD, Miller MJGoblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestineNature.(2012 Mar 14)
24.^Min SY1, Park KS, Cho ML, Kang JW, Cho YG, Hwang SY, Park MJ, Yoon CH, Min JK, Lee SH, Park SH, Kim HYAntigen-induced, tolerogenic CD11c+,CD11b+ dendritic cells are abundant in Peyer's patches during the induction of oral tolerance to type II collagen and suppress experimental collagen-induced arthritisArthritis Rheum.(2006 Mar)
25.^Park MJ1, Min SY, Park KS, Cho YG, Cho ML, Jung YO, Park HS, Chang SH, Cho SG, Min JK, Park SH, Kim HYIndoleamine 2,3-dioxygenase-expressing dendritic cells are involved in the generation of CD4+CD25+ regulatory T cells in Peyer's patches in an orally tolerized, collagen-induced arthritis mouse modelArthritis Res Ther.(2008)
26.^Baker AM1, Batchelor DC, Thomas GB, Wen JY, Rafiee M, Lin H, Guan JCentral penetration and stability of N-terminal tripeptide of insulin-like growth factor-I, glycine-proline-glutamate in adult ratNeuropeptides.(2005 Apr)
28.^Takeuchi Y1, Nakayama K, Matsumoto TDifferentiation and cell surface expression of transforming growth factor-beta receptors are regulated by interaction with matrix collagen in murine osteoblastic cellsJ Biol Chem.(1996 Feb 16)
29.^Takeuchi Y1, Suzawa M, Kikuchi T, Nishida E, Fujita T, Matsumoto TDifferentiation and transforming growth factor-beta receptor down-regulation by collagen-alpha2beta1 integrin interaction is mediated by focal adhesion kinase and its downstream signals in murine osteoblastic cellsJ Biol Chem.(1997 Nov 14)
30.^Gimsa U1, Sieper J, Braun J, Mitchison NAType II collagen serology: a guide to clinical responsiveness to oral toleranceRheumatol Int.(1997)
31.^Guzman RE1, Evans MG, Bove S, Morenko B, Kilgore KMono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: an animal model of osteoarthritisToxicol Pathol.(2003 Nov-Dec)
32.^De Ceuninck F1, Sabatini M, Pastoureau PRecent progress toward biomarker identification in osteoarthritisDrug Discov Today.(2011 May)
33.^De Ceuninck F1, Sabatini M, Renoux V, de Nanteuil G, Pastoureau PUrinary collagen type II C-telopeptide fragments are sensitive markers of matrix metalloproteinase-dependent cartilage degradation in rat adjuvant-induced arthritisJ Rheumatol.(2003 Jul)
34.^van Amelsfort JM1, Jacobs KM, Bijlsma JW, Lafeber FP, Taams LSCD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluidArthritis Rheum.(2004 Sep)
35.^Möttönen M1, Heikkinen J, Mustonen L, Isomäki P, Luukkainen R, Lassila OCD4+ CD25+ T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritisClin Exp Immunol.(2005 May)
36.^de Kleer IM1, Wedderburn LR, Taams LS, Patel A, Varsani H, Klein M, de Jager W, Pugayung G, Giannoni F, Rijkers G, Albani S, Kuis W, Prakken BCD4+CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritisJ Immunol.(2004 May 15)
37.^Ruprecht CR1, Gattorno M, Ferlito F, Gregorio A, Martini A, Lanzavecchia A, Sallusto FCoexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synoviaJ Exp Med.(2005 Jun 6)
38.^Wehrens EJ1, van Wijk F, Roord ST, Albani S, Prakken BJTreating arthritis by immunomodulation: is there a role for regulatory T cellsRheumatology (Oxford).(2010 Sep)
39.^de Jager W1, Hoppenreijs EP, Wulffraat NM, Wedderburn LR, Kuis W, Prakken BJBlood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional studyAnn Rheum Dis.(2007 May)
40.^Harada S1, Yamamura M, Okamoto H, Morita Y, Kawashima M, Aita T, Makino HProduction of interleukin-7 and interleukin-15 by fibroblast-like synoviocytes from patients with rheumatoid arthritisArthritis Rheum.(1999 Jul)
42.^Min SY1, Hwang SY, Park KS, Lee JS, Lee KE, Kim KW, Jung YO, Koh HJ, Do JH, Kim H, Kim HYInduction of IL-10-producing CD4+CD25+ T cells in animal model of collagen-induced arthritis by oral administration of type II collagenArthritis Res Ther.(2004)
43.^Thomé R1, Fernandes LG, Mineiro MF, Simioni PU, Joazeiro PP, Tamashiro WMOral tolerance and OVA-induced tolerogenic dendritic cells reduce the severity of collagen/ovalbumin-induced arthritis in miceCell Immunol.(2012 Nov)
44.^Yoshinari O1, Shiojima Y, Moriyama H, Shinozaki J, Nakane T, Masuda K, Bagchi MWater-soluble undenatured type II collagen ameliorates collagen-induced arthritis in miceJ Med Food.(2013 Nov)
45.^Heo YJ1, Joo YB, Oh HJ, Park MK, Heo YM, Cho ML, Kwok SK, Ju JH, Park KS, Cho SG, Park SH, Kim HY, Min JKIL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population of rheumatoid arthritis patientsImmunol Lett.(2010 Jan 4)
46.^Trentham DE1, Dynesius-Trentham RA, Orav EJ, Combitchi D, Lorenzo C, Sewell KL, Hafler DA, Weiner HLEffects of oral administration of type II collagen on rheumatoid arthritisScience.(1993 Sep 24)
47.^Barnett ML1, Kremer JM, St Clair EW, Clegg DO, Furst D, Weisman M, Fletcher MJ, Chasan-Taber S, Finger E, Morales A, Le CH, Trentham DETreatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trialArthritis Rheum.(1998 Feb)
48.^Thorbecke GJ1, Schwarcz R, Leu J, Huang C, Simmons WJModulation by cytokines of induction of oral tolerance to type II collagenArthritis Rheum.(1999 Jan)
49.^Moses HL1, Arteaga CL, Alexandrow MG, Dagnino L, Kawabata M, Pierce DF Jr, Serra RTGF beta regulation of cell proliferationPrincess Takamatsu Symp.(1994)
50.^Nakae S1, Nambu A, Sudo K, Iwakura YSuppression of immune induction of collagen-induced arthritis in IL-17-deficient miceJ Immunol.(2003 Dec 1)
51.^Henningsson L1, Eneljung T, Jirholt P, Tengvall S, Lidberg U, van den Berg WB, van de Loo FA, Gjertsson IDisease-dependent local IL-10 production ameliorates collagen induced arthritis in micePLoS One.(2012)
52.^Yang M1, Deng J, Liu Y, Ko KH, Wang X, Jiao Z, Wang S, Hua Z, Sun L, Srivastava G, Lau CS, Cao X, Lu LIL-10-producing regulatory B10 cells ameliorate collagen-induced arthritis via suppressing Th17 cell generationAm J Pathol.(2012 Jun)
53.^Iizuka M1, Wakasa Y, Tsuboi H, Asashima H, Hirota T, Kondo Y, Matsumoto I, Takaiwa F, Sumida TSuppression of collagen-induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of type II collagenPlant Biotechnol J.(2014 Jul 2)
54.^Belz GT1, Heath WR, Carbone FRThe role of dendritic cell subsets in selection between tolerance and immunityImmunol Cell Biol.(2002 Oct)
55.^Maldonado RA1, von Andrian UHHow tolerogenic dendritic cells induce regulatory T cellsAdv Immunol.(2010)
56.^Fallarino F1, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, Belladonna ML, Fioretti MC, Alegre ML, Puccetti PModulation of tryptophan catabolism by regulatory T cellsNat Immunol.(2003 Dec)
58.^Oishi Y1, Fu ZW, Ohnuki Y, Kato H, Noguchi TMolecular basis of the alteration in skin collagen metabolism in response to in vivo dexamethasone treatment: effects on the synthesis of collagen type I and III, collagenase, and tissue inhibitors of metalloproteinasesBr J Dermatol.(2002 Nov)
59.^Quan T1, He T, Kang S, Voorhees JJ, Fisher GJSolar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-beta type II receptor/Smad signalingAm J Pathol.(2004 Sep)
60.^Fisher GJ1, Datta S, Wang Z, Li XY, Quan T, Chung JH, Kang S, Voorhees JJc-Jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acidJ Clin Invest.(2000 Sep)
61.^Fisher GJ1, Datta SC, Talwar HS, Wang ZQ, Varani J, Kang S, Voorhees JJMolecular basis of sun-induced premature skin ageing and retinoid antagonismNature.(1996 Jan 25)
62.^Iwai K1, Hasegawa T, Taguchi Y, Morimatsu F, Sato K, Nakamura Y, Higashi A, Kido Y, Nakabo Y, Ohtsuki KIdentification of food-derived collagen peptides in human blood after oral ingestion of gelatin hydrolysatesJ Agric Food Chem.(2005 Aug 10)
63.^Shigemura Y1, Iwai K, Morimatsu F, Iwamoto T, Mori T, Oda C, Taira T, Park EY, Nakamura Y, Sato KEffect of Prolyl-hydroxyproline (Pro-Hyp), a food-derived collagen peptide in human blood, on growth of fibroblasts from mouse skinJ Agric Food Chem.(2009 Jan 28)
64.^Ohara H1, Iida H, Ito K, Takeuchi Y, Nomura YEffects of Pro-Hyp, a collagen hydrolysate-derived peptide, on hyaluronic acid synthesis using in vitro cultured synovium cells and oral ingestion of collagen hydrolysates in a guinea pig model of osteoarthritisBiosci Biotechnol Biochem.(2010)
65.^Ohara H1, Ichikawa S, Matsumoto H, Akiyama M, Fujimoto N, Kobayashi T, Tajima SCollagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblastsJ Dermatol.(2010 Apr)
66.^Kawada C, Yoshida T, Yoshida H, Matsuoka R1, Sakamoto W, Odanaka W, Sato T, Yamasaki T, Kanemitsu T, Masuda Y, Urushibata OIngested hyaluronan moisturizes dry skinNutr J.(2014 Jul 11)
67.^Schwartz SR1, Park JIngestion of BioCell Collagen(®), a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signsClin Interv Aging.(2012)
68.^Yoshinari O1, Marone PA, Moriyama H, Bagchi M, Shiojima YSafety and toxicological evaluation of a novel, water-soluble undenatured type II collagenToxicol Mech Methods.(2013 Sep)
69.^Adam M1, Spacek P, Hulejová H, Galiánová A, Blahos JPostmenopausal osteoporosis. Treatment with calcitonin and a diet rich in collagen proteinsCas Lek Cesk.(1996 Jan 31)
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