Type-II Collagen - Scientific Review On Usage, Dosage, Side Effects - Examine

16/12/2017 Type-II Collagen - Scientic Review on Usage, Dosage, Side Effects | Examine.
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SUPPLEMENTS NUTRITION STORE
Type-II Collagen
Type II collagen (CII) is a peptide and component of joint cartilage. It's oral ingestion appears to reduce autoimmunity
to the body's own CII, resulting in less in ammation in instances of osteoarthritis and rheumatism and bene ts to
joint health.
This page features 70 unique references to scienti c papers.
History (/history/type-ii-collagen/)
THINGS TO KNOW HOW TO TAKE HUMAN EFFECT MATRIX SCIENTIFIC RESEARCH CITATIONS
Follow this Page for updates
Things to Know
Also Known As
hydrolyzed collagen, solubilized collagen, CII, shark gelatin, gelatin, collagen
Do Not Confuse With

Colostrum (/supplements/colostrum/) (di erent protein with a similar name)
Things to Note
CII supplements are derived from animals and thus not vegan-friendly
Is a Form Of
Joint Health
Protein supplement
https://examine.com/supplements/type-ii-collagen/ 1/14
16/12/2017 Type-II Collagen - Scientic Review on Usage, Dosage, Side Effects | Examine.com
Caution Notice
()
Examine.com Medical Disclaimer (/disclaimer)
How to Take
Recommended dosage, active amounts, other details
Collagen supplements are taken in one of two di erent forms, either in the form of hydrolyzed collagen or in the form of an
undenatured type II collagen; both forms have di erent dosing strategies and while their bene ts may share some similarities can be
considered two di erent supplements.
Hydrolyzed collagen is taken in doses of around 10g a day for skin health and some bene ts to joints, and can be taken with meals. It
should not be taken in higher doses as a protein supplement (/supplements/protein-supplement/) (for muscle gain and fat loss) due
to having less e cacy than other protein sources and a lacklustre amino acid pro le.
Undenatured collagen is taken at a lower dose of approximately 40mg once daily for the treatment of osteoarthritis and rheumatoid
arthritis when there is an autoimmune component to it, 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.
Human E ect Matrix
The Human E ect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what e ects type-ii
collagen has on your body, and how strong these e ects are.
GRADE LEVEL OF EVIDENCE
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
()
LEVEL OF OUTCOME MAGNITUDE OF EFFECT CONSISTENCY OF RESEARCH RESULTS NOTES
EVIDENCE
? ? ?
-
Pain (/topics/pain/) - See all 5 studies
(/rubric/e ects/view/839b39e8cef9fbc65648eed925d9bb30/359502a00fa29552278471ce3a9e4b72/all/)
C-Reactive Protein -
(/topics/c-reactive- - See study
protein/) (/rubric/e ects/view/839b39e8cef9fbc65648eed925d9bb30/e330349211447ab4b950446e202f1994/all/)
Exercise-induced
-
Joint Pain - See study
(/topics/exercise-
(/rubric/e ects/view/839b39e8cef9fbc65648eed925d9bb30/e7feac1c417180f2ca8f73a7ce2fe1af8655f480/all/)
induced-joint-pain/)
Immunoglobulin A -
(/topics/immunoglo - See study
bulin-a/) (/rubric/e ects/view/839b39e8cef9fbc65648eed925d9bb30/276e5d70198c835f332dd7a89e04655b37c3291a/all/
Immunoglobulin G -
(/topics/immunoglo - See study
bulin-g/) (/rubric/e ects/view/839b39e8cef9fbc65648eed925d9bb30/114361518a221eab8e2e4e57a4902d12cb279ec5/all
Symptoms of
-
Osteoarthritis - See 2 studies
(/topics/symptoms-
(/rubric/e ects/view/839b39e8cef9fbc65648eed925d9bb30/846e9c6e95a32a8d804f103 dde3f80/all/)
of-osteoarthritis/)
Symptoms of
Rheumatoid
-
Arthritis - See all 3 studies
(/topics/symptoms-
(/rubric/e ects/view/839b39e8cef9fbc65648eed925d9bb30/8ae640cee7e3edaf86b5bcc003d24557/all/)
of-rheumatoid-
arthritis/)
Studies Excluded from Consideration

Note: The above HEM contains information on both hydrolyzed collagen supplements and undenatured collagen
supplements despite signi cant dose di erences between the two
Used alongside calcitonin injections[1]
Confounded with chondroitin (/supplements/chondroitin/) and hyaluronic acid[2]
Scienti c Research
Table of Contents:
1 Sources and Composition
1.1 Sources and Composition
1.2 Physicochemical Properties
()
1.3 Biological Relevance
1.4 Formulations and Variants
2 Molecular Targets
2.1 Tolerogenic Dendritic Cells
3 Pharmacology
3.1 Absorption
3.2 Distribution
3.3 Elimination
4 Neurology
4.1 Neurogenesis
5 Bone and Joint Health
5.1 Osteoblasts
5.2 Collagen and Joints
5.3 Osteoarthritis
5.4 Rheumatoid Arthritis
6 In ammation and Immunology
6.1 Interferons and Immunglobulins
6.2 Interleukins
6.3 T Cells
7 Interactions with Aesthetics
7.1 Skin
8 Safety and Toxicology
8.1 General
1 Sources and Composition
1.1. Sources and Composition
()
Type II collagen is a particular type of collagen prevalent in humans, and is synonymous with the dietary supplements such as shark
gelatin[3] and gelatin[4] while in the process of making the collagen more water soluble it can be referred to as solubilized collagen;
collagen type II is commonly appreviated as CII, and will be the phrasing used throughout the course of this article for consistency.
CII's main supplemental purpose is for the treatment of joint pain and arthritic conditions, as for a dietary protein source (collagen or
gelatin protein) despite good absorption from the intestinal tract[4][5] it has lower concentration of essential amino acids and is devoid
of L-cysteine.[6][7]
CII primarily refers to:
Various CII peptides ranging between 1,000-30,000 Da in weight,[8] and these peptides have been noted to be absorbed intact from the
intestinal tract of rats when orally administered[4] with one peptide in particular being designated 250-270 as that appears to be the
weight range where the most active peptides are located in[9]
Various tripeptides containing Glycine (/supplements/glycine/) such as Gly-Pro-Hyp (Glycine-Proline-Hydroxyproline, which can reach up
to 8% weight after enzymatic treatment of collagen[10]), Gly-Pro-Glu (Glycine-Proline-Glutamine (/supplements/glutamine/)[11]) and Pro-
Gly-Pro (Proline-Glycine-Proline[11])
There are various peptides contained within CII with the active ones appearing to be fairly low molecular weight and are
likely small peptides (like tripeptides) comprised of a high amounts of glycine and proline, two amino acids that are
prominent in collagen protein
With sources of CII being:
Shark-derived CII appears to be 12kDa in weight and e ective for similar purposes[12]
Porcine CII ha shown e cacy at similar doses to other types[13]
Chicken sternum has shown to be a source of CII and a brand name product from this source is UC-II[14][15]
CII may also be derived from bovine articular cartilage, but due to bovine spongiform encephalopathy (Mad Cow Disease) alternate
sources are sought after since some authors believe that there is a risk of infection associated with bovine sources;[12] a similar
concern led to modern phosphatidylserine (/supplements/phosphatidylserine/) supplements being derived from soy rather than
bovine cortex.
Various mammals and sh have been shown to be possible sources of CII, and each source appears to be quite similar
in potency when supplemented in rodents and humans
1.2. Physicochemical Properties

Denaturation refers to the irreversible process of unwinding peptide chains into their constituent amino acids, and is used in the
processing of gelatin protein supplements via heating;[16] this process when carried to completion is known to degrade CII into its
constituent amino acids and ablate its bene ts hence why CII supplements that are active in arthritic conditions are sometimes touted
to be undenatured (ie. UC-II[17]).
Hydrolyzed collagen refers to the process of hydrolysis on collagen, which has a heat and acid component.[18] However, as hydrolysis
of collagen tends to break down peptides from larger forms into smaller ones which are in the weight range for known bioactive
peptides[19] supplemental hydrolyzed collagen may have a similar supplemental role; it has shown joint pain reducing properties in
humans although at a much higher dose of 10g.[20]
()
The process of hydrolysis and denaturation break down peptides into smaller peptide chains and ultimately into their
constituent amino acids, and upon reaching the nal solution of amino acids bene ts associated with the CII peptide will
not occur (as CII is destroyed). Hydrolyzed collagen shows some bene ts to joint pain despite this process, but requires
a signi cantly higher oral dose
1.3. Biological Relevance

There are numerous types of collagen in mammals including collagen type II, III, VI, IX, X, XI, XII, and XIV which contribute to the
mature matrix while collagens II, IX, and XI contribute to a developing matrix;[21] CII is the most prominent, with over 80% of total
collagen being comprised of this type in youth possibly increasing to over 90% in mature articular cartilage.[21]
The synthetic capacity of CII in articular chondrocytes appears to decrease after skeletal tissue stops growing,[21] and its synthesis has
been noted to be increased after joint injury.[22]
1.4. Formulations and Variants

Undenatured CII (UC-II) is a patented form of collagen derived from chicken sternum that is glycosylated[23] and has been used in a
few rodent[17][23][24] and industry-funded human studies.[14][15] and appears to be well tolerated in rats with a very high LD50 value
(greater than 5,000mg/kg)[17] and at the active dose of 40mg in human subjects.[14]
UC-II is a glycosylated form of CII derived from chicken cartilage and appears to be an e ective supplemental form in
humans and rodents
2 Molecular Targets
2.1. Tolerogenic Dendritic Cells

The rst site of activity for oral ingestion of CII in instances of autoimmune in ammation appears to be at the level of dendritic
(antigen presenting) immune cells in the intestines, areas known as peyer's patches which have a high population of dendritic cells.
Tolerogenic refers to the capacity to form a tolerance to an antigen via in uencing other immune cell populations such as T cells.
Ingestion of low doses of CII appears to cause a change in these dendritic cells which promote T cells to di erentiate into a more
antiin ammatory form known as a T regulatory (Treg) cell, observed via the receptors they express; Treg cells that are relevant to CII
ingestion are CD4+CD25+Foxp3+ Treg cells which reduce di erentiation of T cells into CD4+.
CD4+CD25+Foxp3+ Treg cells produce more of a cytokine known as interleukin 10 (IL-10) and this interleukin suppresses the actions of
another type known as IL-17; as IL-17 exacerbates rheumatism, increasing IL-10 concentrations reduces its actions and the
subsequent joint pain.
Continuing production of CD4+CD25+Foxp3+ Treg cells from CII is known as 'tolerance', which is achieved within a month of CII
supplementation and can be continually held until supplementation is stopped where T cell populations and the two interleukins
produced from them normalize about a month later resulting in symptoms recurring.
Via a dendritic cell -> Treg cell -> IL-10 pathway oral ingestion of CII can produce a state of transient tolerance, similar in
concept to providing an antigen prior to an infection, which results in less in ammatory cytokine activity and analgesic
e ects on joints of those a ected with in ammatory joint disorders.
()
Citations for the above can be found in the In ammation and Immunology section under Interleukins and T cells
3 Pharmacology
3.1. Absorption
In rats given an oral dose of hydrolyzed collagen (gelatin hydrolysate) at 10g/kg bodyweight, the overall bioavailability of the protein
supplement over the course of the next 12 hours was 95% reaching peak plasma concentrations after six hours;[4] when testing the
serum, peptides ranging from 500 daltons to 15 kilodaltons in weight from collagen appear to be absorbed intact.[4]
The role of type II collagen in immunology may not require absorption, as intestinal goblet cells are involved in deliverying antigens to
tolerogenic dendritic cells (DCs)[25] which are located in intestinal Peyer's patches.[26][27]
3.2. Distribution
Oral ingestion of 10g/kg hydrolyzed collagen in rats, despite being 85% eliminated from plasma within 24 hours, appeared to
accumulate in the skin as after peak levels are seen in the skin (after 12 hours) there is still 58% of the dose detectable in the skin after
192 hours;[4] other organs measured (liver, kidney, spleen, and skeletal muscle) did not appear to accumulate hydrolyzed collagen
relative to amino acid control.[4]
The aforementioned ingestion of hydrolyzed collagen did appear to accumulate in rat cartilage after 12 hours, maintaining
concentrations for the entire 192 hour observation period without signi cant decline.[4]
3.3. Elimination
With oral ingestion of 10g/kg hydrolyzed collagen in rats, despite good absorption 85% of the radioactivity of the labelled amino acids
disappeared from plasma within 24 hours.[4]
4 Neurology
4.1. Neurogenesis
In mice fed collagen peptides either of low molecular weight (2,000 and 8% Gly-Pro-Hyp) or high molecular weight (30,000) as control,
both in the drinking water for four weeks, noted that the low molecular weight peptides appeared to enhance neurogenesis in the
dentate gyrus (of the hippocampus) about 20% more than control and these e ects occurred alongside mild anxiolytic e ects.[10] It
was hypothesized that the peptides worked centrally,[10] as a similar tripeptide (Gly-Pro-Glu) has shown blood brain barrier
penetrative capacities[28] and peptides (like Noopept (/supplements/noopept/)) have the potential to mimick larger neurotrophic
proteins like BDNF and NGF.[29]
While the mechanisms are largely hypothetical at this point, it is suggested that peptides found in low molecular weight
collagen supplements may increase neurogenesis after oral administration
5 Bone and Joint Health

()
5.1. Osteoblasts
The de novo synthesis of type I collagen appeaers to have a role in promoting osteoblastic di erentiation.[30][31]
5.2. Collagen and Joints

Supplementation of CII is thought to confer some bene ts to otherwise healthy subjects in part because when assessing serum
antibodies towards the body's own structural CII it is detectable to a similar degree in both normal subjects as well as rheumatic
subjects.[32]
Oral supplementation of undenatured CII at 40mg a day (for four months) in subjects reporting joint pain but with no history of
arthritis noted that supplementation was e ective in improving knee range of motion (from 73.2 to 81 with no change in placebo)
and a longer time for joint pain to occur during exercise and faster recovery, maximal bene ts occurring three months after
supplementation and maintaining;[14] this study, however, failed to notice any in uence on daily joint pain as assessed by KOOS.[14]
Low dose collagen appears to be e ective for joint pain experienced during exercise despite not a ecting whole-day
joint pain scores relative to placebo
5.3. Osteoarthritis
In osteoarthritic (induced by monoiodoacetate, which promotes cartilage erosion[33]) rats fed low dose type II collagen (1-10mg/kg) for
two weeks appeared to exert analgesic e ects with highest e cacy at 1mg/kg associated with an attenuation of plasma CTX-II (40-
53%; no e ect without osteoarthritis) with no in uence on CPII, suggesting a protective mechanism[13] as CTX-II is produced by action
of metalloproteinases acting upon type II collagen[34] and is a relevant biomarker for osteoarthritis.[35]
Oral supplementation of UC-II (undenatured CII from chicken sternum) in osteoarthritic subjects at 40mg once daily over 90 days
noted that it was e ective (relative to baseline values) in improving WOMAC, VAS, and Lequesne scores of osteoarthritic pain and
mobility in a somewhat time dependent manner.[15] This study compared UC-II against a combination of glucosamine
(/supplements/glucosamine/) hydrochloride (1,500mg) with chondroitin sulphate (1,200mg) and found either equipotency or (in the
case of WOMAC) more e cacy with UC-II.[15]
Oral supplementation of 10g hydrolyzed collagen daily for six months in subjects with osteoarthritis was noted to reduce pain
assessed by VAS and WOMAC but failed to a ect other parameters of WOMAC such as sti ness and function relative to placebo.[20]
5.4. Rheumatoid Arthritis

T regulatory (Treg) cells play a role in arthritis as they appear to accumulate at sites of in ammation relative to peripheral blood in
arthritic patients despite no alterations in count overall relative to healthy controls,[36][37] and these Treg cells appear to be more
e ective at suppressing e ector T cells[38][39] and have numerous surface receptors (Foxp3 mRNA, CTLA-4, and GITR as examples)
overexpressed relative to other Treg cell types[40] with higher serum in ammatory factors being produced in these tissue (ex. IL-6 and
TNF-) relative to synovial uid from normal controls.[41][42]
Administration of the active peptide fragment (250-270) to the serum of rheumatic patients is able to increase CD3+ T cell populations
and particularly both CD3+CD25+ and CD3+CD69+ subsets.[9]
Rheumatism is a disease state associated with abnormal and elevated T regulatory cell function in synovial uid of those
a ected
In rodent models of rheumatism such as collagen-induced arthritis (high concentrations of collagen injections can cause autoimmune
rheumatism[43]) oral ingestion of the CII component known as peptide 250-270 in mice (0.1-0.5mg) for one week before induction of
arthritis is able to reduce the severity of subsequent arthritis[9][44] or prevent it from occurring in a few samples.[9] Other models of
rheumatism such as ovalbumin-induced[45] and Complete Freunds Adjuvant-induced[46][12] also see bene t with oral CII administration
by similar mechanisms.
The bene ts seen in rodent studies are associated with less immunoreactivity from splenocytes[9] and less CII-speci c IgG being
()
produced[9] speci cally IgG2A as IgG1 is increased.[44] T cells seem to take a CD3+CD25+ phenotype producing more IL-10[44][45] (which
suppresses the pro-rheumatic functions of IL-17[47]) and TGF- while T cells overall proliferate less when subsequently exposed to CII
in vitro;[44]
IFN- can be stimulated with higher concentrations in vitro (40g/mL) but are unaltered during oral tolerance[44] and the T cells which
produce it have been noted to be lessened in content after tolerance.[45]
The oral administration of CII prior to induction of collagen-induced rheumatoid arthritis functions similar to an oral
vaccination, allowing immune cells to become tolerant to CII and preventing or reducing the expected adverse
autoimmune responses to induction of rheumatism
Oral ingestion of solubilized type II collagen (0.1mg for one month, 1mg for two months) in subjects with severe active rheumatoid
arthritis for 90 days appeared to improve symptoms on joints (swelling, pain, and tenderness) and preserved 15m walking time
relative to placebo which bene tted to a lesser degree[48] with four subjects in the collagen group (14% of the sample) reporting
resolution of rheumatism.[48]
One human study noting bene t with supplementation also noted that cessation of supplementation for three months was
associated with symptoms returning, supplementation after this period reintroduces bene ts.[48] The bene ts seen with
supplementation correlate with the reduction in CII-speci c antibodies detectable in serum,[49][32] and while microgram doses seem to
outperform low milligrams doses (1-2.5mg[49]) 10mg has also been noted to outperform lower (1mg) doses.[32]
6 In ammation and Immunology
6.1. Interferons and Immunglobulins

Oral ingestion of a subactive dose of CII to mice (15g) prior to induction of arthritis has been noted to become more potent when
coadministered alongside TGF1 due to more T cell (CD8+) induction,[50] a property known to apply to TGF inherently.[51]
Some rheumatic patients have serum IgA and IgG antibodies to CII at baseline, and despite not changing throughout the course of
oral CII therapy (20-2,500g for 24 weeks) their presence may predict responsiveness to therapy.[49] Overall antibody titres do not
appear to correlate with disease status nor with improvement seen with oral supplementation of CII.[32]
6.2. Interleukins
Oral ingestion of CII (0.1-1mg/kg) to mice later give arthritis via collagen injections (an animal model of rheumatism) has been noted
to alter T cell populations in a manner that promotes IL-10 secretion, by encouraging di erentiation into CD4+CD25+ T cells;[44] the
cytokine itself is known to be antiin ammatory via suppressing the in ammatory cytokine IL-17 (required in the pathology of
autoimmune rheumatism[52]) and is itself therapeutic in instances of rheumatism[53] by this suppressive mechanism.[47][54]
Studies assessing concentrations of IL-17 itself do not appear to note any changes with ingestion of CII peptides relative to control
groups.[55]
The activity of IL-10 appears to be increased secondary to higher concentrations of this interleukin, which suppress the
activity of IL-17 despite not changing concentrations of the latter; the change of signalling in this interleukin axis, which
is due to T cell population changes, mediated the antiin ammatory e ects of supplementation
In mice given rheumatism oral supplementation of CII appears to reduce circulating concentrations of IL-6 relative to arthritic control
while increasing IL-2 concentrations, also thought to be related to the alteration in T cell di erentiation seen during oral tolerance.[46]
6.3. T Cells
It seems in mice given type II collagen orally (0.1mg) before induction of arthritis (by collagen injection with Freund's adjuvant) can
()
reduce the severity of arthritis[26][27] which has been noted to be related to a higher intestinal concentration of indoleamine 2,3-
dioxygenase (IDO) expressing (aka. CD11c+) dendritic cells.[27] Dendritic cells have a role in stimulating naive T cells[56] and CD11c+ cells
in these immunized mice hinder collagen-stimulated CD4+ T cell proliferation secondary to increasing activity of CD4+CD25+Foxp3+
regulatory T cells dependent on IDO,[27] as the latter T cell phenotype can independently increase IDO expression in dendritic cells.[57]
[58]
Orally supplemented type II collagen can promote a particular type of T regulatory cell (CD4+CD25+Foxp3+) to prevent
overactivity of another type of T cell (CD4+) in response to collagen, which reduces the potential autoimmune reaction to
collagen exacerbating symptoms of osteoarthritis
When assessing T cell proliferation overall (assessed via thymidine uptake), in rheumatic patients given 1mg or 10mg of CII for twelve
weeks there appeared to be suppression of proliferation in most subjects.[32]
7 Interactions with Aesthetics
7.1. Skin
Type I collagen comprises approximately 80% of the total collagen of the adult human dermis[59] and is known to be responsive to
serum factors such as glucocorticoid therapy (decreasing type I collagen content[60]) and UV irradiation (reduces procollagen I
content[61][62]) thought to contribute to the e ects of stress and sun exposure (respectively) on photoaging; preventing decreases of
procollagen I actually underlies the protective e ects of low concentrations of Vitamin A (/supplements/vitamin-a/) when topically
applied.[62][63]
Type II collagen is not a major constituent of skin like it is in articular cartilage, as types I and III have more of a presence in skin,[59]
although CII can still accumulate in the skin following oral ingestion of hydrolyzed collagen supplements in the rat.[4]
In skin under normal conditions, the CII content is much less than is found in articular cartilage and instead type I and
type II cartilage predominate. Alterations in the production of type I collagen underlie visual changes in the skin in
response to environmental factors
Hydrolyzed collagen is thought to be a supplement for skin health since oral ingestion increases serum levels of some dipeptides and
tripeptides[64] of which one of them, proline-hydroxyproline (Pro-Hyp), can stimulate broblasts to produce the molecule known as
hyaluronic acid (200M[65])[66][67] which is in and of itself a skin health supplement;[68] this e ect is also seen in chondrocytes, thought
to underlie some joint health properties.[66]
Fibroblasts incubated with Pro-Hyp also see an increase in cellular proliferation[65][67] associated with hyaluron synthase 2 (HAS2)
induction, dependent on PKA activation.[67]
Ingestion of CII is thought to increase synthesis of type I collagen and hyaluronic acid in the skin secondary to being a
good source of the dipeptide known Pro-Hyp
In an open-label study with females with some signs of skin aging then given hydrolyzed collagen (Biocell; comprised of peptides
ranging from 1,000-2,500kDa in weight and some hyaluronic acid with chondroitin) at 1g a day for 12 weeks noted that
supplementation was associated with transient increases in wrinkling and crow's feet at six weeks while at the end of the study crow's
feets normalized while wrinkles were reduced relative to baseline (13.2%);[2] hydration showed a similar trend over time, ultimately
being improved after 12 weeks.[2]
An increase in hemoglobin content of the skin has been noted with supplementation of the Biocell formulation at both 6 and 12
()
weeks, thought to be re ective of increased dermal microcirculation.[2] Dermal collagen content was noted to be increased at both
time points while melanin was not a ected.[2]
8 Safety and Toxicology
8.1. General
Undenatured CII (UC-II) appears to be safe in rodents with an acute oral LD50 of greater than 5,000mg/kg and acute dermal LD50 of
over 2,000mg/kg with 90 days continuous ingestion nding no abnormalities[17] and other studies also using chicken sternum CII
nding a similar degree of safety in rats and dogs.[69]
Scienti c Support & Reference Citations
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2.SchwartzSR1,ParkJ.IngestionofBioCellCollagen(),anovelhydrolyzedchickensternalcartilageextractenhancedbloodmicrocirculationandreducedfacialagingsigns
(http://www.ncbi.nlm.nih.gov/pubmed/22956862).ClinIntervAging.(2012)
3.NomuraY1,etal.Increaseinbonemineraldensitythroughoraladministrationofsharkgelatintoovariectomizedrats(http://www.ncbi.nlm.nih.gov/pubmed/16308135).Nutrition.(2005)
4.OesserS1,etal.Oraladministrationof(14)Clabeledgelatinhydrolysateleadstoanaccumulationofradioactivityincartilageofmice(C57/BL)(http://www.ncbi.nlm.nih.gov/pubmed/10498764).JNutr.(1999)
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7.NEUMANRE.Theaminoacidcompositionofgelatins,collagensandelastinsfromdifferentsources(http://www.ncbi.nlm.nih.gov/pubmed/15405718).ArchBiochem.(1949)
8.WuJ1,etal.Assessmentofeffectivenessoforaladministrationofcollagenpeptideonbonemetabolismingrowingandmaturerats(http://www.ncbi.nlm.nih.gov/pubmed/15490264).JBoneMinerMetab.(2004)
9.ZhuP1,etal.OraladministrationoftypeIIcollagenpeptide250270suppressesspecificcellularandhumoralimmuneresponseincollageninducedarthritis(http://www.ncbi.nlm.nih.gov/pubmed/17045846).Clin
Immunol.(2007)
10.KakoiC1,etal.Collagenpeptidesenhancehippocampalneurogenesisandreduceanxietyrelatedbehaviorinmice(http://www.ncbi.nlm.nih.gov/pubmed/23124247).BiomedRes.(2012)
11.Glyprolinesinregulatorytripeptides(http://link.springer.com/article/10.1134%2FS1819712407030014).
12.OralAdministrationofSharkTypeIICollagenSuppressesCompleteFreundsAdjuvantInducedRheumatoidArthritisinRats(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763645/).
13.DiCesareMannelliL,etal.LowdosenativetypeIIcollagenpreventspaininaratosteoarthritismodel(http://www.ncbi.nlm.nih.gov/pubmed/23915264).BMCMusculoskeletDisord.(2013)
14.LugoJP,etal.UndenaturedtypeIIcollagen(UCII)forjointsupport:arandomized,doubleblind,placebocontrolledstudyinhealthyvolunteers(http://www.ncbi.nlm.nih.gov/pubmed/24153020).JIntSocSports
Nutr.(2013)
15.CrowleyDC1,etal.SafetyandefficacyofundenaturedtypeIIcollageninthetreatmentofosteoarthritisoftheknee:aclinicaltrial(http://www.ncbi.nlm.nih.gov/pubmed/19847319).IntJMedSci.(2009)
16.DENATURATIONOFCOLLAGENVIAHEATING:AnIrreversibleRateProcess(http://www.annualreviews.org/doi/abs/10.1146/annurev.bioeng.4.101001.131546).
17.MaronePA1,etal.SafetyandtoxicologicalevaluationofundenaturedtypeIIcollagen(http://www.ncbi.nlm.nih.gov/pubmed/20170336).ToxicolMechMethods.(2010)
18.MoskowitzRW.Roleofcollagenhydrolysateinboneandjointdisease(http://www.ncbi.nlm.nih.gov/pubmed/11071580).SeminArthritisRheum.(2000)
19.KhiariZ1,NdagijimanaM1,BettiM2.Lowmolecularweightbioactivepeptidesderivedfromtheenzymatichydrolysisofcollagenafterisoelectricsolubilization/precipitationprocessofturkeybyproducts
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Via HEM and FAQ:

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(Common misspellings for Type-II Collagen include colligin, collagan, collogon, collogen, colligen)
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Human E ect Matrix

GRADE LEVEL OF EVIDENCE

Robust research conducted with repeated double-blind clinical trials

Single double-blind study or multiple cohort studies

Uncontrolled or observational studies only

Studies Excluded from Consideration

Used alongside calcitonin injections[1]

Confounded with chondroitin (/supplements/chondroitin/) and hyaluronic acid[2]

1.1 Sources and Composition

1.2 Physicochemical Properties

1.4 Formulations and Variants

2.1 Tolerogenic Dendritic Cells

5 Bone and Joint Health

5.2 Collagen and Joints

5.4 Rheumatoid Arthritis

6 In ammation and Immunology

6.1 Interferons and Immunglobulins

7 Interactions with Aesthetics

8 Safety and Toxicology

1 Sources and Composition

1.1. Sources and Composition

CII primarily refers to:

With sources of CII being:

Porcine CII ha shown e cacy at similar doses to other types[13]

1.2. Physicochemical Properties

1.3. Biological Relevance

1.4. Formulations and Variants

2.1. Tolerogenic Dendritic Cells

5 Bone and Joint Health

5.2. Collagen and Joints

5.4. Rheumatoid Arthritis

6 In ammation and Immunology

6.1. Interferons and Immunglobulins

7 Interactions with Aesthetics

8 Safety and Toxicology

Scienti c Support & Reference Citations

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Whey Protein (/supplements/whey-protein/)

Detoxes: an unde ned scam (/nutrition/detoxes-an-unde ned-scam/)

Top 10 Nutrition Myths (/nutrition/10-awful-myths-perpetuated-by-the-media/)

How can I increase testosterone naturally? (/nutrition/how-can-i-increase-testosterone-naturally/)

Is diet soda bad for you? (/nutrition/is-diet-soda-bad-for-you/)

Are eggs healthy? (/nutrition/are-eggs-healthy/)

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