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153
Review ARticle
Collagen supplementation as a complementary therapy for the
prevention and treatment of osteoporosis and osteoarthritis: a
systematic review
Elisângela Porfírio1
Gustavo Bernardes Fanaro1
1
Universidade Estácio de Sá, Progra ma de Pós-graduação em Nutrição Clínica: metabol ismo, prática e
terapia nut ricional. São José dos Campos, SP, Brasil.
Correspondence
Elisângela Porfírio
E-mail: elisaporfirio@hotmail.com
Abstract
Introduction: Collagen hydrolysate is recognized as a safe nutraceutical, whose combination
of amino acids stimulates the synthesis of collagen in the extracellular matrix of cartilage
and other tissues. Objective: to conduct a systematic review of literature on the action
of collagen hydrolysate in bone and cartilaginous tissue and its therapeutic use against
osteoporosis and osteoarthritis. Method: a study of the PubMed, MEDLINE, LILACS,
and SciELO databases was performed. Articles published in English and Portuguese
in the period of 1994 to 2014 were considered. Results: the sample comprised nine
experimental articles with in vivo (animals and humans) and in vitro (human cells) models,
which found that the use of different doses of collagen hydrolysate were associated
with the maintenance of bone composition and strength, and the proliferation and cell
growth of cartilage. Conclusion: hydrolyzed collagen has a positive therapeutic effect
on osteoporosis and osteoarthritis with a potential increase in bone mineral density, a
protective effect on articular cartilage, and especially in the symptomatic relief of pain.
Key word: Collagen;
Osteoarthritis; Osteoporosis;
Elder ly.
http://dx.doi.org/10.1590/1809-9823.2016.14145
154 Rev. BRa s. GeRiatR. G eRontol., Rio de Jan eiRo, 2016; 19(1):153-164
INTRODUCTION
The human body goes through several stages:
childhood, puberty, maturity or stabilization and
then aging. Aging occurs through several changes,
and begins as early as the second decade of life. At
first, these changes are barely noticeable, but by the
end of the third decade many important functional
and/or structural changes have taken place1.
Evidence indicates that many chronic diseases
result from the interaction of various factors,
including genetic, environmental and lifestyle.
Those that are classified as modifiable include:
smoking, alcohol intake, eating habits, a sedentary
lifestyle, stress, while those classified as not
modifiable are heredity, gender and age.2
Osteoporosis (OP) constitutes a disease of the
skeleton of multifactorial cause that is characterized
by reduced bone mass and deterioration of the
anatomical and structural integrity of the bones,
leading to increased bone fragility and susceptibility
to fracture. The group most affected by OP are
older women whose decreased estrogen production
after menopause accelerates bone loss.3
Among joint diseases, osteoarthritis (OA)
is the most prevalent and evolves slowly over
decades, manifesting itself in episodes of pain
and culminating in the loss of joint function.
Inconclusive studies indicate that bone changes
can initiate or inf luence the degradation of
cartilage. Despite many efforts, there is so far no
cure for OA, and the treatments available, both
pharmacological and non-pharmacological, only
act in reducing the symptoms, especially pain,
inflammation and immobility.4,5
Nutraceuticals are substances which can act
as adjuvants in the prevention and treatment of
chronic diseases, in particular OA. The term
nutraceutical comes from the combination of
the words "nutrition" and "pharmaceutical". It
corresponds to foods or products that not only
provide health benefits, but are also, by definition
and regulation, devoid of adverse effects. Collagen
hydrolysate (CH) is recognized as a safe food
with minimal adverse effects, whose amino acid
composition provides elevated levels of glycine
and proline, which accumulate when properly
digested, preferentially in cartilage.4
Both aging and a poor diet can affect the level
of collagen in the body. These changes are not
noticeable in the early stages of life, but become
evident in the mature phase, in which food intake
does not meet the recommended requirements
as effectively, in terms of energy and macro and
micronutrients.
6
Also at this stage the chances
of developing bone and joint disorders are
higher. Balanced nutrition is essential not only
for preventing chronic diseases, but also for
maintaining a healthy body and ensuring its proper
functioning.7
Thus, the aim of this study was to perform a
systematic review of literature on the action of
collagen hydrolysate in bone and cartilage tissue,
and its therapeutic effects on osteoporosis and
osteoarthritis.
METHOD
A systematic review of literature was carried
out, focusing on scientific articles that studied
the action of collagen hydrolysate on cartilage
and bone, as well as their possible therapeutic
support in cases of osteoarthritis and osteoporosis.
The PubMed, MEDLINE, LILACS and SciELO
databases were consulted, and the descriptors used
for research were collagen hydrolysate, combined with
osteoporosis, osteoarthritis, bone, cartilage, aging, ingestion
and supplement. The search period was from January
1994 to May 2014. The review was conducted from
January to May 2014.
The inclusion criteria were: experimental
articles, in English and Portuguese, published
between January 1994 and May 2014, with the
object of study the action of collagen hydrolysate in
bone and cartilage tissue as well as its therapeutic
effects in osteoporosis and osteoarthritis. Excluded
from the search were meta-analyses, notes, case
reports, theses; articles involving other causes of
Collagen supplementation on osteoporosis and osteoarthritis 155
bone and/or joint disease; articles that combined
drugs with oral supplementation of collagen; and
duplicated items indexed in more than one of the
selected databases.
The process for inclusion of articles in the study
involved the reading the titles and abstracts by two
independent reviewers, who applied the inclusion
and exclusion criteria. In case of disagreement, the
study was selected for evaluation of the full text.
RESULT S
The initial search, based on a combination of
terms, identified 187 articles. After verification
of the existence of duplicity, 57 were excluded.
Considering the titles and abstracts based on a wide
selection of work that would likely be of interest,
62 articles were excluded, leaving 68 studies, 47
in PubMed and 21 in MEDLINE, LILACS and
SciELO. Articles that met the eligibility criteria
were retrieved so the full text could be read, with
a view to further evaluation. At this stage 59
publications were excluded that did not meet the
purpose of this research.
Nine experimental articles were identified
as the basis for discussion in this review. The
nine included: five research articles with human
models, three with animal models, and one that
evaluated, respectively, in vitro models (human
cells) and animal models.
Table 1 presents the experimental data of the
articles included in this systematic review.
Tabl e 1 . Distribution of articles according to author, sample, method, results and conclusion. May, 2014.
Author Sample Method Results Conclusion
Hays et al.
24
Humans:
nine elderly
women
(between 65-85
years of age)
Whey protein (0.85
g/kg/weight/day)
15 days
CH (0,81 g/kg/
wei g h t /d ay)
15 days
Whey protein group:
Lower weight;
higher excretion of
nitrogen
CH group:
Maintaining of weight;
Lower excretion of
nitrogen
Maintaining
of weight and
muscle mass
Guillerminet et
al.
26
In vivo
Mice
CH 10 or 25 g/kg/
wei g h t /d ay
4-12 weeks
Bone mineral
density
Higher growth and
differentiation of
osteoblasts;
higher growth and
differentiation of
osteoclasts
Osteoprotective
action
Jackix et al.
27
Rats, six groups
CH 50 mg; 100 mg,
control (gelatin)
Sample of femur
and vertebral
column.
Supported weight four-
times heavier;
Higher percentage of bone
protein;
Higher bone
mineralization
Greater
conservation of
the composition
and bone
strength
156 Rev. BRas . GeRiatR. Ge Rontol., R io de JaneiRo, 2016; 19(1):153-164
Author Sample Method Results Conclusion
Kim et al.
28
In vitro
Human cells Gene COL1A1
Increased osteoblast
differentiation by gene
expression Osteoprotective
action
In vivo
Rats
CH 150; 500 mg/
kg /we i ght/day
12 weeks
Vertebrae, lumbars
Increase of bone mineral
density
Clark et al.
34
Humans:
147 at hle tes
CH 10 g
placebo (xanthan
gum)
Inflammation,
mobility and joint
pain
Significant improvement
in pain
(knee arthralgia)
Reduction of
pain, protection
of cartilage
Sugihara et al.
37
Humans:
five individuals
CH 8 g
Blood samples 0,5;
1; 2; 4 hours
Pro-Hyp; Hyp-Gly
Increase of AA, di- and
tripeptides in peripheral
blood
Proliferation
and cell growth,
as well as
protection of
cartilage
Hartog et al.
38
Rats
CH 12,5; 25; 50 mg
Three consecutive
days
Induced
inflammation in
the ear
Blood sample
Higher concentration
of glycine in plasma;
swelling reduction;
proinflammatory
cytokines
Potential
reduction in
pain (hip and
knee)
Shigemura et al.
39
Humans:
Healthy
volunteers
n= 4
Different doses
of CH/kg/weight
(30,8; 153,8; 384,6
mg/kg/weight
Blood sample
before, 15, 30,
60, 120, 240, 360
minutes after
ingestion
Dose-dependent increase
of 6.43; 20.17; 32.84
nmol/mL in the plasma
concentration of Hyp,
respectively.
Increase of
Hp in plasma
and potential
of increase in
amino acid
absorption
Bruyère et al.
40
Humans:
200 patients
older than 50
years of age
CH 12 g
Placebo (gel
capsules)
6 month treatment,
improvement in symptoms
according to EVA-D scale;
tolerability
Efficacy and
safety of
supplementation
Collagen supplementation on osteoporosis and osteoarthritis 157
DISCUSSION
Due to the progressive decrease in adaptive
responses to environmental factors in elderly
bodies, it is possible that aging is accompanied
by chronic diseases that often require continuous
treatment, causing functional limitations and
some level of dependency. In several countries
the elderly population receives new forms of
treatment, as well as preventive care that fits the
profile of the elderly individual in order to avoid
unnecessary hospitalizations and thus consequent
increases in health spending.8 Alves et al.9 points
out that the aging process is not directly related to
incapacitating diseases, but that chronic diseases
are often associated with the effects of age.
Due to being asymptomatic, OP is often
underdiagnosed and undertreated. The
consequences of osteoporotic fractures include
increased morbidity and mortality and an impact
on social, emotional and financial quality of life.
Among the fractures with greatest impact on
mobility, the hip is considered the most devastating
type of osteoporotic fracture, as in addition to loss
of mobility, it increases the need for long-term care.
Other types of fractures can also cause impact on
quality of life, such as multiple or severe vertebral
fractures, which are associated with significant
pain; reduced lung function; decreased stature
and kyphosis, which can restrict movement and
increase the risk of further falls and fractures.
10
Bone is a complex mineralized tissue, whose main
function is to resist mechanical forces. It presents
specific characteristics, not only in the amount of
bone tissue, but also its qualities, specifically the
geometry and shape, trabecular microarchitecture,
deposition of minerals and quality of collagen in
the organic matrix.11
OA is a degenerative joint disease characterized
mainly by a slow and gradual destruction of
cartilage with a narrowing of joint space, osteophyte
formation and bone sclerosis synovitis12,13 and its
exact cause is still unknown.14 It usually affects
middle-aged adults and although it is one of the
main causes of chronic disability, conventional
therapeutic treatments are still limited, as their
results are minimal, and prolonged use of these
drugs can cause toxicity. As a result, the dietary
supplement industries are increasingly investing
in the development of supplements in order to
delay the disease by directly supplying natural
compounds, in order to inhibit or enhance the role
of biological mediators to preserve the structural
integrity of the joint.15
The collagen molecule is composed of a
repeating sequence of three amino acids (Gly-
X-Y), where Gly is glycine; X is often proline, and
Y is hydroxyproline or hydroxylysine. In general,
collagen contains about 30% glycine, 12% proline,
11% alanine, 10% of hydroxyproline and 1% of
hydroxylysine. From a nutritional point of view,
collagen is considered an inferior quality protein,
as there is a predominance of the described
amino acids and minimal or no amounts of most
of the essential amino acids such as tryptophan,
methionine, cystine and tyrosine.
16
Nevertheless, it
has nutritional value because of its atypical amino
acid profile which stimulates the synthesis of
collagen in cartilage and the extracellular matrix
of other tissues.17
Collagen, as well as other ingested proteins
such as collagen, is not absorbed. Most protein
digestion, approximately 80%, occurs in the
duodenum and jejunum and is caused by the
action of the pancreatic juice, while only 10-20%
occurs in the stomach, due to hydrochloric acid
and pepsin. Luminal hydrolysis of proteins and
polypeptides in free amino acids (AA) and short
peptides occurs in the small intestine through
the action of enteropeptidase. This process, at
neutral pH, activates trypsinogen and trypsin,
which, in turn, promotes the activation of other
propeptidases in the pancreatic juice. The AA and
small peptides are hydrolyzed by brush border
peptidases into AA, dipeptides and tripeptides,
which are mainly absorbed at the proximal jejunum
158 Rev. BRas . GeRiatR. Ge Rontol., R io de JaneiRo, 2016; 19(1):153-164
by simple diffusion, facilitated diffusion or active
transference by co-transport. AA peptides are
intended to perform numerous functions, including
the synthesis of collagen itself.18 Experiments with
mice performed by Oesser et al.,
19
to quantify
the distribution of radioactive collagen peptides,
indicated that after intestinal absorption, peptides
derived from CH accumulate preferentially in
cartilage and bone.
In connective tissue, type I collagen or
tropocollagen is the most abundant, and a source
of partially hydrolyzed collagen (gelatin) and
collagen hydrolysate. The difference between
the collagen hydrolysate and gelatin is that the
collagen hydrolysate is dissolved in water or brine
thus making its digestion and absorption easier,
allowing the production of collagen by the body
from the free amino acids.20 The most important
feature of collagen hydrolysate is the prevalence of
glycine and proline in its composition. These amino
acids are essential for the stability and regeneration
of cartilage.21
Although OA and OB are diseases related to
skeletal disorders, epidemiological surveys rarely
associate one disease with the other. Rather, the
presence of one can be considered a protective
factor for the other, because the increase of bone
conformity in OP can maintain and preserve the
articular cartilage. While there are few reports on
OA in its initial stage, recent studies have reported
severe microscopic changes in bone cartilage
in advanced stages of OA, such as an increase
in the volume of subchondral bone, low bone
mineralization and mechanical strength, as well
as considerable deterioration in articular cartilage.
This suggests a correlation of development of
OA in patients with OP, which also means that
OP treatment can help prevent the progression
of OA.22,23
A study carried out by Hays et al.24 tested
the supplementation of women aged between
65 and 85 years. The nitrogen balance was
compared following supplementation with two
protein compounds, "whey protein" and collagen
hydrolysate. Although the amount of protein was
the same for both supplements, the women who
consumed the whey-based supplement experienced
a decrease in body weight without a change in
body profile, suggesting a loss of lean body mass,
whereas the women who ingested the collagen
supplement experienced no significant changes in
body weight. Furthermore, nitrogen excretion was
lower with the collagen hydrolysate than with the
whey, thus maintaining nitrogen balance and lean
body mass. Also according to Hays et al.
24
the study
data, combined with previous estimates of protein
requirements in the diet of older people, strongly
indicate that the current recommended dietary
intake (RDA) may be inadequate or marginal,
even in normocaloric diets. They also noted
that although collagen hydrolysate is deficient in
essential amino acids, combining it with a diet
featuring adequate amounts of protein could
promote nitrogen balance.
According to Takeda et al.,
25
type I collagen
represents 25% of the total body protein and 80%
of connective tissue in humans. The synthesis of
type I collagen also plays an important role in
osteoblast differentiation, enhancing bone mineral
density, bone mineral content and increasing the
amount of type I collagen in the bone matrix.
Bone loss is due to an imbalance between bone
formation and resorption, especially in women
after menopause. This imbalance is characterized
by excessive activity of osteoclasts on osteoblasts,
leading to increased bone remodeling. According
to Guillerminet et al.,26 in order for the effect of
collagen administration to be positive, the collagen
must be hydrolyzed. In their in vivo studies on
mice, they noted that proteins are essential for
bone health and prevention of OP. The collagen
modulates bone formation and mineralization
of bone matrix with increased growth and
differentiation of osteoblastic cells and reduction
of osteoclastic cells. All collagens tested were able
to increase the osteoblast activity. These results
and previous observations show that the structure
and amount of peptides derived from collagen
after oral administration depends, not only on
the collagen source, but also the molecular size
of the collagen hydrolysate, suggesting that not all
the collagen molecule interacts with bone cells.
Collagen supplementation on osteoporosis and osteoarthritis 159
Jackix et al.27 noted that collagen hydrolysate
contributed to bone conservation, composition
and strength. This study27 evaluated the result
of collagen application in order to counteract
the effects of ovariectomy on bone mass,
biomechanical strength, protein content and
serum osteocalcin levels in six groups of eight
rats: three ovariectomized groups, one negative
control group that had undergone sham surgery,
and two intact groups. One month after surgery,
the rats received a diet supplemented with gelatin
(control) or CH on two levels, (1) an amount equal
to five times the recommended amount for humans
(10g / day), and the other (2) with levels ten times
higher, all according to the following criteria: two
intact groups, gelatin and CH (ten times); three
ovariectomized groups, gelatin, CH (five times) and
CH (ten times); a group of sham CH (ten times).
After eight weeks, samples of the femur, spine and
blood were evaluated. The group that received
the highest dose of CH withstood four times
as much load, in addition to having the highest
percentage of bone protein, mineral content and
osteocalcin content among the groups. The group
with the highest level of supplementation (OVX-
CH10) showed divergence in levels of osteocalcin.
In terms of the alkaline phosphatase results, an
increase was identified in this group, but the
relevance of this study was limited because the
increased alkaline phosphatase may be associated
with enzyme activity, as a compensatory reaction
to the surgery.
A study by Kim et al.
28
considered bone loss to
be a non-uniform process because the cancellous
bone, the main component of the vertebrae,
represents a higher risk than the cortical bone,
the main component of the femur. Therefore, the
lumbar vertebrae play a key role in monitoring
OP. In this study, the authors demonstrated the
functional effects of collagen hydrolysate in vitro
and in vivo. In the in vitro tests, it was observed
that CH enhances osteoblastic differentiation in
human cells via the expression of the COL1A1
gene involved in the synthesis of collagen; in the
in vivo tests, a significant increase in bone mineral
density in the lumbar vertebrae was found, just like
within the bodies of ovariectomized rats (OVX)
treated for 12 weeks with diets containing 0.3%
and 1% CH 150mg/kg and 500mg/kg. These
results suggest that CH exercises an osteoprotective
action, highlighting it as a potential therapeutic
alternative for the treatment and prevention of
OP. High levels of bone markers in OVX rats
can mask the effects of treatment with additional
CH. In addition, measurements at a single time
point may not determine subtle effects between
the treatment and responses of bone markers.
The positive effect of the protein on bone
formation is related to the composition, or in other
words 50% of the bone is formed by collagen and
the other half by calcium. Therefore, an unsuitable
diet, not only in calcium, but also in protein would
hinder bone reconstruction.29
Rezende & Gobbi30 and Rezende & Campos31
highlight in their research a cause other than aging
for OA, whose therapeutic proposal would cover
all aspects of the disease. The pathogenesis of
OA comes from inflammatory and mechanical
factors: inflammatory, in responses mediated by
chondrocytes and synovitis; mechanical, associated
with the movement and physical strength that is
especially concentrated in joints. OA would result
from inflammation of the joints in an attempt
to correct abnormal mechanical stress. Still, for
Rezende & Gobbi
30
and Rezende & Campos,
31
inflammatory responses are higher in patients with
OA and enhanced aging, while the mechanical
responses comprise a combination of physiological
and genetic factors, and in both obesity would
be an aggravating factor. Obesity increases the
load on the joints and activates the production of
proinflammatory adipokine receptors present on
the surface of chondrocytes, osteoblasts, and both
synovial and subchondral membranes.32
Zague et al.,33 state that there is a consensus
that the effects promoted by collagen peptides
intake are related to their hydrolyzed form. For the
authors,
33
food supplements and pharmacological
CH are justified because they have beneficial
biological functions far beyond the reduction of
pain in patients with OA. Besides being involved
in the cartilage matrix synthesis, some collagen
peptides exhibit both anti-hypertensive and
160 Rev. BRa s. GeRiatR. G eRontol., Rio de Ja neiRo, 2016; 19(1):153-164
cardioprotective activity, through the regulation
of nitric oxide as well as the intercellular adhesion
molecule and the inhibition of the converting
enzyme of angiotensin I, along with antioxidant
activities in different oxidation systems.
Clark et al.
34
monitored 147 athletes for 24
weeks. Although there was no evidence of joint
disease, this was considered to be a high risk group.
The subjects were divided into two groups, one
receiving a formulation containing 25ml of liquid
that contained 10g of collagen hydrolysate, and
another group receiving a placebo consisting of
25ml of liquid with xanthan gum. Parameters
including inflammation, mobility and joint pain;
pain whilst walking, standing, the joints in a state
of rest, carrying objects and lifting were evaluated.
There was significant improvement in the group
supplemented with collagen hydrolysate in terms
of pain, in all evaluated parameters, especially in
the subgroup with knee arthralgia.
Oesser & Seifert35 suggest that collagen
hydrolysate stimulates collagen biosynthesis
in chondrocytes, articular cells responsible for
the synthesis, maintenance and organization of
the ECM extracellular matrix. Changes in the
ECM composition provoke collagen turnover
which stimulates chondrocyte activity, inducing
synthesis and continued remodeling. Based on
their experiments and a literature review, Bello
& Oesser
36
concluded that collagen hydrolysate
administered orally may accumulate in the
cartilage as well as stimulate significant increase
in the synthesis of ECM macromolecules by
chondrocytes.
With the assumption that certain amino acids
play active roles in bone tissue, Sugihara et al.
37
accessed the levels of hydroxyproline (Pro-Hyp) and
glycine hydroxyl (Hyp-Gly) present in the blood of
five healthy subjects following oral ingestion of CH.
Volunteers ingested 8g of CH dissolved in 100ml of
water and blood samples were collected before; 30
minutes, and 1, 2 and 4 hours after ingestion. The
concentration of Hyp-Gly and Pro-Hyp in plasma
reached its peak after an hour at a proportion of
6.3% to 22.1%, respectively. After oral ingestion
of CH, not only amino acids, but also di- and
tripeptides are assimilated and remain for a relatively
long time in human peripheral blood. It is estimated
that these peptides promote cell proliferation and
growth, hyaluronic acid synthesis in cultured
dermal fibroblasts and synovial cells as well as the
chondroprotective effect on articular cartilage. A
limitation of this study is the lack of standardization
in relation to sports activities. Better results could
be obtained with the inclusion of athletes engaged
in sports such as soccer or basketball.
In order to evaluate the anti-inflammatory
potential of glycine, Hartog et al.38 administered
CH in different amounts, leading to ear
inflammation in mice. CH was administered daily
by oral gavage in the following amounts: control
(0); 12.5, 25 and 50mg for three consecutive days,
and inflammation was induced on the third day by
the intra-dermal injection of zymosan. The plasma
levels of glycine, in the collected blood samples,
increased in accordance with the concentration
of applied CH, suggesting its ability to neutralize
locally induced inflammation, according to the
reduction in ear edema, as well as reducing the
production of IL-6, and lipopolysaccharide (LPS).
Glycine is a non-essential amino acid found in
many different proteins and is one of the major
structural units of collagen, amounting to about
30% of the amino acids. The effects of glycine in
inhibiting proinflammatory cytokine expression
have been studied in vitro and confirmed in different
animal models, especially for beneficial effects in
reducing pain in OA of the hip and knee.38
Apart from glycine, there is a relation between
the intake of collagen and hydroxyproline levels
in human plasma. Hydroxyproline is an amino
acid specifically present in collagen, and studies39
have shown that its presence in the plasma inhibits
mineralization chondrocytes and modulates the
expression of the RUNX1 gene (runt-related
transcription factor 1) and osteocalcin, stimulates
the production of hyaluronic acid in the synovial
cell cultures and increases the production of skin
fibroblasts in rats.
To estimate the effective dose for beneficial
effects on human health, Shigemura et al.
39
dosed
the concentration of Hyp in human plasma from
Collagen supplementation on osteoporosis and osteoarthritis 161
different doses of CH with one week intervals
between each ingestion. Four healthy adults with
a mean age of 27 years, ingested 2, 10, and 25g
per 65kg of body weight of CH and venous blood
samples were collected before, 15, 30, 60, 120, 240
and 360 minutes after administration. According
to the analyzes, the concentration of Hyp peptide
increased in a dose-dependent manner 30 minutes
after ingestion and reached its maximum level after
two hours, and although the Hyp level reduced to
two thirds of its maximum level six hours after
ingestion, it was still significantly higher than
before the administration of CH. The results
showed that larger doses of CH cause increases
in the concentration of Hyp in plasma, as well
as heightening the absorption potential of the
amino acids.
Bruyère et al.
40
evaluated the efficacy and safety
of CH supplementation in a randomized double-
blind study with 200 patients of both genders, aged
50 years or older, and who suffered from joint
pain. For six months half of the group of subjects
received a daily dose equivalent to 1,200mg of
CH and the other half received a placebo (gel
cap). In terms of safety and tolerability, there
was no difference between the placebo group
and the CH group. As for the clinical response,
by the third month of treatment there was no
significant difference, however, in the sixth month,
the improvement was significantly higher in the
group that ingested the CH capsules.
Despite the great expectations for the positive
results of studies such as Bello & Oesser,36
Schadow et al.,41 concluded in their clinical trials
with radioactive proline in vitro models that even
at high doses (10mg/ml), collagen does not exert
a stimulatory effect on collagen biosynthesis
by human cartilage, regardless of the degree of
change in OA. Different results can occur between
studies because of differences in applied analytical
methods, species, and the age and health of the
joints. Furthermore, the determination of the
radioactive proline incorporation rate without
specific separation of total proteins does not reflect
the true collagen synthesis rate, since the proline
enrichment in the collagen compared to other
proteins is not described. However Schadow et
al.41 stated that collagen hydrolysate preparations
could contain therapeutically active peptides, but
extensive studies are needed, as well as clinical
trials, before these are applied as nutraceuticals.
CONCLUSION
Collagen hydrolysate has a positive therapeutic
role in osteoporosis and osteoarthritis: potentially
increasing bone mineral density, having a protective
effect on articular cartilage and, primarily,
providing symptomatic relief of pain. Although
there is no consensus in the scientific literature
searched on the collagen hydrolysate dosage to
be administered, it was noted that with a daily
supplementation of 8g there was an increase in
glycine and proline concentration in plasma.
Also, daily doses equivalent to 12g promoted
a significant improvement in the symptoms of
osteoarthritis and osteoporosis. However, further
studies are needed to determine the pathogenic
factors involved in osteoporosis and osteoarthritis,
its early diagnosis, and from which stage of life it
would be recommended to start supplementation,
as well as the suitable dosage, in order to achieve
significant therapeutic potential.
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Received: 30 September, 2014
Reviewed: 28 May, 2015
Accepted: 5 Aug ust, 2015
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