ArticlePDF Available

Collagen supplementation as a complementary therapy for the prevention and treatment of osteoporosis and osteoarthritis: a systematic review

Authors:
  • Universidade da Força Aérea (UNIFA)

Abstract and Figures

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) andin 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.
Content may be subject to copyright.
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.
REFERENCES
1. Gottlie MGV, Carvalho D, Schneider R H, Cruz
IBM. Aspectos genéticos do envelhecimento e
doenças associadas: uma complexa rede de interações
entre genes e ambiente. Rev Bras Geriatr Gerontol
[Internet] 2007 [acesso em 19 fev. 2014];10(3):
273-83. Disponível em: http://revista.unati.uerj.
br/scielo.php?script=sci_arttext&pid=S1809-
98232007000300002&lng=pt&nrm=iso
2. Casado l, Vianna lM, Thulerl CS. Fatores de
risco para doenças crônicas não transmissíveis no
Brasil: uma revisão sistemática. Rev Bras Cancerol
[Internet] 2009 [acesso em 5 mar. 2014];55(4):379-88.
Disponível em: http://www.inca.gov.br/rbc/n_55/
v04/pdf/379_revisao_literatura1.pdf
162 Rev. BRas . GeRiatR. Ge Rontol., R io de JaneiRo, 2016; 19(1):153-164
3. Inderjeeth CA, Poland KE. Management of
osteoporosis in older people. J Pharm Pract Res
[Internet] 2010 [acesso em 16 fev. 2014];40(3):229-
34. Disponível em: http://jppr.shpa.org.au/lib/
pdf/2010_09/C_Inderjeeth_GT.pdf
4. Henrotin Y, Lambert C, Couchourel D, Ripoll C,
Chiotelli E. Nutraceuticals: do they represent a new era
in the management of osteoarthritis? A narrative review
from the lessons taken with five products. Osteoarthr
Cartil [Internet] 2011 [acesso em 16 fev. 2014];19(1):1-21.
Disponível em: http://www.oarsijournal.com/article/
S1063-4584(10)00358-4/fulltext
5. Tonge DP, Pearson MJ, Jones SW. The hallmarks
of osteoarthritis and the potential to develop
personalised disease-modifying pharmacological
therapeutics. Osteoarthr Cartil [Internet] 2014 [acesso
em 16 fev. 2014];22(5): 609-21. Disponível em: http://
www.oarsijournal.com/article/S1063-4584(14)00996-
0/fu l lt e xt
6. Franzen JM, Santos JMSR, Zancanaro V. Colágeno:
uma abordagem para a estética. Rev Interdiscipl Estud
Saúde [Internet] 2013 [acesso em 5 mar. 2014];2(2):49-
61. Disponível em: http://www.uniarp.edu.br/
periodicos/index.php/ries/article/view/161/171
7. Cosgrove MC, Franco OH, Granger SP, Murray PG,
Mayes AE. Dietary nutrient intakes and skin-aging
appearance among middle-aged American women.
Am J Clin Nutr [Internet] 2007 [acesso em 8 jan.
2014];86(4):1225-31. Disponível em: http://ajcn.
nutrition.org/content/86/4/1225.long
8. Carneiro IAF, Campino ACC, Leite F, Rodrigues
CG, Santos GMM, Silva ARA. Envelhecimento
populacional e os desafios para o sistema de saúde
brasileiro [Internet] . São Paulo: IESS; 2013.
Disponível em: http://www.ibedess.org.br/imagens/
biblioteca/939_envelhecimentopop2013.pdf
9. Alves lC, Leimann BCQ, Vasconcelos MEL,
Carvalho MS, Vasconcelos AGG, Fonseca TCO, et
al. A influência das doenças crônicas na capacidade
funcional dos idosos do Município de São Paulo,
Brasil. Cad Saúde Pública [Internet] 2007 [acesso
em 19 jan 2014];23(8):1924-30. Disponível em:
http://www.scielo.br/scielo.php?script=sci_
arttext&pid=S0102-311X2007000800019
10. Lewiecki EM. Current and emerging pharmacologic
therapies for the management of postmenopausal
osteoporosis. J Women's Health [Internet]
2009 [acesso em 22 fev 2014];18(10):1615-26.
Disponível em: http://online.liebertpub.com/doi/
pdfplus/10.1089/jwh. 2008.1086
11. Lotz M, Martel-Pelletier J, Christiansen C, Brandi
ML, Bruyère O, Chapurlat R, et al. Value of
biomarkers in osteoarthritis: current status and
perspectives. Ann Rheum Dis [Internet] 2013
[acesso em 1 maio 2014];72(11):1756-63. Disponível
em: http://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3812859
12. Staines KA, Pollard AS, Mcgonnell IM, Farquharson
C, Pitsillides AA. Cartilage to bone transitions in
health and disease. J Endocrinol [Internet] 2013
[acesso em 15 maio 2014];219(1):1-12. Disponível
em: http://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3769078/
13. Suantawee T, Tantavisut S, Adisakwattana S,
Tanavalee A, Yuktanandana P, Anomasiri W, et al.
Oxidative stress, vitamin E, and antioxidant capacity
in knee osteoarthritis. J Clin Diagn Res [Internet]
2013 [acesso em 30 de maio 2014];7(9):1855-9.
Disponível em: http://www.ncbi.nlm.nih.gov/pmc/
articles/PMC3809620/
14. Vermeij EA, Koenders M L, Blom AB, Arntz
OJ, Bennink MB, Van Den Berg WB, et al. In
vivo molecular imaging of cathepsin and matrix
metalloproteinase activity discriminates between
arthritic and osteoarthritic processes in mice. Mol
Imaging 2014;13(2):1-10.
15. Vista ES, Lau CS. What about supplements for
osteoarthritis?: A critical and evidenced-based review.
Int J Rheum Dis 2011;14(2):152–8.
16. Prestes RC. Colágeno e seus derivados: características
e aplicações em produtos cárneos. UNOPAR Cient
Ciênc Biol Saúde [Internet] 2013 [acesso em jan.
2014];15(1):65-74. Disponível em: http://bases.bireme.
br/cgi-bin/wxislind.exe/iah/online/?IsisScript=iah/
iah.xis&src=google&base=LILACS&lang=p&nextAc
tion=lnk&exprSearch=661307&indexSearch=ID
17. Roman JA, Sgarbieri VC. Caracterização físico-
química do isolado protéico de soro de leite e gelatina
de origem bovina. Braz J Food Technol [Internet]
2007 [acesso em 19 jan. 2014];10(2):137-43. Disponível
em: http://www.sncsalvador.com.br/artigos/
caracterizaco-fisico-quimica-isolado-proteico-soro-
de-leite-gelatina-bovina.pdf
18. Frenhani PB, Burini RC. Mecanismos de absorção de
aminoácidos e oligopeptídios. Controle e implicações
na dietoterapia humana. Arq Gastroenterol [Internet]
1999 [acesso jan. 2014];36(4):227-37. Disponível em:
http://www.scielo.br/scielo.php?script=sci_arttext&p
id=S0004-28031999000400011
Collagen supplementation on osteoporosis and osteoarthritis 163
19. Oesser S, Adam M, Babel W, Seifert J. Oral
administration of 14C labeled gelatin hydrolysate
leads to an accumulation of radioactivity in cartilage
of mice (C57/BL). J Nutr [Internet] 1999 [acesso em
19 de jan. 2014];129(10):1891-5. Disponível em: http://
jn.nutr ition.org /content/129/10/18 91.f u l l.p df+ht m
20. Prestes RC, Golunski SM, Toniazzo G, Kempka AP,
DiLuccio M. Caracterização da fibra de colágeno,
gelatina e colágeno hidrolisado. Rev Bras Prod
Agroindustr [Internet] 2013 [acesso em 5 maio
2014];15(4):375-82. Disponível em: http://ww w.deag.
ufcg.edu.br/rbpa/rev154/Art1546.pdf
21. Silva TF, Penna ALB. Colágeno: características
químicas e propriedades funcionais. Rev Inst
Adolfo Lutz [Internet] 2012 [acesso em 3 maio
2014];71(3):530-9. Disponível em: http://revistas.bvs-
vet.org.br/rialutz/article/view/5336/4600
22. Bobinac D, Marinovic M, Bazdulj E, Cvijanovic O,
Celic T, Maric I, et al. Microstructural alterations of
femoral head articular cartilage and subchondralbone
in osteoarthritis and osteoporosis. Osteoarthr Cartil
[Internet] 2013 [acesso em 16 maio 2014];21(11):1724-
30. Disponível em: http://www.oarsijournal.com/
article/S1063-4584(13)0 0866-2/fulltext
23. Kamimura M, Nakamura Y, Ikegami S, Mukaiyama
K, Uchiyama S, Kato K. The pathophysiology of
primary hip osteoarthritis may originate from bone
alterations. Open Rheumatol J [Internet] 2013 [acesso
em 15 maio 2014];7: 112-8. Disponível em: http://
www.ncbi.nlm.nih.gov/pmc/articles/PMC3866704/
24. Hays NP, Kim H, Wells AM, Kajkenova O, Evans
WJ. Effects of whey and fortified collagen hydrolysate
protein supplements on nitrogen balance and body
composition in older women. J Am Diet Assoc
20 09;109(6):1082- 87.
25. Takeda S, Jong-Hoon P, Kawashima E, Ezawa I, Omi
N. Hydrolyzed collagen intake increases bone mass
of growing rats trained with running exercise. J Int
Soc Sports Nutr [Internet] 2013 [acesso em 6 maio
2014];10(35). Disponível em: http://ww w.jissn.com/
content/pdf/1550-2783-10-35.pdf
26. Guillerminet F, Beaupied H, Fabien-SouléV, Tomé D,
Benhamou CL, Roux C, et al. A. Hydrolyzed collagen
improves bone metabolism and biomechanical
parameters in ovariectomized mice: an in vitro and in
vivo study. Bone 2010;46(3):827-34.
27. Jackix EA, Cúneo F, Amaya-Farfan J, Assunção JV,
Quintaes KD. A food supplement of hydrolyzed
collagen improves compositionaland biodynamic
characteristics of vertebrae in ovariectomizedrats. J
Med Food 2010;13(6):1-6.
28. Kim HK, K im MG, Leem KH. Osteogenic activity
of collagen peptide via ERK/MAPK pathway
mediated boosting of collagen synthesis and its
therapeutic efficacy in osteoporotic bone by back-
scattered electron imaging and microarchitecture
analysis. Molecules [Internet] 2013 [acesso em 15
maio 2014];18(12):15474-89. Disponível em: http://
www.mdpi.com/142 0 -3049/18/12/15474
29. Montilla RNG, Aldrighi JM, Marucci MFN.
Relação cálcio/proteína da dieta de mulheres no
climatério. Rev Assoc Med Bras [Internet] 2004
[acesso em 5 maio 2014];50(1):52-4. Disponível
em: http://www.scielo.br/scielo.php?pid=S0104-
42302004000100035&script=sci_arttext
30. Rezende MU, Gobbi RG. Tratamento medicamentoso
da osteoartrose do joelho. Rev Bras Ortop [Internet]
2009 [acesso em 8 maio 2014];44(1):14-9. Disponível
em: http://www.scielo.br/scielo.php?pid=S0102-
36162009000100002&script=sci_arttext
31. Rezende UM, Campos GC. A osteoartrite é uma
doença mecânica ou inf lamatória? Rev Bras Ortop
[Internet] 2013 [acesso em 1 maio 2014];48(6):471-4.
Disponível em: http://www.rbo.org.br/PDF/48-6-
port/07-87.pdf
32. King IK, March I, Anandacoomarasamy A. Obesity
& osteoarthritis. Indian J Med Res [ Internet] 2013
[acesso em 15 maio 2014];138(2);185-93. Disponível
em: http://www.ncbi.nlm.nih.gov/pmc/articles/
PMC378 8203/
33. Zague V, Freitas V, Rosa MC, Castro GA, Jaeger RG,
Santelli GM. Collagen hydrolysate intake increases
skin collagen expression and suppresses matrix
metalloproteinase 2 activity. J Med Food [Internet]
2011 [acesso em 6 maio 2014];14(6):618-24. Disponível
em: http://online.liebertpub.com/doi/abs/10.1089/
jmf.2 010.0 085
34. Clark K L, Sebastianelli W, Flechsenhar KR,
Aukermann DF, Meza F, Millard RL , et al. 24-Week
study on the use of collagen hydrolysate as a dietary
supplement in athletes with activity-related joint pain.
Curr Med Res Opin 2008;24(5):1485-96.
35. Oesser S, Seifert J. Stimulation of type II collagen
biosynthesis and secretion in bovine chondrocytes
cultured with degraded collagen. Cell Tissue Res
2003;311(3):393-9.
36. Bello AE, Oesser S. Collagen hydrolysate for the
treatment of osteoarthritis and other joint disorders:
a review of the literature. Curr Med Res Opin
2006;22(11):2221-32.
164 Rev. BRa s. GeRiatR . GeRontol ., Rio de JaneiRo , 2016; 19(1):153-164
Received: 30 September, 2014
Reviewed: 28 May, 2015
Accepted: 5 Aug ust, 2015
37. Sugihara F, Inoue N, Kuwamori M, Taniguchi M.
Quantification of hydroxyprolyl-glycine (Hyp-Gly) in
human blood after ingestion of collagen hydrolysate. J
Biosci Bioeng 2012;113(2):202-3.
38. Hartog A, Cozijnsen M, Vrij G, Garssen J. Collagen
hydrolysate inhibits zymosan-induced inflammation.
Exp Biol Med 2013;238(7):798-802.
39. Shigemura Y, Kubomura D, Sato Y, Sato K. Dose
dependent changes in the levels of free and peptide
forms of hydroxyproline in human plasma after
collagen hydrolysate ingestion. Food Chem [Internet]
2014 [acesso em 16 maio 2014];159:328-32. Disponível
em: http://www.sciencedirect.com/science/article/
pi i/S03 0 8 8146140 02763
40. Bruyère O, Zegels B, Leonori I, Rabenda V, Janssen
A, Bourges C, Reginster JY. Effect of collagen
hydrolysate in articular pain: A 6-month randomized,
double-blind, placebo controlled study. Complement
Ther Med [Internet] 2012 [acesso em 16 maio
2014];20(3):124-30. Disponível em: http://www.
complementarytherapiesinmedicine.com/article/
S0965-2299(12)00002-7/fulltext
41. Schadow S, Siebert HC, Lochnit G, Kordelle J,
Rickert M, Steinmeyer J. Collagen metabolism
of human osteoarthritic articular cartilage as
modulated by bovine collagen hydrolysates. PLoSOne
[Internet] 2013 [acesso em 1 maio 2014];8(1).
Disponível em: http://www.plosone.org/article/
info%3Adoi%2F10.1371%2Fjournal.pone.0053955
... Neste ínterim, a aparência passa a ser apontada como um duplo padrão de envelhecimento. A sociedade atual valoriza a aparência física que remete a juventude e beleza, haja visto que rugas e flacidez são sinais indesejáveis, ambos causados pela perda de colágeno da água corporal com o decorrer da idade, fatores que se sobrepõem às mudanças biológicas (Porfírio & Fanaro, 2016). Assim sendo, a nutrição balanceada é essencial, pois ajudará a estimular a síntese do colágeno tipo I, prevenindo as fraturas osteoporóticas, na pós-menopausa, porque ajuda na formação e na reabsorção óssea. ...
... Assim sendo, a nutrição balanceada é essencial, pois ajudará a estimular a síntese do colágeno tipo I, prevenindo as fraturas osteoporóticas, na pós-menopausa, porque ajuda na formação e na reabsorção óssea. Nesse caso, a suplementação do colágeno hidrolisado é mais efetiva, segundo Porfírio e Fanaro (2016). Sabe-se que Ca + é importante para diversas funções no organismo, como a transmissão dos impulsos nervosos, e a vit. ...
Article
Full-text available
A menopausa é um processo fisiológico natural na vida da mulher caracterizado pelo fim da função ovariana. Apesar de não ser uma patologia, nessa fase ocorre o declínio dos hormônios estrogênio e progesterona. O presente estudo teve como objetivo verificar, durante a senescência, como a alimentação pode influenciar na redução de sinais e sintomas da menopausa, com foco na qualidade de vida. O estudo foi feito com base na revisão de dados da literatura científica nacional e internacional, utilizando as bases de dados Scielo, Pubmed e Google acadêmico, com pesquisas em artigos científicos e documentos institucionais. A terapia de reposição hormonal (TRH) ajudou amenizar os sintomas da menopausa relacionados ao declínio do estrogênio como a secura vaginal, os fogachos, a insônia e a ansiedade, mas apenas durante o uso, porque essa fase está diretamente associada ao estresse oxidativo progressivo das funções fisiológicas potencializando a perda da densidade mineral óssea (DMO) induzindo a perda da massa magra e aumentando a massa gorda. As intervenções nutricionais mais efetivas foram a dieta DASH, que ajudou reduzir a hipertensão, e a Mediterrânea (MedD), que ajudou reduzir os eventos cardiovasculares, combinada com dietas hiperproteicas associadas com atividade física regular. As opções de tratamento para os sintomas do climatério incluíram a terapia de reposição hormonal (TRH) de estrogênio e progesterona combinada por via oral ou transdérmica isolado ou combinado, e também opções naturais, como o uso de isoflavonas (soja) e a folha de amora, entre outros.
... The combination of amino acids in collagen hydrolysate, known as a safe nutraceutical, stimulated the production of collagen in the extracellular matrix of cartilage and other tissues. Porfírio performed research on the action of collagen hydrolysate in bone and cartilaginous tissue and its therapeutic use against osteoporosis and osteoarthritis, discovering a connection between the maintenance of bone strength and composition, as well as cartilage cell development and proliferation, and the administration of various doses of collagen hydrolysate [147]. This study concluded that hydrolyzed collagen has a protective effect on articular cartilage, and especially helps with symptomatic pain reduction considering the ability to raise bone mineral density [147]. ...
... Porfírio performed research on the action of collagen hydrolysate in bone and cartilaginous tissue and its therapeutic use against osteoporosis and osteoarthritis, discovering a connection between the maintenance of bone strength and composition, as well as cartilage cell development and proliferation, and the administration of various doses of collagen hydrolysate [147]. This study concluded that hydrolyzed collagen has a protective effect on articular cartilage, and especially helps with symptomatic pain reduction considering the ability to raise bone mineral density [147]. Therefore, it has a good therapeutic effect on osteoporosis and osteoarthritis. ...
Article
Full-text available
Fish collagen garnered significant academic and commercial focus in the last decades featuring prospective applications in a variety of health-related industries, including food, medicine, pharmaceutics, and cosmetics. Due to its distinct advantages over mammalian-based collagen, including the reduced zoonosis transmission risk, the absence of cultural-religious limitations, the cost- effectiveness of manufacturing process, and its superior bioavailability, the use of collagen derived from fish wastes (i.e., skin, scales) quickly expanded. Moreover, by-products are low cost and the need to minimize fish industry waste’s environmental impact paved the way for the use of discards in the development of collagen-based products with remarkable added value. This review summarizes the recent advances in the valorization of fish industry wastes for the extraction of collagen used in several applications. Issues related to processing and characterization of collagen were presented. Moreover, an overview of the most relevant applications in food industry, nutraceutical, cosmetics, tissue engineering, and food packaging of the last three years was introduced. Lastly, the fish- collagen market and the open technological challenges to a reliable recovery and exploitation of this biopolymer were discussed. https://www.mdpi.com/2085206
... Collagen hydrolysates in liquid and powder form as food supplements are recommended by experts for both bone and tissue health and skin health. In terms of elderly nutrition, it is possible to add collagen to foods that the elderly consume frequently [10,11]. ...
Article
Full-text available
Background: This study aimed to develop a highly consumable collagen-containing bar that contributes to enriching the diets of elderly individuals, in terms of energy and nutrients. Method: For this purpose, five different bar samples (C, P1, P2, D1, D2) containing different amounts of collagen, date puree, and pumpkin puree were developed and subsequently evaluated in terms of their sensory and nutritional properties by a panel of 30 adult trained sensorial analysists. Results: The bars with the highest flavor score were those with high levels of collagen and pumpkin puree (P2) and date puree (D2). For the analyses of multiple criteria among multiple samples, the TOPSIS technique showed that among the snack bar samples with different contents, the most liked sample was the one with a high level of collagen and date puree (D2). One serving of the developed bars contains approximately 300-400 kcal of energy and 6.8-8.8 g of protein. Considering age-related decreased appetite, as well as chewing and swallowing problems in elderly individuals, regular consumption of nutrient-rich small meals or snacks with enhanced sensory characteristics could contribute to improving nutritional and functional status.
... Collagen hydrolysates in liquid and powder form as food supplements are recommended by experts for both bone and tissue health and 2 skin health. In terms of elderly nutrition, it is possible to add collagen to foods that the elderly consume frequently [4,5] ...
Preprint
Full-text available
Background: This study aimed to develop a highly consumable collagen-containing bar that contributes to enriching the diets of elderly individuals in terms of energy and nutrients. Method: For this purpose, after the development of 5 different bar samples (C, P1, P2, D1, D2) containing different amounts of collagen, date puree, and pumpkin puree, they were evaluated in terms of sensory and nutritional properties. Results: The highest flavor score bars were those with high levels of pumpkin puree (P2) and date puree (D2). By applying the TOPSIS technique, which is used when there are multiple crite-ria among multiple samples, to the snack bar samples with different contents, the most liked sample was found to be the snack bar (D2) with a high level of date puree. One serving of the developed bars contains approximately 300-400 kcal of energy and 6.8-8.8 g of protein. Consid-ering age-related decreased appetite and chewing and swallowing problems in elderly individ-uals, regular consumption of nutrient-rich small meals or snacks with enhanced sensory charac-teristics will contribute to improving their nutritional and functional status.
... Collagen hydrolysate (CHs) or hydrolyzed collagen is similar to gelatin in amino acid but differ in chemical properties. Collagen hydrolysate is well known to dissolve in water that makes its digestion and absorption easier as a free amino acids (26) .Variable peptide sequences and molecular weights are produced after many processing events on native collagen. Variation between these products can affect the biological action of them on joint inflammation and subsequent effects on bone. ...
Article
Full-text available
Osteoarthritis is a degenerative disease affecting joints that is chronic and disables the movement of patients with increasing pain and decreasing their quality of life with age. Available treatments are only symptomatic with no cure. Recent methods for managing osteoarthritis involve using pharmacological, non-pharmacological treatments or both for improving physical function in patients and alleviating pain. Clinical trials were conducted to reveal the extent of benefits obtained from different nutraceuticals and food supplements, such as collagen with growing use and fairly good results in the treatment of osteoarthritis. The goal of this study is to review the current information about the rational use of collagen in osteoarthritis
... The use of collagen hydrolysate provides the products with distinct therapeutic-preventive properties since collagen participates in the formation of connective tissue in the human body and thus can act as a biologically active additive with chondroprotective properties [19][20][21]. Oral intake of 10 g of collagen hydrolysate per day over three months reduces joint pain and improves bone fracture healing and joint function in patients [22,23]. ...
Article
Full-text available
Recently, increasing attention has been focused on developing new products based on goat’s milk. Consumers positively perceive fermented goat’s milk products as health-promoting due to their nutritional value, digestibility, and potential source of probiotics. This study aimed to evaluate the possibility of using different doses of collagen and collagen hydrolysate in the production of probiotic goat’s milk fermented by four monocultures: Lacticaseibacillus casei 431® Lactobacillus acidophilus LA- 5®, Lacticaseibacillus paracasei LP26, and Lacticaseibicillus rhamnosus Lr- 32®. A total of 20 experimental groups were prepared, including control groups (without additives), and due to the added probiotic (Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus paracasei, and Lacticaseibacillus rhamnosus), various collagen doses (1.5% and 3.0%) and collagen types (hydrolysate and bovine collagen). Physicochemical, organoleptic, and microbiological characteristics were evaluated after 1 and 21 days of cold storage. The applied additives increased the acidity of the milk even before fermentation. However, milk with bovine collagen and hydrolysate had a higher pH value after fermentation than control milk. The study showed higher than 8 log cfu g−1 viability of probiotic bacteria in goat’s milk products during storage due to the proper pH, high buffering capacity, and rich nutrient content of goat’s milk. The best survival rate was shown for the L. casei strain after 21 days in milk with collagen protein hydrolysate. Moreover, collagen in milk fermented by L. rhamnosus decreased syneresis compared to its control counterpart. The addition of collagen, especially the hydrolysate, increased the gel hardness of the fermented milk. The collagen additives used in the milk, both in the form of hydrolysate and bovine collagen, caused a darkening of the color of the milk and increased the intensity of the milky-creamy and sweet taste.
Article
Full-text available
Collagens are abundant structural proteins found in connective tissues such as bones, swim bladder, skin, blood vessels, intestines, and cartilage. They make up around 30% of the total protein. The purpose of this paper is to provide a summary of the current knowledge about collagen isolated from marine organisms and its possible applications. Collagen is widely used in pharmaceuticals, food, biomedical and cosmetic industries due to its cell adhesion, biocompatibility, and safety properties. This review discusses various methods for extracting collagen from marine vertebrates and its physicochemical properties. Enzymatic extractions might be a more effective at extracting collagen than acidic extractions. Peptides derived from collagen hydrolysates have biological activity that promotes health and relieves symptoms caused by chronic diseases. Aquaculture can help with collagen availability but an integrated technology for processing raw materials is necessary to address the negative effects of production waste. Marine collagen has many benefits over terrestrial sources including its versatility in healing skin damage and slowing down the aging process. The advantages of marine collagen over terrestrial sources are discussed along with its potential biotherapeutic applications in bone and skin injuries. The development of effective cosmetic products can become a strategic direction for technological development.
Article
Full-text available
The figure of the digital influencer has become fundamental within social networks in reaching the consumer public market since it determines the direction of its thousands and even millions of followers. As a consequence of this whole range of influence, companies, brands, and industries from the most diverse branches began to establish partnerships for advertising and publicizing their products in the field of beauty, food, fashion, and, mainly, health, for example, corroborating with self-medication. Digital Influencer refers to an individual who is a reference and who has the power to influence his followers, managing to increase sales of the product he promotes. Because of the above, the methodology adopted was descriptive, exploratory, and observational, with a cross-sectional design, through the application of a semi-structured questionnaire. This study aims to evaluate digital influencers and their strategies that increase the risk of irrational drug use by students of undergraduate courses in the health area. As for the results obtained from the collected data, it was found that most of the respondents were female; the age of participants in the samples ranged from 17 to 48 years. Regarding the irrational use of medication, the majority, 90.8% (n = 128), claimed to know the subject, and 75.7% (n = 109) stated that influencers generally suggest some medication with the purpose of self-medication. About using medication due to digital influencers, 73.2% (n = 115) claimed not to use medication recommended by “influencers.” Finally, it can be seen that the present research that the analyzed theme demonstrated the complexity and the need to have a follow-up of the supervisory bodies about what is produced by influencers in social networks, above all, in the field of self-medication, since it became Of course, the use of drugs without proper authorization from the professional is dangerous and may cause irreversible damage.
Article
Collagen is considered a nutraceutical, and its consumption has been expanding due to the increased life expectancy, rising per capita income, and increased consumer awareness of health care. This study aimed to evaluate consumers' perceptions, knowledge, attitudes, and practices about the consumption of collagen-based products by using an online questionnaire and to correlate them with socio-economic data. A market survey (pharmacy stores and online) was also conducted to evaluate the available products. In total, 275 participants answered the survey, 73.3% from the Southeast region, mostly female (84.0%). Most participants reported three months as the period of collagen intake (31.6%), and the consumption period was associated with the perception of the health benefits (p < 0.001). Furthermore, the participants' knowledge and perceptions regarding collagen intake are frequently associated with dermatological and orthopedic changes. Collagen-based products supplementation is a growing market with a broad target audience (genders, age groups, and socio-economic levels). The commercial presentation of collagen has been diversified over the years, and powder collagen is the most consumed (52.7%) and cheapest compared with capsules, pills, or gummies. The results of the present study demonstrate that most consumers of this type of supplement associate its benefits with aesthetic care such as skin, hair, and nails, although the scientific literature has shown its effects in treating osteoarticular diseases, for example. Undoubtedly, the correct dose prescription, treatment time, and choice of product presentation must be analyzed carefully, as they significantly impact treatment results.
Article
Full-text available
Collagen is a protein and one of the main building blocks of our skin. It is found in bones, tendons, ligaments, internal organs, blood vessels, and the lining of the intestines. In our body, collagen enables the cohesion of tissues and organs, affects hydration, resistance and elasticity of the skin, reduces the risk of developing degenerative joint diseases. Its production decreases with age. As a result, more and more people are taking collagen supplements. It has been proven that doing so can bring many benefits to the body. Taking collagen orally can be an effective way to improve the quality of the skin, increase hydration and delay the aging process. Collagen peptides are potential therapeutic agents for treating osteoarthritis and maintaining joint health. Collagen supplementation may be an element of preventive medicine in the field of cardiovascular diseases. as it significantly reduces fat mass and increases lean mass, it also leads to lower LDL concentrations. A beneficial effect was also noted on hair and nails, as well as on brain function.
Article
Full-text available
Resumo O envelhecimento é um processo dinâmico, no qual ocorrem modificações do nível molecular ao morfo-fisiológico, logo após a maturidade, que induzem ao declínio orgânico, aumentando a susceptibilidade e vulnerabilidade a doenças e à morte. A genética do envelhecimento dedica-se ao estudo da contribuição hereditária da espécie e sua interação com o ambiente, que incidem no aumento de modificações biológicas ao longo do tempo. Fez-se uma revisão sobre estudos realizados na área e que sugerem que o envelhecimento está sob um controle genético-ambiental. Exceto em síndromes, a contribuição genética, tanto para o tempo de vida quanto algumas doenças crônicas (Alzheimer, doenças cardiovasculares e diabetes mellitus tipo 2), é relativamente baixa. Este fato demonstra que fatores ambientais, como estilo de vida e dieta, desempenham papel fundamental no fenótipo do envelhecimento. Ou seja, a genética não é uma rota determinística, e cada vez mais pode ser “manipulada” em benefício da saúde. Além disso, o conhecimento da genética do envelhecimento e doenças associadas proporciona, cada vez mais, a elaboração de instrumentos clínicos para o benefício das pessoas idosas.
Article
Full-text available
No Brasil, devido às mudanças nos perfis demográfico, epidemiológico e nutricional da população e ao controle conseguido em um número de enfermidades transmissíveis, vêm observando-se, nas últimas décadas, uma inversão do perfil epidemiológico com redução das doenças infecciosas e o aumento significativo da prevalência das doenças crônicas não transmissíveis (DCNTs). Essa mudança justifica o estudo dos fatores de risco e determinantes sociais das doenças crônico-degenerativas no país. O presente trabalho teve por objetivo conhecer a prevalência da exposição da população aos principais fatores de risco para o desenvolvimento de DCNTs no Brasil. Foi realizada uma revisão sistemática dos artigos publicados na literatura científica, a partir das bases de dados on-line Lilacs e Medline, entre 2003 e 2008, em português. As prevalências variaram conforme os critérios utilizados e as características das populações estudadas, sendo obtidos os seguintes valores mínimo e máximo para cada um dos fatores de risco estudados: tabagismo 8,7% a 28,8%, uso abusivo de álcool 0,1% a 37,7%, excesso de peso 1,5% a 49,0%, obesidade 9,4% a 17,6%, sedentarismo 20,1% a 43,1%, hipertensão arterial 5,3% a 34,0%, diabetes mellitus 2,7% a 7,8%. A variação no grau de exposição da população aos fatores de risco presentes nos diversos estudos aponta para a necessidade de padronização dos instrumentos de medida, a fim de que os resultados obtidos nas diferentes localidades possam ser comparados. Além disso, as altas prevalências observadas em algumas áreas indicam a necessidade de intervenções imediatas por meio da implementação de estratégias de prevenção e promoção da saúde dirigidas à redução da exposição da população brasileira aos fatores associados ao risco de desenvolvimento das DCNTs.
Article
Full-text available
Rheumatoid arthritis (RA) and osteoarthritis (OA) are serologically and clinically distinctive, but at the local level, both diseases have many molecular pathways in common. In vivo molecular imaging can unravel the local pathologic processes involved in both diseases. In this study, we investigated matrix metalloproteinase (MMP) and cathepsin activity during cartilage destruction, in an RA and an OA mouse model, using biophotonic imaging of substrate-based probes. Mice with collagen-induced arthritis (CIA) or destabilization of the medial meniscus (DMM) were imaged using near-infrared fluorescent probes, activated by several cathepsins or MMPs. Fluorescence signal intensity was compared to synovial gene expression, histology, and cartilage staining of a neoepitope of aggrecan cleaved by MMPs with the amino acids DIPEN. Increased cathepsin and MMP activity was seen during CIA, whereas the DMM model only showed increased MMP activity. DIPEN expression was seen only during CIA. A possible explanation can be differences in gene expressions; MMP3 and -13, known to produce DIPEN neoepitopes, were upregulated in the CIA model, whereas MMP12, known to be involved in elastin degradation and chemokine inhibition, was upregulated in the DMM model. Thus, molecular imaging showed no cathepsin activity at the time of cartilage damage in the DMM model, whereas both cathepsins and MMPs are active in the CIA model during disease progression.
Article
Full-text available
Traditionally considered “wear and tear” disease, the pathogenic mechanisms of osteoarthritis has not yet been elucidated. The increasing number of articles demonstrating the influence of inflammatory factors in the onset and progression of the disease currently raises great debate in the literature about the importance of each of the factors involved in the disease. Even the choice between the terms “Osteoarthritis” and “Osteoarthrosis” generates controversy, since the first term implies the presence of inflammation as the key generator of the disease, and the latter denotes a degenerative/mechanical causal factor. The aim of this revision article is to promote a debate on the influence of inflammatory factors and mechanical factors in the pathogenesis of OA.
Article
Full-text available
Osteoarthritis is an age-related condition and the leading cause of pain, disability and shortening of adult working life in the UK. The incidence of OA increases with age, with 25% of the over 50s population having OA of the knee. Despite promising preclinical data covering various molecule classes, there is regrettably at present no approved disease modifying OA drugs. With the advent of next generation sequencing technologies, other therapeutic areas, in particular oncology, have experienced a paradigm shift towards defining disease by its molecular composition. This paradigm shift has enabled high resolution patient stratification and supported the emergence of personalised or precision medicines. In this review we evaluate the potential for the development of OA therapeutics to undergo a similar paradigm shift given that OA is increasingly being recognised as a heterogeneous disease affecting multiple joint tissues. We highlight the evidence for the role of these tissues in OA pathology as different “hallmarks” of OA biology and review the opportunities to identify and develop targeted disease-modifying pharmacological therapeutics. Finally, we consider whether it is feasible to expect the emergence of personalised disease modifying medicines for patients with OA and how this might be achieved.
Article
Full-text available
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.
Article
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.
Article
The presence of hydroxyproline (Hyp)-containing peptides in human blood after collagen hydrolysate ingestion is believed to exert beneficial effects on human health. To estimate the effective beneficial dose of these peptides, we examined the relationship between ingested dose and food-derived Hyp levels in human plasma. Healthy volunteers (n = 4) ingested 30.8, 153.8 and 384.6 mg per kg body weight of collagen hydrolysate. The average plasma concentration of Hyp-containing peptides was dose-dependent, reaching maximum levels of 6.43, 20.17 and 32.84 nmol/ml following ingestion of 30.8, 153.8 and 384.6-mg doses of collagen hydrolysate, respectively. Ingesting over 153.8 mg of collagen hydrolysate significantly increased the average concentrations of the free and peptide forms of Hyp in plasma. The Hyp absorption limit was not reached with ingestion of as much as 384.6 mg of collagen hydrolysate. These finding suggest that ingestion of less than 30.8 mg of collagen hydrolysate is not effective for health benefits.