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Collagen peptides improve knee osteoarthritis in elderly women: A 6-month randomized, double-blind, placebo-controlled study

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As the global population gets older, joint-related health concerns are increasingly common, such as osteoarthritis causing pain and reducing mobility. Collagen peptides have been proposed as nutraceuticals to improve joint health in patients with osteoarthritis. We performed a prospective, randomized, double-blind, placebocontrolled study in elderly women with mild-to-moderate knee osteoarthritis and showed that the oral intake of collagen peptides (Peptan®) for a duration of 6 months significantly reduces joint pain and improves physical mobility as assessed by two wellestablished scoring systems (WOMAC and Lysholm score). This study confirms that collagen peptides are a highly efficient nutraceutical to improve joint health which can help to maintain an active lifestyle throughout ageing.
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KEYWORDS: Collagen peptides, osteoarthritis, joint pain, healthy ageing, nutraceutical
AbstractAs the global population gets older, joint-related health concerns are increasingly common, such as
osteoarthritis causing pain and reducing mobility. Collagen peptides have been proposed as
nutraceuticals to improve joint health in patients with osteoarthritis. We performed a prospective, randomized, double-blind, placebo-
controlled study in elderly women with mild-to-moderate knee osteoarthritis and showed that the oral intake of collagen peptides
(Peptan®) for a duration of 6 months significantly reduces joint pain and improves physical mobility as assessed by two well-
established scoring systems (WOMAC and Lysholm score). This study confirms that collagen peptides are a highly efficient
nutraceutical to improve joint health which can help to maintain an active lifestyle throughout ageing.
Collagen peptides improve knee
osteoarthritis in elderly women
A 6-month randomized, double-blind, placebo-controlled study
INTRODUCTION
Population ageing
Worldwide, the population is increasingly ageing, with a
greater proportion of people getting old and old people
reaching an even higher age than before. In 2009,
10% of the population were 60 years and older and this
fraction is estimated to increase up to 20% by 2050 (1).
This demographic development is associated with an
increase in age-related diseases (2) concurrently building
a strong case for the maintenance of health throughout
ageing and the focus of interest of the pharmaceutical
and nutraceutical industry.
Osteoarthritis
One age-related disease with rising prevalence is
osteoarthritis with 10% of all men and 20% of all women
over 60 years old already suffering from it today (3).
Osteoarthritis is a degenerative disease of the articular
cartilage in joints of the knee, hip, spine and hand.
Pain, stiffness and locking of the joint are key symptoms
reducing mobility and strongly impacting on the quality of
life of the patient.
The hyaline cartilage of the joint consists mainly of
extracellular matrix composed of collagen, proteoglycans
(e.g. aggrecan) and glycosaminoglycans such as
hyaluronic acid. Chondrocytes present in the cartilage
maintain the matrix in a finely-tuned turnover process
balancing synthesis and breakdown. In osteoarthritis,
a dysregulation of this balance leads to a shift towards
degradation with a subsequent loss of cartilage. In
addition to cartilage degradation, the inflammation
of the lining surrounding the joint space, the synovium,
as well as alterations in the bone underlying the
joint cartilage, such as sclerosis and the formation
of osteophytes, are involved in the pathological
manifestation of osteoarthritis (4).
Currently, osteoarthritis cannot be cured and available
treatment is mostly symptomatic. To treat pain, mainly
analgesics and non-steroidal anti-inflammatory drugs
(NSAIDs) are used, which at long-term or high-dose use
may cause heavy side effects, such as gastrointestinal
bleeding and cardiovascular disease (5, 6). Suggested as
a safe alternative, the dietary supplements glucosamine
and chondroitin sulfate have been used to treat
osteoarthritis. However, a systematic, multi-centred study
at a large scale did not find a general beneficial effect of
glucosamine or chondroitin sulfate. Only a small subgroup
of patients with moderate-to-severe pain significantly
benefited from a combined treatment with glucosamine
HEALTHY AGEING
JIAN-XIN JIANG1, SHEN YU1, QI-REN HUANG2, XIAN-LONG ZHANG1,
CHANG-QING ZHANG1, JIAN-LIE ZHOU3*, JANNE PRAWITT4*
*Corresponding authors
1. Department of Osteology, Shanghai 6th People’s Hospital,
Jiaotong University, 600 Yishan Road, Shanghai 200233, PR China
2. Department of Osteoporosis, Shanghai 6th People’s Hospital,
Jiaotong University, 600 Yishan Road, Shanghai 200233, PR China
3. Medical Consultant of Rousselot AP, 25/A,
18 North Cao Xi Road, Shanghai 200230, PR China
4. Rousselot BVBA, Meulestedekaai 81, B-9000 Gent, Belgium
Jiaotong University, 600 Yishan Road, Shanghai 200233, PR China
Jian-Xin Jiang
Jian-Lie Zhou
Janne Prawitt
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Agro FOOD Industry Hi Tech - vol 25(2) - March/April 2014
sclerosis and possible deformation of the bone contour;
grade IV - marked narrowing of the joint space, large
osteophytes, severe sclerosis and definite deformation
of the bone contour. Only subjects with a Kellgren-
Lawrence score of 0-I to III (excluding stage IV of severe
osteoarthritis), without allergies and with normal liver
and kidney function were included, who had not used
nutraceuticals or analgesics within the last 6 months.
Patients were randomly assigned to receive a daily
oral dose of 8g collagen peptides or 8g placebo for a
duration of 6 months. The administered collagen peptide
was Peptan®B 2000 (Rousselot) of bovine origin, while
maltodextrin was used as placebo. Compliance was
defined as the percentage of those subjects who took the
treatment in agreement with the protocol guidelines of all
subjects designated to the respective treatment group.
Assessment of safety parameters and treatment efficacy
Patients were examined at baseline as well as 3 and
6 months after the start of the treatment. Blood and
urine were sampled for the analysis of liver and kidney
parameters by standard biochemical procedures.
Joint pain and function were assessed using two well-
established scoring systems based on standardized
questionnaires, the WOMAC (23) and the Lysholm score
(24). The primary endpoint of the study was defined as the
difference of the WOMAC and Lysholm score between
the placebo and the collagen peptide group after 6
months of treatment. The WOMAC score evaluates 24
parameters for pain, stiffness and physical function of
the joint which are recorded on a visual analogue scale
with a high score indicating more severe symptoms of
osteoarthritis. The Lysholm score assesses 6 parameters for
knee joint function (e.g. limping, stair climbing, running,
jumping). A high score is associated with a better knee
function.
Statistical analysis
All values are indicated as mean with standard deviation
unless indicated otherwise. Statistical analysis was
performed by means of Student’s T-Test , repeated
measurement ANCOVA or Fisher’s exact test. Differences
were considered significant when p<0.05.
RESULTS
Patient characterisation and adherence
The hundred osteoarthritis patients that entered the study
and chondroitin sulfate (7). Thus, the strong need for
alternative symptom-modifying therapies has created a
highly active field of research.
Collagen peptides
Collagen peptides are a specific mix of peptides of
different length, obtained by the enzymatic hydrolysis
of native collagen coming from animal connective
tissues, with a high abundance of the amino acids
hydroxyproline, glycine and proline. Used as a food
ingredient, collagen peptides are proven to be safe (8)
and to have a high bioavailability (9). They have been
shown to exert a beneficial effect on bone and skin (10,
11) and have been proposed as a candidate therapy for
osteoarthritis (12).
Studies in rodents have demonstrated that radio-actively
labeled collagen peptides accumulate in cartilage upon
ingestion (13, 14). Since collagen is the major protein
component of the extracellular matrix in cartilage,
collagen peptides have been suggested to stimulate the
formation of cartilage by simply providing building blocks.
In addition, collagen peptides have been shown to
enhance the synthesis of collagen (15) and proteoglycans
(16) in primary chondrocytes as well as the secretion of
hyaluronic acid from synovial fibroblasts (17) and might
thus be able to actively shift the balance of cartilage
turnover in osteoarthritis towards net formation.
Indeed, several clinical studies have investigated the
effect of collagen peptide treatment in individuals with
joint discomfort or osteoarthritis, reporting different levels
of joint pain improvement upon treatment (18-21) but
with conflicting results on the effect on joint function
(19 - 21). The aim of the present study was to assess the
effect of collagen peptide ingestion on knee joint pain
and function in patients with mild-to-moderate knee
osteoarthritis.
STUDY DESIGN
A prospective, single-centre, randomized, double-
blind, placebo-controlled trial was conducted between
January and July 2012 at the 6th People’s Hospital
affiliated to Shanghai Jiaotong University, China. The
study protocol was approved by the hospital’s ethical
committee which works according to the guidelines of
Good Clinical Practice and the study was registered in
the hospital’s database (Clinical Trial Registration No.
2011-51). All participants gave their informed consent.
Patient recruitment, inclusion criteria and treatment
Hundred women between the age of 40 and 70
presenting themselves with knee joint pain or discomfort
were recruited to participate in the study. This effect
size assures, at a significance level of a=0.05, a power
of 90% for WOMAC score, and of more than 80% for
Lysholm score. Osteoarthritis was diagnosed by x-ray and
quantified using the Kellgren-Lawrence x-ray classification
(22). According to the guidelines the scores were defined
based on the following symptoms: grade I - doubtful
narrowing of the joint space and possible osteophytes
lipping; grade II - definite narrowing of the joint space
and definite osteophytes; grade III - definite narrowing
of the joint space, moderate multiple osteophytes, some
Table 1. Baseline characteristics of the recruited patients.
Values are presented as means ± standard deviation.
Statistical signicance of differences was calculated by
Student’s T-Test. BMI=body mass index.
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Agro FOOD Industry Hi Tech - vol 25(2) - March/April 2014
system. The WOMAC score is composed of subscale
scores for pain, stiffness and physical function. As shown
in Figure 1, the values of the WOMAC score decreased
over time in patients treated with collagen peptides
indicating a gradual improvement of joint pain and
function. At 3 months of treatment, a small but already
highly significant effect was visible (treatment difference
of 0.002 in the placebo vs. -1.07 in the collagen peptide
group, p<0.001) which developed into a pronounced
and highly significant improvement of knee osteoarthritis
after 6 months of treatment with collagen peptides
(treatment difference of -0.77 in the placebo vs. -3.93 in
the collagen peptide group, p<0.001).
The difference between the WOMAC scores of the
collagen peptide group and the placebo group after six
months was significant for all three WOMAC subscales
(Table 4), demonstrating an improvement in knee pain
and stiffness as well as in physical function.
The Lysholm score which emphasizes on a comprehensive
evaluation of joint function demonstrated an
improvement over time by gradually increasing values in
patients treated with collagen peptides (Figure 2). In line
with the results of the WOMAC score a highly significant
effect already detectable at 3 months of treatment
(treatment difference of 0.25 in the placebo compared
to 2.39 in the collagen peptide group, p<0.001) further
increased into a clear and significant effect at 6 months
were equally randomized to the two treatment groups,
placebo or collagen peptides.
Over the course of the study, two patients dropped out
of the placebo group (for reasons of non-adherence
and lateral thigh pain), and four patients dropped out
of the collagen peptide group (three had already taken
collagen peptides before the study and one presented
septic arthritis). As shown in Table 1, there were no
significant differences at baseline between both groups
regarding age, height, weight, body mass index (BMI),
WOMAC score and Lysholm score.
Importantly, the level of osteoarthritis quantied using
the Kellgren-Lawrence X-ray classication (Table 2) was
distributed in a comparable manner without signicant
differences between the placebo and the collagen peptide
group. Around half the patients of each group presented
mild osteoarthritis in one or both knees (score I-II).
Treatment safety
At baseline as well as after 6 months of treatment,
parameters of liver function (SGOT, SGPT) and kidney
function (blood urea nitrogen, serum creatinine, serum
uric acid) were within the normal range for all patients
with no significant differences between the placebo and
the collagen peptide group neither at baseline nor after
6 months of treatment (Table 3). Compared to baseline,
the improvement of liver parameters and blood urea
nitrogen was significant in the collagen peptide group,
even though the change from baseline was very
small. Serum creatinine showed a small but significant
increase from baseline in the placebo and to a lesser
extent in the collagen peptide group. Overall, this
result demonstrates that the treatment of osteoarthritis
patients with 8g collagen peptides daily over a duration
of 6 months is safe.
Treatment efficacy
The effect of the treatment on joint pain and function
was evaluated by the WOMAC and the Lysholm scoring
Table 2. Kellgren-Lawrence score of the recruited patients at
baseline. Statistical signicance of differences was calculated by
Fisher’s exact test. Levels of osteoarthritis are dened as 0=None,
I=Doubtful, II=Minimal, III=Moderate (22).
Table 3. Parameters of liver and kidney function were measured in
blood and urine at baseline and after 6 months of treatment with
placebo or collagen peptides. Values are presented as means
± standard deviation. Statistical signicance of differences was
calculated by Student’s T-Test. SGOT=serum glutamic oxaloacetic
transaminase; SGPT=serum glutamic pyruvic transaminase;
BUN=blood urea nitrogen.
Figure 1. Effect of collagen peptide treatment on osteoarthritis
assessed by the WOMAC score. Score values at baseline, after
3 months and 6 months of treatment are presented as mean ±
standard error mean. Statistical signicance of differences was
calculated by ANCOVA. A low WOMAC score indicates a low
degree of osteoarthritis. *** p<0.001.
Table 4. Effect of collagen peptide treatment on the WOMAC
subscale scores for pain, stiffness and function. Score values at
baseline and after 6 months of treatment are presented as mean
± standard deviation. Statistical signicance of differences was
calculated by ANCOVA. A low WOMAC subscale score indicates
a low degree of pain or stiffness, and a lower degree of difculty
in physical function.
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Agro FOOD Industry Hi Tech - vol 25(2) - March/April 2014
of treatment (treatment difference of 0.77 in the placebo
compared to 5.00 in the collagen peptide group,
p<0.001). Thus the beneficial effect of collagen peptide
treatment on joint pain and function in osteoarthritis
patients could be shown independently by two different
evaluation systems.
DISCUSSION
Collagen peptides are nutraceuticals used in dietary
supplements and as a food ingredient offering health
benefits at different levels. Their positive effect on skin
physiology, increasing skin hydration and elasticity (11),
stimulating synthesis of skin matrix components (25, 26)
and decreasing skin collagen fragmentation (Rousselot,
unpublished data), is well documented. Several in
vivo studies have further reported a positive impact
of collagen peptides on bone formation, resulting in
increased bone strength and bone mineral density
helping to reduce osteoporosis (10, 27, 28). Lately,
collagen peptides have been vividly discussed as a
symptom-modifying agent for osteoarthritis (12). Based
on their application in functional foods as a bioactive
ingredient they are thought to act at a rather early
stage of the disease helping to prevent or delay the
manifestation of osteoarthritis.
We performed a randomized, double-blind, placebo-
controlled trial in elderly women to evaluate the
effect of collagen peptides on the symptoms of knee
osteoarthritis. Since the variability of results in other
clinical trials has been attributed to the investigation
of rather heterogeneous patient cohorts, we recruited
only women within a defined age and BMI range, who
presented with mild knee osteoarthritis. The relative
homogeneity of the study groups was confirmed by
the fact that over 50% of all subjects in each group
presented a rather low score of I-II on the Kellgren-
Lawrence scale, indicating mild osteoarthritis.
In the present study, the administration of collagen
peptides at a dose of 8g/d was highly efficient to
decrease joint pain and stiffness and to improve joint
Figure 2. Effect of collagen peptide treatment on osteoarthritis
assessed by the Lysholm score. Score values at baseline, after
3 months and 6 months of treatment are presented as mean ±
standard error mean. Statistical signicance of differences was
calculated by ANCOVA. A high Lysholm score indicates a low
degree of osteoarthritis. *** p<0.001.
function in comparison to the placebo, with a significant
effect already observed after 3 months of treatment.
The improvement of pain evaluated with the help of the
WOMAC score is in line with the results of several other
clinical studies. Benito-Ruiz et al. observed a decrease
in pain according to two different pain scales (VAS
and WOMAC) in a gender-mixed cohort with mild knee
osteoarthritis (19). Another trial showed that collagen
peptides performed even better than glucosamine in
reducing pain in osteoarthritis patients as early as 3
months after the treatment start (20).
In addition to the WOMAC score, we used the Lysholm
scoring system for the assessment of joint function.
The Lysholm score has been developed specifically
to evaluate knee function, by integrating information
on limping, stair climbing, locking, giving way of the
knee during activity and the ability to squat the joint.
Corresponding to the results of the WOMAC rating, the
Lysholm score significantly improved over the study
duration in patients treated with collagen peptides
in comparison to the placebo group. This finding is
remarkable since only one other study has described
such an effect (20). Two other trials assessed joint
function by WOMAC or Quality of Life scores but did not
find an effect of collagen peptide treatment (19, 21).
However, both studies used a much more heterogeneous
group of subjects presenting with general joint pain, not
diagnosed osteoarthritis, and performed a combined
evaluation of different joints (knee, hip, spine, etc.),
which might explain why no effect on joint function was
observed.
The presented data provide strong evidence for the
symptom-relieving effect of collagen peptides in knee
osteoarthritis, but the study design does not allow to
conclude on potential mechanisms of action. A recent
study has investigated the effect of collagen peptides
on joint structure in a small group of patients using a
MRI technique which can visualise cartilage (29). The
result suggests that collagen peptides increase the
proteoglycan content in knee cartilage after 6 months
of treatment, which is consistent with the in vitro data
showing a stimulation of extracellular matrix synthesis by
collagen peptides (15, 16).
Even if the differences observed after 6 months are
highly significant in the current study, more investigations
should be initiated in future to confirm the efficacy of
collagen peptides as a protective factor of cartilage
in randomized, placebo controlled clinical studies of
bigger scale, and with diverse patient characteristics
to overcome the current study’s limitations of sex,
ethnicity of the subjects and the cause and location of
osteoarthritis. In addition, mechanistic and biochemical
parameters (e.g. MRI, uCTX-I, uCTX-2) could be assessed,
and efforts could be made to investigate the potential
differences between collagen peptide products from
different sources and different production processes.
The present study demonstrates a clear beneficial effect
of collagen peptide (Peptan®) treatment on joint pain
and function in patients with mild knee osteoarthritis.
Their safety record and demonstrated absence of side
effects make collagen peptides a valuable alternative
symptom-modifying treatment for osteoarthritis. Thus, they
present a highly useful nutraceutical to help maintain the
quality of life during ageing.
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Agro FOOD Industry Hi Tech - vol 25(2) - March/April 2014
ACKLOWLEDGMENTS
The authors thank Hongshan Tan (Department of
Occupational and Environmental Medicine, School of
Public Health, Fudan University, Shanghai, PR China) for
his support of statistical analysis.
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Agro FOOD Industry Hi Tech - vol 25(2) - March/April 2014
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... In fact, in a meta-analysis by Van Vijven et al. [27], the evidence was found to be of moderate to low quality, among others, because of methodological shortcomings in the included studies. Very importantly, our findings indicate that there is consensus among clinical research authors that further research is needed to confirm these preliminary results [61,63,65] and, particularly, to elucidate the mechanisms of action [61,64] of collagen derivatives and their effectivity in delaying the natural history of cartilage degradation in OA patients [58, 65,67]. The need for high-quality and long-term clinical trials in larger populations has also been advocated by the authors of all the meta-analyses on collagen derivatives in OA [27,28,31]. ...
... In fact, in a meta-analysis by Van Vijven et al. [27], the evidence was found to be of moderate to low quality, among others, because of methodological shortcomings in the included studies. Very importantly, our findings indicate that there is consensus among clinical research authors that further research is needed to confirm these preliminary results [61,63,65] and, particularly, to elucidate the mechanisms of action [61,64] of collagen derivatives and their effectivity in delaying the natural history of cartilage degradation in OA patients [58, 65,67]. The need for high-quality and long-term clinical trials in larger populations has also been advocated by the authors of all the meta-analyses on collagen derivatives in OA [27,28,31]. ...
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IntroductionThere is currently no disease-modifying drug for osteoarthritis (OA), and some safety concerns have been identified about the leading traditional drugs. Therefore, research efforts have focused on alternatives such as supplementation with collagen derivatives. The objective of this scoping review is to examine the extent, range, and nature of research, and to summarize and disseminate research findings on the effects of collagen derivatives in OA and cartilage repair. The purpose is to identify gaps in the current body of evidence in order to further help progress research in this setting.Methods The databases Medline, Scopus, CENTRAL, TOXLINE, and CDSR were comprehensively searched from inception to search date. After studies selection against eligibility criteria, following recommended methods, data were charted from the retrieved articles and these were subsequently synthesized. Numerical and graphical descriptive statistical methods were used to show trends in publications and geographical distribution of studies.ResultsThe systematic literature search identified a total of 10,834 records. Forty-one published studies were ultimately included in the review, 16 of which were preclinical studies and 25 were clinical studies (including four systematic reviews/meta-analyses). Collagen hydrolysate (CH) and undenatured collagen (UC) were the two types of collagen derivatives studied, with a total of 28 individual studies on CH and nine on UC. More than a third of studies originated from Asia, and most of them have been published after 2008. Oral forms of collagen derivatives were mainly studied; three in vivo preclinical studies and three clinical trials investigated intra-articularly injected CH. In most of the clinical trials, treatment durations varied between 3 and 6 months, with the shortest being 1.4 months and the longest 11 months. All in vivo preclinical studies and clinical trials, regardless of their quality, concluded on beneficial effects of collagen derivatives in OA and cartilage repair, whether used as nutritional supplement or delivered intra-articularly, and whatever the manufacturers of the products, the doses and the outcomes considered in each study.Conclusions Although current evidence shows some potential for the use of CH and UC as an option for management of patients with OA, there is still room for progress in terms of laboratory and clinical research before any definitive conclusion can be made. Harmonization of outcomes in preclinical studies and longer randomized placebo-controlled trials in larger populations with the use of recommended and validated endpoints are warranted before collagen derivatives can be recommended by large scientific societies.
... Other clinical trials also showed reduction in joint pain upon CH daily consumption for periods ranging from 3 months to one year. In all these clinical trials an improvement in the WOMAC index as well as other indexes of joint functionality and discomfort were observed [9][10][11][12][13]. ...
... Participants were randomly assigned to either a CP group (n = 100) that received a CP supplement (Peptan B2000, Rousselot, Gent, Belgium, molecular weight 2000 Da) for 10 g per day that was derived from bovine hide (hydrolyzed collagen; proline/hydroxyproline (23%), glycine (21%), glutamic acid (12%), arginine (8%), alanine (8%), essential amino acids (16%), and other amino acids (12%)) or a placebo group (n = 100) that received 10 g of maltodextrin on a daily basis. Peptan B2000 has proven efficacy to support joint health in both mice (Dar et al. 2017) and humans (Jiang et al. 2014), respectively, while in both studies a different Peptan B2000 batch was used. Moreover, participants in our study used CP supplements from a single batch. ...
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Chapter
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Osteoarthritis is thought to be the most prevalent chronic joint disease. The incidence of osteoarthritis is rising because of the ageing population and the epidemic of obesity. Pain and loss of function are the main clinical features that lead to treatment, including non-pharmacological, pharmacological, and surgical approaches. Clinicians recognise that the diagnosis of osteoarthritis is established late in the disease process, maybe too late to expect much help from disease-modifying drugs. Despite efforts over the past decades to develop markers of disease, still-imaging procedures and biochemical marker analyses need to be improved and possibly extended with more specific and sensitive methods to reliably describe disease processes, to diagnose the disease at an early stage, to classify patients according to their prognosis, and to follow the course of disease and treatment effectiveness. In the coming years, a better definition of osteoarthritis is expected by delineating different phenotypes of the disease. Treatment targeted more specifically at these phenotypes might lead to improved outcomes.
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Collagen hydrolysates (CHs) are mixtures of peptides obtained by partial hydrolysis of gelatins that are receiving scientific attention as potential oral supplements for the recovery of osteoarticular tissues. The effect of supplementing the diets with a CH was assessed in 48 ovariectomized rats by analyzing the compositional and biomechanical characteristics of the bone. Six groups of rats (three ovariectomized, one sham-operated, and two intact) were fed a standard diet, supplemented with either CH or gelatin (Control), at two levels: a dose equivalent to five times the amount suggested for humans (10 g/day) or another 10 times greater. After 8 weeks, the femora and vertebrae were excised, the blood was collected, and serum alkaline phosphatase and osteocalcin were determined. Bone weight, total protein, and biomechanical strength were also determined. The vertebrae of the ovariectomized group that received the higher dosage of CH withstood a load four times greater and exhibited higher levels of protein and osteocalcin content than those receiving either gelatin or no supplement. CH supplementation at the higher level in the ovariectomized rat had an unequivocal contribution in the conservation or preservation of vertebral mass, protein content, and mechanical strength not seen when gelatin was used as a supplement. Similar treatment of the intact rat with the CH, however, appeared to have the opposite effect.
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The effects of repeatedly brewed green tea infusion on the formation of nitrosamine in vitro and in vivo, and on cancer mortality were examined. The first and second brews of green tea infusion inhibited the formation of nitrosomorpholine in the presence of morpholine and nitrite (nitrosation of morpholine), but the third to eighth brews accelerated it. The green tea infusion brewed from 5 g of leaves in 200 ml hot water (strong tea infusion) inhibited the nitrosation of morpholine, but that brewed from 2.5 g or less (weak tea infusion) promoted the nitrosation. The brewed green tea infusion that inhibited nitrosation of morpholine contained catechins at a high concentration, and that that promoted nitrosation contained catechins at a low concentration. The effects of green tea administered to Wistar male rats and that consumed by humans on the formation of nitrosamines were also examined. In both rats and humans, nitrosamine formation was inhibited by strong green tea extract but was increased by weak green tea extract. The concentration of catechins in the green tea infusion brewed by the general households in tea-producing areas was significantly higher than that brewed in non-producing areas. We examined the relationship between the concentration of catechins in green tea infusion brewed in different areas and the standardized mortality ratio (SMR) of cancer in respective areas, and found that the catechin concentration in green tea infusion correlated inversely and significantly with the SMR of cancer in that area. We concluded that strong green tea might inhibit the formation of nitrosamines and decrease the risk of carcinogenesis.
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Objective: Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. Collagen derivatives are candidates for disease-modifying OA drugs. This group of derivatives can be divided into undenatured collagen (UC), gelatine and collagen hydrolysate (CH). Collagen derivatives are marketed as having direct chondroprotective action and reducing complaints of OA. This review summarizes the evidence for the effectiveness of symptomatic and chondroprotective treatment with collagen derivatives in patients with OA. Methods: Eligible randomised controlled trials (RCTs) and quasi-RCTs were identified by searching PubMed, Embase and the Cochrane Central Register of Controlled Trials until November 2011. Methodological quality was assessed using methods of the Cochrane Back Review Group. Results: Eight studies were identified: six on CH, two on gelatine, and one on UC. The pooled mean difference based on three studies for pain reduction measured with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index comparing CH with placebo was -0.49 (95% CI -1.10-0.12). However, some studies report significant between-group differences in pain when measured with a visual analogical scale (VAS) or other instruments, or when CH is compared with glucosamine sulphate. For disability no significant between-group mean differences were found when comparing CH with placebo. Gelatine compared with placebo and with alternative therapies was superior for the outcome pain. UC compared with glucosamine+chondroitin showed no significant between-group differences for pain and disability. The most reported adverse events of collagen derivatives were mild to moderate gastro-intestinal complaints. The overall quality of evidence was moderate to very low. Conclusions: There is insufficient evidence to recommend the generalized use of CHs in daily practice for the treatment of patients with OA. More independent high-quality studies are needed to confirm the therapeutic effects of collagen derivatives on OA complaints.
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Prolylhydroxyproline (Pro-Hyp), which is derived from collagen hydrolysate, has been shown to be beneficial for skin and joint health. However, little is known about the distribution of Pro-Hyp in these tissues. In the present study, we investigated the biodistribution of orally administered [(14)C]Pro-Hyp in rats. Whole-body autoradiography at 30 min after administration of [(14)C]Pro-Hyp showed that radioactivity is widely distributed in tissues including skin and articular cartilage, with the highest level of radioactivity observed in the gastric and intestinal walls. Incorporation of radioactivity into cells known to respond to Pro-Hyp such as dermal fibroblasts, synovial cells, chondrocytes, osteoblasts, and osteoclasts was observed. The chemical form of [(14)C]Pro-Hyp-derived radioactivity detected in the tissues was investigated by thin layer chromatography. The radioactive constituents in cartilage extract were two proline-modified peptides (56%), intact Pro-Hyp (5%), and two nonpeptide metabolites (28%). Similar results were obtained for skin and bone marrow. Plasma analysis at 3 to 30 min post-dose suggested that the majority of Pro-Hyp is modified in its proline residue by a first-pass effect without peptide bond hydrolysis. In conclusion, we demonstrated that Pro-Hyp is partly distributed in observed tissues including skin and cartilage in its intact form, which might be responsible for its biological functions.
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To determine whether either of two magnetic resonance imaging approaches - delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC), or T2 mapping - can detect short-term changes in knee hyaline cartilage among individuals taking a formulation of collagen hydrolysate. Single center, prospective, randomized, placebo-controlled, double-blind, pilot trial of collagen hydrolysate for mild knee osteoarthritis (OA). Participants were allowed to continue the prior analgesic use. The primary outcome was change in dGEMRIC T1 relaxation time in the cartilage regions of interest at the 24-week timepoint. Secondary endpoints included the change in dGEMRIC T1 relaxation time between baseline and 48 weeks, the change in T2 relaxation time at 0, 24 and 48 weeks, the symptom and functional measures obtained at each of the visits, and overall analgesic use. Among a sample of 30 randomized subjects the dGEMRIC score increased in the medial and lateral tibial regions of interest (median increase of 29 and 41 ms respectively) in participants assigned to collagen hydrolysate but decreased (median decline 37 and 36 ms respectively) in the placebo arm with the changes between the two groups at 24 weeks reaching significance. No other significant changes between the two groups were seen in the other four regions, or in any of the T2 values or in the clinical outcomes. These preliminary results suggest that the dGEMRIC technique may be able to detect change in proteoglycan content in knee cartilage among individuals taking collagen hydrolysate after 24 weeks.
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Proline-hydroxyproline (Pro-Hyp) stimulated hyaluronic acid production in cultured synovium cells. It was detected in guinea pig blood after oral ingestion of collagen hydrolysates. Oral administration of collagen hydrolysates increased the amount of proteoglycans in the epiphyses. It also reduced the morphological changes associated with osteoarthritic cartilage destruction of the knee joint. The results suggest that collagen hydrolysates have therapeutic potential for treatment of osteoarthritis.