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Oral Supplementation of Specific Collagen Peptides Has Beneficial Effects on Human Skin Physiology: A Double-Blind, Placebo-Controlled Study

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  • SIT Skin Invest. & Technol. Hamburg GmbH

Abstract and Figures

Various dietary supplements are claimed to have cutaneous anti-aging properties; however, there are a limited number of research studies supporting these claims. The objective of this research was to study the effectiveness of collagen hydrolysate (CH) composed of specific collagen peptides on skin biophysical parameters related to cutaneous aging. In this double-blind, placebo-controlled trial, 69 women aged 35-55 years were randomized to receive 2.5 g or 5.0 g of CH or placebo once daily for 8 weeks, with 23 subjects being allocated to each treatment group. Skin elasticity, skin moisture, transepidermal water loss and skin roughness were objectively measured before the first oral product application (t0) and after 4 (t1) and 8 weeks (t2) of regular intake. Skin elasticity (primary interest) was also assessed at follow-up 4 weeks after the last intake of CH (t3, 4-week regression phase). At the end of the study, skin elasticity in both CH dosage groups showed a statistically significant improvement in comparison to placebo. After 4 weeks of follow-up treatment, a statistically significantly higher skin elasticity level was determined in elderly women. With regard to skin moisture and skin evaporation, a positive influence of CH treatment could be observed in a subgroup analysis, but data failed to reach a level of statistical significance. No side effects were noted throughout the study. © 2013 S. Karger AG, Basel.
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Original Paper
Skin Pharmacol Physiol 2014;27:47–55
DOI: 10.1159/000351376
Oral Supplementation of Specific Collagen
Peptides Has Beneficial Effects on Human Skin
Physiology: A Double-Blind, Placebo-Controlled
Study
E. Proksch
a
D. Segger
c
J. Degwert
c
M. Schunck
b
V. Zague
d
S. Oesser
b
a
Department of Dermatology, University of Kiel, and
b
CRI, Collagen Research Institute, Kiel , and
c
Skin Investigation and
Technology, Hamburg , Germany;
d
Department of Cell and Developmental Biology, Institute of Biomedical Sciences,
University of São Paulo, São Paulo , Brazil
ment, a statistically significantly higher skin elasticity level
was determined in elderly women. With regard to skin mois-
ture and skin evaporation, a positive influence of CH treat-
ment could be observed in a subgroup analysis, but data
failed to reach a level of statistical significance. No side ef-
fects were noted throughout the study.
© 2013 S. Karger AG, Basel
Introduction
The epidermis, the fibrous collagen and elastin net-
work of the dermis, and the subcutaneous fat tissue give
rise to the biomechanical and physiological properties of
the skin
[1] . Several factors influence the appearance,
structure and integrity of the skin, including aging, hor-
mones, UV radiation and nutrition. During aging, quali-
tative and quantitative changes occur in the skin. Loss of
elasticity, reduction in the epidermal thickness and col-
lagen content and increased wrinkling are the features of
aging skin
[2] .
An important trend in skin care is the use of diet and
oral supplements to improve the skin’s appearance and
structure. Healthy skin largely reflects the general health
Key Words
Collagen peptides · Collagen hydrolysate · Skin · Elasticity ·
Hydration · Roughness
Abstract
Various dietary supplements are claimed to have cutaneous
anti-aging properties; however, there are a limited number
of research studies supporting these claims. The objective of
this research was to study the effectiveness of collagen hy-
drolysate (CH) composed of specific collagen peptides on
skin biophysical parameters related to cutaneous aging. In
this double-blind, placebo-controlled trial, 69 women aged
35–55 years were randomized to receive 2.5 g or 5.0 g of CH
or placebo once daily for 8 weeks, with 23 subjects being al-
located to each treatment group. Skin elasticity, skin mois-
ture, transepidermal water loss and skin roughness were ob-
jectively measured before the first oral product application
(t0) and after 4 (t1) and 8 weeks (t2) of regular intake. Skin
elasticity (primary interest) was also assessed at follow-up
4 weeks after the last intake of CH (t3, 4-week regression
phase). At the end of the study, skin elasticity in both CH dos-
age groups showed a statistically significant improvement in
comparison to placebo. After 4 weeks of follow-up treat-
Received: November 2, 2012
Accepted after revision: March 24, 2013
Published online: August 14, 2013
Prof. Dr. Dr. E. Proksch
Christian-Albrechts-University of Kiel, Department of Dermatology
Schittenhelmstrasse 7
DE–24105 Kiel (Germany)
E-Mail EProksch
@ dermatology.uni-kiel.de
© 2013 S. Karger AG, Basel
1660–5527/14/0271–0047$39.50/0
www.karger.com/spp
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Proksch /Segger /Degwert /Schunck /
Zague
/Oesser
Skin Pharmacol Physiol 2014;27:47–55
DOI: 10.1159/000351376
48
status and as such the skin is influenced by the consump-
tion of dietary substances, including vitamins and anti-
oxidants, fatty acids and hydrolyzed proteins
[3] . There-
fore, the effects of nutritional factors on the skin have
received increasing attention, and a number of clinical
studies indicated that dietary supplementation can mod-
ulate skin functions
[4] .
Collagen hydrolysate (CH) has long been used in phar-
maceuticals and food supplements for improving skin
and cartilage tissues. It is absorbed in the digestive tract,
appears in the human blood partly in a small peptide form
[5, 6] and is accumulated in skin for up to 96 h as shown
by Oesser et al.
[7] . On the basis of in vitro studies, col-
lagen peptides (CPs) have shown the ability of exerting
potent antioxidative activities in different oxidative sys-
tems
[8–11] .
Moreover, CH has been reported to have beneficial bi-
ological functions in skin. Studies have shown that food-
derived CPs in human blood are chemotactic for skin fi-
broblasts
[12] and increase the migration and growth of
mouse skin fibroblasts
[13] . Matsuda et al. [14] investi-
gated effects of CH ingestion on fibroblast and collagen
densities of pig skin and showed that density and diam-
eter of fibroblasts and density of collagen fibrils were sig-
nificantly larger in the CH group than in the control
groups. Tanaka et al.
[15] demonstrated that CH inges-
tion inhibited UVB-induced decrease of type I collagen,
thus improving skin conditions in mice.
Recently, Zague et al. [16] investigated the effect of
daily ingestion of CH on skin extracellular matrix pro-
teins in rats. The relative amount of type I and IV colla-
gens was significantly increased after CH intake com-
pared with the reference diet group (casein). Moreover,
CH uptake significantly decreased both pro-enzyme and
active forms of matrix metalloproteinase-2 compared
with casein and control groups. This implied that the ef-
fect of CH was protein-specific and did not depend
merely on an increase of amino acid intake. The authors
suggested that CH may reduce aging-related changes of
the extracellular matrix by stimulating anabolic process-
es in skin tissue.
Although there is convincing evidence, from the pre-
clinical perspective, that CH ingestion may improve skin
conditions and even protect skin from UV damage, little
is known about the clinical effects of CH on skin param-
eters and health. The aim of our study was to evaluate the
potential benefits of an oral supplement containing spe-
cific CP on skin parameters related to cutaneous physiol-
ogy and aging, including skin elasticity, hydration, rough-
ness and transepidermal water loss (TEWL).
Materials and Methods
Test Product
The test product used in this study was a CH composed of dif-
ferent specific CPs derived from a special hydrolysis of porcine type
I collagen. The product was provided by GELITA AG (Eberbach,
Germany), commercially available under the name VERISOL
®
.
The product is clearly defined by MALDI-MS mass peak finger-
print with specific CPs of an average molecular weight of 2.0 kDa.
Study Design
The study was carried out as a monocentric, double-blinded,
randomized, placebo-controlled supplementation study on the ef-
fects of a specific CH on skin elasticity (primary interest) and skin
hydration, as well as on TEWL and skin roughness (secondary in-
terests) after 8 weeks of daily intake.
The study was approved by the Freiburger Ethik-Kommission
International, Freiburg, Germany, and adhered to current Good
Clinical Practice regulations. All test subjects received detailed in-
formation listing every relevant single parameter to the study. All
subjects gave signed informed consent after written information
and a possibility for further questioning.
S u b j e c t s
A total of 69 healthy female subjects were enrolled in the study;
23 subjects were randomized to each of 3 treatment groups to re-
ceive a daily dose of either 2.5 or 5.0 g of CH or 2.5 g of the placebo
(maltodextrin). There were no differences between the treatment
and the placebo groups ( table1 ) with regard to age (p = 0.664).
The products were taken orally by the subjects at home accord-
ing to the instructions given by the investigator. The powder was
to be dissolved in water or any other cold liquid.
Prior to the beginning of oral treatment and data acquisition a
preconditioning period of at least 7 days was conducted. Within
Table 1. Demographic data of the volunteers per treatment group
Subjects, n 2.5 g CH 23
5 g CH 23
2.5 g placebo 23
Age (mean) 2.5 g CH 48.7
5 g CH 47.2
2.5 g placebo 47.9
Age (SD) 2.5 g CH 4.8
5 g CH 5.7
2.5 g placebo 5.2
Age (min.) 2.5 g CH 35.3
5 g CH 36.1
2.5 g placebo 36.2
Age (max.) 2.5 g CH 55.4
5 g CH 54.9
2.5 g placebo 54.3
Age is expressed in years.
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Beneficial Effects of Specific Collagen
Peptides on Human Skin Physiology
Skin Pharmacol Physiol 2014;27:47–55
DOI: 10.1159/000351376
49
this period the volunteers had to refrain from using any leave-on
products on the test areas. The study participants were not allowed
to change their usual skin care routine. Moreover, treatment with
dermatological therapeutics on the test areas was not allowed with-
in 6 weeks prior to the start of the study. In addition to that, chang-
es in living or dietary habits, consumption of any additional nutri-
tional supplement or vitamin preparations, treatment of the volar
forearms with cosmetic and dermatological skin care products and
intensive exposure to sun or UV light were prohibited during the
study.
Inclusion Criteria
The inclusion criteria were as follows: healthy females ranging
in age from 35 to 55 years (homogeneous distribution between
treatment groups); dry skin on forearms according to self-assess-
ment; phototype I–IV (Fitzpatrick scale); general good health and
mental condition; personal informed consent to participate in the
study; personal presence on the predefined days at the institute,
and willingness and capability to follow the study rules and a fixed
schedule.
Exclusion Criteria
The exclusion criteria was as follows: any deviation from the
above-mentioned inclusion criteria; acute skin diseases (e.g. atop-
ic eczema, neurodermatitis or psoriasis) on the test areas or other
dermatological disorders (e.g. scars, sunburn or moles); food aller-
gies against ingredients of the test products; gastrointestinal dis-
eases or indigestions; tattoos on the test areas; topical medication
on the test area within 6 weeks prior to study start; systemic med-
ication with anti-inflammatory agents or antibiotics within 2
weeks prior to study start; systemic medication with corticoids
and/or antihistamines within 4 weeks prior to study start; other
systemic medication within 4 weeks prior to study start; systemic
illness of the subject at the beginning of the study; pregnancy or
period of breast feeding; immunological disorders; severe disor-
ders within 6 months prior to study start (e.g. cancer, acute car-
diac and circularity disorders, severe diabetes, or alcohol or drug
abuse); participation in other studies with cosmetic products on
the test areas within 2 weeks prior to study start or during the
study; participating in a study with a pharmaceutical preparation
within 4 weeks prior to study start; intake of nutritional supple-
ments within 4 weeks prior to study start and, except for the test
products, during the study; change in lifestyle or eating habits dur-
ing the study; treatment with leave-on products or oily or moistur-
izing skin-cleansing products on arms; change in usual skin care
routine; intensive sun or artificial UV exposure (solarium) on the
test areas within 1 week prior to study start or during the study;
swimming, sauna or intensive sport within 1 day prior to measure-
ments; lack of compliance, and intellectual or mental inability to
follow the study instructions.
A s s e s s m e n t s
Test Areas
The test areas were the inner aspects of both forearms (1 test
area per volar forearm). The test areas on the forearms reached an
area of 5 × 5 cm. Skin hydration, skin elasticity and TEWL were
measured on the left forearm while skin roughness was assessed on
the right forearm. On every measurement day, the subjects had to
expose their uncovered test areas to the indoor climate conditions
(21.5 ± 1
° C and 50 ± 5% relative humidity) for at least 30 min.
Measurement Times
There were 4 measurement times: immediately before starting
the product treatment (t0), after 4 (t1) and 8 weeks (t2) of daily
product intake, and 4 weeks after the last intake (t3, 4-week regres-
sion phase, only for the skin elasticity parameter).
The subject’s compliance (dosage and way of intake) and toler-
ance towards the products were checked after 1, 4 and 6 weeks of
intake.
Measurement of Skin Elasticity
Skin elasticity was performed with the Cutometer
®
MPA 580
(Courage & Khazaka, Cologne, Germany) as described by Segger
et al.
[17] and Segger and Schonlau [18] . Briefly, the extension of
the skin was tested in response to a suction vacuum induced above
the skin test area with a 350-mbar vacuum (5-second exposure and
non-exposure period) and 1 cycle per measurement was detected.
To analyse skin elasticity, the R5 value (Ur/Ue, immediate recov-
ery/elastic deformation) was recorded. This parameter has proven
to be most suitable in detecting age-related skin alterations
[19,
20]
. The measurement of each test area was repeated 3 times.
Measurement of Skin Hydration
Assessment of skin surface hydration by electrical capacitance
was carried out using the Corneometer
®
CM 825 (Courage &
Khazaka), which measures the reactive capacitance of the skin, us-
ing the stratum corneum as a dielectric membrane. Measurements
are arbitrarily expressed as indices of hydration, which increase
with increasing skin hydration; 10 individual measurements per
application site and control were performed.
Measurement of TEWL
Using the DermaLab
®
(Cortex Instruments, Regensburg, Ger-
many) device, the TEWL expressed in g/m
2
/h was evaluated on
each site by continuous data logging over a 45-second period.
From the continuous TEWL plots, the mean value and the corre-
sponding standard deviations of the last 8 determined TEWL data
during this measurement sequence were computed. The measure-
ment of each test area was repeated 3 times.
Measurement of Skin Roughness
The skin roughness was assessed by silicone imprints using the
PRIMOS Compact (GFMesstechnik, Teltow, Germany) device for
analysis with a measuring field size of 40 × 30 mm and a lateral to
spatial resolution of 62 to 6 µm. Immediately after mixing the
hardening agent with the silicone rubber, the material was applied
onto the defined test areas and left for 5 min to harden. Then, the
imprints were carefully removed from the skin and allowed to
harden completely for 24 h. Each replica was analysed with the
optical measuring instrument, PRIMOS Compact. The measure-
ment parameters were ‘replica fine’ and ‘slow measurement’.
Three separate sites of each replica were analysed. The relief pic-
ture was computed according to the standard procedure using the
polynom level 5. Skin roughness was evaluated by analysing the
roughness parameter area (SQ value). The total area for the SQ
evaluation was about 18.4 × 13.8 mm, with the single areas for the
SQ evaluations being about 3.7 × 2.8 mm.
Statistical Analysis
The study objectives were analysed by Skin Investigation and
Technology Hamburg GmbH, Hamburg, Germany, using the
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50
computer software Microsoft Excel and STATISTICA. Microsoft
Excel was used for the calculation of the relative data, minimum
and maximum values, means and standard deviations. STATIS-
TICA was used to analyse the data distribution (Kolmogorov-
Smirnov test) and to analyse the significance of differences (one-
way ANOVA with the post hoc Fisher LSD test or Kruskal-Wallis
ANOVA with post hoc multiple comparison of mean ranks for all
groups). The hypothesis of a normal distribution was accepted
when there was a p value >0.025 (primary interests). Concerning
the differences between the treatment situations, a p value of 0.05
was considered as a statistically significant difference.
To test for significance of differences between the treatment
groups, either the one-way ANOVA (the post hoc Fisher LSD) for
normally distributed data or the Kruskal-Wallis ANOVA (post
hoc multiple comparison of mean ranks for all groups) for not nor-
mally distributed data was to be used. The following treatment
situations were compared: treatment situations at points in time t0
(original data), t1, t2 and t3 (data relative to t0). The data relative
to t0 were computed as follows: treatment situation at tx = 1, 2, 3/
treatment situation at t0.
In addition, a subgroup analysis was done between the 3
treatment groups. All volunteers within the groups were subdi-
vided as being younger or older than 50 years ( table2 ). To test
for significance of differences between treatment groups the
one-way ANOVA (the post hoc Fisher LSD) for normally dis-
tributed data was used. The following treatment situations were
compared: t2 and t3 (data relative to t0). The data relative to t0
were computed as follows: treatment situation at tx = 2, 3/treat-
ment situation at t0.
R e s u l t s
There were 7 dropouts, none of which were related to
the product intake or the study procedure in general. The
t0 data of only 1 subject from the placebo group was ex-
cluded from data analysis because there were no post-
baseline data available. There were no discomfort or ad-
verse reactions reported.
S k i n E l a s t i c i t y
There was no significant difference in skin elasticity
levels between the treatment and placebo groups prior to
the product treatment (p = 0.46). The starting level (R5
value = Ur/Ue) was about 0.85–0.89 (±0.11–0.13). Con-
cerning the data relative to placebo, both dosages of CH
showed statistically significant improved skin elasticity
levels after 4 and 8 weeks of intake (mean 7%; p < 0.05 in
all cases), as shown in figure 1 . There were no statistically
significant differences between the two dosages of CH. In
a more detailed subgroup analysis it could be demonstrat-
ed that the positive impact of CH treatment on skin elas-
ticity seemed to be more pronounced in elderly women
aged over 50 years ( fig.2 ).
At 4 weeks after the last product intake (4-week regres-
sion phase), the treatment subgroup of elderly women
still showed statistically significantly higher skin elasticity
levels than the placebo group (p < 0.05, fig.3 ), with about
98% of the positive effect for skin elasticity after having
stopped CH intake (data not shown).
Skin Hydration
The starting level of skin hydration was about 27.9–
30.0 AU (±4.3–6.1) with no statistical difference between
treatment groups and placebo control at the baseline (p =
0.31). Considering the data relative to placebo of the en-
tire studied group overall, there was no statistically sig-
nificant difference in skin hydration levels between the
treatment and placebo groups after 4 (p = 0.90) and 8
weeks (p = 0.96) of daily intake ( fig.4 ). However, sub-
group analysis revealed an increased skin hydration by
11–14% in women over 50 years old, but data failed sta-
tistical significance ( fig.5 ).
Transepidermal Water Loss
At the beginning of the observation period no statisti-
cally significant difference in the TEWL levels between
Table 2. Age-related subcategories per treatment group
Treatment group <50 years, n ≥50 years, n
2.5 g CH 14 9
5 g CH 15 8
2.5 g placebo 13 9
0.95
1.00
1.05
1.10
1.15
VERISOL 2.5 g/day VERISOL 5 g/day
x-fold of placebo
Baseline
4 weeks 8 weeks
Fig. 1. Skin elasticity changes during the time of treatment. Prior to
the beginning of the treatment, no statistically significant difference
in skin elasticity was detected in comparison to the placebo group.
Both CH-treated groups showed a statistically higher elasticity after
4 and 8 weeks of CH ingestion (mean ± SEM, n 22, p < 0.05).
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Beneficial Effects of Specific Collagen
Peptides on Human Skin Physiology
Skin Pharmacol Physiol 2014;27:47–55
DOI: 10.1159/000351376
51
treatment and placebo groups could be observed (p =
0.99). The starting level was about 8.0 g/m
2
/h (±1.2–1.3).
Concerning the data relative to placebo, there was no sta-
tistically significant difference in skin evaporation be-
tween treatment and placebo groups after 4 (p = 0.88) and
8 weeks (p = 0.90) of daily intake ( fig.6 ). In women over
50 years of age skin evaporation was reduced by 6–7%.
There was no statistically significant difference in the
moisturizing effect in this subgroup ( fig.7 ).
Skin Roughness
There was no statistically significant difference in skin
roughness between treatment and placebo groups at the
baseline (p = 0.59). The starting level was about 18.3–19.9
m (±4.2–6.9). As demonstrated in figure 8 , changes of
skin smoothness relative to placebo failed to reach a level
of statistical significance between the treatment and pla-
cebo groups after 4 (p = 0.61) and 8 weeks (p = 0.63) of
daily intake.
0.9
1.0
1.1
1.2
1.3
4 weeks 8 weeks
x-fold of placebo
2.5 g/day VERISOL 5 g/day VERISOL
women <50 years
4 weeks 8 weeks 4 weeks 8 weeks
2.5 g/day VERISOL 5 g/day VERISOL
ZRPHQ\HDUV
4 weeks 8 weeks
Fig. 2. Skin elasticity changes in age-related
subgroups. Skin elasticity was statistically
significantly increased in elderly women
(50+) after both CH dosages in comparison
to the placebo control treatment (n 9).
0.8
0.9
1.0
1.1
1.2
1.3
CH
2.5 g/day
CH
5 g/day
CH
2.5 g/day
CH
5 g/day
Subclass age <50 6XEFODVVDJH
x-fold of placebo
0
0.20
0.40
0.60
0.80
1.00
1.20
VERISOL 2.5 g/day VERISOL 5 g/day
x-fold of placebo
Baseline
4 weeks 8 weeks
Fig. 3. Long-lasting effect on skin elasticity changes in age-related
subcategories. At 4 weeks after the last CH intake, skin elasticity in
elderly women (50+) was statistically significantly increased in
both CH dosages in comparison to the placebo control treatment
(mean ± SEM, n 9, p < 0.05).
Fig. 4. Skin hydration changes during the time of treatment. With-
in the entirety of both CH-treated groups, no skin hydration
effects were observed during the time of treatment (mean ± SEM,
n 22).
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Discussion
Human skin physiology changes during the course of
life. While chronological or intrinsic aging is character-
ized by a reduction of skin thickness, loss of skin elastic-
ity, collagen fibre degeneration, xerosis and wrinkle for-
mation
[21–27] , extrinsic or photoaging caused by sun-
light exposition leads to deep-wrinkled, dyspigmented
skin and the formation of small dilated blood vessels near
the skin surface (telangiectasia)
[28] . It can be assumed
that the most prominent physiological alterations in
chronological and photoaging are localized in the dermis
and caused by the metabolism of dermal collagen fibres.
During the last decade the influence of ingested CH on
skin physiology has been investigated by several groups.
In experimental studies the authors examined fibroblast
growth, dermal extracellular matrix synthesis, antioxida-
tive protection and reduction of skin wrinkle formation
[11, 13, 15, 22, 23, 29–34] . These investigations suggested
that CPs may improve skin appearance and function in
skin tissue.
So far, only a few controlled clinical studies have been
performed to investigate the effect of orally administered
CH on various skin parameters
[4, 35] .
To the best of our knowledge, the present study is the
first clinical trial demonstrating the efficacy of a specific
low dosage (2.5 g/day) of CH on skin physiology. The re-
sults clearly revealed that both dosages (2.5 and 5.0 g) of
the specific CH had a beneficial effect on skin physiology,
as indicated by increased skin elasticity after 4 weeks of
daily consumption. The observed effect was statistically
significant (p < 0.05) after 4 and 8 weeks in the treatment
groups compared to placebo. In some women a maximum
increase of skin elasticity up to 30% could be observed af-
ter an 8-week treatment. Interestingly, only a relatively
small number of 23 women per group were needed to
0
0.20
0.40
0.60
0.80
1.00
1.20
VERISOL 2.5 g/day VERISOL 5 g/day
x-fold of placebo
Baseline
4 weeks 8 weeks
0.4
0.6
0.8
1.0
1.2
1.4
4 weeks 8 weeks
x-fold of placebo
2.5 g/day VERISOL 5 g/day VERISOL
women <50 years
4 weeks 8 weeks 4 weeks 8 weeks
2.5 g/day VERISOL 5 g/day VERISOL
ZRPHQ\HDUV
4 weeks 8 weeks
Fig. 5. Skin hydration changes in age-relat-
ed subgroups. Skin hydration was in-
creased in elderly women (50+) 8 weeks af-
ter both CH dosages in comparison to the
placebo control treatment (n 9).
Fig. 6. Skin evaporation changes during the time of treatment.
Within the entirety of both CH-treated groups, no skin evapora-
tion effects were observed during the time of treatment (mean
± SEM, n 22).
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Beneficial Effects of Specific Collagen
Peptides on Human Skin Physiology
Skin Pharmacol Physiol 2014;27:47–55
DOI: 10.1159/000351376
53
clearly demonstrate the efficacy of the verum. The group
size was predefined by a power calculation (test power
80%) based on previously published investigations.
In a subgroup analysis it could be demonstrated that
the statistically significant increase in skin elasticity after
CH ingestion was even more pronounced in women aged
over 50 years compared to younger women (p < 0.05).
The validity of these results could be confirmed by a pow-
er calculation. Due to the small variances within the mea-
sured data a test power of more than 90% was determined.
The fact that this positive effect was still detectable at the
end of the 4-week washout phase suggests a long-lasting
dermal physiological effect. These findings are in contrast
to topical products which should be mostly effective in
the skin ageing-encountered superficial dermis and epi-
dermis
[36] , where improved skin elasticity is predomi-
nantly caused by an increase in epidermal hydration
[37,
38]
. Xhauflaire-Uhoda et al. [39] investigated anti-wrin-
kle effects of topically used skin care products. They
found no evidence of skin moisturizing after stopping
treatment and, moreover, the low increase in skin hydra-
tion corresponded to normal newly generated corneo-
cytes from deeper skin layers. They found out that the
tested cream and lotion did not penetrate deeply into the
skin barrier, and an anti-wrinkle effect after topical treat-
ment could have been the result of the generating of a skin
surface film which hindered water evaporation. More-
over, beyond the effectivity of topical treatments, Burac-
zewska et al.
[40] (2007) could show that a topical long-
term treatment with hydrocarbon cream did not elevate
skin hydration but led to an impaired skin barrier and an
increased TEWL.
Skin elasticity is a very important marker for skin aging.
In a clinical study on postmenopausal women, Su mino et
al.
[26] investigated the decline of skin elasticity per year
in comparison to premenopausal subjects. From the find-
ing that skin elasticity was negatively correlated with age
0.7
0.8
0.9
1.0
1.1
1.4
1.3
1.2
1.5
4 weeks 8 weeks
x-fold of placebo
2.5 g/day VERISOL 5 g/day VERISOL
women <50 years
4 weeks 8 weeks 4 weeks 8 weeks
2.5 g/day VERISOL 5 g/day VERISOL
ZRPHQ\HDUV
4 weeks 8 weeks
0
0.20
0.40
0.60
0.80
1.00
1.20
VERISOL 2.5 g/day VERISOL 5 g/day
x-fold of placebo
Baseline
4 weeks 8 weeks
Fig. 8. Skin roughness changes during time of treatment. Within
the entirety of both CH-treated groups no skin roughness effects
were observed during the time of treatment (mean ± SEM, n 22).
Fig. 7. Skin evaporation changes in age-re-
lated subgroups. TEWL was reduced in el-
derly women 4 and 8 weeks after CH treat-
ment in comparison to placebo adminis-
tration (n 9).
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Proksch /Segger /Degwert /Schunck /
Zague
/Oesser
Skin Pharmacol Physiol 2014;27:47–55
DOI: 10.1159/000351376
54
and years after the climacteric period, they calculated a
0.55% declining skin elasticity per year after menopause.
It is well known that besides skin hydration, elasticity is
especially influenced by dermal collagen [41, 42] . This re-
lation was observed by Marini et al.
[43] , who described a
correlation between skin elasticity and hydration and col-
lagen type I RNA expression after oral treatment.
Experimental studies on primary human dermal fibro-
blasts demonstrated a stimulatory effect of the specific CH
used in this study on the expression of skin extracellular
matrix macromolecules. After supplementation of the
CPs to fibroblast cultures a pronounced increase of type I
collagen expression as well as in the expression of proteo-
glycans like biglycan, decorin and versican could be ob-
served (data not shown). Although further investigations
are needed, it could be speculated that the observed posi-
tive effect of CH on skin elasticity might be caused by an
increase of dermal matrix macromolecule biosynthesis.
With regard to the investigated skin moisturizing pa-
rameters, overall results revealed that skin evaporation
and skin hydration were unchanged in both CH treat-
ment groups. However, a tendency of reduced skin evap-
oration and an increased skin moisturizing effect were
observed in elderly women as indicated in the subgroup
analysis. Besides loss of skin elasticity, xerosis is described
as a common skin problem of the elderly
[44–46] . Thus,
data suggest that, especially in this group, CH treatment
might have a positive impact on skin hydration.
Interestingly, although skin moisture content and
TEWL should correlate with skin microtexture and skin
roughness, no changes of this parameter could be mea-
sured in the present study.
Over the treatment period of 8 weeks no visible chang-
es of the skin roughness by CH ingestion in comparison
to placebo were detectable. It might be speculated that the
duration of treatment and localization of measurement at
the sunlight-protected inner side of the forearm might be
responsible for these observations. On the other hand,
Sato et al.
[47] observed a significant correlation between
skin roughness and the thickness of the stratum corneum.
As it is known that skin thickness decreases with age, this
aspect could possibly explain the lack of a pronounced ef-
fect of CH on skin roughness, as detected in the present
study
[1] .
In conclusion, the results of the study clearly demon-
strated that the oral intake of a specific CH led to a statis-
tically significant increase in skin elasticity. Moreover, a
skin moisturizing effect could be observed in elderly
women, although results did not reach a level of statistical
significance. In contrast to most topically applied sub-
stances this positive effect of orally applied CH on skin
health seems to be long-lasting, especially in women over
50 years of age. Overall CH intake over a longer period
seems to have a positive impact on skin health. It has to
be stated that the demonstrated efficacy refers to the spe-
cific CP composition (VERISOL) used in this study and
could not be extrapolated to CH in general.
More research is needed, especially regarding the
mode of action and to confirm the clinical efficacy. In a
follow-up clinical study it could be interesting to investi-
gate the effect of a CP supplementation on dermal matrix
macromolecule synthesis and the clinical efficacy, for ex-
ample on wrinkle formation.
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... In another RCT, women were allocated to 4 different arms [20]. The first arm received 2.5 grams of collagen hydrolysate, the second arm was given 5.0 grams of collagen hydrolysate, the third arm received 2.5 grams of a placebo, and the fourth arm was given 5.0 grams of placebo [20]. ...
... In another RCT, women were allocated to 4 different arms [20]. The first arm received 2.5 grams of collagen hydrolysate, the second arm was given 5.0 grams of collagen hydrolysate, the third arm received 2.5 grams of a placebo, and the fourth arm was given 5.0 grams of placebo [20]. Participants were followed for around 60 days, and it was found that each treatment arm with a different dose of collagen hydrolysate showed a statistically noteworthy rise in the elasticity of the skin when juxtaposed with their counterparts in 2 placebo groups. ...
... Participants were followed for around 60 days, and it was found that each treatment arm with a different dose of collagen hydrolysate showed a statistically noteworthy rise in the elasticity of the skin when juxtaposed with their counterparts in 2 placebo groups. Improvement in elasticity was noticed among elderly women relatively earlier (ie, at 1-month follow-up) [20]. ...
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In recent years there has been an increasing interest in the use of nutritional supplements to benefit human skin. Molecular evidence substantiating such effects, however, is scarce. In the present study we investigated whether nutritional supplementation of women with the standardized pine bark extract Pycnogenol® will improve their cosmetic appearance and relate these effects to expression of corresponding molecular markers of their skin. For this purpose 20 healthy postmenopausal women were supplemented with Pycnogenol for 12 weeks. Before, during and after supplementation, their skin condition was assessed (i) by employing non-invasive, biophysical methods including corneometry, cutometry, visioscan and ultrasound analyses and (ii) by taking biopsies and subsequent PCR for gene expression analyses related to extracellular matrix homeostasis. Pycnogenol supplementation was well tolerated in all volunteers. Pycnogenol significantly improved hydration and elasticity of skin. These effects were most pronounced in women presenting with dry skin conditions prior to the start of supplementation. The skin-physiological improvement was accompanied by a significant increase in the mRNA expression of hyaluronic acid synthase-1 (HAS-1), an enzyme critically involved in the synthesis of hyaluronic acid, and a noticeable increase in gene expression involved in collagen de novo synthesis. This study provides skin-physiological and for the first time molecular evidence that Pycnogenol supplementation benefits human skin by increasing skin hydration and skin elasticity. These effects are most likely due to an increased synthesis of extracellular matrix molecules such as hyaluronic acid and possibly collagen. Pycnogenol supplementation may thus be useful to counteract the clinical signs of skin aging.
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The collagen present in the dermis of the skin is a fibrous protein that fills the gaps between cells and helps maintain tissue flexibility. Effectively increasing the collagen present in the skin is an important goal for cosmetic research. Recent research has shown that soybean peptide (SP) has anti-fatigue activity, antioxidant activity, and the ability to increase type I collagen, while collagen peptide (CP) has the ability to enhance corneal moisture content and viscoelasticity, as well as to increase levels of hyaluronic acid synthesizing enzymes in human skin. Little documented research, however, has been conducted on collagen formation in relation to these peptides. Therefore, this research applied SP and CP with molecular weights primarily around 500 and preparations containing both SP and CP to normal human dermal fibroblasts together with magnesium ascorbyl phosphate (VC-PMg), and used real-time PCR to determine the gene expression of type I collagen (COL1A1), which contributes to collagen synthesis, and Smad7, which contribute to collagen breakdown. In addition, enzyme linked immuno sorbent assay (ELISA) was used to measure collagen content in the media. COL1A1 gene expression at 24 h after sample addition showed higher tendency in all samples and increased with time at 4, 8 and 24 h after addition. Smad7 gene expression was not substantially different at 4 h after addition. matrix metalloproteinase-1 gene expression was higher following SP addition, but was lower after the addition of CP and SP+CP. Medium collagen content was higher in all samples and increased with time at 8 h after addition. Collagen levels were higher when SP and CP were added together.
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Limited information is available concerning the prevalence and risk factors of xerosis in the elderly. To establish the prevalence of xerosis and associated factors in elderly patients. A national, multicenter, observational, cross-sectional study in patients aged 65 or older was performed. The data collected by general practitioners were demographics and medical history, including history of atopic disease. Xerosis was evaluated using the Overall Dry Skin score. 756 patients were included. The prevalence of xerosis was 55.6%. Xerosis was significantly associated with older age (OR: 1.48, 95% CI: 1.16-1.89), female sex (OR: 1.80, 95 CI%: 1.29-2.53), treatments that can potentially cause xerosis (OR: 2.21, 95 CI%: 1.54-3.17), itching during sweating (OR: 7.11, 95% CI: 3.90-12.95), a history of dry skin (OR: 2.89, 95% CI: 1.65-5.08) and a history of atopic dermatitis (OR: 3.60, 95% CI: 1.99-6.52). Xerosis is highly prevalent in the elderly. A history of atopy, especially atopic dermatitis, is associated with an increased risk of xerosis in the elderly.
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To investigate the long-term effects of marine collagen hydrolysate (MCH) from Chum Salmon skin on the aberrant collagen matrix homeostasis in chronological aged skin, Sprague-Dawley male rats of 4-wk-old were orally administrated with MCH at the diet concentrations of 2.25% and 4.5% for 24 mo. Histological and biochemical analysis revealed that MCH had the potential to inhibit the collagen loss and collagen fragmentation in chronological aged skin. Based on immunohistochemistry and western blot analysis, collagen type I and III protein expression levels in MCH-treated groups significantly increased as compared with the aged control group. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed MCH was able to increase the expressions of procollagen type I and III mRNA (COL1A2 and COL3A1) through activating Smad signaling pathway with up-regulated TGF-βRII (TβRII) expression level. Meanwhile, MCH was shown to inhibit the age-related increased collagen degradation through attenuating MMP-1 expression and increasing tissue inhibitor of metalloproteinases-1 expression in a dose-dependent manner. Moreover, MCH could alleviate the oxidative stress in chronological aged skin, which was revealed from the data of superoxide dismutase activity and the thiobarbituric acid reactive substances level in skin homogenates. Therefore, MCH was demonstrated to have the protective effects on chronological skin aging due to the influence on collagen matrix homeostasis. And the antioxidative property of MCH might play an important role in the process.
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The effect of daily ingestion of collagen hydrolysate (CH) on skin extracellular matrix proteins was investigated. Four-week-old male Wistar rats were fed a modified AIN-93 diet containing 12% casein as the reference group or CH as the treatment group. A control group was established in which animals were fed a non-protein-modified AIN-93 diet. The diets were administered continuously for 4 weeks when six fresh skin samples from each group were assembled and subjected to extraction of protein. Type I and IV collagens were studied by immunoblot, and activities of matrix metalloproteinase (MMP) 2 and 9 were assessed by zymography. The relative amount of type I and IV collagens was significantly (P < .05) increased after CH intake compared with the reference diet group (casein). Moreover, CH uptake significantly decreased both proenzyme and active forms of MMP2 compared with casein and control groups (P < .05). In contrast, CH ingestion did not influence on MMP9 activity. These results suggest that CH may reduce aging-related changes of the extracellular matrix by stimulating anabolic processes in skin tissue.
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Synopsis There have been few reports classifying the biophysical characteristics of Korean women with healthy skin. Consequently, the aim of this study was to find the most useful parameters for categorizing skin types based on a clinical assessment. One hundred and three female volunteers, aged 20-59, participated in this study. We conducted a self-evaluation questionnaire, a clinical assessment of the facial skin, and non-invasive measurements on the cheek under controlled environmental conditions. The questionnaire survey indicated that 72% of respondents had dry skin. However, results of the clinical assessment focusing on skin roughness and scaling of the cheek showed that 6 subjects had very dry skin (6%), 29 had dry skin (28%) and 68 had normal skin with sufficient moisture (66%). We analysed the correlation between the clinical assessment and biophysical parameters. As a result, we obtained six biophysical parameters that had relatively higher correlations with clinical assessment than other parameters. Our study provided general information about the physiological characteristics of normal skin in Korean women and suggested useful parameters for characterizing dry skin. © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.