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Summary
reflectance
confocal
Introduction
Nutrition is known to have a major influence on skin
physiology. Thus, a good nutritional status is reflected
in good skin health perceived as a surrogate for the
persons well-being. A wide range of nutritional supplements have reported to exert benefits on skin health
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Results
Peptan improves skin hydration in humans
Randomized
(n=106)
Allocated to Peptan
(n=54)
Discontinued (n=3)
Discontinued (n=2)
Completed (n=49)
Completed (n=52)
Analyzed (n=48)
Analyzed (n=51)
Randomized
(n=33)
Allocated to Placebo
(n=11)
Allocated to Peptan F
(n=11)
Allocated to Peptan P
(n=11)
Analyzed
(n=11)
Analyzed
(n=11)
Analyzed
(n=11)
Figure 1 Flowchart of the clinical pilot study performed at SOUKEN laboratories, Japan.
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Allocated to Placebo
(n=52)
ticipants completed the study according to the protocol, with 18 subjects (placebo n = 7, Peptan n = 11)
presenting minor deviations from the protocol regarding the product administration (Fig. 3). No adverse
events were reported. Three subjects were withdrawn
from the placebo group, two on their own request and
one for noncompliance. Two subjects were lost to follow-up from the Peptan group. Reflectance confocal
microscopy data on collagen fragmentation was not
2015 The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.
Age (year)
Phototype (Fitzpatrick)
I
II
III
IV
Skin type
Normal
Dry mixed
Dry
Placebo (n = 49)
Peptan (n = 52)
52.4 (2.6)
54.8 (2.6)
0
19 (39%)
29 (60%)
1 (2%)
2
18
31
1
(4%)
(35%)
(60%)
(2%)
13 (27%)
0
36 (73%)
13 (25%)
1 (2%)
38 (73%)
persisted after 12 weeks of treatment, indicating a consistent increase in collagen density in the dermis over
time. After 12 weeks of Peptan intake, the treatment
effect (12w-0w) was significantly higher than in the
placebo group (8.83% vs. no change, respectively,
P = 0.007) (Fig. 4).
Peptan reduces collagen fragmentation in the human
dermis
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glycosaminoglycan
The above presented data show that oral intake of Peptan in humans improves skin hydration and the quality and quantity of the dermal collagen network. To
better understand how Peptan exerts these actions, we
analyzed the general morphology, glycosaminoglycan,
and collagen content of human skin explants in
response to different concentrations of Peptan.
The general morphology of the skin explants was
not affected by the incubation with Peptan. Both
control and Peptan-treated explants exhibited a slight
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Placebo
(a)
Peptan
Placebo
Peptan
12w
0w
(b)
Fragmentation
Placebo
Peptan
0 weeks
4 weeks
12.4 (1.9)
18.8 (2.4)
13.4 (1.7)
15.5 (2.9)
vs 0w
+8.0%
-17.8%
p
0.929
0.036*
12 weeks
13.1 (1.8)
12.9 (2.4)
vs 0w
+5.9%
-31.2%
p
0.933
0.001**
Figure 5 Effect of the daily oral intake of 10 g Peptan compared to placebo on the collagen network fragmentation of the reticular dermis (n = 4851). (a) Exemplary confocal images showing the collagen network of the reticular dermis before and after 12 weeks of daily
oral intake of 10 g Peptan compared to placebo. (b) Quantification. Values are presented as mean (SEM). Statistical differences were calculated by ANOVA and Dunnetts post hoc test with *P < 0.05, **P < 0.01, ***P < 0.001; *comparison with baseline, comparison with
placebo.
parakeratosis, no evidence of stimulation in the epidermis, and a well-cellularized collagen network in the
papillary dermis (data not shown).
As depicted in Figure 6, the glycosaminoglycan level
in the basal epidermis increased in skin explants in
response to Peptan incubation, visible as blue staining
in the histological slides (Fig. 6a). The quantification of
the images (Fig. 6b) shows that this increase was dosedependent within the range of 0.010.1 mg/mL Peptan with a fivefold and a highly significant 18-fold
increase, respectively. At 1 mg/mL Peptan, saturation
of the effect was reached with a significant 17-fold
increase compared to the control.
In line with the glycosaminoglycan content, Sirius
Red staining of human skin explants revealed that the
collagen content of the papillary dermis increased in
response to incubation with Peptan (Fig. 7a). This
increase was dose-dependent with 3% more collagen in
the presence of 0.01 mg/mL Peptan and a significant
maximal increase of 9% in the presence of 0.1 mg/mL
Peptan (Fig. 7b). Again, saturation of the effect was
reached at 1 mg/mL Peptan with a significant increase
of 5.4%. Given the high basal amount of collagen in
the papillary dermis, a 5% increase is considered to be
a clear biological difference.
Thus, Peptan is highly efficacious to increase the
amount of water-binding glycosaminoglycans and the
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Discussion
Collagen peptides are a bioactive ingredient used in
functional foods and dietary supplements, such as
nutricosmetics, to help improve parameters of skin
physiology. In the present study, we report that the
oral supplementation with specific collagen peptides
(Peptan) improves skin hydration as well as the
density and the structure of the collagen network of
the dermis. To our knowledge, this is the first clinical study showing an effect of collagen peptides on
dermal collagen fragmentation. Analysis of human
skin explants cultured ex vivo in the presence of
specific collagen peptides (Peptan(R)) indicated that
an increase in dermal collagen and epidermal GAG
content might be responsible for the observed physiological effects.
The properties of skin are defined by the complex
architecture of its different layers, which are increasingly degraded during aging. Skin contains up to 70%
of collagen, which provides the tissue with tensile
strength. However, the collagen content declines with
age and this process is accelerated in women by the
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(a)
A
100m
OthP Objec f 40
OthP Objec f 40
100m
100m
OthP Objec f 40
OthP Objec f 40
100m
(b)
30
25
***
***
20
15
10
5
0
Control
Figure 6 Glycosaminoglycan (GAG) content of the basal epidermis in human skin explants (a) visualized by Alcian Blue staining after
incubation with (A) control, (B) 0.01 mg/mL Peptan, (C) 0.1 mg/mL Peptan, (D) 1 mg/mL Peptan for 9 days (representative images).
(b) GAG content was quantified using OLYMPUS CELLD Software and expressed as surface %. Values are presented as mean SEM. Statistical differences were calculated by ANOVA and Dunnetts post hoc test with *P < 0.05, **P < 0.01, ***P < 0.001.
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(a)
B
100m
OthP Objec f 25
100m
OthP Objec f 25
100m
OthP Objec f 25
100m
OthP Objec f 25
(b)
100
***
90
**
80
70
60
50
Control
Figure 7 Total collagen content of the papillary dermis of human skin explants (a) visualized by Sirius Red staining after incubation
with (A) control, (B) 0.01 mg/mL Peptan, (C) 0.1 mg/mL Peptan, (D) 1 mg/mL Peptan for 9 days (representative images). (b) Total collagen content was quantified using OLYMPUS CELLD Software and expressed as surface %. Values are presented as mean SEM. Statistical
differences were calculated by ANOVA and Dunnetts post hoc test with *P < 0.05, **P < 0.01, ***P < 0.001.
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skin layers. These data demonstrate that the oral supplementation with specific collagen peptides can
improve skin structure and health from within.
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