Proksch 2014
Proksch 2014
Proksch 2014
E-Mail [email protected]
DE–24105 Kiel (Germany)
www.karger.com/spp
E-Mail EProksch @ dermatology.uni-kiel.de
status and as such the skin is influenced by the consump- Table 1. Demographic data of the volunteers per treatment group
tion of dietary substances, including vitamins and anti-
oxidants, fatty acids and hydrolyzed proteins [3]. There- Subjects, n 2.5 g CH 23
5 g CH 23
fore, the effects of nutritional factors on the skin have 2.5 g placebo 23
received increasing attention, and a number of clinical
studies indicated that dietary supplementation can mod- Age (mean) 2.5 g CH 48.7
5 g CH 47.2
ulate skin functions [4]. 2.5 g placebo 47.9
Collagen hydrolysate (CH) has long been used in phar-
Age (SD) 2.5 g CH 4.8
maceuticals and food supplements for improving skin
5 g CH 5.7
and cartilage tissues. It is absorbed in the digestive tract, 2.5 g placebo 5.2
appears in the human blood partly in a small peptide form
Age (min.) 2.5 g CH 35.3
[5, 6] and is accumulated in skin for up to 96 h as shown
5 g CH 36.1
by Oesser et al. [7]. On the basis of in vitro studies, col- 2.5 g placebo 36.2
lagen peptides (CPs) have shown the ability of exerting
Age (max.) 2.5 g CH 55.4
potent antioxidative activities in different oxidative sys- 5 g CH 54.9
tems [8–11]. 2.5 g placebo 54.3
Moreover, CH has been reported to have beneficial bi-
ological functions in skin. Studies have shown that food- Age is expressed in years.
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
Materials and Methods
densities of pig skin and showed that density and diam-
eter of fibroblasts and density of collagen fibrils were sig- Test Product
nificantly larger in the CH group than in the control The test product used in this study was a CH composed of dif-
groups. Tanaka et al. [15] demonstrated that CH inges- ferent specific CPs derived from a special hydrolysis of porcine type
tion inhibited UVB-induced decrease of type I collagen, I collagen. The product was provided by GELITA AG (Eberbach,
Germany), commercially available under the name VERISOL®.
thus improving skin conditions in mice. The product is clearly defined by MALDI-MS mass peak finger-
Recently, Zague et al. [16] investigated the effect of print with specific CPs of an average molecular weight of 2.0 kDa.
daily ingestion of CH on skin extracellular matrix pro-
teins in rats. The relative amount of type I and IV colla- Study Design
gens was significantly increased after CH intake com- The study was carried out as a monocentric, double-blinded,
randomized, placebo-controlled supplementation study on the ef-
pared with the reference diet group (casein). Moreover, fects of a specific CH on skin elasticity (primary interest) and skin
CH uptake significantly decreased both pro-enzyme and hydration, as well as on TEWL and skin roughness (secondary in-
active forms of matrix metalloproteinase-2 compared terests) after 8 weeks of daily intake.
with casein and control groups. This implied that the ef- The study was approved by the Freiburger Ethik-Kommission
fect of CH was protein-specific and did not depend International, Freiburg, Germany, and adhered to current Good
Clinical Practice regulations. All test subjects received detailed in-
merely on an increase of amino acid intake. The authors formation listing every relevant single parameter to the study. All
suggested that CH may reduce aging-related changes of subjects gave signed informed consent after written information
the extracellular matrix by stimulating anabolic process- and a possibility for further questioning.
es in skin tissue.
Although there is convincing evidence, from the pre- Subjects
A total of 69 healthy female subjects were enrolled in the study;
clinical perspective, that CH ingestion may improve skin 23 subjects were randomized to each of 3 treatment groups to re-
conditions and even protect skin from UV damage, little ceive a daily dose of either 2.5 or 5.0 g of CH or 2.5 g of the placebo
is known about the clinical effects of CH on skin param- (maltodextrin). There were no differences between the treatment
eters and health. The aim of our study was to evaluate the and the placebo groups (table 1) with regard to age (p = 0.664).
potential benefits of an oral supplement containing spe- The products were taken orally by the subjects at home accord-
ing to the instructions given by the investigator. The powder was
cific CP on skin parameters related to cutaneous physiol- to be dissolved in water or any other cold liquid.
ogy and aging, including skin elasticity, hydration, rough- Prior to the beginning of oral treatment and data acquisition a
ness and transepidermal water loss (TEWL). preconditioning period of at least 7 days was conducted. Within
130.240.43.43 - 9/3/2013 3:22:14 PM
Lulea Tekniska Universitet
x-fold of placebo
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 1.05
groups). The hypothesis of a normal distribution was accepted
when there was a p value >0.025 (primary interests). Concerning 1.00
the differences between the treatment situations, a p value of 0.05
was considered as a statistically significant difference. 0.95
To test for significance of differences between the treatment VERISOL 2.5 g/day VERISOL 5 g/day
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- Fig. 1. Skin elasticity changes during the time of treatment. Prior to
mally distributed data was to be used. The following treatment the beginning of the treatment, no statistically significant difference
situations were compared: treatment situations at points in time t0 in skin elasticity was detected in comparison to the placebo group.
(original data), t1, t2 and t3 (data relative to t0). The data relative Both CH-treated groups showed a statistically higher elasticity after
to t0 were computed as follows: treatment situation at tx = 1, 2, 3/ 4 and 8 weeks of CH ingestion (mean ± SEM, n ≥ 22, p < 0.05).
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 Table 2. Age-related subcategories per treatment group
for significance of differences between treatment groups the
one-way ANOVA (the post hoc Fisher LSD) for normally dis- Treatment group <50 years, n ≥50 years, n
tributed data was used. The following treatment situations were
compared: t2 and t3 (data relative to t0). The data relative to t0 2.5 g CH 14 9
were computed as follows: treatment situation at tx = 2, 3/treat- 5 g CH 15 8
ment situation at t0. 2.5 g placebo 13 9
1.2
x-fold of placebo
1.1
1.0
0.9
Fig. 2. Skin elasticity changes in age-related 4 weeks 8 weeks 4 weeks 8 weeks 4 weeks 8 weeks 4 weeks 8 weeks
subgroups. Skin elasticity was statistically
2.5 g/day VERISOL 5 g/day VERISOL 2.5 g/day VERISOL 5 g/day VERISOL
significantly increased in elderly women
women <50 years ZRPHQ\HDUV
(50+) after both CH dosages in comparison
to the placebo control treatment (n ≥ 9).
1.3 1.20
Baseline 4 weeks 8 weeks
1.2 1.00
x-fold of placebo
x-fold of placebo
1.1 0.80
1.0 0.60
0.9 0.40
0.8 0.20
CH CH CH CH
2.5 g/day 5 g/day 2.5 g/day 5 g/day 0
Subclass age <50 6XEFODVVDJH VERISOL 2.5 g/day VERISOL 5 g/day
Fig. 3. Long-lasting effect on skin elasticity changes in age-related Fig. 4. Skin hydration changes during the time of treatment. With-
subcategories. At 4 weeks after the last CH intake, skin elasticity in in the entirety of both CH-treated groups, no skin hydration
elderly women (50+) was statistically significantly increased in effects were observed during the time of treatment (mean ± SEM,
both CH dosages in comparison to the placebo control treatment n ≥ 22).
(mean ± SEM, n ≥ 9, p < 0.05).
1.2
x-fold of placebo
1.0
0.8
0.6
0.4
Fig. 5. Skin hydration changes in age-relat- 4 weeks 8 weeks 4 weeks 8 weeks 4 weeks 8 weeks 4 weeks 8 weeks
ed subgroups. Skin hydration was in-
2.5 g/day VERISOL 5 g/day VERISOL 2.5 g/day VERISOL 5 g/day VERISOL
creased in elderly women (50+) 8 weeks af-
women <50 years ZRPHQ\HDUV
ter both CH dosages in comparison to the
placebo control treatment (n ≥ 9).
0.80
During the last decade the influence of ingested CH on
0.60 skin physiology has been investigated by several groups.
0.40 In experimental studies the authors examined fibroblast
0.20 growth, dermal extracellular matrix synthesis, antioxida-
tive protection and reduction of skin wrinkle formation
0
VERISOL 2.5 g/day VERISOL 5 g/day [11, 13, 15, 22, 23, 29–34]. These investigations suggested
that CPs may improve skin appearance and function in
skin tissue.
Fig. 6. Skin evaporation changes during the time of treatment. So far, only a few controlled clinical studies have been
Within the entirety of both CH-treated groups, no skin evapora- performed to investigate the effect of orally administered
tion effects were observed during the time of treatment (mean
± SEM, n ≥ 22).
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-
Discussion sults clearly revealed that both dosages (2.5 and 5.0 g) of
the specific CH had a beneficial effect on skin physiology,
Human skin physiology changes during the course of as indicated by increased skin elasticity after 4 weeks of
life. While chronological or intrinsic aging is character- daily consumption. The observed effect was statistically
ized by a reduction of skin thickness, loss of skin elastic- significant (p < 0.05) after 4 and 8 weeks in the treatment
ity, collagen fibre degeneration, xerosis and wrinkle for- groups compared to placebo. In some women a maximum
mation [21–27], extrinsic or photoaging caused by sun- increase of skin elasticity up to 30% could be observed af-
light exposition leads to deep-wrinkled, dyspigmented ter an 8-week treatment. Interestingly, only a relatively
skin and the formation of small dilated blood vessels near small number of 23 women per group were needed to
130.240.43.43 - 9/3/2013 3:22:14 PM
Lulea Tekniska Universitet
1.4
1.3
x-fold of placebo
1.2
1.1
1.0
0.9
0.8
0.7
Fig. 7. Skin evaporation changes in age-re- 4 weeks 8 weeks 4 weeks 8 weeks 4 weeks 8 weeks 4 weeks 8 weeks
lated subgroups. TEWL was reduced in el- 2.5 g/day VERISOL 5 g/day VERISOL 2.5 g/day VERISOL 5 g/day VERISOL
derly women 4 and 8 weeks after CH treat-
women <50 years ZRPHQ\HDUV
ment in comparison to placebo adminis-
tration (n ≥ 9).
The fact that this positive effect was still detectable at the
1.20 end of the 4-week washout phase suggests a long-lasting
Baseline 4 weeks 8 weeks
1.00
dermal physiological effect. These findings are in contrast
to topical products which should be mostly effective in
x-fold of placebo
0.80
the skin ageing-encountered superficial dermis and epi-
0.60 dermis [36], where improved skin elasticity is predomi-
0.40 nantly caused by an increase in epidermal hydration [37,
0.20 38]. Xhauflaire-Uhoda et al. [39] investigated anti-wrin-
0
kle effects of topically used skin care products. They
VERISOL 2.5 g/day VERISOL 5 g/day found no evidence of skin moisturizing after stopping
treatment and, moreover, the low increase in skin hydra-
tion corresponded to normal newly generated corneo-
Fig. 8. Skin roughness changes during time of treatment. Within cytes from deeper skin layers. They found out that the
the entirety of both CH-treated groups no skin roughness effects tested cream and lotion did not penetrate deeply into the
were observed during the time of treatment (mean ± SEM, n ≥ 22).
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-
clearly demonstrate the efficacy of the verum. The group over, beyond the effectivity of topical treatments, Burac-
size was predefined by a power calculation (test power zewska et al. [40] (2007) could show that a topical long-
80%) based on previously published investigations. term treatment with hydrocarbon cream did not elevate
In a subgroup analysis it could be demonstrated that skin hydration but led to an impaired skin barrier and an
the statistically significant increase in skin elasticity after increased TEWL.
CH ingestion was even more pronounced in women aged Skin elasticity is a very important marker for skin aging.
over 50 years compared to younger women (p < 0.05). In a clinical study on postmenopausal women, Sumino et
The validity of these results could be confirmed by a pow- al. [26] investigated the decline of skin elasticity per year
er calculation. Due to the small variances within the mea- in comparison to premenopausal subjects. From the find-
sured data a test power of more than 90% was determined. ing that skin elasticity was negatively correlated with age
130.240.43.43 - 9/3/2013 3:22:14 PM
Lulea Tekniska Universitet
References
1 Smalls LK, Randall WR, Visscher MO: Effect 6 Iwai K, Hasegawa T, Taguchi Y, Morimatsu F, 9 Mendis E, Rajapakse N, Kim SK: Antioxidant
of dermal thickness, tissue composition, and Sato K, Nakamura Y, Higashi A, Kido Y, Na- properties of a radical-scavenging peptide pu-
body site on skin biomechanical properties. kabo Y, Ohtsuki K: Identification of food-de- rified from enzymatically prepared fish skin
Skin Res Technol 2006;12:43–49. rived collagen peptides in human blood after gelatin hydrolysate. J Agric Food Chem 2005;
2 Calleja-Agius J, Muscat-Baron Y, Brincat MP: oral ingestion of gelatin hydrolysates. J Agric 53:581–587.
Skin ageing. Menopause Int 2007;13:60–64. Food Chem 2005;53:6531–6536. 10 Mendis E, Rajapakse N, Byun HG, Kim SK:
3 Draelos ZD: Nutrition and enhancing youth- 7 Oesser S, Adam M, Babel W, Seifert J: Oral Investigation of jumbo squid (Dosidicus gi-
ful-appearing skin. Clin Dermatol 2010; 28: administration of 14C-labeled gelatin hydro- gas) skin gelatin peptides for their in vitro
400–408. lysate leads to an accumulation of radioactiv- antioxidant effects. Life Sci 2005; 77: 2166–
4 Zague V: A new view concerning the effects of ity in cartilage of mice (C57/BL). J Nutr 1999; 2178.
collagen hydrolysate intake on skin proper- 129:1891–1895. 11 Li B, Chen F, Wang X, Ji B, Wu Y: Isolation
ties. Arch Dermatol Res 2008;300:479–483. 8 Kim SK, Kim YT, Byun HG, Park PJ, Ito H: and identification of antioxidative peptides
5 Ohara H, Matsumoto H, Ito K, Iwai K, Sato Purification and characterization of antioxi- from porcine collagen hydrolysate by consec-
K: Comparison of quantity and structures of dative peptides from bovine skin. J Biochem utive chromatography and electrospray ion-
hydroxyproline-containing peptides in hu- Mol Biol 2001;34:219–224. ization mass spectrometry. Food Chem 2007;
man blood after oral ingestion of gelatin hy- 102:1135–1143.
drolysates from different sources. J Agric
Food Chem 2007;55:1532–1535.
130.240.43.43 - 9/3/2013 3:22:14 PM
Lulea Tekniska Universitet