VERISOL WHITE PAPER 2014

VERSION 2014/1

VERISOL
promotes
Product Definition natural food
clean label (no E numbers)
VERISOL is a composition of different specific collagen peptides derived
highly digestible food
from a special hydrolysis of porcine or bovine type I collagen. The product
non-allergenic food
is clearly defined by MALDI-MS mass peaks fingerprint of numerous specific
collagen peptides with an average molecular weight of 2.0 kD.

Preclinical studies
In several scientific experiments the potential of VERISOL for skin cell metabolism
and skin beauty from within was investigated.

Previous bioavailability studies demonstrated that collagen peptides could be detected

in different organs and connective tissues after oral administration1.

Almost 100 % of the orally applied collagen peptides are rapidly absorbed from
the gastrointestinal tract as indicated by a pronounced increase of these peptides
in blood plasma within first 12 hours. Later on these peptides are detectable in
several organs and tissues, including the skin, in divergent amounts.

Skin is one of the predominantly accumulating organs

caused by a high blood flow rate and good absorption Detection of labelled collagen peptides in skin over
of small collagen peptides in this tissue2 (Fig. 1). 192 hours after one single oral application.

In addition to the excellent bioavailability, a positive

effect of VERISOL on skin cell metabolism could be 140

demonstrated in several experiments.

120

Experimental studies on different primary human skin

Radioactivity in skin

100
(Bql/1g tissue)

cell types revealed a stimulatory effect of VERISOL on

the biosynthesis of skin extracellular matrix macromole 80

cules. Treatment of epidermal skin cells (keratinocytes)

60
led to an up-regulation of filaggrin, loricrin and involucrin,
cornified envelope proteins which are important for 40
a healthy epidermal skin barrier and skin moisturizing
(data not shown) 3-5 . 20
0 24 48 72 96 192
Time (h)

Figure 1
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In dermal fibroblasts an increased RNA expression of The RNA expression of different dermal matrix
collagen type I and proteoglycans like versican, decorin molecules was significantly increased in human
and biglycan could be detected (Fig. 2). These structural fibroblasts by VERISOL treatment.
macromolecules are important for skin hydration and
essential factors for elastic or collagen fibre formation
2,5
in the skin 6, 7.

2,0
In addition to a stimulatory efficacy of VERISOL, a
significant anti-oxidative effect as well as an increase

(x-fold of control)
RNA Expression
1,5
of the primary antioxidant enzyme (manganese dependent
superoxide dismutase MnSOD) was demonstrated in
healthy human dermal cells. This positive effect was even 1,0

more pronounced in irritated cells (data not shown).

0,5

In vitro studies were confirmed in an additional random-

ized, placebo controlled animal study on skin hairless mice. 0
VERISOL Decorin Versican Collagen
The efficacy of orally administered VERISOL was inves Type I
tigated on healthy and skin irritated mice. As expected
in both experimental set ups an increased RNA expres- Figure 2
sion of MnSOD in mouse skin was observed. In addition,
inflammatory processes after irritation were down regu-
lated in VERISOL treated animals seen by a decreased Skin elasticity was statistically significantly
expression of inflammatory cytokines, TNF, IL-1 and increased in irritated mouse skin 23 weeks
IL-6 (data not shown). after orally administration of VERISOL.

Moreover, experimental data on several standardized

1,4
skin parameters were performed. The data demonstrated
a disturbed skin barrier function characterized by an 1,2
increased transepidermal water loss (TEWL) in the placebo
1,0
fed animals whereas in VERISOL treated animals TEWL was
(x-fold of control)
Skin Elasticity

unchanged. According to this observation, a significantly 0,8

increased skin moisturizing was detected after VERISOL

0,6
administration in healthy and irritated skin, respectively
(data not shown). In addtion, statistically significantly 0,4

increased skin elasticity was determined 23 weeks after

0,2
VERISOL administration in irritated mouse skin in com-
parison to placebo fed control mice (Fig. 3). 0
VERISOL Placebo

Figure 3
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The observed increased elasticity of the skin in mice after VERISOL treatment could
be explained by an increased biglycan synthesis (Fig. 4), as biglycan is an important
factor for generation of elastic fibre bundles in the skin.

In conclusion, pre-clinical data clearly demonstrate

stimulatory effects of VERISOL on the metabolism Expression of biglycan was pronounced stimulated
of extracellular matrix molecules in skin cells and skin by VERISOL treatment in dermal fibroblasts mice skin.
tissue. VERISOL has a positive impact on skin barrier
function and promotes skin water balance. Moreover,
2,5
VERISOL has a positive influence on the maintenance
and regeneration of skin elasticity.
2,0

Byglycan Expression
(x-fold of control)
Clinical Study
1,5
8

1,0
In a double-blinded, randomized, placebo- controlled
clinical trial the efficacy of orally administered VERISOL
for skin health in two application dosages in comparison 0,5

to a placebo treatment were examined over 12 weeks.

69 qualified, healthy, female voluntary subjects were 0
Dermal normal irritated normal irritated
recruited and subdivided in 23 subjects per treatment Fibroblasts
Placebo VERISOL
group. 68 out of these subjects finished the study cor- Mice Skin
rectly. The volunteers were of ages between 35.3 and
55.4 years (47.8 5.2 years in the mean). Figure 4

Inner sides of both volar forearms (1 test site per forearm) were chosen as test
sites for several standardized skin parameters. Preliminarily before start of orally
treatment and data acquisition, a preconditioning period of at least 7 days was
conducted. Within this period the volunteers had to refrain from using any leave-on
products on the test sites. The study participants were not allowed to change the
usual skin care routine. And the treatment with dermatological therapeutics on the
test areas was not allowed 6 weeks prior to start of the study. In addition to that,
changes of living or dietary habits, consumption of any additional nutritional supple-
ment or vitamin preparations or 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.

Primary Outcome:
skin elasticity (Cutometer SEM 575, 3 repeated measurements)

Secondary Outcome:
transepidermal water loss (TEWL, DermaLab, 3 repeated measurements)
skin hydration (Corneometer CM825, 10 repeated measurements)
skin roughness (micro relief of the skin/replica (SILFLO) analysed by PRIMOS (SQ )
VERISOL WHITE PAPER 2014 Page 4

23 subjects per group were treated with 2.5 g or 5 g of VERISOL or a placebo.

The powder was to be dissolved in water or any other cold liquid. The products
were taken orally by the subjects at home according to the instructions given
by the investigator. The subjects compliance (dosage and way of intake) and
tolerance towards the products were checked after one, four and again after
six weeks of intake.

Before first oral product application (t 0 ), after four (t1) and eight weeks (t 2 )
of intake the transepidermal water loss (TEWL) and skin hydration were measured
at the left forearm and negative casts (replicas, SILFLO) for the analysis of the skin
roughness (microrelief of the skin by PRIMOS (SQ ) were taken at the right forearm.
Skin elasticity was measured before the first oral product application (t 0 ), after
four (t1) and eight weeks (t 2 ) of intake as well as 4 weeks after the last intake
(t 3 , 4-week regression phase).

All procedures were performed in a climate controlled room at 21.5 C ( 1C)

and 50 % ( 5 %) relative humidity after participants had adapted themselves
to this indoor climate for at least 30 minutes.

Drop Outs
There was only one drop out because of not next defined private reasons.

Discomfort Adverse Skin Reactions

There was no discomfort or adverse reactions reported.

Both VERISOL treated groups showed a statistically

Results higher elasticity after 4 and 8 weeks of VERISOL
ingestion (mean SEM, n 22, p < 0.05).
Both VERISOL dosages led to statistically significantly
higher skin elasticity (up to 15 %) compared to placebo
treatment already after 4 weeks of intake and this effect Skin Elasticity Changes in Time of Treatment
1,15
was persistent after 8 weeks of orally VERISOL administra Baseline 4 weeks 8 weeks
tion (Fig. 5). Another 4 weeks after last intake of the product,
VERISOL application still showed higher skin elasticity 1,10
(x-fold of placebo)

levels than in the placebo treated volunteers by trend.

Skin Elasticity

1,05

1,00

0,95
VERISOL VERISOL
2.5 g/day 5 g/day

Figure 5
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In more detailed subgroup analysis it could be demon- Skin elasticity was statistically significantly increased
strated that the positive impact of VERISOL treatment by VERISOL treatment. This positive effect was already
on skin elasticity seems to be more pronounced in elderly sufficient with a daily dosage of 2.5 g of VERISOL and
women aged 50 + (Fig. 6). clearly more pronounced in elderly women ( 50 years).

The positive effect on skin elasticity was persisting Skin Elasticity Changes in Age related Subcategories
over a wash-out period of 4 weeks. In a follow-up exami 1,15
VERISOL 2.5 g/day
nation without VERISOL intake 92 98 % of the positive > 50 years
VERISOL 5 g/day
effect for skin elasticity were still seen in both age sub- Placebo
1,10
categories (Fig. 7).

(x-fold of placebo)
Skin Elasticity
< 50 years
In addition to these observations VERISOL treatment 1,05

led to an increased hydration of skin (1114 %) in women.

This moisturizing effect of VERISOL was also attended 1,00
with lower skin evaporation (6-7 %) which indicates that
VERISOL treatment improves epidermal barrier regene
0,95
ration and matrix synthesis of dermal proteoglycans in Beginning Time of Treatment 8 weeks
aged skin (Fig. 8 a, b).
Figure 6

Skin evaporation (a) and hydration (b) are both Four weeks after last VERISOL (CH) intake skin elasticity
indications for a healthy skin barrier function and in elderly women (50+) was statistically significantly
implicate a stimulatory effect of VERISOL treatment increased after both CH dosages in comparison to placebo
for regeneration of cutaneous matrix molecules. control treatment (mean SEM, n 9, p < 0.05).

a Skin Evaporation Changes in Age related Subcategories Long-lasting Effect on Skin Elasticity Changes
1,50 in Age related Subcategories
VERISOL 2.5 g/day 1,3
1,40
VERISOL 5 g/day VERISOL CH 2.5 g/day VERISOL CH 5 g/day
1,30
(x-fold of placebo)

1,2
Skin Evaporation

1,20
(x-fold of placebo)
Skin Elasticity

1,10 1,1

1,00
1,0
0,90

0,80 0,9
0,70
eks weeks weeks weeks eks weeks weeks weeks
4 we 8 4 8 4 we 8 4 8 0,8
subclass age < 50 subclass age > 50 subclass age < 50 subclass age > 50

b Skin Hydration Changes in Age related Subcategories

1,40
Figure 7

1,20
(x-fold of placebo)
Skin Hydration

1,00

0,80

Figure 8 a, b
0,60

0,40
Changes of skin smoothness was also evaluated in this study
eks weeks weeks weeks eks weeks weeks weeks
4 we 8 4 8 4 we 8 4 8 but results failed to reach level of statistically significance. Skin
subclass age < 50 subclass age > 50
roughness after low dosage VERISOL treatment was decreased
by trend (24 %) in all included volunteer subjects.
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Clinical Follow up Study 9

In a monocentric 12 weeks double-blinded, randomized, placebo-controlled
clinical follow up study, the efficacy of orally administered VERISOL for skin
wrinkle improvement of eye wrinkles as a primary objective in comparison to
a placebo treatment were examined. The secondary objective of the study was
the detection of accumulated pro-collagen type I, tropo-elastin and fibrillin
in suction blister fluids.

115 qualified, healthy, female voluntary subjects were recruited and subdivided
in 57 subjects per treatment group. 114 out of these subjects finished the study
correctly. The volunteers were of ages between 45.0 and 65.4 years (55.6 6.0 years
in the mean). 48 out of the 115 subjects (24 per treatment group) were included
for the suction blister generation.

Inner side of right volar forearm was chosen as collecting sites for suction blister
fluid, the wrinkle area around the left eye for eye wrinkle measurements and the
whole face for photo documentation. Preliminarily before start of orally treatment
and data acquisition a preconditioning period of at least 7 days was conducted.
Within this period the volunteers had to refrain from using any leave-on, oily or
moisturizing products on the right arm and eye areas. The study participants were
not allowed to change the usual skin care routine or expose test sites intensively
to UV light. And the treatment with dermatological therapeutics on the test areas
was not allowed 4 weeks prior to start of the study. In addition to that, changes
of living or dietary habits, consumption of any additional nutritional supplement
or vitamin preparations or treatment of the right volar forearm with cosmetic and
dermatological skin care products were prohibited.

Primary Outcome:
in vivo measurement of the volume of one selected eye wrinkle using the 3D
in vivo skin measuring system PRIMOS compact (3 repeated measurements in mm3,
wrinkle volume computed by means of a generated height image)

Secondary Outcome:
suction blister generation for subsequent quantitative analysis of pro-collagen
type I, tropo-elastin and fibrillin
photo documentation using the FotoFinder mediscope studio (portrait pictures
in an angle of 45, pictures were to be handed over to the sponsor in agreement
with the subjects)
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57 subjects were treated with VERISOL and 57 subjects with placebo over 8 weeks
followed by a 4-week wash out phase. A dosage of 2.5 g was applied once daily.
The powder was to be dissolved in water or any other cold liquid. The products were
taken orally by the subjects at home according to the treatment diary and the instruc-
tions given by the investigator. The subjects compliance (correct dosage and way
of intake, dietary habits) and tolerance towards the products were checked after one
and six weeks of intake.

Before first oral product application (t 0 ), after four (t1) and eight weeks (t 2 ) of
intake, and four weeks after the last intake (t 3, 4-week regression phase) eye wrinkle
volume was measured on the respective test sites. Photo documentation was made
before starting the treatment (t0 ) and after eight weeks of intake (t2 ). For a subgroup
suction blisters were generated before starting the treatment (t 0 ) and after eight
weeks (t 2 ) of intake.

All procedures were performed in a climate controlled room at 21.5 C ( 1C) and
50 % ( 5 %) relative humidity after the subjects had adapted with their uncovered
test areas to these indoor climate conditions for at least 30 minutes.

Drop Outs
There were 8 drop outs (5 of VERISOL and 3 of placebo treatment) because
of private reasons, illness or lack of compliance.

Discomfort Adverse Skin Reactions

Seven subjects (2 of VERISOL group, 5 of placebo group)
reported about feeling of discomfortment and indiges-
tions (flatulence, stomach ache or pyrosis). This was not Orally administered VERISOL led to a statistically signi
considered to be related to the product intake or any study ficantly reduction of eye wrinkle volume after 4 and
procedure. There were no other recorded discomfort 8 weeks of treatment. Over the same period of time eye
adverse reactions. wrinkle volume in the placebo treated group increased
continuously (mean SEM; n = 57, p < 0.05 - 0.01).

Results Volume Changes of Eye Wrinkles

in the Period of Treatment
The results indicated that a daily intake of 2.5 g of 0,5
Eye Wrinkle Volume/ Original Data

VERISOL Placebo
VERISOL led to a pronounced, statistically significant **
reduction in eye wrinkle volume (7.2 %; p < 0.05) com- *
0,4
pared to the placebo group after 4 weeks of treatment.
This clear effect was even more pronounced after 8 weeks,
(mm3)

where the eye wrinkle volume in the verum group was

0,3
statistically significantly decreased (20.1 %) compared
to the placebo group (Fig. 9 a).
0,2
Baseline 4 weeks 8 weeks

Figure 9 a
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Applied to the baseline situations at the beginning Reduction of eye wrinkle volume persisted in
of the study a wrinkle volume difference of 32.2 % VERISOL treated volunteers 4 weeks after last
between the verum and placebo group was calculated intake (mean SEM; n = 57; p < 0.01).
after 8 weeks treatment. Wrinkle volume after VERISOL
treatment had decreased by 17.7 % (maximum levels of Long-lasting Effect on Eye Wrinkle Volume Reduction
50 % reduction) compared to the baseline, whereas in 4 weeks after the End of the Treatment

Eye Wrinkle Volume/ Original Data

0,5
the placebo group in the same time period the wrinkle VERISOL Placebo
volume had increased by 14.5 %.
0,4 **

(mm3)
At the end of a 4-week wash-out phase wrinkle
volume in the verum group was still reduced by 16 % 0,3
compared to the women having received the placebo
(Fig. 9 b; p < 0.05).
0,2
4 weeks
In addition, VERISOL treatment led to a pronounced
accumulation of important dermal elastic fibre com Figure 9 b
ponents in suction blister fluids (Fig.10). Results demon-
strated a statistically significant increase of pro-collagen After this treatment period of time beside collagen and elastin
(65 %, p < 0.01) and elastin (18 %, p < 0.01) after also a statistically significantly accumulation of biglycan (40 %),
an 8-week daily intake of 2.5 g of VERISOL compared important bivalent proteoglycan for formation of elastic fibre
to placebo. Moreover, fibrillin concentration was also bundles as well as hydration in the skin, was detected in relation
increased by 6 %. to placebo (Fig.11).

In summary it can be concluded that a daily intake of 2.5 g

The amount of pro-collagen type I and elastin was of VERISOL has a beneficial impact on skin health, as indicated
statistically significantly increased 8 weeks after by a pronounced, statistically significant reduction in eye wrinkle
VERISOL administration, in contrast to placebo volume. Moreover, data suggest that this positive effect is
treatment. The content of fibrillin in suction blister caused by the detected increase of dermal collagen, elastin
fluid was increased after 8 weeks of VERISOL inges- and biglycan synthesis.
tion by trend (mean SEM; n = 20; p < 0.05).

Accumulation of Extracellular Matrix Molecules Accumulation of extracellular matrix molecules,

after 8 weeks of Orally Ingestion biglycan, elastin and collagen type I was statistically
2,0
* VERISOL Placebo
significantly increased 8 weeks after oral VERISOL
Extracellular Matrix Molecules

1,6
ingestion in comparison to placebo treatment.
(x-fold of baseline)

*
Accumulation of

1,2
1,8 VERISOL Placebo
(x-fold of control)
ECM Synthesis

1,6
0,8
1,4
1,2
0,4
1,0
p < 0.05 p < 0.01 p < 0.05
0,8
0
Pro-collagen Elastin Fibrillin 0,6
Type I Biglycan Elastin Collagen Type I

Figure 10 Figure 11
 VERISOL WHITE PAPER 2014 Page 9

Overall Summary
VERISOL reduced skin depth by more than 30 % VERISOL
after an 8-weeks daily intake of 2.5 g in comparison
to placebo treatment. The positive effect of VERISOL Baseline 8 week Treatment
in wrinkle reduction was sustained and clearly visible
4 weeks after the end of VERISOL treatment (16 %).
This clinical improvement on skin health corresponds
to the increase in collagen and elastin synthesis Patient No. 54
(1.2 -1.6 fold).

The increase in skin elasticity by VERISOL treatment

(2.5 g and 5 g daily) is about 6 8 % after 4 and 8 weeks
of intake in comparison to placebo treated volunteers. Patient No. 61

The fact that the increase in skin elasticity is not

only due an improvement of skin hydration in the outer
epidermis indicates that beside regeneration of skin
barrier stimulatory effects of VERISOL are mainly located Placebo
in dermal tissue. Alongside enhanced skin elasticity it
seems that orally administered VERISOL has positive Baseline 8 week Treatment
influence in dermal matrix molecule metabolism.

VERISOL treatment led to an increased expression of

collagen type I and are moreover involved in formation Patient No. 47
of elastic skin fibres. Hence, an increase in skin elasticity,
most important parameter with a positive influence in
skin-aging, is caused by remarkable alterations in the
dermis after orally VERISOL treatment.
Patient No. 87

Conclusion
Epidermis
Wrinkle In summary it can be concluded that a daily intake of
2.5 g of VERISOL has a beneficial impact on skin health,
as indicated by a pronounced, statistically significant
reduction in wrinkle volume and significantly improved
Dermis skin elasticity. Moreover, data suggest that this positive
effect is caused by the detected increase of dermal collagen,
fibrillin, biglycan and elastin synthesis.

Collagen fiber
VERISOL WHITE PAPER 2014 Page 10

L I T ER AT URE REFERENCE S
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Oesser S, Adam M, Babel W, Seifert J: Oral administration of (14)C labeled gelatin
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2
Watanabe-Kamiyama M, Shimizu M, Kamiyama S, Taguchi Y, Sone H, Morimatsu F,
Shirakawa H, Furukawa Y, Komai M: Absorption and effectiveness of orally administered
low molecular weight collagen hydrolysate in rats.
J Agric Food Chem 27-1-2010;58:835 841.
3
Rawlings AV, Harding CR: Moisturization and skin barrier function.
Dermatol Ther 2004;17 Suppl 1:43 48.
4
Sandilands A, Sutherland C, Irvine AD, McLean WH: Filaggrin in the frontline:
role in skin barrier function and disease.
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Primavera G, Berardesca E: Clinical and instrumental evaluation of a food supplement
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6
Shin JE, Oh JH, Kim YK, Jung JY, Chung JH: Transcriptional regulation of proteoglycans
and glycosaminoglycan chain-synthesizing glycosyltransferases by UV irradiation in
cultured human dermal fibroblasts.
J Korean Med Sci 2011;26:417 424.
7
Reinboth B, Hanssen E, Cleary EG, Gibson MA: Molecular interactions of biglycan and
decorin with elastic fiber components: biglycan forms a ternary complex with tropoelastin
and microfibril-associated glycoprotein 1.
J Biol Chem 8-2-2002;277:3950 3957.
8
Proksch E, Segger D, Degwert J, Schunck M, Zague V, Oesser S: Oral Supplementation of
Specific Collagen Peptides has Beneficial Effects on Human Skin Physiology: A Double-Blind,
Placebo-Controlled Study.
Skin Pharmacol Physiol 2014;27:47 55.
9
Proksch E, Schunck M, Zague V, Segger D, Degwert J, Oesser S: Oral Intake of Specific
Bioactive Collagen Peptides Reduces Skin Wrinkles and Increases Dermal Matrix Synthesis.
Skin Pharmacol Physiol 2014;27:113-119.
VERISOL WHITE PAPER 2014 Page 11

NOT E S
VERISOL WHITE PAPER 2014 Page 12

NOT E S