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Dietary Supplementation with Specific Collagen Peptides Has a Body Mass Index-Dependent Beneficial Effect on Cellulite Morphology

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In this double-blind, placebo-controlled clinical study, we investigated the efficacy of specific bioactive collagen peptides (BCP) on the cellulite treatment of normal and overweight women. In total, 105 women aged 24-50 years with moderate cellulite were randomized to orally receive a daily dosage of 2.5 g BCP or a placebo over 6 months. The degree of cellulite was evaluated before starting the treatment and after 3 and 6 months of intake. In addition, skin waviness, dermal density, and the length of subcutaneous borderline were assessed. BCP treatment led to a statistically significant decrease in the degree of cellulite and a reduced skin waviness on thighs (P < 0.05) in normal weight women. Moreover, dermal density was significantly improved (P < 0.05) compared to placebo. The subcutaneous borderline showed a significant shortening after BCP intake compared to the beginning of the study, indicating cellulite improvement, but the data failed to reach statistical significance compared to placebo. The efficacy of BCP treatment was also confirmed in overweight women, although the impact was less pronounced in comparison with women of normal body weight. The results of the study demonstrated that a regular ingestion of BCP over a period of 6 months led to a clear improvement of the skin appearance in women suffering from moderate cellulite. Based on the current data, it can be concluded that a long-term therapy with orally administered BCP leads to an improvement of cellulite and has a positive impact on skin health.
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FULL COMMUNICATION
Dietary Supplementation with Specific Collagen Peptides
Has a Body Mass Index-Dependent Beneficial Effect on Cellulite Morphology
Michael Schunck,
1
Vivian Zague,
2
Steffen Oesser,
1
Ehrhardt Proksch
3
1
CRI, Collagen Research Institute, Kiel, Germany.
2
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sa
˜oPaulo,Sa
˜o Paulo, Brazil.
3
Department of Dermatology, Christian-Albrechts-University of Kiel, Kiel, Germany.
1
ABSTRACT In this double-blind, placebo-controlled clinical study, we investigated the efficacy of specific bioactive
collagen peptides (BCP) on the cellulite treatment of normal and overweight women. In total, 105 women aged 24–50 years
with moderate cellulite were randomized to orally receive a daily dosage of 2.5 g BCP or a placebo over 6 months. The degree
of cellulite was evaluated before starting the treatment and after 3 and 6 months of intake. In addition, skin waviness, dermal
density, and the length of subcutaneous borderline were assessed. BCP treatment led to a statistically significant decrease in
the degree of cellulite and a reduced skin waviness on thighs (P<0.05) in normal weight women. Moreover, dermal density
was significantly improved (P<0.05) compared to placebo. The subcutaneous borderline showed a significant shortening after
BCP intake compared to the beginning of the study, indicating cellulite improvement, but the data failed to reach statistical
significance compared to placebo. The efficacy of BCP treatment was also confirmed in overweight women, although the
impact was less pronounced in comparison with women of normal body weight. The results of the study demonstrated that a
regular ingestion of BCP over a period of 6 months led to a clear improvement of the skin appearance in women suffering
from moderate cellulite. Based on the current data, it can be concluded that a long-term therapy with orally administered BCP
leads to an improvement of cellulite and has a positive impact on skin health.
KEY WORDS: bioactive collagen peptide body mass index cellulite collagen hydrolysate dermis density dietary
supplement oral administration randomized controlled clinical trial
INTRODUCTION
Cellulite is a complex problem that affects *85% of
women over the age of 20. It occurs mainly on the
thighs, buttocks, and abdomen and is characterized by or-
ange peel or cottage cheese appearance.
1
Cellulite involves multifactorial etiologies, including
genetic predisposition, gender differences, age, ethnicity,
diet, sedentary lifestyle, and pregnancy.
2,3
It is characterized
by the presence of excess subcutaneous fat that bulges into
the dermis, blood, and lymphatic disturbances and altered
dermal extracellular matrix.
Although cellulite is often present in healthy nonobese
patients, it is exacerbated by overweight. Clinical grades of
cellulite are positively correlated with body mass index
(BMI).
4
Mirrashed et al.
4
and Hexsel et al.
5
reported that
affected individuals with higher BMIs have a weaker, less
dense connective tissue structure, leading to the increased
extrusion of adipose tissue lobules into the dermis.
A variety of therapies have been proposed for the cellulite
treatment, including weight loss, exercises, massage, and
various topical agents, as well as oral supplements and
functional foods.
2,6,7
However, there are few scientifically
reported studies examining the extent to which they improve
the condition. Successful treatment of cellulite will ulti-
mately depend on an improvement in the understanding of
the pathophysiology of cellulite adipose tissue.
6
It is com-
monly accepted that dermal and subcutaneous connective
tissue, which has been weakened by altered and disordered
extracellular matrix, plays a key role in the pathophysiology
of cellulite and contributes to the irregular and dimpled
appearance of cellulite-affected skin. Consequently, thera-
pies aiming to restore the normal structure of the dermis and
subcutaneous tissue can be a meaningful approach to im-
proving the cellulite condition.
2,3,6,7
Dietary supplementation with collagen peptides has dem-
onstrated a notably stimulatory effect on dermal cellular
metabolism, improving the biosynthesis of extracellular ma-
trix proteins and, consequently, restoring dermal structure.
Manuscript received 11 February 2015. Revision accepted 31 August 2015.
Address correspondence to: Ehrhardt Proksch, MD, PhD, Department of Dermatology,
Christian-Albrechts-University of Kiel, Schittenhelmstr. 7, Kiel D-24105, Germany,
E-mail: eproksch@dermatology.uni-kiel.de
#Michael Schuncket al. 2015; Published by MaryAnn Liebert, Inc. This Open Accessarticle is distributedunder the terms of the CreativeCommons Attribution Noncommercial License(http://
creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
JOURNAL OF MEDICINAL FOOD
J Med Food 00 (0) 2015, 1–9
DOI: 10.1089/jmf.2015.0022
1
There is an agreement that biological effects promoted by
food-derived collagen peptides are related to the ingestion of
collagen in its hydrolyzed form. Collagen peptides are a
bioavailable food supplement without any side effects that are
derived from native collagen by heat denaturation and further
enzymatic hydrolysis.
8,9
Specific and complex multistep hy-
drolysis gives rise to biologically active collagen peptides,
which have been proven to stimulate dermal metabolism and
have positive effects on skin properties.
10,11
Although it is generally believed that collagen-derived
products are hydrolyzed into amino acids in the gastrointestinal
tract before being absorbed into the blood circulation system,
there is considerable evidence showing that peptides can be
absorbed partially intact.
9,12
Several human and animal bio-
availability studies with orally administered collagen peptides
have shown that food-derived collagen peptides are absorbed
mostly as free amino acids like other protein sources, but also
as collagen-derived peptides.
9,12–17
Therefore, orally ingested
collagen peptides are able to cross the intestinal barrier and
enter the blood circulation system, from where they are
transported to the skin.
9,16,17
Inside the target connective tissue,
collagen peptides affect the metabolic processes of the skin.
Specific bioactive collagen peptides’ (BCP) intake stim-
ulated the dermal metabolism of rats by increasing type I
and IV collagen expression and reducing MMP-2 activity.
10
Moreover, Proksch et al.
11
demonstrated a notable im-
provement in skin elasticity on healthy women who ingested
2.5 g/day of specific collagen peptides for 8 weeks. In an-
other clinical trial conducted by Proksch et al.,
18
a signifi-
cant increase of collagen I and elastin content was observed
in the skin of women who consumed the same specific
collagen peptides and dosage for 8 weeks.
Based on the previous findings that have demonstrated the
efficacy of specific collagen peptides on improving dermal
strength and skin elasticity, it can be speculated that the oral
supplementation of such peptides may also have a positive
impact on cellulite-affected skin.
In this clinical study, for the first time, the influence of
specific BCP ingestion on the treatment of cellulite in nor-
mal and overweight women was investigated after 6 months
of daily intake.
MATERIALS AND METHODS
BCP
The specific BCP used in this study was composed of col-
lagen peptides derived from a complex multistep procedure of
porcine skin type I collagen degradation. The product was
provided by GELITA AG, commercially available as VER-
ISOL
. The product is clearly defined by a MALDI-MS mass
peaks fingerprint with specific collagen peptides of an average
molecular weight of 2.0 kDa. The product had proven its high
safety when administered orally in previous clinical studies.
11,12
Study design
The study was carried out as a monocentric, double-blind,
randomized, placebo-controlled supplementation study on
the effects of specific BCP on the degree of cellulite on
thighs and skin surface profile and dermal density after 6
months of daily intake.
The study was approved by the Freiburger Ethik-
Kommission International, Freiburg, Germany, adhered to
current good clinical practice regulations, and was in ac-
cordance with the revised Declaration of Helsinki. All test
subjects received detailed information listing of every single
parameter relevant to the study. All subjects gave signed
informed consent after receipt of the written information and
having had a possibility for further questions.
Subjects
A total of 105 healthy female subjects with moderate
cellulite on the thighs (score 2–3 according to a modified
score by Nu
¨rnberger and Mu
¨ller
19
) were included in the
study and randomized for treatment with a daily dose of
2.5 g of BCP or placebo (maltodextrin). In both treatment
groups, the subjects were classified, depending on their
BMI, as being of normal weight (BMI <25) or being over-
weight (BMI >25).
A daily dosage of 2.5 g of the product or placebo was
taken orally by the participants in accordance with the in-
structions given by the investigator. The powder was to be
dissolved in water or any other liquid.
Before the beginning of oral treatment and data acquisi-
tion, there was a preconditioning period of at least 7 days.
During this period and throughout the entire length of the
study, the subjects had to refrain from using any leave-on
products and oily or moisturizing skin cleansing products on
the thighs. Moreover, any change of their usual skin cleaning
routine on the test sites was prohibited. It was also forbidden
to intensively expose the test sites to UV light (sun or solar-
ium). The subjects were not allowed to visit saunas, swim-
ming pools, or do intensive sport on the day before the study
visits. Massages or any kind of anticellulite treatment on the
test site was prohibited 3 months before study start.
Furthermore, any change in their lifestyle, dietary habits,
or sport activities, 2 weeks before study start and the con-
sumption of any additional nutritional supplement or vita-
min preparations 3 months before study start were also
prohibited. The treatment of the test areas with the following
medications was barred before the start and during the
study: dermatological therapeutics (6 weeks prior), corti-
costeroids and antihistamines (4 weeks prior), anti-
inflammatory drugs and antibiotics (2 weeks prior).
Inclusion criteria
The inclusion criteria were as follows: healthy females
ranging from 25 to 50 years of age (homogeneous distri-
bution between treatment groups), moderate cellulite on the
thighs: score 2–3 according to a modified score by Nu
¨rn-
berger and Mu
¨ller
19
phototypes I to III (Fitzpatrick scale), in
general good health and mental condition, personal in-
formed consents to participate in the study, personal pres-
ence on the predefined days at the institute, willing and able
to follow the study rules, and a fixed schedule. The criteria
2SCHUNCK ET AL.
of inclusion were checked by the investigator before study
start. If there had been divergence from these criteria, the
subject would not have been included in the data analysis of
the study.
Exclusion criteria
The exclusion criteria were as follows: any deviation from
the above-mentioned inclusion criteria, acute skin diseases
(e.g., atopic eczema, atopic dermatitis, psoriasis) on the test
sites, or other dermatological disorders (scars, sunburn,
moles), food allergies against ingredients of the test products,
gastrointestinal diseases or indigestion, tattoos on the test
sites, topical medication used on the test area within 6 weeks
before the start of the study, systemic medication with anti-
inflammatory agents or antibiotics within 2 weeks before the
start, systemic medication with corticoids and/or antihista-
mines within 4 weeks before the start, medication with other
systemic medication within 4 weeks before the start, systemic
illness of the subject at the beginning of the study, pregnancy
or a period of breast feeding, immunological disorders, se-
vere disorders within 6 months before the start, for example,
cancer, acute cardiac and circularity disorders, severe dia-
betes, alcohol and drug abuse, participation in other studies
with cosmetic products on the test areas within 2 weeks be-
fore the start or during the study, participation in a study with
a pharmaceutical preparation within 4 weeks before the start,
intake of nutritional supplements within 4 weeks before the
start and, except for the test products administered during the
study, change in lifestyle or eating habits during the study,
treatment with leave-on products and oily or moisturizing
skin cleansing products on the thighs, or a change in the usual
skin care routine, massage or any kind of anticellulite treat-
ment on the test site 3 months before study start and during
the study exposure to intensive sunlight or artificial UV
(solarium) on the test sites within 1 week before the start,
swimming, sauna or intensive sport within 1 day before
measurements, lack of compliance, intellectual or mental
inability to follow study instructions.
Assessments
Test sites. All tests were performed in a defined area on
the thighs. For the cellulite degree assessment (pinch test),
the left thigh and buttock were used. Skin waviness and
dermal density were performed on the left thigh.
On every measurement day, the subjects had to expose
their uncovered test sites to the indoor climatic conditions
(21.5C; 50% relative humidity) for at least 30 minutes.
Measurement times. There were three measurement
times for all test parameters. Data were collected at the
beginning of the study before the product treatment (t0),
after 3 months (t1), and after 6 months (t2) of a daily product
intake.
Compliance. The subjects were instructed to enter each
product intake into the diary. Compliance and tolerance
were checked after 1 and 4 weeks and 3 and 5 months of
intake and at each measurement time at the institute (t1 =3
months; t2 =6 months) by checking the study diary, dosage,
dietary habits, and by questioning the subjects for potential
intake gaps and misses.
If there had been a deviation in weight from the baseline
measurement of 5%, the subject would have been excluded
from the study. On each compliance check and measure-
ment day, the subjects were asked again if they had adhered
to all the restrictions and instructions. Had there been any
deviation from the restrictions, this subject would have been
excluded from the study.
Measurement of cellulite degree (pinch test). The grade
of cellulite was visually/tactilely assessed on the test site by
the so-called pinch test. In brief, the assessor pinched the
skin on the outer thigh between her index finger and her
thumb, evaluated the visible dimpling, and graded cellulite
appearance. The grade of cellulite was defined according to
a modified score by Nu
¨rnberger and Mu
¨ller
19
(Table 1).
Measurement of the skin surface profile (waviness, Wt)
with PRIMOS
Pico. The skin surface profile (parameter
Wt, waviness) was measured in vivo on the thighs using the
optical measuring instrument PRIMOS Pico (GFM). The
device allows detailed 3D skin surface scanning and pro-
vides high-resolution assessment of skin surfaces by using
phase-shifted light stripes projected by micromirrors to
generate a 3D profile of the measured skin surface (area
18 ·13 mm
2
). The reflected light is captured by a high-
resolution camera, and a software package converts the
image into a color-coded picture of the skin surface, with
different colors for different heights.
The measurements were performed on the left thigh on a
site prior marked with a permanent marker, while the sub-
jects were standing. Three pictures were taken per test site.
Height images were computed according to the standard
procedure using mathematical filters. These height images
were used to calculate star roughness. For the calculation of
star roughness, intersections are arranged in a star shape by
the program. Three stars with different locations of their
Table 1. Grade of Cellulite, According
to a Modified Score by Nu
¨rnberger and Mu
¨ller
19
Score Description
0–<0.5 No cellulite
0.5–1.5 Smooth surface of skin while lying down and standing
Mattress phenomenon upon pinch test
>1.5–2.5 Smooth surface of skin while lying down
Dimpling at the inner and outer sides of the thigh and at
the back of the thigh while standing
Mattress phenomenon clearly visible upon pinch test
>2.5–3.5 Slightly dimpled surface of skin while lying down
Dimpling at the entire thigh and buttock while standing
Mattress phenomenon very clearly visible upon pinch test
>3.5–4 Severely dimpled surface of skin at thigh and buttock
while lying down and standing. Belly and upper arms
may be affected too.
SPECIFIC COLLAGEN PEPTIDE EFFECT IN CELLULITE TREATMENT 3
central point were defined. The calculation of the parameter
occurs according to the determination of the line roughness
(separate for every star shape-arranged intersection).
The parameter waviness (Wt) was analyzed. It represents
the sum of the height of the largest profile peak and the
largest profile valley of the waviness profile. It is presented
in millimeter. The mean of the three single measurements
was calculated for each test site and point in time.
Dermis density and length of borderline between dermis
and subcutis by ultrasound (DermaScan
C). At each
measurement point in time, dermis density and the length of
the borderline between dermis and subcutis were measured
using the DermaScan C 20 MHz ultrasound device and
the DSCANV3 application software (Cortex Technology).
The device was operated according to the manufacturer’s
instructions.
The probe was configured with a 20 MHz transducer,
which offers a 60 ·130 lm resolution and a 10 mm pene-
tration depth. Before use, the ultrasound probe was prepared
for scanning by mounting a plastic membrane and injecting
distilled water into the probe. Finally, a small amount of gel
was applied into the open slit of the gel spacer.
Three single B-mode scans on each test site were conducted,
using a defined gain profile that was adjusted to the depth and
density distribution in the tissue being scanned (thigh). This
gain profile was the same for all subjects. The gain level was
adjusted for each subject, but was the same for all measure-
ments performed on this subject for all points in time. Ad-
justing the gain level makes it possible to compensate for the
attenuation of the ultrasound signal through the tissue. Signals
are amplified by the gain as a function of depth.
Echo-free structures such as fat and lymphatic fluid are
displayed as black regions in the ultrasound images, while
connective tissue structures appear in green, red, or yellow.
Because the ultrasound reflection intensity is related to the
relative density of the targeted tissue, it also provides in-
formation on the arrangement of the collagen and elastic
fibers. Echogenicity reflects dermal extracellular matrix
organization; that is, the more organized and abundant the
collagen tissue is, the higher the echogenicity.
The borderline between dermis and subcutis (line 2) was
defined using the freehand function. The length of the de-
fined line was measured automatically by the software. The
measurement values were presented in millimeter. The
length is a measure for the degree of cellulite. The wavier
the line due to protrusion of adipose tissue into the dermis
(papillae adipose), the longer the line is and the more pro-
nounced the cellulite is.
Statistical analysis
Statistically significant differences in age, body weight,
BMI, and grade of cellulite at baseline between both treat-
ment groups were analyzed by the Mann–Whitney U-Test
for all participants and considering normal and overweight
subdivision. For a P-value <0.05, the difference was ac-
cepted as statistically significant.
Statistically significant changes in the grade of cellulite
within the treatment groups were calculated with the Wil-
coxon signed-rank test in comparison to the baseline situa-
tion. For a P-value <0.05, the difference was accepted as
statistically significant.
Changes within the treatment groups for the other mea-
surement parameters, such as skin waviness, dermal density,
and length of borderline, were tested with the Wilcoxon
signed-rank test in comparison to the baseline situation.
Differences between both treatment groups were analyzed
with the Student’s t-test for two independent samples. For a
P-value <0.05, the difference was accepted as statistically
significant.
RESULTS
Subjects and dropouts
A total of 105 women between 24.8 and 53.5 years of age
(40.6 7.4) were initially included in the study. Ninety-
seven of the 105 subjects finished the study correctly, re-
presenting the evaluate per-protocol population. At baseline,
no statically significant differences between the treatment
group and the placebo group (Table 2, P=0.529) could be
observed.
During the study period, five subjects dropped out (one
placebo, four BCP) due to private reasons and three subjects
(two placebo, one BCP) dropped out because of lacking
compliance or illness.
None of the dropouts was product related, and no side
effects or discomfort were observed during the study. No
adverse reactions were recorded in any of the study partic-
ipants.
Study groups
The results of 105 subjects (53 in the BCP group, 52
in the placebo group) were included in the data analysis
Table 2. Demographic Data of Study Population
Per Treatment Group
BCP Placebo
Total (n)5352
Cellulite score 2.4 0.4 2.4 0.4
Normal BMI £25 (n)2426
Age (years) 39.9 7.2 39.0 6.5
Weight (kg) 61.8 5.1 62.0 4.7
BMI 22.2 1.2 22.4 1.1
Cellulite score 2.2 0.3 2.3 0.4
Overweight BMI >25 (n)25 22
Age (years)* 38.4 6.5 42.6 6.6
Weight (kg) 74.8 6.7 76.3 6.1
BMI 26.5 1.6 26.7 1.5
Cellulite score 2.5 0.1 2.6 0.1
No statistically significant differences in age, body weight, and BMI
between both treatment groups were determined at study baseline. Only in the
overweight subgroup a difference in age was observed (*P<0.05, mean SD,
n=number of subjects).
BCP, bioactive collagen peptides; BMI, body mass index.
4SCHUNCK ET AL.
(ITT population). At baseline, study groups were balanced
regarding the age body weight, BMI, and grade of cellulite
showing no statistically significantly differences between
both treatment groups (Table 2). Only in the study group
representing participants with a BMI >25 was an inhomo-
geneous distribution of the age observed (P<0.05).
Cellulite degree assessment (pinch test)
After 3 months of BCP treatment, a decrease in the
cellulite score could be observed (2.17 0.5) compared
to the baseline situation (2.37 0.4). This statistically
significant decrease (P<0.05) continued for the next 3
months, reaching a maximal score decrease of 0.3 score
points at the end of the study (P<0.05) (Table 3). A clear
improvement compared to the placebo group was detected.
After 3 and 6 months of BCP treatment, a statistical and
significant reduction of the cellulite score was determined
(P<0.05).
In the normal BMI (£25) study group, the data revealed a
decreased cellulite score of 5.3% compared to placebo after 3
months of treatment. At the end of the study at 6 months, the
observed effect was even more pronounced reaching a mean
reduction in the score of about 9% compared to placebo
(Table 3). These findings reflected a clear attenuation of
mattress phenomenon upon the pinch test, a smoother surface
of the thighs while lying down, and a decrease in the dimpling
of the thigh while standing. This improvement could also be
confirmed in the group of women with a BMI >25, although
the beneficial effect after 6 months of treatment was less
pronounced. In this study, a score reduction of 4% could be
observed in comparison to the untreated women (Table 3).
Skin surface profile measurement (waviness)
In examinations of the skin surface profile, it could be
demonstrated that the relative waviness of the skin in the
women treated with BCP was reduced by 2% compared to
the placebo group after 3 months. This trend was even more
pronounced after 6 months of BCP intake. Compared to the
placebo group, a statistically significant reduction (P<0.05)
of 8% in skin waviness could be observed after 6 months of
treatment (Fig. 1). There was a noticeable improvement in
skin waviness promoted by BCP, which can be seen in the
representative 3D colored images of Figure 2, in which each
color is related to a height. The cellulite-affected area in
both placebo (Fig. 2A) and BCP (Fig. 2B) groups, at base-
line, showed a typical skin profile with marked red and
yellow areas, indicating the skin depression and relief as for
skin surface, respectively. In contrast, a remarkable im-
provement of skin depression with attenuated red areas and
Table 3. The Cellulite Score in the Overall Study Population and Normal and Overweight Women, Before and After
Oral Supplementation with Specific Bioactive Collagen Peptide in Comparison with Placebo Group
BMI Treatment nBaseline 3 Months 6 Months
Total study population BCP 49 2.37 0.4 2.17 0.5*
,#
2.08 0.4*
,#
Placebo 48 2.44 0.4 2.23 0.5* 2.19 0.5*
Normal (BMI <25) BCP 24 2.19 0.3 1.96 0.4 1.86 0.4*
,#
Placebo 26 2.31 0.4 2.07 0.5* 2.04 0.5*
Overweight (BMI >25) BCP 25 2.54 0.5 2.37 0.4* 2.30 0.4*
,#
Placebo 22 2.59 0.4 2.40 0.6* 2.40 0.5*
*Intragroup comparison, P<0.05 versus baseline.
#
Intergroup comparison, P<0.05 versus placebo after 3 and 6 months treatment, mean SD, n=number of subjects).
FIG. 1. Skin surface profile of tight skin
before and after 3 and 6 months of oral sup-
plementation with bioactive collagen peptide
(BCP) or placebo, measured by PRIMOS
Pico. Skin waviness of thigh was statistically
significantly decreased (P<0.05) after 6
months of BCP daily intake in the overall
study subjects in comparison with placebo
treatment (mean standard error of mean,
n.s. not statistically significant).
SPECIFIC COLLAGEN PEPTIDE EFFECT IN CELLULITE TREATMENT 5
a more homogeneous skin surface was observed in the BCP
group after 6 months (Fig. 2B), while the placebo group did
not change visibly (Fig. 2A).
In women with a maximum BMI of 25, a statistically
significant improvement could already be observed after 3
months of BCP intake compared to the beginning of the
study (P<0.01). Compared to the placebo group, waviness
was significantly reduced (P<0.05) after BCP treatment.
At the end of the study (6 months), a pronounced decrease in
waviness of 11.1% could be detected. This improvement in
the skin appearance was statistically significant compared to
placebo (P<0.05).
In overweight participants (BMI >25), BCP treatment
also led to a skin waviness reduction of 3.6% after 6 months
in comparison to placebo, but the data failed to reach the
level of statistical significance.
Dermis density measurement
Evident improvement in dermal density owing to 6
months of BCP intake can be visualized by the ultrasound
representative images in Figure 3A. At baseline, for both the
placebo and BCP groups, the interface between the dermis
and subcutis appeared as a broken irregular line, a high
amount of black areas (fat cells and lymphatic fluid), and a
low degree of dermal density (green areas). After 6 months
of BCP treatment, the skin tissue becomes measurably more
compact, indicating a strengthening of connective tissue,
with echo-free interspaces (black areas) being reduced and
clearly high dermal density (red and yellow areas).
Measurement of the dermis density demonstrated a pro-
gressive loss in density over 6 months in all women assigned
to the placebo group (6.85–6.45). This statistically signifi-
cant (P<0.01) decrease of 3.1% could not be observed in
FIG. 2. Representative 3D color-coded height images of tight skin
surface, before (t0) and after 6 months (t6) of oral supplementation
with BCP or placebo; measured by PRIMOS Pico. Each color is
related to a height with red and yellow areas, indicating the skin
depression and relief as for skin surface, respectively. At the external
margins of the measuring fields, the resolution is limited seen by
lower colour intensity in green and blue.(A) Placebo group. (B) BCP
group. A notable improvement in skin waviness can be seen in the
BCP group, showing more homogeneous skin surfaces.
FIG. 3. Dermis density of cellulite-affected area in tights after
6 months of BCP or placebo intake, measured by DermaScan.
(A) Representative ultrasound cross-sectional images (single B scan)
of BCP and placebo groups. The epidermis of the skin pictures is left
located (yellow line). The dermis connective tissues are showing
several degrees of dermal density (green low and red to yellow high
density). Black structures are fat and lymphatic fluid. Note that before
therapy (baseline), the interface between the dermis and the subcutis
appears as a broken and irregular line and many black areas appear.
After 6 months of BCP daily supplementation, dermis tissue has
become measurably more compact, indicating a strengthening of the
connective tissue. Black interspaces have been reduced. (B) Relative
dermis density of BCP group to placebo, showing an increased der-
mal density after BCP treatment (7.29–7.66).
6SCHUNCK ET AL.
the BCP group. Overall, data revealed that a BCP treatment
over 6 months led to a statistically significant (P<0.05)
increased dermal density compared to placebo (Fig. 3B).
Measurement of the borderline length
between dermis and subcutis
Examinations of the borderline length between dermis and
subcutis showed a clear statistically significant (P<0.05)
shortening of the borderline after a BCP intake over 6 months
compared to the beginning of the study (data not shown). As
the length of the borderline correlates with the degree of
cellulite, the data demonstrated a statistically significant
improvement of cellulite after BCP treatment. Further eval-
uation of the data, including the results representing normal
and overweight women, failed to reach level of statistical
significance in comparison with the placebo.
DISCUSSION
The term cellulite is often used to describe a complex
architectural disorder of the skin with multifactorial eti-
ologies.
3
In general, the formation of cellulite is a natural
process and not a disease, reflected by an incidence of about
85% in adult females. However, the appearance of cellulite
can negatively affect the quality of life in women and some
seriously suffer from their dimpling orange peel skin.
The pathophysiology of cellulite is not yet fully under-
stood, but it is generally accepted that, beside an altered
connective tissue structure and a disturbed dermal extra-
cellular matrix, overweight also has a negative effect on
cellulite-prone skin areas such as thighs and buttocks.
Mirrashed et al.
4
demonstrated a correlation between over-
weight and cellulite pathophysiology in a pilot study with
magnetic resonance imaging technique. Even though cel-
lulite formation is exacerbated in combination with being
overweight, it is predominantly dependent on the perpen-
dicular orientation and status of dermal septae with regard to
the skin surface. These dermal septae are much thinner and
more radially oriented in cellulite-affected females com-
pared to unaffected men and women.
20
Today, a wide variety of cellulite treatment options ex-
ist,
21
ranging from topically applied products and massages
to laser and intense pulsed light treatment among others.
1
Recently, an oral supplementation with polyphenol-rich
chokeberry juice taken over a period of 90 days improved
cellulite with a marked reduction in the subcutaneous tissue
thickness and edema.
22
Most therapeutic approaches focus
on the induction of lipolysis. However, the efficacy of such
cellulite treatments seems to be less than completely satis-
fying, as reported by Wanner and Avram.
23
In contrast to these various forms of treatment, an oral
therapy with BCP is based on the premise that specific
collagen peptides can improve and increase dermal firmness
and skin elasticity from the inside.
It is known that the improvements of dermal strength
and skin elasticity are two important therapeutic aims in
cellulite treatment.
21
Incidentally, Ortonne et al.
24
observed
that, regardless of age, the presence of cellulite corresponds
to a thinning of the dermal layer, a greater length of the
dermis–hypodermis interface, and a decrease of dermal
density and biomechanical parameters of skin elasticity and
extensibility that are negatively affected by the degree of
involvement of cellulite. The authors argue that women with
cellulite exhibit skin characteristics typical of older ages.
In addition, Dobke et al.
25
observed that women without
cellulite had a better skin quality (firmer, with less com-
pliance, laxity, and capacity of deformation) in the upper
posterior part of the thigh. In contrast, women with cellulite
showed greater laxity and weakness of the dermis and
connective tissue, which extended into the superficial fascia.
The efficacy of the BCP used in this study (VERISOL) on
skin health and dermal connective tissue metabolism was re-
cently demonstrated in two monocentric, double-blinded,
randomized, placebo-control clinical trials on healthy women.
Proksch et al. demonstrated that skin elasticity increased sta-
tistically significantly by up to 30% (average 7%) after 8 weeks
of oral BCP ingestion in comparison to placebo treatment.
11
In
addition, in a follow-up study, an elastic improvement of the
skin resulting from an increased biosynthesis of collagen and
elastin in the dermal connective tissue was shown.
18
Hundred
and fourteen women aged 45–65 years received 2.5 g BCP or
placebo once daily. After 8 weeks of intake, a statistically
significant higher content of new generated procollagen type I
(65%) and tropoelastin (18%) in interstitial skin fluid com-
pared to the placebo treatment was observed.
In the present study, it could be demonstrated that a daily
dosage of 2.5 g BCP has a positive impact on women af-
fected by moderate cellulite. Beside a significant improve-
ment in the cellulite score, results also revealed a significant
decrease in the waviness of the thigh skin as well as dermis
density strengthening after BCP treatment.
With regard to the mode of action, it could be speculated
that the efficacy of BCP on cellulite treatment is based on its
positive impact on dermal connective tissue synthesis. This
assumption was confirmed by the results of the dermal
density measurements. After 6 months of oral BCP intake, a
statistically significant higher dermal density (P<0.01)
could be detected compared to placebo.
One of the reasons for the dimpling effect in skin seems to
be an abnormal pattern of distribution of elastic and collagen
fibers in dermal septae.
26
In cellulite-prone skin, both fiber types are unevenly located
and partly clumped and, contrarily, in other parts of the dermal
septae, rare and thinly distributed. The irregular strength of the
connective tissue septae is considered as the most important
distinguishing characteristic between cellulite-prone skin and
unaffected skin.
3
It is known that fibrillin, as the main com-
ponent of elastic fibers, is of particular importance for the in-
tegrity of these fiber bundles.
27
In a previous study, it could be
demonstrated that, beside type I collagen and elastin, the fi-
brillin syntheses were also affected by the oral administration
of BCP (VERISOL).
18
This increased synthesis of the fiber
matrix molecules became clinically apparent in a statistically
significant reduction of eye wrinkle deepness of 20% com-
pared to the placebo group.
SPECIFIC COLLAGEN PEPTIDE EFFECT IN CELLULITE TREATMENT 7
Based on these findings, it could be speculated that the
improvement in skin waviness in cellulite-prone skin ob-
served here might be caused by the same effect. In com-
parison to the control group, a statistically significantly
reduced skin waviness (-11%) was detected on thighs in
normal weight volunteers after BCP administration.
The efficacy of a BCP treatment could also be confirmed in
overweight women (BMI >25), although the impact in this
group was less pronounced in comparison to the results in
women of normal weight. This observation was reflected by
almost all the results obtained from the different investigations.
It could be speculated that, especially in the group of
overweight women, the duration of the treatment might be
too short to see the maximum effect, as the data revealed an
improvement trend but failed to reach statistical signifi-
cance. It has to be stated that, at baseline, the degree of
cellulite in the overweight women was statistically signifi-
cantly (P<0.01) more pronounced than with women of
normal weight, so that an extended therapy might be useful.
Moreover, as the therapeutic effect of a BCP treatment
seems to predominantly influence the dermal matrix syn-
thesis and, thus, strengthen dermal connective tissue, the
observed effect might be more distinct when the cellulite is
specifically caused by connective tissue alterations. This
may support the hypothesis that BCP treatment particularly
influences the positive impact on fiber septae regeneration.
The evaluation of the ultrasound images documents a vi-
sually detectable change in tissue structure. It was observed
that the network of collagen/elastic fibers in the dermis and
subcutis becomes denser.
It has been shown that noninvasive measures such as skin
profile and those obtained from ultrasound images exhibit a
positive correlation among them and the subjective percep-
tion of cellulite.
28
Dermal thickness may be reduced when it
is more compact, and the dermal/hypodermal interface may
be shortened when the invagination of adipose tissue toward
the deep dermis is reduced as in the slight degree of cellu-
lite.
29,30
Ultrasound images captured before treatment clearly
represented the irregular broken line between dermis and
hypodermis, and hypoechoic structures can be interpreted as
fat bulging from subcutaneous tissue into the upper-layer
dermal tissue. After treatment with BCP, a significant re-
duction in dermal thickness, elevated echogenicity indicat-
ing increased and organized collagen tissue, and reduction of
hypoechoic areas were demonstrated.
The results obtained in this study demonstrated that an
oral supplementation with specific BCP over a period of 6
months led to a clear improvement of the skin appearance in
women suffering from moderate cellulite. In addition, the
data showed the marked potential of BCP to improve the
skin morphology of cellulite-affected areas, providing new
evidence of BCP’s beneficial effects and postulating a new
therapy strategy for cellulite treatment.
AUTHOR DISCLOSURE STATEMENT
V.Z. is an employee of GELITA Brazil Ltd. No com-
peting financial interests exist for S.O., M.S., and E.P.
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SPECIFIC COLLAGEN PEPTIDE EFFECT IN CELLULITE TREATMENT 9
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... These doses would roughly correspond to a range from 2 g to 8 g in humans. The dose of HC alone or combined with GAGs used for clinical investigations ranges from 200 mg/day to 10 g/day (mostly 1 g/day) for a period of time generally encompassing 2 to 6 months [27,28,40,41]. In a very recent ex vivo clinical study, volunteers received 25 g of HC from bovine origin in a single shot without any side effects [16]. ...
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... In another study involving Verisol®, a randomised, double-blind, placebo-controlled clinical trial of 105 women affected by cellulite (of which 97 completed the trial), aged 24-50, were randomly allocated to an experimental group (n = 53) and a placebo group (n = 52), given 2.5 g of Bioactive CP (BCP) derived from porcine skin collagen type I in powder (Verisol®), to be taken dissolved in liquid once daily for 6 months or given a placebo of maltodextrin to be taken by the same method by the placebo group [28]. ...
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The term cellulite originates from the French medical literature and has been known for more than 150 years. Cellulite is a metabolic disease that primarily affects the hypodermis-the subcutaneous fat layer. In modern cosmetology, cellulite is a term that defines the condition of the skin, in which its relief is disturbed due to the uneven accumulation of subcutaneous adipose tissue and circulatory problems.Research shows that 80-90% of women suffer from cellulite. Almost all women sooner or later face this problem. To date, there is still no guaranteed and long-term solution to deal with cellulite. For this reason, cellulite is seen as a medical problem rather than a cosmetic one. The multifactorial etiology and its complex etiopathogenesis, as well as long and persistent treatment most often lead to temporary results. This gives grounds to study the problem of cellulite in depth by students majoring in "Rehabilitation Therapist" and "Medical Cosmeticiаn" in massage training. In this way, you could achieve through your competencies to cover a large contingent of women with cellulite in need of treatment. The purpose of this report is to study in depth the origin of cellulite, its morphological features and the latest achievements in its prevention, as well as the need to find its place in the education of students majoring in "Rehabilitation Therapist" and "Medical Cosmeticiаn". Material and methods: Study of modern literature sources on the relevance of the problem and the latest achievements in the fight against cellulite. Conclusion: A number of modern studies prove that natural remedies are more favorable and safer, including special gymnastics, manual and eastern massage techniques and proper diet. Special attention should be paid to the greater variety of specialized devices methods in medical cosmetics to combat cellulite. Through their impact, a selective reduction of cellulite in the treated areas of the body can be achieved, the negative phenomena can be overcome and an aesthetically beautiful silhouette can be achieved. Медицински колеж, Тракийски университет-Стара Загора, Р България, kmollova@abv.bg Анушка Узунова Медицински колеж, Тракийски университет-Стара Загора, България, anu6ka70@abv.bg Резюме: Терминът целулит произхожда от френската медицинска литература и е познат повече от 150 години. Целулитът представлява обменно заболяване, което засяга преди всичко хиподермата-подкожния мастен слой. В съвременната козметология целулитът е термин, определящ състояние на кожата, при което нейният релеф се нарушава в следствие на неравномерно натрупване на подкожна мастна тъкан и циркулаторни проблеми. Научните изследвания сочат, че 80-90% от жените страдат от целулит. Почти всички жени рано или късно се сблъскват с този проблем. Към днешна дата все още няма гарантирано и дългосрочно решение за справяне с целулита. По тази причина на целулита се гледа по-скоро като медицински проблем, отколкото козметичен. Многофакторната етиология и сложната му етиопатогенеза, както продължителното и упорито лечение най-често води до временни резултати. Това дава основание проблемът целулит да се изучава задълбочено от студентите от специалностите "Рехабилитатор" и "Медицински козметик" в обучението по масаж. Така те биха могли чрез своите компетенции да обхванат големия контингент жени с целулит, нуждаещи се от лечение. Целта на настоящият доклад е да се проучи задълбочено произхода на целулита, неговите морфологични особености и последните постижения за предотвратяването му, както и необходимостта да намери своето място в обучението на студентите от
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Background Cellulite refers to skin relief alterations in women′s thighs and buttocks, causing dissatisfaction and search for treatment. Its physiopathology is complex and not completely understood. Many therapeutic options have been reported with no scientific evidence about benefits. The majority of the studies are not controlled nor randomized; most efficacy endpoints are subjective, like not well standardized photographs and investigator opinion. Objective measures could improve severity assessment. Our purpose was to correlate non-invasive instrumental measures and standardized clinical evaluation.Methods26 women presenting cellulite on buttocks, aged from 25-41 were evaluated by: body mass index; standardized photography analysis (10-point severity and 5-point photonumeric scales) by five dermatologists; cutometry and high-frequency ultrasonography (dermal density and dermis/hypodermis interface lenght). Quality of life impact was assessed. Correlations between clinical and instrumental parameters were performed.ResultsGood agreement among dermatologists and main investigator perceptions was detected. Positive correlations: body mass index and clinical scores; ultrasonographic measures. Negative correlation: cutometry and clinical scores. Quality of life score was correlated to dermal collagen density.Conclusion Cellulite caused impact in quality of life. Poor correlation between objective measures and clinical evaluation was detected. Cellulite severity assessment is a challenge and objective parameters should be optimized for clinical trials.This article is protected by copyright. All rights reserved.
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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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Plasma levels of prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly) in healthy volunteers (n=5) after ingestion of collagen hydrolysate were estimated by liquid chromatography-tandem mass spectrometry. The ratio of Hyp-Gly to Pro-Hyp was distributed in the range of 0.063-0.221. This is a first report for quantification of food-derived Hyp-Gly in human plasma.
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Cellulite is characterized by alterations to the skin surface, presenting as dimpled or puckered skin of the buttocks and posterior and lateral thighs. It mainly affects women. Cellulite occurrence is believed to be due to structural, inflammatory, morphological and biochemical alterations of the subcutaneous tissue. However, its pathogenesis is not completely understood. Topical treatments for cellulite include many agents, such those that increase the microcirculation flow, agents that reduce lipogenesis and promote lipolysis, agents that restore the normal structure of dermis and subcutaneous tissue, and agents that scavenge free radicals or prevent their formation. There are many cosmetic and medical treatments for cellulite. However, there is little clinical evidence of an improvement in cellulite, and none have been shown to lead to its resolution. The successful treatment of cellulite will ultimately depend upon our understanding of the physiopathology of cellulite adipose tissue.