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An Oral Supplementation Based on Hydrolyzed Collagen and Vitamins Improves Skin Elasticity and Dermis Echogenicity: A Clinical Placebo-Controlled Study

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The aim of this study was to evaluate the clinical efficacy of an oral supplementation based on hydrolyzed collagen and vitamins in the improvement of aged skin conditions using biophysical and skin imaging techniques. In this doubleblind, placebo-controlled trials, 60 woman aged between 40-60 years were randomized to receive the product containing hydrolyzed collagen and vitamins (Group A) or the placebo (Group B), once daily for 90-days period. Skin elasticity, dermis echogenicity, hydration and, number of pores and wrinkles were measured before and at the end of the study. The results showed an improvement of the dermis echogenicity and skin elasticity, as well as a reduction of wrinkles and total amount of pores on the skin of the group A when compared with placebo group. Thus, it was concluded that oral supplementation under study present itself as a potential to act effectively on aged skin. Finally, the study contributes to the improvement of effective strategies to skin care beyond topical products use.
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Clinical Pharmacology
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ISSN: 2167-065X
Patrícia Maia Campos et al., Clin Pharmacol Biopharm 2015, 4:3
DOI: 10.4172/2167-065X.1000142
Volume 4 • Issue 3 • 1000142
Clin Pharmacol Biopharm
ISSN: 2167-065X CPB, an open access journal
An Oral Supplementation Based on Hydrolyzed Collagen and Vitamins
Improves Skin Elasticity and Dermis Echogenicity: A Clinical Placebo-
Controlled Study
Patrícia Maia Campos MBG*, Maísa O Melo, Lívia S Calixto and Marina M Fossa
Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil
Abstract
The aim of this study was to evaluate the clinical efcacy of an oral supplementation based on hydrolyzed collagen
and vitamins in the improvement of aged skin conditions using biophysical and skin imaging techniques. In this double-
blind, placebo-controlled trials, 60 woman aged between 40-60 years were randomized to receive the product containing
hydrolyzed collagen and vitamins (Group A) or the placebo (Group B), once daily for 90-days period. Skin elasticity,
dermis echogenicity, hydration and, number of pores and wrinkles were measured before and at the end of the study.
The results showed an improvement of the dermis echogenicity and skin elasticity, as well as a reduction of wrinkles and
total amount of pores on the skin of the group A when compared with placebo group. Thus, it was concluded that oral
supplementation under study present itself as a potential to act effectively on aged skin. Finally, the study contributes to
the improvement of effective strategies to skin care beyond topical products use.
Keywords: Hydrolyzed collagen; Oral supplementation; Biophysical
and skin imaging techniques; Skin elasticity; Clinical study
Introduction
Technological innovations in the area associated with the search
for new methods to prevent and/or treat skin aging are emerging,
and in this context, the concept of nutricosmetics appeared, which,
by denition, are products for oral administration that have been
specically formulated for cosmetic improvements of the skin and
appendices, and may be in the form of pills, food, liquids or tablets.
ese were created from the partnership between the cosmetic and
food industries, and are also known as In & Out treatments and are
mainly used for anti-aging proposes without invasive approaches [1,2].
However, according to the current resolutions, the nutricosmetics or
oral supplementation, must also have studies and scientic evidence to
prove its safety without medical supervision, which should not include
health claims referring to the cure or prevention of any disease [3].
In addition, there is currently a strong tendency for facial treatments
with oral supplementation for an improvement of the appearance as
a whole. A healthy skin can be consequence of the substances that
are consumed throughout the day, such as the ingestions of liquids,
alimentary habits, solar exposure, age and use of oral supplementation,
with vitamins and antioxidants. us, the approach of topical and oral
treatments for skin benets led to the creation of a new concept product
called nutricosmetics [4] to complement the topical treatment. is
way, products composed with collagen hydrolyzed and micronutrients
have been proposed to oral supplementation, since they can act
improving skin conditions, especially for mature skin consumers.
ere are approximately 27 dierent types of collagen in the body,
being the collagen type I the most abundant in the body [5,6]. In the
skin, collagen types I and III represents, respectively, 85 to 90% and 8 to
11% of total collagen synthesized [7]. Collagen is essential for a proper
maintenance of skin health, since both photoaging (caused by exposure
to environmental factors as nutrition, ultraviolet radiation, etc, that
leads to a degradation of collagen bers and intrinsic aging (aging
caused by the “chronological” natural eects of the metabolism), causes
a decrease in the levels of this protein in the body [8], which leads to a
decrease in the skin’s thickness and rmness and loss of elasticity and
hydration, that are mainly related with the reduction and modication
of all skin elements: the broblasts become scarce, causing a slowdown
in the collagen synthesis, which loses its regular and exible appearance
[8,9]. In addition, the muscles become accid, bone density is reduced
and the joints and ligaments lose elasticity [10,11]. Vitamins A, C and
E are among the most commonly studied. Vitamin E (tocopherol) is a
fat-soluble nutrient with a primary function of protecting long-chain
polyunsaturated fatty acids of cell membranes and lipoproteins against
oxidation [12]. As for the vitamin C or L-ascorbic acid, in addition to
its great antioxidant potential. Vitamin A is essential, among other
factors, to cell proliferation and dierentiation [13,14]. Zinc has
antioxidant protection both in vivo and in vitro, and these actions can
be directly related to the prevention of premature skin aging [15,16].
ere are recent studies related with oral supplementation of
hydrolyzed collagen in combination with vitamins, minerals or
botanical extracts. Recently, an overview of the benecial eects of
Hydrolyzed Collagen was published, focusing on its eects on the
skin [17]. e authors related studies concerning the bioavailability of
hydrolyzed collagen, in vitro and in vivo scientic studies on the ecacy
of collagen peptides, showing the benets of collagen peptides on skin
and the importance of controlled clinical trials to prove ecacy of this
kind of products. However, double-blinded, randomized, placebo-
controlled studies to evaluate the clinical benets using biophysical
and skin imaging techniques of oral supplementations with hydrolyzed
collagen based products added or not with vitamins and others anti-
aging ingredients are still scarce.
Finally, given the trends to complement the cosmetic use with
oral supplementation and the benets of hydrolyzed collagen and
vitamins, a randomized and double-blind controlled clinical study is
*Corre sponding author: Patrícia Maia Campos MBG, Faculty of Pharmaceutical
Sciences of Ribeirão Preto, University of São Paulo Av. do Café, s/n, Ribeirão Preto,
SP, Brazil, Tel: +5516 33154197; E-mail: pmcampos@usp.br
Received July 21, 2015; Accepted August 11, 2015; Published August 18, 2015
Citation: Patrícia Maia Campos MBG, Meloo MO, Calixto LS, Fossa MM (2015)
An Oral Supplementation Based on Hydrolyzed Collagen and Vitamins Improves
Skin Elasticity and Dermis Echogenicity: A Clinical Placebo-Controlled Study. Clin
Pharmacol Biopharm 4: 142. doi:10.4172/2167-065X.1000142
Copyright: © 2015 Patrícia Maia Campos MBG, et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided
the original author and source are credited.
Citation: Patrícia Maia Campos MBG, Meloo MO, Calixto LS, Fossa MM (2015) An Oral Supplementation Based on Hydrolyzed Collagen and Vitamins
Improves Skin Elasticity and Dermis Echogenicity: A Clinical Placebo-Controlled Study. Clin Pharmacol Biopharm 4: 142. doi:10.4172/2167-
065X.1000142
Page 2 of 6
Volume 4 • Issue 3 • 1000142
Clin Pharmacol Biopharm
ISSN: 2167-065X CPB, an open access journal
e study participants were also asked to not change their usual
skin care routine or be part of any dermatological treatments on the
test areas.
Inclusion criteria
e inclusion criteria were as follows: healthy females ranging in
age from 40 to 60 years (homogeneous distribution between treatment
groups); phototype II-IV (Fitzpatrick scale); general good health and
mental condition; avoid sun exposure during the study period; personal
informed consent to participate in the study; personal presence on the
predened days at the institute, and willingness and capability to follow
the study rules and a xed schedule, know that the data could be used
to share the project. It was also instructed to the volunteers to not use
other cosmetic products and to not change their alimentary habits
during the study period.
Exclusion criteria
e exclusion criteria was as follows: any deviation from the
above-mentioned inclusion criteria: pregnancy (or intention to
become pregnant) or in period of breast feeding; skin diseases (e.g.,
atopic eczema, neurodermatitis or psoriasis) on the test areas or other
dermatological disorders (e.g., scars, sunburn or moles), whose therapy
could inuence the results of the study, such as systemic steroids
or antibiotics, steroids or local immunomodulatory topics three
months prior to the study; smoking habit; severe disorders within 6
months prior to study start (e.g., cancer, acute cardiac and circularity
disorders, severe diabetes, or alcohol or drug abuse); history of
medical or cirurgical events that could signicantly aect the outcome
of the study, including any cardiovascular disease, skin disease,
gastrointestinal diseases, indigestion, hypertension (>160/95 mm Hg
on repeated measurements); participation in any other clinical study;
medical treatments on the study area 30 days before the study start; use
of tanning beds or self-tanning products a month before or during the
study; any other condition that, in the opinion of the investigator, may
interfere with the results or involves a risk to the subject.
Assessments
Test areas: e test areas were the frontal, periorbital and nasolabial
regions of the face, being the periobital and nasolabial sides randomly
chosen. On every measurement day, the subjects had to expose their
uncovered test areas to the indoor climate conditions (21.5 ± 1ºC and
50 ± 5% relative humidity) for 20 min.
Measurement times: ere measures were made immediately
before starting the product treatment (baseline values) and aer 90
days (D90) of daily product intake.
Measurement of the stratum corneum water content: e water
content of the stratum corneum was measured with a skin capacitance
meter (CorneometerTMCM 825, Courage and Khazaka Electronic
GmbH, Cologne, Germany). e device determines the water content
of the supercial epidermal layers down to a depth of about 0.1mm
and expresses the values in arbitrary units. e average values of 5
measurements/ site were used in subsequent calculations [21].
Measurement of skin elasticity: For this evaluation, the
equipment Cutometer® SEM 575 was utilized. It features a probe
with negative pressure on the skin, and the captured light intensity
is proportional to the skin penetration [22]. e Cutometer® analyses
the mechanical parameters: Ua/Uf, the ratio of total retraction to total
distension, called gross elasticity; Ur/Ue, net-elasticity of the skin
without viscous deformation; Ur/Uf, the ratio of immediate retraction
very important to assess the eectiveness of a daily intake of hydrolyzed
collagen based product, enriched with vitamins A, C, E and zinc, when
compared to placebo in the improvement and maintenance of the
elasticity, density and rmness of the facial skin.
is way, the presented study contributes to a better understanding
of the benets of oral supplementation to skin, giving scientic
evidence of the eectiveness of these products on the skin, beneting
consumers about the long-term clinical ecacy of functional food
in elasticity and structural characteristics of the skin. In summary, it
presents the clinical evaluation of the oral supplementation benets on
the skin employing advanced technologies of imaging analysis.
Material and Methods
Test product
e product under study is composed of a combination of Amino
acids (Peptides of Hydrolyzed Collagen) and vitamin A, C, E, Zinc and
excipients according to Table 1 and Table 2.
e presented treatment product contains a high concentration of
the three main amino acids involved in the collagen synthesis: Proline,
glycine and hidroxyproline. is combination of amino acids, when
in association with the antioxidant complex of vitamins A, C, E and
zinc, helps to promote a protection against the action of Reactive
Oxygen Species (ROS), that causes oxidative stress, which are negatively
correlated with the inammation process and collagen synthesis [18].
Furthermore, the addition of Vitamin C is essential in the intracellular
phase of collagen synthesis, promoting the hydroxylation of the amino
acids proline and lysine into hydroxyproline and hydroxylysine,
which results in the pro-collagen, a precursor molecule [19]. e
placebo product also used in this study was composed of maltodextrin
(carbohydrate from enzymatic conversion of corn starch) and
excipients, which is a classic protocol for this type of clinical studies, as
it does not aect directly the skin physiology [20].
Study design
e study was carried out as a monocentric, double-blinded,
randomized, placebo-controlled study on the eects of an oral
supplementation based on hydrolyzed collagen and vitamins on skin
elasticity, dermis echogenicity and skin microrelief aer 90 days of
daily intake.
e study was approved by the Ethics Committee of the Faculty of
Pharmaceutical Sciences of Ribeirão Preto/SP (CEP / FCFRP 339) and
followed current Good Clinical Practice regulations. All test subjects
received detailed information listing every relevant single parameter
to the study and all the procedures involved. All subjects gave signed
informed consent aer written information and a possibility for further
questioning.
Subjects
A total of 60 healthy female subjects were enrolled in the study: 30
subjects were randomized to each of 2 treatment groups to receive a
daily dose of either 10 g of collagen and a mix of vitamins A, C, E and
zinc or 10 g of the placebo (maltodextrin).
The products were taken orally by the subjects at home according
to the instructions given by the investigator. The powder was to be
dissolved in water or any other cold liquid. Prior to the beginning of
the study and data acquisition, it was asked to the volunteers avoid
the use of any anti-aging cosmetics as a preconditioning period
during 7 days.
Citation: Patrícia Maia Campos MBG, Meloo MO, Calixto LS, Fossa MM (2015) An Oral Supplementation Based on Hydrolyzed Collagen and Vitamins
Improves Skin Elasticity and Dermis Echogenicity: A Clinical Placebo-Controlled Study. Clin Pharmacol Biopharm 4: 142. doi:10.4172/2167-
065X.1000142
Page 3 of 6
Volume 4 • Issue 3 • 1000142
Clin Pharmacol Biopharm
ISSN: 2167-065X CPB, an open access journal
to total distension, called biological elasticity; and Uv/Ue, the ratio of
viscoelastic to elastic distension [23]. e measurement of each test
area was repeated 3 times. e R5 value (Ur/Ue, immediate recovery/
elastic deformation) was utilized as it is proven to be the most suitable
in detecting age-related skin alterations [24].
Measurement of skin by high resolution photography: e
Visioface® digital photography imaging system (Courage and Khazaka)
was utilized for the evaluation of facial skin, consisting of a cabin
attached to a high resolution digital camera (10 megapixels) and 200
white LED. is apparatus is connected to research soware that
enables evaluation of visible pores and wrinkles [25].
Measurement of dermis echogenicity: To the evaluation of the
dermis echogenicity, 20 MHz ultra-sound equipment (Dermascan® C,
Cortex Technology) was utilized. e ultrasonic wave (speed of 1,580
m/s) is partially reected by the skin structure, giving rise to echoes
of dierent amplitudes. To calculate the echogenicity, the number
of pixels with low echogenicity is measured by means of the image
analysis soware and related to the total number of pixels [26].
Statistical analysis: Two-way ANOVA and Bonferroni post-test
were used in this study. Statistical dierences between placebo and
collagen groups were ascertained by paired Student’s T-tests for basal
and T90 measurements for each parameter evaluated (GraphPad
Soware Inc., La Jolla, CA, USA). Dierences were accepted as
statistically signicant at p < 0.05.
Results and Discussion
Measurement of the stratum corneum water content
Aer 90 days of treatment, the group receiving the product
containing collagen and vitamins presented a signicant eect in the
stratum corneum water content parameter, but only in the frontal
region, when compared to baseline values. However, this result is
not signicant when compared to placebo group. is hydration
was in accordance with what was described by Proksch et al, where
no statistical dierence between the treatment group and placebo
control at the baseline was observed [27]. Futhermore, Skovgaard et
al, that studied an oral supplementation with similar composition,
also observed a signicant increase in hydration from baseline values
when utilizing the treatment product, but it was not signicant when
compared to the placebo group [28].
Considering that Xhauaire-Uhoda et al. demonstrated that the
low increase of skin hydration can be related to the normal behavior
of newly generated corneocytes from deeper skin layers [29], in this
study, the presence of vitamin A in the product could to promote
this feature. A study by Gianeti and Maia Campos undertaken at
our research laboratory, using the same equipments, with a topical
formulation containing an association of fat-soluble derivatives of
vitamins A, C and E and botanical extracts showed, aer a 30 day-
period of treatment, a signicant decrease of trans-epidermal Water
Loss, increase of hydration and reduced wrinkles and skin roughness
[30]. In addition, topical treatments with products containing peptides
increased skin hydration [31] and also decrease the trans-epidermal
water loss, improving skin barrier function.
These results suggest the importance of the association of both
oral supplementation and cosmetic use for skin hydration and
protection. Furthermore, the combined use of topical and oral
peptides would enhance the effects, benefiting the skin appearance
in many aspects.
Measurement of skin elasticity
According to the statistical analysis, only the group who received
hydrolyzed collagen and vitamins product (A) presented signicant
dierences in all evaluated parameters aer 90 days of treatment when
compared to the baseline values. is way, an increase of variables
related to the immediate retraction, immediate distension and total
distention ratio indicate an increase of elasticity and viscoelasticity
of the skin. Furthermore, the signicant increase of the immediate
retraction / distension of the skin (Ur / Ue - R5 parameter) were
obtained only on group A, when compared with baseline values and
with the placebo group (Figure 1).
Borumand and Sibilla and Proksch et al [32,33] evaluated similar
products and analyzed by the same equipments, observed a non-
signicant improvement of skin elasticity (R5 parameter) when
compared to the placebo. In our study, the treatment with hydrolyzed
collagen and vitamins product was eective, once an improvement
of the skin elasticity was noted aer 12 weeks of use, when compared
to the placebo group. is result show the importance of the oral
supplementation to improve skin age conditions once a loss of the
structural support of the dermis is common in mature ages, leading to
a less elastic skin that is also thinner and less able to resist to mechanical
changes. With that, the present elastic bers have the tendency to
become deformed and less exible. is decrease of collagen bers
in epithelial tissue is a result of the decreased broblasts metabolic
activity, which are responsible for its synthesis [34]. So, the increase
of skin elasticity parameters suggests an improvement of skin mechanical
proprieties aer the treatment with the oral supplementation under study.
Evaluation of skin by high resolution photography
Figure 2 shows a three-dimensional image shown where an evident
reduction of wrinkles on the forehead to treatment with the product
(collagen) is visible. Alterations of collagen and elastin can directly
the aect wrinkle [35]. As the oral supplementation acts in the increase
of collagen bers and, along with the presence of vitamins C, E and
zinc, with their antioxidant properties, eectiveness in the reduction of
wrinkles and improving the appearance of the skin as a whole was noted
[36]. Similar results in the reduction of wrinkles aer the treatment
with oral supplementation and analyzed with other techniques was
related in the literature, demonstrating this way, the eectiveness of
this type of products in the improvement skin appearance [32].
Aspartic Acid 531 mg Proline 1206 mg Metionine 81 mg Histidine 72 mg
Treonine 144 mg Glycine 1574 mg Isoleucine 117 mg Lisine 378 mg
Serine 288 mg Alanine 801 mg Tirosine 18 mg Arginine 819 mg
Glutamic Acid 1026 mg Valine 216 mg Fenilalanine 198 mg Hidroxyproline 1161 mg
Table 1: Composition of amino acids presented in 10 g the treatment product under study.
Vitamin A (Retinyl Palmitate) 600 μg
Vitamin C (Sodium Ascorbate) 45 mg
Vitamin E (Tocopheryl Acetate) 10 mg
Zinc (Zinc Sulfate Monohydrate) 7 mg
Table 2: Composition of other active ingredients presented in 10 g of the treatment
product.
Citation: Patrícia Maia Campos MBG, Meloo MO, Calixto LS, Fossa MM (2015) An Oral Supplementation Based on Hydrolyzed Collagen and Vitamins
Improves Skin Elasticity and Dermis Echogenicity: A Clinical Placebo-Controlled Study. Clin Pharmacol Biopharm 4: 142. doi:10.4172/2167-
065X.1000142
Page 4 of 6
Volume 4 • Issue 3 • 1000142
Clin Pharmacol Biopharm
ISSN: 2167-065X CPB, an open access journal
In addition, 81% of the volunteers in Group A (hydrolyzed collagen
based product) presented a reduction of the total number of pores and
in 72% of volunteers in the Group B (placebo) presented an increase
of the number of pores. ese results are showed in the Figure 3 and
Figure 4, which represent high resolution images of the reduction of
large and small pores in the Collagen-based product volunteers group
(collagen) and increase of pores in group B (placebo). Skin aging, and
consequently, the loss of skin elasticity, leads to an increase in both
pores size and numbers [37]. is way, the improvement of skin
elasticity, as previously demonstrated, led to the reduction of skin
pores size and number.
Measurement of dermis echogenicity
e high-frequency ultrasound provide measures of parameters
related to the skin histology, analyzing the skin aging process and
the echogenicity of the dermis - which is important as it varies with
the chronological aging (intrinsic) and photoaging (extrinsic). is
equipment also quanties and qualies the collagen and elastin bers in
the skin, being this way, an important contribution to clinical ecacy
studies of dermocosmetic formulations [38].
is study showed an increase in the dermis echogenicity
aer 90 days of treatment with the hydrolyzed collagen based oral
supplementation (Group A -Figure 5) when compared to the placebo
treatment (Figure 6). is way, the product acted on the dermis,
increasing of broblast density, enhancing the formation of collagen
brils, and acting as a repairman of the present damages, slowing
the chronological aging and photoaging process, increasing the
echogenicity of the dermis and improving the skin density [39-41].
A high dermis echogenicity is related to a high content of collagen
bers, so the lower this ratio is, the more echogenic the skin. us, the
treatment A has improved the dermis echogenicity when compared to
placebo treatment in the frontal and nasolabial regions. e Figure 7
shows the Echogenicity Ratio of all three study regions. is parameter
reects the number of hypo echoic pixels / total number of pixels that
increases during the aging process.
Skovgaard et al also studied an oral supplementation with a
multifunctional product analyzed with dierent ultrasound equipment
(DUBplus 20 - Taberna, Pro Medicum, AG, USA) and observed an
increase of dermis thickness, suggesting that the treatment could
stimulate the production of collagen in post-menopausal women [28].
In Summary, the treatment with the hydrolyzed collagen based product
under study improved the echogenicity of the dermis (decreased
echogenicity ratio), suggesting an increase of dermis density and this
way, the rmness and elasticity of skin as well.
In addition, an improvement in skin elasticity was noted by
signicant alterations in the parameters related to the mechanical
properties of the skin aer 90 days-period of treatment with only
hydrolyzed collagen-based product. e obtained high resolution
Net Elasticity (R5) in the frontal region of the face
Placebo
Collagen Based
0.2
0.3
0.4
0.5
0.6
D0
D90
*
Figure 1: R5 Parameter (Net Elasticity – The closer to the value is to 1, the
more elastic the skin) in the frontal region in groups A and B before (baseline)
and after 90 days of treatment.
Figure 2: Three-dimensional images of the frontal area (glabella) at baseline
and after 90 days of treatment with product A - collagen based, obtained with
Visioface software Quick®.
Figure 3: High resolution images of the frontal region of the face at baseline
and after 90 days of treatment with product A - obtained at the Visioface Quick®
software. Note the visible reduction in the number of pores.
Figure 4: High resolution images of the frontal region of the face at baseline
and after 90 days of treatment with product B - obtained at the Visioface Quick®
software. Note the visible increase in the number of pores.
Figure 5: Dermis Echogenicity of a volunteer (Group A) before (baseline) and
after 90 days of treatment. Echogenicity color scale: white > yellow > red >
green > blue > black.
Citation: Patrícia Maia Campos MBG, Meloo MO, Calixto LS, Fossa MM (2015) An Oral Supplementation Based on Hydrolyzed Collagen and Vitamins
Improves Skin Elasticity and Dermis Echogenicity: A Clinical Placebo-Controlled Study. Clin Pharmacol Biopharm 4: 142. doi:10.4172/2167-
065X.1000142
Page 5 of 6
Volume 4 • Issue 3 • 1000142
Clin Pharmacol Biopharm
ISSN: 2167-065X CPB, an open access journal
images showed a reduction in the depth of wrinkles and ne lines on
the frontal and periorbital regions of the face aer 90 days of treatment
with product A. ere was also a signicant reduction in the total
content of pores in volunteers who received treatment A (collagen),
being more signicant reduction in the frontal region (81%).
According to an overview of the benecial eects of Hydrolyzed
Collagen on the skin recently published [17], the results obtained in
the present study is in accordance to what were reported on this review
and showed signicant eects in the improvement of skin hydration,
elasticity, density and reduction of wrinkles and pores, evaluated by
high-end imaging techniques in combination with the traditional
biophysical techniques oering this way, real benets to aged skin
consumers.
Finally, the study described is an innovative proposal because
it shows the importance of oral supplementation to improve skin
elasticity and dermis echogenicity with hydrolyzed collagen and
vitamins in combination evaluated by clinical studies using biophysical
and skin imaging techniques.
Conclusion
Under the experimental conditions of this study, it was possible
to conclude that the proposed hydrolyzed collagen based oral
supplementation was eective in the improvement of skin elasticity
and structure of the dermis. Moreover, the product had a positive
eect reducing wrinkles and large pores aer three months of use.
erefore, supplementation with a collagen based and vitamins A, C,
E and zinc presents itself as a potential product to act eectively on the
improvement on the aged skin conditions.
Acknowledgements
The authors gratefully acknowledge the nancial support of Fundação de
Amparo à Pesquisa do Estado de Sao Paulo (Fapesp).
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Figure 6: Dermis Echogenicity of a volunteer (Group B) before (baseline) and
after 90 days of treatment. Echogenicity color scale: white > yellow > red >
green > blue > black.
Echogenicity Ratio
Frontal
asolabia
P
eriorbita
l
-10
-5
0
5
10
Placebo
Collagen
**
Difference between D90 e D0 (%)
Figure 7: Difference (in percentage %) between the echogenicity ratio (number
of hypo echoic pixels / total number of pixels) of the face regions of groups A
(Hydrolyzed Collagen) and B (placebo), before (baseline) and after 90 days of
treatment. * Signicant difference from placebo (p < 0.05).
Citation: Patrícia Maia Campos MBG, Meloo MO, Calixto LS, Fossa MM (2015) An Oral Supplementation Based on Hydrolyzed Collagen and Vitamins
Improves Skin Elasticity and Dermis Echogenicity: A Clinical Placebo-Controlled Study. Clin Pharmacol Biopharm 4: 142. doi:10.4172/2167-
065X.1000142
Page 6 of 6
Volume 4 • Issue 3 • 1000142
Clin Pharmacol Biopharm
ISSN: 2167-065X CPB, an open access journal
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... Randomised, blinded, placebo-controlled clinical trials on the effects of orally consumed collagen peptides on human skin are scarce (Campos et al. 2015). Two placebo-controlled clinical trials published within one paper assessed the effect of a daily oral collagen peptide supplement on objective markers of skin appearance (Asserin et al. 2015). ...
... A randomised, double-blind study compared the effects of a supplement containing hydrolysed collagen peptides plus 600 lg vitamin A, 45 mg vitamin C, 10 mg vitamin E and 7 mg zinc, with a placebo (maltodextrin) on skin condition. Sixty female subjects consumed either the supplement or placebo every day for 90 days (Campos et al. 2015). At the end of the trial, there was no significant difference in skin hydration between the treatment and placebo groups. ...
... Of the four studies providing supplements that included collagen, two reported a significant increase in objectively measured skin elasticity, with one also reporting an increase in dermal thickness and density and a blood marker of collagen synthesis, though this study was not placebo-controlled (De Luca et al. 2016)), and one found an increase in self-reported elasticity, though differences in study design and supplement composition make direct comparisons difficult. Only one study reported a significant reduction in wrinkles, and a concomitant increase in collagen fibres was also found (Campos et al. 2015). Not all studies collected enough data to ascertain potential mechanisms of action (e.g. ...
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The rise of the nutraceutical market, specifically oral nutrition supplements claiming to improve skin appearance, is striking. This paper aims to examine the published scientific evidence for beneficial effects of nutraceuticals on skin appearance. An overview of skin physiology and intrinsic and extrinsic ageing is provided which underlies the potential physiological processes nutraceuticals purport to counter. Common ingredients used are explored. Some of these (vitamins A, C, B2, B3, B7, copper, iodine, zinc) have authorised skin-related health claims, but many do not. Current evidence for those without existing authorised claims (e.g. green tea extract, pomegranate extract, carotenoids, evening primrose oil, borage oil, fish oil, collagen and co-enzyme Q10) is reviewed, focussing primarily on evidence from randomised controlled trials where available, in relation to skin parameters including wrinkles and hydration. Issues of safety are also considered, and the postulated mechanisms for some emerging ingredients, such as cocoa flavanols and probiotics, are explored. Evidence from high quality human trials demonstrating clear benefit is required by regulatory authorities in order for foods and nutrition supplements to carry a health or beauty claim. To date, the evidence for many ingredients in relation to skin appearance is limited, not sufficiently robust and/or inconsistent. Although there are a small number of human studies suggesting a potential benefit and some plausible biological mechanisms, much of the evidence to date comes from animal and in vitro studies. There are simply not enough good quality randomised controlled trials in this area to draw firm conclusions about the benefit of nutraceuticals to skin appearance.
... Collagen is a highly sought-after protein, finding use in regenerative medicine, in cosmetics, used as casings, in supplements, films, pharmaceuticals, as a precursor to biodegradable materials, for use in tissue engineering and more recently in 3D printing [3][4][5][6][7][8]. The demand for collagen is rising at approximately 20% annually and global collagen-based biomaterials market is predicted to reach US$5 billion by 2025. ...
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Industrial processing of bovine hides into leather results in many unusable hide off-cuttings, shavings and trimmings. This waste raw material is under-utilised and presents a waste valorisation opportunity to derive a high-value product such as collagen. Collagen is a highly sought-after protein which consists of three polypep-tide chains, comprising 30% of the mammalian body's protein, being the main component of skin, connective tissue and cartilage. The demand for collagen is rising at approximately 20% annually and global collagen-based biomaterials market is predicted to reach US$5 billion by 2025. This chapter presents a waste valorisation opportunity to extract collagen from waste bovine hide off-cuttings. Further, it discusses collagen extraction method optimization and methods used to investigate physicochemical properties of collagen are reviewed.
... Improvement of stratum corneum hydration and/or skin elasticity by collagen peptides has been reported in recent years, and this study supports such findings. [7][8][9][10] The ONS used in this study contained three major amino acids involved in collagen synthesis (proline, glycine, and hydroxyproline) and was abundant in antioxidants (vitamins A, C, and E and zinc). Vitamin C is a potent antioxidant that can neutralize and remove oxidants such as those found in environmental pollutants and after exposure to UV radiation. ...
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Objective: The purpose of this randomized open-label study was to investigate the effect of an oral nutrition supplement containing collagen peptides on stratum corneum hydration and skin elasticity. Methods: The study protocol was registered at the UMIN Clinical Trials Registry (UMIN 000027347). Once-a-day oral administration of a nutrition supplement containing collagen peptides (10.0 g) was instituted in 39 inpatients 65 years or older who were assigned to either the intervention or the control group using a block-randomization design. Stratum corneum hydration and skin elasticity were measured at baseline and at 2, 4, 6, and 8 weeks after the start of the intervention. Results: Mean stratum corneum hydration was significantly increased from 43.7 at baseline to 51.7 at postintervention week 8 in the intervention group (P = .001). Differences in skin elasticity from baseline were significant at postintervention week 6 (P = .026) and week 8 (P = .049). Conclusions: Oral nutrition supplements containing collagen peptides may reduce skin vulnerability in older adults and thus prevent conditions such as skin tears.
... Campos et al (34) performed a study on a product composed of a combination of amino acids (hydrolyzed collagen peptides: glycine, proline and hydroxyproline), supplemented with hydrosoluble vitamins (A and C) and lyposoluble vitamins (E) and zinc. They tested the effectiveness of the treatment by biophysical techniques and imaging of the skin. ...
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Ageing is a complex, multi-step process which involves, among others loss of collagen and elastin. Collagen is found in large amounts in the body, especially in the dermis layer. These fibers provide the skin's normal strength, hydration and mechanical properties. Collagen is largely available, as it can be extracted from many animal sources, it can be easily absorbed upon topical administration, hence it is largely used in the cosmetic and pharmaceutical industry for the treatment of premature aging. Bioactive peptides, such as collagen hydrolyzate, are among the most used ingredients for the development of nutraceuticals - food or food ingredients that have defined physiological effects. Numerous studies have demonstrated that peptides resulted from ingestion of hydrolysate collagen and detected in the blood stream have chemotactic properties for skin fibroblasts, helping the skin restoration process. The purpose of this minireview is to present an update on the use of hydrolyzed collagen for skin care.
... Purified collagen can be used for regenerative medicine and cosmetics, such as collagen injections for improving appearance, in body lotions and mascaras [4,5]. Collagen is also used in casings [6], supplements [7], films [8], pharmaceuticals [9], as a precursor to biodegradable materials, for tissue engineering and more recently in 3D printing [1,. Demand for collagen is rising at approximately 20% annually and global collagen and hyaluronic acid (HA) based biomaterials market predicted to reach US$4.6 billion by 2020 [21,35]. ...
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Purpose Hide is a by-product of meat production and is mostly used for leather production. Collagen is the main protein in mammalian skin, connective tissue and cartilage and presents an opportunity for value addition to waste hide off-cuttings by extracting collagen. Three different extraction methods were applied to five different hide sources. The hide sources differed with respect to the animal’s age, sex, diet and environment and influenced collagen extractables yield, and therefore the economic benefit of extraction. Methods Acid-solubilisation (AS), acid-enzyme solubilisation (AES1) and modified acid-enzyme solubilisation (AES2) were used to extract collagen from bull, calf, cow, face-pieces and ox-hides. Results The highest dry collagen content was from cow hides using the AES2 method (75.13%), followed closely by bull hides at 74.45%. On the other hand, the lowest collagen content was from cow hides (3.80%) with the AS extraction method and the AS method proved to be inefficient for collagen extraction from bull, cow, face-piece and ox-hide sources. Analysis concluded that all the samples were of Type I collagen with α, β, and γ chains. Conclusions Waste bovine hide off-cuttings can be used to extract high value product of collagen. AES2 proved to be the most preferable method of extraction out of the three methods applied and considering leather to collagen revenue, these waste bovine hide off-cuttings could potentially result in substantial revenue. Graphic Abstract Open image in new window
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Skin aging has become a recurring concern even for younger people, mainly owing to increased life expectancy. In this context, the use of nutricosmetics as supplements has increased in recent years. Moreover, numerous scientific studies have shown the benefits of hydrolyzed collagen supplementation in improving the signs of skin aging. The objective of this study was to summarize the evidence on the effects of hydrolyzed collagen supplementation on human skin through a systematic review followed by a meta‐analysis of clinical trials focusing on the process of skin aging. A literature search was conducted in the Medline, Embase, Cochrane, LILACS (Latin American and Caribbean Health Sciences Literature), and Journal of Negative Results in BioMedicine databases. Eligible studies were randomized, double‐blind, and controlled trials that evaluated oral supplementation with hydrolyzed collagen as an intervention and reported at least one of the following outcomes: skin wrinkles, hydration, elasticity, and firmness. After retrieving articles from the databases, 19 studies were selected, with a total of 1,125 participants aged between 20 and 70 years (95% women). In the meta‐analysis, a grouped analysis of studies showed favorable results of hydrolyzed collagen supplementation compared with placebo in terms of skin hydration, elasticity, and wrinkles. The findings of improved hydration and elasticity were also confirmed in the subgroup meta‐analysis. Based on results, ingestion of hydrolyzed collagen for 90 days is effective in reducing skin aging, as it reduces wrinkles and improves skin elasticity and hydration.
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Objectives In view of the lack of studies about the morphological and structural changes caused by solar radiation in young people, the aim of the present study was to evaluate the photoaging‐related changes in the skin of different age groups by Biophysical and Imaging techniques. Methods Forty‐four healthy female subjects were divided into two age groups: G1: 18‐35 years old and G2: 40‐60 years old. The skin of malar region of the face was evaluated in terms of mechanical properties, disorder in the pigmentation pattern, morphological and structural changes using the Cutometer®, Colorimeter®, Visioface® and Dermascan C® devices and Reflectance Confocal Microscopy ‐ RCM (Vivascope®). Results The results showed that the main changes in the skin of G1 were related to the pigmentation pattern, the papilla format and depletion of thin collagen fibers. These alterations were also observed in the skin of G2, but with more pronounced effects. Conclusion The knowledge about the skin changes caused by photoaging obtained in this study is very important for the development of dermocosmetic products for more effective treatments particularly focused on this type of skin. Finally, objective characterization of photoaging showed the importance of photoprotective habits since the first years of life in order to retard the appearance of skin changes caused by solar radiation. This article is protected by copyright. All rights reserved.
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This study presents the association of active antioxidants substances in a multifunctional cosmetic formulation with established efficacy against signs of aging. A multifunctional cosmetic formulation containing an association of UV filters and antioxidant substances (liposoluble vitamins A, C and E, Ginkgo biloba and Phorphyra umbilicalis extracts) was evaluated. This formulation was submitted to a clinical efficacy study using biophysics techniques and skin images analysis (digital photography imaging systems, 20 MHz ultrasound, and reflectance confocal microscopy). The volunteers applied the formulation containing the UV filters and antioxidant substances during the day and the formulation with antioxidant substances and without the UV filters at night, for 90 days. The formulation increased the hydration and protected the skin barrier function after a single application. At the long term assessment the formulation provided an improvement in skin barrier function and skin hydration to the deeper layers of the epidermis, leading to an improvement in skin appearance by reducing wrinkles and skin roughness. The multifunctional cosmetic formulation studied can be suggested to preventing signs of aging and improving skin conditions. In addition, this study presents the benefits of associating different active antioxidants substances in a single cosmetic formulation to prevent skin aging.
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Dietary consumption of food supplements has been found to modulate skin functions and can therefore be useful in the treatment of skin aging. However, there is only a limited number of clinical studies supporting these claims. In this double-blind, placebo-controlled study, the effectiveness of the specific bioactive collagen peptide (BCP) VERISOL® on eye wrinkle formation and stimulation of procollagen I, elastin and fibrillin biosynthesis in the skin was assessed. A hundred and fourteen women aged 45-65 years were randomized to receive 2.5 g of BCP or placebo, once daily for 8 weeks, with 57 subjects being allocated to each treatment group. Skin wrinkles were objectively measured in all subjects, before starting the treatment, after 4 and 8 weeks as well as 4 weeks after the last intake (4-week regression phase). A subgroup was established for suction blister biopsies analyzing procollagen I, elastin and fibrillin at the beginning of the treatment and after 8 weeks of intake. The ingestion of the specific BCP used in this study promoted a statistically significant reduction of eye wrinkle volume (p < 0.05) in comparison to the placebo group after 4 and 8 weeks (20%) of intake. Moreover a positive long-lasting effect was observed 4 weeks after the last BCP administration (p < 0.05). Additionally, after 8 weeks of intake a statistically significantly higher content of procollagen type I (65%) and elastin (18%) in the BCP-treated volunteers compared to the placebo-treated patients was detected. For fibrillin, a 6% increase could be determined after BCP treatment compared to the placebo, but this effect failed to reach the level of statistical significance. In conclusion, our findings demonstrate that the oral intake of specific bioactive collagen peptides (Verisol®) reduced skin wrinkles and had positive effects on dermal matrix synthesis. © 2014 S. Karger AG, Basel.
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The skin is supplied with an antioxidant system that includes enzymatic and nonenzymatic components. This complex system is the skin's first-line defense against free-radical attacks. Antioxidants are essential in protecting the epidermis from damage by free radicals generated both by environmental and endogenous factors. This role of free radicals in etiology of disease and how antioxidants are used to offset or prevent oxidative damage are discussed.
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Skin ageing is divided into chronological ageing and photoageing due to the cumulative effects of solar ultraviolet radiation. It is, however, difficult to measure the degree of photoageing and chronological ageing in humans in vivo. Here, we have evaluated the usefulness of ultrasonography for measurement of chronological ageing and photoageing in vivo. Twenty megahertz ultrasonography was performed in 90 individuals (29 men, 61 women, age 18-94) to describe age-related changes in sun-exposed regions with different levels of sun exposure (dorsal and ventral forearm, forehead, ankle) and non-exposed buttock skin. Skin thickness and skin echogenicity in different layers of the dermis were measured in ultrasound images. Additionally cutaneous photodamage was scored clinically. Age-related changes were dependent on body site as well as layer of the dermis. A progressive, age-related decrease in echogenicity of the upper dermis was found in sun-exposed regions (dorsal forearm, forehead), but not in moderately exposed regions (ventral forearm, ankle). In the buttock. an increase in echogenicity was observed. The echogenicity of the lower dermis increased in all examined sites. Skin thickness increased with age in the forehead and buttock, but decreased in the extremity skin. Our findings show that photoageing causes a decrease in echogenicity in the upper dermis. In contrast, chronological ageing is associated with an increase in echogenicity in the lower dermis. Although both increases and decreases in skin thickness were observed in different anatomical regions, there was no general relationship between skin thickness and age. Dermal echogenicity was deemed valuable for in vivo study of chronological ageing and photoageing.
Article
Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.