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Dermatology
Practical & Conceptual
Original Article | Dermatol Pract Concept. 2022;12(1):e2022018 1
Collagen Supplements for Aging and Wrinkles:
A Paradigm Shift in the Fields of Dermatology
and Cosmetics
Hend Al-Atif1
1 College of Medicine, King Khalid University, Saudi Arabia
Key words: aging, oral collagen, topical collagen, collagen supplements, wrinkling
Citation: Al-Atif H. Collagen supplements for aging and wrinkles: a paradigm shift in the fields of dermatology and cosmetics.
Dermatol Pract Concept. 2022;12(1):e2022018. DOI: https://doi.org/10.5826/dpc.1201a18
Accepted: May 26, 2021; Published: January 2022
Copyright: ©2022 Hend Al-Atif. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Corresponding author: Hend Al-Atif, College of Medicine, King Khalid University, Saudi Arabia. E-mail: hmsalatif@yahoo.com
Introduction: Slowing the aging process by use of collagen supplements has become a driving force
in the field of dermatology and cosmetics. Generally, oral and topical collagen are used in anti-aging
products, as reported in the literature.
Objectives: The overarching goal of this research is to collate the consequences of oral collagen with
those of topical collagen in reducing or delaying the aging process.
Methods:We executed an electronic search in Google Scholar and PubMed. We considered a study
eligible if it was original research, published in English between 2010 and 2020, and if it provided in-
formation on the topic of collagen and aging. We retrieved 12 full-text articles, and these were assessed
by reviewers independently.
Results:All human studies included in the review were randomized controlled trials mainly conducted
in high- to middle-income countries which highlighted that both oral and topical collagen supplements
help to delay the aging process, with no differences arising between the two types of collagen. The
evidence from the reviewed studies suggested that both collagen supplements improve skin moisture,
elasticity, and hydration when orally administered. Additionally, collagen reduces the wrinkling and
roughness of the skin, and existing studies have not found any side effects of its oral supplements.
Conclusions: Both oral and topical collagen can contribute to reducing or delaying skin aging. Future
epidemiological studies with large sample sizes and thorough follow-up measures would be required to
comprehensively understand the potential effects of these two types of collagen on the aging process.
ABSTRACT
2 Original Article | Dermatol Pract Concept. 2022;12(1):e2022018
Introduction
Aging of the skin is a continuous process related to a depletion
in the physiological function of the skin [1]. Both natural and
unnatural factors cause human beings and animals to experi-
ence physiological alterations in different organs as time passes
[2]. Cutaneous aging is a multifactorial activity dependent on
both inherent (genetic, hormonal, and metabolic), and extrinsic
factors (perennial exposure to UV rays, smoking, air pollution,
chemicals and poor nutrition) [3,4]. Aging has a detrimental
effect on connective tissue in the skin, leading to declines in
elastin and collagen fibers and thus resulting in fine lines and
wrinkles [3]. Furthermore, aging reduces the production of
proteoglycans and glycosaminoglycan (such ashyaluronic acid)
in the skin, as well as cartilage [4]. As a result, skin tissue weak-
ens, losing its integrity, and the skin becomes dry, unable to
retain enough moisture. Although multiple intrinsic processes
can affect the aging process, factors such as exposure to sun,
liquid intake, lifestyle, and pollution can exacerbate the aging
process [1]. Moreover, skin wrinkling also progresses as dermal
thickness is reduced over time due to decreased collagen [5,6].
Most of the collagen supplements recommended by
experts are enriched with peptides containing amino acids -
including proline, glycine, and hydroxyproline - considered
to be essential components of collagen [7-9]. Beyond this,
researchers have claimed that increasing peptide production
of hyaluronic acid in skin fibroblasts induces fibroblast
migration and strengthens collagen, thus raising the amount
of moisture in the stratum corneum [10]. Hence, the existing
data suggest that the presence of these proteins in the body
helps to maintain the amount of collagen in the skin [10].
Furthermore, collagen is considered crucial for skin health
because both photo-aging and intrinsic aging decrease its
presence in the body [11]. This in turn causes a decrease
in the skin thickness, as well as a loss of elasticity and
flexibility [12].
In recent years, collagen supplements have been increas-
ingly used, as they are advertised as a potential remedy
against the aging process [13]. It has been found that marine
fish collagen has homology with human collagen and there-
fore it has been widely utilized as nutritional addendum along
with collagen peptides [14]: they have a very good safety
profile, biocompatibility, high bioavailability in the human
gastrointestinal barrier, safety, and high bioactivity [15].
Objectives
Current research reveals that collagen use could result in
a reduction of wrinkles, rejuvenation of skin, and reversal
of skin aging [16], which may improve skin hydration and
elasticity [17]. However, the available evidence regarding
types of collagen or its mechanism of action, duration to
produce desired results and side effects have not been rigor-
ously reviewed or synthesized. This could create controversy
in using collagen to reverse the aging process. Moreover, it
is yet unclear which type of collagen (topical or oral) needs
to be used to produce these coveted effects. Therefore, we
undertook this research to collate the consequences of oral
collagen with those of topical collagen in reducing or delaying
the aging process.
Methods
The researcher conducted this research to appraise, synthe-
size, and aggregate the available evidence to measure how
both oral and topical collagen are used to reduce or delay
the aging process.
Inclusion and Exclusion Criteria
The researcher carried out an electronic search on different
attributes of collagen, such as the benefits of collagen supple-
ments, types, mechanisms of action, and side effects, as well
as how long it takes to produce results. Study inclusion eligi-
bility was contingent on whether the research had focused the
effects of collagen supplements on aging reversal and whether
it was an original study published in English from 2010 to
2020 across both developed and developing countries. The
researcher excluded secondary data, letters to the editor, case
reports, and gray literature from this review.
Information Sources and Search Strategy
The research was conducted by the researcher who completed
a search of published articles in 2020, scanning databases
such as PubMed and Google Scholar. An independent search
was carried out by the author, who examined the results for
potentially appropriate studies, retrieving any needed full-text
articles. The researcher grouped search terms into 4 major
categories by PICOS (Population, Intervention, Comparison,
Outcomes and Study) design as a framework to formulate
eligibility criteria. The researcher identified a combination
of Medical Subject Heading (MeSH) keywords and text
words. The most prevalent search terms found in abstracts
and titles included the following: “collagen supplement and
aging,” “collagen supplement and wrinkles,” “role of collagen
supplement in skin rejuvenation, “collagen supplement and
aging reversal,” “benefits of collagen supplements in reducing
aging,” “types of collagen in reducing aging,” “mechanism of
collagen supplements in reducing aging” and “side effects of
collagen supplements used for anti-aging”.
Data Extraction
All appropriate research studies were imported into the ref-
erence manager software (Endnote, Clarivate Analytics) file,
where each study was reviewed, and titles were also screened
for duplicates. The abstracts were not considered for further
Original Article | Dermatol Pract Concept. 2022;12(1):e2022018 3
review, which did not explicitly explore the study objective.
Finally, the full-text articles of the remaining germane articles
were obtained and examined. This action was followed by
abstracting and summarizing the articles that met the eli-
gibility criteria using a proforma standard. Aside from this,
the bibliography of the remaining studies was scrutinized to
avoid missing any useful studies. This process of searching the
articles was carried out independently by the author, and their
judgments and extracted summaries were matched to identify
the differences and to resolve them accordingly.
Independent reviewers filled out a standardized data
extraction sheet for the eligible research articles. The review-
ers compared the data extraction tables to ensure including
the imperative findings of the eligible studies and pilot tested
these sheets before beginning the extraction process. Besides,
prevailing research articles on the chosen topic were reviewed
to describe the data extraction proforma objectives. Any dis-
crepancies between the independent reviewers were resolved
by consensus between two other reviewers.
Results
Decisions Reached Regarding the Search Strategy
The researcher screened the identified articles initially by
titles, then by abstracts, and finally, a full-text article assess-
ment was carried out, discarding any articles not meeting the
pre-defined eligibility criteria. As a result, the initial search
identified 820 citations in PubMed and Google Scholar;
however, 150 articles were duplicates. Of the remaining 670
unique studies, the researcher reviewed titles and abstracts,
finding 150 relevant abstracts. Upon reviewing the latters,
135 articles did not meet the eligibility criteria. Hence, the
researcher was able to retrieve the complete texts of 15 arti-
cles, though more than 12 articles met the necessary criteria
and were included in the review, as shown in Figure 1.
Usage of Oral Collagen Supplements: Evidence from
Human Studies
A study was conducted in Japan in which authors gave
collagen peptides to patients with aging, wrinkled skin
(Table 1). These patients included 66 women from Japan
who were more than 40 years old, about whom research-
ers recorded any improvements in skin parameters. These
patients were given either 10 g of collagen for 56 continu-
ous days or no treatment at all (placebo) [18]. The authors
observed a statistically noteworthy dissimilarity in the mois-
ture of the skin throughout the experiment, accompanied by
a substantial increase in the moisture for the group under
treatment when compared with the placebo group. Skin
moisture analyzers were utilized to test skin moisture; they
are portable devices that test different skin factors utilizing
RECORDS IDENTIFIED THROUGH
DATA BASE SEARCHING
N=820 AFTER REMOVAL OF
DUPLICATE STUDIES
N=150
NUMBER OF UNIQUE STUDIES
N=670
NUMBER OF RELEVANT
ABSTRACTS
N=150
NUMBER OF FULL TEXTS
N=15
NUMBER OF ARTICLES
INCLUDED IN THE REVIEW
N=12
INCLUDED ELIGIBILITY SCREENING IDENTIFICATION
ELIGIBILITY CRITERIA NOT
MET
N=3
ELIGIBILITY CRITERIA NOT
MET
N=135
NUMBER OF IRRELEVANT
TITLES AND ABSTRACTS
N=520
Figure 1. Flow chart summarizing the identification and selection of papers.
4 Original Article | Dermatol Pract Concept. 2022;12(1):e2022018
bioelectric impedance analysis. The level of skin moisture is
ascertained by the time it takes for the current to travel across
the skin. Additionally, the same study enrolled French women
of more than 40 years old and followed a similar protocol
for collagen treatment for about 3 continuous months. At
the completion of treatment, the author found a noteworthy
moisture elevation in the collagen treatment group compared
with the placebo group [18].
Moving forward, researchers undertook a randomized
controlled trial (RCT) in order to evaluate the potency of
collagen peptides [19]. Recruited participants were randomly
assigned to ingest either oral liquid supplements containing
collagen peptides (50 ml) or placebo daily for 12 weeks [19].
No noteworthy dissimilarity in skin elasticity was noticed
between the 2 arms (Table 1). However, in the subgroup
analysis, the authors noticed that study participants who
underwent cosmetic surgeries in the treatment group showed
improvement in skin elasticity, as opposed to their coun-
terparts, who showed no improvement. At the completion
of the study, participants in the therapeutic arm achieved
higher marks in some skin parameters like hydration and
elasticity [19].
In another RCT, women were allocated to 4 different arms
[20]. The first arm received 2.5 grams of collagen hydrolysate,
the second arm was given 5.0 grams of collagen hydrolysate,
the third arm received 2.5 grams of a placebo, and the fourth
arm was given 5.0 grams of placebo [20]. Participants were
followed for around 60 days, and it was found that each
treatment arm with a different dose of collagen hydrolysate
showed a statistically noteworthy rise in the elasticity of the
skin when juxtaposed with their counterparts in 2 placebo
groups. Improvement in elasticity was noticed among elderly
women relatively earlier (ie, at 1-month follow-up) [20].
Furthermore, a positive correlation was observed between
treatment with collagen hydrolysate and skin moisture and
evaporation, with statistically insignificant results [20].
Another double-blinded RCT was undertaken to assess
the collagen (with low molecular weight) effects on the elas-
ticity of the skin elasticity, hydration, and finally wrinkling
[21]. This study was conducted with Korean women at least
40 years old (n = 64) who were randomized to 1000 mg
of collagen or to placebo every day for 3 months [21]. The
authors found noteworthy elevations in skin hydration in the
treatment arm even at 6 weeks of follow-up when compared
to the placebo group. Furthermore, different parameters of
skin wrinkling (all 3 parameters) and skin elasticity (1/3
parameters) were notably elevated in the treatment arm when
compared with the placebo group, as shown in Table 1 [21].
In the same vein, 1 more RCT was conducted to find out
the effects of collagen hydrolysate constituted of the bioac-
tive dipeptides, prolylhydroxyproline, and hydroxypropyl-
glycine on Chinese women (n = 85) of at least 35 years of
age [22]. The study was comprised of 3 main groups: 1 was
randomized to receive collagen peptides (higher content), 1
was randomized to collagen peptides (lower content), and
the last group received placebo [22]. The total duration
of the study was roughly 2 months, and participants took
their respective treatments daily. Both intervention arms
demonstrated substantial improvement in skin moisture,
especially around the cheek and canthus, as opposed to
the placebo group, which displayed no such improvements.
Moreover, the findings also showed a substantial increase in
the moisture and elasticity of the skin, as well as a reduction
in wrinkling and roughness in the first treatment group,
unlike either the second or the placebo groups, as shown in
Table 1 [22].
Usage of Oral Collagen Supplements: Evidence from
Animal Studies
Apart from studies conducted on human beings, animals have
been examined as well to assess the effect of collagen [23]. In
animal models, the authors have used clinical and histological
appearance, along with gene expression, to study the neces-
sary outcomes. One research was carried out to assess the
consequences of collagen hydrolysates on 9-month-old mice
for 24 weeks. The results of the study revealed a significant
increase in both distribution and density of said collagen and
ratio between type I and type III collagen, with a particular
dose-response relationship [23].
In another study, collagen peptides were given to mice
for one and a half months [24]. The authors found a higher
expression of genes, along with their upregulation in the skin
[24]. One more study was conducted on mice, in which they
were fed a diet containing collagen hydrolysate for roughly
3 months. The study revealed improvements in the water
content of their skin and an increase in elasticity, as opposed
to the mice in the control group, who experienced no such
benefits [25]. Lastly, mice were observed on a diet rich in
prolylhydroxyproline and hydroxypropylglycine for around
5 weeks in one more study. The mice that received collagen
hydrolysates showed increased skin hydration [26].
Usage of Topical Collagen Application on Delaying
the Aging Process
Generally, there have been fewer studies assessing the effect
of topical collagen on the aging process when compared
with the studies conducted for oral collagen supplements.
For instance, one conducted by Sanz et al in 2015 revealed
that those women who were asked to apply a product con-
taining collagen performed better than those in the control
group [27]. More specifically, around three quarters of the
treated women showed anti-wrinkling effects and substantial
increases in the dermal density and elasticity of their skin after
7 days of treatment [27]. Similarly, Matthias et al conducted
a retrospective study in Germany and South Africa on 480
Original Article | Dermatol Pract Concept. 2022;12(1):e2022018 5
Table 1. Previous usage of Oral Collagen Supplements: Evidence from Human Studies
Study
Author
Study
Year Country
Study
Design
Sample
Size Participants Age (Years) Intervention Control Arm Study Results
Adverse
Effects
Sangsuwan
et al [40]
2020 Thailand RCT 36 Post-
menopausal
women
50-60 5 grams of
oral collagen
hydrolysate
Placebo ‐ Skin elasticity was found to be signifi-
cantly different between intervention and
control groups.
None
Žmitek
et al [39]
2020 Germany RCT 34 Caucasian
Healthy
females
40–65 10 mL of a
syrup having
sh collagen
and other active
ingredients
10 mL of
colored
placebo
having avors
without active
ingredients
‐ Dermis density was improved.
‐ Periorbital wrinkle area was reduced
‐ Improvement in skin smoothness.
‐ Skin hydration improved.
‐ Dermis thickness, trans-epidermal water
loss and viscoelasticity did not improve.
None
Campos
et al [29]
2019 RCT 60 Healthy
study
participants
40-50 Topical and
hydrolyzed
collagen
Placebo in
oral form
‐ Topical collagen improved skin elasticity
and viscoelasticity parameters.
‐ Skin elasticity, hydration and echogenicity
of dermis were improved after 1 month
of topical collagen application, as well as
oral collagen.
None
Bolke et al
[41]
2019 Germany RCT 72 Healthy
females
≥ 35 2.5 grams of
collagen and
other active
ingredients
Placebo ‐ Hydration of skin, elasticity and density
were improved.
‐ There was reduction in skin roughness.
‐ All test parameters were different between
intervention and placebo groups, which
also remained at the time of follow-up.
None
Kim et al
[21]
2018 Korea RCT 64 Korean
women
40–60 Collagen with
low molecular
weight
Placebo ‐ The intervention group showed improve-
ment in the hydration values of skin at 6
and 12 weeks.
‐ Three parameters of skin wrinkling
improved drastically in the intervention, as
opposed to the placebo.
‐ 1/3 parameters improved substantially in
the intervention group after 12 weeks as
opposed to placebo group.
‐ 2/3 parameters in the intervention arm
improved after 12 weeks.
None
Table1 continues
6 Original Article | Dermatol Pract Concept. 2022;12(1):e2022018
Study
Author
Study
Year Country
Study
Design
Sample
Size Participants Age (Years) Intervention Control Arm Study Results
Adverse
Effects
Inoue et al
[22]
2017 China RCT 85 Chinese
women
35–55 Collagen
hydrolysate
having a
higher content
of bioactive
collagen-
Collagen
hydrolysate
having a
lower content
of bioactive
collagen
Placebo ‐ The intervention arm demonstrated a sig-
nificant improvement over the placebo
arm in moisture, elasticity, wrinkles, and
roughness.
None
Genovese
et al [19]
2017 Rome
(Italy)
RCT 120
F:111
M: 9
Volunteer
subjects
47.72 (6.5)
49.65 (6.5)
50mL of
collagen
Placebo ‐ -No difference was seen between the inter-
vention and placebo arms for skin elasticity.
-Subjects who had cosmetic surgeries
demonstrated increased skin elasticity.
No
adverse
events
Sanz et al
[27]
2015 Spain Open and
intra‐
individual
study clinical
Study
32
women
Women with
sensitive
skin bearing
wrinkles
45-55
(median: 49)
Serum containing
an amalgamation
of pro‐collagen
lipopeptide,
extract of apple,
creatine, and
urea
Self-control ‐ 71% of the women in the intervention
group experienced anti-wrinkle effects.
‐ Dermal density improved by 11%
after 1 week.
‐ Significant improvement was seen in cuta-
neous hydration and cutaneous elasticity
(cheekbone) after 1 week when compared
with baseline.
Not
reported
Asserin
et al [42]
2015 Japan
and
France
RCT 66
Japanese
and 106
French
women
Japanese
and French
women
40‐59
40‐65
10 g of collagen Placebo ‐ Significant improvement in skin hydration
and dermis density after 8 weeks of intake
‐ A significant reduction was seen in the
fragmentation of the dermal collagen
network.
None
Proksch
et al [20]
2013 Not
reported
RCT 69 women 35‐55years
old
2.5g of CH, and
5.0g of CH
2.5g of
placebo,
and 5.0g of
placebo
‐ A significant improvement was seen in
elasticity of skin in both intervention arms,
as compared to the placebo arm.
‐ Elderly women showed a statistically sig-
nificantly higher skin elasticity level.
‐ No effect of CH was seen on skin hydra-
tion and evaporation.
None
Table 1. Previous usage of Oral Collagen Supplements: Evidence from Human Studies (continued)
Table1 continues
Original Article | Dermatol Pract Concept. 2022;12(1):e2022018 7
Study
Author
Study
Year Country
Study
Design
Sample
Size Participants Age (Years) Intervention Control Arm Study Results
Adverse
Effects
Byrne et al
[30]
2010 Ireland RCT 22 Caucasian
female
subjects
39 to 60 Triple peptide
complex (3%)
Placebo ‐ There was substantial reduction in the
frequency of wrinkles, total wrinkle sur-
face average, wrinkle length and average
wrinkle depth in the intervention group,
as opposed to placebo group.
‐ There was improvement in the wrinkle
parameters by 10–19% compared with
the untreated baseline, and this improve-
ment was 13–28% when compared to the
placebo group.
None
Aust et al
[28]
2008 Germany Retrospective
analysis
480
F: 400
M: 80
Patients The mean
(SD) was 49
± 15.5 years
Percutaneous
collagen
Self-control ‐ There was improvement in the skin by 60
to 80%.
‐ A substantial upsurge in collagen and elas-
tin deposition on histological examination
was observed in the subset of patients.
‐ There was a roughly 40% thickening of
the epidermis mainly stratum spinosum
after 1 year of treatment.
Not
reported
CH = collagen hydrolysate; SD = standard deviation; RCT = randomized control trial.
Table 1. Previous usage of Oral Collagen Supplements: Evidence from Human Studies (continued)
8 Original Article | Dermatol Pract Concept. 2022;12(1):e2022018
patients with wrinkles, lax skin, scarring, and stretch marks
[28]. These patients were administered percutaneous collagen
after preparing their skin with necessary vitamins and creams
for at least 1 month [28]. The findings demonstrated that
patients were found to have skin 60% to 80% improved
from before the treatment. Furthermore, researchers carried
out a histologic examination on a subset of patients that
demonstrated a substantial upsurge in collagen and elastin
deposition. There was around 40% thickening of the epider-
mis, mainly stratum spinosum, 1 year after treatment [28].
Similarly, Campos et al evaluated the consequences of
topical and oral collagen additions in the skin enhancement of
60 healthy female subjects. The findings showed that females
who were given a topical product demonstrated a substantial
rise in skin hydration and elasticity at the end of 1 month. On
the other hand, the group with oral supplementation showed
more noticeable results in dermal echogenicity and decreasing
pore size at the end of 3 months without any adverse effects
[29]. Another study demonstrated that those patients who
received topical treatment showed a noteworthy depletion in
the total wrinkle surface, number of wrinkles, and average
wrinkle length and depth were observed in comparison with
those who underwent placebo.
In addition, the anti-wrinkle activity of the topical tri-
ple peptide complex (3%) has been reported by a clinical
research conducted by Byrne et al in 2010. Their findings
suggested that topical application significantly improves the
photo-damaged skin by the end of 1 month when compared
with the placebo group [30]. These studies revealed notewor-
thy relative depletions in the number of wrinkles and total
wrinkle surface - in conjunction with increase in their mean
depth and length - at the end of 1 month, ranging from 10%
to 28% [30].
Mechanism of Action of Collagen Supplements
One of the proteins found in abundance in human beings is
collagen, and it helps to maintain the structure, stability, and
strength of the dermal layers [31]. The studies have shown
antioxidant and established reparative actions of collagen in
wrinkled or damaged skin. Skin experiences the double action
of collagen: first, it provides the skin essential components for
both elastin and collagen, and second, it is attached to the
fibroblast receptors in the dermis to initiate the production of
elastin and hyaluronic acid [32]. So far, oral collagen has been
studied to a greater extent than topical collagen. The available
literature suggests that the topical application of collagen
improves both skin elasticity and texture. However, topical
collagen does not infiltrate the skin completely owning to
its high molecular weight [33]. In contrast, oral collagen
ingestion has been found to improve mechanical properties
by increasing both the density and the diameter of collagen
fibrils [34]. Orally consumed collagen bioactive peptides are
absorbed relatively quickly because such collagen products
have lower molecular weights, distributing these peptides
easily across several tissues [35]. Additionally, evidence from
the animal models suggested that oral administration of
collagen reduces the intensity of skin hydration caused by
UV radiation and also reduces hyperplasia of the epidermis
caused by UV rays [36]. Furthermore, oral intake of collagen
enhances the moisture content of the skin, especially the stra-
tum corneum, as well as the elasticity of the skin, reducing
wrinkling and roughness [37]. Overall, collagen causes an
increase in fibroblasts and extracellular matrix proteins and a
decrease in metalloproteinase. These rising fibroblasts found
in the various layers of the human dermis produce a plethora
of extracellular matrix proteins that enhance skin health and
thus slow skin aging [38].
Side Effects of Collagen Supplements Reported in
Human Studies
Generally, no adverse effects of oral and topical collagen
have been observed in any of these studies [39]. There have
been no side effects such as vomiting, diarrhea, nausea, or
constipation reported in the treatment or control groups
of any of the studies [40]. For example, trials conducted in
2019 and 2020 found no adverse effects of collagen until they
observed their participants [39,41]. These findings were also
confirmed by a research by Inoue et al in 2017, where they
conducted a RCT to assess the effect of high versus low doses
of collagen and placebo [22]. Likewise, Genovese et al had
shown analogous findings concerning the side effects during
the period of study while comparing the effect of supplements
on skin elasticity, wrinkling, and roughness with the placebo
[19]. Besides, these findings were further endorsed by a study
conducted in 2013 by Proksch et al: the authors found no side
effects in any of the 4 groups that were assigned to high-dose
collagen, low-dose collagen, a high-dose placebo, or a low-
dose placebo [20]. One more double-blinded RCT conducted
on Korean women showed no adverse events related to the
treatment or intervention throughout the study period [21].
Similarly, there were no adverse effects of topical collagen in
various studies [28-30].
Conclusions
Based on the existing literature from both animal and human
studies, it seems that oral collagen supplements improve skin
elasticity, turgor, and hydration and reduce skin wrinkling
and roughness. The existing premise reveals that neither oral
nor topical collagen is superior to the other; rather, both
types reduce or delay skin aging. Thus, products of collagen
peptides can be considered to be anti-aging remedies by der-
matologists, especially in cosmetics. However, the existing evi-
dence has not provided enough robust evidence for collagen
Original Article | Dermatol Pract Concept. 2022;12(1):e2022018 9
supplements due to differences in the weights of collagen
being topically and systemically absorbed. Hence, more epide-
miological and interventional studies with large sample sizes
and required follow-up appointments are requested to assess
the effectiveness of the topical compounds containing colla-
gen on wrinkled and aging skin while comparing the same to
the oral collagen supplement instead of the placebo. As the
trend of both forms of collagen supplement use might con-
tinue to rise, more thorough research is required to validate
their potential positive effects before they are widely used.
One of the strengths of the included studies was research
design, as all the studies on human beings were RCTs that
provided solid evidence due to the balance of known and
unknown confounders between the treatment and control
groups. However, the types and doses of collagen were not
similar across the studies; therefore, further studies with
consistent doses in different settings may be required before
making any judgments about the use of oral collagen. This is
crucial because some of the proponents of collagen might try
to apply the results of animal models to human beings, but
animal studies cannot be generalized to humans due to differ-
ences in physiological and biological mechanisms.In the same
way, these collagen products have usually been tested in the
developed or high-income sectors of different age groups. Thus,
there is no evidence about whether these products could pro-
duce analogous results in the various populations residing in
low- to middle-income countries with limited resources. Hence,
this warrants the replication of similar studies in developing
countries by using a similar study design. Lastly, the review
found no side effects of either topical or oral collagen treatment
during the study period, and most of the studies had followed
their participants for 12-24 weeks. Thus, there is no clear
evidence about how these collagen products function after the
study ends and whether these products tend to produce adverse
effects in the long run that need to be further explored.
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