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ORIGINAL CONTRIBUTION
Oral supplementation with specific bioactive collagen
peptides improves nail growth and reduces symptoms of
brittle nails
Doris Hexsel MD
1
|
Vivian Zague PhD
2
|
Michael Schunck PhD
3
|
Carolina Siega
BSc
1
|
Fernanda O Camozzato MD
1
|
Steffen Oesser PhD
3
1
Brazilian Center for Studies in
Dermatology, Porto Algre, Brazil
2
Department of Cell and Developmental
Biology, Institute of Biomedical Sciences,
University of S~
ao Paulo, S~
ao Paulo, Brazil
3
Collagen Research Institute (CRI), Kiel,
Germany
Correspondence
Dr. Doris Hexsel, Brazilian Center for
Studies in Dermatology, Porto Algre, Brazil.
Email: doris@hexsel.com.br
Summary
Background: Brittle nail syndrome is a common problem among women and refers
to nails that exhibit surface roughness, raggedness, and peeling.
Aim: The goal of this study was to investigate whether daily oral supplementation
with collagen peptides alleviates the symptoms of brittle nails and improves nail
growth rate.
Methods: In this open-label, single-center trial, 25 participants took 2.5 g of specific
bioactive collagen peptides (BCP, VERISOL
â
) once daily for 24 weeks followed by a 4-
week off-therapy period. Nail growth rate and the frequency of cracked and/or
chipped nails as well as an evaluation of symptoms and global clinical improvement
score of brittle nails were assessed by a physician during treatment and 4 weeks after
discontinuation.
Results: Bioactive collagen peptides treatment promoted an increase of 12% nail
growth rate and a decrease of 42% in the frequency of broken nails. Addition-
ally, 64% of participants achieved a global clinical improvement in brittle nails,
and 88% of participants experienced an improvement 4 weeks post-treatment.
The majority of participants (80%) agreed that the use of BCP improved their
nails’appearance, and were completely satisfied with the performance of the
treatment.
Conclusions: This study demonstrated that the daily ingestion of BCP increased nail
growth and improved brittle nails in conjunction with a notable decrease in the fre-
quency of broken nails.
KEYWORDS
bioactive collagen peptides, brittle nails, collagen hydrolysate, dietary supplements, fragile nails,
nail growth
1
|
INTRODUCTION
Brittle nail syndrome is a disorder characterized by the increased fra-
gility of the nail plate, exhibiting surface roughness, raggedness (fray-
ing of the distal edge), and peeling.
1,2
It affects about 20% of the
population, and women are affected twice as often as men.
2
Patients
usually complain that their nails are soft, dry, weak, easily breakable,
and incapable of growing long.
2
The pathogenesis of brittle nails is usually related to an impaired
water-binding capacity. This may reflect an abnormality in keratin,
keratin-associated proteins, and/or lipid content.
2
The treatment of
brittle fingernails has been a big challenge for dermatologists.
3
Accepted: 18 July 2017
DOI: 10.1111/jocd.12393
J Cosmet Dermatol. 2017;1–7. wileyonlinelibrary.com/journal/jocd ©2017 Wiley Periodicals, Inc.
|
1
Several topical and systemic therapies have been tried.
1,4,5
Dietary
supplements, nail moisturizers, nail strengtheners, etc., have been
used, but there is no evidence-based data proving their effective-
ness.
1
Collagen peptides have long been used as a food source and/or
supplement.
6
Interestingly, food-derived collagen peptides have not
only been demonstrated to reach the blood stream,
7-9
but also to nota-
bly stimulate the dermal cellular metabolism, improving the biosynthesis
of extracellular matrix proteins and, consequently, restoring the dermal
structure.
6,10-13
In two prospective randomized placebo-controlled clini-
cal trials, Proksch et al
14,15
showed improvement in skin elasticity,
decrease in wrinkle volume, and increase in the collagen I and elastin
content in the skin of women who ingested, during 8 weeks, 2.5 g/d of
the bioactive collagen peptides (BCP) used in the present study.
Although nail assessments were not the objective of those studies, an
improvement in nail quality among the study participants was noticed
as a positive side effect (Proksch E, Schunck M, Zague V, Segger D,
Degwert J & Oesser S, 2014, unpublished data).
Additionally, there is a long-standing belief among consumers that
the ingestion of collagen peptides is good for nails. There is, however,
no scientific-based evidence that it is effective for this purpose. For
this reason, we investigated whether the daily ingestion of 2.5 g of a
specific BCP for 6 months could have a positive influence on the
symptoms of brittle nails and promote nail growth and strength.
2
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MATERIALS AND METHODS
2.1
|
Investigational product
The BCP used in this study present high safety profile and derive
from a complex multistep procedure by the degradation of porcine
type I collagen (VERISOL
â
, Gelita AG, Eberbach, Germany). The pro-
duct is clearly defined by a matrix-assisted laser desorption ioniza-
tion mass spectrometry mass peaks fingerprint with specific collagen
peptides of an average molecular weight of 2.0 kD. It should be dis-
solved preferably in water and ingested everyday according to the
instructions given by the investigator.
2.2
|
Study design
This was an open, single-center clinical trial carried out in the Brazil-
ian Center for Studies in Dermatology, Porto Alegre, Brazil. The
Ethics Committee of the Hospital Moinhos de Vento, Porto Alegre,
Brazil, approved the study. All the patients gave written informed
consent before the study.
2.3
|
Subjects
Twenty-five healthy women were enrolled in the study for treatment
with a daily dose of 2.5 g of BCP for 6 months followed by a 4-
week observation period off therapy.
Participants were aged from 18 to 50 and displayed at least
one of the following signs of brittle nails: lamellar splitting of the
free edge (lamellar peeling), fissuring of the distal nail plate
(edge irregularities), and longitudinal ridging/grooves (nail
roughness).
The main exclusion criteria were pregnancy or lactation; meno-
pause; smoking; acute skin diseases; diseases, medications, products
or procedures that could interfere with the results; nail-biting habit;
taking vitamins and other supplements; food allergies against the
ingredients of the test products; gastrointestinal diseases; changes in
lifestyle or eating habits during the study. Moreover, subjects were
advised to retain their daily occupational and nail care routines, and
to avoid long-term exposure to water, use of abrasive or aggressive
products, and trimming cuticles.
2.4
|
Measurement time points
At the screening visit (4 weeks before baseline), an experienced der-
matologist clinically evaluated all the patients and collected data on
demographic characteristics. Photographs and markings on the nails
for subsequent growth measurements were also performed.
Photographs, clinical assessments, nail growth rate, and fre-
quency of broken nails were performed at baseline (t
0
), after 12 and
24 weeks (t
12
and t
24
) of daily product intake, and 4 weeks after the
last intake (washout phase). Adverse events, compliance, and toler-
ance to the product were assessed during the study. The satisfaction
questionnaire was conducted at the last visit.
2.5
|
Clinical assessments
The dermatologist evaluated the brittle nail symptoms and overall
improvement of the nails at each visit. The assessment of the brit-
tle nail symptoms included nail peeling, edge irregularities, and nail
roughness,
1,16,17
and was performed according to the grading sys-
tem proposed by Sherber et al
16
: none, slight, moderate, and
severe.
The global improvement was defined as excellent, good, fair, no
improvement, or worse,
16
as described in the subjective 5-point
scale suggested by Sherber et al
16
The investigator compared the
photographs of each participant’s nails taken at baseline (t
0
) to those
taken at each of the following visits.
2.6
|
Frequency of cracked and/or chipped nails
The subjects received a form in which they should record daily how
many times their nails had been cracked or chipped on each hand.
2.7
|
Nail growth assessment
The nails of the middle fingers were marked at the edge of the
lunula 4 weeks before the baseline (t
0
) to ascertain the basal growth
rate of each participant. The investigator measured the distance
from the edge of the lunula to the marked point at each visit and
confirmed the results with Mirror-DPS 7.02
â
software (Canfield Sci-
entific Inc., Fairfax, NJ, USA).
2
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HEXSEL ET AL.
2.8
|
Satisfaction questionnaire
A satisfaction questionnaire assessed patient satisfaction with the
treatment on a 5-point scale (very satisfied, satisfied, neither satis-
fied nor unsatisfied, unsatisfied, and very unsatisfied). Patients were
also asked to rate the overall improvement of their nails from 0 to
10, and to answer the following questions: (i) Do you think your
nails are stronger? (ii) Do you think your nails are growing faster?
2.9
|
Statistical analysis
One-way ANOVA with the multiple comparisons Fischer post-test
method was used to compare numerical variables. Significance was
defined as P<.05 using the data analysis software Minitab, version
15.1.1.0 (Minitab Inc, State College, PA, USA). Each value was
expressed as mean standard deviation (SD). The categorical vari-
ables were represented by a percentage.
3
|
RESULTS
Twenty-five participants were enrolled in the study, but one partici-
pant withdrew prior to the last visit. The data of the 24 subjects
who completed the study were included in the analysis. The partici-
pants’mean age SD was 39.3 7.6 years (range: 26-50 years).
No adverse reactions related to the product intake were reported.
3.1
|
Clinical assessments
After 12 weeks of treatment, the number of participants displaying
“severe”or “moderate”nail peeling halved (16 to 8 out of 24), and
those with the score “slight”doubled (8 to 16 out of 24). The most
noticeable results were measured after 24 weeks, when only 6 of 24
participants (25%) had the score “severe”or “moderate,”and 8% of
the participants showed no symptoms. The positive results contin-
ued after the washout phase (Figure 1A).
The positive results on the longitudinal split of the free edge
appeared after 24 weeks of treatment with BCP, where only 4% of
participants scored “severe.”After the washout phase, none of the
participants had the score “severe,”and the percentage of “slight”
scores increased from 17% to 38% (Figure 1B). No clinically relevant
changes were observed before and after treatment with BCP for nail
roughness (Figure 1C).
Of all the 24 participants analyzed, 13 participants (54%) had fair
improvement on nail symptoms at week 12 compared with baseline
(Figure 2). At week 24, 64% achieved notably global improvement
(excellent/good/fair). After the washout phase, 21 participants (88%)
showed excellent/good/fair improvement (Figure 3).
3.2
|
Frequency of cracked and/or chipped nails
Before starting the treatment, the participants’frequency of broken
nails were on average 10 times/mo (10.5 8.4). It significantly
(P<.05) decreased to 6 times/mo (6.4 4.9) after 24 weeks of
treatment, representing a reduction of 42%. This improvement con-
tinued during the washout phase (Figure 4).
3.3
|
Nail growth
The basal nail growth rate of the participants was on average
2.65 0.42 mm/mo. After 12 weeks of treatment with BCP, the
growth rate improved significantly (P<.05) to 2.90 0.47 mm/mo.
These results showed an improvement in nail growth of 10% after
12 weeks of BCP intake. This increased to 12% after 24 weeks, and
to 15% 4 weeks after the last intake (Figure 5).
3.4
|
Satisfaction questionnaire
The majority of participants (80%) agreed that the use of BCP had
improved their nails’appearance and were totally satisfied or satis-
fied with the performance of the treatment. In contrast, only 20%
were indifferent about or unsatisfied with the treatment. The overall
improvement was in average 7.3 2.9 scale points on the 0-10
scale as assessed by the participants. Of the 24 participants who
completed the study correctly, 11 rated the overall improvement
with 9 or 10 scale points (46% of all study participants). Moreover,
75% of patients perceived their nails as stronger, and 71% felt that
their nails were growing faster and longer.
4
|
DISCUSSION
The present authors investigated whether the daily ingestion of
specific BCP for 24 weeks could positively influence the symptoms
of brittle nails and improve nail growth and strength. We detected a
considerable clinical improvement, an increase in nail growth rate,
and a significant decrease in the frequency of broken nails. In accor-
dance with these findings, most participants perceived their nails as
stronger and were satisfied with the treatment. To the best of our
knowledge, no data have been reported regarding the effects of
BCP intake on nails, and the present study is the first clinical trial
demonstrating the efficacy of a specific dosage (2.5 g/d) of
VERISOL
â
on nail growth and brittle nails syndrome.
In this study, the daily intake of BCP clearly attenuated the
symptoms of brittle nails after 24 weeks: 64% of women showed
clinical global improvement. And it was even more pronounced after
the 4-week washout period, when 88% of participants showed clini-
cal global improvement, suggesting a positive effect of BCP treat-
ment is likely caused by the direct effect of BCP on the nail matrix
and nail bed.
When administered orally, BCP are absorbed in the form of small
collagen peptides and free amino acids.
7-9,18
Free amino acids pro-
vide building blocks for the formation of dermal extracellular matrix
proteins and for the epidermal structure, whereas collagen peptides
act as bioactive messengers, activating different signaling pathways
and stimulating dermal and epidermal metabolism.
10,13,19
Hence,
HEXSEL ET AL.
|
3
clinical improvements in brittle nails symptoms observed in the pre-
sent study may not only be a consequence of the protein intake, but
also due to the stimulatory effects of specific collagen peptides on
epidermal and dermal metabolism.
Patients who perceive nail fragility usually complain about slower
nail growth, which may prolong the exposure of the nail plate to
external damaging factors that worsen brittle nail syndrome.
17
The
nails show a continuous growth over a lifetime, controlled by a vari-
ety of cell-cell, cell-matrix, and cell-tissue interactions as well as sig-
naling factors, many of which are not yet clearly defined.
20
It also
depends on age, blood supply, nutrients, environmental, and occupa-
tional factors.
17
The formation of the nail plate requires epidermal proliferation
and nail matrix differentiation.
1
Le Vu et al
19
revealed that collagen
peptides supplementation was associated with the development of
the epidermis with a 5.3-fold enrichment. It does so by upregulating
genes such as Gprc, Krt, and Krtap, which code for structural com-
ponents of epidermis and skin appendages such as hair, hair follicles,
and nails. These findings suggest the potential benefits of BCP treat-
ment on nail growth.
FIGURE 1 Clinical improvement of
brittle nail symptoms after 24 wk of oral
supplementation with bioactive collagen
peptides, followed by 4-wk washout
period. A. Lamellar peeling. B. Fissuring of
the distal nail plate (edge irregularities). C.
Longitudinal ridging/grooves (nail
roughness)
4
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HEXSEL ET AL.
Nail fragility is also determined by the nail plate’s water content.
Experimental trials have shown that BCP may improve the synthesis
of important proteins for the epidermal barrier, turnover, and mois-
ture. Treatment of epidermal skin cells (keratinocytes) led to an
up-regulation of filaggrin, loricrin, and involucrin, cornified envelope
proteins which are important for a healthy epidermal skin barrier and
skin moisturizing (Collagen Research Institute’s data; not published).
Data from clinical
15,21
and animal
22,23
trials have also demonstrated
FIGURE 2 Exemplary pictures of
participants before (t
0
) and after 12 wk
(t
12
) of oral supplementation with bioactive
collagen peptides (BCP). A. The distal
portion of the nail plate showed a lamellar
exfoliation into fine horizontal layers and
triangular pieces could easily be torn from
the free margin at baseline visit (t
0
). After
12 wk (t
12
) lamellar splitting improved
notably. B. Isolated split at the free edge,
which sometimes extended proximally, was
visible at baseline visit (t
0
) and evidently
attenuated after 12 wk (t
12
)
FIGURE 3 Global clinical improvement
of brittle nail syndrome after 24 wk of
daily oral supplementation with bioactive
collagen peptides, followed by 4-wk
washout period
FIGURE 4 Frequency of cracked and/
or chipped nails after daily treatment with
bioactive collagen peptides for 24 wk,
followed by 4-wk washout period.
(mean SEM; n =24; *P<.05)
HEXSEL ET AL.
|
5
the improvement of the epidermal barrier and moisture after colla-
gen peptides supplementation. Therefore, the improvement of nail
strength demonstrated in this trail may be a result of the increased
water-binding capacity of brittle nails promoted by BCP supplemen-
tation. It might help to explain the positive effects even after treat-
ment ceased.
As an open, noncontrolled trial, the results presented herein
should have the inherent biases considered. It can be assumed that
the positive effect is based on the supplementation of VERISOL;
however, a certain influence of behavioral changes of some partici-
pants could not be fully excluded.
With many different measurements taken at each visit, perhaps
the most telling result is the high participant satisfaction. Interest-
ingly, most participants reported they previously tried other treat-
ments without success. Both the physician and the participants
noticed a clear improvement and were satisfied with the treatment.
The ingestion of specific BCP led to a pronounced global clinical
improvement in brittle nails, a significant increase in nail growth rate,
and a decrease in the frequency of cracked or chipped nails in the
present trial. Further research with larger samples and prolonged
treatment is needed to explore the mechanism of action that leads
brittle nails improvements, and larger, placebo-controlled studies are
required to confirm the observed results.
ACKNOWLEDGMENT
The authors thank Aline Flor Silva for her assistance with study
administration.
REFERENCES
1. Iorizzo M, Pazzaglia M, Piraccini BM, et al. Brittle nails. J Cosmet Der-
matol. 2004;3:138-144.
2. Dimitris R, Ralph D. Management of simple brittle nails. Dermatol
Ther. 2012;25:569-573.
3. Cashman MW, Sloan SB. Nutrition and nail disease. Clin Dermatol.
2010;28:420-425.
FIGURE 5 Nail growth improvement
after daily oral supplementation with
bioactive collagen peptides. A. The nail
growth rate increased significantly at
12 wk and was even more pronounced at
24 wk in contrast to baseline
(mean SEM; n =24; *P<.05). B.
Exemplary pictures of participants’nail
growth before (t0) and after 12 wk of
treatment (t
12
) (the nail growth rate at
week 12 was calculated by subtracting the
baseline value and dividing by 3). A
respective improvement in nail growth of
41% (top) and 20% (bottom) is shown in
the representative pictures
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HEXSEL ET AL.
4. Iorizzo M. Tips to treat the 5 most common nail disorders. Brittle
nails, onycholysis, paronychia, psoriasis, onychomycosis. Dermatol
Clin. 2015;33:175-183.
5. Iorizzo M, Piraccini BM, Tosti A. Nail cosmetics in nail disorders. J
Cosmet Dermatol. 2007;6:53-58.
6. Zague V. A new view concerning the effects of collagen hydrolysate
intake on skin properties. Arch Dermatol Res. 2008;300:479-483.
7. Oesser S, Adam M, Babel W, Seifert J. Oral administration of (14)C
labeled gelatin hydrolysate leads to an accumulation of radioactivity
in cartilage of mice (C57/BL). J Nutr. 1999;129:1891-1895.
8. Watanabe-Kamiyama M, Shimizu M, Kamiyama S, et al. Absorption
and effectiveness of orally administered low molecular weight colla-
gen hydrolysate in rats. J Agric Food Chem. 2010;58:835-841.
9. Iwai K, Hasegawa T, Taguchi Y, et al. Identification of food-derived
collagen peptides in human blood after oral ingestion of gelatin
hydrolysates. J Agric Food Chem. 2005;53:6531-6536.
10. Zague V, De FV, Rosa C, Jaeger RG. Collagen hydrolysate intake
increases skin collagen expression and suppresses matrix metallopro-
teinase 2 activity. J Med Food. 2011;14:618-624.
11. Ohara H, Ichikawa S, Matsumoto H, et al. Collagen-derived dipep-
tide, proline-hydroxyproline, stimulates cell proliferation and hyaluro-
nic acid synthesis in cultured human dermal fibroblasts. J Dermatol.
2010;37:330-338.
12. Maia-Campos P, Melo MO, Calixto LS, Fossa MM. An oral supple-
mentation based on hydrolyzed collagen and vitamins improves skin
elasticity and dermis echogenicity: a clinical placebo-controlled
study. Clin Pharmacol Biopharm. 2015;4:1-6.
13. Liang J, Pei X, Zhang Z, et al. The protective effects of long-term
oral administration of marine collagen hydrolysate from chum sal-
mon on collagen matrix homeostasis in the chronological aged skin
of Sprague-Dawley male rats. J Food Sci. 2010;75:H230-H238.
14. Proksch E, Schunck M, Zague V, et al. Oral intake of specific bioac-
tive collagen peptides reduces skin wrinkles and increases dermal
matrix synthesis. Skin Pharmacol Physiol. 2014;27:113-119.
15. Proksch E, Segger D, Degwert J, et al. Oral supplementation of
specific collagen peptides has beneficial effects on human skin phys-
iology: a double-blind, placebo-controlled study. Skin Pharmacol Phys-
iol. 2014;27:47-55.
16. Sherber NS, Hoch AM, Coppola CA, et al. Efficacy and safety study
of tazarotene cream 0.1% for the treatment of brittle nail syndrome.
Cutis. 2011;87:96-103.
17. Van De Kerkhof PCM, Pasch MC, Scher RK, et al. Brittle nail syn-
drome: a pathogenesis-based approach with a proposed grading sys-
tem. J Am Acad Dermatol. 2005;53:644-651.
18. Shigemura Y, Kubomura D, Sato Y, Sato K. Dose-dependent changes
in the levels of free and peptide forms of hydroxyproline in human
plasma after collagen hydrolysate ingestion. Food Chem.
2014;159:328-332.
19. Le Vu P, Takatori R, Iwamoto T, et al. Effects of food-derived colla-
gen peptides on the expression of keratin and keratin-associated
protein genes in the Mouse Skin. Skin Pharmacol Physiol.
2015;28:227-235.
20. Haneke E. Onychocosmeceuticals. J Cosmet Dermatol. 2006;5 :95-100.
21. Inoue N, Sugihara F, Wang X. Ingestion of bioactive collagen hydro-
lysates enhance facial skin moisture and elasticity and reduce facial
aging signs in a randomized double-blind placebo-controlled clinical
study. J Sci Food Agric. 2016;96:4077-4081.
22. Shimizu J, Asami N, Kataoka A, et al. Oral collagen-derived dipep-
tides, prolyl-hydroxyproline and hydroxyprolyl-glycine, ameliorate
skin barrier dysfunction and alter gene expression profiles in the
skin. Biochem Biophys Res Commun. 2015;456:626-630.
23. Oba C, Ohara H, Morifuji M, et al. Collagen hydrolysate intake
improves the loss of epidermal barrier function and skin elasticity
induced by UVB irradiation in hairless mice. Photodermatol Photoim-
munol Photomed. 2013;29:204-211.
How to cite this article: Hexsel D, Zague V, Schunck M,
Siega C, Camozzato FO, Oesser S. Oral supplementation with
specific bioactive collagen peptides improves nail growth and
reduces symptoms of brittle nails. J Cosmet Dermatol.
2017;00:1–7. https://doi.org/10.1111/jocd.12393
HEXSEL ET AL.
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