Piroctone Olamine 0.8% Shampoo

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Scalp application of the antioxidant piroctone olamine reduces hair shedding


in an 8‐week randomized, double‐blind, placebo‐controlled clinical study

Article in International Journal of Cosmetic Science · August 2021


DOI: 10.1111/ics.12737

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Received: 17 March 2021
| Accepted: 1 August 2021

DOI: 10.1111/ics.12737

ORIGINAL ARTICLE

Scalp application of the antioxidant piroctone olamine


reduces hair shedding in an 8-­week randomized,
double-­blind, placebo-­controlled clinical study

Michael G. Davis1 | Melissa P. Piliang2,3 | Wilma F. Bergfeld2,3 |


Tamara L. Caterino1 | Brian K. Fisher1 | Jarek P. Sacha1 | Greg J. Carr1 |
Laura T. Moulton1 | Deborah J. Whittenbarger1 | Supriya Punyani4 |
James R. Schwartz1

1
The Procter & Gamble Company,
Mason, Ohio, USA Abstract
2
Department of Dermatology, Objective: Increasing scalp hair fullness is a global unmet consumer need. An
Cleveland Clinic, Cleveland, Ohio, USA approach to decrease hair shedding by reducing scalp stratum corneum oxidation
3
Department of Pathology, Cleveland via a combination of antioxidant and barrier-­enhancing technologies has been
Clinic, Cleveland, Ohio, USA
4
previously demonstrated. The purpose of this study was to test the effectiveness
The Procter & Gamble Company,
Singapore, Singapore of the individual antioxidant piroctone olamine in two different product forms
Correspondence
(shampoo or leave-­on product) for activity to improve hair retention.
Michael G. Davis, The Procter & Methods: Female subjects with self-­perceived hair thinning participated in an
Gamble Company, Mason, Ohio, USA. 8-­week, double-­blind, placebo-­controlled, randomized clinical study to evaluate
Email: [email protected]
either a piroctone olamine (PO) containing shampoo or a PO containing leave on
Funding information treatment, each relative to their corresponding placebo formulation Too many
P&G Beauty
periods. Results for phototrichograms, TEWL, and biomarker analysis of scalp
condition for the shampoo treatments are discussed. Phototrichogram results are
shared for the assessment of the leave on treatment.
Results: Statistically significant increases in hair amount were observed by pho-
totrichogram after use of both PO-­containing products versus placebo formula-
tions. The PO shampoo treatment also significantly decreased oxidative stress on
the hair and scalp, and improved scalp condition as assessed by TEWL and scalp
biomarker values.
Conclusion: These results illustrate the effectiveness of a cosmetic antioxidant
to improve scalp condition thereby improving hair retention. The observed im-
provements in scalp condition are consistent with previous reports with other
antioxidant technologies and suggest that the hair retention effect was achieved
by preventing oxidative damage to the scalp.

KEYWORDS
antioxidant, hair growth, hair loss, hair shedding, hair treatment, scalp, skin barrier

© 2021 Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.

26 | wileyonlinelibrary.com/journal/ics
 Int J Cosmet Sci. 2021;43(Suppl. 1):26–33.
DAVIS et al.    | 27

I N T RO DU CT ION treatment. Due to the demonstrated efficacy of this treat-


ment regimen, we decided to investigate whether a single-­
Once hair is lost, there are few non-­surgical reliable op- component technology containing PO alone would also
tions to re-­grow it [1]. A more viable solution to non-­ demonstrate hair retention benefits via this cosmetic anti-
patterned premature hair thinning is to inhibit loss before oxidant approach.
age-­related acceleration begins. Thus, we have undertaken The previous 24-­week study utilizing a combination
clinical studies to evaluate practical cosmetic materials in of antioxidant technologies demonstrated significant dif-
a preventative strategy to diffuse hair loss. That strategy is ferences between treatment and placebo groups at 8, 16
based on the hypothesis that premature hair shedding is, and 24 weeks [2]. This manuscript describes the results
in part, due to increase in scalp oxidative stress [2]. of a shorter placebo-­controlled 8-­week clinical study per-
We have previously shown [2] that topical delivery of formed to evaluate one of those technologies, piroctone
a mixture of materials with direct and indirect antiox- olamine, delivered either via a shampoo or a leave-­on
idant activities can create a scalp environment that re- treatment for hair retention effectiveness.
duces premature hair loss. This is based on substantial
observational and treatment data that relate a poor scalp
condition to increased hair shedding and impaired nor- MATERIALS AND METHODS
mal pre-­emergent hair maturation via oxidative stress [3].
Since the skin's surface natural antioxidant defences can Two cosmetic clinical studies (a shampoo study and a
be overwhelmed by exogenous oxidant stress [4–­7], sup- leave-­on treatment study) were conducted using the for-
plementing the scalp with topically applied cosmetic an- mulations shown in Table 1. The study was approved by an
tioxidant materials is a rational approach to shielding the IRB as well as regulatory, legal, clinical and toxicology per-
skin from oxidative stress so that it can naturally restore sonnel at the test facility (Comprehensive Research Group,
normalcy and reduce premature hair loss. Minneapolis, MN, USA) and at The Procter & Gamble
The prior approach [2] employed an antioxidant and Company (P&G). ICH E6 and Good Clinical Practices
barrier-­enhancing combination of zinc pyrithione (ZPT), guidelines were followed. All subjects read and signed an
zinc carbonate (ZC) and piroctone olamine (PO) in a informed consent before participating in the study. A P&G
shampoo in combination with a ZPT-­containing leave-­on clinical monitor and board-­certified dermatologist from

T A B L E 1 Compositions of treatment
Treatment Leave-­on
formulations
Function Materials (all USP grade) shampoo treatment
Surfactants Sodium laureth sulphate Xa
Sodium C10-­15 pareth sulphate X
Cocamide MEA X
Hair/skin Bis-­aminopropyl dimethicone X
conditioners Glycerine X
Bis-­PEG / PPG-­16/16 PEG / X
PPG16/16 dimethicone
Thickeners Acrylates/C10-­30 alkyl acrylate X
crosspolymer X
Acrylates copolymer
Stabilizer Glycol distearate X
Solvents Water X X
SD alcohol 40-­B X
Deposition aid Guar hydroxypropyltrimonium X
chloride
Cosmetic Piroctone olamineb 0.8% 0.45%
functional
ingredient
a
X denotes present in the formulation; specific levels are proprietary.
b
Not included in placebo control products.
28 |    PIROCTONE OLAMINE DECREASES HAIR SHEDDING

the Cleveland Clinic visited the test facility to observe all hundred and forty-­four subjects finished the study (71 in
study procedures to verify adherence to the protocol. The the placebo group and 73 in the treatment group). Subjects
studies were conducted from April to June 2019. were also resupplied with a commercial conditioner along
with test formulations with instructions to apply only to
the last few inches of hair and avoid direct application to
Study design and subjects the scalp. Subjects were instructed to use only the supplied
products provided for the entire study period: shampoo 4
These were randomized, double-­ blind studies among times per week and conditioner ad lib only at the tips of the
healthy female subjects (ages 25–­65) with Fitzpatrick skin hair. Subjects were provided enough products and formula-
type I-­IV [8] who had self-­perceived thinning hair to eval- tions for 2 months of typical usage. All products and for-
uate the effectiveness of either a shampoo treatment or a mulations were stored at room temperature. Measurements
leave-­on treatment relative to their corresponding placebo were taken at baseline and after 8 weeks of treatment.
formulations. Scalp redness was evaluated by a trained
grader at baseline. Any subject with a grade of 2.0 or
higher (on a 6-­point scale) was dismissed from participa- Study design and sample size for
tion in the study. Protocol deviations were recorded to de- assessment of the leave-­on treatments
termine which subjects, endpoints and timepoints should
be excluded from subsequent data analysis. This was a left-­right, split-­scalp comparison of a leave-­on
Subjects were instructed (verbally and in writing) re- 0.45% piroctone olamine treatment formulation applied
garding proper use of the test products and formulations. to one side of the scalp vs. a placebo leave-­on formula-
Subjects also kept a diary of their product usage. Product tion without cosmetic functional ingredients applied to
containers were weighed as a measure of product usage. the other side of the scalp (Table 1). The remaining 43 of
All subjects were supplied the same commercial sham- the enrolled subjects were placed in this treatment study.
poo and conditioner products to use 4 times per week in a That number was determined to provide 80% power to
2-­week washout phase. After the washout phase, 189 sub- detect differences in the phototrichogram measurement.
jects were enrolled into the studies. Since this was a split-­scalp design, the side of the scalp
During the treatment phase, subjects were permitted to receiving treatment was randomized. All enrolled subjects
colour or trim their hair within one week after a clinical were supplied a commercial shampoo and conditioner to
site visit, but they could not change hair style for the dura- use during the treatment phase and were coached in 1-­
tion of study, nor have any salon procedures such as per- on-­1 supervised sessions on proper procedure for formula-
manent waves, chemical relaxing or straightening. They tion application at baseline and at a 4-­week return visit to
were instructed to avoid sun exposure on the scalp and the clinical site. Subjects applied 7 pumps (~1.5 g) of prod-
could not use other leave-­on hair treatments. No other re- uct from the supplied pump container and rubbed it into
strictions were applied. the entire half scalp once per day. Measurements were
taken at baseline and after 8 weeks of treatment. Forty-­
two subjects completed the study.
Study design and sample size for
assessment of the shampoo treatments
Study procedures
Assuming 80% power to detect a statistically significant
difference in hair count by phototrichogram and allow- The study procedures are described in the companion
ing for drop rate, 146 of the enrolled subjects were rand- manuscript [2] and are summarized here. Hair measure-
omized to either the treatment shampoo or a placebo ments were done at baseline and after 8 weeks of test for-
shampoo. Randomization balanced for the following hair mulation usage. Measurements for subjects treated with
loss and scalp health baseline factors: number of shed hairs shampoo included phototrichogram, trans-­ epidermal
collected during screening (low, medium, high), a derma- water loss (TEWL) measurements and tape strips for
tologist assessment of hair loss (Ludwig grade I-­1, I-­2, I-­3), biomarker assessments. For the subjects on the leave-­on
Adherent Scalp Flaking Score [9] as judged by a qualified treatment, phototrichogram assessment was performed.
grader on 8 regions of the scalp and age (25–­40, 41–­49, 50–­ All phototrichogram analysis was performed using the
65). Subjects were randomized to one of two groups: whole automated AI algorithm previously described [2, 10]. The
head treatment shampoo formulation containing 0.8% pi- details of the measurements follow.
roctone olamine or identical whole head placebo shampoo Two days prior to each clinical site visit and evaluation,
formulation that lacked piroctone olamine (Table 1). One subjects were instructed to shampoo their hair with the
DAVIS et al.    | 29

provided shampoo, apply conditioner ad lib only to the the remaining short hairs within the clipped areas were
tips of their hair, rinse off the conditioner and refrain from cut to approximately 0.5 mm in length using a #2041
using any hair care or styling implements until after their Doodle Blade® attached to a corded Wahl® hair clipper
clinical site visit. Subjects were also instructed to refrain (Wahl Home Products) in preparation for imaging. At
from consuming any foods or beverages containing caf- subsequent visits, short regrowth hairs in the clipped
feine or to use nicotine products for 2 h prior to a clinical areas were cut from the scalp with scissors before being
site visit. trimmed as above before imaging.
For biomarker analysis, the skin samples on tape strips A Canfield VEOS Macro Imaging System (Canfield
were analysed as reported previously [11]. Scientific) was used to capture images of the left and
Hair measurements were done at baseline and site right scalp clipped areas, using the scalp tattoos and
visits after 8 weeks of product. At all timepoints, visits the imaging system contact plate to reposition the cam-
were comprised of 2 sequential days in order to prop- era to the same scalp area, angle and distance for each
erly sequence the measurements to minimize manipula- time point. A trained operator used the imaging sys-
tions for the subjects and undue measurement artefacts. tem. Hair counts were analysed with a novel machine-­
Measurements included Canfield macro imaging, self-­ learning algorithm for counting hairs [10]. This method
assessment questionnaire, TEWL in a controlled tem- was qualified with data from previous hair quantifica-
perature and controlled humidity (CTCH room) and tape tion studies.
strips. The details of those measurements follow. Outside of the clipped areas, 5 tape strip locations were
Hair baseline shedding quantitation: A novel method selected on either side of the head corresponding to the
for hair shedding analysis was developed for this study treatment site for each side. The first started 1” from the
and was executed as follows: in a controlled temperature frontal hairline, and each successive tape strip location
and controlled humidity, a study Cosmetologist removed was next to the prior tape strip location moving towards
the hair from the ponytail, while the subject was seated in the back of the head. The adjacent, non-­overlapping tape
a massage chair, with the subject's head positioned over a strip sites did not extend into the clipped areas. Two strips
collection box to capture any loosened hairs from the po- with D-­Squame® tape (CuDerm Corp., 22-­mm discs, D-­
nytail fall. Using the coarse teeth of a Conair Detangle & 100) were done at each of the five sites. Any adhering
Style comb (Style Comb #935022, Conair Corp.), hair was hairs were removed with tweezers. The strips were frozen
gently detangled. Then, the hair was combed with the fine until assayed for skin biomarkers.
teeth for 100 strokes downwards into the collection box,
combing all hairs on the entire scalp. Shed hairs were col-
lected on Cling VinylTM sheets (Creative-­Coldsnow.com), Statistics
which were subsequently stained with rhodamine B dye
(Sigma-­Aldrich) to highlight the shed telogen hair bulbs All statistical analysis followed ICH-­ E9 Statistical
[12]. The hairs were counted manually, twice by each Principles for Clinical Trials. For all endpoints, treat-
of 3 separate qualified graders. Each grading session in- ment effects were assessed for the measured response (or
cluded control standards inserted randomly for validating a transformation of it) with the analysis of covariance to
the grading accuracy. Broken hair fibres were not counted adjust for the baseline response level. For the split-­scalp
in the hair shedding analysis. portion, a mixed model was used since the subject is the
For relocating the same sites on the scalp for each experimental/statistical unit.
visit, a small site (1.9 × 1.9 cm) to be clipped was se-
lected on the left and right sides of the centre of the
scalp (directly above the ears) by a licensed cosmetolo- RESULTS
gist. A licensed tattoo artist then made a small tattoo dot
to mark each site. At baseline, there were no significant differences between
Within the clipped areas, the hairs were drawn into control and treatment groups. At baseline, the average
a bundle and secured with tape. The bundled hairs were total Adherent Scalp Flaking Score (ASFS) was 7.2, con-
then clipped with scissors as close as possible to the sidered asymptomatic/non-­flaking scalp [9]. All subjects
scalp. The long hairs were pinned away from the clipped were classified as having minimal clinical signs of hair
sites to expose the scalp to ambient conditions during loss.
the 20-­min acclimation period in a CTCH room prior Biomarker analysis after 8 weeks of shampoo treat-
to taking trans-­epidermal water loss (TEWL) measure- ment is summarized in Figure 1a-­e. S100A12 is a common
ments of the clipped sites (AquaFluxTM AF-­200 TEWL biomarker of many non-­ optimal skin conditions [13].
Towson). Following completion of TEWL measurements, Treatment with the PO shampoo significantly reduced
30 |    PIROCTONE OLAMINE DECREASES HAIR SHEDDING

F I G U R E 1 Skin health biomarkers


measured from scalp tape strips after
8 weeks of shampoo use. The specific
p-­value is indicated in the text. (#
significant from placebo). (a) S100A12
(picogram (pg) S100A12 protein per
microgram (μg) total protein). (b) MPO
(picogram (pg) myeloperoxidase protein
per microgram (μg) total protein).
(c) Scalp HODE (nanogram (ng) of
C9+C13 hydroxyoctadecadienoic acid
per nanogram (ng) linoleic acid). (d) HSA
(picogram (pg) human serum albumin
protein per microgram (μg) total protein).
(e) TEWL (grams (g) water lost per square
meter (m2) per hour)

the level of S100A12 in tape strips versus the placebo shampoo (Figure 1e). A lower TEWL indicates improved
shampoo (p = 0.0013) (Figure 1a). The PO shampoo also barrier and better scalp condition.
significantly reduced oxidative stress biomarker myelop- Analysis of hydroxyoctadecadienoic acid (HODE), an
eroxidase (MPO) (p = 0.0082; Figure 1b). HODE (hy- oxidation product of linoleic acid and marker of hair shaft
droxyoctadecadienoic acid) is an oxidation product of oxidative damage, showed a significant reduction for the
linoleic acid and is thus a marker of scalp oxidative stress PO shampoo versus the placebo shampoo (p = 0.0136) at
status. HODE measured from scalp tape strips was statis- week 8 (Figure 2).
tically significantly reduced (p ≤ 0.0025) in subjects using
the hair treatment regimen versus the placebo shampoo
after 8 weeks of treatment (Figure 1c). For human serum Total hair counts
albumin (HSA), a marker of skin barrier function, the PO
shampoo showed a directional effect (p = 0.0822) versus Phototrichogram images within the scalp hair-­ clipped
the placebo shampoo (Figure 1d). While this observation areas were analysed by an in-­ house automated algo-
is not statistically significant, the numerical effect is con- rithm [1, 10]. Total hair counts were greater in sub-
sistent with the TEWL data (i.e. improved barrier func- jects using the piroctone olamine (PO) shampoo versus
tion). The PO shampoo showed a statistically significant those using the placebo shampoo (Figure 3a). After only
(p = 0.0477) decrease in scalp TEWL versus the placebo 8 weeks of product usage, the PO shampoo showed a
DAVIS et al.    | 31

F I G U R E 2 Hair shaft oxidative stress measurements.


Comparison of hydroxyoctadecadienoic acid (HODE) levels at
8 weeks. Measurements are represented as micrograms (ng) of
C9+C13 HODE normalized to weight of hair used in the analysis
(grams (g)). (# significant difference from placebo)

statistically significant increase in hair count of 2.8 hairs/


cm2 (p = 0.0437). Within the clipped areas, the total num-
ber of hairs was greater for the side of the scalp that had
the piroctone olamine leave-­on treatment applied versus
the side of the scalp with the placebo leave-­on product
with an increase of 3.2 hairs/cm2 (p = 0.0310; Figure 3b).

DI S C US S I O N
F I G U R E 3 Quantification of hair counts by the
As mentioned in the introduction, once hair is lost, there phototrichogram machine learning algorithm method after 8 weeks
are few non-­surgical reliable options to re-­grow it [1]. Our of the PO test product usage versus the corresponding placebo
hypothesis [2, 3] is that premature hair loss is due to non-­ product. The specific p value is indicated in the text. (# significant
optimal scalp condition resulting in an environment that is from placebo). (a) Phototrichogram hair counts after 8 weeks of
not maximally supportive of normal hair fibre maturation PO shampoo (SH) usage. (b) Phototrichogram hair counts after
and retention. The cause-­and-­effect association between 8 weeks of PO containing leave-­on treatment (LOT) usage
scalp condition and maturation of pre-­emergent hair fibre
is well established based on epidemiological and treat-
ment studies of compromised scalp conditions with spe- Piroctone olamine (PO) is a well-­known treatment for
cific symptomologies [3]. It is likely that these disturbed improving scalp condition (reduction of dandruff) [20].
scalp conditions create an environment that perturbs nor- Additionally, previous reports demonstrate that (PO) is
mal fibre maturation during the near two-­week transit to also a metal chelator [21]. Metals, such as iron, can con-
the scalp surface impairing optimal fibre anchorage. tribute to the progression of adverse reactions such as the
The means of transmission of a compromised scalp to formation of hydroxyl radicals and metal chelators have
the nascent hair fibre are likely oxidative stress. All the been shown to prevent iron-­catalysed oxidative damage
disrupted scalp conditions studied that have shown detri- [22–­25]. As discussed in the companion work to this
mental impacts to the associated hair have oxidative stress manuscript [2], oxidation of stratum corneum can result
as a common etiological element [14]. Additionally, it is in damage to the scalp skin barrier via multiple mech-
widely accepted that normal human ageing is also a con- anisms and thus lead to more complex problems that
sequence of a progression of oxidative stress [15, 16]. The can result in premature hair loss and shedding. Since PO
sources and consequences of oxidative stress with respect was effective in improving the measures of these prob-
to the hair are well documented [11, 17–­19]. lems (i.e. TEWL and skin biomarkers), this antioxidant
32 |    PIROCTONE OLAMINE DECREASES HAIR SHEDDING

4. J. J. Thiele, Oxidative targets in the stratum corneum. A new


can be an important supplement for the scalp surface to basis for antioxidative strategies. Skin Pharmacol. Appl. Skin
combat the damage to scalp skin barrier and overall scalp Physiol. 14S, 87–­91 (2001).
condition. 5. J. J. Thiele, C. Schroeter, S. N. Hsieh, M. Podda, L. Packer, The
These studies demonstrate that PO improves scalp con- antioxidant network of the stratum corneum. Curr. Probl.
dition and retains more hair on the scalp relative to placebo Dermatol. 29, 26–­42 (2001).
controls. These effects were detected in several independent 6. C. S. Sander, H. Chang, S. Salzmann, C. S. L. Muller, Ekanavake-­
technical measures (hair counts, TEWL and biomarkers). Mudiyanselage, Elsner P and Thiele JJ, Photoaging is associ-
ated with protein oxidation in human skin in vivo. J. Invest.
Effects were seen with both a PO-­containing shampoo and
Dermatol. 118, 618–­625 (2002).
with PO-­containing leave-­on treatment, thus providing op- 7. G. Valacchi, A. van der Vliet, B. C. Schock, T. Okamoto, U.
tions for applying this technology to consumer use. Obermuller-­Jevic, C. E. Cross, L. Packer, Ozone exposure acti-
As with a previous study, these studies evaluated sub- vates oxidative stress responses in murine skin. Toxicology. 179,
jects with an otherwise non-­symptomatic scalp that did not 163–­170 (2002).
fit the pattern of genetic hair loss [2]. These data further 8. T. B. Fitzpatrick, The validity and practicality of sun-­reactive
demonstrate significant improvement in scalp condition skin types I through VI. Arch. Dermatol. 124, 869–­871 (1988).
9. R. A. Bacon, H. Mizoguchi, J. R. Schwartz, Assessing therapeu-
and hair amount with an antioxidant treatment in an other-
tic effectiveness of scalp treatments for dandruff and seborrheic
wise “normal” scalp, indicating that even under apparently
dermatitis, part 1: a reliable and relevant method based on the
normal conditions, the scalp experiences hidden stress. This adherent scalp flaking score (ASFS). J. Dermatol. Treat. 25,
was also true for hair shaft oxidation, suggesting defects in 232–­236 (2014).
hair shaft formation due to scalp oxidative stress. 10. J. P. Sacha, T. L. Caterino, B. K. Fisher, G. J. Carr, R. S.
Previous studies have shown increases in scalp hair Youngquist, B. M. D’Alessandro, A. Melione, D. Canfield, W. F.
count after treatment with a piroctone olamine shampoo Bergfeld, M. P. Piliang, et al., Development and qualification
[20]. Additionally, a regimen of PO-­containing hair and of a machine learning algorithm for automated hair count-
ing. Int. J. Cosmet. Sci. 43(Suppl. 1), 34–­41 (2021). https://doi.
scalp formulations reduced hair shed, thus increasing
org/10.1111/ics.12735
scalp hair count [2]. Therefore, the present studies further 11. J. R. Schwartz, J. P. Henry, K. M. Kerr, H. Mizoguchi, L. Li, The
support these previous observations. role of oxidative damage in poor scalp health: ramifications to
causality and associated hair growth. Int. J. Cosmet. Sci. 37S2,
ACKNOWLEDGEMENTS 9–­15 (2015).
The authors wish to thank Donald L. Bissett, Ph.D., and Jeni 12. D. Van Neste, T. Leroy, S. Conil, Exogen hair characterization in
Thomas, Ph.D., for their assistance who wrote this manu- human scalp. Skin Res. Technol. 13(4), 436–­443 (2007).
script. The authors also wish to thank Brandon Lane and 13. J. Zhao, A. Zhong, E. E. Friedrich, S. Jia, P. Xie, R. D. Galiano, T.
A. Mustoe, S. J. Hong, S100A12 induced in the epidermis by re-
Debora Chang for product formulation, Abby Newland,
duced hydration activates dermal fibroblasts and causes dermal
Yvonne DeAngelis, Andrew Peplow, Michael Marmor and fibrosis. J. Invest. Dermatol. 137(3), 650–­659 (2017).
Suska Bentz for study execution and data management. All 14. R. D. Sinclair, J. R. Schwartz, H. L. Rocchetta, T. L. Dawson, B.
funding for this research was provided by The Procter & K. Fisher, K. Meinert, E. A. Wilder, Dandruff and seborrheic
Gamble Company (Cincinnati, OH, USA). dermatitis adversely affect hair quality. Eur. J. Dermatol. 19,
410–­411 (2009).
ORCID 15. M. A. Birch-­Machin, A. Bowman, Oxidative stress and ageing.
Br. J. Dermatol. 175S, 26–­29 (2016).
Michael G. Davis https://orcid.org/0000-0002-4756-3295
16. R. M. Trueb, Oxidative stress and its impact on skin, scalp and
Jarek P. Sacha https://orcid.org/0000-0001-6705-4669
hair. Int. J. Cosmet. Sci. 43(Suppl. 1), 9–­13 (2021). https://doi.
James R. Schwartz https://orcid.org/0000-0001-7694-2780 org/10.1111/ics.12736
17. R. M. Trüeb, J. P. Henry, M. G. Davis, J. R. Schwartz, Scalp con-
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