Vol.:(0123456789)
1 3
Archives of Dermatological Research (2023) 315:2271–2281 
https://doi.org/10.1007/s00403-023-02588-4
ORIGINAL PAPER
Clinical study of a spray containing birch juice for repairing sensitive 
skin
Xiaohong Shu1 · Shizhi Zhao3 · Wei Huo1 · Ying Tang1 · Lin Zou1 · Zhaoxia Li1 · Li Li1,2 · Xi Wang1,2
Received: 2 August 2022 / Revised: 14 December 2022 / Accepted: 16 February 2023 / Published online: 24 March 2023 
© The Author(s) 2023
Abstract
Sensitive skin is described as an unpleasant sensory response to a stimulus that should not cause a sensation. Sensitive skin 
affects an increasing proportion of the population. Sixty-seven participants who tested positive to lactic acid sting test were 
recruited and randomized into two groups to observe the clinical efficacy and safety of a new birch juice spray for repairing 
sensitive skin. One group used test spray A, while the other group used spray B as a control. Both groups were sprayed six 
times daily for 28 days. Noninvasive testing instruments were used to measure stratum corneum hydration, sebum content, 
transepidermal water loss rates, skin blood perfusion and current perception threshold before and after using spray. Facial 
images were captured by VISIA-CR, and the image analysis program (Image‐Pro Plus) was used to analyze these to obtain the 
redness value of the facial skin. Moreover, lactic acid sting test scores and participants’ self-assessments were also performed 
at baseline, week 2 and week 4. Both sprays A and B significantly decreased the lactic acid sting test score, transepidermal 
water loss rates, skin blood perfusion, and redness, while increasing the stratum corneum hydration. Compared to spray B, 
spray A increased sensory nerve thresholds at 5 Hz and decreased the transepidermal water loss rates, skin blood perfusion, 
and lactic acid sting test score. Sprays containing birch juice improved cutaneous biophysical properties in participants with 
sensitive skin.
Keywords Birch juice · Sprays · Sensitive skin · Clinical efficacy
Introduction
Sensitive skin refers to a high reaction state occurring 
under physiological or pathological conditions, mainly in 
the face, manifested as the skin being prone to burning, 
tingling, itching, and tension when stimulated by physi-
cal, chemical, physiological, and psychological factors, 
accompanied or not accompanied by erythema, scales, tel-
angiectasia and other objective signs [1, 2]. Sensitive skin 
symptoms often occur repeatedly and seriously affect the 
appearance of a patient, causing great physical and psycho-
logical pressure [3].
Factors affecting sensitive skin include external and inter-
nal factors. External factors include environmental factors 
(humidity, temperature/climate change, environmental pol-
lution, ultraviolet radiation, wind) and lifestyle (cosmet-
ics, diet, and alcohol), while internal factors include sex, 
age, hormone level, emotion, stress, and genetic factors [4, 
5]. Recently, the number of people with sensitive skin has 
increased due to air pollution and the diversified use of cos-
metics. Approximately 50% of people claim that they have 
sensitive skin, and this proportion is gradually rising [6–8]. 
Therefore, nursing sensitive skin is increasingly important.
The pathophysiology of sensitive skin includes damage to 
the skin barrier, an enhanced immune response, and height-
ened neurosensory sensitivity. In the Muizzuddin classifi-
cation, skin sensitivity can be classified into three types: 
skin barrier damage type, inflammatory response type, and 
nerve hyper-response type [4]. These types can influence and 
interact with each other, suggesting that in nursing sensitive 
skin, considering the three dimensions is crucial. At present, 
 * Xi Wang 
 
625412062@qq.com
1 
Cosmetics Evaluation Center, West China Hospital, Sichuan 
University, Chengdu, Sichuan, People’s Republic of China
2 
Department of Dermatology, West China Hospital, 
Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 
Sichuan 610041, People’s Republic of China
3 
Yoseido (Shanghai) Cosmetics R&D Co., Ltd., Shanghai, 
People’s Republic of China
2272
 
Archives of Dermatological Research (2023) 315:2271–2281
1 3
studies on sensitive skin care have been more extensive [9], 
although reports on the comprehensive clinical care of sensi-
tive skin from multiple dimensions are few.
Birch juice, a colorless and transparent or can be slightly 
yellow fresh juice from the birch, contains rich nutrients 
and biologically active material. It is often regarded as a 
kind of simple and quick beverage, and it also has medicinal 
and cosmetic effects [10–14]. To date, birch juice contains 
11 kinds of fatty acids, 18 kinds of amino acids, 4 kinds 
of vitamins and 18 kinds of mineral elements as well as 
compounds of nicotinic acid, essential oil, betula bud 
acid, saponin, cell division elements, growth elements, 
sulfur ammonia elements, and pyridoxine [15–17]. 
Among them, amino acids, fatty acids, and vitamins play 
an important role in maintaining the skin barrier function, 
reducing inflammation, skin moisturizing, wound healing, 
and whitening [18–22]. The rich mineral elements in 
birch juice are also very valuable for skin care [23, 24]. 
However, the clinical application of birch juice for repairing 
sensitive skin has not been reported. Thus, this study used 
multidimensional methods to evaluate the repair effect of a 
moisturizing spray containing natural birch sap on sensitive 
skin and compared it with commercially available sprays.
Materials and methods
Study design
This randomized, double-blind, clinical study was 
conducted. The research protocol was reviewed and 
approved by the Institutional Ethics Committee. All 
participants provided informed consent.
Study participants
Altogether, 67 people were selected, of which 33 were 
assigned to the Group A and 34 were in the Group B by ran-
dom software distribution. The inclusion criteria were as fol-
lows: aged between 18 and 60; in good health; with positive 
lactic acid stimulation test and experiences skin discomfort 
when the season changes in previous years; participated 
in the study voluntarily and signed the informed consent 
form; and able to strictly comply with the requirements of 
the study protocol, use the product as required, and complete 
follow-up. The exclusion criteria were as follows: pregnant 
or lactating women; with skin diseases (such as psoriasis, 
eczema, psoriasis, and skin cancer), evident erythema, sun-
burn, wound, wear, and tattoo, in or near the test area; have 
participated in other clinical studies or been treated by der-
matologists within the last 3 months; and used any other 
anti-allergy products within the last 3 months. Rejection and 
termination were considered when the participants requested 
to discontinue the test or when adverse reactions occurred, 
respectively.
Test spray
The test product (A) was a spray containing natural birch 
juice and birch bark extract. The control product (B) was 
a spray containing thermal spring water on the market. 
The main ingredients of spray A and spray B are shown in 
Table 1.
Treatments
All participants were asked to use the spray six times a day 
15–20 cm from the face by pressing the pump head in a 
circular motion and spraying on the face without it. One 
group received spray A, and the other received spray B. To 
ensure dose compliance, the volume of residual spray in the 
container was examined at each follow-up. Assessments of 
skin biophysical properties were performed at the indicated 
times.
Evaluation method
The VISIA-CR 4.1 skin analysis imaging system (Can-
field Imaging Systems, Fairfield, NJ, USA) equipped with 
a Canon EOS-5Ds Mk III SLR camera was used to cap-
ture images from the front and left and right sides at 45°. 
The images were captured under the following lighting 
Table 1  Main ingredients of spray A and spray B
No
Name
Main functional ingredient
1
Spray A
Betula alba juice ≥ 88%
Betula alba juice:
Mineral elements (calcium, potassium, magnesium, manganese, sodium, zinc, barium, 
boron, strontium, ferrum, silicon, cuprum, cobalt, nickel, cadmium), amino acid (lysine, 
alanine, threonine, cystine, histidine, serine, valine, Isoleucine, methionine, leucine, glycine, 
phenylalanine, arginine, thyroxine, tryptophan, proline, aspartic acid, glutamic acid), aliphatic 
acid, monosaccharide, Vitamin (Vitamin C, Vitamin B1, Vitamin B2, Vitamin H)
2
Spray B
Silice, trace elements (Al, Ba, Li, Sr, Zn), cations  (Co2+,  Mg2+,  Na+), anions  (HCO3
−,  SO4 2−,  Cl−)
2273
Archives of Dermatological Research (2023) 315:2271–2281 
1 3
conditions: standards 1 and 2, cross-polarized, parallel-
polarized, and UV.
Tewameter® TM300 (MPA, Courage-Khazaka 
Electronic GmbH, Koln, Germany) was used to investigate 
transepidermal water loss rates (TEWL) and  Corneometer® 
CM825 (MPA, Courage-Khazaka Electronic GmbH, Koln, 
Germany) was used for detecting stratum corneum (SC) 
hydration. TEWL was measured in triplicate on the perioral 
areas for each subject. SC hydration was tested thrice on the 
cheekbones. These values were calculated based on their 
average.
Skin blood flow in the cheek was monitored by laser 
Doppler flowmetry (PeriFlux 5000; Perimed AB, Sweden). 
The amount of blood perfusion was used to measure 
skin microcirculation, and the higher the redness of the 
participant’s facial skin, the greater the value.
The current perception threshold (CPT) test was 
conducted using a  Neurometer® CPT/C quantitative 
sensory nerve detector (Neurotron Inc., Baltimore, MD, 
United States) via a standardized automatic double-blind 
test method. The lower maxillary branch of the trident 
meridian was tested. The electrode water was placed 
horizontally in the middle of one side of the mandibular 
bone. The  Neurometer® CPT/C at three different frequencies 
(2000 Hz, 250 Hz, and 5 Hz) is an electric current generator 
that provides selective stimulation for three subpopulations 
of sensory nerve fibers in the skin. Typical skin sensory 
nerves are composed of three main subgroups of nerve 
fibers: Aβ fibers, which conduct skin sensation and pressure; 
Aδ fibers, which conduct temperature, pressure, and acute 
pain; and C fibers, which conduct temperature and chronic 
pain. The current perception threshold (CPT) of the skin 
can be quantitatively measured using a CPT/C neurometer 
which reflects the skin’s sensitivity to stimulation; the lower 
the CPT value, the more sensitive the sensory nerves in the 
skin are to stimuli, and vice versa [25].
The photographs under Visia-CR cross-polarized light 
were evaluated for redness value assessed using an image 
analysis program (Image Pro-plus 7.0; Media Cybernetic 
Inc., Rockville, MD, USA). The software quantified the 
color of the facial skin using the L, a, and b color spaces, 
where L was lightness, a denoted redness, and b indicated 
yellowness. The higher the a-value, the reddish the skin.
The lactic acid sting test (LAST) was conducted as 
follows: 50 µl of 10% lactic acid solution was applied on one 
side of the nasolabial sulcus and cheek, and distilled water 
was applied on the other side, randomly left and right. The 
participants were asked about regarding their self-conscious 
symptoms at 2.5 min and 5 min, respectively, and scored on 
a 4-point scale (0 for no stinging, 1 for slight stinging, 2 for 
moderate stinging, and 3 for strong stinging). The two scores 
were then summed, and a total score ≥ 3 was classified as the 
LAST positive participant.
In the participants’ subjective evaluation, they evaluated 
their skin condition at the second and fourth week of 
follow-up. To evaluate whether the skin discomfort 
caused by changing seasons is less than in previous years, 
the improvement standard is divided into five levels as 
follows: more evident discomfort, no change, slightly 
reduced, reduced, and significantly reduced. The number of 
participants with significant reduction, reduction and slight 
reduction is the reduction rate. The evaluation parameters 
also included prevented the occurrence of new sensitives, 
repaired sensitivity and no irritation. The score was 
divided into the following five levels: completely disagree, 
somewhat disagree, disagree, not disagree, somewhat agree, 
and completely agree. The total number of participants of 
complete agreement and some agreement is the agreed rate. 
In the week 4, the satisfaction evaluation was conducted, 
and the standard was divided into four levels: very satisfied, 
satisfied, general, and dissatisfied. The number of very 
satisfied and satisfied cases is the satisfaction rate.
The parameters were evaluated before application and 
after 2 and 4 weeks of use. The testing environment was 
maintained at a constant 22 ℃ ± 1 ℃ and 50% ± 5% humidity. 
Before sampling, the participants sat in a temperature-
controlled room quietly for 20 min.
Statistical analysis
The data were analyzed using SPSS version 19.0 and are 
expressed as the mean ± standard deviation. The data that 
followed approximate positive distribution were compared 
using mixed linear models. For participants’ self-assessment, 
the Wilcoxon test was used to compare W0 at different time 
points in the same group, and the Mann–Whitney U test was 
used to compare the same time difference between groups. 
Significance was set at p < 0.05.
Results
Screening results of participants
Overall, 67 participants were included in the study, of 
which 33 were in the Group A, and 34 were in the Group B. 
Two participants in the Group A and one participant in the 
Group B could not complete the entire study due to personal 
reasons. Finally, 31 participants in the Group A, and 32 
participants in the Group B completed the trial. The average 
age of the participants in the Group A was 37.9 ± 12.5 years, 
while that of the Group B was 39.7 ± 12.7  years. The 
baseline data for participants were comparable between the 
two groups (Table 2).
2274
 
Archives of Dermatological Research (2023) 315:2271–2281
1 3
Improvement of skin barrier function
Both groups showed significant reductions on the TEWL 
value over time (F = 9.156, P < 0.05). After 4 weeks of using 
spray, the TEWL value was significantly lower than base-
line (P < 0.05) (F = 4.151, P < 0.05), and the TEWL value 
in group A was significantly lower than that in group B 
(estimate: A:0, B:0.299). No significant interaction effects 
for Group and times were observed (F = 2.625, P > 0.05) 
(Fig. 1).
As the intervention time increases, the hydration value of 
participants in the two groups were significantly improved 
(F = 24.709, P < 0.05), significant differences were found 
at W0 and W2 (P < 0.05), W0 and W4 (P < 0.05). No sig-
nificant difference is found between the groups (F = 3.827, 
P > 0.05).There was no interaction effect between time 
points and groups (F = 1.423, P > 0.05)(Fig. 2).
Improvement of facial redness
A laser Doppler blood flow meter is used to measure the 
amount of skin microcirculation blood perfusion; the more 
serious the skin redness is, the higher the value of blood 
perfusion. The blood perfusion decreased significantly 
over time (F = 5.053, P < 0.05), significant differences 
were found at W0 and W4 (P < 0.05). Significant between-
group differences were seen (F = 12.733, P < 0.05), group 
A had significantly lower blood perfusion compared to the 
group B. (estimate: A: 0, B: 37.107); there was no inter-
action effect between time points and groups (F = 0.197, 
P > 0.05)(Fig. 3).
Before and after using the spray, an image analysis 
program was employed to analyze the photos under the 
cross-polarized light of Visa CR, and obtain the value of 
facial redness. The facial redness of the participants in the 
two groups decreased significantly over time (F = 3.485, 
P < 0.05). There was no group significant difference 
(F = 1.124, P > 0.05) and group × time interaction effect 
(F = 0.084, P > 0.05) (Fig. 4). Figure 5 depicts the compar-
ison of three participants before and after using spray A.
Table 2  The baseline data
Items
Group A (n = 31)
Group B (n = 33)
P value
Age, years
37.94 ± 12.50
39.76 ± 12.72
0.554
Sex, female (%)
31 (100)
33 (100)
1.000
Hydration value
60.62 ± 12.44
60.80 ± 12.84
0.748
TEWL
20.23 ± 3.31
17.57 ± 4.94
0.013
Blood perfusion
89.81 ± 62.62
112.49 ± 89.37
0.308
Redness value
6.56 ± 3.80
7.26 ± 3.71
0.803
Current perception threshold (2000 HZ)
105.18 ± 22.32
105.08 ± 27.25
0.975
Current perception threshold (250 HZ)
29.03 ± 15.24
31.12 ± 13.75
0.475
Current perception threshold (5 HZ)
16.52 ± 11.88
13.38 ± 8.08
0.857
Last
4.45 ± 0.72
4.33 ± 0.60
0.326
Fig. 1  Transepidermal water 
loss value. P1 = time effect; 
P2 = group effect; P3 = interac-
tion group × time
2275
Archives of Dermatological Research (2023) 315:2271–2281 
1 3
Fig. 2  Hydration 
value. P1 = time effect; 
P2 = group effect; P3 = interac-
tion group × time
Fig. 3  Blood perfu-
sion. P1 = time effect; 
P2 = group effect; P3 = interac-
tion group × time
Fig. 4  A value. P1 = time effect; 
P2 = group effect; P3 = interac-
tion group × time
2276
 
Archives of Dermatological Research (2023) 315:2271–2281
1 3
Improvement of sensory nerve sensitivity
Measurement results of sensory nerve stimulation 
threshold
At 5 Hz, there was no difference over time (F = 1.042, 
P > 0.05) and no effect of interaction between the time 
and group (F = 0.129, P > 0.05). Significant differences 
were observed between the groups for the sensory thresh-
old at 5 Hz (F = 8.563, P < 0.05), which in group A was 
higher than that in group B (estimates, A: 0, B: − 4.87). At 
250 Hz, there was no significant difference in time effect 
(F = 0.065, P > 0.05), group effect (F = 1.070, P > 0.05), 
and time × group effect (F = 1.414, P > 0.05). At 2000 Hz, 
there was no effect over time (F = 0.165, P > 0.05), no 
difference between groups (F = 0.404, P > 0.05), and no 
interaction between the two variables (F = 0.534, P > 0.05) 
(Fig. 6).
Experimental results of LAST
After 2  weeks and 4  weeks of using sprays A and B, 
respectively, the LAST score of the participants in the two 
groups decreased gradually, and a significant difference was 
noted compared to baseline (P < 0.05). The comparison 
between groups indicated that at week 4, the scores of LAST 
in group A were more significantly reduced than those in 
group B (P < 0.05) (Table 3).
Subjective evaluation
Subjective evaluation of the participants
Before and after using the spray, the participants self-
assessed their skin condition. After using spray A for 
4 weeks, 83.87% of the participants believed that their 
skin discomfort caused by changing seasons was reduced 
compared with that in previous years. After 4 weeks of using 
spray B, 78.79% of the participants felt less skin discomfort 
caused by changing seasons compared with previous years. 
There was no significant difference between the groups 
(Table 4).
As shown in Table 5, the participants believed that the 
spray prevented the occurrence of new sensitivities and 
repaired sensitive skin at W4 visit, the percentage of A and 
B for both groups was 96.78% and 87.88%, respectively. 
The difference between the two groups was significant. Most 
participants in both groups agreed that spray could repaired 
sensitive skin (96.77% and 93.94% in Group A and Group 
B, respectively). Significant differences were found between 
the two groups. More than 96% of the participants rated the 
Fig. 5  Representative images of three participants before and after 
the application of spray A
2277
Archives of Dermatological Research (2023) 315:2271–2281 
1 3
products as non-irritating in both the groups, no significant 
differences between groups.
As shown in Fig. 7, the satisfaction rate of the participants 
in group A reached 96.77% after 4 weeks of using spray A, 
while that of the participants in group B reached 93.94% 
after 4 weeks of using spray B. There was a significant dif-
ference in satisfaction rate between the two groups.
Discussion
After the use of the birch spray by the Group A, SC hydration 
increased significantly, and the TEWL and redness degree 
were significantly reduced, while the CPT was increased, 
and the LAST score was significantly decreased. Thus, the 
spray containing natural birch juice can effectively improve 
the skin barrier function, relieve discomfort such as redness 
and tingling caused by inflammation, and reduce the sensory 
nerve sensitivity of the skin.
The epidermis is the interface where the human body 
makes contact with the external environment, and one of its 
main functions is the barrier function. Impaired skin barrier 
function is a common pathological mechanism of sensitive 
skin [4]. The barrier function of the epidermis is closely 
related to the various lipids, proteins, water, inorganic 
salts, and other metabolites of the epidermis. The cuticle 
Fig. 6  Current perception threshold. P1 = time effect; P2 = group effect; P3 = interaction group × time
Table 3  The results of the lactic acid sting test at week 4
Compared with week 0; *P < 0.05. Compared with Group  B; 
#P < 0.05
Test time
Group A
Group B
W0
4.45 ± 0.72
4.33 ± 2.60
W2
3.68 ± 1.22*
3.79 ± 2.06*
W4
2.84 ± 1.16*,#
3.42 ± 1.00*
Table 4  Subjective evaluation of skin discomfort due to the change of season at week 4
a The number of participants with significant reduction, reduction, and slight reduction is defined as the reduction rate
Group
Compared with previous years, whether the skin discomfort caused by the change of season was reduced
More obvious
No change
Slightly reduced
Reduced
Significantly reduced
Reduced ratio (%) P
Group A
0 (0%)
5 (16.13%)
15 (48.39%)
7 (22.58%)
4 (12.9%)
83.87
0.595
Group B
0 (0%)
7 (21.21%)
14 (42.42%)
12 (36.37%)
0 (0%)
78.79
Table 5  Participants' self-assessment at week 4
# P < 0.05
a The total number of participants expressing complete agreement and some agreement is the agreed rate
Compared with Group B
Group
Completely 
disagree
Somewhat 
disagree
Not disagree
Somewhat agree
Completely agree
Agreed rate (%)
P
To prevent the 
occurrence of a new 
sensitivity
Group A
0 (0%)
0 (0%)
1 (3.23%)
8 (25.81%)
22 (70.97%)
96.78
0.001#
Group B
0 (0%)
0 (0%)
4 (12.12%)
20 (60.61%)
9 (27.27%)
87.88
Repaired sensitive skin
Group A
0 (0%)
0 (0%)
1 (3.23%)
10 (32.26%)
20 (64.52%)
96.77
0.028#
Group B
0 (0%)
0 (0%)
2 (6.06%)
19 (57.58%)
20 (36.36%)
93.94
No skin irritation
Group A
0 (0%)
0 (0%)
0 (0%)
1 (3.23%)
30 (96.77%)
100
0.982
Group B
0 (0%)
0 (0%)
1 (3.03%)
0 (0%)
32 (96.97%)
96.97
2278
 
Archives of Dermatological Research (2023) 315:2271–2281
1 3
protects the body, is an important penetration barrier of the 
skin, and can hinder the loss of percutaneous evaporation 
of water. TEWL reflects the amount of water evaporation 
from the skin surface and is therefore an important indica-
tor for evaluating skin barrier function [26]. After 4 weeks, 
the TEWL value was significantly lower (P < 0.05) (Fig. 1), 
and the SC hydration was significantly different compared 
to the baseline (P < 0.05) (Fig. 2). Hence, the use of natural 
birch juice-containing spray significantly improved the skin 
barrier function in the participants.
In recent years, products for sensitive skin have 
continuously emerged, and the common ingredients in 
these products are mainly minerals and plant extracts. 
An impaired skin barrier is one of the main mechanisms 
of sensitive skin, whose barrier function is mainly 
undertaken by the cuticle. Calcium ions are closely related 
to the division and differentiation of keratinocytes, as 
well as the barrier function of the epidermis. Yuspa et al. 
have reported that through keratinocyte cultures, high 
extracellular concentrations of calcium promote keratinocyte 
differentiation and stratification and glutamine transferase 
expression, formation of keratinocyte envelopes, and cellular 
differentiation indicators such as keratin 1, keratin 10 and 
filromerin; therefore, calcium is essential for the formation 
of the cuticle barrier [27]. In vitro experiments also revealed 
that if the isolated skin does not have sufficient calcium ions 
in the culture medium after the disruption of the barrier 
function, the calcium ion concentration and concentration 
gradient will not return to normal and subsequently delay 
the recovery of the barrier function [28, 29]. In this study, 
the participants with sensitive skin had significantly reduced 
TEWL after using a spray containing natural birch juice 
(Fig. 1), which may be due to the calcium ions in the birch 
juice that facilitate the repair of the skin barrier function.
Here, using the spray containing natural birch juice 
4  weeks resulted in a gradual decrease in blood flow 
perfusion values (Fig. 3), and each value was significantly 
different from its baseline value (P < 0.05). Additionally, 
according to the images under cross-polarized light mode, 
both sprays have the effect of improving the degree of 
redness when used alone. The difference between the two 
groups was not statistically significant. Only positive control 
was set up and no negative control was set up, which is the 
limitation of this study. That is, negative controls were 
not used to eliminate the influence of variables such as 
environmental, seasonal and participants’ own changes on 
the results.
Yamasaki and Gallo have proposed that the innate 
immune system triggers inflammatory reactions and 
mediates symptoms of sensitive skin, resulting in skin 
redness and erythema [6, 30]. Spa therapy is an effective 
treatment for skin inflammation, and trace elements such 
as strontium and selenium may be the main effective 
elements of this therapy. Using a recombinant skin model, 
Kelerier et al. investigated the regulatory effects of strontium 
and selenium on inflammatory skin cytokines (IL-1α, 
TNF-α, and IL-6) and have reported that both strontium 
and selenium can effectively reduce the production of 
inflammatory cytokines in inflamed skin [31]. Birch juice 
contains strontium and selenium, which may be one of 
the reasons for its ability to reduce skin inflammation and 
redness.
The current perception threshold (CPT) of skin can be 
quantitatively measured by a CPT/C neurometer, which 
Fig. 7  Percentage of participants with different satisfaction scores in groups A and B at week 4. P: Group A compared to Group B
2279
Archives of Dermatological Research (2023) 315:2271–2281 
1 3
reflects the sensitivity of skin to stimulation. The lower 
the measured CPT value is, the more sensitive the sensory 
nerve of the skin is to the stimulus, and conversely, the less 
sensitive it is [25]. This study results revealed that after 2 
and 4 weeks of spraying with the natural birch sap spray, the 
CPT value did not increase at 2000 Hz and 5 Hz. However, 
at 250 Hz, after 2 weeks and 4 weeks of spray application, 
the CPT value increased (Fig. 6), which indicated that the 
spray A reduced the sensitivity of skin sensory nerves to a 
certain extent. Studies have suggested that when strontium 
salt is used to treat faces with sensitive skin, the CPT value 
is significantly increased, indicating that strontium salt can 
improve skin sensitivity to stimulation [25]. In 1999, Hahn 
also reported that strontium salt can significantly reduce the 
sensory stimulation caused by some substances [32].
Sting sensation is considered to be one of the important 
characteristics of sensitive skin, so the sting sensation 
test is widely used in identifying sensitive skin [33]. The 
lactic acid sting test has been used as a method to identify 
facial skin sensitivity in many studies. The test is generally 
targeted at the nasolabial sulcus because this area has high 
permeability of the cuticle, high density of accessory organs, 
and a rich sensory neural network. The higher the LAST 
score is, the more sensitive the skin is; the lower the score 
is, the less sensitive the skin is [34, 35]. This study’s results 
indicated that after 2 and 4 weeks of using the spray A, the 
participants’ LAST scores decreased gradually (Table 3), and 
a significant difference was observed (P < 0.05) compared 
with baseline. The LAST score of people with sensitive skin 
decreased after using repair products have been reported in 
literature before [36, 37]. We found that the use of both 
sprays significantly reduced LAST scores, possibly because 
both sprays contain calcium and magnesium ions, resulting 
in enhanced epidermal barrier function in subjects with 
sensitive skin.
Moreover, the birch spray can reduce the sensory nerve 
sensitivity of the skin. A previous work by Eunyoung Lee 
et al. may explain the underlying mechanism behind these 
benefits [31].
It has been reported in literature that LAST scores 
positively correlated with TEWL, a* and EI value [38], 
were negatively correlated with stratum corneum hydration 
and current perception threshold (CPT) at 250 Hz [39]. 
The results of spray A in this study are consistent with the 
correlation demonstrated in the above literature. That is, the 
LAST score, TEWL and redness score decreased, CPT at 
250HZ and hydration value increased during the 4 weeks 
of experimental period. Impaired skin barrier function is t
he main reason for sensitive skin [6]. When the barrier 
function of SC is impaired, it is less effective at preventing 
water from overevaporating, resulting in TEWL increases, 
stratum corneum hydration decrease [40], susceptibility to 
irritation enhanced (the scores of lactic acid sting incread). 
However, other factors may also have an impact, such as 
changes in the nervous system and/or epidermal structure. 
People with sensitive skin often have less hydration, more 
erythema and more skin with dilated distal blood vessels. 
From  the  preceding  discussion, calcium ions in birch 
juice aids in the skin’s barrier functionality, and reducing 
TEWL and LAST score, increases and maintains the mois-
ture content of the skin. Strontium salt of birch juice could 
improve skin sensitivity to stimulation and increase CPT 
value. And strontium and selenium could also reduce skin 
inflammation and redness.
Spray B was selected as the control in this study because 
thermal spring water has been widely reported to improve 
sensitive skin in several studies [41–44]. Spray A has a 
higher satisfaction rate than spray B, possibly because of its 
superior benefit in improving some symptoms of sensitive 
skin. As mentioned above, some spray A components, 
such as strontium and selenium, are minerals that reduce 
the production of inflammatory cytokines in inflammatory 
skin, reducing inflammation and redness. Calcium ions 
promote the repair of the skin barrier function. Therefore, 
Spray A may be more effective than Spray B in improving 
these symptoms and therefore has a higher satisfaction 
rate. However, we initially asked about overall satisfaction, 
which may make these results more positive. If we asked 
this question at the end of the subject’s self-assessment, they 
would have had the opportunity to review the shortcomings 
of the product in detail, and the overall satisfaction would 
have likely reduced. And this trial is a preliminary study, 
more research is needed to confirm this hypothesis.
There are two limitations to this experiment. First, we 
did not consider the impact of the environment on sensitive 
skin, that is, there was no negative control group. Our test 
site was Chengdu, Sichuan, China (102° 54′–104° 53′ E and 
30° 05′–31° 26′ N), and the time was from mid-November 
to mid-December (average temperature was 6–12 ℃). This 
period just includes the transition from the end of autumn to 
the beginning of winter. Seasonal alternation, temperature 
change, sunlight, and other factors could aggravate sensitive 
skin [4, 45]. Cold environmental conditions could exert 
a negative effect on the skin. People exposed to severe 
weather in winter may experience dry and itchy skin, or their 
existing skin diseases may worsen [46, 47]. Therefore, the 
improvement effect of A and B may be masked by seasonal 
changes. The second was randomization without hierarchical 
grouping. The basic value distribution of TWEL in the two 
groups was unbalanced, and the difference was statistically 
significant. Thus, we adopted a mixed linear model for 
statistical analysis, and the differences in baselines would 
not affect the statistical results.
In future tests, we will comprehensively consider the 
influence of age, redness degree, TWEL, and other factors 
conducting stratified grouping. In addition, considering that 
2280
 
Archives of Dermatological Research (2023) 315:2271–2281
1 3
sensitive skin is prone to relapse, it is necessary to extend 
the test time, include a suitably sized negative control group, 
and increase the number of cases.
Conclusion
The birch spray is safe and effective for repairing sensitive 
skin, with efficacy and safety comparable to that of a 
widely accepted sensitive skin repair product. The results 
of the present study may provide a new option for the 
repair of sensitive skin.
Author contributions Conceptualization, methodology and design: 
XW and SZ; Data acquisition, data analysis and interpretation: XS, 
WH, YT, LZ and ZL; Writing—original draft preparation: XS and 
YT; Writing—review and editing: LL and XW. All authors reviewed 
the manuscript.
Funding None.
Data availability The data that support the findings of this study are 
available from the corresponding author upon reasonable request.
Declarations 
Conflict of interest The authors have no conflict of interest to declare.
Ethics approval This study was approved by the Biomedical Ethics 
Committee of West China Hospital, Sichuan University (2018年审
(351)号).
Consent to participate Written informed consent was obtained from 
all participants.
Consent for publication Participants signed informed consent regard-
ing publishing their data.
Open Access This article is licensed under a Creative Commons 
Attribution 4.0 International License, which permits use, sharing, 
adaptation, distribution and reproduction in any medium or format, 
as long as you give appropriate credit to the original author(s) and the 
source, provide a link to the Creative Commons licence, and indicate 
if changes were made. The images or other third party material in this 
article are included in the article's Creative Commons licence, unless 
indicated otherwise in a credit line to the material. If material is not 
included in the article's Creative Commons licence and your intended 
use is not permitted by statutory regulation or exceeds the permitted 
use, you will need to obtain permission directly from the copyright 
holder. To view a copy of this licence, visit http:// creat iveco mmons. 
org/ licen ses/ by/4. 0/.
References
 1. Draelos ZD (1997) Sensitive skin: perceptions, evaluation, and 
treatment. Am J Contact Derm 8(2):67–78
 2. Sulzberger M, Worthmann AC, Holtzmann U et al (2016) 
Effective treatment for sensitive skin: 4-t-butylcyclohexanol 
and licochalcone A. J Eur Acad Dermatol Venereol 30(Suppl 
1):9–17
 3. Misery L (2017) Neuropsychiatric factors in sensitive skin. Clin 
Dermatol 35(3):281–284
 4. Inamadar AC, Palit A (2013) Sensitive skin: an overview. Indian 
J Dermatol Venereol Leprol 79(1):9–16
 5. Misery L, Morisset S, Séité S et al (2021) Relationship between 
sensitive skin and sleep disorders, fatigue, dust, sweating, food, 
tobacco consumption or female hormonal changes: results from 
a worldwide survey of 10 743 individuals. J Eur Acad Dermatol 
Venereol 35(6):1371–1376
 6. Berardesca E, Farage M, Maibach H (2013) Sensitive skin: an 
overview. Int J Cosmet Sci 35(1):2–8
 7. Misery L, Weisshaar E, Brenaut E et al (2020) Pathophysiology 
and management of sensitive skin: position paper from the spe-
cial interest group on sensitive skin of the International Forum 
for the Study of Itch (IFSI). J Eur Acad Dermatol Venereol 
34(2):222–229
 8. Misery L, Ständer S, Szepietowski JC et al (2017) Definition of 
sensitive skin: an expert position paper from the special interest 
group on sensitive skin of the international forum for the study 
of itch. Acta Derm Venereol 97(1):4–6
 9. Achmon Y, Fishman A (2015) The antioxidant hydroxytyrosol: 
biotechnological production challenges and opportunities. Appl 
Microbiol Biotechnol 99(3):1119–1130
 10. Smiljanic S, Messaraa C, Lafon-Kolb V et al (2022) Betula alba 
bark extract and empetrum nigrum fruit juice, a natural alter-
native to niacinamide for skin barrier benefits. Int J Mol Sci 
23(20):12507
 11. Isidorov V, Szoka Ł, Nazaruk J (2018) Cytotoxicity of white birch 
bud extracts: perspectives for therapy of tumours. PLoS ONE 
13(8):e0201949
 12. Softa M, Percoco G, Lati E et al (2019) Birch sap (betula alba) and 
chaga mushroom (inonotus obliquus) extracts show anti-oxidant, 
anti-inflammatory and dna protection/repair activity in vitro. J 
Cosmet Dermatol Sci Appl 9(2):188–205
 13. Wnorowski A, Bilek M, Stawarczyk K et al (2017) Metabolic 
activity of tree saps of diferent origin towards cultured human 
cells in the light of grade correspondence analysis and multiple 
regression modeling. Acta Soc Bot Pol 86(2):1–10
 14. Svanberg I, Sõukand R, Luczaj L et al (2012) Uses of tree saps in 
northern and eastern parts of Europe. Acta Soc Bot Pol 81(4):343
 15. Ozolinčius R, Bareika V, Met R et al (2009) Chemical composi-
tion of silver birch (Betula pendula Roth) and downy birch (Betula 
pubescens Ehrh) Sap. Balt For 22(2):222–229
 16. Ahtonen S, Kallio H (1989) Identification and seasonal variations 
of amino acids in birch sap used for syrup production. Food Chem 
33(2):125–132
 17. Kallio H, Ahtonen S, Raulo J et al (1985) Identification of the 
sugars and acids in birch sap. J Food Sci 50(1):266–269
 18. Solano F (2020) Metabolism and functions of amino acids in the 
skin. Adv Exp Med Biol 1265(1):187–199
 19. Yang M, Zhou M, Song L (2020) A review of fatty acids influenc-
ing skin condition. J Cosmet Dermatol 19(12):3199–3204
 20. Michalak M, Pierzak M, Bet K et al (2021) Bioactive compounds 
for skin health: a review. Nutrients 13(1):203
 21. Reins RY, Hanlon SD, Magadi S et al (2016) Effects of topi-
cally applied vitamin d during corneal wound healing. PLoS ONE 
11(4):e0152889
 22. Pullar JM, Carr AC, Vissers MCM (2017) The roles of vitamin C 
in skin health. Nutrients 9(8):866
 23. Liu ML, Chun-Hui LV (2015) Application of vitamins and their 
derivatives in cosmetics. Jiangxi Chem Ind 02:7–8
 24. Huang R (2012) Application of minerals in cosmetics. Deterg 
Cosmet 6:43–46
2281
Archives of Dermatological Research (2023) 315:2271–2281 
1 3
 25. Lee E, An S, Lee TR et al (2009) Development of a novel method 
for quantitative evaluation of sensory skin irritation inhibitors. 
Skin Res Tech 15(4):464–469
 26. Angelova-Fischer I (2016) Irritants and skin barrier function. Curr 
Probl Dermatol 49:80–89
 27. Yuspa SH, Kilkenny AE, Steinert PM et al (1989) Expression of 
murine epidermal differentiation markers is tightly regulated by 
restricted extracellular calcium concentrations in vitro. J Cell Biol 
109(3):1207–1217
 28. Elias P, Ahn S, Brown B et al (2003) Origin of the epidermal 
calcium gradient: regulation by barrier status and role of active 
vs passive mechanisms. J Invest Dermatol 119(6):1269–1274
 29. Elias PM, Wu Y, Chen C et al (2010) Regulation of epidermal 
barrier functions by calcium. J Clin Dermatol 39(2):135–137
 30. Yamasaki K, Gallo RL (2009) The molecular pathology of rosa-
cea. J Dermatol Sci 55(2):77–81
 31. Celerier P, Richard A, Litoux P et al (1995) Modulatory effects 
of selenium and strontium salts on keratinocyte-derived inflam-
matory cytokines. Arch Dermatol Res 287(7):680–682
 32. Hahn GS (1999) Strontium is a potent and selective inhibitor of 
sensory irritation. Dermatol Surg 25(9):689–694
 33. Farage MA, Katsarou A, Maibach HI (2006) Sensory, clinical and 
physiological factors in sensitive skin: a review. Contact Derm 
55(1):1–14
 34. Seidenari S, Francomano M, Mantovani L (1998) Baseline bio-
physical parameters in subjects with sensitive skin. Contact Derm 
38(6):311–315
 35. Querleux B, Dauchot K, Jourdain R et al (2008) Neural basis of 
sensitive skin: a fMRI study. Skin Res Tech 14(4):454–461
 36. Jeong S, Lee SH, Park BD et al (2016) Comparison of the efficacy 
of atopalm multi-lamellar emulsion cream and physiogel intensive 
cream in improving epidermal permeability barrier in sensitive 
skin. Dermatol Ther (Heidelb) 6(1):47–56
 37. Zhang Y, Jin Y, Humbert P et al (2021) An herbal cream reduces 
erythema of sensitive skin. J Cosmet Dermatol 20(3):792–797
 38. Pan Y, Ma X, Song Y et al (2021) Questionnaire and lactic acid 
sting test play different role on the assessment of sensitive skin: a 
cross-sectional study. Clin Cosmet Inv Derm 14:1215–1225
 39. Jiang W, Wang J, Zhang H et al (2022) Seasonal changes in the 
physiological features of healthy and sensitive skin. J Cosmet Der-
matol 21(6):2581–2589
 40. Berardesca E, Maibach HI (1990) Transepidermal water loss and 
skin surface hydration in the non invasive assessment of stratum 
corneum function. Derm Beruf Umwelt 38(2):50–53
 41. Ferreira MO, Costa PC, Bahia MF (2010) Effect of São Pedro 
do Sul thermal water on skin irritation. Int J Cosmet Sci 
32(3):205–210
 42. Zeichner J, Seite S (2018) From probiotic to prebiotic using ther-
mal spring water. J Drugs Dermatol 17(6):657–662
 43. Merial-Kieny C, Castex-Rizzi N, Selas B, Mery S, Guerrero D 
(2011) Avène Thermal Spring Water: an active component with 
specific properties. J Eur Acad Dermatol Venereol 25(Suppl 
1):2–5
 44. Bieber T (2011) More scientific evidence for the therapeutic ben-
efit of hydrotherapy in Avène. J Eur Acad Dermatol Venereol 
25(Suppl 1):1
 45. Berardesca E, Farage M, Maibach H (2013) Sensitive skin: an 
overview. Indian J Dermatol Venereol Leprol 35(1):2–8
 46. Engebretsen KA, Johansen JD, Kezic S, Linneberg A, Thyssen 
JP (2016) The effect of environmental humidity and temperature 
on skin barrier function and dermatitis. J Eur Acad Dermatol 
Venereol 30(2):223–249
 47. Brenaut E, Barnetche T, Gall-Ianotto CL et al (2020) Triggering 
factors in sensitive skin from the worldwide patients’ point of 
view: a systematic literature review and meta-analysis. J Eur Acad 
Dermatol Venereol 34(2):230
Publisher's Note Springer Nature remains neutral with regard to 
jurisdictional claims in published maps and institutional affiliations.

Clinical study of a spray containing birch juice for repairing sensitive skin.
Shu, Xiaohong,Zhao, Shizhi,Huo, Wei,Tang, Ying,Zou, Lin,Li, Zhaoxia,Li, Li,Wang, Xi