J Clin Dermatol, March 2022, Vol．51, No．3 175

Clinical efficacy of a topical formula containing glycolic acid, salicylic acid, capryloyl salicylic
acid, and niacinamide in patients with mild to moderate acne
LI Shu-ting, HE Xiao-feng, ZHANG Zhong-xing, Julie CRIBIER, Sabina MERALLI-BALLOU, Andrew STEEL, JU Qiang,
NIU Yue-qing
（Research and Innovation Center, L ’Oréal China, Shanghai 201206, China）

[Abstract] Objective: To evaluate the effectiveness and safety of a topical formula containing glycolic acid, salicylic acid,
CAPRYLOYL SALICYLIC acid, and niacinamide in patients with mild to moderate acne. Methods: Sixty-six subjects with mild to
moderate acne were recruited and used test product for 28 d and then stopped for 14 d. Dermatological evaluations were
performed to count acne lesions, quantify post-inflammatory erythema and hyperpigmentation, and grade the extent of pore
visibility and skin tone evenness. Standard facial photos were taken, and image analysis was conducted. The subjects also filled
self-assessment ques- tionnaires. Results: Forty-two subjects completed the whole study. Comparing to baseline, the test
formula reduced non-in- flammatory and inflammatory lesions, and improved pore visibility and skin tone evenness at 7 d
and 28 d after use. The im- provement sustained for 14 d after stopping the use of the product. The test formula also produced
improvement in skin tone, ery- thema intensity and area, and blood flow, according to the image analysis parameters. The
product presented good skin toler- ance and the subjects showed satisfaction and willingness for long-term use of it.
Conclusion: The topical formula containing glycolic acid, salicylic acid, CAPRYLOYL SALICYLIC acid, and niacinamide showed
good effectiveness and safety in patients with mild to moderate acne. It not only reduced lesion count, but also improved
post-inflammatory erythema and hyperpigmentation, as well as skin texture and color.
[Key word] acne
[J Clin Dermatol，2022，51（3）：175-179]

Acn e is a ch ro n i c in f la m m a t o ry de rm a t o lo g i c co n d it i o n
in vo lv in g fo l li cu l a r se b a ce o u s gl a n d un i t s. Ho rm o n e -
in du c e d ov e rp ro d u c t io n of li pi d s by se b a ce o u s gl an d s ,
ab n o rm a l ke ra t i n iz at i o n of se b a ce o u s gl a n d du c t s,
pro l if e ra t i o n of fo l li cu l a r mi cr o o rg a n is m s su ch as
Pro p io n i b a ct e ri u m ac n e s, as we ll as in f la m m a t o ry an d
imm u n e re sp o n s e s are ge n e t i ca l ly lin k e d to th e
de ve l o p m e n t of ac n e [1 ] . An t i -co m e d o g e n ic ski n ca re
pro d u c t s, ei t h e r al o n e or in co m b in a t i o n wit h me d ic a l
re g i m e n s, ha v e be c o m e a co m m o n to o l fo r ac n e
ma n a g e m en t [ 2 ] . Ke ra t o l yt i c an d an t i- in f l am m a t o ry
in gr e d ie n t s are of t e n us e d in an t i -a cn e ski n ca re pr o d uc t s
to ad d r e ss fo l li cu l a r se b a ce o u s gl a n d du c t ke ra t i n iz at i o n
an d in f la m m a t io n . To ev a lu a t e th e ef f i ca c y an d sa f e t y of
a to p i ca l fo r m ul a t io n co n t a in i n g gl yc o li c ac id , sa li cy li c
ac id , ca p ry ly l sa li cy li c ac id , an d ni a ci n a m id e , we
co nd u c t e d a cli n ic a l st u d y in pa t ie n t s wit h mi ld to
mo d e ra t e ac n e .

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 176 临床皮肤科杂志 2022 年 51 卷第 3 期 J Clin Dermatol, March 2022, Vol．51, No．3

1 Information and Methods rated for pore visibility (on a scale of 0-7 according
1.1 General information
A total of 66 female patients with acne were recruited to the Skin Aging Atlas Asia Volume [3]) and skin
from November 2020 to January 2021 by a third-party tone homogeneity (on a scale of 0-9 according to
clinical testing organization [SGS (Shanghai) Co., Ltd.],
and 62 completed the self-assessment questionnaire, the Modified Griffiths Classification).Standard and
of which 42 underwent clinical assessment at the orthogonal polarization modes of the VISIA-CR
same time, with a mean age of (25.1±6.2) years. The
main inclusion criteria were: women aged 18-37 years Facial Skin Analysis System (Canfield, USA) were
with mild to moderate acne (according to the used to take standard photographs of the face.
International Modified Classification of Acne), with
enlarged pores, uneven skin tone, and mild post- The image analysis was used to calculate the
inflammatory erythema and hyperpigmentation of acne; overall skin color (ITA), erythema (R-G: red-green
and agreement to refrain from the use of any other
acne-specific treatments or skincare regimens other channel difference) and perfusion (TiVi [4]: a
than those provided in the trial. The main exclusion metric defined based on the difference in red and
criteria were: severe acne; occupational or medicated
acne; oral retinoic acid in the last 6 months and other green light absorption by red blood cells, which is
acne medications in the last 3 months; topical acne positively correlated with the concentration of red
medications in the last 3 months; topical anti-acne skin blood cells in the skin) in a 1000 × 1000 pixel area
care products in the last 1 month; and other
dermatologic, integumentary, and immune system of the cheek; the analysis of the above metrics was
disorders. The study was approved by the Ethics repeated for a selected 300 × 300 pixel area
Committee (Grant No. SHCPCH201110875), and all
patients understood the study process and signed the containing the skin lesion, and its R-G grayscale
informed consent form. image was analyzed using ImageJ (52p) software.
1.2 Methods The analysis of the above metrics was repeated for
1.2.1 Test Product The test product is a topical formula selected 300 × 300 pixel areas containing skin
containing glycolic acid, salicylic acid, caprylyl salicylic acid, and lesions, and the R-G grayscale images were used
niacinamide (trade name: SkinSpring Tri-Acid Resurfacing to extract the erythematous extent of acne lesions
Serum). All patients used the test product continuously for 28 and calculate the percentage of erythematous area
d. Apply 3 drops of the test product to the entire face once per by applying the Renyi Entropy auto-thresholding
night; substitute the standard moisturizer and standard method of the ImageJ (1.52p) software.
sunscreen provided with the test for the corresponding skin In addition, patients were asked to fill out a
care products. Discontinue use of the test product after 28 d. self-assessment questionnaire to provide feedback
Maintain other standard skin care regimens until 42 d. on their experience and skin tolerance.
1.2.2 Assessment Methods The following clinical 1.3 Statistical analysis
assessments are performed prior to product use, at 7 and 28 d All data were analyzed using the statistical
software SPSS 25.0. The data were expressed as x±
of use, and at 7 and 14 d of discontinuation. The patient
s, and the percentage change of each time point
should be kept in a constant temperature and humidity
after using the test products compared with that
environment for 30 minutes prior to the assessment.
before using the test products was calculated.
A dermatologist will assess the patient's face for non- Comparison of the differences between the time
inflammatory acne lesions (including blackheads and points after the use of the test products and
whiteheads), inflammatory acne lesions (including papules and before the use of the test products: for the data
pustules), and post-inflammatory acne erythema. that conform to normal distribution, the paired t-
Non-inflammatory acne lesions (including blackheads and test was used; for the data that do not conform to
whiteheads), inflammatory acne lesions (including papules and normal distribution, the Wilcoxon test was used.
pustules), and post-inflammatory acne erythema and Differences were considered statistically significant
hyperpigmentation were counted by the dermatologist and at P<0.05.
(c)1994-2022 china Academic Journal Electronic publishing House. All rights reserved. http://www.cnki.net
 J Clin Dermatol, March 2022, Vol．51, No．3
2 Results
2.1 Acne lesion count
Compared with the pre-use period, the counts of
non-inflammatory and inflammatory acne lesions
decreased after 7 and 28 days of using the test
product, with statistically significant differences (all
P<0.01) (Fig. 1); the counts of non-inflammatory acne
lesions were reduced by 12.54% and 25.85%, and the
counts of inflammatory acne lesions were reduced by
23.37% and 40.00%, respectively, compared with pre-
use; and the counts of post-inflammatory erythema
and hyperpigmentation decreased after 7 days of
using the test product, with statistically significant
differences (P<0.01), and decreased by 11.55%,
compared with the pre-use period. The counts of post
-inflammatory erythema and hyperpigmentation of
acne decreased after 7 d of use of the test product,
with a statistically significant difference (P<0.01) and a
decrease of 11.55% compared with the pre-use counts.
The counts of non-inflammatory and inflammatory
acne lesions were still statistically significant (all
P<0.01) lower at 7 and 14 d after discontinuation of
the test product, suggesting that the improvement in
acne lesions could be maintained up to 14 d after
discontinuation of the test product (Table 1). 2.2 Pore
and Skin Tone Ratings Compared to pre-use, pore
visibility ratings showed significant improvement (all
P<0.01) after 7 and 28 d of test product use, with
10.39% and 18.14% improvement over pre-use,
respectively; skin tone evenness ratings showed
significant improvement (P<0.05) after 28 d of test
product use, with a 2.77% improvement over pre-use.
Pore visibility and skin tone evenness ratings remained
significantly improved (all P<0.05) after 7 and 14 d of
discontinuation of the test product, suggesting that
improvements in skin texture and skin tone could be
maintained up to 14 d of discontinuation of the test
product (Table 1).
2.3 Acne lesion image analysis
The overall skin color and degree of erythema
improved statistically (all P<0.05) after 7 d and 28 d
of use and 7 d and 14 d of discontinuation of the
test product compared to pre-use (Fig. 2). The
extent of erythema in individual lesions extracted by
image analysis was highly consistent with that seen
A~E ：正交偏振照片显示，使用测试产品 7 d 和 28 d 后，整体肤色改善 、红斑减轻，停用 7 d 和 14 d 后维持改善；F~
J ：红绿通道差（ R-G ）伪彩图显示，使用测试产品 7 d 和 28 d 后，整体红斑信号减弱，停用 7 d 和 14 d 后后维持改善
图2 痤疮患者皮损的肤色和红斑程度在使用测试产品前 后的变化（左侧面颊 1000×1000 像素区域）
177
by the naked eye (Figure 3). The skin color
and erythema extent of the lesions improved
statistically (all P<0.01) after 7 and 28 d of
use and 7 and 14 d of discontinuation of the
test product, and the erythema area of the
lesions improved statistically (all P<0.05) and
by 13.79% (all P<0.05) compared to the pre-
use level. There were statistically significant
differences (all P<0.05) in the erythema area
of the lesions after 28 d of using the test
product and 7 d and 14 d of discontinuing
the test product, and the differences were
statistically significant (all P<0.01) compared
with those before use (Table 2).
2.4 Self-assessment questionnaire
After 28 d of use of the test product, 71%
of the patients believed that "the number of
acne has decreased", 76% believed that "acne
has become less visible", 76% believed that
"the discomfort caused by acne has
decreased", 77% believed that "the
discomfort caused by acne has decreased",
and 77% believed that "the discomfort
caused by acne has decreased". 76% of the
patients felt that "the discomfort caused by
acne was reduced", 77% of the patients felt
that "the oiliness of the skin was improved",
81% of the patients were "satisfied with the
product as a whole", and 95% of the patients
"would like to continue to use the product".
"The product has been used for a long time
and is now being used for many years.
2.5 Safety evaluation
The tested product showed good skin
tolerance in 66 patients, of which 42
completed all clinical assessments and
questionnaires, 20 only participated in the
questionnaires without clinical assessments, 2
dropped out of the follow-up, and 2 withdrew
on their own initiative for personal reasons.
Fifteen patients reported mild tingling
immediately after product application, which
disappeared within 2-3 minutes, without
localized erythema or other skin
manifestations.
、
 Table 1 Comparison of le sion count s and pore and skin color ratings of acne pat ients
bef ore and af ter use of the tes t products.
pr e - us e After 7 d of After 28 d of After 7 d of After 14 d
use use inactivation of
inactivation
Count of non-inflammatory acne 15.38±5.67 13.45±6.24** 11.4±5.38** 11.67±6.45** 10.98±5.60**
lesions (nos.)
Inflammatory acne lesion counts 9.88±1.97 7.57±3.53** 5.93±4.03** 6.17±4.77** 5.71±4.78**
(individuals)
Counts of po st-inflammator y 7.21±4.32 6.38±4.13** 6.31±3.53 6.83±3.55 6.93±3.29
erythema and hyp erpigmenta tion
in ac ne (nos.)
Pore Visibility Rating (0 to 7) 3.44±0.47 3.08±0.52** 2.81±0.48** 2.71±0.52** 2.57±0.50**
Skin tone evenness rating (0~9 scale) 5.16±0.82 5.07±0.70 5.01±0.74*
4.94±0.76*
4.88±0.76**
*P<0.05; **P<0.01 compared to before use of test products

(c)1994-2022 china Academic Journal Electronic publishing House. All rights reserved. http://www.cnki.net

A~E ：正交偏振照片显示，使用测试产品 7 d 和 28 d 后，整体肤色改善 、红斑减轻，停用 7 d 和 14 d 后维持改善；F~

J ：红绿通道差（ R-G ）伪彩图显示，使用测试产品 7 d 和 28 d 后，整体红斑信号减弱，停用 7 d 和 14 d 后后维持改善
图2 痤疮患者皮损的肤色和红斑程度在使用测试产品前 后的变化（左侧面颊 1000×1000 像素区域） 、
 178 J Clin Dermatol, March 2022, Vol．51, No．3

Table 2 Comparison of image analysis indexes of skin lesions in acne patients before
and after the use of test products

pr e - us e After 7 d of use After 28 d of use After 7 d of After 14 d of

inactivation inactivation
Overall

35.56±8.32 36.50±8.13** 37.17±7.92** 37.69±8.03** 37.87±8.13**

Color (ITA ° )
Degree of erythema (R-G) 46.99±8.84 45.84±7.6 *
44.95±7.65 **
44.92±8.13**
45.03±8.09**
Blood perfusion (TiVi) 0.1258±0.0090 0.1253±0.0081 0.1244±0.0083 0.1242±0.0094 *
0.1245±0.0089
Skin lesions

28.67±11.91 30.23±11.29** 31.08±11.17** 31.32±11.11** 31.33±11.85**

Skin color (ITA ° )
48.31±9.59 46.19±8.45** 44.58±8.72** 44.26±8.95** 44.34±8.93**
Degree of erythema (R-G)
Erythema area (%) 8.12±6.30 7.99±6.97 7.00±8.77** 5.25±3.86** 6.20±5.84*
Blood perfusion (TiVi) 0.1289±0.0089 0.1274±0.0086** 0.1256±0.0091** 0.1253±0.0102** 0.1254±0.0097**

3 Discussion lipophilicity, making it easier to penetrate into intercellular

Keratolytic or exfoliating ingredients such as ɑ-hydroxy acid and
salicylic acid can effectively inhibit epidermal keratinization, eliminate
follicular plugs, and reduce and inhibit the formation of acne[2] .
Glycolic acid is a small molecule, hydrophilic ɑ-light acid with
excellent transdermal absorption properties. Salicylic acid, on the
other hand, is a lipophilic β-hydroxy acid that is easily absorbed by
the sebaceous glands of the hair follicles and has better targeting
properties for acne lesions. capryloyl salicylic acid has an octanoyl
ester chain added to the salicylic acid structure to further enhance its
lipids to loosen keratin bridges and achieve more effective
and gentle exfoliation, as well as antimicrobial and anti-
inflammatory activities [5]. Niacinamide is a classic
multifunctional skincare ingredient with whitening, barrier
repair and oil control properties [6]. The combination of these
two ingredients can promote the regression of acne lesions,
reduce the occurrence of post-inflammatory erythema and
hyperpigmentation, and prevent the occurrence of new
lesions.

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 临床皮肤科杂志 2022 年 51 卷第 3 期 J Clin Dermatol, March 2022, Vol．51, No．3 179

Fun ctiona l ski nca re produ cts ta rge tin g showed high levels of satisfaction
th e pathogen esi s of acne can be an with the product experience and a
importa nt adjun ct to th e treatme nt of acne willingness to continue using it.
[2], and th ei r effic acy and adverse effects in Compared with standard
cli ni cal use nee d to be th orough ly eval uate d clinical protocols for acne
and vali date d. In thi s study, we eval uate d treatment, the limitations of this
study are the short observation
th e cli ni cal effic acy of a topi cal formu lati on
period, the absence of a control
contai nin g gl ycol ic acid, sa li cyl i c acid,
group, the fact that the early
oc tanoyl sal ic yl ic aci d and nia cin amide in
efficacy of the test product was
patie nts wi th mi ld to mode ra te acne . The
only observed 28 days after use,
re sul ts showed tha t th e te st produ cts we re
and the fact that it was not
effecti ve in redu ci ng th e number of non-
compared with standard
infl amma tory and infl amma tory les ions, treatment protocols or placebo. It
improvi ng pore siz e an d unev en sk in tone is important to note that
after 7 and 28 d of use compared to pre -u se, maintenance therapy plays an
and th at th e improveme nts were sustai ne d important role in the overall
for 14 d after di sconti nu ation of use. The treatment of acne and is usually
sign ifi cant re ducti on in pos tinfl ammatory given for a period of 3 to 12
acne ery thema and hype rpi gmen ta tion months[1]. Topical retinoids are
counts early in th e tri al and th e lac k of the first line of maintenance
chang e later in th e tri al may be rel ate d to therapy for acne, and studies have
th e conversi on of some of th e infl amma tory shown a 38.91% and 46.49%
les ions to posti nfla mmatory acne erythe ma reduction in non-inflammatory
and hyperpi gmenta tion. In additi on to the and inflammatory lesions,
trad iti onal eval uati on me thods based on respectively, after 4 weeks of
acne grad ing and les ion coun ts, the adapalene (3rd generation topical
retinoid) compared to the pre-
deve lopment of nonin vasi ve te stin g
administration period [8]. In
te chn iqu es has provi ded new perspec tive s
contrast, the products tested in
for th e evalu ati on of mi ld to mode ra te acne
this study showed a slightly lower
[7]. To fu rth er eval uate th e effects of the
improvement in non-inflammatory
te st produ ct on pos t-i nfl amma tory erythe ma
and inflammatory lesions (25.85%
and hype rpi gmenta tion in acne , we took
and 40.00% reduction from pre-
standa rdi ze d photograph s of the fa ce an d
use, respectively), but were better
anal yz ed the image s, and fou nd th at th e te st tolerated by the skin and may be
produ ct was effecti ve in improvi ng ski n an alternative to topical retinoic
color and erythe ma on th e whole body an d acid in cases where it is not
les ions, as well as ery thema and perfusi on in tolerated. In this study, a
les ions after 7 and 28 d of use compa re d to discontinuation phase of 14 d
th e pre -u se period, and th at th e after the intervention phase was
improve ment wa s sustai ne d up to 14 d of conducted to observe the
disc on tin uati on of th e te st produ ct. Th is maintenance of the test product
me thod can be used as a suppl ement to during the discontinuation phase
trad iti onal acne evalu ation me thods an d for the improvement of lesions,
shoul d be fu rth er vali date d an d improve d in which in clinical practice is
subse quen t studi es. recommended as an adjunctive
hroughout the trial, the product was well and maintenance treatment for
tolerated by the patients, with only a few acne, and can be used for a long
experiencing a slight tingling at the moment period of time.
of use, which quickly subsided. Patients
(c)1994-2022 china Academic Journal Electronic publishing House. All rights reserved. http://www.cnki.net
 The results of this study showed that the
topical formulations containing glycolic acid,
salicylic acid, caprylyl salicylic acid, and
niacinamide showed good improvement in
mild to moderate acne lesions, as well as
reduction of post-inflammatory erythema
and hyperpigmentation, improvement of skin
texture and tone, and good experience and
skin tolerability during use.
(c)1994-2022 china Academic Journal Electronic publishing House. All rights reserved.
References
[1] China Acne Treatment Guidelines Expert Group . Chinese
acne treatment guidelines (2019 revised edition) [J].
Journal of Clinical Dermatology , 2019 , 48(9): 583-588.
[2] Chinese Expert Group on Application Guidelines for Anti-
Acne Skincare Products . Guidelines for the application
of anti-acne skin care products in acne[J]. Chinese
Journal of Dermatology and Venereology , 2019 , 33(10):
1107-1109.
[3] Bazin R, Flament F. Skin Aging Atlas Volume 2: Asian Type
[M]. Paris: Editions Med 'Com, 2010: 60-61.
[4] O 'Doherty J, Henricson J, Anderson C, et al. Sub -
epidermal imaging using polarized light spectroscopy
for assessment of skin microcirculation[J]. Skin Res
Technol, 2007, 13(4): 472-484.
[5] Zeichner JA. The use of capryloyl salicylic acid in skin care
and acne treatment[J]. J Clin Aesthet Dermatol, 2016,
9(11): 40-43.
[6] Zhu HQ , Zhu WY , Fan WX . Progress of nicotinamide in
topical topical skin application [J]. Journal of Clinical
Dermatology , 2007 , 36(3): 189-190.
[7] JIANG Wencai , XU Yafei , ZHOU Hong , et al. A
preliminary study of noninvasive testing technology in
the early evaluation of the efficacy of acne vulgaris [J].
Journal of Clinical Dermatology , 2019 , 48(10): 601-605.
[8] ZHU Zhen , CAO Haipeng , FU Xuedong , et al.
Observation on the efficacy of tanshinone combined
with adapalene gel in the treatment of mild and
moderate acne[J]. Journal of Clinical Dermatology , 2019,
48(8): 514-515.
http://www.cnki.net