Efficacy and safety of a facial serum and a mask containing salicylic acid and lipohydroxy acid in acne management: A randomized controlled trial

Abstract

Background

Inflammatory and non‐inflammatory acne lesions constitute a significant clinical challenge in acne subjects.

Aim

To evaluate the efficacy and safety of a facial serum and a mask containing salicylic acid and lipohydroxy acid for improving skin conditions.

Methods

This randomized controlled trial included adults with comedones, post‐inflammatory erythema (PIE) and/or hyperpigmentation (PIH) in Shanghai, China in July 2021. Participants were randomly assigned 1:1 to receive the study Serum + Mask or serum alone for 8 weeks. Acne severity, comedones, papules, pustules, PIE, PIH, skin pores, skin tone evenness, sebum secretion, skin hydration, and trans‐epidermal water loss were evaluated at T0d, T1d, T7d, T14d, T28d, and T56d.

Results

Eighty‐three participants were included, including 41 and 42 in the Serum + Mask and Serum groups, respectively. Acne severity, density of skin pores, skin tone evenness, PIH foci on face, PIE foci on nose, intensity of PIE and PIH, closed comedones on face, open comedones on nose, sebum secretion, and skin hydration were significantly improved from baseline after 8 weeks of treatment in both groups (all p < 0.05). Addition of the mask improved the number of closed comedones (−6.56 ± 0.39 vs. −5.19 ± 0.44, p = 0.022) and acne severity (−0.39 ± 0.08 vs. −0.12 ± 0.09, p = 0.026) substantially more than using the serum alone. No adverse reaction was reported in either group.

Conclusions

The study serum improved skin conditions by regulating skin barrier function and achieving a balance of skin hydration and sebum secretion, removing comedones and improving PIE and PIH. Addition of the mask accelerated the effects without compromising safety.

INTRODUCTION

Acne vulgaris is a chronic skin disease characterized by inflammatory and non-inflammatory skin eruptions, including pustules, papules, and open and closed comedones. From a pathogenetic perspective, the development of facial acne might be influenced by the regulatory activity of sebaceous glands and disturbances in the sebum composition. Subjects with even mild acne can show defective skin barrier, decreased skin hydration and increased sebum secretion. Pigmentary alterations, such as post-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH), represent a clinical challenge; they are reported in more than 80% of all acne patients and could last up to 5 years. Those alterations are developed simultaneously with acne, due to the inflammatory process stimulating excess melanogenesis and abnormal melanin deposition. Although PIH is reported more often in patients with darker skin phototypes (Fitzpatrick III–VI) and PIE in lighter skin, both could be more distressing than active acne lesions and constitute a significant clinical challenge. These chronic skin conditions have been reported to affect the health-related quality of life on multiple dimensions, including psychosocial consequences such as anxiety and depression.

Topical retinoids, benzoyl peroxide, azelaic acid, and combinations of topical agents are currently considered the first-line choice in the management of acne. Combining retinoids with other topical agents, procedures and oral therapies is also recommended. Although some of these agents could effectively prevent PIE and/or PIH, clinical studies addressing their use are limited and often biased by small sample sizes. Moreover, the question of combining various skin care products and cosmetics that may also stimulate hyperpigmentation is rarely addressed.

It was reported that lipohydroxy acid (LHA) formulation significantly decreased both the number and total size of microcomedones in 2 weeks in acne-prone subjects. In previous reports, salicylic acid (SA) was shown to effectively treat acne vulgaris and PIH, while serum containing diacid, glycolic acid, SA, LHA, citric acid and hydroxyethyl piperazine ethyl sulfonic acid (HEPES) significantly improved PIH and helped control sebum production.

Based on the above, this randomized controlled study aimed to evaluate the efficacy and safety of a facial serum and a mask containing multiple components, including SA and LHA, for improving the skin condition and acne management in adult acne in combination with sebum dysregulation.

METHODS

Study design and subjects

This randomized controlled study enrolled adults with inflammatory and non-inflammatory acne lesions as well as self-assessed sebum dysregulation in Shanghai, China, in July 2021.

Inclusion criteria were as follows: (1) 18–45 years of age; (2) ≥10 blackheads on the nose, as examined by the dermatologist; (3) ≥8 non-inflammatory acnes on the face; (4) visible symptoms of PIE and/or PIH; (5) visible grade ≥3 pores confirmed by the dermatologist; and (6) ability to participate and to comply with all the requirements of the study protocol.

Key exclusion criteria were as follows: (1) use of other topical or oral treatments, including retinol, hormones or anti-oxidant health-care products; (2) pregnancy or breast-feeding (or planned for the duration of the study); (3) other skin diseases in the test areas, for example, rosacea and eczema; (4) history of allergy to cosmetic or personal care products or ingredients; (5) excessive exposure to sunlight or UV radiation according to the investigator's assessment, regular practice in aquatic or nautical sports, and frequent sauna use; (6) history of skin cancer or malignant melanoma, or other severe systemic diseases; (7) use of antihistamines, antibiotics, corticosteroids, non-steroidal anti-inflammatory drugs or immune-suppressants in the last 6 months before the study; and (8) inability to participate due to other reasons as assessed by the investigators.

This study was approved by the ethics committee (Review No.: SECCR/2021-94) and registered in (Registration ID: ChiCTR2200061221). All subjects provided signed informed consent before enrollment.

Randomization and blinding

The subjects were randomly assigned 1:1 to the Serum and Serum + Mask groups using a random number table. Due to the clear difference between the procedures, the subjects could not be blinded; however, the dermatologist who evaluated treatment efficacy and safety was blinded to grouping.

Intervention

Participants allocated to the Serum group treated the face with a cleanser and a standard moisturizer and applied the study serum twice daily. They were also asked to use standard sunscreen in the morning. In addition to the above treatment, participants allocated to the Serum + Mask group applied the study mask in the evening (once every 2 days at T0d–T6d; once every 3 days at T9d–T54d). The mask was used before the serum, usually for 10–15 min.

Clinical assessment

Assessment of the skin condition was performed by the same dermatologist blinded to grouping in a climate-controlled facility at T0d, T1d, T7d, T14d, T28d, and T56d. The average temperature was 20.9 ± 0.13°C with 47.48% ± 0.59% relative humidity.

Acne severity was assessed with the investigator global assessment (IGA) scale, ranging from 0 to 4 points, with 0 representing clear and no inflammatory signs of dermatitis, and 4 representing severe, widespread disease. The numbers of open comedones (blackheads), closed comedones (whiteheads), papules, pustules, and foci of PIE and PIH were counted by the dermatologist. The intensities of PIE and PIH were assessed by the visual analogue scale (VAS), ranging from 0 to 9 points, with 0 representing none and similar to the bare skin, and 9 points representing very dark and significant pigmentation. Skin tone evenness was also assessed by the VAS score, ranging from 0 to 9 points, with 0 representing even and healthy skin color, and 9 representing uneven and discolored appearance (brown and/or red foci).

Instrumental assessment

The density of skin pores was assessed with the Dermascore® system (L'Oreal, Paris, France) with grades ranging from 0 to 7, with 0 representing absence of pores and 7 representing extreme presence (Figure ).

Sebum secretion of the forehead skin (Figure ) was measured with a Sebumeter® SM815 (Courage & Khazaka), based on grease spot photometry.

Skin hydration was assessed by capacitance measurements (Corneometer® CM825, Courage & Khazaka). The tested areas located on the left and right cheeks according to Figure , using the 3M Transparent template for positioning. Consecutive readings were collected to ensure a variation tolerance of less than ±5. Three consecutive valid measurements were averaged.

Transepidermal water loss (TEWL) was evaluated with a Vapometer® (Delfin Technologies). Vapometer measurements were performed at the tested areas on face skin according to Figure , using the 3M Transparent template for positioning.

Facial images were captured with the Canfield Visia-CR system (Canfield) on the left, front, and right sides with cross-polarized light, parallel polarized light and ultraviolet light operated by a trained technician. The percentage of the area containing blackheads on the nose was calculated using the local extremum algorithm of the China-norm software (Shanghai China-norm Quality Technical Service Co., Ltd.).

Participant-reported outcomes

A self-assessment questionnaire of product efficacy evaluation was filled out by each subject at T14d and T56d. Scores for each question were 1–5 points: 5, agreement; 4, relative agreement; 3, neutrality; 2, relative disagreement; and 1, disagreement. The proportion of subjects with 4 or 5 points for each question was calculated.

Statistical analysis

Statistical analysis was performed with SPSS (version 25.0, IBM). Continuous data with normal distribution were expressed as mean ± standard deviation (SD) and compared between the two groups by the Student's t test. Continuous data with non-normal distribution were expressed as median (interquartile range) and analyzed by non-parametric tests. Repeated measured continuous data were analyzed by ANOVA or the Wilcoxon rank-sum test. Categorical data were expressed as frequency and percentage, and analyzed by the Chi-square test or Fisher's exact test. Two-sided p < 0.05 was considered statistically significant.

RESULTS

Study flowchart

A total of 154 subjects were screened, of whom 61 did not meet the eligibility criteria. Thus, 93 participants were enrolled and randomized, including 45 and 48 in the Serum + Mask and Serum groups, respectively. Four subjects in the Serum + Mask group and 6 in the Serum group voluntarily withdrew from the study without follow-up. Finally, 41 and 42 subjects in the Serum + Mask and Serum groups were included in the analysis, respectively (Figure ).

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Baseline characteristics of the participants

Mean ages of the participants were 33.15 ± 7.00 and 32.95 ± 6.50 years in the Serum + Mask and Serum groups, respectively; 75.90% of the participants were women, and 21.68% had self-assessed sensitive skin. PIE intensities at baseline were 3.71 ± 0.20 and 3.76 ± 0.19 in the Serum + Mask and Serum groups, respectively. PIH intensities at baseline were 4.20 ± 0.09 and 4.29 ± 0.14, respectively. As shown in Table , the skin condition at baseline was balanced between the two groups, without significant differences.

TABLE 1 Baseline patient characteristics.

Characteristic	Serum + Mask	Serum
(n = 41)	(n = 42)
Age (years)	33.15 ± 7.00	32.95 ± 6.50
Sex (female)	31 (75.6%)	32 (76.2%)
Self-assessed sensitivity
Sensitive	9 (22.0%)	9 (21.4%)
Non-sensitive	32 (78.0%)	33 (78.6%)
Evaluations at T0d
Number of open comedones on the nose	19.80 ± 1.95	20.71 ± 2.01
Percentage of area containing blackheads on the nose (%)	1.72 ± 0.11	1.70 ± 0.11
Number of closed comedones on the face	10.95 ± 0.62	10.36 ± 0.49
Number of papules on the nose	0.10 ± 0.05	0.14 ± 0.07
Number of papules on the face	2.76 ± 0.37	2.45 ± 0.41
Number of pustules on the nose	0.02 ± 0.02	0.02 ± 0.02
Number of pustules on the face	0.61 ± 0.17	0.69 ± 0.20
IGA acne severity	1.73 ± 0.07	1.71 ± 0.09
Number of PIE foci on the nose	0.85 ± 0.15	1.14 ± 0.19
Number of PIE foci on the face	4.46 ± 0.53	4.81 ± 0.66
PIE intensity	3.71 ± 0.20	3.76 ± 0.19
Number of PIH foci on the nose	1.15 ± 0.18	1.17 ± 0.16
Number of PIH foci on the face	4.12 ± 0.30	4.71 ± 0.44
PIH intensity	4.20 ± 0.09	4.29 ± 0.14
Skin pore density	4.92 ± 0.12	4.96 ± 0.13
Skin tone evenness	4.44 ± 0.11	4.38 ± 0.10
Sebum secretion	149.68 ± 6.62	148.18 ± 5.55
Skin hydration	38.54 ± 1.37	38.53 ± 1.06
TEWL	19.58 ± 1.16	21.09 ± 1.21

Treatment efficacy in the two groups

After 8 weeks of treatment, the IGA score of acne severity was significantly improved from baseline in the Serum + Mask group but not in the Serum group (Figure ). The density of skin pores was significantly improved from baseline in both groups from week 2 post-treatment (Figure ). In the Serum + Mask group and Serum group, skin tone evenness significantly improved compared with baseline at weeks 1 and 8 post-treatment, respectively (Figure ). Typical cases achieving improvement in skin tone evenness are presented in Figures .

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In terms of inflammatory lesions (papules and pustules) on the face and nose, both groups showed no significant improvement compared with baseline within 8 weeks of treatment (Figure ). As for non-inflammatory lesions, the numbers of closed comedones on the face and open comedones on the nose were significantly improved compared with baseline in both groups from weeks 2 and 4 post-treatment, respectively (Figure ). Typical cases achieving a reduction in the number of open comedones on the nose are presented in Figure . The percentages of the area containing blackheads on the nose were not significantly different from baseline in either group (Figure ). At week 8 post-treatment, the numbers of PIH foci on the face and PIE foci on the nose were significantly reduced in both groups (Figure ), while the numbers of PIE foci on the face and PIH foci on the nose were similar to baseline values (Figure ). In both groups, PIE and PIH intensities improved significantly from baseline at week 2 post-treatment (Figure ).

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Regarding the balance of water and sebum contents, sebum secretion and skin hydration were significantly improved from baseline starting at weeks 2 and 4 post-treatment in the Serum + Mask and Serum groups, respectively. TEWL levels were similar to baseline values in both groups after treatment, except for a significant improvement at week 8 post-treatment in the Serum group (Figure ).

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Advantages of study mask in addition to the serum

A difference in efficacy was noted at some points between the two groups. Particularly, at T56d, acne severity in the Serum + Mask group was significantly improved compared with baseline (p = 0.002), and the improvement was significantly more pronounced than that of the Serum group (−0.39 ± 0.08 vs. −0.12 ± 0.09, p = 0.026) (Figure ). In addition, the number of closed comedones on the face was improved in the Serum + Mask group compared with the Serum group at this time point (−6.56 ± 0.39 vs. −5.19 ± 0.44, p = 0.022; Figure ). The improvement of skin tone evenness from baseline was faster in the Serum + Mask group than in the Serum group, starting at 1 and 8 weeks post-treatment, respectively (Figure ). At T56d, the improvement in PIH intensity was significantly more pronounced in the Serum + Mask group than in the Serum group (Figure ).

Participant-reported outcomes

At weeks 2 and 8, more than 88% of the subjects thought that the study products were enjoyable to use, and the skin felt more comfortable (Table ). From week 2 to week 8, the proportion of subjects who were willing to continue using the serum and mask increased (both ≥98% at week 8) (Table ). No burning sensation, tingling sensation, allergy, and other adverse reactions or skin discomfort were observed during the study in either group.

TABLE 2 Self-assessment.

Question	Serum + Mask (n = 41)	Serum (n = 42)
T14d	T56d	T14d	T56d
Reduced acnes	80%	90%	64%	69%
Reduced blackheads	78%	83%	76%	76%
Pores look less visible	76%	83%	71%	81%
Skin feels oil control	90%	90%	88%	81%
Skin dullness looks reduced/Skin looks brighter	83%	88%	81%	86%
The overall skin appearance looks improved	85%	88%	81%	86%
Relieve the discomfort of acne	83%	85%	90%	88%
Skin feels softer	95%	90%	90%	90%
Skin feels more comfortable	90%	95%	93%	88%
Skin feels breathable	90%	93%	88%	100%
The product is gentle	98%	95%	98%	95%
The aspect/texture of the product is pleasant	90%	93%	95%	93%
Skin feels cared	90%	95%	93%	95%

TABLE 3 Subject satisfaction on the test Mask and Serum.

Question	Mask (n = 41)	Serum (n = 83)
T14d	T56d	T14d	T56d
Overall preference for the product	90%	85%	87%	90%
Overall satisfaction for the product	90%	90%	94%	88%
Willing to continue using (Yes)	85%	98%	83%	100%

DISCUSSION

This randomized controlled study evaluated the efficacy, safety, and tolerance of a facial serum and a mask containing multiple components, including SA and LHA, for improving the skin condition in adults with inflammatory and non-inflammatory acne lesions and sebum dysregulation. After 8 weeks of treatment, acne severity, density of skin pores, skin tone evenness, PIH foci on face, PIE foci on nose, intensity of PIE and PIH, closed comedones on face, open comedones on nose, sebum secretion, and skin hydration were significantly improved from baseline in both groups. The addition of mask significantly reduced the number of closed comedones and acne severity compared with serum alone. Both serum and mask showed promising safety profiles, with no adverse reaction reported.

The efficacy of chemical peels used to treat acne, such as SA and LHA, has been demonstrated in a variety of clinical trials. In addition, the study serum contained carnosine (β-alanyl-l-histidine). The antioxidant and pH-buffering properties of carnosine as well as its protective capacity against advanced glycation and lipoxidation end-products have already been tested in different therapeutic schemes, including cosmetic products. A previous randomized, placebo-controlled study reported its effectiveness for facial skin aesthetics and well-being. Our results indicate that the study serum was highly effective against both inflammatory and non-inflammatory acne lesions, which was consistent with previous reports.

Topical agents used for facial acne treatment usually have a comparatively rapid onset of action. Some of the previous trials showed that combinations of stearic acid/glycolic acid/SA/LHA/citric acid/HEPES and clindamycin/benzoyl peroxide usually show improvement within 2–4 weeks. Improvement in PIH symptoms, however, requires a longer treatment period (up to 8 weeks) in the trials of serum containing HEPES and 30% SA. In this study, PIE and PIH intensities, as well as skin pore density and sebum secretion were significantly different from baseline after 2 weeks of treatment, but the most promising results were observed during the later visits. SA reduces melanin levels and tyrosinase activity in normal epidermal melanocytes and inhibits melanocyte melanogenesis and melanin transport, and, thus, improves skin pigmentation.

This study found that the addition of a mask accelerated the effects of treatment without compromising safety. When exposure was prolonged by combining the serum with a mask, the improvements of closed comedones on the face, acne severity, PIH intensity, and skin tone evenness were more pronounced than using the serum alone. Both the serum and mask contained SA, which may enhance the efficacy of dissolving oil and dredging pores. Bamboo activated carbon base, used in the mask, can strengthen oil adsorption on skin surface. As a result, adding the mask could improve acne severity (−0.39 ± 0.08 vs. −0.12 ± 0.09, p = 0.026) and closed comedones on the face (−6.56 ± 0.39 vs. −5.19 ± 0.44, p = 0.022) more significantly than simply using serum. Furthermore, the study mask contained nicotinamide, which has been shown to improve PIH intensity and skin tone evenness. High-molecular-weight sodium hyaluronate, another component in the study mask, showed remarkable efficacy in anti-inflammation and could improve the anti-inflammatory properties of carnosine.

In contrast to a previous study of SA, no adverse reactions, including burning sensation, exfoliation, and acne outbreak, were reported in the present study, suggesting that the study product could be safely used for a long period. Skin hydration in both groups was significantly improved compared with baseline, while TEWL was similar to baseline. In addition, sebum secretion was significantly improved from baseline in both groups. Consequently, the two products tested had excellent safety profiles due to their ability to moisturize and control sebum secretion while not compromising skin barrier function. It is noteworthy that acne-prone subjects usually require daily skin care to maintain a balance of skin hydration and sebum contents, and the study serum and mask were appropriate for long-term daily use.

Although to achieve statistical significance the number of participants should most likely be higher, about one fifth of all subjects had sensitive skin, and more than 90% of subjects felt more comfortable during the final visit. There was a high degree of satisfaction with both products after 8 weeks, with 98% and 100% of the subjects willing to continue using the mask and serum.

This study had some limitations. First, the Global Evaluation Acne (GEA) scale was not applied for the assessment of acne severity, as the subjects had mild-to-moderate acne that only required daily skin care rather than comprehensive treatment. Second, this study was not designed to be split-face controlled, as half-face use of the mask may cause issues with compliance and impair self-assessment by the subjects.

In conclusion, using the study serum for 8 weeks improved the skin condition by regulating skin barrier function and achieving a balance of skin hydration and sebum secretion, removing acne and closed comedones, and reducing PIE and PIH intensities. Addition of the mask further improved closed comedones, skin tone evenness and acne severity, and accelerated the therapeutic effects without compromising safety. According to the participant-reported outcomes, both study products were comfortable for daily use.

AUTHOR CONTRIBUTIONS

Shuting Li, Xiaofeng He, and Zhongxing Zhang conceived, coordinated, and designed the study. Shuting Li carried out the data collection, data analysis, and wrote the paper. Shuting Li, Xiaofeng He, Zhongxing Zhang, Xianghua (Succi) Zhang, Yueqing (Gloria) Niu, Andrew Steel, and Hequn (Tracy) Wang carried out the data collection and data analysis and revised the paper. All authors reviewed the results and approved the final version of the manuscript.

ACKNOWLEDGMENTS

This study was funded by L'Oreal.

CONFLICT OF INTEREST STATEMENT

No conflict of interest was reported by the authors.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

ETHICS STATEMENT

This study was approved by Shanghai Ethics Committee for Clinical Research (Review No.: SECCR/2021–94) and registered in (Registration ID: ChiCTR2200061221). All subjects provided signed informed consent before enrollment.

PHOTO CONSENT STATEMENT

All subjects provided signed informed consent.

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