Effect of 5% glycolic acid complex and 20% glycolic acid on mild-to-moderate facial acne vulgaris

To the Editor: Acne vulgaris is a chronic, inflammatory, and disfiguring skin disease with lesions, post-inflammatory hyperpigmentation, and scarring. Chemical peeling is a simple and well-tolerated procedure for mild-to-moderate acne. Glycolic acid (GA) is water-soluble and has the smallest molecular weight among all the alpha-hydroxy acids. High-concentration GA (20%–70%), applied at 2 to 4-week intervals in the hospital or cosmetology clinic, have proved effective for acne.^[1] Low-concentration GA (≤10%) is safe and convenient, and can be used at home.^[2] Up to now, differences in efficiency between low and high concentrations of GA for acne vulgaris have not been reported. This study compared the efficacy and safety of 5% GA complex and 20% GA for acne patients, to guide GA selection at different concentrations.

The Ethics Committee of Beijing Friendship Hospital approved the study protocol (No. 2019-P2-007-01). All patients provided written informed consent. The trial identification number is ChiCTR2000031393 in the Chinese Clinical Trail Register of the World Health Organization. This randomized controlled clinical trial was performed with 80 acne patients, from March 1 to May 31, 2019. The inclusion criteria were as follows: mild or moderate acne (Pillsbury grade I–III, Fitzpatrick skin types IV–VI); aged ≥18 years; and no topical or systemic treatment within 1 month. The exclusion criteria were as follows: active or recurrent herpes infection; history of hypertrophic scarring or keloid; use of oral isotretinoin, steroid, or immunosuppressive agent in the past 6 months; sensitive or photosensitive skin; pregnant or lactating; menstrual disorders; polycystic ovary syndrome; hirsutism; or refusal to give consent.

Patients were randomly divided into two groups. In group A, 5% GA complex (Cosmocos, Korea) consisting of alpha-hydroxy acid peel and essence repairing factors such as sodium hydroxide, allantoin, trehalose, and Portulaca oleracea extract was applied once daily. In group B, the patients underwent four treatment sessions with 20% GA (NeoStrata, NJ, USA), biweekly. All the participants were followed up 2 weeks after the last treatment (day 70).

The skin lesion scores, patient satisfaction, and adverse effects for each patient were recorded before treatment (baseline) and after treatment (day 70) by the same two dermatologists. The severity of active acne was evaluated according to the Michaëlsson grading system, in which comedones were non-inflammatory lesions, and papules, pustules, and infiltrates were inflammatory lesions.^[3] Satisfaction was graded from 1 to 4 by visual analog scale. Skin rejuvenation parameters (wrinkles, pores, red area, and brown area) and skin physiological parameters (transepidermal water loss [TEWL] and skin hydration) were recorded using the VISIA system (Canfield Imaging Systems, NJ, USA) and CK Multi-Probe Adapter (MPA580, Courega-Khazaka, Cologne, Germany) before and after treatment. The lactic acid stinging test (LAST) was performed to assess skin sensitivity.

Categorical data were assessed using the chi-squared test. For continuous data with normal distribution, paired and unpaired t tests were used within and between groups. For data that were not normally distributed, the non-parametric test was used. Statistical analyses were performed using SPSS 23.0 (IBM Corp, Armonk, NY, USA). P values <0.05 were considered statistically significant.

All patients completed this trial. At baseline, the basic data between the two groups were comparable [Supplementary Table 1]. After treatment, in both groups, the clinical efficacy, number of lesions, and lesion severity index improved significantly compared to the baseline, with an additional significant decrease in the brown area score, and a significant increase in TEWL (P < 0.05, each; Supplementary Table 2). However, a statistically significant increase in skin hydration was observed only in the 5% GA complex group A [Table 1 and Supplementary Figure 1]. Regarding LAST, after treatment, the time to highest sting intensity was significantly later relative to the baseline in both groups (P < 0.05, each; Supplementary Table 2). Five patients in the 5% GA complex group and eight patients in 20% GA group reported adverse effects, which amounts to a non-significant difference.

Table 1.

Comparison of mean changes between 5% GA complex and 20% GA groups before and after treatment.

Items	5% GA complex	20% GA	t or z†	P-value
Basic information
Lesions (n)	27.60 ± 15.93	18.80 ± 12.14	2.78	<0.01
Non-inflammatory lesions (n)	16.20 ± 12.07	11.80 ± 11.93	1.64	0.11
Inflammatory lesions (n)	11.28 ± 10.50	7.00 ± 6.22	2.22	0.03
Lesion severity index	26.13 ± 16.32	18.55 ± 11.17	2.42	0.02
Satisfaction score	3.25 ± 0.87	2.78 ± 0.80	2.54	0.01
Visia test
Score of wrinkles	40.50 (−37.00, 188.25)	39.5 (−67.75, 39.50)	z = 0.077	0.94
Score of pores	−56.00 (−212.75, 104.50)	146.50 (44.75, 265.75)	z = 4.403	<0.01
Score of red area	−3.75 ± 49.58	8.95 ± 43.09	1.22	0.23
Score of brown area	53.10 ± 61.42	45.00 ± 65.00	0.57	0.57
Skin biophysical properties∗
TEWL (g·m−2·h−1)	2.43 ± 5.68	6.52 ± 4.91	3.45	<0.01
Skin hydration	11.91 ± 17.86	2.08 ± 13.82	2.75	<0.01
LAST
Decrease of the highest intensity score	0.15 ± 1.00	0.15 ± 0.92	0.00	1.00
Increase in moment of the highest intensity (s)	83.25 ± 162.83	71.25 ± 166.78	0.33	0.75
Increase in moment of sting (s)	19.50 ± 222.73	32.63 ± 174.83	0.29	0.77
Decrease of total scores	0.35 ± 2.58	0.65 ± 2.13	0.57	0.57

GA: Glycolic acid; LAST: Lactic acid stinging test.

^∗Mean change of skin biophysical properties represents the results of post-treatment data minus pre-treatment data; mean change of the remaining parameters was calculated from the difference in the results of pre-treatment data and post-treatment data.

^†The normality of distribution was first analyzed. For normal distribution data, the form of mean ± standard deviation was applied, and t-tests were used; for non-normal distribution data, the form of median with interquartile range was applied, and a non-parametric test was used.

The intergroup comparisons showed that patients given 5% GA complex showed better results in terms of total and inflammatory lesions, lesion severity index, skin hydration, and satisfaction scores than did the patients administered 20% GA (P < 0.05). Also, patients treated with 20% GA showed a lower score for pores and higher TEWL compared with patients given 5% GA (P < 0.05, respectively). Similar effects were shown in the improvement of wrinkles, red area, brown area, and LAST [Supplementary Figures 1–3].

Previous studies in mice showed that GA at high concentrations (≥3%) caused epidermal separation, resulting in skin irritation or chemical burns. GA at low concentrations (≤2%) might have an anti-inflammatory effect via epigenetic modifications, and decreased corneocyte cohesion and epidermal thickness.^[3,4] Human skin has better tolerance than mouse skin; ≤5% GA was usually considered the low-concentration group in clinical application, while ≥20% GA group was defined as high. After treatment, each group experienced a significant decrease in skin lesions.

Two obvious differences between two groups were found in our study. First, the decrease of pores in 20% GA group was better than that in 5% GA group. Pore improvement may be attributed to collagen remodeling in the group with higher concentration. This indicates that 20% GA acts as both a superficial and medium-depth peel, while the 5% GA complex was associated with superficial peels. Second, the epidermal barrier function was evaluated by TEWL and skin hydration in this study. After treatment, the TEWL of each group had increased significantly relative to the baseline, and a greater increase of TEWL was observed in the 20% GA group than in the 5% group. Skin hydration was significantly higher in the 5% GA complex group compared with the baseline, but did not change significantly in the 20% group. On the one hand, the higher concentration may be an irritant to the skin barrier, but on the other, the 5% GA complex contains repairing factors which may help improve the skin barrier signs. Moreover, the anti-inflammatory effects of the 5% GA complex may have contributed to the significant decrease in the inflammatory lesions of the patients. LAST is a skin sensitivity assessment that was used to confirm whether skin sensitivity changed after treatment. In our study, the patients were able to tolerate LA stimulation for a longer time after treatment. The differences in other LAST indicators between the groups were not significant, indicating that skin sensitivity of patients after either 5% GA or 20% GA treatment was improved.

There were some limitations in our study. The study design would be more convincing by the addition of an age- and gender-matched control group, who used the same facial cleanser or vitamin E moisturizing cream as the 80 participants in this study who had acne. Besides, since this is a single-center study, the source of patients may be limited. Thus, the generalization of the results may not be universal.

In conclusion, 20% GA and 5% GA complex were both effective on mild-to-moderate acne. Twenty percent GA is more suitable for acne patients presenting with large pores, whereas 5% GA complex, which could repair the skin barrier, is appropriate for acne patients with inflammatory lesions.

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 82273555) and Beijing Natural Science Foundation (No. 722240).

Conflicts of interest

None.