Evaluation of the effects of 10% and 30% gluconolactone chemical peel on sebum, pH, and TEWL

Gluconolactone (GLA) exhibits antioxidant and moisturizing effects. It also presents soothing effects, protects elastin fibers from UV‐induced degradation, and improves the function of the skin barrier.

The molecule is a tetrahydropyrate ring substituted directly with one ketone group, three hydroxyl groups, and one hydroxymethyl group (Figure 1).In nature, GLA can be found in honey, tofu, cheese, wine, bread, fruit juices, among others, as a food additive with the European number E575. 4 GLA and other PHAs can be formed as internal metabolites or intermediates of carbohydrate metabolism in tissues, for example, from glucose in the pentose phosphate pathway in the process of nucleic acid biosynthesis from ribose. 3 Alpha hydroxy acids (AHAs) and PHAs can modulate the function of the skin barrier.PHAs are becoming increasingly popular because, compared to AHAs, they are less prone to irritation during application, so they can be an alternative for sensitive skins, such as those with rosacea or atopy.GLA exhibits antioxidant and moisturizing effects.[7][8] The purpose of this study is to assess the effect of GLA in the form of a 10% and 30% chemical peel on selected skin parameters such as pH, sebum, and TEWL.

| Materials
The study involved 16 healthy female subjects.All participants were instructed not to change their daily care for the duration of the study.Additionally, approximately 12 h before each examination, they were asked not to apply any cosmetic products.The subjects had no contraindications to the treatments.They were asked to refrain from other cosmetic and dermatological treatments of the facial skin during the study.1. on the forehead (about 2 cm above the eyebrow, in a straight line from the center of the pupil of the eye), 2. around the eye (about 2 cm in a straight line from the outer corner of the eye), 3. on the cheek (at the level of the wing of the nose, at points between the pupil and the outer angle of the eye), 4. in the nose wing (due to the high sensitivity of the tewameter probe, this parameter was not measured on the nose).

| Methods
The evaluations were carried out according to the EEMCO guidelines.All measurements were carried out with a 15-min preexamination acclimatization in the measurement room, with constant temperature (24-26°C) and humidity (33%-41%).
The study was approved by the Ethics Committee and followed the principles of the Declaration of Helsinki.All respondents gave their informed consent to participate in the study.

| Statistical analysis
Statistical analysis was performed using the IBM SPSS Statistics 28 program.A value of 0.05 was used as the level of significance.The Shapiro-Wilk test was chosen to test whether the data were normally distributed.To examine changes in data distributions between groups, a group of nonparametric tests for the dependent variables was chosen (due to the lack of normal distribution in most subgroups): the Wilcoxon Rank-Sum test for two groups and Friedman analysis of variance for the number of groups greater than 2 (the Bonferroni test was chosen as the post hoc test).

| RE SULTS
The results of the tests were used to evaluate the effect of GLA in the form of a chemical peel on the following skin parameters: sebum level, TEWL, and pH.Results were considered including the percentage concentration and the location of the measurement.Statistical analysis F I G U R E 1 Chemical structure of gluconolactone.

| pH
The results on the forehead, for the first pH measurement on both sides of the face, were shown to be significantly higher than for the third (left side p = 0.024, right side p = 0.005) and fourth (p < 0.001 right and left sides), and for the second measurement the results were much higher than for the fourth measurement (left side p = 0.001, right side p = 0.017).
For the eye area on the left side, there was a significant decrease in pH at measurement 3 (p = 0.020) and 4 (p < 0.001) compared to the first measurement.The pH also decreased on the right side of the face in the eye area, but a significant difference compared to the first measurement was observed only after the treatment series was complete.
The results for the fourth measurement were much lower than those for the first (p < 0.001), second (p = 0.006), and third (p = 0.047).
On the left cheek, the results for the first measurement were significantly higher than for the third (p = 0.047) and fourth (p = 0.005).
On the right side, the results for the fourth measurement were significantly lower than for the first (p = 0.001) and the second (p = 0.009).
On both the left and right sides of the nose, pH showed a decreasing trend in the third (left side p < 0.001; right side p = 0.002) and fourth measurements (p < 0.001 for both sides).
Detailed results for pH measurements are presented in Figure 2.

| TEWL
The level of TEWL for the left forehead was much lower during the fourth measurement than during the other measurements (p = 0.009).The results obtained are shown in the diagram (Figure 3).
A decrease in TEWL was also shown for the right cheek.The results for the fourth measurement were significantly lower than for the first (p = 0.003), second (p = 0.001), and third (p < 0.001) measurements (Figure 4).Statistical analysis of the TEWL parameter for the eye area on both sides of the face showed significant differences in measurements with a decreasing trend.For the left side, the results for the fourth measurement were much lower than for the second (p = 0.004) and third (p = 0.020), while on the right side, the results for the fourth measurement were significantly lower than for the first (p = 0.003), second (p = 0.001), and third (p < 0.001).The results are presented in graphs (Figure 5).

| Sebum
Statistical analysis for the skin oiliness level parameter showed significant differences at one measurement site on both sides of the face.For both the left and right cheeks, the results for the fourth measurement were significantly lower than for the first measurement (left side p = 0.006, right side p = 0.003) (Figure 6).

| COMPARISON OF 10% AND 3 0% G LUCONOL AC TONE
Statistical analysis revealed that there were no significant differences among the measurements 1 and 4 for all parameters studied and at all measurement sites (Table 1).

| DISCUSS ION
GLA (D-gluconic acid-delta-lactone (C 6 H 10 O 6 )) is a chelating and skin conditioner agent.Physiologically, GLA participates in a number of enzymatic reactions.
PHAs can be assumed to be the next generation of AHAs.PHAs include lactobionic acid and GLA, which have larger molecules than AHAs, allowing weaker skin penetration and nonirritating exfoliation.PHAs also contain antioxidant and humectant properties; furthermore, they improve the barrier functions of the stratum corneum.Therefore, PHAs provide skin-smoothing benefits without sensory irritating side effects like stinging and burning. 9PHAs can be used for acne, sensitive skin, rosacea, atopic dermatitis, after cosmetic procedures, or as an aesthetic treatment with therapeutic value.For example, GLA can be used in combination with, for example, retinoids, azelaic acid, or procedures such as non-ablative laser, microneedling, chemical peels, or microdermabrasion, hydrogen purification to enhance the therapeutic effect, or provide additional benefits to therapy. 9,10drolytic (water-dependent) enzymes break down corneodesmosomes in the skin, and in conditions of low skin moisture, these enzymes do not work properly and their activity decreases.There is a decrease in the hydration and accumulation of stratum corneum corneocytes.Therefore, an improvement in skin hydration is achieved through the use of active substances that stimulate the exfoliation process and the formation of the skin barrier.GLA shows a beneficial effect on the skin as it has TEWL-reducing properties and is very well tolerated.GLA includes several hydroxide groups It was found that its protective effect may be due to its ability to function as a chelating agent (and its ability to eliminate free radicals). 7Furthermore, compared to glycolic acid (GA), GLA did not show a sun-sensitizing effect in the sunburn cell model. 8The lower effect of the irritant compared to GA is believed to be due to its molecular size (GLA molecular weight 178, where GA is 76). 12wano et al. carried out measurements of skin properties, that is, TEWL was evaluated using Tewameter TM300 and, in addition, skin hydration was measured using a Corneometer CM825.skin (reducing TEWL) and oral GLA has a stronger effect on strengthening the layers of the dermis by improving the viscoelasticity of the skin by improving the quality of the interstitial fluid throughout the fibrous network. 13 skin care processes, it should also be borne in mind that the acidic pH of the skin's mantle affects the proper course of physiological processes, such as lipid barrier formation and stratum corneum homeostasis (pH-dependent enzyme work, exfoliation, and antimicrobial defense).Proper pH regulation is necessary to prevent infections and reduce the susceptibility of the skin to inflammation.
Additionally, it is important to maintain skin smoothness.Aesthetic treatments with a pH greater than 7 can weaken the skin barrier.The elderly in particular should benefit from treatments with a pH between 4 and 7, as older skin is slower to recover from alkaline damage.In our study, we used GLA as a chemical peel with pH = 2.3 and 1.5.In an objective measurable sebumometric analysis, we showed that GLA affects the decrease in sebum measurement values regardless of concentration.Thus, it can be assumed that GLA exhibits seboregulatory values.
PHAs are capable of improving the function of the epidermal barrier through their actions on desquamation-regulating enzymes and lipid processing.GLA improves lipid metabolism, promotes water-molecule binding (reduction of TEWL), inhibits corneosome breakdown, and also acts in acidifying the pH of the epidermis, which limits the growth of pathogenic skin flora.Puigdemont et al.
examined the efficacy of topical treatment with GLA of ichthyosis in dogs.The extent and size of the scales were statistically significant (p < 0.001) by 60% and 75% after 14 and 30 days of treatment, respectively.Furthermore, biopsies showed improvement in stratum corneum morphology. 11 1992, GLA was indicated to be used in the treatment of acne as agents that modify keratinization also due to comedolytic properties and anti-inflammatory activity.This study shows that GLA is a useful treatment for acne and also that it does not show a significant irritating effect. 14Due to this effect, gluconlactone was used in the study that evaluated the efficacy in acne vulgaris of adapalene monotherapy versus a combination of GLA, GA, salicylic acid, licochalcone, and 0.1% adapalene.This combined cosmeceutical product showed some benefits in reducing acne complications.
Moisturizing products (such as GLA) have also been indicated to be used in conjunction with drugs such as adapalene. 15 a study by Draelos et   the permeability of the stratum corneum and, therefore reduced the vascular reactivity of the skin.Therefore, an effect of GLA on blood vessels is indicated.Furthermore, a statistically significant decrease in the incidence of skin dryness was observed after the use of GLA cosmetics, and better tolerance was reported to itching and stinging.The rationale for the good tolerability of GLA also appears to be related to its high molecular weight. 16In our study, using PHA improves lipid processing and inhibits corneodesmosome degradation.The authors also showed the lack of toxicity of polyhydroxyl acid applications on mouse skin, showing an effect limited to the superficial layers of the epidermis.Furthermore, a reduction in pH does not produce hyperplasia, inflammation, or changes in lipid synthesis, and PHA does not affect the underlying nucleated cell layers. 17The mechanism of GLA may be associated with inhibiting mediators of inflammation in the skin (IL-1a-induced PGE2) and decreasing corneocyte cohesion. 18 our previous study, we showed that GLA increased epidermal hydration regardless of concentration, 6 while in the current study we observed decreases in TEWL, which may also have a positive effect on hydration.Furthermore, Algiert-Zielińska.assessed the comparative level of hydration after the application of 10% and 30% lactobionic acid. 19Similarly to the own research on GLA, there were no significant differences in the moisturizing effect between 10% of the lactobionic acid concentration and 30% concentration.Therefore, it can be assumed that both LA and GLA have a moisturizing effect regardless of the concentration.Both acids are also substances that facilitate corneodesmosomal degradation.They have a multidirectional beneficial effect on the skin.
Collagen fibrillation is pH dependent and GLA is known as an

CO N FLI C T O F I NTE R E S T S TATE M E NT
The authors declare no conflict of interest.The authors themselves are responsible for the content and writing of the paper.

2 . 3 |
Three procedures were carried out at weekly intervals.GLA solution was applied based on a split-face model: 30% chemical peel (INCI: Aqua, gluconodelta-lactone, pH = 1.5) on the right side and 10% (INCI: Aqua, glucose delta-lactone, pH = 2.3) on the left side of the face.Three layers of GLA chemical peeling were applied at intervals of several minutes (the total treatment time was 20 min) and then washed with water.Evaluation of efficacy Skin parameters were measured at weekly intervals using the probes (Sebumeter® SM 815, pH-Meter® PH 905, Tewameter® TM 300) of the Courage & Khazaka 580 Multi Probe Adapter device (Courage + Khazaka electronic GmbH).Measurements were taken before each treatment and 7 days after the last procedure.The measurement points on both sides of the face were the following:

F I G U R E 2
Evaluation of the pH of the locations examined for 10% gluconolactone (GLA) chemical peel (A,C,E,G) and 30% GLA chemical peel (B,D,F,G).* means extreme values, ° means outliers.(-OH)that form hydrogen bonds with water.Thus, molecules of water are retained around GLA.11 Berardesca et al. investigated the effects of the application of alpha and PHAs, including GLA, on the function of the skin barrier, which is reflected in TEWL measurements, among others.Application for 4 weeks of the respective formulations resulted in lower TEWL values compared to the control sample.Furthermore, after SLS provocation, a significant increase in TEWL levels was obtained in all groups; however, the subgroups treated with GLA and tartaric acid had a lower increase than the others, indicating that regular use of a GLA formulation can reduce the sensitivity of the skin barrier to irritant damage.5In our study, the decrease in the TEWL measurement values was statistically significant in the eye area, the forehead (left side), and for the right cheek.It should be noted that a decrease in TEWL values was observed for all measurement points (for the right and left sides).Thus, even a nonstatistical but homogeneous decreasing trend may indicate TEWL-reducing properties for GLA regardless of the concentration as well.As is well-known, chronic dry skin increases susceptibility to adverse effects of physical (temperature, UV radiation, wind, and microtrauma), chemical (detergents and water), or biological (microorganisms) factors.We have shown a decrease in the TEWL values, so we can point to a strengthening of the epidermal barrier and thus protective properties against UV.In addition, GLA has antioxidant properties.Bernstein et al. in an in vitro transgenic model of cutaneous photoaging, showed that GLA provided some UV ray protection.
Volunteers were randomly assigned to the placebo group or the gluconoδ-lactone (GDL) group (2000 mg Day 1).Subjects took GDL orally for 6 months.No significant treatment effect on skin hydration was found.However, dietary GDL increased ceramides and free fatty acids in stratum corneum by 27.9% and 26.4%, respectively, compared to baseline.GLA significantly increased the values of the cutometrical parameters of the elasticity and viscoelasticity.Therefore, dietary GDL could improve skin barrier function, elasticity, and viscoelasticity.Comparing the results of our own study with those above on the use of oral GLA, we can conclude that topical GLA has a moisturizing effect on the most superficial layers of the F I G U R E 3 TEWL assessment of the forehead for 10% gluconolactone.* means extreme values, ° means outliers.F I G U R E 4 TEWL assessment of the cheek for 30% gluconolactone.* means extreme values, ° means outliers.F I G U R E 5 Evaluation of TEWL for the eye area: (A) left side and (B) right side.* means extreme values, ° means outliers.
al. GLA as an adjunct to azelaic acid therapy (15% gel) in rosacea resulted in a better therapeutic effect and fewer side effects in the form of burning or pinching.The PHA products used in the study were a cleansing product with 4% pH 3.3 GLA and a moisturizing cream with 10% pH 3.5 GLA.Statistically significant effectiveness in terms of severity of erythema for the GLA-containing skin care regimen.It is assumed that GLA reduced F I G U R E 6 Evaluation of the sebum level of the cheeks using a Sebumeter for the left side (A) and the right side (B).TA B L E 1Comparative analysis for 10% and 30% gluconolactone (GLA) including measurement locations.
we measured the change in skin pH using a pH meter.The results indicate a decrease in pH after GLA treatments.Increasing the pH of the normally acidic skin surface has adverse effects on stratum corneum cohesion, thus on skin barrier homeostasis.The applied treatments may have had a beneficial effect on strengthening epidermal defense function, which clearly coincides with the results of a decrease in TEWL.Therefore, our assumptions are in line with the purpose of the study and the results obtained in the study by Hachem et al. in which they showed that acute acidification of SC acidifier.Jayamani et al. investigated the property of GLA on collagen.They demonstrated the antifibrotic properties of GLA and suggest that it may have a potential role in the development of the treatment of fibrosis diseases by. 20In the study, Lee et al. showed that GLA reduces the expression of MMP in vivo under hypoxia.It might help to synthesize Type V collagen.They imply that oxygen concentration plays a key role in collagen biosynthesis.Therefore, GLA could affect the structure of the dermis. 216 | CON CLUS IONS GLA has been shown to have multiple skin benefits, making it an ideal ingredient for use in cosmetic, cosmetologic, and dermatologic procedures.AUTH O R CO NTR I B UTI O N S Sylwia Jarząbek-Perz developed the concept of the study, performed a series of treatments, measured skin parameters, collected data, performed the statistical study, and wrote the text of the publication.Marta Dziedzic's participation in this work included supervision of the collection of results and consultation of the publication text.Helena Rotsztejn and Anna Kołodziejczak critically reviewed the content of the manuscript.All authors read and approved the final manuscript.ACK N OWLED G M ENTS This study was supported by Statutory Research Activity Department of Cosmetology and Aesthetic Dermatology, Faculty of Pharmacy, Medical University of Lodz no: 503/3-066-01/503-31-001-19-00.