Efficacy and safety of treating body aging with a dermocosmetic containing retinaldehyde, glycolic acid, and nicotinamide

Received on: 02/02/2012
Approved on: 09/06/2012
This study was carried out at Medcin Instituto
da Pele - Osasco (SP),
Brazil.
Financial support: Theraskin Farmacêutica
Ltda. – São Paulo (SP), Brazil, have sponsored
this study.
Conflict of interest: Theraskin Farmacêutica
Ltda. sponsored this study.

Abstract

Introduction: The aging process of areas of the body that are frequently exposed to the sun has a clinical pattern different from that of facial photoaging. According to a number of published studies, the combination of retinaldehyde, glycolic acid, and nicotinamide presents promising results. Objective: To evaluate the efficacy and safety of a new dermocosmetic formulation in the treatment of body photoaging. Methods: Clinical, prospective, open, and monocentric study that evaluated 60 volunteers (phototypes I to III) with signs of photoaging in the neck region. Clinical and instrumental measurements (cutometry, corneometry, evaporimetry, and profilometry) were taken in the initial visits and 30 and 60 days after using the study product, which was applied at night, combined with the daytime application of sunscreen. Results: After using the test product, the categories of clinical parameters (wrinkles, smoothness, hydration, and sagging) and biophysical hydration (measured using corneometry) presented statistically significant improvement (p < 0.05) in the intermediate and final visits. Despite showing improvement, the biophysical measurements of skin viscoelasticity and roughness were not statistically significant. Conclusion: This combination was effective in the clinical improvement of body photoaging, and is an effective and safe alternative for treating this condition.

Keywords: SKIN AGING, COSMETICS, THERAPEUTICS

INTRODUCTION

Cutaneous aging is a biological process dependent upon intrinsic factors (such as genetic predisposition), and extrinsic factors (primarily sun exposure).1 Ultraviolet radiation causes direct damage to the keratinocytes'''''''' mitochondrial DNA, promoting oxidative phenomena in the tissue (such as the release of inflammatory cytokines and metalloproteinases) that degrade lipids and collagen. These biochemical alterations translate into skin photoaging, which is characterized by the loss of elasticity and hydration, changes in the pigmentation and surface, and the appearance of wrinkles and telangiectasias.1-3

These signs are noticeable on the whole body, especially in the upper thorax region, which constitute a frequent complaint in dermatological practices; their treatment is strictly related to the severity of skin body photodamage.

In cosmeceutical-based treatments, the strategy of combining different active principles may provide a synergistic effect and enhance benefits. A formulation containing the active principles retinaldehyde, glycolic acid, and nicotinamide has recently been introduced. This new formulation was designed to decrease the effects of photoaging.

Retinaldehyde is a natural precursor of tretinoin, which exerts the same biological effects as retinoids. It inhibits the activity of enzymes that break down collagen, in turn increasing the synthesis of glycosaminoglycans and therefore stimulating collagen synthesis through the increase of Transforming Growth Factor-B. Furthermore, it causes fewer adverse effects than tretinoin. 4-7

Glycolic acid – an alpha hydroxy acid derived from sugar cane, which decreases the adhesion of corneocytes at concentrations of 5-15% – improves the penetration of other agents and reduces the hyperkeratotic appearance of photoaged skin. 8

Finally, clinical studies have shown that nicotinamide has considerable antioxidant properties, since it is a precursor of nicotinamide adenine dinucleotide phosphate (NADP), a coenzyme of crucial importance in the catalytic oxidative process. Moreover, nicotinamide has immunomodulatory and antiinflammatory actions. 9

Considering the relevance of this formulation for countering the effects of photoaging, the authors proposed a study to verify its effectiveness using predetermined clinical evaluations and biophysical measurements. This approach allowed the assessment of the hydration, surface, and viscoelasticity of the treated skin, under actual conditions of use, compared to untreated skin.

This study''''''''s objective was to evaluate the efficacy and safety of a dermocosmetic formulation (test product) when applied for 60 consecutive days in the treatment of photoaging in the upper thorax region

METHODS

This was an open, monocentric clinical study, carried out with clinical and instrumental evaluations. With the Research Ethics Committee''''''''s approval, 60 female volunteers (aged 35-55) with Fitzpatrick phototype I to III and mild to moderate photoaging in the anteroposterior region of the chest, were recruited and studied from April 2010 to July 2010. All volunteers signed a term of free and informed consent prior to undergoing any of the procedures described in the clinical protocol.

Exclusion criteria included: pregnancy or potential risk of pregnancy, breastfeeding, use of topical or systemic anti-inflammatory and/or immunosuppressives, use of antihistamines for up to 15 days prior to the beginning of the study, previous reaction to cosmetic products in the same body area, atopic or allergic history, active cutaneous pathologies (local and/or widespread) that could interfere with the results of the study, pathologies that cause immune suppression, intense exposure to the sun within 15 days before the beginning of the study, body aesthetic treatments within four weeks of study selection, dermatological treatments in the same part of the body up to four months prior to study selection, a history of similar composition dermocosmetic inefficiency, and any other condition that the investigator physician considered cause for disqualification.

All volunteers underwent an initial dermatologic evaluation for signs of photoaging in the upper thorax region, which were rated according to a 5-point scale (1-5) for the parameters wrinkles, hydration, sagginess, and softness. After the clinical assessment, each volunteer was photographed with an Omnia device (Canfield Imaging Systems) and cutometry, corneometry, evaporimetry, and profilometry measurements were performed.

Two additional visits to the Research Center (30 and 60 days after daily use of the test product) were scheduled in order to obtain new photographs, clinical evaluations, and further instrumental measurements, and to assess adverse events.

In order to allow a better assessment of biophysical properties (hydration, elasticity, and skin roughness) instrumental measurements were taken using the following methods. All measurements were taken both in the treated and control (untreated) areas.

Evaporimetry: the Tewameter®TM 300 device (Courage & Khazaka) quantified the amount of transepidermal water loss (TEWL) and, therefore, the functional integrity of the stratum corneum barrier. The greater the integrity of the cutaneous barrier, the lower the TEWL.

Corneometry: the Corneometer® MPA 580 (Courage & Khazaka) evaluated the hydration level by measuring the electrical conductivity of the skin, which is due to the presence of water. The greater the measurement, the higher the water content in the skin''''''''s surface.

Cutometry: the Cutometer® MPA 580 (Courage & Khazaka) is used to quantify the variations in the skin''''''''s viscoelasticity through various intrinsic measurements, depending on the purpose of the evaluation. In this study, firmness (R0) and elasticity (R2 and R7) were measured. The R0 measurement evaluates the skin''''''''s deformability due to suction, thus the lower the measure, the firmer the skin. R2 and R7 measurements gauge the skin''''''''s ability to return to its original state following the deformation caused by suction. The closer the measurement is to 1, which corresponds to its original state, the more elastic the skin is. Photoaged skin presents more marked deformation and less resilience.

Profilometry: the skin''''''''s relief was assessed using the Skin Visiometer® device (Courage & Khazaka). Fast-drying silicone was applied on the skin in order to produce mold, on which bundles of rays of light were beamed. Since part of those rays is absorbed differently at each point according to the thickness of the skin, it was possible to determine the depth of lines and wrinkles accurately.

The parameters analyzed in this study were volume, contrast, and the R1 parameter. Volume indicates the amount needed (in mm3) to fill all the "grooves", from the surface to the level of the highest "peak." Hence, the smaller the volume, the smoother the skin.

Contrast indicates the variation in the depth of the grooves and peaks on the skin''''''''s surface by varying the gray hue of the mold''''''''s image of the mold. The lower its value, the lower the variation on the surface – and therefore the smoother the skin.

Finally, the R1 parameter indicates the difference between the highest peak and the deepest valley in the area, evaluated through the measurement of diverse profiles. The lower its value, the smoother and more uniform the surface of the skin.

The test product was supplied to each volunteer together with sunscreen, for exclusive use during the study period. The treatment began at T0, with the topical application of the product on clean skin in the upper thorax region at night. The volunteers were instructed to remove the product the following morning and to apply sunscreen every three hours during the day for 60 consecutive days.

RESULTS

Clinical Efficacy
Of the 60 volunteers who began the study, 57 completed it; three withdrew due to personal reasons. Ten volunteers experienced adverse effects and were excluded from the analyzed population since they discontinued their use of the test product. Therefore, only the data from the 47 volunteers who completed the study without reference or confirmation of adverse events were used to assess clinical and instrumental efficacy. The clinical evaluation was performed in the volunteers'''''''' upper thorax region.

Figure 1 shows images of a volunteer at baseline (T0) and the final time point (T60).

Graph 1 shows the mean values initially obtained in the clinical evaluation of efficacy – Visit 1 (initial visit): T0, Visit 2 (intermediate visit): T30, and Visit 3 (final visit): T60 – according to the specific criteria for those evaluations and the photographic analysis of the treated region.

Table 1 shows the change in mean values of the experimental times in percentage terms and the statistical data of each parameter assessed. The results showed that there was statistically significant improvement between time points T30 and T60 compared to baseline in all evaluated parameters. A gradual improvement between Visit 2 and Visit 3 was also observed.

Instrumental Effectiveness Assessed using Corneometry The ratio between the values obtained in the treated vs. control areas was calculated for each volunteer in each experimental time in order to eliminate the effect of the control area. Graph 2 shows the mean values of the ratios (treated area/control area) obtained at T0, T30, and T60.

Table 2 shows the statistical data and percentage of variation in the mean values of the experimental times. The results show that there was a statistically significant increase in epidermal water content at T30 and T60 compared to baseline.

Instrumental Effectiveness Assessed using Evaporimetry Graph 3 shows the mean values of the ratios (treated area/control area) obtained at T0, T30, and T60, according to the instrumental assessment carried out through evaporimetry (TEWL). Table 3 shows the statistical data and the variation of the mean values for TEWL in percentage terms. There was a statistically significant increase in TEWL when comparing the initial time point to T30 and T60.

Instrumental Effectiveness Assessed using Cutometry
Graph 4 depicts the mean values of the ratios (treated area/control area) initially obtained at T0, T30, and T60, according to the instrumental assessment using cutometry. Table 4 shows the statistical data and the variation in mean values in percentage terms. Despite the improvement seen in all parameters at T30 and T60, no statistically significant difference was observed in this evaluation due to the greater dispersion of results.

Instrumental Effectiveness Assessed using Profilometry Graph 5 depicts the mean values obtained at T0, T30, and T60 of the study, as assessed through profilometry. Table 5 shows the statistical data and the variation in mean values in percentage terms. There was improvement in the parameters evaluated, for there was a reduction in their variation between time points. That improvement, however, was not statistically significant.

DISCUSSION

Photoaging is manifested in different ways, depending on individual phenotypic features such as skin color, erythematogenic response to sunlight, the affected area of the body, and the amount of sun exposure. 10

Areas of the body that are highly photoexposed (such as the anterior and posterior neck region, the upper thorax region – and the extensor surfaces of the forearms) are more prone to aging, particularly in individuals with fair skin. 11

It is possible to clinically verify the presence of sagging in the skin linked to the solar elastosis process, a more rough and dry appearance, and the presence of wrinkles and alterations in pigment, such as melanosis and leukoderma punctata. 2

Cosmetic products for the treatment of signs and symptoms resulting from the aging process should promote the partial improvement of these characteristics by increasing skin hydration and reversing – if only partially – the mechanisms that lead to tissue damage, such as collagen degeneration and alterations in the superficial epidermis and melanocytic activity.

In this study, the authors evaluated a dermocosmetic formulation used in the treatment of body photoaging using clinical and instrumental (biophysical measurements of roughness, and skin hydration and viscoelasticity) criteria. In the evaluation of the formulation''''''''s safety, 10 volunteers presented photodermatitis in the pre-sternal and décolleté regions. In four of these 10 patients, the photodermatitis was confirmed to be caused by the use of the product. In the remaining six patients, the cause was not clearly defined.

Notwithstanding the supply of sunscreen and the instruction not to expose areas with thinner epidermis, such as the upper thorax region, to the sun, the photodermatitis reaction can be explained by the presence of glycolic acid (which has a mild irritating action) in the formulation – especially in conditions of low pH and areas of high sun exposure. 12

In most cases, suspension of the product followed by reintroduction did not cause a recurrence of the condition, suggesting that the irritative potential of the test product is limited and dependent on the application and the volunteers'''''''' individual sensitivity.

Regarding the clinical evaluations of efficiency, the results prove that the test product is effective in reducing the major signs of photoaging in the region, with statistically significant improvement in hydration, smoothness, wrinkles, and sagging at both T30 and T60, with considerably significant results.

The positive effects observed in skin hydration (measured using corneometry), and the clinical assessments performed by dermatologist physicians, were all statistically significant and noteworthy.

Evaporimetry measurements in the evaluation of TEWL are indirect measures of the skin barrier''''''''s integrity. The increase in the rates observed in the present study is probably correlated to the glycolic acid''''''''s action on the stratum corneum, which disrupts the corneocytes'''''''' adhesion and promotes cell renewal.

Despite the positive results observed, the cutometry and profilometry measurements were not statistically significant – possibly due to the relatively short study period.

As usual in clinical studies that assess biophysical parameters, measurements related to epidermal phenomena, such as hydration, are influenced earlier by the use of topical products than measurements related to dermal phenomena, such as viscoelasticity and skin roughness.

CONCLUSION

The use of the combination of retinaldehyde, glycolic acid, and niacinamide in the cosmetic treatment of body photoaging produced positive results in the skin''''''''s clinical and biophysical measurements in the assessed volunteer patients, which suggests this is a safe product.

The recommendation for the treatment to be accompanied by photoprotection should be highlighted, in view of the adverse photoirritation events observed in some volunteer patients.

References

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