Open study comparing sodium L-ascorbyl-2-phosphate 5% lotion versus adapalene 0.1% gel for acne vulgaris

  • Ikeno Clinic of Dermatology
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We are reporting on an evaluator-blinded, multicenter, open-label clinical study to compare the efficacy and safety of sodium L-ascorbyl-2-phosphate (APS) 5% lotion with that of adapalene (ADP) 0.1% gel for facial acne treatment. Sixty patients were randomized to apply either APS or ADP for 12 weeks. Among 53 patients who completed the study, APS treatment was consistently superior to ADP treatment in inflammatory acne lesion reduction at any study period. The overall study results show the superior efficacy and safety of APS 5% lotion compared with that of ADP 0.1 % gel in the treatment of acne vulgaris. APS is a vitamin C derivative and is very effective in removing active oxygen species. Oxidation of squalene or fatty acid is thought to induce comedogenesis and is, therefore, pathogenic of acne.The efficacy of APS in acne treatment may be attributed to its oxidation inhibitory action on squalene and fatty acid by removing the active oxygen species.

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... 6 The efficacy of topical APS in the treatment of acne has been demonstrated in open label studies as both monotherapy and in combination with other therapies. [7][8][9][10][11] In this study, we examined 5% APS in a double-blinded placebo-controlled trial as a novel treatment for acne based on its potent antioxidant activity. ...
... Additional open label studies have supported the efficacy of APS in the treatment of acne as both monotherapy and in combination with other agents. [7][8][9][10] Vitamin C, also known as ascorbic acid, is the most abundant antioxidant in the skin. 14 Topical formulations of vitamin C are typically modified to improve stability. ...
... Previous open label studies have demonstrated the efficacy of APS in acne vulgaris. [7][8][9][10][11] We present the first double-blinded, vehicle-controlled study to demonstrate the efficacy of vitamin C in acne vulgaris. This study demonstrates that 5% APS is efficacious as monotherapy for the treatment of acne. ...
Antioxidants are becoming increasingly important in the treatment of skin disease. In addition to their known anti-inflammatory effects, antioxidants may act to prevent the oxidation of sebum which has been proposed to be comedogenic in acne patients. Sodium L-ascorbyl-2-phosphate (APS) is a stable vitamin C derivative and highly effective antioxidant that has demonstrated efficacy in acne in open label studies. To evaluate the efficacy and safety of APS 5% lotion for the treatment of acne in a blinded controlled study. A total of 50 subjects were randomized in a double-blind controlled trial to receive APS 5% lotion or vehicle for 12 weeks. Evaluation included an Investigator's Global Assessment Score, a Subjects' Global Assessment Score, lesion counts, cutaneous tolerability, and adverse events. APS 5% lotion demonstrated statistically significant improvement when compared to vehicle in all of the parameters measured. The adverse event frequency and cutaneous tolerability profile for APS 5% lotion were similar to vehicle. Adjunctive topical or oral agents and their impact on acne were not studied in this trial. This study demonstrates that 5% sodium L-ascorbyl-2-phosphate is efficacious as monotherapy for the treatment of acne. APS 5% lotion offers a novel addition to our current acne armamentarium.
... [8][9][10][11] There are also studies on the efficacy of antioxidant ingredients such as sodium l-ascorbyl-2-phosphate (SAP) for the treatment of acne vulgaris. 12,13 On the basis of these studies, we postulated that accumulation of LPO in comedones is involved in the progression of comedogenesis and inflammatory changes in comedones. Substantial confirmation to demonstrate our hypothesis clearly has not yet been established. ...
... Significantly higher quantities of LPO in inflammatory comedones may indicate the correlation between LPO quantity and inflammatory changes. This, theoretically, corresponds to the research by Ottaviani et al. and may also explain the clinical results of the studies on SAP by Ikeno et al. [11][12][13] Our results suggest that a certain amount of LPO accumulation in the content of comedones may be involved in the progression of comedogenesis, and may further lead to inflammatory changes in comedones in acne vulgaris (Figure 4). ...
Previous studies reported that lipid peroxide (LPO) caused by oxidation of sebum is associated with the progression of acne vulgaris, and that therapy with antioxidative ingredients is efficacious for treatment. In this study, we hypothesized that lipid accumulation in comedones induces progression of comedogenesis and inflammatory changes in comedones, and investigated the possible role of accumulated LPO in comedogenesis and its inflammatory changes. We first sampled comedones and the stratum corneum from patients with acne vulgaris. The quantities of LPO, interleukin-1-alpha (IL-1alpha), and NF-kappa-B (NF-kappaB) in comedones and in the stratum corneum from each patient were measured for comparison. Next, comedones were sampled again from the same patients and classified into five groups: microcomedo (MC), noninflammatory open comedo (NIOC), noninflammatory closed comedo (NICC), inflammatory open comedo (IOC), and inflammatory closed comedo (ICC). We measured quantities of LPO in each group. The quantities of LPO, IL-1alpha, and NF-kappaB were significantly higher in the content of comedones than those in the stratum corneum. The quantities of LPO in the content of IOC and ICC were significantly higher than those of MC, NIOC, and NICC; however, there were no significant differences in quantities of LPO between the content of MC, NIOC, and NICC. We conclude that the accumulation of a certain amount of LPO in the content of comedones may play an important role in the progression of comedogenesis and the excessive accumulation of LPO may be involved in inflammatory changes in comedones.
... There are also studies on the efficacy of antioxidative ingredients for the treatment of acne vulgaris. 9,10 In our previous study, we suggested that stimulation of lipid peroxide may help to induce a progression of acne vulgaris. 11 To our knowledge, there are only a few reports that examine the relationship between antioxidative component in the body and acne vulgaris. ...
Some past studies reported that oxidative stress components such as reactive oxygen species (ROS) or lipid peroxide (LPO) are involved in the pathogenesis and progression of acne vulgaris. In this study, we hypothesized that the pathogenesis of acne vulgaris may depend on the differences in antioxidative activity among antioxidants in our body. We collected samples of stratum corneum from acne patients and healthy subjects and compared the quantity of gluthathione (GSH), one of many antioxidative components in our body, for comparison. Samples of stratum corneum were collected from facial acne-involved lesion, facial uninvolved area, and the medial side of the upper arm in acne vulgaris patients. Similarly, samples were collected from a facial uninvolved area and the medial side of the upper arm in healthy subjects. The quantity of GSH was measured in each area. In vitro effects of alpha-melanocyte stimulating hormone (α-MSH) on GSH synthesis-related gene were also examined. The quantity of GSH in stratum corneum from each area was significantly lower in acne vulgaris patients than that of healthy subjects. There was no significant difference in quantity of GSH between the acne-involved lesion and uninvolved area in acne patients. In vitro studies showed that the expression level of Glutamate-cysteine ligase catalytic subunit (GCLC), one of the GSH synthesis-related genes, was significantly decreased by the additional use of α-MSH. We conclude that a decline in antioxidative activity led by a decrease in GSH quantity may play an important role in pathogenesis of acne vulgaris. The use of α-MSH may further decrease the GSH level.
Among the multiple roles of vitamin C in keratinocyte and dermal tissue, the role of scavenging active oxygen species is one of the most important. We postulated that 5% sodium L-ascorbyl-2-phosphate lotion (APS), a vitamin C derivative, would be an effective topical agent for treating patients with acne vulgaris because of its active oxygen scavenging property. As a result, we conducted a multicenter, open-label clinical trial comparing the efficacy and tolerability of APS versus 1% clindamycin phosphate lotion (CL) in the treatment of facial acne vulgaris. APS demonstrated efficacy in the topical treatment of acne vulgaris and superiority to CL for this indication.
The quenching abilities of sodium L-ascorbyl-2-phosphate (APS) and ascorbic acid 2-glucose (AG) against UVB/A-generated free radicals in cultured mouse skin were investigated using electron spin resonance (ESR). The relation between their quenching ability and protective effects against photodamage were also compared to those of ascorbic acid (AsA) pretreatment. Both APS and AG were able to scavenge UVB/A-generated hydroxyl radicals under aqueous conditions (pH 7.2) in a manner similar to that seen with AsA; however, APS was a more effective scavenger than AG. Similar results were obtained ex vivo. Both derivatives could protect skin from UVB/A-induced photodamage, as determined by a reduction in the presence of sunburn cells and DNA fragmentation. However, AsA pretreatment had the weakest protective effect, even though cutaneous, its level was the highest among the three agents tested before irradiation. These results indicated that the superior protective effect of APS is related to its direct free radical scavenging ability, rather than to its conversion to AsA.
Effects of superoxide dismutase (SOD) (100–3000 U/ml), catalase (300–3000 U/ml), xanthine (1–10 mM/ml) and D-mannitol (30–300 mM ml) were examined in the pathogenesis of sunburn cells. These agents were considered to quench oxygen intermediates. The skin specimens from clipped trunk of female ICR mice were irradiated in vitro with UV-B (6o-120 mJ/cm2). and then incubated for 24 h. The scavengers were added during both UV irradiation and incubation. In one of the SOD groups, SOD was added only during the UV irradiation.The number of sunburn cells is increased when the dose of UV-B increased and all of the scavengers suppressed sunburn cell formation in a dose dependent manner to the level of the unirradiated group.Although the oxygen intermediates alone cannot explain the whole process of sunburn cell production, it appears likely that ultraviolet-induced oxygen intermediates are involved in sunburn cell formation.