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Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: Double-blind study vs. placebo
Abstract
Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing.
A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the ‘global score’, on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations.
Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing.
... While it is frequent to see lotions or serums with concentrations of up to 30% on the market, most studies use concentrations under 10%. 7,12,13 Only one of the included RCTs assessed the effect of vitamin C in a concentration of 20% 14 which also shows the scarcity of evidence we currently have for highly prescribed high-concentration formulas. In vitro studies have also shown that the maximal concentration for optimal percutaneous absorption was 20%, 15 not supporting the routine use of products over such concentration. ...
... Yokota et al. 16 13 Global score (physician + volunteer assessment) was 6.7 ± 1.6 at baseline, 5.0 ± 1.0 at 3 M and 4.4 ± 0.7 at 6 M (p < 0.05). Hydration, wrinkles, glare, and brown spots improved in both groups and roughness, suppleness and small wrinkle scores improved significantly only in the vitamin C group. ...
... Since the levels of vitamin C available in the skin after oral ingestion are limited by regulatory mechanisms, topical delivery became attractive. 13 However, vitamin C is a water-soluble and charged molecule that is repelled by the epidermal cells. 2 To overcome this challenge, it is necessary that the pH level is below 4 and that the molecule is stable enough not to oxidate. 17 To overcome this challenge, several derivatives, lipid-soluble analogues, conjugates, and protocols have been created to assist the transport into the epidermis. ...
Background:
Vitamin C is a micronutrient present in high concentrations in normal skin and a highly prescribed cosmeceutical, well known for protecting against ultraviolet-induced pigmentation and regulating collagen production. However, there is a lack of studies evaluating the efficacy of topical vitamin C in photoaging and melasma, with this systematic review being the first to assess the existing evidence.
Aim:
This systematic review aims to assess whether topical vitamin C could be effective in reversing photoaging signs and treating melasma.
Methods:
Prospective, randomized controlled trials assessing protocols with topically applied vitamin C in patients with melasma or photodamage were searched in Medline, CENTRAL, and Scopus databases until the 12th of May 2022. Risk of bias was conducted in accordance with Cochrane Collaboration's tool for assessing the risk of bias in randomized trials, using RevMan 5.0.
Results:
Seven publications were included, with 139 volunteers in total. Studies that evaluated the topography of skin indicated that the treated skin appeared smoother and less wrinkled, which was supported by biopsies data. On objective assessments of pigmentation, there was a significant lightening of the skin treated. Hydration improved equally in the vitamin C and placebo-treated sites.
Conclusions:
This study revealed that vitamin C is effective in treating uneven, wrinkled skin and has depigmenting properties, but long-term use may be needed to achieve noticeable changes. Q-switched Nd:YAG laser-associated protocols appear beneficial in enhancing vitamin C effects. Topical vitamin C may be a suitable alternative for melasma and photoaging, but more studies are needed to confirm these results and assess the ideal vitamin C concentration.
... The investigation found a total of 145 studies and, of these, 122 were excluded. Therefore, for this review, 23 articles were selected that have proposed in vitro and/or in vivo studies and/or literature reviews containing the use of topical ascorbic acid, its selected derivatives, and/or strategies of delivery of any type of vitamin C, and 14 were considered the most relevant ones and are detailed in Tables 1 and 2 [34][35][36][37][38][39][40][41][42][43][44][45][46]. ...
... In vivo -Humbert et al. (2003) [35] evaluated a topical cream with ascorbic acid in 20 volunteers with photoaged skin for 6 months. The formulation was found to be effective and well-tolerated. ...
... In vivo Alster et al. (1998) [34] Other ingredients of formulation were not mentioned. Humbert et al. (2003) [35] Phototypes of the participants were not mentioned. The other ingredients of the formula were also not mentioned. ...
Background
the topical use of vitamin C has been explored for many decades due to its antioxidant potential, whitening action, and the essential role it plays in the synthesis and maintenance of collagen. As Ascorbic Acid (AA) is unstable, derivative molecules and stabilization strategies have been explored to facilitate its incorporation into dermatological products. Even though these molecules are already for sale, there is still a shortage of scientific data regarding efficacy studies of these assets, especially in vivo.
Objective
the purpose of this review was to investigate and discuss issues regarding the topical application of vitamin C and its most common derivatives, including the difficulties, biases, and prospects for future clinical studies to better elucidate its effects.
Method
a literature review was carried out to select studies that evaluated the topical use of ascorbic acid and/or its derivatives. The studies which are “fully available”, “in vivo”, and “in vitro” were used as inclusion criteria.
Results
due to the instability of Ascorbic Acid, it is essential to study derivative molecules that maintain or even improve their effectiveness in dermatological products. Despite this, the studies of these derivatives, presented in the scientific literature, are mostly in vitro. In recent years, it has been possible to observe an increase in in vivo efficacy tests, and this trend is expected to continue in the future. However, they present very different approaches and issues.
Conclusion
studies of stability, safety, adverse reactions, and especially in vivo efficacy studies with a relevant number of subjects and standardized parameters are essential for better elucidating the effects of the topical application of vitamin C derivatives in comparison with ascorbic acid formulations for the skin.
... In another clinical trial, 5% AA cream and one of several cosmeceuticals were applied twice a day to the extensor surface of one forearm for 2 weeks, and the level of procollagen I in the skin biopsy was analyzed [68]. Statistical analysis of all 19 subjects who applied 5% AA cream did not show a significant increase in procollagen level compared to the baseline before treatment. ...
... Clinical evidence has been reported that topical treatment of AA alleviates the symptoms of skin aging. In a randomized, double-blind, placebo-controlled study enrolling 19 healthy female volunteers, topical application of 5% AA cream on the sun-exposed upper chest and forearm once a day for 6 months significantly increased the density of skin microrelief, decreased the deep furrows, and improved ultrastructure of the skin, compared to the excipient treatment [68]. In a split-face study enrolling 20 women subjects with photo-aged skin, topical treatment of 23.8% AA serum with iontophoresis on one side of the face once a day for 2 weeks improved hyperpigmentation, surface roughness, and fine lines on the treated side significantly compared to the other side spared for participants' self-control [69]. ...
... The results of several clinical trials suggest that AA and its precursor reduce wrinkles and increase the elasticity of the skin by preventing the loss of collagen in the process of photoaging and the natural aging of the skin [67][68][69]89]. External supplementation of AA can have a beneficial effect especially when the level of AA in the body is significantly lower than the normal state [67]. ...
Ascorbic acid (AA) is an essential nutrient and has great potential as a cosmeceutical that protects the health and beauty of the skin. AA is expected to attenuate photoaging and the natural aging of the skin by reducing oxidative stress caused by external and internal factors and by promoting collagen gene expression and maturation. In this review, the biochemical basis of AA associated with collagen metabolism and clinical evidence of AA in increasing dermal collagen and inhibiting skin aging were discussed. In addition, we reviewed emerging strategies that have been developed to overcome the shortcomings of AA as a cosmeceutical and achieve maximum efficacy. Because extracellular matrix proteins, such as collagen, have unique amino acid compositions, their production in cells is influenced by the availability of specific amino acids. For example, glycine residues occupy 1/3 of amino acid residues in collagen protein, and the supply of glycine can be a limiting factor for collagen synthesis. Experiments showed that glycinamide was the most effective among the various amino acids and amidated amino acids in stimulating collagen production in human dermal fibroblasts. Thus, it is possible to synergistically improve collagen synthesis by combining AA analogs and amino acid analogs that act at different stages of the collagen production process. This combination therapy would be useful for skin antiaging that requires enhanced collagen production.
... Although in vitro permeation studies show low passive diffusion of vitamin C and its precursors across the skin, the standard clinical treatment still involves the application of a topical formulation and passive diffusion to treat skin ageing and melasma [43][44][45][46]. When applied regularly and for a moderate time such procedure has a reasonable degree of efficacy, namely in the treatment of epidermal melasma and fine wrinkles [4,45,47]. ...
... Although in vitro permeation studies show low passive diffusion of vitamin C and its precursors across the skin, the standard clinical treatment still involves the application of a topical formulation and passive diffusion to treat skin ageing and melasma [43][44][45][46]. When applied regularly and for a moderate time such procedure has a reasonable degree of efficacy, namely in the treatment of epidermal melasma and fine wrinkles [4,45,47]. However, for treatments in deeper skin layers (deep wrinkles) this approach is very limited and usually requires a considerably long timeframe and a daily regiment application [45,46]. ...
... When applied regularly and for a moderate time such procedure has a reasonable degree of efficacy, namely in the treatment of epidermal melasma and fine wrinkles [4,45,47]. However, for treatments in deeper skin layers (deep wrinkles) this approach is very limited and usually requires a considerably long timeframe and a daily regiment application [45,46]. Considering that PA waves deliver higher amounts of AA2G and that they can reach deeper layers of the skin, one can expect an increase in collagen production and the consequent attenuation of wrinkles when the topical application of AA2G is combined with PA waves [45]. ...
Objective:
Ascorbic acid (i.e., vitamin C) is an important antioxidant present in skin. The protective role of vitamin C against photoaging motivated numerous attempts to promote its topical delivery, with a success limited by its chemical instability and poor skin permeability. Vitamin C precursors, such as ascorbic acid 2-glucoside (AA2G), that are metabolized to vitamin C by enzymes present in the skin, solve the problem of stability but are limited by low skin permeability. We developed a 2% (w/v) gel formulation of AA2G application (viscosity 4.30 × 104 Pa.s, pH 5.94) and compared its passive dermal delivery with the delivery promoted by photoacoustic waves that transiently perturb the skin barrier.
Methods:
Photoacoustic (PA) waves were generated by laser pulses absorbed by piezophotonic (light-to-pressure) transducers. Pig skin samples were exposed to the 2% AA2G formulation alone or combined with 5 minutes of PA waves. One hour later, AA2G was extracted from the skin and quantified by reverse-phase HPLC. AA2G transdermal fluxes using Franz cells with 760 μm thick pig skin samples were also measured.
Results:
PA waves transiently enhanced skin permeability and increased dermal delivery of AA2G. AA2G was released from the formulation nearly quantitatively (92.6 ± 6.2%) in 24 hours, showing a non-Fickian behaviour controlled by diffusion and swelling. AA2G dermal delivery with exposure for 5 minutes to PA waves was compared with passive delivery to pig skin. PA waves increased the delivery of AA2G to the skin by a factor of 15 fold with respect to passive delivery, as measured from skin extracts after 1 hour of contact of the formulation with the skin.
Conclusion:
5 minutes of exposure to PA waves is a safe and effective method to deliver large quantities of AA2G to the skin.
... L-ascorbic acid and its derivatives (ascorbyl palmitate, magnesium ascorbyl phosphate, tetraisopalmitoyl ascorbic acid), are and the basic ingredients in anti-ageing products, due to their potent antioxidant activities, photoprotective properties and involvement in collagen biosynthesis [1][2][3][4][5][6]. By interfering with tyrosinase, L-ascorbic acid can treat hyperpigmentation, melasma and sunspots [7,8]. ...
... L-Ascorbic acid and meta-phosphoric acid (MPA) was purchased from Sigma-Aldrich. 3 ...
L-ascorbic acid represents one of the most potent antioxidant, photoprotective, anti-aging and anti-pigmentary cosmeceutical agents, with a good safety profile. However, the challenge remained to design the stable topical formulation, with such a permeability of L-ascorbic acid as active that the optimal effects on skin could be achieved. The aim of our research was to evaluate the difference between the penetration ability of ascorbyl palmitate incorporated in the same percentage (2%) within the creams and emulgels as carriers, as well as to determine the impact of its incorporation into liposome on the kinetics of penetration. Tape stripping was applied for studying the penetration of the ascorbyl palmitate into the stratum corneum. In addition, the sensory and textural properties of examined formulations were determined. In both cases (liposomal and non-liposomal formulations), creams exhibited a better penetration profile of active substance compared to the use of emulgel. Encapsulation of ascorbyl palmitate into liposomes led to an increase in the adhesiveness and density of the prepared cream and emulgel samples. The best spreadability and absorption during application were detected in liposomal samples. The obtained results confirmed improved dermal penetration of ascorbyl palmitate, either cream or emulgel bases were employed, which further indicates the advantages of its liposomal encapsulation.
... Various stabilization strategies have been attempted to address the instability of AA, such as liposomal encapsulation [29,30], anhydrous suspensions [31], and the use of vitamin C derivatives [32,33]. Despite its low skin permeability and instability, AA remains widely used in dermatology and cosmetic formulations as a skin-whitening and anti-aging agent [34,35], owing to its excellent antioxidant properties, ability to inhibit melanin synthesis [36,37], and promotion of collagen formation [38,39]. ...
... Various stabilization strategies have been attempted to address the instability of AA, such as liposomal encapsulation [29,30], anhydrous suspensions [31], and the use of vitamin C derivatives [32,33]. Despite its low skin permeability and instability, AA remains widely used in dermatology and cosmetic formulations as a skinwhitening and anti-aging agent [34,35], owing to its excellent antioxidant properties, ability to inhibit melanin synthesis [36,37], and promotion of collagen formation [38,39]. ...
L-ascorbic acid (AA), a potent antioxidant, is commonly used topically in the pharmaceutical and cosmetic fields. However, the incorporation of AA into topical formulations is difficult because of its highly unstable nature and relatively poor skin permeability. In this study, we propose an alternative strategy for improving the solubility and topical delivery of AA through its conversion to a therapeutic deep eutectic system (THEDES). AA and betaine (Bet)-based THEDESs were prepared at certain molar ratios and characterized using polarized optical microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Solubility tests showed that AA in the form of THEDES was readily soluble in various polyols (glycerin, 1,3-butylene glycol, dipropylene glycol, and 1,3-propanediol) at a high concentration (approximately 40%). Furthermore, compared to AA alone or the physical mixture of AA and Bet, AA-based THEDES significantly enhanced AA delivery through porcine skin. In an in vivo human study, THEDES-containing serum reduced the markers of aging and induced an even skin tone. These findings indicate the utility of AA and Bet-based THEDES as novel transdermal delivery systems for AA. Furthermore, our approach also showed good extension to developing gluconolactone, a well-known natural antioxidant, and Bet-based THEDES, showing potential application in transdermal delivery systems.
... A dose recomendada para manutenção de nível de saturação da vitamina C no organismo é de cerca de 100mg por dia para adultos,60 mg/dia para crianças, 70 mg/dia para gestantes e 90 mg/dia para lactantes. [2][3][4][5][6][7][8][9][10][11][12] Segundo Reichstein e colaboradores, em 1933, conseguiram comprovar que o ácido Lascórbico sintetizado possui a mesma atividade biológica da substância natural. Podendo então ser suplementada através da ingestão da vitamina C industrial e em rotinas de skincare, é indicada a sua utilização de uso tópico. 2 Quando se fala em pele, a busca por ativos que demonstrem capacidade em devolver qualidade ao tecido e funções como prevenção de oxidação celular e fatores antienvelhecimento, a vitamina C desempenha papel importante nesses quesitos. ...
... Incluindo também a síntese de colágeno, ação clareadora, uma vez que age na melanina sintetizada e promove ação antioxidante. [1][2][3][4][5] Sabemos que o que mantém a pele saudável é o equilíbrio, a homeostasia, e para manter esse equilíbrio a tecnologia vem estudando cada vez mais a ação de ativos que possam devolvê-lo à pele, de modo que possa promover a prevenção do envelhecimento cutâneo e até mesmo a melhora de quadros mais avançados, de envelhecimento tecidual. 1 Através das pesquisas, tem sido comprovada a eficácia da utilização de princípio ativos com pH baixo, para melhor permeabilização na pele, sendo que os de ativos com capacidade antioxidante tem consideravelmente minimizado os efeitos do envelhecimento, por inibição dos radicais livres. ...
O envelhecimento cutâneo ocorre através da perda de qualidade de tecido/pele (ressecamento, rugas e linhas de expressão e manchas), sendo a maior queixa do público que recorre a tratamentos estéticos atualmente. Este envelhecimento pode ser ocasionado por alguns fatores como idade, genética, maus hábitos e até mesmo questões patológicas. Porém, evidências científicas têm demonstrado que o uso de ácido ascórbico ou vitamina c (como é comumente conhecido), nas rotinas de cuidados diários com a pele, diminuiu significativamente o fotoenvelhecimento cutâneo e demonstrou grande capacidade em retardar o surgimento de linhas e sulcos e clarear ou prevenir o surgimento de manchas. Sua função é promover rejuvenescimento facial através de sua ação antioxidante e despigmentante, prolongando o tempo de vida de células saudáveis e promovendo maior qualidade celular através da síntese de colágeno. A presente pesquisa descreve, por intermédio do estudo de publicações e artigos científicos, a eficácia do uso deste ativo no rejuvenescimento facial, na melhora da qualidade tecidual, formas de utilização e resultados obtidos através de seu uso diário.
... In addition to anthocyanins, flavonoids and phenolic acids, vitamin C was also identified in M nigra, which is a strong antioxidant with an important role on the skin [10][11][12]. ...
... Also in this stage, phagocytic cells are concentrated at the level of the wound, which practically clean the wound and act as antimicrobial elements. The MnE extract is a rich source in phenolic acids, flavonoids, phytocompounds which are proven to have antimicrobial activity and can be considered a stimulator of wound scar formation [10][11][12]. ...
Natural compounds are used in modern dermal treatments to avoid side effects commonly associated with conventional treatments. The aim of our study was to develop a liposomal formulation including black mulberry extract and to highlight its potential on the healing of normal human dermal fibroblasts (NHDF) in vitro using the scratch test. Mulberry-loaded liposomes (Mn_L) were prepared using a thin-film hydration method based on cholesterol (C) and phosphatidylcholine (PC) in a 1:3 (w/w) ratio. The liposomal formulation was characterized by analyzing its size, electric surface potential, morphology, entrapment efficiency, and in vitro healing effects. Also, the black mulberry fruits (Morus nigra L.) were characterized from point of view of polyphenolic compounds and antioxidant capacity by Ferric-Reducing Antioxidant Power (FRAP) assay. HPLC-DAD-MS (ESI+) (high performance liquid chromatography-photodiode array detection-mass spectrometry (electrospray ionization)) analysis indicated the presence of phenolic compounds namely from hydroxybenzoic and hydroxycinnamic acids and flavonols. Among flavonols, quercetin-glucoside represented 50.56%, and chlorogenic acid was the predominant compound among hydroxycinnamic acids (37.06%). In vitro fibroblast wound closure was more effective with mulberry-loaded liposomes (L_Mn) than extracts of mulberries. According to our study, mulberry-loaded liposomes have been shown to be effective in wound healing and can be used as a natural treatment.
... Vitamin C (Vit C) or L-ascorbic acid is a hydrophilic molecule with low molecular weight, which is fundamental to the proper functioning of the human body 1,2 . One of the most recognized properties of Vit C is its antioxidant capacity: in-vitro and in-vivo studies confirm the ability of this molecule to protect the cells against UV-induced damage by scavenging free radicals [3][4][5][6] . Besides, Vit C is able to regenerate other antioxidants species, such as alpha-tocopherol (vitamin E), inhibiting indirectly lipid peroxidation 3-9. ...
... Due to these advantageous effects, Vit C has been used in personal-care formulations for many years 2,13 . However, it is necessary to take into account that Vit C must be kept stable in order to maintain its biological activity 5 . During the degradation process, Vit C is easily oxidized to dehydroascorbic acid and afterward to diketogluconic acid. ...
Vitamin C (ascorbic acid) is widely used in skin care products, yet it is a challenging compound due to its physical and chemical instability. Several strategies have been applied to improve the stability of vitamin C, such as the addition of other antioxidants in the system (e.g., Vitamin E, ferulic acid, and sodium metabisulfite). In addition, clay minerals have been used in cosmetic preparations due to their high ion-exchange capacity, thermal stability, softness, the small size of their particles, and their attractive adsorptive properties. In this study, we proposed the association of kaolin clay and well-known antioxidants and chelators to improve the stability of vitamin C. Although the kaolin clay alone did not improve the stability of the vitamin C, the clay mineral in association with certain chelators and/or antioxidants could improve the stability of formulations containing vitamin C.
... Humbert et al. who used 5% topical ascorbic acid reported that hydration, wrinkles, glare, roughness, and brown spots were improved [20]. ...
Several treatment modalities have been used for the treatment of melasma. Topical metformin is an anti-diabetic drug, which has melanopenic action. Vitamin C acts on melanin by inhibiting the tyrosinase enzyme, thus inhibiting melanogenesis. To compare the efficacy and safety of microneedling combined with topical metformin solution versus microneedling combined with topical vitamin C in the treatment of melasma. A spitted-face interventional comparative on 30 female patients suffering from melasma. The right side of the face was treated with microneedling and topical metformin, while the left side was treated with microneedling and topical vitamin C solution. Hemi-MASI score decreased significantly after treatment from before treatment in both groups P-value < 0.001. The percentage of improvement of Hemi-MASI score metformin group was 48.29%, While with vitamin C group was 37.19%. There was a significant improvement in dermoscopic findings in microneedling with topical metformin than with topical vitamin C group. Microneedling with topical metformin or topical vitamin C solution can be an effective and safe therapeutic option for treating melasma with no significant side effects.
... Stabilizing Vitamin C requires careful attention to pH, as it is more stable at a pH below 3.5, but maintaining this low pH can be difficult and may not be suitable for all skin types, especially sensitive skin [8]. 2 Effective concentrations of Vitamin C in skincare products typically range from 5% to 20%. Lower concentrations may not provide significant benefits, while higher concentrations can increase the risk of skin irritation and sensitivity [9,10]. Additionally, different countries have varying regulations on the maximum allowable concentration of Vitamin C in cosmetic products. ...
Introduction: This study explores the stabilization and efficacy enhancement of Vitamin C in dermocosmetic formulations through its association with Poly-L-lysine dendrimers. Vitamin C, critical for collagen synthesis and skin hydration, faces challenges due to its instability and low bioavailability. The research aims to evaluate the liposolubility of Vitamin C in the presence of Poly-L-lysine vectors, assess its stability in both aqueous and emulsion media, and determine the moisturizing efficacy of second-generation Poly-L-lysine (diameter: 4.5 nm, PM: 8.6 kDa) and third-generation Poly-L-lysine (diameter: 7 nm, PM: 22 kDa). Methods : Methods included high-performance liquid chromatography (HPLC) for concentration analysis, partition coefficient determination, and stability assessments under various conditions. Hydration potential and kinetics were evaluated on 11 volunteers using a corneometer. Results: The liposolubility of Vitamin C increased by over 300% with Poly-L-lysine, enhancing its stability. Emulsion stability tests confirmed that formulations with Poly-L-lysine maintained their physical and chemical properties under stress conditions. Physiological tests showed significant improvements in skin hydration with the Poly-L-lysine/Vitamin C formulations, achieving 66.2% hydration increase at T3h for third-generation dendrimers. Conclusion In conclusion, Poly-L-lysine vectors significantly enhance the stability and moisturizing efficacy of Vitamin C in dermocosmetic formulations. These findings suggest that Poly-L-lysine can mitigate Vitamin C's instability and improve its dermocosmetic benefits, offering a promising approach for advanced skincare solutions.
... L-ascorbic acid and its derivatives (ascorbyl palmitate, magnesium ascorbyl phosphate, tetraisopalmitoyl ascorbic acid) are basic ingredients in anti-aging products due to their potent antioxidant activities and photoprotective properties and their involvement in collagen biosynthesis [1][2][3][4][5][6]. By interfering with tyrosinase, L-ascorbic acid can treat hyperpigmentation, melasma, and sunspots [7,8]. ...
L-ascorbic acid represents one of the most potent antioxidant, photoprotective, anti-aging, and anti-pigmentation cosmeceutical agents, with a good safety profile. However, the main challenge is the formulation of stable topical formulation products, which would optimize the penetrability of L-ascorbic acid through the skin. The aim of our research was to evaluate the performance of ascorbyl palmitate on the skin, incorporated in creams and emulgels (2%) as carriers, as well as to determine the impact of its incorporation into liposomes on the penetration profile of this ingredient. Tape stripping was used to study the penetration of ascorbyl palmitate into the stratum corneum. In addition, the sensory and textural properties of the formulations were determined. The liposomal formulations exhibited a better penetration profile (p < 0.05) of the active substance compared to the non-liposomal counterpart, leading to a 1.3-fold and 1.2 fold-increase in the total amount of penetrated ascorbyl palmitate in the stratum corneum for the emulgel and cream, respectively. Encapsulation of ascorbyl palmitate into liposomes led to an increase in the adhesiveness and density of the prepared cream and emulgel samples. The best spreadability and absorption during application were detected in liposomal samples. The obtained results confirmed that liposomal encapsulation of ascorbyl palmitate improved dermal penetration for both the cream and emulgel formulations.
... Compared with placebo, vitamin C led to a clinically apparent improvement in the overall appearance of photodamaged skin as well as a decrease in deep furrows. 22 Another study found that using 20% vitamin C, vitamin E, and raspberry leaf extract led to an improvement in most signs of skin aging, including the periorbital region, namely darkening, smoothness, and wrinkles. 11 ...
Background
Due to the periorbital region’s high susceptibility to damage from external factors, along with its tendency to demonstrate early signs of aging, periorbital skin is a common target for antiaging therapy.
Objective
This review aims to evaluate the efficacy of active ingredients commonly found in eye creams, particularly focusing on their impact on periorbital skin concerns.
Methods
A comprehensive review of the literature on active ingredients in eye creams, including retinoids, vitamins C and E, peptides, ceramides, hyaluronic acid, caffeine, and niacinamide, was conducted. Clinical studies assessing the efficacy of these ingredients in addressing periorbital concerns were examined.
Results
Studies demonstrate the potential of these ingredients to improve various aspects of periorbital skin, including hydration, elasticity, collagen synthesis, and reduction of inflammatory mediators. Ingredients such as retinoids, vitamin C, and caffeine show promise in addressing wrinkles and hyperpigmentation, while peptides and hyaluronic acid aid in collagen production and hydration. Niacinamide and ceramides offer benefits in reducing wrinkles and enhancing the skin barrier function.
Limitations
The lack of clinical trials specifically targeting eye cream formulations and periorbital skin is a notable limitation. Furthermore, the variability in study designs, sample sizes, and concentrations of active ingredients across studies complicates direct comparisons.
Conclusion
The reviewed studies highlight the potential of active ingredients in eye creams to address various periorbital concerns. Further research, particularly large-scale clinical trials focusing on eye cream formulations and their efficacy on periorbital skin, is warranted to establish their significance and comparability with other dermatologic products.
... Additionally, Sauermann et al. [52] pointed to the partial restoration of the anatomical structure of the epidermal-dermal junction in young skin, as well as an increase in the nutritive loops of blood vessels in the papillary dermis in the aging skin of postmenopausal women. Xu et al. [53] demonstrated a reduction in surface roughness and fine wrinkles in subjects treated with locally applied 23.8% L-ascorbic acid serum, which also inhibited elastin synthesis in vitro [54]. It has also been shown that ferulic acid plays a protective role in important skin structures, such as collagen, keratinocytes, and elastin fibroblasts [14]. ...
Antioxidants (including Vitamin C, ferulic acid, and phloretin) are among the compounds used in skincare products. The purpose of this study was to evaluate the effect of a combination containing L-ascorbic acid, ferulic acid, and phloretin. The delivery of active substances was facilitated by micro-needle mesotherapy and sonophoresis. The study was completed by 22 volunteers. The study resulted in a significant reduction of erythema and an improvement in skin hydration. According to participants, the therapy yielded visible anti-aging effects. The combination of up to three antioxidant-active ingredients and the use of transdermal application methods proved to be both safe and effective.
... Adverse reports of stinging (55%), erythema (24%), and dry skin (0.05%) resolved with moisturizer [8]. In 2 other doubleblind, vehicle-controlled RCTs, topical ascorbic acid was effective and well tolerated in improving wrinkles and appearance of photoaged skin [10,11]. ...
Cosmeceuticals, the bridge between pharmaceuticals and cosmetics, contain biologically active ingredients that may improve the skin's overall appearance. As the market, accessibility, and popularity of cosmeceuticals increase, it is essential to understand the safety and efficacy of such products. This systematic review aims to examine published clinical studies involving the use of cosmeceuticals for antiaging to provide evidence-based recommendations based on available efficacy and safety data. PubMed, Embase, and Cochrane were systematically searched on January 1, 2023 using PRISMA guidelines. Strength of evidence was graded using the Oxford Centre for Evidence-Based Medicine guidelines. Clinical recommendations were made based on the quality of the existing literature. A total of 153 articles regarding the use of cosmeceuticals for treatment of antiaging were identified. After screening of titles, abstracts, and full text, 32 studies involving 1236 patients met inclusion criteria, including 20 randomized controlled trials (RCTs) and 12 non-randomized open-label clinical trials for Vitamin C, Retinol, Bakuchiol, Tetrahydrojasmonic acid, Growth Factors, Methyl Estradiolpropanoate, Timosaponin A-III (TA-III), Protocatechuic acid, Grammatophyllum speciosum, and Jasmine rice panicle extract. Retinol and vitamin C for antiaging received a Grade A for recommendation. Methyl estradiolpropanoate, bakuchiol, tetrahydrojasmonic acid, and growth factors received a recommendation grade of C. The remaining ingredients were assigned an inconclusive grade of recommendation due to lack of evidence. Cosmeceuticals included in the review had favorable safety profiles with few significant adverse events. The review analyzes numerous different ingredients to provide an evidence-based approach to decision-making for consumers and physicians on the use of cosmeceuticals for antiaging. Limitations to our review include a limited number of randomized controlled trials and a need for long-term data on each cosmeceutical's efficacy and safety. Future research is needed to establish the long-term effectiveness and safety of cosmeceuticals.
... Being an electron donor, AA serves as an important quality indicator of foods and drinks due to its low-molecular-weight antioxidant property [5]. Owing to many studies that have presented the advantage of topical application of AA for skin-lightning, anti-aging and photoprotection purposes, AA has been widely used in the cosmetic industry [6][7][8][9]. The skin-lightning effect of AA can be attributed to its reduction in melanin synthesis through the suppression of tyrosine's catalytic activity [10]. ...
Ascorbic acid plays a significant role in regulation of various bodily functions with high concentrations in immune cells and being involved in connective tissue maintenance. Commonly it is detected through various colorimetric methods. In this study, we propose a one-step simple method based on the inhibitory activity of ascorbic acid on horseradish peroxidase and hydrogen peroxide. The detection is observed by colorimetric changes to TMB (3,3′,5,5′ tetramethylbenzidine). The enzyme inhibition unit was optimized with a high level of linearity (r² = 0.9999) and the level of detection and level of quantification were found to be 1.35 nM and 4.08 nM, respectively with higher sensitive compared to the HPLC method (11 μM). Both intra and inter-assays showed high correlations at different AA concentrations. (r² > 0.9999). Similar results were also observed for vitamin C tablets, ascorbate salts, fruits, and market products (r² = 0.999). There was negligible effect of interference by citric acid, lactic acid, tartaric acids, and glucose with high recoveries (>98%) at 1 mg/mL to 0.0078 mg/mL concentration ranges. The recovery error (RE%) was found to be less than 10%. Our detection method is distinguished by its simplicity, nano-level of detection, reproducibility, and potential application and adaptability as a point-of-use test.
... Several clinical trials and in vivo studies have demonstrated that the topical use of vitamin C at different concentrations shows high efficacy in the treatment of skin damaged by PA, with evidence of its inhibitory effect on MMP-1 [84], a decrease in PA scores of the face, an increase in collagen production [85], a significant increase in cutaneous microrelief density, a reduction in deep wrinkles [86], the suppression of genetic mutations associated with UV exposure [87], and protection against erythema [88] and skin hyperpigmentation [89]. The joint use of vitamins C and E generates a synergistic effect on the antioxidant activity of both compounds. ...
Photoaging (PA) is considered a silent disease affecting millions of people globally and is defined as skin damage due to prolonged exposure to ultraviolet radiation (UVR) from the sun. Physiologically, the skin is in a state of renewal and synthesis of components of the extracellular matrix (ECM). However, exposure to UVR affects the production of the ECM, and the functioning and response of skin cells to UVR begins to change, thus expressing clinical and phenotypic characteristics of PA. The primary mechanisms involved in PA are direct damage to the DNA of skin cells, increases in oxidative stress, the activation of cell signaling pathways responsible for the loss of skin integrity, and cytotoxicity. The medical and scientific community has been researching new therapeutic tools that counteract PA, considering that the damage caused by UVR exceeds the antioxidant defense mechanisms of the skin. Thus, in recent years, certain nutraceuticals and phytochemicals have been found to exhibit potential antioxidant and photoprotective effects. Therefore, the main objective of this review is to elucidate the molecular bases of PA and the latest pharmaceutical industry findings on antioxidant treatment against the progression of PA.
... The results of this clinical trial confirm that topical application of 5% vitamin C over 6 months significantly improves the clinical appearance of photodamaged skin as compared to vehicle alone. (53) RCT was carried out by Pattarawan Rattanawiwatpong on the Anti-aging and brightening effects of a topical treatment containing vitamin C, vitamin E, and raspberry leaf cell culture extract. The results of the trial show that vitamin C, vitamin E, and raspberry leaf cell culture extract serum have anti-aging and brightening effects on the skin. ...
Rationale: Now a days, prescribing antioxidant drugs has become very much common. Their usefulness in certain long term, chronic conditions where oxidative stress plays a vital role is well explained. But in many other conditions, their role is yet not fully discovered or explained as well their duration of use, type of antioxidant to be used, their pros and cons as well as role of free radicals in our body need to be understood by the prescribing physicians. Up to date research on this and knowledge will change attitude and practice and therefore will have positive impact on physical, mental and economic wellbeing of the patients. Aim: It is to study the use of antioxidants in clinical practice and analyze the rationality in terms of their appropriate use, duration, cost, safety and efficacy. Methodology: This review article has been prepared by going through various literature like research articles, text books and drug indexes available on the same topic. This review article focuses on various research on the pharmacological activities of natural and synthetic antioxidant molecules as well as addresses their rationality in current practice. Discussion and Conclusion: Free radicals (FR) are atoms or molecules with unpaired electrons. Endogenous production of free radicals takes place in mitochondria, peroxisomes, endoplasmic reticulum, etc. Exogenous factors like cigarette smoking, chronic alcohol intake, toxic environmental products, etc. also contribute to the production of FR. When pro-oxidative processes overwhelm cellular antioxidant defense, there is a development of oxidative stress. Antioxidants protect cells from damages caused by free radicals. Antioxidants act as free radical scavengers and further classified into endogenous & exogenous antioxidants. Antioxidants prolong or delay the occurrence of neurodegenerative disorders, eye diseases, liver diseases, cancer and ageing. Also, antioxidants are found useful in some dermatological conditions, endometriosis and periodontitis. But studies conducted throughout world shows that free radicals are harmful but are also important in human body for many physiological processes and antioxidants though considered protective and useful may have their own harmful effects. So a balance has to be maintained to get a positive outcome in clinical practice
... When used topically, ascorbic acid can significantly improve photoageing scores for cheek and the perioral area, 100 and reduce skin roughness and wrinkling. 102 These clinical improvements are thought to be mediated via the proliferation of keratinocytes and fibroblasts, 103 increased expression of collagen I and collagen III, 100,102,104 newly synthesized elastic fibres in the papillary dermis, 105 and also increased expression of ECM protease inhibitors such as TIMPS. 104 In addition to increased expression of collagen, topical ascorbic acid also improves collagen fibre organization and cross-linking, which together enhance the strength and stability of the ECM. ...
Skin ageing is a complex process involving the additive effects of skin’s interaction with its external environment, predominantly chronic sun exposure, upon a background of time-dependent intrinsic ageing. Skin health and beauty is considered one of the principal factors perceived to represent overall ‘health and wellbeing’; thus, the demand for skin rejuvenation strategies has rapidly increased, with a worldwide annual expenditure expected to grow from US44.5 billion by 2030 (https://www.databridgemarketresearch.com/reports/global-facial-rejuvenation-market). Skin rejuvenation can be achieved in several ways, ranging from laser and device-based treatments to chemical peels and injectables; however, topical skin care regimes are a mainstay treatment for ageing skin and all patients seeking skin rejuvenation can benefit from this relatively low-risk intervention. While the most efficacious topical rejuvenation treatment is application of tretinoin (all-trans retinoic acid) – a prescription-only medicine considered to be the clinical ‘gold standard’ – a hybrid category of ‘cosmeceutical’ products at the midpoint of the spectrum of cosmetics and pharmaceutical has emerged. This article reviews the clinical manifestations of skin ageing and the available topical treatments for skin rejuvenation, including retinoids, peptides and antioxidants.
... Vitamin C, or L-ascorbic acid, is an antioxidant that is essential for collagen synthesis, and indirectly scavenges superoxide by formation of an intermediate radical [4,11]. In clinical studies, a 3% oil-in-water (O/W) emulsion was shown to reduce facial wrinkles and a 5% cream was shown to facilitate elastic tissue repair involving dermal papillae [57,58]. Vitamin E, or d-α-tocopherol, is an antioxidant that has been shown to inhibit molecularly induced oxidative changes including AP-1 binding in UV-irradiated keratinocytes in a dose-dependent manner [59]. ...
Successful aging" counters the traditional idea of aging as a disease and is increasingly equated with minimizing age signs on the skin, face, and body. From this stems the interest in preventative aesthetic dermatology that might help with the healthy aging of skin, help treat or prevent certain cutaneous disorders, such as skin cancer, and help delay skin aging by combining local and systemic methods of therapy, instrumental devices, and invasive procedures. This review will discuss the main mechanisms of skin aging and the potential mechanisms of action for commercial products already on the market, highlighting the issues related to the permeation of the skin from different classes of compounds, the site of action, and the techniques employed to overcome aging. The purpose is to give an overall perspective on the main challenges in formulation development, especially nanoparticle formulations, which aims to defeat or slow down skin aging, and to highlight new market segments, such as matrikines and matrikine-like peptides. In conclusion, by applying enabling technologies such as those delivery systems outlined here, existing agents can be repurposed or fine-tuned, and traditional but unproven treatments can be optimized for efficacious dosing and safety.
... Sauermann et al. [35] report that the application of 3% vitamin C on the forearm of women improved the density of dermal papillae, probably via angiogenesis, suggesting that this compound can partially correct aging-related regressive structural changes. A double-blind, randomized trial revealed that topical application of 5% vitamin C on photoaged skin was associated with marked intensification of the density of skin microrelief as well as a reduction of the deep furrows [36]. Such treatment was not only effective but also well-tolerated. ...
Combined methods of applying chemical peels and antioxidants could be an option for skin rejuvenation with no down-time. The penetration of active substances can be enhanced by microneedle mesotherapy. The study was conducted on a group of 20 female volunteers, aged 40–65 years. All volunteers received a series of eight treatments performed every seven days. The whole face was first treated with azelaic acid; following this, the right side received a 40% solution of vitamin C and the left side 10% vitamin C with microneedling. Hydration and skin elasticity were markedly improved, with better results observed on the microneedling side. Melanin and erythema index decreased. No significant side effects were seen. The combination of active ingredients and delivery techniques have great potential to enhance the effectiveness of cosmetic preparations, probably by multidirectional ways of action. In our study, we demonstrated that both 20% azelaic acid + 40% vitamin C treatment and 20% azelaic acid + 10% vitamin C + microneedle mesotherapy efficiently improved the assessed parameters of aging skin. However, the use of microneedling mesotherapy as a means of direct delivery of active compound to the dermis enhanced the effectiveness of the studied preparation.
... The changes in the skin over time are from a combination of the physiologic decline in the integrity and synthesis of collagen as well as ultraviolet light damage from sun exposure. This process is both slowed and improved with regular application of topical vitamin C to sun-exposed areas, with Humbert et al. showing considerable benefit after six months of topical therapy [39]. At the cellular level, vitamin C increases the mRNA levels of type I and type III collagen in the human dermis when skin biopsies were taken from areas on the forearm treated with topical vitamin C compared to skin that was not treated. ...
The outbreak of the COVID-19 pandemic has left clinicians around the world searching for viable prevention and treatment options to use against the virus. The important physiologic properties of vitamin C have been well documented regarding its use by immune cells and its role as an antioxidant. It has previously shown potential as a prophylactic and treatment option for other respiratory viruses, and because of this, there has been intrigue into whether these positive outcomes translate into a cost-effective prevention and treatment option for COVID-19. To this point, there have only been a few clinical trials performed to assess the validity of this notion, with very few showing definitive positive outcomes when vitamin C has been incorporated into prophylactic or treatment protocols to use against coronavirus. When being used to specifically treat the severe complications that arise from COVID-19, vitamin C is a reliable option to treat COVID-19-induced sepsis but not pneumonia or acute respiratory distress syndrome (ARDS). As a treatment option, high-dose therapy has shown flashes of promise in a few studies although investigators in these studies often subject the testing group to multimodal therapies that include vitamin C as opposed to just vitamin C alone. Given the role that vitamin C has shown to uphold regarding the human immune response, it is currently advised for all individuals to maintain a normal physiologic range of plasma vitamin C through diet or supplements for adequate prophylactic protection against the virus. More research with definitive outcomes will be needed before it is recommended to provide high-dose vitamin C therapy to prevent or treat COVID-19.
... Topical ascorbic acid was shown to significantly reduce the incidence of skin tumors in hairless mice after chronic exposure to UVR [45]. In a double-blind randomized trial performed for 6 months, where the action of the 5% of vitamin C cream and control (excipient) on photoaged skin was compared, ascorbic acid led to a clinical improvement of the photoaging skin signs [75]. Ascorbyl palmitate shielded the porcine skin from UV-induced free radicals [76]. ...
Ultraviolet (UV) radiation promotes the generation of reactive oxygen species (ROS) and nitrogen species (RNS), resulting in skin damage. Cosmetic industries have adopted a strategy to incorporate antioxidants in sunscreen formulations to prevent or minimize UV-induced oxidative damage, boost photoprotection effectiveness, and mitigate skin photoaging. Many antioxidants are naturally derived, mainly from terrestrial plants; however, marine organisms have been increasingly explored as a source of new potent antioxidant molecules. This work aims to characterize the frequency of the use of antioxidants in commercial sunscreens. Photoprotective formulations currently marketed in parapharmacies and pharmacies were analyzed with respect to the composition described on the label. As a result, pure compounds with antioxidant activity were found. The majority of sunscreen formulations contained antioxidants, with vitamin E and its derivatives the most frequent. A more thorough analysis of these antioxidants is also provided, unveiling the top antioxidant ingredients found in sunscreens. A critical appraisal of the scientific evidence regarding their effectiveness is also performed. In conclusion, this work provides an up-to-date overview of the use of antioxidants in commercial sunscreens for a better understanding of the advantages associated with their use in photoprotective formulations.
... AA is widely used in dermatology and the cosmetic industry as a skin conditioning agent. Numerous clinical studies support the use of topically applied AA for photoprotection, anti-aging, and skin-lightening purposes [6][7][8][9]. The function of AA as an antioxidant and an enzyme cofactor is essential in maintaining skin health and preventing skin aging. ...
Nowadays, micro-sized sensors have become a hot topic in electroanalysis. Because of their excellent analytical features, microelectrodes are well-accepted tools for clinical, pharmaceutical, food safety, and environmental applications. In this brief review, we highlight the state-of-art electrochemi-cal non-enzymatic microsensors for quantitative detection of ascorbic acid (also known as vitamin C). Ascorbic acid is a naturally occurring water-soluble organic compound with antioxidant properties and its quantitative determination in biological fluids, foods, cosmetics, etc., using electrochemical microsensors is of wide interest. Various electrochemical techniques have been applied to detect ascorbic acid with extremely high sensitivity, selectivity, reproducibility, and reliability, and apply to in vivo measurements. This review paper aims to give readers a clear view of advances in areas of electrode modification, successful strategies for signal amplification, and miniaturization techniques used in the electroanalytical devices for ascorbic acid. In conclusion, current challenges related to the microelectrodes design, and future perspectives are outlined.
... Ascorbic acid is a representative water-soluble antioxidant. Two different mechanisms are described for the antioxidant properties of ascorbic acid [16]. First, it reacts with free radicals in aqueous components of the body, such as cytoplasm, plasma, and extracellular fluid, and inactivates them [17]. ...
Various substances, including collagen (Naticol®) and ascorbic acid, that inhibit and prevent skin aging have been studied. Collagen prevents skin aging, has anti-inflammatory effects, and assists in normal wound healing. Ascorbic acid is a representative antioxidant that plays a role in collagen synthesis. To achieve a synergistic effect of collagen and ascorbic acid on all skin types, we prepared a product named “TEENIALL.” In addition, we used a container to separate ascorbic acid and collagen to prevent the oxidation of ascorbic acid. To confirm the effects of TEENIALL, we first confirmed its penetrability in fibroblasts, keratinocytes, melanocyte, and human skin tissues. Thereafter, we confirmed the collagen synthesis ability in normal human fibroblasts. Based on the results of in vitro tests, we conducted a clinical trial (KCT0006916) on female volunteers, aged 40 to 59 years, with skin wrinkles and hyperpigmentation, to evaluate the effects of the product in improving skin wrinkles, skin lifting, and pigmentation areas before using the product, and after 2 and 4 weeks of using the product. The values of nine wrinkle parameters that were evaluated decreased and those for skin sagging, pigmentation, dermal density, and mechanical imprint (pressure) relief were improved. Skin wrinkle and pigmentation were evaluated to ensure that the improvement effect was maintained even after 1 week of discontinuing the product use. The evaluation confirmed that the effects were sustained compared to those after 4 weeks of using the product. Additionally, skin wrinkles, skin lifting, radiance, and moisture content in the skin improved immediately after using the product once. Based on the results of in vitro and ex vivo experiments and the clinical trial, we show that the product containing ascorbic acid and collagen was effective in alleviating skin aging.
... The following is a summary of typical antioxidants ( Table 1). Oxygen radicals scavenger (trolox [62], lutein [63], allicin [64], resveratrol [65], isoflavones [66], quercetin [67], catechin [68], theaflavin [69], curcumin [70], chlorogenic acid [71], and superoxide dismutase [72]), singlet oxygen quencher (astaxanthin, histidine [73], and lycopene [74]), hydrogen peroxide scavengers (catalase and glutathione peroxidase), and scavengers for all type of ROS (ascorbic acid [75], ergothioneine [76], L-cysteine, glutathione [77], and tocopherol [78]) are suggested to be effective in suppressing UVA-photosensitization. ...
Skin aging is classified into chronological aging and photoaging, involving ultraviolet radiation (UV), visible light, and others. UVA and UVA-photosensitizers (involving photocatalysis) contribute to the production of chronically induced skin damage that results in photoaging, especially wrinkles that are associated with histopathological actinic elastosis in the dermis. Hydrogen peroxide produced by the photosensitization involving photocatalysis, such as flavin, has been proposed as a risk factor for photoaging. It was also revealed that hydrogen peroxide production by UVA is amplified through the following reactions. The photosensitization of type I and type II by riboflavin as an initiator oxidizes coexisted amino acids and vitamins. The oxidized amino acids and vitamins produce reactive oxygen species (ROS), including hydrogen peroxide, through secondary UVA-photosensitization. Finally, we proposed a screening method for detecting the effects of antioxidants on UVA-photosensitization. In our previous study, histidine and other antioxidants did not inhibit UVA-photosensitized by riboflavin, even though they have been reported to scavenge singlet oxygen and superoxide. In contrast, we demonstrated that ergothioneine suppressed the production of hydrogen peroxide by UVA-photosensitization. The purpose of this report is to provide new findings for the prevention of photoaging by discussing the characteristics of UVA-photocatalysts in the skin.
... In such research, it has been found that vitamin C helps in the synthesis of collagen fibres, which results in the removal of aging and dark spots from the skin surface. It also helps in increasing skin hydration, which makes the skin glow forever [4][5]. ...
... Other compounds like ascorbic acid (7.83 mg/g), salicylic acid (11.29 mg/g), caffeic acid (0.55 mg/g), chlorogenic acid (8.77 mg/g), and rutin (3.95 mg/g) was higher in concentration as compared to available literature (Swaroop et al., 2005). Ascorbic acid is a free radical scavenger, which aids in the treatment of neurodegenerative diseases (Alzheimer's and Parkinson's diseases), inflammatory responses (Osterioscleriosis), heart disease, chronic inflammatory diseases, and anti-aging (Humbert et al., 2003) as well as in viral infection such COVID-19 (Miranda-Massari et al., 2020). These natural phytochemicals are essential for balanced health as well as for nutraceuticals and cosmeceuticals industries. ...
Rhododendron arboreum Smith flowers constitute a valuable dietary supplement or food additive and are novel therapeutic agents. The present work demonstrates and optimizes an effective, enzyme-based ultrasonic approach for polyphenols extraction as a potential alternative to conventional extraction methods. Enzyme-based extraction constitutes an efficient, benign, sustainable, and eco-friendly extraction technology. A Box-Benkhen design with 31 experimental runs was used to investigate and optimize parameters such as solvent concentration (50%-90%), solvent-to-sample ratio (10:1 mL/g-60:1 mL/g), enzyme concentration (0.25%-1.25%), and extraction temperature (35ºC-55ºC). Under linear, quadratic, and interaction effects, the extraction parameters have a significant (p<0.05) impact on polyphenol extraction. The model demonstrated good fitness, with a significant model F-value (p<0.05) and a non-significant lack of fit. The phenolic composition of the extract was quantified using High-Performance Liquid Chromatography – Photo Diode Array (HPLC-PDA), among which catechin (33.64 mg/g) was recorded as the most abundant polyphenol, followed by gallic acid (23.92 mg/g), while caffeic acid (0.55 mg/g) was the least. In addition, thermal stability kinetics experimentation revealed that phytochemicals and the antioxidant properties of R. arboreum were thermally stable even at 80ºC. The first-order kinetic model in terms of reaction rate constant was determined to describe the stability mechanism, and the latter Arrhenius model was computed to determine respective activation energies. Overall, the findings of this study revealed that enzyme-based extraction could be investigated as a cutting-edge, environmentally friendly technology for recovering optimal amounts of phenolic compounds, with potential applications in the formulation of health-promoting beverages and modulating functional food derivatives at a larger scale.
Objective
To develop a stabilized 12% pure Vitamin C‐based serum at a pH close to that of the skin for use in anti‐aging.
Material and Methods
At acidic pH (<3), under oxidative conditions, the ascorbate anionic form of VC rapidly undergoes transformations leading to a Xylosone by‐product, resulting in important chemical losses of VC. Buffering the ascorbate anionic moiety with alkaline agents largely decreases its transformation and the loss of VC. The use of a cationic polymer (Polyquaternium 67, PQ67) enables binding of the ascorbate anion by creating an ionic network, at pH 6 and slows down the slight yellowing of the serum.
Results
By exposing this complex to a temperature of 45°C for a two‐month period, more acceptable degradation was obtained, with less VC chemical loss (approx. 5%–10%). Although a slight yellowish colour developed, it was found non redhibitory through consumer tests. As a result, such combination still leaves an important concentration of pure VC (over 10%) likely able to express its efficacy as anti‐aging ingredient. Further refinements of this association were performed to reach adequate organoleptic properties of the formula, in view of a future clinical test, as proof of performance of VC efficacy at pH 6.
Conclusion
The stabilized formulation of VC at a pH close to that of the skin, apt at being tested in vivo, offers new possibilities for skin anti‐aging routines strategy, by avoiding too acidic conditions (∼pH 3 or below) in daily use cosmetics and thereby allowing better tolerance and an increased adherence of the consumers.
Background
Vitamin C is a well‐known product used in cosmeceuticals for its various topical application benefits ranging from antioxidative, antiaging, anti‐inflammatory, and anti‐pigmentary among others. The main problems encountered with vitamin C products include the stability, penetrance into the skin, and tolerance of vitamin C's various forms.
Aims
This paper aims to explore current literature on the role of Vitamin C in cosmetic dermatology and present a review on how products have developed for certain purposes and their outcomes.
Methods
A literature search was conducted on PubMed reviewing vitamin C in cosmetic and non‐cosmetic formulations and its utility for cosmetic dermatologic conditions. Research produced by various journals was then investigated to highlight its uses and potential in the field.
Results
Numerous studies support the varied claims regarding topical vitamin C, particularly in its role as an antioxidant, antiaging, anti‐pigmentary, and anti‐inflammatory agent. The integration of Vitamin C with other cosmetic ingredients is rapidly developing, ranging from vitamin E and natural plant extracts to several exfoliative acids and growth factors. The cosmetic industry's next steps involve better stabilization to improve the synergistic mechanisms with other ingredients and without lowering its bioavailability, efficacy, or absorption.
Conclusions
Vitamin C has proven to be a powerful player in cosmetic dermatology, both as a stand‐alone element and in combination with cosmetic ingredients. This review showcases some of the most pertinent clinical studies that support its efficacy in mitigating photoaging, oxidative stress, abnormal pigmentation, and inflammation among other cosmetic concerns, underscoring the promise behind vitamin C.
Objective
To assess, clinically and instrumentally, the efficacy of a stabilized 12% Vitamin C (VC)‐based serum (pH 6) on skin photoageing of women of various age and phototype.
Materials and Methods
Eighty women, with Phototypes I to VI, of various age (45–70y) living in Mauritius, participated in an open, uncontrolled study. After a two‐week period of washout, they applied the Vitamin C‐based serum twice a day for 2 months onto their whole face as well as a hydrating cream every evening to ensure a comparable skin hydration level in all subjects. At set time intervals (D0, D immediate, D14, D28 and D56), a local dermatologist graded eight facial signs by visual or tactile assessments, using a 0–9 structured scale. At each time interval, the facial skin was imaged by standardized technique (Colorface™) and through echography (Dermascan™) to record its thickness and density. Skin elasticity was recorded by a the Cutometer® device under a controlled suctional stress. A questionnaire was filled out by all subjects recording their self‐assessments of the serum's effects and several organoleptic properties.
Results
Compared with the baseline values (D0), the skin of all subjects showed progressive and significant changes in glow, tone evenness, radiance, firmness, softness and smoothness, associated with a reduction in fine lines. Deep wrinkles, only observed on 26 subjects, were found to be reduced. Self‐assessments corresponded well with both clinical and instrumental results and indicated excellent skin tolerance. Ultrasound recordings exhibited significantly thicker and denser skin at D56.
Conclusion
If certain changes in some skin facial signs (skin tone and related items, firmness, sagging…) are linked to the high concentration of VC, a complementary impact of increased skin hydration remains possible due to the glycerol present in the serum and hydrating cream. These significant performance results in vivo showed that a very acidic medium (∼pH 3) is not a prerequisite to an efficient VC cosmetic formula, as has long been accepted in the cosmetics industry. Such a low pH can fragilize the skin equilibrium over time. As second originality, the studied formula seemed to fit all phototypes.
This study explores the incorporation of 10% 3-O-ethyl L-ascorbic acid (ETVC), a derivative of vitamin C, into two lipid gel systems: a hydrogel (HG) consisting exclusively of lipids and water and a bigel (BG) combining the hydrogel with an oleogel made from olive oil and beeswax. We investigated the ETVC release profiles from both materials using synthetic membranes and measured their permeation through porcine skin in vitro. Additionally, the interaction of these lipid gel systems with the stratum corneum (SC) was determined. Results from the release study indicate that the BG exhibited slower ETVC release compared to the HG. The permeation experiments showed that the presence of lipids in the formulations enhanced ETVC retention in the skin. The HG delivered a higher amount to the SC, while the BG achieved greater retention in the epidermis. This difference is attributed to the different lipophilic nature of each material. The structural analysis of SC lipids revealed that the organization of surface lipids remained unaltered by the application of the gels. Finally, an in vitro efficacy test in porcine skin using methylene blue indicated that our ETVC gels exhibited antioxidant activity. These findings provide valuable insights into the potential of lipid-based gels for topical applications.
O envelhecimento da pele ocorre por acúmulo de radicais livres nas células epiteliais. Existem dois tipos de processos de envelhecimento: o intrínseco, de natureza genética, e o extrinseco causado por exposições repetitivas aos raios solares ultravioleta. O objetivo deste estudo foi revisar na literatura evidências da utilização da vitamina C na prevenção do envelhecimento. Ácido ascórbico é um antioxidante aliado na prevenção do envelhecimento, com capacidade de varrer esses radicais livres. Este nutriente pode ser administrado de maneira tópica, na forma de cremes contendo o nutriente ou seus derivados; e de maneira oral com ingestão de alimentos ou suplementos, sendo ambos eficazes na prevenção e proteção do envelhecimento cutâneo. Existem vários estudos experimentais que demonstram a eficácia desta vitamina na proteção a processos oxidativos. No entanto, há mais relatos de estudos na utilização tópica, sendo necessárias mais evidências sobre o uso oral da vitamina C na prevenção do envelhecimento cutâneo.
Skin ageing is a complex phenomenon that results in alterations to the physiological functioning of the skin as well as very noticeable phenotypic changes. Particularly, hyaluronic acid, collagen, and elastin fibres experience structural and functional alterations as they age
Rosa spp., commonly known as rosehips, are wild plants that have traditionally been employed as herbal remedies for the treatment of a wide range of disorders. Rosehip is a storehouse of vitamins, including A, B complex, C, and E. Among phytonutrients, vitamin C is found in the highest amount. As rosehips contain significant levels of vitamin C, they are perfect candidates for the development of skincare formulations that can be effectively used in the treatment of different skin disorders (i.e., scarring, anti-aging, hyperpigmentation, wrinkles, melasma, and atopic dermatitis). This research focuses on the vitamin C content of several Rosa sp. by their botanical and geographic origins, which according to research studies are in the following order: R. rugosa > R. montana > R. canina > R. dumalis, with lower levels in R. villosa and R. arvensis, respectively. Among rosehip species, R. canina is the most extensively studied species which also displays significant amounts of bioactive compounds, but also antioxidant, and antimicrobial activities (e.g., against Propionibacterium acnes, Staphylococcus aureus, S, epidermis, and S. haemolyticus). The investigation also highlights the use of rosehip extracts and oils to minimise the harmful effects of acne, which primarily affects teenagers in terms of their physical appearance (e.g., scarring, hyperpigmentation, imperfections), as well as their moral character (e.g., low self-confidence, bullying). Additionally, for higher vitamin C content from various rosehip species, the traditional (i.e., infusion, maceration, Soxhlet extraction) and contemporary extraction methods (i.e., supercritical fluid extraction, microwave-assisted, ultrasonic-assisted, and enzyme-assisted extractions) are highlighted, finally choosing the best extraction method for increased bioactive compounds, with emphasis on vitamin C content. Consequently, the current research focuses on assessing the potential of rosehip extracts as medicinal agents against various skin conditions, and the use of rosehip concentrations in skincare formulations (such as toner, serum, lotion, and sunscreen). Up-to-date studies have revealed that rosehip extracts are perfect candidates as topical application products in the form of nanoemulsions. Extensive in vivo studies have revealed that rosehip extracts also exhibit specific activities against multiple skin disorders (i.e., wound healing, collagen synthesis, atopic dermatitis, melasma, and anti-aging effects). Overall, with multiple dermatological actions and efficacies, rosehip extracts and oils are promising agents that require a thorough investigation of their functioning processes to enable their safe use in the skincare industry.
Background
Skin photoaging and uneven pigmentation are common dermatological concerns. Tetrahexyldecyl ascorbate (THDA) and acetyl zingerone (AZ) are potent antioxidants that have been shown to have anti‐photoaging and anti‐pigmentation effects. THDA is a more stable and penetrable form of vitamin C. AZ is an antioxidant derived from ginger which has clinical evidence for improving photoaging. However, no studies have assessed how they may synergistically act on the skin.
Aims
This study aims to assess whether a serum containing both THDA and AZ can improve photoaging and the appearance of uneven facial pigmentation.
Patients/Methods
This open‐label study was conducted on 35 healthy individuals aged 21–55. All subjects were instructed to use three to five drops of the topical serum (Power‐C Serum, Image Skincare, Lantana, FL) daily for 12 weeks. Videomicroscopy and high‐resolution photography and various skin biophysical measurements were taken at baseline, 1, 4, and 12 weeks. Outcomes included skin tone and pigmentation, transepidermal water loss (TEWL), skin smoothness, firmness, and elasticity.
Results
Compared to baseline, the results at 12 weeks revealed significant decreases in skin pigmentation (p < 0.0001), decreased fine lines and wrinkles (p < 0.0001), and increased smoothness (p < 0.0001), firmness (p < 0.0001), and elasticity (p < 0.0001). Additionally, transepidermal water loss was significantly decreased at 4 weeks compared to baseline (p = 0.01), indicating an increased epidermal barrier integrity.
Conclusions
Overall, these findings provide evidence for the combined use of THDA and AZ to address skin photoaging and dyspigmentation changes.
With ever-improving life expectancy, skin aging has become the first casualty of exuberant health. People are progressively seeking remedies for their age-related skin problems. Understanding the aging process is unfolding newer realms in the molecular biology of the skin, giving us new insights to combat senescence more effectively. Epidermal dysfunction, compromised permeability homeostasis, elevated skin pH, diminished stratum corneum hydration, and dermal extracellular matrix aberrations with changes in its cellular composition are now well understood. Thus, a more scientific approach can be utilized while evolving various specific anti-aging therapies. The present communication attempts to address both the process of skin aging and various therapies to combat it in a concise yet succinct way.
Context
Photoaging correlates with ultraviolet radiation (UVR). In addition to direct and indirect DNA damage, UVR leads to a breakdown of collagen, resulting in enlarged pores, visible wrinkles, also uneven skin tones and pigmentations. Amniotic membrane stem cell (AMSC) can be a useful modality in cell regeneration. Vitamin C has been known as an agent of depigmentation, antioxidants, and collagen synthesis. A topical combination of amniotic membrane stem cell-conditioned medium (AMSC-CM) and vitamin C is expected to improve photoaging. Fractional CO2 laser and microneedling served as transdermal drug delivery.
Aims
To compare between microneedling and fractional CO2 laser for the administration of AMSC-CM and vitamin C in photoaging treatment.
Methods and Material
Sixty Indonesian women with photoaged skins participated in this experimental analytic, controlled, matching research and were divided into two groups. Thirty women received fractional CO2 laser, and others received microneedling. All participants received a topical combination of AMSC-CM and vitamin C. Three treatment sessions were repeated at a four-week interval for fractional CO2 laser and a two-week interval for microneedling. We evaluated the progression and side effects using a skin analyzer on weeks 0, 4, and 8 for the microneedling group and for the fractional CO2 laser group on weeks 0, 4, and 12.
Results
Assessment of wrinkles, UV spots, skin tone, and pore revealed a statistically significant effect of a topical combination of AMSC-CM and vitamin C after fractional CO2 laser (p < 0.05).
Conclusions
Combination of AMSC-CM and vitamin c using fractional CO2 laser can improve photoaging and is better compared to microneedling.
The term cosmeceutical refers to a category of skincare products that are purported to have active ingredients whose physiological or pharmacological actions are capable of inducing cosmetic enhancements to the skin. Given a demand for brighter, healthier, younger‐appearing skin, and relatively limited regulatory control, thousands of different cosmeceutical formulations have found their way onto store shelves and onto the skin of hopeful consumers, despite a lack of scientific evidence. This chapter summarizes new and old, common and rare cosmeceutical ingredients; their uses and side effects; and the science, where available, behind the claims.
Background:
Skin aging is regulated by multiple physiological processes, such as oxidative stress. Natural products have been considered as a promising source of antioxidant compounds. As a result, few innovative products on the market based on natural products tackle additional underlying mechanisms of skin aging.
Aims:
The present work reports the nonclinical evaluation of a novel extract from the skin of V. vinifera fruits (codified as ACH37 extract), with the aim of supporting its use as an antiaging cosmetic ingredient candidate in clinical trials.
Methods:
We employed enzymatic, phenotypic, and gene expression assays, both in vitro and ex vivo, to investigate the action of the ACH37 extract in different biological processes that could be related to skin aging mechanisms.
Results:
The ACH37 extract was able to scavenge reactive oxygen species (DPPH, O2 - ), prevent inflammation (LPS- and UV-induced COX-2, IL-1β, and IL-8 expression), modulate extracellular matrix remodeling (inhibiting elastase, MMP-1, MMP-3, and MMP-12, as well as associated expression), increase telomere length, telomerase activity, and reverse the UV-induced suppression of genes involved in skin protection. In addition, the ACH37 extract permeated human skin explants and presented antioxidant efficacy ex vivo.
Conclusion:
The results indicated that the ACH37 extract acts on multiple targets commonly related to skin aging, being a promising antiaging active ingredient candidate to be further investigated in clinical trials.
Photoaging is a complex process of skin changes associated with chronic ultraviolet exposure. Prevention with photoprotection and treatment with topical retinoids are the core components of a topical antiaging regimen. Other topicals such as hydroquinone, vitamin C, niacinamide, and alpha hydroxyl acid can be added based on specific concerns. However, caution must be used with some of these products as the stability and absorption are major considerations. A simple topical regimen will reduce irritability and enhance compliance.
This chapter discusses the importance of air pollution in human health, outlining its relationship with cutaneous tegument and in particular with early aging, atopic dermatitis, urticaria, acne, melasma, and skin cancer. Aspects of epidemiology and physiopathology of such associations are discussed. Preventive medical interventions are proposed to improve the population’s quality of life.KeywordsAir pollutionFree radicalsSkin barrierMicrofloraDermatosesSkinEarly agingAtopic dermatitisUrticariaAcneMelasmaSkin cancer
The skin aging process is caused by an interaction of epigenetic, genetic, and environmental factors. Thus, skin suffers from extrinsic and intrinsic factors enhancing this process. Both factors contribute to ROS formation in skin aging. ROS is necessary for intrinsic aging; it is produced mainly in mitochondria due to aerobic metabolic reactions. As for extrinsic aging, smoking, UV, and hyperglycemia lead to ROS generation. In skin aging process, generated excessive ROS activates MAPKs and thus induces NF-κB transcription factors. This activation inhibits TGF-β signaling pathway and increases MMPs expression, leading to decreased collagen synthesis and breakdown. Excess ROS related to aging-associated diseases also accelerates skin aging.On the other hand, metformin, an antidiabetic agent, via inactivating NF-kB, inhibits oxidative stress, ameliorates inflammatory reactions, improves mitochondrial function, and regulates cell death. Up-to-date evidence suggests that NF-kB signaling dysfunction and dysregulation are related to skin aging. There are current mechanisms and novel strategies for the therapeutic manipulation of NF-kB in treating skin aging. This chapter summarizes the current role of NF-kB in dermal aging, underlines the molecular mechanism of metformin in skin aging, attributes its effects to the modulation of NF-kB, and presents novel therapeutic approaches to skin aging through this modulation.
Keywords: NF-κB signaling pathway. Metformin. Skin aging. Collagen. MMP
The mitochondrion is the energy plant of the cell, and the place of adenosine triphosphate production thanks to the process of respiration. This activity uses dioxygen and generates reactive oxygen species. Consequently, any dysfunction in the mitochondria can cause oxidative stress, which, when uncontrolled, can lead to further cellular and tissue damage. Mitochondrial dysfunctions are linked to many diseases from age-related and degenerative diseases to metabolic and cardiovascular diseases, in addition to genetic mitochondrial disorders. Nutritional interventions could represent interesting therapeutic strategies by targeting specific mitochondrial targets, pathways, and/or functions. The main classes of these nutrients are reviewed here, along with their main cellular, preclinical, and clinical data. A special focus is given to the topical use of certain nutrients for dermo-cosmetic applications.
Vit C or L-ascorbic acid is a weak sugar acid that can occur in reduced or oxidized form structurally related to glucose. Vit C is a collective term describing several vitamers with Vit C activity in animals, including ascorbic acid, ascorbate, their salts, and some oxidized forms of the molecule, such as dehydroascorbic acid (DHA). The name “Vit C” always refers to the L-enantiomer of ascorbic acid and its oxidized forms. The D-enantiomer, which does not occur in nature and can only be synthesized artificially, lacks biological activity.
Photoaging is a complex process of skin changes associated with chronic ultraviolet exposure. Prevention with photoprotection and treatment with topical retinoids are the core components of a topical antiaging regimen. Other topicals such as hydroquinone, vitamin C, niacinamide, and alpha hydroxyl acid can be added based on specific concerns. However, caution must be used with some of these products as the stability and absorption are major considerations. A simple topical regimen will reduce irritability and enhance compliance.
background.Aging of the population, in particular the “baby boomers,” has resulted in increased interest in methods of reversal of photodamage. Non-invasive treatments are in high demand, and our knowledge of mechanisms of photodamage to skin, protection of the skin, and repair of photodamage are becoming more sophisticated and complex.objective.The objective of this study is to determine if the topical use of a vitamin C preparation can stimulate the skin to repair photodamage and result in clinically visible differences, as well as microscopically visible improvement.methods.Ten patients applied in a double-blind manner a newly formulated vitamin C complex having 10% ascorbic acid (water soluble) and 7% tetrahexyldecyl ascorbate (lipid soluble) in an anhydrous polysilicone gel base to one-half of the face and the inactive polysilicone gel base to the opposite side. Clincial evaluation of wrinkling, pigmentation, inflammation, and hydration was performed prior to the study and at weeks 4, 8, and 12. Two mm punch biopsies of the lateral cheeks were performed at 12 weeks in four patients and stained with hematoxylin and eosin, as well as in situ hybridization studies using an anti-sense probe for mRNA for type I collagen. A questionnaire was also completed by each patient.results.A statistically significant improvement of the vitamin C-treated side was seen in the decreased photoaging scores of the cheeks (P = 0.006) and the peri-oral area (P = 0.01). The peri-orbital area improved bilaterally, probably indicating improved hydration. The overall facial improvement of the vitamin C side was statistically significant (P = 0.01). Biopsies showed increased Grenz zone collagen, as well as increased staining for mRNA for type I collagen. No patients were found to have any evidence of inflammation. Hydration was improved bilaterally. Four patients felt that the vitamin C-treated side improved unilaterally. No patient felt the placebo side showed unilateral improvement.conclusion.This formulation of vitamin C results in clinically visible and statistically significant improvement in wrinkling when used topically for 12 weeks. This clinical improvement correlates with biopsy evidence of new collagen formation.
After prolonged exposure to ascorbate, collagen synthesis in cultured human skin fibroblasts increased approximately 8-fold with no significant change in synthesis of noncollagen protein. This effect of ascorbate appears to be unrelated to its cofactor function in collagen hydroxylation. The collagenous protein secreted in the absence of added ascorbate was normal in hydroxylysine but was mildly deficient in hydroxyproline. In parallel experiments, lysine hydroxylase (peptidyllysine, 2-oxoglutarate:oxygen 5-oxidoreductase, EC 1.14.11.4) activity increased 3-fold in response to ascorbate administration whereas proline hydroxylase (prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase, EC 1.14.11.2) activity decreased considerably. These results suggest that collage polypeptide synthesis, posttranslational hydroxylations, and activities of the two hydroxylases are independently regulated by ascorbate.
Low-density-lipoprotein (LDL) oxidation was examined in 22 subjects (10 men, 12 women) after a daily dose of 18 mg beta-carotene, 900 mg vitamin C, and 200 mg alpha-tocopherol for 6 mo. Control subjects (12 men, 11 women) took no vitamin supplements. After 3-mo supplementation plasma concentrations of beta-carotene, alpha-tocopherol, and ascorbic acid increased fivefold (P < 0.001), 55% (P < 0.01), and 27% (P < 0.05), respectively. There was no difference from baseline in rate of oxidation or total amount of conjugated diene produced between subjects taking or not taking vitamins. Malondialdehyde in LDL before and after oxidation was not different between the two groups. Lag time before the onset of oxidation was significantly lengthened after antioxidant supplementation (28% and 35% after 3 and 6 mo, respectively, P < 0.001). There was a significant independent correlation between percent change in lag time and percent change in plasma alpha-tocopherol (r = 0.47, P < 0.01).
Vitamin C (L-ascorbic acid) is one of the body's primary protections from reactive oxygen damage, but it is depleted during ultraviolet (UV) injury. Because body control mechanisms limit the amount of ingested vitamin C available to skin, topical antioxidant therapy becomes an attractive way to target vitamin C directly into skin, provided the unstable L-ascorbic acid molecule can be stabilized and penetrate skin - conditions which have precluded use in topical formulations - until recently. A new technology for stabilizing high concentrations of L-ascorbic acid that get into skin has been developed. The result: it is now possible to deliver more vitamin C into skin topically than ever can be achieved by diet, thus adding to the body's natural reservoir of antioxidant protection. Topical vitamin C (L-ascorbic acid) therapies provide several benefits for skin. Topical vitamin C protects against UV radiation, including UVA - an action spectra linked to cause photoaging and some skin cancers, and one that is not protected fully by currently-available sunscreens. Topical vitamin C prevents DNA mutations and UV immunosuppression, a reaction that occurs in over 90% of all skin cancer patients. Topical vitamin C controls inflammation and reduces erythema. Topical vitamin C promotes wound healing and stimulates collagen synthesis.
A profilometric apparatus (Talysurf 5®) was used to quantitatively analyze the human skin surface and to perform three-dimensional (3-D) topographic representations of the same surface. Positive replicas of abdominal and volar forearm skin surfaces were analyzed in this study. The skin microtopography was scanned with the stylus of the Talysurf 5®, recording the x, y, and z coordinates of each point on the surface. The 3-D images revealed the skin surface microstructure accurately (furrows, pores, etc...) and allowed a better understanding of the quantitative evaluation of the human skin surface profiles, as traced by the Talysurf 5®. Use of additional statistical parameters (Skewness, Kurtosis, etc...) provided new perspectives for analyzing the skin surface and the possibility of detecting the effects of drugs and cosmetics on the human skin surface.
In this paper we show two new developments in the three-dimensional characterisation of rough surfaces. The basic idea is to consider roughness as a combination of components defined by the roughness amplitude, wave length, local and overall direction of various components. The anisotropic topography is dealt with in two ways: •- the anisotropy between form, waviness and roughness;•- the local anisotropy of three-dimensional motifs.The directional parameter is used both to identify and separate the anisotropic components by appropriate anisotopic filtering and by a complete characterisation of surface motifs. This allows the decomposition of the topography into local motifs with a representation similar to the two-dimensional Fourier transform, where the direction represents the topographic phase in the form of a morphological rose.
Ascorbic acid (vitamin C) is a cofactor required for the function of several hydroxylases and monooxygenases. It is not synthesized in humans and some other animal species and has to be provided by diet or pharmacologic means. Its absence is responsible for scurvy, a condition related in its initial phases to a defective synthesis of collagen by the reduced function of prolylhydroxylase and production of collagen polypeptides lacking hydroxyproline, therefore, they are unable to assemble into stable triple-helical collagen molecules. In fibroblast cultures, vitamin C also stimulates collagen production by increasing the steady-state level of mRNA of collagen types I and III through enhanced transcription and prolonged half-life of the transcripts. The aim of the experimental work has been to evaluate the effect on dermal cells of a preparation of vitamin C topically applied on one side vs placebo on the other side of the dorsal face of the upper forearm of postmenopausal women. Biopsies were collected on both sides and the level of mRNA measured by non competitive reverse transcription–polymerase chain reaction made quantitative by the simultaneous transcription and amplification of synthetic RNA used as internal standards. The mRNA of collagen type I and type III were increased to a similar extent by vitamin C and that of three post-translational enzymes, the carboxy- and amino-procollagen proteinases and lysyloxidase similarly increased. The mRNA of decorin was also stimulated, but elastin, and fibrillin 1 and 2 were not modified by the vitamin. The expression of matrix metalloproteinases 1, 2, and 9 was not significantly changed, but an increased level of tissue inhibitor of matrix metalloproteinase 1 mRNA was observed without modification of tissue inhibitor of matrix metalloproteinase 2 mRNA. The stimulating activity of topical vitamin C was most conspicuous in the women with the lowest dietary intake of the vitamin and unrelated to the level of actinic damage. The results indicate that the functional activity of the dermal cells is not maximal in postmenopausal women and can be increased.Keywords: ADAMTS2, BMP1, decorin, elastin, matrix metalloproteinases
Synopsis
A method of skin profilometry is presented. The data generated using this method are used to (a) uncover sources of variation in skin profilometry, (b) provide information regarding the choice of roughness parameters best suited for characterizing the skin's topography, and (c) determine if skin profilometry is a valuable tool for quantitatively assessing changes in the skin's surface pattern.
The data show the roughness parameter values to be dependent on the orientation of the tracings with regard to the major grooves and ridges present in the surface patterns. Large variabilities of roughness parameter values obtained for multiple scans within small areas of replicas are indicative of the nonhomogeneity of the skin's surface. The number of peaks, mean peak size, mean depth of roughness, depth of smoothness, and residual profile length appear to be the most utile roughness parameters for quantifying changes in the skin's topography. The ability of skin profilometry to detect subtle changes in the skin's surface pattern due to hydration indicates the method is a sensitive means of quantifying the skin's topography.
Quantification de la topographie de la pedu par la profilométrie de la pedu
Synopsis
An image analysis method to measure the human skin microrelief has been previously proposed.
This new method has been recently automated, using a ‘robot’electronically driven by a Quantimet 900. This ‘robot’consists of a change‐over specimen driven by four motors, and allows forty Silflo® replicas to be analysed in 6 hours, each analysis giving the main directions of the furrows, their density and their mean depth.
For example, the volar forearm microrelief was studied from the detected shadows created by a 26° angle lighting, in the range of 5 to 100 μ m deep furrows. A 38° angle lighting allows such measurements from 50 to 1000 μ m and is used for studying ‘crow's feet’wrinkles of the face.
Results clearly show that deep wrinkles appear as early as 30 years old on the human face. The consequences of actinic and mechanical stresses over the life span are discussed.
Un système automatique pour l'étude du relief cutané chez l'homme
The skin relief influences the exterior aspect of the skin which is very sensitive to aging. It could also be related to the mechanical properties and structure of both dermis and stratum corneum. Consequently, quantitative measurement of the skin surface roughness would seem most useful, as it would permit a quantification of skin aging, an in vivo analysis of mechanical forces acting on the skin structure, and the detection of abnormalities otherwise not visible. The method described comprises three steps: (1) making a silicone rubber negative replica, (2) making an Araldite positive cast, (3) roughness measurement of the cast with a device commonly used in engineering, which provides quantitative parameters: Ra, Rp, Rt, Rmax and others. The reliability of each of these steps was checked, and also the absolute need to locate precisely the site of sampling and to know the angle of the scanning direction with the main axis of the limb or the body. The method seems useful for studying aging, either normal or affected by UV rays and other physiopathological events influencing the skin surface.
Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin C (L-ascorbic acid) functions as a biological co-factor and antioxidant due to its reducing properties. Topical application of vitamin C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ's innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and therefore shows promise as a broad-spectrum photoprotectant.
Computerized image analysis of silicone replicas, a reproducible, objective technique for measuring skin topography, was used in addition to clinical measures in two multicenter, double-blind, randomized, controlled studies of tretinoin emollient cream, a new formulation for treating photodamaged skin. Previously, the skin replica technique had been successfully used in a pilot study of tretinoin 0.05% cream by one investigator. In the present studies, subjects treated for 24 weeks with tretinoin emollient 0.05% cream consistently showed more improvement in skin topography than did vehicle-treated patients. A 0.01% concentration of tretinoin emollient cream also improved skin topography to a greater extent than the vehicle, while the lowest concentration tested (0.001%) showed little difference from vehicle. These results, reflecting a smoothening of the skin surface in tretinoin emollient cream-treated subjects, were consistent with clinical data showing greater improvement in fine wrinkling and roughness after tretinoin emollient cream therapy than after vehicle therapy. Findings from these multicenter studies confirm the value of the skin replica technique and help establish the efficacy of tretinoin emollient 0.05% cream for photodamaged skin.
During developmental growth, collagens are believed to be continuously deposited into an extracellular matrix which is increasingly stabilized by the formation of covalent cross-links throughout life. However, the age-related changes in rates of synthetic and degradative processes are less well understood. In the present study we measured rates of collagen synthesis in vivo using a flooding dose of unlabelled proline given with [14C]proline and determining production of hydroxy[14C]proline. Degradation of newly synthesized collagen was estimated from the amount of free hydroxy [14C]proline in tissues 30 min after injection. Collagen fractional synthesis rates ranged from about 5%/day in skeletal muscle to 20%/day in hearts of rats aged 1 month. At 15 months of age, collagen fractional synthesis rates had decreased markedly in lung and skin, but in skeletal muscle and heart, rates were unchanged. At 24 months of age, synthesis rates had decreased by at least 10-fold in all tissues, compared with rates at 1 month. The proportion of newly synthesized collagen degraded ranged from 6.4 +/- 0.4% in skin to 61.6 +/- 5.0% in heart at 1 month of age. During aging the proportion degraded increased in all tissues to maximal values at 15 months, ranging from 56 +/- 7% in skin to 96 +/- 1% in heart. These data suggest that there are marked age-related changes in rates of collagen metabolism. They also indicate that synthesis is active even in old animals, where the bulk of collagens produced are destined to be degraded.
Albino hairless mice (Skh:HR-1) exposed chronically to suberythemal doses of ultraviolet radiation develop visible skin changes, histological alterations, and tumors. Topical treatment of mice with solutions of superoxide-scavenging antioxidants (such as alpha-tocopherol, ascorbic acid, propyl gallate and Trolox) prior to each UVB radiation exposure reduced significantly the severity of these events. Tocopherol esters and ascorbyl palmitate were not as effective as the parent compounds in providing protection. The data suggest a role for superoxide in UVB radiation-induced skin photoaging and the protective potential of superoxide scavengers. In contrast, the severity of UVA radiation-induced mouse skin damage was not reduced by topical application of the antioxidants tested here.
It has long been suspected that ascorbic acid is involved in many cellular reactions. This is evident from the multitude of seemingly unrelated symptoms seen in scurvy. However, until recently, our understanding of its involvement was confined to its role in the synthesis of collagen. Studies in the past few years have unveiled mechanisms of its actions in collagen formation and many other enzymatic reactions. In addition, numerous physiological responses are reportedly affected by ascorbic acid. From the well-characterized enzymatic reactions involving ascorbic acid, it has become clear that in animal cells the ascorbate does not seem to be directly involved in catalytic cycles. Rather its major function seems to keep prosthetic metal ions in their reduced form. The role of ascorbate as a reductant in these enzymatic reactions complements its other antioxidant functions which have been recently appreciated, including that as a scavenger of free radicals. Therefore, it seems that the major function of ascorbate is to protect tissues from harmful oxidative products and to keep certain enzymes in their required reduced forms. However, it remains unclear how the deficiency of ascorbate leads to the pathological symptoms found in scurvy.
As the population ages, common skin disorders of the elderly demand greater attention. Moreover, the many clinical, histologic, and physiologic changes that characterize old skin are increasingly implicated in its vulnerability to environmental injury and certain diseases. Thus it behooves dermatologists to study the basic biologic process of aging in the skin and the separable process of photoaging, which itself is a major clinical problem. To date studies at the cellular level have demonstrated major functional losses, particularly in proliferative capacity between infancy and adulthood, with definite further loss between early and late adulthood and as a result of chronic sun exposure. Continued careful, quantitative assessment of aging and photoaging in human skin both in vivo and in vitro will be critical to a better understanding of these processes and particularly to their successful therapeutic modification.
Facial fine lines and wrinkles can be faithfully captured by silicone rubber impression materials. Computerized digital image processing of such specimens provides objective measurement of the skin's topography, which has a significant degree of correlation with clinical grading. Optical profilometry provides a dimension of objectivity that can complement clinical assessment in the study of agents that may be useful in the therapy of photodamaged skin.
• L-Ascorbic acid stimulates procollagen synthesis in cultured human skin fibroblasts without appreciably altering noncollagen protein synthesis. The effect is unrelated to intracellular degradation of newly synthesized procollagen. Levels of mRNA for pro α1(I), pro α2(I), and pro α1(III), measured by hybridization with the corresponding cDNA probes, are elevated in the presence of ascorbic acid, whereas the level of mRNA for fibronectin is unchanged. Levels of functional mRNA for procollagen, measured in a cell-free translation assay, are specifically increased in the presence of ascorbic acid. Thus, ascorbic acid appears to control the expression of three different procollagen genes, each of which is located on a separate chromosome. It is proposed that intracellularly accumulated procollagen in ascorbate deficiency may lead to a translational repression of procollagen synthesis. Ascorbic acid may relieve this block by promoting hydroxyproline formation and, consequently, secretion of procollagen from the cell. The increased level of procollagen mRNA under the influence of ascorbic acid may be secondary to increased synthesis of procollagen polypeptides; the control point may be gene transcription or mRNA degradation.
(Arch Dermatol 1987;123:1684-1686)
Free radicals are chemical species characterized by an odd number of orbital electrons or by pairs of electrons of similar directional spin isolated singly in separate orbitals. Consequently most of these agents are highly reactive and usually exhibit an extremely short half-life, although due to steric and resonance effects some exceptions occur. Some radicals and their precursors, such as the diradical O2 which exists in the triplet state, represent a critical and essential element of normal metabolism of aerobic organisms where, under normal circumstances, controlled reduction of reactive oxygen species occurs via the cytochrome oxidase or cytochrome P-450 mixed function monooxygenase systems. In addition to reactive oxygen species, organisms may be subjected to a wide-range of other free radicals or their precursors, including those of both exogenous and endogenous origin. Elaborate defense mechanisms have evolved to avoid cellular damage from these highly reactive species. Enzymes, such as the superoxide dismutase, the glutathione peroxidase/reductase system, and catalase; interactions with conjugated diene systems such as those found in melanins, carotenoids, and tocopherols; and direct reduction by sulphydryl compounds, phenols, and purines represent but a few of these natural defense systems.
Prolyl and lysyl hydroxylase activities in cultures of human skin fibroblasts from fetal to 94-yr-old donors were measured. In contrast to earlier studies with whole skin, neither prolyl nor lysyl hydroxylase activity was found related to donor age. Prolyl hydroxylase activity increased 3- to 6-fold when cell extracts were incubated with ascorbate and other hydroxylation cofactors before assay. A similar increase in prolyl hydroxylase activity occurred when cells were incubated with ascorbate. Lysyl hydroxylase activity remained unaltered under these conditions.
Studies with confluent human skin fibroblasts maintained in 0.5% serum supplemented medium have given new insight into the regulatory influences of ascorbate. These include a reduction of prolyl hydroxylase activity, a stimulation of lysyl hydroxylase activity, and an acceleration of collagen production. The lack of parallel between prolyl hydroxylase activity and collagen production indicates that the rate of collagen synthesis is not controlled by the level of prolyl hydroxylase.
In confluent human skin fibroblasts maintained in 0.5% serum-supplemented medium. L-ascorbate specifically stimulated the rate of incorporation of labeled proline into total collagenase-sensitive protein, without changing the specific activity of the intracellular free proline. This influence of ascorbate reached a maximum at 30 microM and continued for at least 4 days, resulting in a 4-fold increase. The ascorbate effect occurred in cells at both confluent and subconfluent densities and was evident at all serum concentrations from 0.5-20%. The effect was independent of duration of the radioactive pulse between 2-6 h. D-Ascorbate, D-isoascorbate, and L-dehydroascorbate also stimulated collagen synthesis but at considerably higher concentrations, i.e., 250-300 microM. The stimulation of collagen synthesis by ascorbate and its analogs was accompanied by a decline in prolyl hydroxylase activity and a rise in lysyl hydroxylase activity; again L-ascorbate was found to be most effective. Dimethyltetrahydropterine and L-lactate failed to produce these effects.
We studied by light and electron microscopy the elastic fibers in he sun exposed and sun protected skin of normal and psoriatic individuals of different ages in order to separate the changes of actinic damage from those of chronological aging. The sun exposed skin showed 2 types of elastic fiber abnormalities-one related to actinic damage and the other to chronological aging. The sun protected buttock skin showed only the latter. From ages 30 to 70, a minority of the elastic fibers exhibited abnormalities that appeared to represent a process of fiber disintegration. After age 70, the majority of elastic fibers showed these abnormalities. These abnormalities were present without accompanying inflammatory cells. Also, there was morphological evidence of continuing synthesis of elastic fibers during the lifetime of these subjects, except that from ages 50-93, the fibers appeared to be loosely, rather than compactly, assembled. Incubation of dermal slices from buttock skin of young adults with porcine pancreatic elastase and bovine chymotrypsin produced elastic fiber degradation that closely simulated the changes that were observed in aged sun protected skin. We propose that one of the features of cutaneous aging is a slow, spontaneous, progressive degradative process inherent in the elastic fiber that can be enzymatically accelerated from decades to hours by elastase and chymotrypsin.
Several events are associated with cellular aging: alterations in the extracellular matrix, loss of the cell's proliferative capacity, and decreased responsiveness to growth factors. In skin, a major component of the extracellular matrix is collagen; an important regulator of collagen synthesis is ascorbic acid, which may also have growth factor-like properties. To investigate the relationship of the extracellular matrix and proliferative capacity to aging, we examined the effects of ascorbic acid on cell proliferation and collagen expression in dermal fibroblasts from donors of two age classes, newborn (3-8 d old) and elderly (78-93 years old). In the absence of ascorbic acid (control) proliferative capacities were inversely related to age; newborn cell lines proliferated faster and reached greater densities than elderly cell lines. However, in the presence of ascorbic acid both newborn and elderly cells proliferated at a faster rate and reached higher densities than controls. To determine whether there are age-related differences in extracellular matrix production and ascorbic acid responsiveness we examined and found that collagen biosynthesis (collagenase-digestible protein) was inversely related to age, but the stimulation by ascorbic acid appeared age independent. The increase in collagen synthesis was reflected by coordinate increases in steady-state pro alpha 1(I) and pro alpha 1(III) collagen mRNAs, suggesting a pretranslational mechanism. Ascorbic acid appears capable of overcoming the reduced proliferative capacity of elderly dermal fibroblasts, as well as increasing collagen synthesis in elderly cells by similar degrees as in newborn cells even though basal levels of collagen synthesis are age dependent.
One of the vital roles of ascorbic acid (vitamin C) is to act as an antioxidant to protect cellular components from free radical damage. Ascorbic acid has been shown to scavenge free radicals directly in the aqueous phases of cells and the circulatory system. Ascorbic acid has also been proven to protect membrane and other hydrophobic compartments from such damage by regenerating the antioxidant form of vitamin E. In addition, reduced coenzyme Q, also a resident of hydrophobic compartments, interacts with vitamin E to regenerate its antioxidant form. The mechanism of vitamin C antioxidant function, the myriad of pathologies resulting from its clinical deficiency, and the many health benefits it provides, are reviewed.
Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen. A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection.
Stimulation of the synthesis of type I and III collagens by 0.15 mM L-ascorbic acid (AA) was investigated in primary cultures of dermal fibroblasts form 30 females aged between 19 and 70 years. At this concentration allowing maximal stimulation, fibroblast cultures responded to this agent by an increase in collagen secretion, but to a lower extent for type III compared to type I, leading to an increase in the type I/III collagen ratio. We showed that AA stimulation of type I and III collagen secretion decreased in a statistically significant linear manner with donor age (slope = 1.9; p = 0.0014 and slope = -0.5; p = 0.0164, respectively). We also observed an age-related AA stimulation of the cell-associated collagen pool for type I collagen but not for type III (slope = 0.29; p = 0.015). This might indicate that a reduced ability of fibroblasts to secrete the newly synthesized type I collagen is involved in loss of the cellular response to AA stimulation. Analysis of AA stimulation as a function of body site showed that during aging, the loss of AA stimulation of type I and III collagen synthesis was more for periauricular (slope = 2.7; p = 0.0280 and slope = -0.8; p = 0.0309, respectively) than for mammary skin (slope = 2.1; p = 0.0071 and slope = 0.1; p = 0.7337, respectively). This led us to consider that UV-exposed cutaneous sites may accelerate cellular dermal aging in terms of response to AA, making this parameter a quantitative indicator of human dermal cell aging.
Decreased collagen synthesis and loss of responsiveness to growth factors are well known phenomena in in vivo or in vitro aged cells. Ascorbic acid and some cytokines such as transforming growth factor-beta and interferon-gamma are important regulators of collagen synthesis. To investigate the responsiveness of fibroblasts with regard to the photoaging and aging process, we examined the effect of ascorbic acid, TGF-beta, and IFN-gamma on collagen synthesis in dermal fibroblasts from three newborn foreskins (1 day old) and in both exposed and unexposed skin fibroblasts from 4 old individuals (60-76 years old) cultured in monolayer and in collagen gel. We demonstrated that basal levels of collagen synthesis decreased with increasing age. Photoaged fibroblasts in collagen gel showed greater basal collagen synthesis than aged fibroblasts in the same individuals, but similar basal collagen synthesis in monolayer cultures. Even though basal levels of collagen synthesis in collagen gel are downregulated in a photoaging- and aging-dependent manner, collagen synthesis by ascorbic acid in collagen gel, and by TGF-beta and IFN-gamma in both monolayer culture and collagen gel were regulated in a photoaging- and aging-independent manner. In monolayer culture, however, the responsiveness to ascorbic acid in newborn fibroblasts was greater than in photoaged and aged fibroblasts. Our results suggest that there are differences in collagen synthesis between photoaged and aged cells, depending on culture conditions. Responsiveness to ascorbic acid, TGF-beta and IFN-gamma related to collagen synthesis in photoaged and aged fibroblasts in collagen gel appears to be the same as in newborn fibroblasts, even though basal levels of collagen synthesis are downregulated in a photoaging- or aging-dependent manner.
We compared the activity and tolerance profile of a 0.05% retinaldehyde cream with a 0.05% retinoic acid cream and the retinaldehyde vehicle in patients with photodamaged skin of the face.
A silicone replica of the left crow's feet area was taken at baseline and at weeks 18 and 44. Skin replicas were then analyzed by means of an optical profilometry technique. Standard wrinkle and roughness features were then calculated and statistically analyzed. The tolerance profile of the test products was also clinically evaluated during the entire study.
A total of 125 patients (40 in the retinoic acid group, 40 in the retinaldehyde group, and 45 in the vehicle group) were studied. At week 18, a significant reduction of the wrinkle and roughness features was observed with both retinaldehyde and retinoic acid. At week 44, a less pronounced reduction was demonstrated in both active groups. No statistically significant changes were observed with the retinaldehyde vehicle at any assessment point. A total of 135 patients constituted the safety population. Retinaldehyde was well tolerated during the entire study. In contrast, retinoic acid caused more local irritation, and affected compliance of the patients.
Retinaldehyde was efficacious and well tolerated in patients with photodamage.
To determine the efficacy of topical ascorbic acid application in treating mild to moderate photodamage of facial skin using an objective, computer-assisted image analysis of skin surface topography and subjective clinical, photographic, and patient self-appraisal questionnaires.
A 3-month, randomized, double-blind, vehicle-controlled study.
Facial plastic surgery private practice.
Nineteen evaluable volunteer sample patients aged between 36 and 72 years with Fitzpatrick skin types I, II, and III who were in good physical and mental health with mild to moderately photodamaged facial skin were considered for analysis.
Coded, unmarked medications were randomly assigned to the left and right sides of each subject's face, one containing the active agent, topical ascorbic acid (Cellex-C high-potency serum; Cellex-C International, Toronto, Ontario), the other, the vehicle serum (Cellex-C International). Three drops (0.5 mL) of each formulation were applied daily to the randomly assigned hemifaces over the 3-month study period. Treatment assignments were not disclosed to subjects, clinicians, or personnel involved in analyzing skin replicas.
Specific clinical parameters were evaluated and graded on a 0- to 9-point scale (0, none; 1-3, mild; 4-6, moderate; and 7-9, severe). Reference photographs were used to standardize grading criteria. Overall investigator scores were compared with baseline and graded as excellent (much improved), good (improved), fair (slightly improved), no change, or worse. Patient self-appraisal questionnaires rated the degree of improvement (much improved, improved, slightly improved, no change, or worse) and reported adverse effects (burning, stinging, redness, peeling, dryness, discoloration, itching, and rash). Standard photographs were taken at baseline, including anteroposterior and left and right oblique views to facilitate subsequent clinical evaluations, and at the end of therapy for comparison. Optical profilometry analysis was performed on the skin surface replicas of the lateral canthal (crow's feet) region, comparing baseline to end-of-study specimens. Using this computer-based system, the resulting image was digitally analyzed, and numeric values were assigned to reflect surface features. The parameters obtained included Rz, Ra, and shadows. These values provided objective data that document pretreatment and posttreatment texture changes proportional to the degree of wrinkling, roughness, and other surface irregularities.
Optical profilometry image analysis demonstrated a statistically significant 73.7% improvement in the Ra and shadows north-south facial axis values with active treatment greater than vehicle control, as well as a trend for improvement in the Rz north-south facial axis parameter, showing a 68.4% greater improvement of active treatment vs vehicle control. Clinical assessment demonstrated significant improvement with active treatment greater than control for fine wrinkling, tactile roughness, coarse rhytids, skin laxity/tone, sallowness/yellowing, and overall features. Patient questionnaire results demonstrated statistically significant improvement overall, active treatment 84.2% greater than control. Photographic assessment demonstrated significant improvement, active treatment 57.9% greater than control.
A 3-month daily regimen of topical ascorbic acid provided objective and subjective improvement in photodamaged facial skin. Skin replica optical profilometry is an objective method for quantification of the skin surface texture changes.
Aging of the population, in particular the "baby boomers," has resulted in increased interest in methods of reversal of photodamage. Non-invasive treatments are in high demand, and our knowledge of mechanisms of photodamage to skin, protection of the skin, and repair of photodamage are becoming more sophisticated and complex.
The objective of this study is to determine if the topical use of a vitamin C preparation can stimulate the skin to repair photodamage and result in clinically visible differences, as well as microscopically visible improvement.
Ten patients applied in a double-blind manner a newly formulated vitamin C complex having 10% ascorbic acid (water soluble) and 7% tetrahexyldecyl ascorbate (lipid soluble) in an anhydrous polysilicone gel base to one-half of the face and the inactive polysilicone gel base to the opposite side. Clincial evaluation of wrinkling, pigmentation, inflammation, and hydration was performed prior to the study and at weeks 4, 8, and 12. Two mm punch biopsies of the lateral cheeks were performed at 12 weeks in four patients and stained with hematoxylin and eosin, as well as in situ hybridization studies using an anti-sense probe for mRNA for type I collagen. A questionnaire was also completed by each patient.
A statistically significant improvement of the vitamin C-treated side was seen in the decreased photoaging scores of the cheeks (P = 0.006) and the peri-oral area (P = 0.01). The peri-orbital area improved bilaterally, probably indicating improved hydration. The overall facial improvement of the vitamin C side was statistically significant (P = 0.01). Biopsies showed increased Grenz zone collagen, as well as increased staining for mRNA for type I collagen. No patients were found to have any evidence of inflammation. Hydration was improved bilaterally. Four patients felt that the vitamin C-treated side improved unilaterally. No patient felt the placebo side showed unilateral improvement.
This formulation of vitamin C results in clinically visible and statistically significant improvement in wrinkling when used topically for 12 weeks. This clinical improvement correlates with biopsy evidence of new collagen formation.
Microtopography of the skin and aging
- P Agache
- J Mignot
- Makki
Agache P, Mignot J, Makki S. Microtopography of the skin and aging. In: Kligman A M, Takase Y, eds. Cutaneous Aging. Tokyo: University of Tokyo Press, 1988: 475–499.
Mor-phological study of human skin topography
- J Mignot
- Rondot H D Zahouani
- Nardin Ph
Mignot J, Zahouani H, Rondot D, Nardin Ph. Mor-phological study of human skin topography. Int J Bioeng Skin 1987: 3: 177–196.
Status : Postprint (Author's version)
Published in : Experimental Dermatology (2003)
Status : Postprint (Author's version)
Cellular functions of ascorbic acid
- Padh
Padh H. Cellular functions of ascorbic acid. Biochem Cell Biol 1990: 68: 1166-1173.
Morphological study of human skin topography
- Mignot J