INTRODUCTION
Skin aging is a complex process resulting in wrinkling, loss of elasticity, textural changes, and uneven skin tone. Though cutaneous manifestations of aging are known to significantly affect self-perception,1 the ability to now digitally enhance the skin's appearance has led to grossly unrealistic standards.2 Accordingly, social media and the use of photo-editing applications have become major motivating factors in the pursuit of cosmetic procedures,3 leading to progressively younger populations being targeted with anti-aging strategies. Indeed, in 2019, greater than 50% of 18- to 24-year-old women employ wrinkle-defying products in their skin care routines.4 This expansion in consumer base has ballooned the global anti-aging product market to an estimated $40.49 billion, with a projected compound annual growth rate of 5.4% by 2028.5
The principal cause of extrinsic skin aging is exposure to ultraviolet radiation (UV-R), which penetrates the skin and induces the formation of free radicals that accelerate aging through oxidative stress.6 This effect is primarily achieved through oxidation of type I collagen, the most abundant structural protein in the dermis. Although the collagen content of the skin normally diminishes with age due to decreased synthesis by dermal fibroblasts and increased degradation by collagenases,6 the process is accelerated by UV-R-induced free radicals.7,8 Moreover, the ensuing tissue repair response to oxidative stress greatly enhances the activity of collagenases, furthering collagen loss.9 Accordingly, the additive effects of age and UV-R greatly reduce the collagen content in the skin, lessening the structural integrity of the dermis, thereby causing accelerated wrinkle formation.10
Vitamin C is an essential nutrient that functions as an antioxidant, protecting cells from free radical damage. In addition, it functions as a coenzyme in the biosynthesis of collagen fibrils.11 Furthermore, in vitro analysis of dermal fibroblasts suggest that vitamin C can stimulate collagen gene expression as well as prevent collagen degradation via inhibition of collagenases.12,13 With respect to human skin, vitamin C is found at relatively high levels in both the dermis and epidermis of youthful skin.14 However, levels in the skin inversely correlate with age and exposure to ultraviolet radiation.14 For these reasons, vitamin C has become an increasingly popular ingredient in topical anti-aging skin care products, particularly in the fight against wrinkles.15 Beauty consumers have consequently indulged in purchasing topicals that claim vitamin C as an active ingredient with the promise of reducing the appearance of wrinkles. However, to our knowledge, there is no systematic evaluation of the current body of evidence delineating the efficacy of topical vitamin C. Accordingly, we have critically assessed vitamin C's potential role in wrinkle reduction via a systematic literature review of the recent clinical evidence.
The principal cause of extrinsic skin aging is exposure to ultraviolet radiation (UV-R), which penetrates the skin and induces the formation of free radicals that accelerate aging through oxidative stress.6 This effect is primarily achieved through oxidation of type I collagen, the most abundant structural protein in the dermis. Although the collagen content of the skin normally diminishes with age due to decreased synthesis by dermal fibroblasts and increased degradation by collagenases,6 the process is accelerated by UV-R-induced free radicals.7,8 Moreover, the ensuing tissue repair response to oxidative stress greatly enhances the activity of collagenases, furthering collagen loss.9 Accordingly, the additive effects of age and UV-R greatly reduce the collagen content in the skin, lessening the structural integrity of the dermis, thereby causing accelerated wrinkle formation.10
Vitamin C is an essential nutrient that functions as an antioxidant, protecting cells from free radical damage. In addition, it functions as a coenzyme in the biosynthesis of collagen fibrils.11 Furthermore, in vitro analysis of dermal fibroblasts suggest that vitamin C can stimulate collagen gene expression as well as prevent collagen degradation via inhibition of collagenases.12,13 With respect to human skin, vitamin C is found at relatively high levels in both the dermis and epidermis of youthful skin.14 However, levels in the skin inversely correlate with age and exposure to ultraviolet radiation.14 For these reasons, vitamin C has become an increasingly popular ingredient in topical anti-aging skin care products, particularly in the fight against wrinkles.15 Beauty consumers have consequently indulged in purchasing topicals that claim vitamin C as an active ingredient with the promise of reducing the appearance of wrinkles. However, to our knowledge, there is no systematic evaluation of the current body of evidence delineating the efficacy of topical vitamin C. Accordingly, we have critically assessed vitamin C's potential role in wrinkle reduction via a systematic literature review of the recent clinical evidence.
MATERIALS AND METHODS
Search Strategy
This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.16 A systematic search of the literature from January 2015 to September 2022 was performed across the following databases: Scopus, Web of Science, and PubMed. A list of predetermined Medical Subject Heading (MeSH) search terms and keywords were employed, including but not limited to various combinations of the following: "Topical Vitamin C OR Ascorbic acid", "Vitamin C efficacy", "dermatology", "cosmetology", and "skin anti-aging". No restrictions were placed on language or research group characteristics.
Study Selection
Full text articles with in vivo clinical evidence available in English were considered eligible for inclusion. Full inclusion and exclusion criteria are listed in Table 1. Record screening was performed by 2 independent reviewers (BS and HM). Records with non-unanimous decisions were reconciled by a third reviewer (LB). The remaining studies then underwent full-text review for determination of inclusion eligibility.
Data Extraction
Eligible full-text studies were independently assessed by 2 independent reviewers (BS and HM) for data extraction. Any discrepancies in data interpretation were settled by a third reviewer (LB). Data extracted included the study type, study location, duration of study, sample size, patient description, type and ingredients of the topical formulation, outcome, outcome measurement, results, and adverse events. Outcomes were further stratified based on the specific effects of vitamin C, including effects on wrinkles, elasticity, and collagen. Quality assessment of the level of evidence was performed per the Journal of the American Academy of Dermatology guidelines (Table 3).17
Statistical Analysis
Statistical Analysis
Counts and frequencies of categorical data are reported using standard descriptive statistics. Continuous variables are reported as "mean ± standard deviation" or median (interquartile range [IQR]), where appropriate. Categorical variables are reported as counts (n) and percentages (%) within their corresponding variable groups.
RESULTS
Study Retrieval and Characteristics
A total of 5,428 records were initially identified through literature search, of which 79 duplicates were removed. The ensuing 5,349 unique records were screened based on title and abstract relevancy. 5,185 records did not meet inclusion criteria and were thus excluded. Of the remaining 164 records, 157 records were excluded with reason, leaving 7 relevant papers focused on wrinkles that were included in this systematic literature review (Figure 1). Relevant study characteristics are listed in Table 2. Of the 7 articles, 4 met Level IB criteria, 1 met Level IIA criteria, and 2 met Level IIB criteria.
Effects of Topical Vitamin C on the Appearance of Facial Wrinkles One study by Escobar et al, which met level IB criteria, conducted an open clinical study using peptide-C ampoule containing hyaluronic acid which was applied twice daily to the face and neck of 47 subjects aged 40 to 60 for 28 days.18 Changes in the appearance of subject's crow's feet wrinkles, forehead wrinkles, and nasolabial fold were evaluated using an anatomical atlas (Dynamical Atlas) to clinically score the whole face on day 0 and day 28. The subjects also conducted a self-assessment questionnaire on day 0 and day 28. The authors reported a significant decrease (P<0.005) in the mean clinical grades of crow's feet wrinkles (9% decrease), forehead wrinkles (11% decrease), and nasolabial folds (5.2% decrease) on day 28. When subjects completed a self-assessment, 64% reported less visible fine lines after 28 days of applying peptide-C ampoules. However, because the ampoules contained a variety of ingredients, conclusions based on individual ingredients could not be made and the study was limited by its short duration and lack of vehicle control.18
Effects of Topical Vitamin C on the Appearance of Facial Wrinkles One study by Escobar et al, which met level IB criteria, conducted an open clinical study using peptide-C ampoule containing hyaluronic acid which was applied twice daily to the face and neck of 47 subjects aged 40 to 60 for 28 days.18 Changes in the appearance of subject's crow's feet wrinkles, forehead wrinkles, and nasolabial fold were evaluated using an anatomical atlas (Dynamical Atlas) to clinically score the whole face on day 0 and day 28. The subjects also conducted a self-assessment questionnaire on day 0 and day 28. The authors reported a significant decrease (P<0.005) in the mean clinical grades of crow's feet wrinkles (9% decrease), forehead wrinkles (11% decrease), and nasolabial folds (5.2% decrease) on day 28. When subjects completed a self-assessment, 64% reported less visible fine lines after 28 days of applying peptide-C ampoules. However, because the ampoules contained a variety of ingredients, conclusions based on individual ingredients could not be made and the study was limited by its short duration and lack of vehicle control.18
