Application of Vitamin C in Melasma: A Meta‐Analysis and Systematic Review

Melasma is a chronic acquired facial hyperpigmentation disorder that remains a persistent clinical challenge due to its high recurrence rate and lack of a definitive cure. It imposes a substantial psychological burden on affected individuals, often leading to significant impairment of health‐related quality of life. Vitamin C (ascorbic acid) has emerged as a promising depigmenting agent for melasma, and this systematic review and meta‐analysis aimed to evaluate the efficacy and safety of vitamin C–containing depigmenting formulations for melasma treatment. Systematic literature searches were conducted in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Web of Science, Google Scholar, and Scopus up to October 2024, following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Statistical analyses were performed using Review Manager 5.4 software, and the Cochrane risk‐of‐bias tool for randomized controlled trials (RCTs) was used to assess study quality. A total of 11 eligible studies involving 301 melasma patients were included. Compared with control interventions, vitamin C showed a trend toward reduced melasma severity (standardized mean difference [SMD] = −0.49, 95% confidence interval [CI]: −1.08 to 0.10, p = 0.095). Subgroup analysis by administration route revealed topical vitamin C as the most effective (SMD = −1.13, 95% CI: −1.68 to −0.58), followed by iontophoresis (SMD = −0.51, 95% CI: −1.26 to 0.25), injection (SMD = −0.50, 95% CI: −1.16 to 0.16, I 2 = 70.5%), and microneedling (SMD = −0.47, 95% CI: −1.39 to 0.46; I 2 = 82.0%), with no significant differences across routes ( p = 0.367). For dosage, the low‐dose group had an SMD of −0.57 (95% CI: −1.10 to −0.05, I 2 = 63.0%), while the high‐dose group had an SMD of −0.51 (95% CI: −1.28 to 0.27, I 2 = 83.5%). There was no statistically significant difference between the two groups ( p = 0.894), indicating no dose‐dependent enhancement of therapeutic effects within the included dosage range. Regarding treatment regimens, vitamin C combination therapy was numerically superior to monotherapy but not statistically significant ( p = 0.197). Notably, vitamin C as an adjuvant significantly improved the efficacy of chemical peeling (combined therapy vs. peeling alone: SMD = −0.97, 95% CI: −1.33 to −0.62, p < 0.001, I 2 = 0.0%). Vitamin C demonstrated a favorable safety profile with low rates of adverse events. Limitations of this meta‐analysis include small sample sizes of included RCTs and substantial heterogeneity in some subgroups.