Double-blind, Placebo-controlled Trial to Evaluate the Effectiveness of Polypodium Leucotomos Extract in the Treatment of Melasma in Asian Skin: A Pilot Study.

Introduction: Melasma is a common pigmentary disorder with a multifactorial etiology that can hinder its management. The aqueous extract of the fern Polypodium leucotomos (PLE), Fernblock® (IFC, Madrid, Spain), has demonstrated antioxidant and photoprotective activities and has been used for the treatment of several pigmentary disorders. The aim of this study was to evaluate the efficacy and safety of oral PLE in the treatment of melasma in Asian patients. Methods: Forty healthy adult patients with clinical diagnoses of melasma who were receiving treatment with topical 4% hydroquinone cream and sunscreen with a sun protection factor (SPF) of 50+ were recruited for inclusion in this study from the National Skin Centre in Singapore. They were randomized to receive either oral PLE supplementation or placebo for 12 weeks. Patients were assessed at baseline, Day 28, Day 56, and Day 84 using the modified Melasma Area and Severity Index (mMASI); melanin and erythema indexes; VISIA® photography (Canfield Scientific, Parsippany, New Jersey, USA); and the Melasma Quality of Life (MelasQoL) questionnaire. Adverse events were recorded. Results: Following four, eight, and 12 weeks of treatment, there were statistically significant differences between the mMASI scores of both groups as compared with the baseline scores (p≤0.01). mMASI scores of the PLE group at eight and 12 weeks were also significantly lower than those of the placebo group (p≤0.05). At the end of the study, a significant improvement was reached in both groups (both p≤0.01), with no significant differences between them. The scores of the melanin and erythema indices displayed a slight improvement in both groups, without significant differences among them. MelasQoL score showed an improvement in the PLE group versus the placebo group. Our results demonstrate that the PLE aqueous extract product significantly improves and accelerates the outcome reached with hydroquinone and sunscreen almost from the first month of treatment in comparison with the placebo. There were no significant side effects reported. Conclusions: The oral PLE aqueous extract product appears to be a safe and effective adjunctive treatment for melasma in combination with topical hydroquinone and sunscreen.