A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention
Background: Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carci- noma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B ) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses.
Methods: In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month intervention period, the number of nonmelanoma skin cancers in the 6-month postintervention period, and the safety of nicotinamide.
Results: At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, −6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell carcino- mas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001). No noteworthy between-group differences were found with respect to the number or types of adverse events during the 12-month intervention period, and there was no evidence of benefit after nicotinamide was discontinued.
Conclusions: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. (Funded by the National Health and Medical Research Council; ONTRAC Australian New Zealand Clinical Trials Registry number, ACTRN12612000625875.)
View full publication – The New England Journal of Medicine
The Impact of Oral Polypodium Leucotomos Extract on Ultraviolet B Response: A Human Clinical Study
Background: There is a rationale for adding systemic photoprotective agents to the current photoprotection regimen.
Objective: This study was designed to objectively evaluate the molecular and photobiologic effects of oral administration of Polypodium leucotomos extract (PLE).
Methods: In all, 22 subjects with Fitzpatrick skin phototype I to III were enrolled. On day 1, subjects were irradiated with visible light, ultraviolet (UV) A1, and UVB (using 308-nm excimer laser). Evaluation was done immediately and 24 hours after irradiation. On days 3 and 4, irradiation and evaluation process was repeated after ingestion of PLE.
Results: Clinical assessments and colorimetry data showed a decrease in UVB-induced changes in 17 of 22 subjects post-PLE administration; histology findings demonstrated such a decrease in all 22 subjects…
View full publication – 2017 Journal of the American Academy of Dermatology – Kohli
Polypodium Leucotomos Extract: A Status Report on Clinical Efficacy and Safety
Abstract: Various extracts of polypodium leucotomos (PLE) applied topically or taken orally have been shown to have several beneficial antioxidant, photoprotectant, antimutagenic, and immunoregulatory effects. Modern studies have evaluated the efficacy of PLE orally as a photoprotective agent and for use in several photo-aggravated dermatologic disorders such as polymorphous light eruption, other photodermatoses, and melasma. No articles have been published evaluating the safety of PLE. We performed a PUBMED search for any randomized clinical trials related to PLE, or anapsos, a synonym. The primary safety endpoint of the review was any mention of an adverse event, side effect, or toxicity. Overall, 19 human and 6 basic science studies were included spanning over 40 years of research. Oral PLE was administered at daily doses ranging from 120 mg to 1080 mg. No adverse effects were reported in laboratory studies. In humans, side effects (gastro intestinal complaints and pruritus) were mild to moderate and found only in very small numbers of patients overall (16/1016 [2%]). This review concludes PLE is well tolerated at all doses administered and associated with a negligible risk of side effects.
View full publication – 2015 Journal of Drugs in Dermatology – Winkelmann
Polypodium Leucotomos: A Potential New Photoprotective Agent
Abstract: As the understanding of the immune system pathways, cytokine balances, and cellular interactions continues to expand, so must the potential applications of therapies that can impact the process of diseases instead of just controlling their symptoms. In the case of Polypodium leucotomos extract, which is derived from a tropical fern of the Polypodiaceae family, the future potential of applications in dermatology and beyond will be better understood as its incorporation into daily routines gives rise to the development of new regimens. Clinicians may position this agent as an option for daily maintenance, accept its use in combinations, or use it as a template for further development of oral supplementation that may evolve into a true immunomodulator…
View full publication – 2015 American Journal of Clinical Dermatology – Bhatia
Sun Protection in a Pill: The Photoprotective Properties of Polypodium Leucotomos Extract
Background: Physical blocks (i.e. wearing appropriate clothing), exposure avoidance, and the use of sunscreens are the main methods of photoprotection currently used. However, phytochemical and natural botanical extracts such as polypodium leucotomos, a tropical fern found in Central and South America, demonstrate a strong potential as adjuncts to sunscreen protection.
Method: A review of the literature was performed focusing on the photoprotective properties of PL extracts, including antioxidant, immunoregulatory, anti-inflammatory and antitumorigenic effects in the context of sunburn, photodermatoses, chronic skin damage, photoaging, and skin cancer…
View full publication – 2014 International Journal of Dermatology – El-Haj
Role of Oral Polypodium Leucotomos Extract in Dermatologic Diseases: A Review of the Literature
Abstract: Polypodium leucotomos extract (PLE), derived from the tropical fern of Polypodiaceae family, has properties ranging from immunomodulatory and antioxidative to photoprotective. It is these multiple mechanisms of action, in combination with a favorable side effect profile, which makes PLE a promising adjunctive treatment for several dermatologic disorders. Studies are summarized on the use and potential applications of PLE in the treatment or management of photodermatoses, vitiligo, melasma, psoriasis, atopic dermatitis, and more recently, in minimizing infections in high-performance athletes. More data, however, with larger sample sizes are needed to confirm these benefits.
View full publication – 2014 Journal of Drugs in Dermatology – Choudry
Double-blind, Placebo-controlled Trial to Evaluate the Effectiveness of Polypodium Leucotomos Extract in the Treatment of Melasma in Asian Skin: A Pilot Study
Abstract: 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.
Conclusions: Our results indicate that oral PLE (Fernblock®, IFC, Madrid, Spain) has multiple beneficial properties and a high safety profile and appears to be a useful adjunctive treatment for melasma.
View full publication – 2018 Journal of Clinical and Aesthetic Dermatology – Goh