James Q. Del Rosso, DO Adjunct Clinical Professor (Dermatology), Touro University Nevada, Henderson, Nevada; Dermatology Private Practice, Lakes Dermatology, Las Vegas, Nevada; Research Director, Del Rosso Dermatology Research Center, Las Vegas, Nevada
Disclosure: Dr. Del Rosso serves as a consultant and speaker for Ferndale Laboratories. The authorship of this article was conceived of and completed in its entirety soley by the author. No individual, including from any company or agency, participated in the content development, writing, or review of this article. The author did not receive honoraria or grant support for authorship or submission of this article.
Abstract
Polypodium leucotomas extract is a natural product derived from a tropical fern that is available as an over-the-counter product in the United States and several other countries. A designated brand of oral Polypodium leucotomas extract has been shown in several research studies to exhibit a variety of antioxidant and photoprotective properties. Clinical research with this same formulation of Polypodium leucotomas extract has demonstrated multiple potential therapeutic applications. This article provides a thorough overview of research completed with Polypodium leucotomas extract and outlines suggested approaches for clinical use. (J Clin Aesthet Dermatol. 2016;9(5):37–42.)
Polypodium leucotomas (PL) is a tropical fern indigenous to Central and South America that has been used both orally and topically for approximately three decades to treat a vast array of inflammatory and pigmentary skin conditions; these include photosensitivity disorders, melasma, vitiligo, eczematous dermatitis, and psoriasis.[1–7] Over approximately the past 15 years, a variety of topical and oral formulations have become available in the marketplace. However, as PL is classified as an oral dietary supplement, assurances that specific formulations are consistent in their content of necessary chemical components and are supported by cogent scientific evidence that can be found in peer-reviewed published medical literature are very limited.[1–7] PL has been noted to exhibit photoprotective, antioxidant, and chemopreventative properties in animal and human studies, and thus PL and PL extracts have been recommended to be used as an oral dietary supplement to protect against the effects of solar exposure, including photoaging, and for adjunctive use in the clinical setting based on scientific evidence demonstrated with a specific formulation of PL extract.[1–20]
Many formulations are marketed in both the United States and globally as “Polypodium leucotomas Extract” (PLE), suggesting that equivalent pharmaceutical methodologies have been used to extract from the PL fern the important components that have been reported to provide both acute and chronic photoprotective benefits.[1–7],[21] However, data on PL and PLE with formulations that demonstrate photoprotective mechanisms of action (MOA) and that scientifically support the alleged clinical benefits are scarce overall, with the exception of a specific brand of PLE. Many publications have reviewed PL and PLE in detail, including information on MOA and clinical use; however, studies supporting the scientific evidence relate to a single individual brand formulation of PLE, marketed under the trade names Heliocare and Fernblock (Ferndale Laboratories, Ferndale, Michigan); the PLE contained in this brand formulation is carefully extracted using quality control methods to assure the content of the final oral formulation.[1–20],[22]
The goals of this article are 1) to provide the clinician with a clinically relevant primer that includes a summary of reported MOAs and clinical effects based on human and animal studies, and 2) discuss when and how clinicians can choose to integrate oral PLE into patient management using a formulation that is supported by cogent scientific evidence. Content is based predominantly on data available from published studies and also includes suggestions from the author.
Why Consider Using Oral Polypodium leucotomas Extract in Clinical Practice?
Widespread concerns regarding the rise in prevalence of skin cancer and the adverse effects of both acute and chronic photodamage emphasize the need for clinicians to educate their patients on how to optimize photoprotection.[23–26] In addition, protection against the effects of sun exposure is an important component of the management plan for patients with disease states that are induced or exacerbated by ultraviolet (UV) light exposure, or in those utilizing medications associated with phototoxicity or photoallergy.[27],[28]The importance of proper and regular sunscreen use and recommended measures of photoprotection are well-recognized; however, compliance with sunscreen use and proper application are not always consistent.[29],[30] Notably, a large body of research evidence has emerged supporting a wide variety of photoprotective effects, therapeutic benefits, and safety of PLE.[1–20],[22] It is suggested that it be utilized adjunctively with sunscreen, and in some cases, to support primary therapeutic modalities.[1–7] A more detailed review of research outcomes and management recommendations is provided below.
Does It Matter What Formulation of Oral Polypodium leucotomas is Recommended to Patients?
Importantly, not all formulations of PLE are created equal. In the Unitd States, the available data demonstrating MOAs and clinical benefits of oral PLE are based on basic science and clinical research completed with a designated brand formulation of PLE, marketed as Heliocare capsules (PLE-hc).[1–20],[22] As oral PL/PLE formulations are available over-the-counter (OTC), and are classified as an oral dietary supplement, there are no requirements mandating that other formulations of PL and PLE exhibit the same physiochemical properties as PLE-hc, and no scientific data that indicate therapeutic equivalence with PLE-hc. In order to be consistent with providing the best evidence-based recommendations, it is important that patients utilize this designated brand formulation of PLE as there is no evidence to support that other formulations maintain the same content of polyphenolic ingredients or that they achieve the same biologic effects that appear to provide therapeutic benefits based on available research.
PLE-hc is available as a dietary supplement in 20 countries, including the United States, Spain, Italy, Belgium, and New Zealand.[31] The standardized formulation of PLE-hc is an aqueous extract from the leaves of the PLE fern completed carefully using specified pharmacologic methodology and after inspection to assure the quality of the source material that is grown in a controlled geographic environment.[1],[2],[22] The qualitative and quantitative content of PLE-hc is consistent in polyphenolic compounds including vanillic acid, caffeic acid, p-coumaric acid, ferulic acid, 4-hydroxycinammic-quinic acid, chlorogenic acid (five isomers), 3,4-dihydroxybenzoic acid, and 4-hydroxybenzoic acid, along with monosaccharides and flavonoids.[1],[2],[22],[31] It cannot be assumed that other formulations of PL or PLE provide the same content qualitatively and quantitatively, and that they exhibit the same photoprotective properties that have been published in studies evaluating PLE-hc. If clinicians are to recommend a product, whether it is by prescription or OTC, it is important that product recommendations to patients be made based on the best data that is available.
What Evidence Has Been Published That Supports Recommending Oral Polypodium leucotomas Extract as an Adjunctive Photoprotective Agent?
A complete review of the basic science and clinical data supporting use of PLE-hc is beyond the scope of this article and is reviewed elsewhere.[1–20],[22],[31–39] Available studies completed in animals and humans evaluate a variety of photoprotective effects that address antioxidant, anti-inflammatory, and immunoregulatory properties including protective activities to decrease DNA mutagenesis and preserve cellular integrity, and clinical assessments and case reports in certain skin disease states. A summary of the available data is depicted in Table 1 .
What is Known About the Safety of Polypodium leucotomas Extract?
Before reviewing clinical applications, it is important to discuss what is known about the safety of PLE-hc. Humans have been exposed to PL and PLE for several decades with a conspicuous absence of published reports related to any major toxicities.[3],[5],[22],[41] The following summarizes published safety information on PLE-hc:
• A PubMed literature search on PLE was completed spanning 40 years of publications (1972–2014) with any mention of adverse events (AEs), side effects, or toxicity; 19 human and six laboratory studies were included. Among 1,016 patients treated, a total of 16 AEs (1.6%) were noted, primarily mild-to-moderate gastrointestinal disturbances and pruritus; no serious AEs were reported. The oral dose range in the included studies was 120 to 1,080mg/day.41
• A double-blind, randomized, placebo-controlled study evaluated the safety and photoprotective activity of PLE-hc 240mg (n=20) versus placebo, ingested twice daily over a duration of two months, in healthy subjects with Fitzpatrick skin types I to IV.3 Despite similar UV exposures, subjects in the PLE-hc study arm showed a sixfold lower risk of sunburn (P=0.04) and a 15-fold greater chance of experiencing reduction in erythema at one or more levels of UVB exposure (P<0.01). All subjects completed the study with no relevant changes in complete blood cell counts, serum chemistry panels, prothrombin time, and partial thromboplastin time reported.[3]
• In studies of patients with photodermatoses (primarily polymorphous light eruption [PMLE]), treated for two weeks with PLE-hc in doses ranging from 480 to 1,200mg/day, no adverse reactions were reported (N=60).[32],[35]
• Comprehensive toxicologic safety assessments conforming to internationally accepted protocols and standards in rat studies were completed with administration of PLE-hc, including 14-day and 90-day repeated oral toxicity studies.[22] Mutagenicity, genotoxicity, and chromosomal aberrations (clastogenicity) were not observed. No treatment-related toxicities including inspection of specific organs and no mortalities were observed. These animal studies predict that a safe human dose is at minimum 840mg/day based on a 100-fold safety factor in a 70kg person.[22]
What Are Practical Recommendastions for Use of Polypodium leucotomas Extract in Clinical Practice?
Although there are some limitations with the available pharmacologic and clinical data with PLE-hc, there is a large body of basic science and clinical evidence that supports its use in a variety of clinical scenarios. Each capsule of PLE-hc contains 240mg. Outlined in Table 2 ; are commonly encountered clinical challenges with recommendations from the author on incorporation of PLE-hc into the management plan. In all cases, PLE-hc is to be used adjunctively with broad spectrum sunscreen and other measures of sun protection (Table 2 ). It is important to note that pharmacokinetic and dose-ranging data are limited with PLE-hc as it is an oral dietary supplement and not a drug. The dosing recommendations above are those of the author based on published literature, clinical impressions, and available safety data.
Closing Comments
PLE-hc is an oral dietary supplement that appears to offer adjunctive therapeutic benefit in the prevention of effects related to acute and chronic photodamage and in the management of certain skin disorders caused or exacerbated by UV exposure. This article attempts to provide background to the clinician to support the use of PLE-hc along with a review of how this agent may be utilized in the management of specific clinical scenarios.
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