Polypodium Leucotomos Extract: A Status Report on Clinical Efficacy and Safety
March 2015 | Volume 14 | Issue 3 | Original Article | 254 | Copyright © March 2015
Richard R. Winkelmann DO,a James Del Rosso DO FAOCD,b and Darrell S. Rigel MD MSc
aRigel Dermatology, New York, NY
bTouro University College of Osteopathic Medicine, Henderson, NV
cClinical Professor, Dept. of Dermatology, NYU School of Medicine, New York, NY
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 (gastrointestinal 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.J Drugs Dermatol
Polypodium leucotomos (PL) is a fern native to Central and South America historically used to treat inflammatory disorders by Native Americans.1 Various extracts of PL applied topically or taken orally have been shown to have several beneficial properties over the last 4 decades. A specific extract of Polypodium leucotomos (PLE) is available commercially (Heliocare, Ferndale Laboratories) and has been evaluated in a variety of basic science and clinical studies. Antioxidant effects of PLE are attributed to its ability to consume superoxide anions, lipid peroxides, and hydroxyl radicals.2,3 As a versatile photoprotectant,4,5 PLE is believed to inhibit the photodamage process, increasing the minimal erythema dose (MED), by maintaining extracellular matrix integrity6,7 and preventing damage to DNA repair enzymes.5,8,9 The anti-mutagenic effects of PLE are attributed to its ability to block ultraviolet (UV) radiation-induced COX-2 expression10,11,12 and promote p53 suppressor gene mutation.8 Finally, PLE has been shown to have immunoregulatory effects in response to UV radiation demonstrated by inhibited infiltration of neutrophils and mast cells as well as reduced loss of antigen presenting Langerhans cells.4
The clinical application of PLE has been studied in order to evaluate its diverse therapeutic potential. Historically, poultices of PL were used by South Americans to treat atopic dermatitis and psoriasis.1 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 (PMLE), other photodermatoses, and melasma.
Despite decades of anecdotal evidence supporting the excellent safety profile of PL, multiple basic science and research studies evaluating PLE, and widespread exposure as a commercially available PLE capsule formulation, no articles have been published evaluating the safety of PLE. The purpose of this review of the literature is to summarize each clinically relevant study of PLE and to capture any relevant side effects associated with PLE administration in humans and animals. Studies and clinical use completed in humans treated with PLE encompass a broad range of potential indications.
We performed a PUBMED search for any randomized clinical trials (RCTs) related to PL, PLE, or anapsos, a synonym and reviewed data on Ames and murine testing. Studies that were not randomized or placebo controlled were included if performed on a large number of patients. Considerable effort was made to find all available articles, including from less common foreign sources. The primary safety endpoint of the review was any mention of an adverse event (AE), side effect, or toxicity.