Polypodium

Polypodium leucotomos (Phlebodium aureum): A Comprehensive Reference

1. Identity and Botanical Classification

Polypodium leucotomos is the deprecated synonym for the tropical fern Phlebodium aureum. P. leucotomos is a member of the Polypodiaceae (common ferns, licorice ferns) family. Synonyms include Phlebodium aureum (L.) J. Sm. (accepted) and Polypodium aureum L. (unaccepted). The name Polypodium leucotomos persists in the biomedical and commercial literature because the bulk of published research and regulatory submissions use it, and it remains the predominant designation in pharmacological monographs.

The fern is native to the continental United States, Caribbean Territories, and Mexico, and is found in Oceania, the Caribbean, as well as North, Central, and South America. P. leucotomos has been used in folk medicine for skin conditions (e.g., psoriasis, atopic dermatitis) and for inflammatory disorders by American Indians. The geographical distribution ranges from Central America to South America, mainly in Bolivia, Brazil, Mexico and Peru. It cultivates in humid environments and grows on developed tree trunks. Its adaptation and vegetation reach heights of 1,200 to 2,200 metres above sea level.

Polypodium leucotomos (PLE) is an epiphytic fern species that was originally native to Central America, where it is also known as "calaguala." It rarely grows on the ground. The plant has a thick, highly branched rhizome covered in red scales. The stems are long and connected to the rhizome by small polypodia. The leaves are 30–150 cm long, 18–50 cm wide, with 10–40 cm long petioles and a blunt, sharp or rounded end; they can be firm, herbaceous, papery or membranous-leathery, and are usually smooth. The fern is now cultivated in plantations in various Latin and South American countries.

Common Names and Trade Names

• The South American P. leucotomos species is known locally as "calaguala" and extracts of this fern are called "anapsos."
• The concentrated hydrophilic extract of the leaves of Polypodium leucotomos, endowed with photoprotective properties, is marketed with the commercial name Fernblock.
• Other commercial formulations include Heliocare® and Antioxidine®.

Common Preparations and Dosage Forms

It is used in complementary and alternative therapies with various pharmaceutical dosage forms (systemic or topical). It is available in both oral supplements and topical skin creams that contain varying amounts of the plant's extract. Thanks to the composition of phytochemical constituents present in the leaves and rhizomes which confer antioxidant and photoprotective activity, it has clinical therapeutic potential to be used as a systemic and topical sunscreen of natural origin for the prevention of different types of skin diseases caused by harmful ultraviolet A and ultraviolet B radiations.

2. Traditional and Historical Use

Polypodium leucotomos (PL) is a tropical fern plant native to Central America and parts of South America. It grows in the rain forest and has a long history of use as an herbal medicine ingested for a variety of ailments by the indigenous people of Honduras. Known locally in Central America as "calaguala," the Mayas used Polypodium leucotomos as a "blood purification tea."

Traditionally, indigenous peoples of Honduras and other regions utilized extracts from this plant for a variety of health concerns. Its most notable historical applications include remedies for skin disorders such as psoriasis, eczema, and vitiligo, as well as for wound healing and to alleviate inflammation. The practice involved preparing infusions or decoctions from the fern's leaves, which were either consumed or applied topically to affected areas.

Indigenous communities in Central and South America used it — referred to locally as calaguala and its extract as anapsos — to treat inflammatory skin conditions and immune-related disorders. Aqueous extracts were introduced into the Spanish pharmaceutical market in the 1970s for conditions including psoriasis, eczema, and vitiligo.

An aqueous P. leucotomos extract has been used in Spain since the 1970s for treatment of various skin conditions (i.e., psoriasis, atopic dermatitis, vitiligo, polymorphous light eruption, melasma) and alone or adjunctively in over-the-counter topical and oral sunscreen formulations.

3. Key Constituents and Active Compounds

Polypodium leucotomos extract (PLE) is made up of phenolic compounds (benzoates and cinnamates) and biological acid molecules (quinic, shikimic, glucuronic, and malic acids). Phenolic compounds are plant metabolites found in fruits, vegetables, coffee beans, and tea leaves. Among the acid molecules, the most represented are 4-hydroxycinnamic acid (p-coumaric), 3-methoxy-4-hydroxycinnamic acid (ferulic), 3-dihidroxycinnamic acid (caffeic), 3-methoxy-4-hydroxybenzoic acid (vanillic), and 3-caffeoliquinic acid (chlorogenic).

Fernblock, an aqueous extract of the aerial parts of the fern Polypodium leucotomos, used as raw material for topical and oral photoprotective formulations, was fractionated by HPLC and its major components were identified. Phenolic compounds were identified as 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, vanillic acid, caffeic acid, 4-hydroxycinnamic acid, 4-hydroxycinnamoyl-quinic acid, ferulic acid, and five chlorogenic acid isomers.

Phenolic components of P. leucotomos extract include chlorogenic acid, coumaric acid, vanillic acid, caffeic acid and ferulic acid, the latter two being the most potent inhibitors of oxidation in vitro. It is also known that its antioxidant capacity is dose-dependent, with the most potent among those listed above being ferulic and caffeic acids.

Polypodium leucotomos has been shown to contain saponins and phenolic compounds: vinyl acid, chlorogenic acid, ferulic acid, caffeic acid, and coumaric acid, extracted from rhizomes and leaves. Additionally, minor flavonoids have been identified; using HPLC-DAD, a small fraction of flavonoids (less than 15% of the total polyphenolic species) was detected, represented by (+)-catechin hydrate, (−)-epicatechin, rutin and hyperoside.

4. Mechanisms of Action

4.1 Antioxidant and Reactive Oxygen Species (ROS) Scavenging

Polypodium leucotomos extract (PL, commercial name Fernblock®) is a powerful antioxidant due to its high content of phenolic compounds. PL is administered orally, with proven safety, and it can also be used topically. Its mechanisms include inhibition of the generation and release of reactive oxygen species (ROS) by ultraviolet (UV) light. It also prevents UV- and ROS-induced DNA damage with inhibition of AP1 and NF-κB and protection of natural antioxidant enzyme systems.

As an antioxidant, PLE enhances the ability of endogenous antioxidant systems to neutralize superoxide anions, lipid peroxides and hydroxyl radicals, which are formed in the skin following exposure to UV and visible radiation. In addition, lower levels of UV-induced COX-2 expression, p53 suppressor gene mutations, cyclobutane pyrimidine dimers, epidermal proliferation, sunburn cells, and inflammatory infiltrate are seen in vitro and in animal models following PLE administration.

4.2 DNA Protection and Anti-Mutagenic Effects

Its short-term effects include inhibition of reactive oxygen species production induced by UV radiation, DNA damage, isomerization and decomposition of trans-urocanic acid, prevention of UV-mediated apoptosis and necrosis, as well as degradative matrix remodeling, which is the main cause of photoaging. These short-term effects translate into long-term prevention of photoaging and photocarcinogenesis.

4.3 Extracellular Matrix Preservation

PLE can block UVR-induced apoptosis in fibroblasts and keratinocytes and re-establish their proliferation. Additionally, PL inhibits the disorganization of the actin cytoskeleton, cell–cell adhesive contacts, and cell matrix. Furthermore, PLE acts on molecular targets: it inhibits MMP-1, 2, 3 and 9; it stimulates TIMPs, TGF-β, elastin, and fibrillin; and it stimulates the deposition of types I and V collagen in UV-irradiated fibroblasts and types I, III, and V collagen in non-irradiated fibroblasts.

4.4 Immunomodulation

Studies have explored its role in supporting the immune system by modulating cytokine production and stimulating immune cells like T lymphocytes and natural killer cells. The herbal medicine also has anti-inflammatory properties, cytokine suppressor and leukotriene inhibitor activity.

4.5 Absorption and Metabolism

The antioxidant capacity of PL components increases in a concentration-dependent manner, with ferulic and caffeic acids the most powerful antioxidants. The apparent permeability results correspond to a human post-oral administration absorption of 70–100% for all tested substances. Coumaric, ferulic and vanillic acids were metabolized by CYP450-dependent mono-oxygenases and partially conjugated to glucuronic acid and sulfate. When orally administered, PLE is absorbed rapidly and efficiently (70–100%). It is overall metabolized within 24 hours in the liver.

4.6 Activity Against Blue Light

Pretreatment with Fernblock® prevents cell death, alteration of mitochondrial morphology, and phosphorylation of p38 in human dermal fibroblasts exposed to blue light. In addition, Fernblock® significantly reduced the activation of Opsin-3 in melanocytes and the photo-oxidation of melanin, preventing its photodegradation. This mechanism is relevant to pigmentary disorders triggered or exacerbated by visible light.

5. Scientific Evidence by Area of Use

5.1 Photoprotection (Sunburn / Minimal Erythema Dose)

A randomized, double-blind, placebo-controlled study was designed to determine the safety of oral Polypodium leucotomos extract administered twice daily to healthy adults for 60 days and to assess its ability to provide protection against exposure to ultraviolet radiation. After two months of treatment, there were no changes in any safety assessments. The subjects in the placebo group showed a greater likelihood of experiencing ≥1 episodes of sunburn (2 vs. 8 subjects; p=0.04). At Day 28, PLE-treated subjects showed greater likelihood of an increased minimal erythema dose (MED) (8 vs. 1 subject; p=0.01) and greater likelihood of decreased UV-induced erythema intensity (10 subjects vs. 3 subjects; p<0.01). Conclusion: Polypodium leucotomos extract 240 mg taken twice daily for 60 days was a safe and effective means for reducing the damaging effects of ultraviolet radiation.

Odds ratio calculations showed subjects in the Polypodium leucotomos extract group had a 22-fold greater likelihood of experiencing an increased MED and a 15-fold greater likelihood of experiencing decreased UV-induced erythema intensity.

Evidence strength: Multiple small randomized controlled trials (RCTs) support photoprotective effects in humans. Study populations tend to be modest in size, and some research has been supported by the manufacturer (Fernblock/IFC Group). Results are nonetheless consistent across studies and independent centers.

5.2 Vitiligo

Three randomized, double-blind, placebo-controlled studies have demonstrated significant improvements in vitiligo when oral Polypodium leucotomos therapy was combined with psoralens plus ultraviolet A and narrowband ultraviolet B.

In one RCT, 50 subjects were randomly assigned to receive either a placebo or 250 mg of PLE three times daily alongside twice-weekly NB-UV-B for 25 weeks. The treatment group achieved higher repigmentation rates (50%) in the head and neck, particularly in Fitzpatrick skin types II and III, compared to the placebo group (19%; P = .002).

A third randomized trial involved 44 vitiligo subjects treated with either twice-weekly full-body NB-UV-B or 480 mg of PLE twice daily or NB-UV-B alone for 6 months. The combined treatment group achieved significantly higher repigmentation rates than controls (47.8% vs 22%, respectively).

Dosages ranging from 720 to 960 mg/day orally plus UV light therapy have been studied for potential to improve repigmentation; treatment durations ranged from 12 to 26 weeks.

Evidence strength: Multiple RCTs with control groups. PLE appears most effective as an adjunct to phototherapy rather than as a standalone treatment. Sample sizes remain modest, and the evidence base, while encouraging, would benefit from larger independent trials.

5.3 Melasma

Based on a review of relevant literature including the results of a randomized, placebo-controlled study, the oral administration of Polypodium leucotomos significantly improved the severity of melasma in women. When taken orally, P. leucotomos provides some degree of protection against the harmful effects of ultraviolet radiation, thereby helping to minimize the photoaging effects of sunlight, including hyperpigmentation and textural changes.

In a double-blind, placebo-controlled pilot study of 40 healthy adult patients with melasma receiving topical 4% hydroquinone cream and sunscreen (SPF 50+), patients 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.

Evidence strength: Positive signals from randomized controlled trials, though studies tend to be pilot-scale or have small samples. PLE is typically studied as an adjunct to established therapies (topical hydroquinone, sunscreen) rather than alone. Additional independent large-scale trials are needed.

5.4 Polymorphous Light Eruption (PLE/PMLE)

Polymorphic light eruption (PLE) is the most common idiopathic photodermatosis. Reactive oxygen species have been implicated in its pathogenesis. Polypodium leucotomos is a natural extract from tropical fern leaves with potent antioxidant and anti-inflammatory properties. A study sought to evaluate whether a concentrated hydrophilic extract of PL might prevent or delay the photoinduction of typical PLE lesions by artificial UV radiation. A total of 35 patients with long-standing PLE were included in this open, uncontrolled bicenter study. PLE was induced by photoprovocation with artificial UVB and UVA light, thereafter oral treatment with PL was initiated. Two weeks later a second photoprovocation was performed while patients were still taking PL.

Several recent open-label studies have demonstrated the ability of P. leucotomos to reduce the frequency and severity of polymorphous light eruption.

Evidence strength: Open-label and uncontrolled studies predominate in this area, providing moderate but not definitive evidence. The 2021 literature review (Zakria et al.) identified 11 RCTs across dermatological indications, with PMLE among those with supporting evidence.

5.5 Atopic Dermatitis (Eczema)

People with eczema — an inflammatory condition marked by itchy and red skin — may benefit from using Polypodium leucotomos in addition to traditional steroid creams and oral antihistamine medications. A 6-month study in 105 children and teens with eczema found that those who took 240–480 mg of Polypodium leucotomos daily were significantly less likely to take oral antihistamines compared to those who did not take the supplement.

Long-term treatment with an extract of P. leucotomos has been shown to reduce inflammation and relieve itching in children and adolescents with atopic dermatitis. A randomized, double-blind, placebo-controlled, multicenter trial (Ramírez-Bosca et al., 2012, Actas Dermosifiliogr) specifically evaluated PLE in atopic dermatitis.

Evidence strength: There is at least one multicenter placebo-controlled RCT in atopic dermatitis. Effect sizes are modest. There is supporting evidence for its use in symptomatic relief in atopic dermatitis.

5.6 Photocarcinogenesis and Skin Cancer Prevention

It was demonstrated that Polypodium leucotomos extract acts as an antioxidant, photoprotectant, antimutagenic, anti-inflammatory, and immunoregulator. It is effective when taken orally and/or applied topically to support the prevention of skin cancers. It also has an important role in preventing photoaging.

PLE demonstrated photoprotective and anti-inflammatory properties in several in vitro and in vivo studies, making it a potentially useful tool to prevent skin photocarcinogenesis. PL has a clinically significant role for the treatment and prevention of certain dermatologic conditions including photocarcinogenesis and photoaging. There is supporting evidence for its use in malignant melanoma high-risk patients and for enhanced actinic keratosis clearance following photodynamic therapy.

Evidence strength: Evidence for cancer prevention is primarily from animal models and in vitro studies. Direct human clinical trial evidence for prevention of skin cancer is limited, and no clinical trial has been powered to measure cancer incidence as a primary endpoint. The mechanistic basis is strong, but translation to clinical prevention requires further study.

5.7 Photoaging

P. leucotomos may owe its ability to help in preventing the photoaging process specifically by maintaining the structural integrity of the extracellular matrix that typically is affected by UV damage through increased matrix metalloproteinase expression and inhibition of collagen synthesis. It stimulates TIMPs, TGF-β, elastin, and fibrillin, and stimulates the deposition of types I and V collagen in UV-irradiated fibroblasts.

Evidence strength: Mechanistic and some in vivo animal evidence is robust. Human clinical trial data specifically measuring photoaging endpoints (wrinkle depth, elasticity) are more limited.

5.8 Psoriasis

P. leucotomos extracts have been used for the treatment of psoriasis in South America and Spain. Clinical investigation for psoriasis was among the earliest formal studies of PLE; a 1974 paper by Padilla, Lainez, and Pacheco in the International Journal of Dermatology described the hydrophilic fraction of Polypodium leucotomos as a new agent for psoriasis management.

Evidence strength: Historical and observational evidence exists for psoriasis; more robust controlled trial data are available for other indications such as vitiligo and melasma. The body of evidence specifically for psoriasis is older and largely predates modern RCT standards.

5.9 Other Investigated Areas

Potential clinical uses that require additional human clinical studies include solar urticaria, post-inflammatory hyperpigmentation, cutaneous lupus erythematosus, and other photosensitive cutaneous disorders.

In 2004, a study examined the effects of oral supplementation with PLE in 10 healthy volunteers undergoing Psoralen UVA (PUVA) therapy. All of the patients were initially exposed to PUVA without receiving oral PLE. There is evidence from this and other studies that PLE can reduce phototoxic skin reactions associated with PUVA phototherapy.

6. Dosage Forms and Reported Clinical Dosages

Oral PLE was administered at daily doses ranging from 120 mg to 1080 mg across human studies reviewed in the literature. Specific dosages reported in published clinical studies include:

• Photoprotection (adults): Polypodium leucotomos extract 240 mg taken twice daily (480 mg/day) for 60 days was studied as a safe and effective means for reducing the damaging effects of ultraviolet radiation.
• Vitiligo (adults, adjunct to NB-UVB): 250 mg of PLE 3 times daily (750 mg/day) alongside twice-weekly NB-UV-B for 25 weeks.
• Vitiligo (adults, adjunct to NB-UVB): 480 mg of PLE twice daily (960 mg/day) for 6 months, combined with twice-weekly NB-UVB.
• Vitiligo (general dosing range): Dosages ranging from 720 to 960 mg/day orally plus UV light therapy; treatment durations ranged from 12 to 26 weeks.
• Atopic dermatitis (children and teens): 240–480 mg daily for 6 months.

PLE is marketed as a dietary supplement (Heliocare®, Antioxidine®, Fernblock®, and others). These are rapidly absorbed and provide early protection that lasts up to 2 hours after administration against the initial signs of sunburn (erythema).

7. Safety Profile

7.1 General Tolerability in Human Studies

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.

Oral PLE supplements have been used in Europe since the 1980s without any side effects being reported. After two months of treatment (240 mg twice daily), there were no changes in any safety assessments, including physical examination, vital signs, hematology, comprehensive metabolic panel, and prothrombin/partial thromboplastin time.

7.2 Formal Toxicology Studies

A battery of toxicological studies was conducted in accordance with internationally accepted standards to investigate the genotoxicity and repeated-dose oral toxicity of Fernblock®. No evidence of mutagenicity was observed in a bacterial reverse mutation test or in vitro mammalian chromosomal aberration test, nor was any genotoxic activity observed in an in vivo mouse micronucleus test. Two repeated-dose oral toxicity studies were conducted in male and female Wistar rats. In the first study, no mortality or toxic effects were observed and no target organs were identified at doses administered for 14 days by gavage up to the maximum dose of 5000 mg/kg bw/day. Based on these results, a 90-day study was conducted at 0, 300, 600, and 1200 mg/kg bw/day.

In a previous battery of toxicological tests on Fernblock®, no genotoxicity was observed and no oral toxicity was observed up to 1200 mg/kg bw/day. Statistically significant dose-related changes included a reduction in creatinine in males as well as an increase in calcium and mean corpuscular volume in females; however, these findings were not considered to be of toxicological significance.

7.3 Pregnancy and Lactation

PLE has not been clinically tested in patients less than 18 years and in pregnant or breastfeeding women; hence there is no data to support its use in these groups. Information regarding safety and efficacy in pregnancy and lactation is lacking.

7.4 Drug and Supplement Interactions

Polypodium leucotomos extract has not been thoroughly tested for interactions with other supplements and drugs. None are well documented. Coumaric, ferulic and vanillic acids are metabolized by CYP450-dependent mono-oxygenases, suggesting a theoretical basis for interactions with other CYP450-metabolized drugs, though no clinical drug–drug interaction studies have been published as of the available literature.

7.5 Topical Use Safety

Low-grade erythema and edema have been reported in isolated cases with topical application.

7.6 Contraindications

Formal contraindications have not been identified in the published clinical literature, though use in pregnancy, lactation, and in individuals under 18 years is not supported by clinical data.

8. Body Systems and Health Areas Associated with Polypodium leucotomos

• Integumentary system (skin): Photoprotection, UV-induced erythema, photoaging, psoriasis, atopic dermatitis, vitiligo, melasma, polymorphous light eruption, actinic keratosis, post-inflammatory hyperpigmentation.
• Immune system: Modulation of cytokine production and stimulation of immune cells including T lymphocytes and natural killer cells.
• Oncology (investigational): Oral and topical application to support the prevention of skin cancers. Evidence is primarily preclinical.
• Cellular / oxidative stress: Systemic antioxidant effects via scavenging of superoxide anions, lipid peroxides, and hydroxyl radicals.

9. Characterization of Overall Evidence Strength

A systematic review querying PubMed/MEDLINE, Embase, and Cochrane Library identified 21 of 152 articles meeting inclusion criteria, including 11 randomized controlled trials and 5 treatment trials. The evidence base for Polypodium leucotomos is strongest for photoprotection (increased MED, reduced erythema), vitiligo (as an adjunct to phototherapy), and melasma. Evidence for psoriasis is largely older and predates modern trial design standards. Evidence for skin cancer prevention is compelling mechanistically but remains preclinical in nature. All human trials published to date have been modest in sample size, and several have involved manufacturer funding or investigator ties to Fernblock/IFC Group, which is a relevant limitation for interpretation. The safety record accumulated over four decades of use in Europe, together with formal toxicology studies showing no genotoxicity and no adverse effects at very high animal doses, supports an overall favorable short- to medium-term safety profile.

References

• Parrado C, et al. Fernblock (Polypodium leucotomos Extract): Molecular Mechanisms and Pleiotropic Effects in Light-Related Skin Conditions, Photoaging and Skin Cancers, a Review. Int J Mol Sci. 2016;17(7):1026. PMC4964402
• Berman B, Ellis C, Elmets C. Polypodium leucotomos – An Overview of Basic Investigative Findings. J Drugs Dermatol. 2016;15(2):224-228. PMC5189711
• Nestor MS, et al. Polypodium leucotomos as an Adjunct Treatment of Pigmentary Disorders. J Clin Aesthet Dermatol. 2014. PMC3970827
• Ionescu MA, et al. Uses of Polypodium leucotomos Extract in Oncodermatology. J Clin Med. 2023;12(2):673. PMC9861608
• Gombau L, et al. Polypodium leucotomos extract: antioxidant activity and disposition. Methods Find Exp Clin Pharmacol. 2006;28(3):157-65. PubMed 16263237
• Garcia F, et al. Phenolic components and antioxidant activity of Fernblock, an aqueous extract of the aerial parts of the fern Polypodium leucotomos. Methods Find Exp Clin Pharmacol. 2006;28(3):157-60. PubMed 16810341
• Nestor MS, et al. Polypodium leucotomos as an Adjunct Treatment of Pigmentary Disorders. J Clin Aesthet Dermatol. 2014;7(3):13-17. PubMed 24688621
• Nestor M, et al. Safety and Efficacy of Oral Polypodium leucotomos Extract in Healthy Adult Subjects. J Clin Aesthet Dermatol. 2015;8(2):19–23.
• Kohli I, et al. The impact of oral Polypodium leucotomos extract on ultraviolet B response: a human clinical study. J Am Acad Dermatol. 2017;77(1):33-41. PMC5730054
• JAAD Case Reports: Improvement in light tolerance with oral Polypodium leucotomos extract in a patient with nonsegmental vitiligo. PMC11179583
• Tanew A, et al. Oral administration of a hydrophilic extract of Polypodium leucotomos for the prevention of polymorphic light eruption. J Am Acad Dermatol. 2012;66(1):58-62. PubMed 21696853
• Goh CL, et al. Double-blind, Placebo-controlled Trial to Evaluate the Effectiveness of Polypodium Leucotomos Extract in the Treatment of Melasma in Asian Skin: A Pilot Study. J Clin Aesthet Dermatol. 2018;11(3):14-19. PMC5868779
• Zakria D, et al. Dermatologic Applications of Polypodium leucotomos: A Literature Review. J Clin Aesthet Dermatol. 2021;14(5):46-51. PubMed 34221229
• Murbach TS, et al. A comprehensive toxicological safety assessment of an aqueous extract of Polypodium leucotomos (Fernblock®). Food Chem Toxicol. 2015;86:328-341.
• Murbach TS, et al. A 28-day oral toxicology study of an aqueous extract of Polypodium leucotomos (Fernblock®). Regul Toxicol Pharmacol. 2017;89:158-164. PMC5615158
• Gonzalez S, et al. Mechanistic insights in the use of a Polypodium leucotomos extract as an oral and topical photoprotective agent. Photochem Photobiol Sci. 2010;9(4):559-563. PubMed 20354651
• Drugs.com Natural Products Database: Polypodium leucotomos. Updated April 2026.
• DermNet NZ: Polypodium leucotomos extract.
• Antioxidant and photoprotective potential of Polypodium leucotomos. Exploration of Medicine. 2022.
• Portillo M, et al. The Aqueous Extract of Polypodium leucotomos (Fernblock®) Regulates Opsin 3 and Prevents Photooxidation of Melanin Precursors on Skin Cells Exposed to Blue Light. Antioxidants. 2021;10(3):400. PMC7998284
• Nestor MS, et al. Polypodium Leucotomos Extract: A Status Report on Clinical Efficacy and Safety. J Drugs Dermatol. 2015;14(3):254-259.