Polypodium leucotomos Uses, Benefits & Dosage - Drugs.com Herbal Database

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# Polypodium leucotomos

Scientific Name(s): Phlebodium aureum (L.) J. Sm., Polypodium aureum L., Polypodium leucotomos
Common Name(s): Calaguala (Spain), Golden polypody, Hares-foot fern

Medically reviewed by Drugs.com. Last updated on May 1, 2022.

## Clinical Overview

### Use

P. leucotomos has been investigated for use in a variety of skin conditions (eg, actinic keratosis, atopic dermatitis, melasma, photoprotection, vitiligo).

### Dosing

Atopic dermatitis: P. leucotomos extract (Anapsos) dosages up to 480 mg/day (treatment duration, 6 months) were evaluated in children with atopic dermatitis to evaluate effects on topical corticosteroid use for treatment of outbreaks.

Actinic keratosis: Initial P. leucotomos extract dose of 960 mg/day orally for 1 month followed by 480 mg/day for 5 months has been used after PDT.

Photoprotection: P. leucotomas extract (eg, Heliocare) dosages ranging from 240 to 480 mg/day have been used to evaluate effects on pigment darkening, photo-induced hypersensitivity dermatitis, subacute cutaneous lupus erythematosus, and vandetanib-induced phototoxic drug rash; P. leucotomas extract was often administered as adjunctive therapy, and treatment durations varied.

Vitiligo: P. leucotomos extract (eg, Fernblock) 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.

### Contraindications

Contraindications have not been identified.

### Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

### Interactions

None well documented.

### Adverse Reactions

Information regarding adverse reactions is lacking. Low-grade erythema and edema have been reported.

### Toxicology

No data.

## Scientific Family

- Polypodiaceae (common fern, licorice fern)

## Botany

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 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.(ITIS 2022a, ITIS 2022b, USDA 2022)

## History

P. leucotomos has been used in folk medicine for skin conditions (eg, psoriasis, atopic dermatitis)(Berman 2016, Parrado 2016, Shakhbazova 2021) and for inflammatory disorders by American Indians.(Aguilera 2013) Extracts are referred to as anapsos.(Berman 2016, Shakhbazova 2021)

An aqueous P. leucotomos extract has been used in Spain since the 1970s for treatment of various skin conditions (ie, psoriasis, atopic dermatitis, vitiligo, polymorphous light eruption, melasma) and alone or adjunctively in over-the-counter topical and oral sunscreen formulations.(Goh 2018, Nestor 2015) Topical and oral formulations have been marketed in Europe since 2000. P. leucotomos is now commercialized in more than 26 countries, including the United States, where it has been available as a dietary supplement since 2006.(Parrado 2016)

## Chemistry

Polyphenols are potent antioxidants that have been identified in P. leucotomos. The most abundant polyphenols found include caffeic, chlorogenic, ferulic, hydroxycinnamic, p-coumaric, and vanillic acids.(Berman 2016, Kohli 2017)

## Uses and Pharmacology

Antioxidant and immunomodulatory effects have been documented. Clinical data support observations made in earlier in vitro and animal studies that documented reductions in sunburn response, photoaging damage, cyclooxygenase 2 (COX-2) levels, and ultraviolet B (UVB)–induced immunosuppression. Mechanisms include neutralization of superoxide anions, lipid peroxides, and hydroxyl radicals, reduced COX-2 expression, lower p53 suppressor gene mutations, and decreased inflammatory infiltrate, as well as increased lymphoblast response to mitogens, higher proportions of cytotoxic/suppressor (CD8+) cells, increased serum immunoglobulin levels, and modulation of interleukin (IL)-1beta, IL-2, and tumor necrosis factor alpha (TNF-alpha).(Berman 2016, Kohli 2017, Mohammad 2019, Sanchez-Rodriguez 2018, Shakhbazova 2021)

### Skin conditions

UV photoprotective effects have been reported with both topical and oral extracts of P. leucotomos via antioxidant mechanisms (prevention of acute sunburn and psoralen phototoxic reactions, attenuation of reactive oxygen species, reversal of elastic fiber loss, and improvement of fibroblast and keratinocyte membrane integrity).(Shakhbazova 2021)

#### Actinic keratoses

#### Clinical data

In a study in adult men with scalp actinic keratoses (N=34), the efficacy of oral P. leucotomos extract supplementation after photodynamic therapy (PDT) was compared with PDT without supplementation. Extract supplementation was initiated 1 week after the last PDT session at 960 mg/day for 1 month followed by 480 mg/day for 5 months. Mean age of participants was approximately 76 years. Both treatments successfully reduced the number of actinic keratoses; however, after 6 months, the extract group was observed to have significantly better clearance (P=0.04). No patients progressed to squamous cell carcinoma, and no major adverse effects were reported.(Auriemma 2015)

#### Atopic dermatitis

#### Clinical data

A phase 4, multicenter, double-blind, randomized, placebo-controlled study conducted in 105 children 2 to 17 years of age with atopic dermatitis investigated the impact of a commercially available, orally administered P. leucotomos extract (Anapsos) on reducing the use of topical corticosteroids for treatment of outbreaks. Dosing was based on age group: younger than 6 years, 6 to 12 years, and older than 12 years, with respective P. leucotomos doses of 240 mg/day, 360 mg/day, and 480 mg/day. After 6 months of treatment, no significant difference was observed between placebo and P. leucotomos groups in reducing the use of topical corticosteroids for outbreaks. However, when assessing the percentage of days per month of topical corticosteroid use, the extract led to significantly fewer days (36% reduction) in the fifth month versus the first month, compared with a 9% reduction with placebo (P=0.02). Similarly, the percentage of days of antihistamine use was significantly lower with the extract compared with placebo (median: 4.5% vs 13.6% of days, respectively; P=0.038), as was the percentage of patients taking antihistamines (P<0.05). The incidence of adverse events was similar between groups.(Ramirez-Bosca 2012)

#### Melasma

#### Clinical data

A systematic review identified 2 randomized, placebo-controlled, 12-week trials evaluating use of a P. leucotomos oral extract in female patients with melasma (N=54). Results were equivocal between the 2 trials, with 1 study reporting significant decreases in severity and quality-of-life scores (P<0.05 each) and the other reporting no statistically significant difference in severity, quality of life, or melanin compared with placebo.(Zhou 2017)

A double-blind, randomized, placebo-controlled pilot study investigated the effect of a commercially available oral P. leucotomos extract (Fernblock) for treating melasma, specifically in an adult Asian population with Fitzpatrick III or IV skin types. The final analyses included data from 33 women (31 Chinese patients and 2 Malaysian patients). After 12 weeks of treatment, disease severity scores were significantly lower for the extract than placebo (49.4% vs 32.6% reduction, respectively; P<0.05), with statistical significance observed starting at day 56. Improvements observed with the extract in melanin index, erythema index, and quality-of-life scores were not significantly different than with placebo. No systemic adverse effects were reported.(Goh 2018)

#### Photoprotection

#### Clinical data

In a small study of participants with Fitzpatrick skin phototypes IV to VI, administration of a commercially available oral P. leucotomos extract (Heliocare) at a dosage of 480 mg/day orally for 28 days led to a significant decrease in relative pigmentation between the persistent pigment darkening and delayed tanning phases after visible light exposure at a dose of 480 J/cm2 (P<0.05). GI upset, pruritus, and dry mouth were reported by 7 participants.(Mohammad 2019) In another small crossover study (N=22) conducted in participants with skin phototypes I to III and exposed to UVB, a significant (19%) decrease in mean investigator's global assessment scores overall was observed after administration of P. leucotomos extract (240 mg orally 2 hours and 1 hour prior to irradiation [ie, 480 mg total]) compared with before supplementation. UVB-induced changes were decreased in 77% of subjects after extract supplementation. Additionally, significant (P<0.05) reductions were noted in all biomarkers associated with deleterious UVB effects (ie, DNA damage, apoptosis, inflammation, COX-2, proliferation).(Kohli 2017) Similar results were reported in another small study (N=20) after 28 days of oral P. leucotomos extract administration; higher minimal erythema dose (MED) (P=0.01) and lower UV-induced erythema intensity (P<0.01) were observed after UV exposure compared with placebo.(Nestor 2015) In a study of patients with dysplastic nevus syndrome, sporadic melanoma, or familial melanoma (N=61), oral P. leucotomos extract administration led to a significant reduction in sensitivity to ultraviolet radiation in terms of increased UVB-MED values (P<0.05). Analysis by gender demonstrated that women had significantly higher MED values after supplementation than men (P<0.05). Of the 61 participants, 65% experienced improved MED, with significant correlations to dark eyes phenotype and a lower baseline MED (P<0.05 each).(Aguilera 2013)

Several cases of adjunctive P. leucotomos extract use have shown improved management of photo-induced skin rashes.(Breithaupt 2012, Korman 2019, Luber 2016, Stump 2022) A case of pruritic photodermatosis (actinic prurigo) in an 11-year-old girl was managed successfully with adjunctive use of P. leucotomos extract (Heliocare 240 mg orally twice daily) with topical corticosteroids.(Stump 2022) After minimal resolution with a 7-month regimen of topical and systemic prescription therapies (ie, steroids, tacrolimus, hydroxyzine, hydroxychloroquine), adjunctive administration of P. leucotomos extract (240 mg/day) orally for 3 months led to complete resolution of chronic photo-induced hypersensitivity dermatitis in a 52-year-old man with Fitzpatrick skin type V. The extract was used in conjunction with continued tacrolimus and topical triamcinolone.(Luber 2016) A 59-year-old man with persistent skin eruptions unresponsive to topical steroid treatment was diagnosed with subacute cutaneous lupus erythematosus. After a moderate response to a 3-month hydroxychloroquine regimen, the addition of an oral P. leucotomos extract (240 mg/day) resolved the remaining rash as well as the majority of reoccurring flares within 4 months. After 37 months of daily extract supplementation, the patient reported only 3 minor flares, all of which responded quickly to topical corticosteroid cream.(Breithaupt 2012)

Similarly, a case of protracted vandetanib-induced phototoxic drug rash resolved with supplementation of P. leucotomos extract in a 55-year-old man with inoperable thyroid cancer. After minimal improvement in rash subsequent to 6 weeks of a corticosteroid regimen, treatment with P. leucotomos extract 240 mg/day orally was started; within 8 weeks, erythema and edematous skin lesions had healed with no postinflammatory or hyperpigmentation noted.(Korman 2019)

#### Vitiligo

#### Clinical data

In a 2021 systematic review that reported on topical or oral herbal-based adjunctive therapies for vitiligo, 2 high-quality, small, double-blind, randomized, placebo-controlled trials evaluated oral P. leucotomos. The 2007 study enrolled 49 patients with vitiligo vulgaris while 19 patients with generalized vitiligo were enrolled in the 2006 study; respective treatments were narrowband UVB twice weekly plus P. leucotomos 250 mg orally 3 times daily for 25 to 26 weeks, and psoralens plus ultraviolet A 3 times weekly plus P. leucotomos 720 mg/day orally for 12 weeks. Significant improvements in repigmentation were reported in both studies for the P. leucotomos groups compared with placebo (P=0.06 and P<0.05, respectively).(Shakhbazova 2021)

In a small, single-blind, randomized, placebo-controlled trial in adults with generalized nonsegmental vitiligo (N=44), oral administration of a standardized P. leucotomos extract (Fernblock) 480 mg twice daily for up to 6 months in combination with narrowband UVB produced significant improvement in repigmentation of the head and neck (85% vs 25% with placebo; P<0.001) and extremities (83% vs 12% with placebo; P=0.001). For the trunk area, 92% of patients receiving the extract achieved moderate or excellent repigmentation, while 44% of patients receiving placebo achieved moderate improvement; however the difference between treatment groups in achieving moderate repigmentation was not statistically significant. Results were more pronounced in those with a shorter disease duration. The incidence of adverse events related to narrowband UVB was significantly lower in the extract group compared with placebo (52% vs 86%, respectively; P=0.023), including for erythema (17% vs 63%; P=0.009).(Pacifico 2021)

### Sunscreen

#### In vitro data

A study of P. leucotomos extract added to 4 different sunscreen formulations noted increased SPF averaging 14%, with increases in other parameters (eg, contact hypersensitivity factors) also observed.(Aguilera 2021)

#### Clinical data

The previously described in vitro study evaluating addition of P. leucotomos extract to various sunscreen formulations helped to confirm mechanisms of action for results of an earlier clinical trial comparing effects of sunscreen with and without the addition of P. leucotomos 0.5% extract in 10 volunteers exposed to solar radiation. The extract provided increased protection against skin changes and damage for all measured outcomes.(Schalka 2019)

### Tonsilitis

#### In vitro data

In a child palatine tonsil model utilizing harvested tissue from 20 children with recurrent tonsillitis who underwent tonsil surgery, P. leucotomos extract (Anapsos) at various doses significantly increased IL-2, IL-10, IL-1beta, interferon-gamma, TNF-alpha, and several immunoglobulins (ie, IgM, IgD, IgG-4) compared with controls. Additionally, natural killer cells were activated that not only released more cytokines but increased in cell population.(Sanchez-Rodriguez 2018)

## Dosing

### Actinic keratosis

Initial P. leucotomos extract dose of 960 mg/day orally for 1 month followed by 480 mg/day for 5 months has been used after PDT.(Auriemma 2015)

### Atopic dermatitis

P. leucotomos extract (Anapsos) dosages up to 480 mg/day (treatment duration, 6 months) were evaluated in children with atopic dermatitis to evaluate effects on topical corticosteroid use for treatment of outbreaks.(Ramirez-Bosca 2012)

### Photoprotection

P. leucotomas extract (eg, Heliocare) dosages ranging from 240 to 480 mg/day have been used to evaluate effects on pigment darkening, photo-induced hypersensitivity dermatitis, subacute cutaneous lupus erythematosus, and vandetanib-induced phototoxic drug rash; P. leucotomas extract was often administered as adjunctive therapy, and treatment durations varied.(Breithaupt 2012, Korman 2019, Luber 2016, Mohammad 2019)

### Sunscreen

Addition of P. leucotomos 0.5% extract to sunscreen has been evaluated in a small study of volunteers exposed to solar radiation.(Schalka 2019)

### Vitiligo

P. leucotomos extract (eg, Fernblock) 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.(Pacifico 2021, Shakhbazova 2021)

## Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

## Interactions

None well documented.

## Adverse Reactions

A systematic review that investigated the safety of medicinal plants used for treatment of vitiligo and hypermelanosis identified 5 small studies using oral P. leucotomos. Study populations ranged from 10 to 40, and 4 of the 5 studies were double-blind, randomized, controlled trials. Only low-grade erythema and edema were reported in 1 uncontrolled small trial (N=10).(Hussain 2021)

## Toxicology

In rats, no mortality was observed with a standardized aqueous extract of P. leucotomos (Fernblock) at doses up to 5,000 mg/kg/day for 28 days. 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.(Murbach 2017)

## Index Terms

- Phlebodium aureum (L.) J. Sm.
- Polypodium aureum

## References

## Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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Aguilera P, Carrera C, Puig-Butille JA, et al. Benefits of oral Polypodium Leucotomos extract in MM high-risk patients. J Eur Acad Dermatol Venereol. 2013;27(9):1095-1100. doi:10.1111/j.1468-3083.2012.04659.x22849563
Auriemma M, Di Nicola M, Gonzalez S, Piaserico S, Capo A, Amerio P. Polypodium leucotomos supplementation in the treatment of scalp actinic keratosis: could it improve the efficacy of photodynamic therapy? Dermatol Surg. 2015;41(8):898-902. doi:10.1097/DSS.000000000000042526218723
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Breithaupt AD, Jacob SE. Subacute cutaneous lupus erythematosus: a case report of Polypodium leucotomos as an adjuvant therapy. Cutis. 2012;89(4):183-184.22611747
Goh CL, Chuah SY, Tien S, Thng G, Vitale MA, Delgado-Rubin A. 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):14-19.29606995
Hussain I. The safety of medicinal plants used in the treatment of vitiligo and hypermelanosis: A systematic review of use and reports of harm. Clin Cosmet Investig Dermatol. 2021;14:261-284. doi:10.2147/CCID.S29834233790609
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Nestor MS, Berman B, Swenson N. Safety and efficacy of oral Polypodium leucotomos extract in healthy adult subjects. J Clin Aesthet Dermatol. 2015;8(2):19-23.25741399
Pacifico A, Damiani G, Iacovelli P, Conic RRZ, Gonzalez S, Morrone A; Young Dermatologists Italian Network (YDIN). NB-UVB plus oral Polypodium leucotomos extract display higher efficacy than NB-UVB alone in patients with vitiligo. Dermatol Ther. 2021;34(2):e14776. doi:10.1111/dth.1477633433041
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