Polypodium Leucotomos (Sun)

Background/Objectives: Oral photoprotection is gaining attention as a complementary approach to conventional sun protection. This randomized double-blind placebo-controlled study evaluated the effects of an 8-week dietary intervention with a syrup supplement containing Polypodium leucotomos extract (PLE), Red Orange Extract (ROE), and vitamins A, C, D, and E on minimal erythema dose (MED), UVB-induced erythema (Δa*), and pigmentation changes (ΔMI). Methods: In total, 54 fair-skinned participants (phototypes I-III) were randomized into either the intervention (IP) or placebo group (n = 27 per group). MED, Δa*, and ΔMI were assessed at baseline after 2 and 8 weeks of supplementation. Results: Throughout the intervention, MED gradually increased, while Δa* decreased in the IP group. While these changes were not statistically significant after 2 weeks, they reached significance after 8 weeks of intervention. By the end of the study, the IP group exhibited a significant 23.8% increase in MED (from 0.447 ± 0.096 to 0.553 ± 0.142 J/cm2; p < 0.05) and a 46.2% reduction in erythema intensity (from 2.40 ± 0.94 to 1.29 ± 1.04 au; p < 0.0001). In contrast, ΔMI in the IP group (from 0.67 ± 0.81 to 0.82 ± 0.96 au) were comparable to those observed in the placebo group, with no significant differences between groups. Conclusions: These findings suggest that supplementation with PLE, ROE, and vitamins A, C, D, and E provides systemic photoprotection by enhancing UV tolerance and reducing erythema without affecting tanning response. This study supports oral supplementation as an adjunct to topical photoprotection, with prolonged use potentially yielding cumulative benefits.

INTRODUCTION: This study describes a prospective, multicentre, randomized controlled, open-label study with three arms aimed at studying the differences between: [Cnt], self-administered sun protection; [T], topical treatment; and [TO], topical + oral treatment; for the management of Actinic Keratosis (AK) in a cohort of subjects of advanced age displaying severe actinic damage (SAD). METHODS: Treatments administered to groups [T] and [TO] had a common component, which is a botanical extract, Fernblock, with demonstrated photoprotective activity. RESULTS: In total, 131 subjects were distributed randomly in the three groups, and followed up clinically at three separate time points, beginning of the study (t = 0) and after 6 and 12 months. Analysis of clinical data and examination using reflectance confocal microscopy (RCM) revealed that group [T] and [TO] displayed decreased clinical AK and field cancerization parameters, including the number of new lesions, and reduced the need for additional interventions in these patients. RCM revealed normalization of the keratinocyte layer. Improvements in AK and field cancerization parameters were greatest in the group [TO], suggesting that topical and oral photoprotection improves the clinical and anatomical outcome compared to control conditions. CONCLUSIONS: The combination of topical and oral immune photoprotection provides an advantage compared to topical photoprotection alone. © 2023 The Authors. Photodermatology, Photoimmunology & Photomedicine published by John Wiley & Sons Ltd.

The extract of Polypodium leucotomos is used as a dietary supplement for its ultraviolet radiation-protective properties. Polypodium leucotomos extract reportedly inhibits CYP3A, which is important for drug metabolism in vitro in human microsomes and in vivo in rats. In this study, we explored the inhibitory effect of the P. leucotomos extract on CYP3A4-mediated midazolam metabolism in humans. This open-label, two-period, fixed-sequence study was performed on six healthy, Japanese, male volunteers. During period 1 (control), midazolam (1 mg) was orally administered. After a wash-out period of at least 5 days, period 2 was initiated. Subjects ingested P. leucotomos extract (240 mg) once in the morning and once at noon on the day before midazolam administration, and once the next morning (thrice overall). Midazolam was administered as in period 1. Blood samples were regularly collected for 8 hours after drug administration, and serum midazolam concentration was determined by ultra-fast liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters of midazolam were calculated and compared between the two periods. The area under the concentration-time curve was 19.18 ± 3.65 ng h/ml, maximum serum concentration was 7.81 ± 1.25 ng/ml, and half-life was 2.32 ± 0.35 hours during period 2. These parameters did not differ from those recorded in period 1 (area under the concentration-time curve: 18.74 ± 2.97 ng h/ml, maximum serum concentration: 8.78 ± 1.67 ng/ml, half-life: 2.52 ± 0.52 h). Therefore, short-term oral administration of P. leucotomos extract did not cause food-drug interactions mediated by CYP3A4 inhibition in humans. © 2022 the International Society of Dermatology.

BACKGROUND: Actinic keratoses (AKs) are chronic, recurrent precancerous lesions primarily induced by long-term sun exposure, commonly found on sun-exposed areas such as the face, neck, hands, forearms, and lower legs. AKs are prevalent, affecting millions worldwide, and pose a significant risk of transforming into invasive squamous cell carcinomas (SCCs). OBJECTIVE: This systematic review aims to update the scientific evidence on the role of oral bioactives, nutraceuticals, or dietary supplements in the treatment of AKs and field cancerization, while evaluating their safety and efficacy profile. METHODS: A review plan was pre-registered in the PROSPERO database (CRD42023485985). Following the PRISMA guidelines, we identified, selected, and included relevant studies. We screened a total of 234 articles, thoroughly reviewed 38 full texts, and ultimately included 21 articles published from 2013 through 2023 for analysis. RESULTS: The selected studies were categorized into three groups based on the chemical nature of the supplements: polyphenols (11 studies), vitamins (8 studies), and others (2 studies). The studies included preclinical (9) and clinical (12) studies. Clinical trials have demonstrated the efficacy profile of polyphenolic supplements, such as Polypodium leucotomos extract (PLE) and others in improving skin health and reducing the risk of skin cancers. Preclinical studies highlighted the protective effects of polyphenols against UV-induced damage and neoplastic transformation. Vitamin supplementation studies revealed mixed results, with clear data showing benefits in reducing the risk of precancerous lesions and skin cancers after nicotinamide (NAM) treatment, while others did not demonstrate significant protective effects. CONCLUSIONS: The review confirms the efficacy of polyphenols in preventing and treating AKs and related skin conditions. However, the role of vitamins and other supplements requires further investigation due to inconsistent and/or scarce findings. Future clinical trials should focus on diverse populations at higher risk of skin cancer and explore new ingredients as well as combinations of various ingredients to optimize therapeutic

Photoprotective effects of various nutritional components and supplements have been demonstrated in animal and in vitro studies. The objective of this systematic review is to assess the photoprotective effects of various dietary supplements. A systematic review of studies assessing dietary supplements on photoprotective outcomes was performed. Human studies were retrieved from PubMed, Embase, and Cochrane in February 2023. Supplement keywords included "dietary supplements," "vitamins," "minerals," "carotenoids," "lutein," "isoflavones," "polyphenols," "Polypodium leucotomos," "heliocare," "herbal medicine," "probiotics," "prebiotics," "astaxanthin," "rosmarinic acid," "botanical," and "herb," and outcome keywords included "photoprotection," "ultraviolet rays," UVA," "UVB," and "blue light." A total of 47 studies were included in the systematic review. Studied supplements included carotenoids, polyphenols, Polypodium leucotomos (PL), melon concentrate, vitamins, coenzyme Q, squalene, and omega-3 and omega-6 fatty acids. Some studies evaluated mixed supplementation and incorporated other active ingredients such as selenium and probiotics. The greatest evidence of photoprotection exists for polyphenols, carotenoid-based, and PL supplementation. While flavanol supplementation exhibited dose-dependency, dose-dependency could not be consistently demonstrated for polyphenol supplementation. The weakest evidence exists for photoprotective effects of isolated vitamin or coenzyme Q supplementation. Dietary supplements may promote enhanced photoprotection, although current evidence is limited by small sample size and short duration. Supplementation with photoprotective active ingredients may be especially favorable for individuals with predisposed ultraviolet sensitivity, such as those with polymorphic light eruption. Future research is necessary to determine optimal dosing and supplementation duration for intended photoprotective outcomes.

Currently available treatment options for melasma include prevention of UV radiation, topical lightening agents, chemical peels, and light-based and laser therapies. However, none have shown effective and sustained results, with incomplete clearance and frequent recurrences. There has been increasing interest recently in oral medications and dietary supplements in improving melasma. We sought to evaluate the efficacy and safety/tolerability of oral medications and dietary supplements for the treatment of melasma. Multiple databases were systematically searched for randomized clinical trials (RCTs) evaluating the use of oral medication for treatment of melasma alone or in combination with other treatments. A total of eight RCTs met inclusion criteria. Oral medications and dietary supplements evaluated include tranexamic acid, Polypodium leucotomos extract, beta-carotenoid, melatonin, and procyanidin. These agents appear to have a beneficial effect on melasma improvement. In conclusion, oral medications have a role in melasma treatment and have been shown to be efficacious and tolerable with a minimal number and severity of adverse events. Therefore, dermatologists should keep oral medications and dietary supplements in their armamentarium for the treatment of melasma. © 2017 The International Society of Dermatology.

Vitiligo is a common, acquired disorder of skin pigmentation that can significantly impact quality of life. It often represents a therapeutic challenge, which has resulted in interest in alternative treatments such as herbal and vitamin supplements. In this review, we provide an overview of the most commonly studied complementary agents, describe proposed mechanisms of action, identify potential adverse effects, and discuss the primary evidence supporting their use. Our discussion focuses on L-phenylalanine, Polypodium leucotomos, khellin, Ginkgo biloba, and vitamins and minerals, including vitamins B12, C, and E, folic acid, and zinc used as monotherapy or in combination with other treatments for the management of vitiligo.

136. J Am Acad Dermatol. 2010 Mar;62(3):511-3. doi: 10.1016/j.jaad.2009.05.045. Decrease of ultraviolet A light-induced "common deletion" in healthy volunteers after oral Polypodium leucotomos extract supplement in a randomized clinical trial. Villa A, Viera MH, Amini S, Huo R, Perez O, Ruiz P, Amador A, Elgart G, Berman B.

BACKGROUND: Around one per cent of the world's population has vitiligo, a disease which causes white patches on the skin. There are a variety of treatments available, most of which are unsatisfactory. OBJECTIVES: To assess all interventions used to manage vitiligo. SEARCH STRATEGY: In November 2009 we updated searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 4, 2009), MEDLINE, EMBASE, AMED, PsycINFO, LILACS and ongoing trials databases. SELECTION CRITERIA: Randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: At least 2 review authors independently assessed study eligibility and methodological quality, and carried out data extraction. Two of the 57 included studies could be combined for meta-analysis. MAIN RESULTS: In this update, 57 trials, including 19 from the original review, were assessed with 3139 participants. Most of the RCTs, which covered a wide range of interventions, had fewer than 50 participants. All of the studies assessed repigmentation, 6 measured cessation of spread, and 5 investigated the effect of treatment on quality of life.Most of the studies assessed combination therapies which generally reported better results. New interventions include monochromatic excimer light (MEL), Polypodium leucotomos, melanocyte transplantation, oral antioxidants, Chinese zengse pill, and pimecrolimus. We analysed the data from 28 studies that met our outcome criteria of improvement in quality of life and greater than 75% repigmentation.Fifteen analyses from studies comparing various interventions showed a statistically significant difference between the proportions of participants achieving more than 75% repigmentation. The majority of analyses showing statistically significant differences were from studies that assessed combination interventions which generally included some form of light treatment.Topical preparations, in particular corticosteroids, reported most adverse effects. However, in the combination studies it was difficult to ascertain which treatment caused these effects. None of the studies was able to demonstrate long-term benefits. Very few stud

BACKGROUND: Polypodium leucotomos extract (PLE), a fern plant product with strong anti-inflammatory and immunomodulatory properties, has been employed to reduce photoaging and skin cancer. PLE may also serve as an adjuvant treatment for psoriasis, vitiligo, atopic dermatitis, photodermatoses, and melasma. This systematic review synthesizes the current data on PLE usage to manage dermatological diseases. METHODS: This systematic review followed the Agency for Healthcare Research and Quality (AHRQ) Methods Guide for Effectiveness and Comparative Effectiveness Reviews and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMSA) guidelines. PubMed/MEDLINE, Embase, and Cochrane Library were queried using keywords. Articles were screened for inclusion and subsequently grouped by dermatological condition. RESULTS: Twenty-one of the 152 identified articles met inclusion criteria, including 11 randomized controlled trials and 5 treatment trials. Implicated dermatological conditions were photoaging/skin cancer (9 studies), actinic keratosis (3), photodermatoses (3), melasma (2), vitiligo (3), and atopic dermatitis (1). A thorough article review revealed several potential applications of PLE. CONCLUSION: PLE exhibits strong therapeutic potential with an encouraging safety profile. It has photoprotective and immunomodulatory properties, underscoring its potential as an adjuvant therapy for multiple dermatological conditions. J Drugs Dermatol. 2025;24(4):346-351. doi:10.36849/JDD.8410R1.

137. An Bras Dermatol. 2023 Mar-Apr;98(2):232-236. doi: 10.1016/j.abd.2022.04.006. Epub 2022 Dec 23. Efficacy of oral Polypodium leucotomos, colchicine cream and ingenol mebutate in the treatment of actinic keratoses and cutaneous field cancerization: a randomized clinical trial. Miola AC(1), Miot HA(2). Author information: (1)Department of Dermatology, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil. Electronic address: [email protected]. (2)Department of Dermatology, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil. DOI: 10.1016/j.abd.2022.04.006 PMCID: PMC9984694 PMID: 36567168 [Indexed for MEDLINE]

Polypodium leucotomos displayed a synergic effect with NB-UVB in psoriasis, but its application on vitiligo remains understudied. The aim of this study was to investigate whether oral supplementation with leaves extract of Polypodium leucotomos (PL) improves narrow band (NB) UVB phototherapy-induced repigmentation. Forty-four patients with generalized vitiligo were enrolled in this randomized, prospective, placebo controlled study. Twenty-three patients were randomly selected to receive combined treatment with NB-UVB phototherapy and 480 mg oral PL twice daily while 21 patients received NB-UVB phototherapy combined with placebo. All subjects were treated with NB-UVB twice weekly for 6 months. Our results demonstrated that oral PL combined with NB-UVB improved repigmentation as well as increased the response rate compared with patients treated with NB-UVB alone (47.8% vs 22%). Our study suggests that oral supplementation of PL and NB-UVB phototherapy enhance the extent of repigmentation. © 2021 Wiley Periodicals LLC.

Background: Vitiligo is an autoimmune skin condition that affects people globally anywhere, from <0.1% to more than 8% of individuals. The disease destroys skin melanocytes, resulting in a patchy depigmentation of the skin. About 50% of all patients develop the disease before their 20s. Methods: We systematically searched the literature and reviewed the evidence for the use of nutritional supplements and diet in the management of vitiligo. Embase and Medline were searched for diet, herbal, and nutrition-based clinical studies. Additional filters were applied that looked for controlled trial or randomized controlled trial and article or article in press or letter and English and clinical study. We selected clinical studies in humans that showed how diet or natural supplements can improve the symptoms of vitiligo in all of our searches. Results: There were 62 manuscripts that resulted from the PubMed search and 259 from the Embase search. A final of 26 studies were reviewed, and other supplemental case and case-control studies were used to introduce diet components that may influence either exacerbation or amelioration of vitiligo. Possible mechanisms of action are introduced for natural and supplemental interventions. Conclusion: Some of the supplements reviewed include Gingko biloba, oral Polypodium leucotomos, alpha lipoic acid, vitamins B12, D, and E, folic acid, phenylalanine, canthaxanthin, Nigella sativa oil, and other combined herbal bio-actives. Overall, the growing evidence is promising, but more studies are needed in this area to further explore the impact that supplements and diet can have on vitiligo management. The most promising therapies included oral phenylalanine as adjuvant therapy with UVA therapy, oral G. biloba as monotherapy, both of which can be used with other traditional therapies, and oral P. leucotomos with phototherapy or photochemotherapy.

OBJECTIVES: Polypodium leucotomos extract is a commonly used systemic photoprotective agent. In an exploratory fashion, the current study aimed to compare the effects of oral supplementation with a fixed Polypodium leucotomos/pomegranate combination (PPmix®) versus Polypodium leucotomos alone (Fernblock®) on skin biophysical parameters of Caucasian adults. METHODS: Forty healthy adult volunteers (20 males and 20 females; mean age: 37.2±5.5 years) were randomized in a 1:1 fashion to a fixed Polypodium leucotomos/pomegranate combination (480 mg/day; n=20) or Polypodium leucotomos alone (480 mg/day; n=20) for 3 months. Six skin biophysical parameters (skin sebum content, hydration, transepidermal water loss [TEWL], erythema index, melanin index, and elasticity) were measured at baseline and after 3 months by personnel blinded to participant allocation. RESULTS: At the end of the study, hydration and elasticity were significantly improved and TEWL was reduced in both groups, without significant intergroup differences. The erythema index was decreased by both treatments, although the fixed Polypodium leucotomos/pomegranate combination was significantly more effective. Finally, melanin index and skin sebum content were reduced by the fixed Polypodium leucotomos/pomegranate combination, whereas Polypodium leucotomos alone did not affect them. CONCLUSIONS: Our results suggest that a fixed Polypodium leucotomos/pomegranate combination provides a greater improvement of skin biophysical parameters compared to Polypodium leucotomos alone in adult Caucasians. Our findings may have implications for optimizing systemic skin photoprotection and beautification strategies.

BACKGROUND: Actinic keratoses (AKs) are a common premalignant skin condition. Many treatments are available for AKs. Photodynamic therapy (PDT) is one of the most effective treatments. However, major concerns exist on the possibility of PDT-induced DNA-mutagenesis/immunosuppression, leading to AKs recurrence/treatment failure. An extract (PLE) from the fern polypodium leucotomos reduces UV-induced immunosuppression and mutagenesis. OBJECTIVE: To assess the ability of PLE to enhance the efficacy of PDT treatment, reducing AKs recurrence on the scalp. MATERIALS AND METHODS: Thirty-four bald patients presenting at least two AKs on the scalp were alternatively assigned to two groups. Both groups underwent two PDT-sessions one-week apart. The first group began oral PLE supplementation one week after the last PDT session. Evaluation of the effect of PLE supplementation was performed by direct inspection of the bald areas, lesions count, and photodynamic diagnosis assessment at 2 and 6 months. RESULTS: Both groups were homogeneous in terms of skin phototype and previous UV exposure. Mean age was 75.7 ± 7.8 years and 76.5 ± 5.5 years, respectively. Both treatment modalities were successful in reducing AKs number (p < .001). However, PLE supplementation increased clearance rate compared with PDT alone (p = .040). CONCLUSION: Polypodium leucotomos improves PDT clearance and decreases AK recurrence rate at 6 months, suggesting its use as a complementary agent in the treatment of field cancerization.

11. J Drugs Dermatol. 2015 Mar;14(3):254-61. Polypodium leucotomos extract: a status report on clinical efficacy and safety. Winkelmann RR, Del Rosso J, Rigel DS. 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.

138. JAMA Dermatol. 2013 Aug;149(8):981-3. doi: 10.1001/jamadermatol.2013.4294. A randomized, double-blinded, placebo-controlled trial of oral Polypodium leucotomos extract as an adjunct to sunscreen in the treatment of melasma. Ahmed AM(1), Lopez I, Perese F, Vasquez R, Hynan LS, Chong B, Pandya AG. Author information: (1)Department of Dermatology, University of Texas Southwestern Medical Center, Dallas. DOI: 10.1001/jamadermatol.2013.4294 PMID: 23740292 [Indexed for MEDLINE]

INTRODUCTION: Topical corticosteroids are used to treat inflammation and relieve itching in atopic dermatitis, but their use is limited by adverse reactions. OBJECTIVES: The main aim of this study was to investigate whether daily treatment with Polypodium leucotomos extract would reduce the use of topical corticosteroids in children and adolescents with atopic dermatitis. We also analyzed oral antihistamine use and changes in disease severity. PATIENTS AND METHODS: We performed a phase IV randomized, double-blind, placebo-controlled, multicenter trial involving 105 patients aged between 2 and 17 years who were receiving topical corticosteroids to treat moderate atopic dermatitis. The patients were randomized to receive, in addition to their standard treatment, Polypodium leucotomos extract or placebo (both in capsule form) for 6 months. The percentage of days on which topical corticosteroids and other atopic dermatitis treatments were used was calculated. RESULTS: Use of Polypodium leucotomos extract did not significantly reduce the mean (SD) percentage of days on which topical corticosteroids were used (11% [12%] vs 12% [11%] for placebo). A significant reduction was, however, observed for oral histamine use (median percentage of days, 4.5% in the Polypodium leucotomos group and 13.6% in the placebo group [P= .038]). The percentage of patients who used oral antihistamines was also lower in the Polypodium leucotomos group. CONCLUSION: Long-term treatment with Polypodium leucotomos extract has benefits for children and adolescents with atopic dermatitis who require pharmacologic treatment to reduce inflammation and relieve itching.