Nine out of 30 (30%) UVA-sensitive and 5 out of 18 (28%) UVB-sensitive subjects had negative photoprovocation tests with the addition of PL. Polypodium leucotomos Extract use to prevent and reduce the risk of infectious diseases in high performance athletes. Not all dark spots are equal- some can be more stubborn than others. Drs. To our knowledge, no studies have been performed to assess the efficacy of PL on prevention of drug-induced phototoxicity, and I believe it a worthwhile avenue of exploration. Patients were exposed to set doses of artificial UVA light with or without pretreatment with PL. Polypodium leucotomos extract has been used as a naturopathic medicine during the last three decades for the alleviation of vitiligo, psoriasis, dermatitis and multiple sclerosis. A second photoprovocation, identical to the first, followed on Days 21–28 at locations in the immediate vicinity to those that had been exposed to UV at baseline. Chemoprophylaxis for acute and chronic phototoxicity (skin cancer, anti-aging, sunburn). The study included 35 bald men with at least two AKs on the scalp that underwent two PDT sessions one week apart. Polypodium leucotomos extract can also be used to protect against photochemotherapy (PUVA)-induced skin phototoxicity. All patients received 720mg of PL in three divided doses plus 360mg in a single dose 24h and 3h prior to a second MED assessment. These dimers down-regulate the tumor suppressor gene, p53, making cells resistant to apoptosis and able to enter mitosis without adequate DNA repair.3,6 Secondly, indirect DNA photodamage (mainly UVA) via ROS formation promotes generation of 8-hydroxy-2’-deoxyguanosine (8-OH-dG), which is a cell marker of oxidative damage. The study concluded that PL is a useful adjunctive for treatment of melasma.12, Photosensitive dermatoses (polymorphic light eruption and solar urticaria). The study hypothesized that combination of PL with topical hydroquinone 4% and sunscreen (SPF50) would be more than effect than the combination of hydroquinone and sunscreen alone. This upregulation causes increased COX-2 and PGE2 production, which contribute to the earliest stages of inflammation. The photo-protective properties of polypodium leucotomos extract are enhanced by using state-of-the-art mineral and chemical filters in the topical products. When taken orally, P. leucotomos provides some degree of protection against the harmful effects of ultraviolet radiation,3,4 thereby helping to minimize the photoaging effects of sunlight, including hyperpigmentation and textural changes.5 P. leucotomos may owe its ability to help in preventing the photoaging process specifically by maintaining the structural integrity of the … Objective: Here, we review the mechanism of action and current dermatologic applications of PL and extrapolate potential future dermatologic applications of PL. Dermatologists explain the polypodium leucotomos benefits for protecting skin from UV rays, sun damage and oxidative stress. Early research also suggests that taking a specific Polypodium leucotomos extract (Difur by Cantabria Farmaceutica) or applying a lotion containing Polypodium leucotomos extract before light exposure might decrease skin damage in people with psoralen-sensitized skin. Topical sunscreens require frequent reapplication, and the dosing is often inconsistent and inadequate.8 Oxybenzone (benzophenone-3) is a widely used UVB and UVA2 sunscreen in the United States. On Day 7, all 30 subjects with a positive reaction to UVA, UVB, or both were started on a daily dose of PL (Fernblock) according to body weight (<55kg=720mg QD, 56–70kg=960mg QD, >70kg=1200mg QD) for two weeks. This encompassing MOA, ability to provide photoprotection that extends beyond UVR, its proven efficacy in PMLE, and two promising case studies revealing efficacy of PL in a patient with SCLE and a patient with PCT, yield promising implications for its use in photosensitive dermatoses.1–35, Based on PL’s documented safety profile11,13 and its potential to reduce phototoxicity and potentially decrease manifestations of certain dermatologic conditions (Table 1),1–35 the authors find it acceptable to recommend use of PL to patients in order to optimize photoprotection in conjunction with daily sunscreen use. The effect might be more pronounced in Fitzpatrick II to III skin types, but Types IV to V were unable to be evaluated due to low patient numbers.21,24. The effects of sun exposure on the skin and specifically those related to pigmentation disorders are well known. The antioxidants found in this fern, caffeic acid and ferulic acid work to protect your skin from the harmful sun exposure. Microscopically, these dark spots are collections of melanin, a type of pigment that looks dark brown or black. MelasQOL (melasma-related quality of life), MASI (melasma assessment severity index), photos, and subject’s self-assessment were used for results. A Retrospective Study of 3,000 Indian Patients with Vitiligo Treated with Phototherapy or Topical Monotherapy, Low-power Fractional Carbon Dioxide Laser Followed by Jessner’s Peel versus Jessner’s Peel Alone for the Treatment of Melasma. Polypodium leucotomos extract (PLE), derived from the tropical fern of the Polypodiaceae family, has properties … Dermal fibroblasts are the major cell type in the dermis and are major contributors to maintenance of the ECM. The results were based on patient report of usual skin manifestation occurrence and if affirmative, the relative severity and number of episodes along with subjective symptoms compared with previous years. Reaching statistical significance, the colorimetry relative-erythema intensity post-PLE was eight percent lower (p<0.05) and the histologic biomarkers of UVB irradiation: DNA damage and apoptosis (sunburn cells, CPDs), inflammation (COX2), proliferation (Cyclin D1, Ki67, and proliferating cell nuclear antigen) were reduced as well (p<0.05).18, A well-known result of chronic phototoxicity is cutaneous carcinogenesis and photoaging. Solar radiation is a human carcinogen ubiquitous in the environment that is responsible for many cutaneous malignancies or skin cancers. On Days 3 and 4, irradiation and evaluation were repeated after ingestion of PLE (240mg PL 2h and 1h prior to exposure). The therapeutic goal in vitiligo treatment is to make the vitiligo less noticeable by restoring lost pigment or eliminating remaining pigment. [23] Acute cutaneous effects of UVR are explored in depth by Jansen et al8 and include: erythema or “sunburn’,” immediate pigment darkening (IPD), persistent pigment darkening (PPD), delayed tanning, epidermal hyperplasia, free radical formation, and vitamin D synthesis. This proposes a potential site of action for PL due to its anti-inflammatory properties observed in in-vitro studies, including ROS scavenging and decreased cytokine and prostaglandin release.21, PL is a natural compound with origins in traditional medicine that the authors, believe has numerous potential clinical benefits in dermatology. These are important pathways in cell proliferation, cell death, and cell survival. Lastly, due to the demonstrated photoprotective properties of PL, the authors suggest that the addition of PL to drug regimens associated with cutaneous phototoxicity, such as doxycycline, might help prevent occurence of this adverse event. This correlate’s PL’s inhibitory effect on keratinocyte elastase activity.7, Pharmacokinetics of Polypodium leucotomos. OBJECTIVE: The purpose of this review is to investigate the beneficial role of Polypodium leucotomos as an adjunct treatment for vitiligo, melasma, and postinflammatory hyperpigmentation. You can take supplements to prevent similar problems. 3, Infrared radiation (IR) is postulated to cause and enhance actinic sun damage (aging) and can be divided into three subcategories: IR-A (760nm–1400nm), IR-B (1400–3000nm), and IR-C (3000nm–1mm). Recent data suggests skin cancer accounts for at least 40 percent of all human malignancies.3 It is also a major cause of photoaging.3,7 While UV light is the most notable offender, recent studies give validity to the role of IR and VIS light in photocarcinogenesis and photoaging as well. Solar urticaria has been minimally studied in Caccialanza’s two human studies,29,30 examining PL’s effect on idiopathic photodermatoses. However, the photoprotective effect of polypodium leucotomos extract extends beyond just decreasing erythema. Vitamin E, niacinamide, polypodium leucotomos, pycnogenol, grape seed extract, amino fruit acids, phytic acid, zinc, silymarin, Korean red ginseng powder, plant extracts, and parsley all have well-demonstrated evidence of antioxidant properties, and these substances have been studied in the context of skin hyperpigmentation. Biopsy is required for diagnosis, which reveals an absence of epidermal melanocytes. Extensive PUVA treatment results in premature ageing changes in the skin (increased dryness, freckling and wrinkling) and can increase the chance of skin cancer. These antioxidants have been shown to suppress ROS formation by an additional 1.7x for SPF 4 and 2.4x for SPF 15 and 50.4,9 There have been a multitude of in vitro and in vivo clinical studies examining the effect of PL on acute and chronic phototoxicity. Polypodium leucotomos stimulated the expression of TIMPs in fibroblasts and melanoma cells, thereby aiding the health of the skin. Journal of Long-Term effects of Medical Implants 2004;14(4):317-340, Middelkamp-Hup MA, Pathak MA, Parrado C et al. MelasQOL scores on Day 84 revealed statistically significant improvement in the PLE group (p<0.05). Post-inflammatory hyperpigmentation occurs as brown macules or patches, often with a poorly defined border, irregular in outline and usually with little surface change. Objective: The purpose of this review is to investigate the beneficial role of Polypodium leucotomos as an adjunct treatment for vitiligo, melasma, and postinflammatory hyperpigmentation. Heliocare helps those of us with melasma, by helping us become more resistant to the sun’s harmful rays from the inside out. » Here's what you need to know. High-dose UVA2 can also result in an “immediate erythema reaction” lasting 48 to 72 hours post-exposure. While the results of PL use in patients with solar urticaria were not favorable, this could be due to low study power and a study with more subjects might be beneficial to determine its effectiveness in this patient population. Also, the inhibition of apoptosis and cell death of fibroblasts and keratinocytes prevents the concomitant local inflammatory response via modulation of the Th1/Th2 response. 3 Locally known as “calaguala” in reference to the species and “anapsos” when referring to the extracts, 1 PL was traditionally used for treatment of the inflammatory skin disorders, psoriasis and atopic dermatitis. In the dermis, cathespins are expressed during abnormal circumstances, such as scarring and inflammation, for example, after exposure to VIS and wIRA light. This allows it to reduce the free radicals generated by both UV and potentially VL radiation. The study resulted in 73.68 percent patients improving: 43.86 percent noted improvement, while 29.82 percent noted complete clearance (p<0.05).5,30. If you have any concerns with your skin or its treatment, see a dermatologist for advice. Polypodium leucotomos This is a fern native to Central and South America. 850mg for a 250lb person. Zhou LL, Baibergenova A. Melasma: Systematic review of the systemic treatments. induced chemokine CXCL10 as key immune mediators for melanocyte destruction in patients with vitiligo.21, A universally effective treatment for vitiligo has not yet been discovered. It was found that PL promoted ELN expression in fibroblasts. Phototoxicity is an ubiquitous concern in dermatologic care and the search for novel agents for photoprotection is ongoing. PL’s photoprotective and immunomodulatory properties can serve as postulated mechanisms of action. The latest in this league is a specific fern extract called Polypodium leucotomos (PL), which seems to be effective to a certain extent in providing photoprotection, when taken orally. The PL group was found to have a statistically significant increased rate of AK clearance compared with PDT alone (p=0.04). Polypodium leucotomos extract (PLE) comes from a tropical fern plant grown in Central and South America. For example, subacute cutaneous lupus erythematosus (SCLE), a photosensitive autoimmune disease might respond favorably to adjunct treatment with PL. It has recently been shown that blue light leads to the induction of oxidative stress and long-lasting pigmentation. Polypodium leucotomos has also been shown to be beneficial for the prevention and potential treatment of several aesthetically relevant conditions. Hyperpigmentation can occur due to nutritional deficiencies, such as a lack of vitamin B 12, especially in darker-skinned people. Grimes PE, Nashawati R. The role of diet and supplements in vitiligo management. PL response rates were higher in patients with lower basal MEDs and dark eyes (p<0.05); both serve as independent positive prognostic indicators.14, Oral PL is beneficial in patients at high risk for MM due to its photoprotective properties (p<0.005). Results: See Table 1 for a summary of dermatologic applications of PL based on available human clinical studies. 700mg for a 200lb person. While results did not reach statistical significance, possibly due to small sample size, there was strong evidence of blunted increase in common deletion in patients treated with PL compared with those without, suggesting PL might prevent UVA-induced photodamage by preventing UVA-dependent mtDNA damage.1,19 Molecular evidence has shown that wIRA and VIS light spectra also contribute to photoaging and in vitro studies using human dermal fibroblasts revealed that PL prevents these changes associated with cutaneous photoaging.7, Vitiligo. Solar elastosis is a haphazard deposit of elastic fibers indicative of cutaneous photoaging. If PL serves to significantly reduce associated pruritus, the atopic population might see clinical benefit via (1) reduced symptomatology, (2) less intake of oral antihistamines, which can cause undesirable side effects such as sedation, and (3) reduced incidence of traumatic excoriation of the lesions leading to quicker healing time and reduced incidence of secondary infection. PL has demonstrated, in vivo, the ability to inhibit glutathione peroxidation in the epidermis and peripheral tissues by a measured increase in GSH/GSSG ratio. Delayed tanning, caused by UVA and UVB, has a timeline that begins three days post-exposure and remains for many weeks. Polypodium leucotomos is a fern from Central America. Long-term follow up would be ideal to monitor efficacy of PL in this population.10,14, Actinic keratoses. Oral PL significantly increased the MED in all patients (p<0.05), with a higher post-PL MED in women compared with men (p<0.05). Infect Drug Resist. VIS and wIRA also result in opposing expression of Elastin (ELN) with VIS causing increased expression and wIRA resulting in decreased expression of Elastin.7. This expression was prevented with PL.7 Fibrillins 1 and 2 (FBN1 and FBN2) are components of extracellular microfibrils that have a role in elastin assembly during elastic fiber formation. It possesses beneficial properties attributed to the presence of numerous compounds with photoprotective and antioxidant properties (Nestor et al., 2014). » Native Americans have used the plant extract for centuries for the treatment of inflammatory disorders and skin diseases. Polypodium leucotomos stimulated collagen in both UV radiated and non-irradiated fibroblasts. Free radical formation occurs after UV exposure in the form of reactive oxygen species: singlet oxygen, hydrogen peroxide, and superoxide radicals. Or alternatively, a topical skin cream containing 0.1% polypodium leucotomos … Additionally, PL has been proposed as a potential agent in vitiligo management due to its antioxidant, anti-apoptotic, immunomodulatory, and anti-inflammatory properties. This patient achieved near total remission with the addition of PL to her treatment regimen, suggesting it might have future applications in photosensitizing dermatoses, including other forms of cutaneous lupus erythematosus.34. For the remaining subjects, the mean number of exposures required to produce PMLE lesions increased from 1.95 at baseline yielded 2.62 with PL for UVA (p=0.005) and from 2.38 at baseline yielded 2.92 with PL for UVB (p=0.047). Breithaupt AD, Jacob SE. Melasma. UVR (200–400nm) is subdivided into three categories: UVA (315–400nm), UVB (280–315nm), and UVC (100–280nm). Sponsored content: melanomas are notoriously difficult to discover and diagnose. Tanew et al,28 conducted a study in to investigate PL’s efficacy in inhibiting the photoinduction of PMLE lesions via repetitive irradiation with artificial UVA and UVB light. Fourteen percent of PL group and 17 percent placebo group reported mild improvement.10,21,25 Ahmed et al27 conducted a RCT with 40 hispanic female subjects with moderate to severe melasma defined by a melanin index >30 (the difference between affected skin and normal skin using narrowband reflectance specrophotometry). Native Americans have used the plant extract for centuries for the treatment of inflammatory disorders and skin diseases. It’s sold under the brand names Kalawalla and Heliocare. VIS has been reported to cause a temporary darkening of the skin called immediate pigment darkening (IPD) that can become a persistent darkening, known as persistent pigment darkening (PPD). Each article was thoroughly studied by all authors and applicable data from each was used for the compilation of this review article. Orally administered Polypodium leucotomos extract decreases psoralen-UVA-induced phototoxicity, pigmentation, and damage of human skin. Repigmentation in the trunk, extremities, hands, and feet was not as successful. PUVA therapy, psoralen-UVA 320–400nm, has been a standard vitiligo therapy for years. Polypodium leucotomos (PL) is a fern with origins in Central and South America where it has a historical role in traditional medicine.1,2 PL belongs to the Polypodiaceae family, genus Phlebodium.3 Locally known as “calaguala” in reference to the species and “anapsos” when referring to the extracts,1 PL was traditionally used for treatment of the inflammatory skin disorders, psoriasis and atopic dermatitis.3 Additionally, its anti-carcinogenic effect has been alluded to for over 50 years.1 PL has demonstrated the ability to lessen the harmful cutaneous effects of solar radiation with action in ultraviolet, infrared, and visible light spectra 3 in multiple in vitro and in vivo human and animal studies. UVC is considered negligible as it is completely filtered by the ozone. These results were expected as previous studies have shown UVA as the major etiological waveband involved in eliciting PMLE lesions. One polypodium leucotomos extract (Fernblock, Cantabria Farmaceutica) has been used safely for up to 2 days. Topics A–Z In addition to preventing many harmful effects associated with sunlight exposure, orally administered Polypodium leucotomos also appears to provide adjunctive benefits in treating and managing vitiligo and melasma, and may have the potential to help with postinflammatory hyperpigmentation. For localized vitiligo the 308nm excimer laser is preferred therapy; efficacy is increased with adjunctive topical agents such as corticosteroids, calcineurin inhibitors, and calcipotriol.21. During analysis, the study found that patients with at least one RHV had a tendency toward lower basal MED. At two months and six months after beginning oral PL, the bald areas were assessed. Abstract: Melasma is a common pigmentary disorder with a multifactorial etiology that can hinder its management. While ELN expression increased with and without VIS and/or wIRA irradiation with PL, ELN expression was markedly increased with prior irradiation followed by PL treatment. Furthermore, a human study13,1 assessed the safety of Heliocare 240mg taken twice daily in 40 subjects based on history, physical exam, and laboratory values. The inflammatory pathogenesis of PIH involves intermediates of the inflammatory COX pathway such as prostaglandin E2, leukotriene C4, leukotriene D4 and thromboxane 2, and resultant ROS generation. Heliocare’s active ingredient is the Polypodium leucotomos fern. Hyperpigmentation refers to the patches of skin that are darker than the surrounding skin, such as freckles, melasma, lentigos, hori’s nevus…etc. The atypical keratinocytes that result from COX-2 are believed to correlate clinically with photodamage and possible AK/SCC.10,33, PL inhibits skin immunosuppression via multiple mechanisms. Genes that confer moderate risk include variants in the melanocortin 1 receptor (MC1R) which produces variable quantities of red/yellow pheomelanin pigment that has a role in inducing oxidative cell-damage instead of the photoprotective black eumelanin. Its photoprotective properties make it an attractive substance to potentially utilize, not only for the prevention of cutaneous phototoxicity, but also for the prevention and treatment of other photosensitive cutaneous conditions. Polypodium leucotomos has also been shown to be beneficial for the prevention and potential treatment of several aesthetically relevant conditions. Melasma, a disorder of pigmentation occurring on sun-exposed areas of skin, is influenced by exposure to UV and visible lights, genetic factors and hormonal influences such as pregnancy and hormonal contraception/replacement. Fair-skinned individuals or those with previous sun or radiation damage are most at risk. The antioxidants found in this fern, caffeic acid and ferulic acid work to protect your skin from the harmful sun exposure. VIS and wIRA had contrasting effects on the expression of Fibrillin 1 (FBN1), a protein with effects on force bearing structural support, and Fibrillin 2 (FBN2), which is involved in elastic fiber assembly: VIS caused an increase in expression of FBN1 and FBN2, while wIRA caused a decrease in expression of both compared with control. These are thought to be a major consequence of UVA and result in deleterious acute effects that include damage to DNA, proteins, and cell membranes. However, there are many reports of allergic and photoallergic contact dermatitis and concerns of environmental contamination of coral reefs.9 PL shows promise as an agent that is both environmentally friendly and as an agent with an ability to block broad spectrum solar irradiation.5 Some sunscreens have already begun to implement antioxidants in their formula: these include vitamin A (retinol), vitamin C (ascorbic acid), vitamin E (a-tocopherol), and a polyphenol component of green tea. “Polypodium leucotomos” was input as the key search criterion. Polypodium leucotomos (Phlebodium aureum) is a tropical fern available in capsules and topical creams. normally functions to allow increases in collagen gene transcription. PL has effects on many molecules in the ECM: for example, it inhibits MMPs, increases TIMPs, increases the secretion of elastin, reduces Cathespin K expression, and increases both Fibrillin 1 and Fibrillin 2 expression.7 Matrix Metalloproteinases (MMPs) are collagenolytic enzymes that break down interstitial Collagen 1, 2, and 3, resulting in production of a substance called gelatin. There are two categories of sunscreens: (1) physical sunscreens: contain zinc oxide and titanium dioxide and (2) chemical sunscreens: contain organic PABA, cinnamates, salicylates, and benzophenones. PL exerts vast biological effects within the human biome, of which not all are relevant to its dermatologic benefits. The subjects were all of Fitzpatrick Skin Type III or IV. (2012) ^ a b c Rodríguez-Yanes E, et al. Author: Vanessa Ngan, Staff Writer, 2005. FUNDING: This study was funded by Topix Pharmaceuticals Inc. In cutaneous porphyrias, porphyrin can accumulate to abnormally high levels and cause photosensitivity.8 The accumulation of water-soluble porphyrins in the skin causes formation of vesicles and bullae on sun-exposed skin.35 With PL’s demonstrated efficacy as a potent antioxidant and demonstrated of activity within the VIS light spectrum,3 the authors suggest it can be of benefit in patients with dermatologic manifestations of cutaneous porphyrias.