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Abstracts

Life Extension Magazine July 2010
Abstracts

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Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin.

BACKGROUND: UV radiation induces damage to human skin. Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL). METHODS: A total of 9 healthy participants of skin types II to III were exposed to varying doses of artificial UV radiation without and after oral administration of PL (7.5 mg/kg). At 24 hours after exposure the erythema reaction was assessed and paired biopsy specimens were obtained from PL-treated and untreated skin. RESULTS: A significant decrease in erythema was found in PL-treated skin (P < .01). Histologically, PL-treated biopsy specimens showed less sunburn cells (P < .05), cyclobutane pyrimidine dimers (P < .001), proliferating epidermal cells (P < .001), and dermal mast cell infiltration (P < .05). A trend toward Langerhans cell preservation was seen. CONCLUSION: Oral administration of PL is an effective systemic chemophotoprotective agent leading to significant protection of skin against UV radiation.

J Am Acad Dermatol. 2004 Dec;51(6):910-8

Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin.

Sunburn, immune suppression, photoaging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photoprotection, are helpful and can be achieved by topical sunscreening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo inmunomodulating properties. Its beneficial photoprotective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photoprotective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photoprotective after topical application as well as oral administration. PL increased UV dose required for IPD (P < 0.01), MED (P < 0.001) and MPD (P < 0.001). After oral administration of PL, MED increased 2.8 +/- 0.59 times and MPD increased 2.75 +/- 0.5 and 6.8 +/- 1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photoprotection of Langherhans cells by oral as well as topical PL. The observed photoprotective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photoprotection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such phototherapies.

Photodermatol Photoimmunol Photomed. 1997 Feb-Apr;13(1-2):50-60

Mechanistic insights in the use of a Polypodium leucotomos extract as an oral and topical photoprotective agent.

Photoprotection is essential to prevent the deleterious effects of ultraviolet (UV) light, including skin cancer, photoaging and immunosuppression. Photoprotective agents can be classified according to their main mechanism of action. Some of them absorb or deflect UV photons (sunscreens), whereas others prevent or fix the deleterious effects of UV exposure. Here, we review recent evidence on the cellular and molecular mechanisms underlying the photoprotective effect of a Polypodium leucotomos fern extract (PL). PL is a natural mixture of phytochemicals endowed with powerful antioxidant properties. 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. A striking property is that PL can exert its effect when administered orally. Together, these effects postulate PL as a natural photoprotective agent and a potential adjuvant to phototherapy for various skin diseases.

Photochem Photobiol Sci. 2010 Apr;9(4):559-63

Incidence estimate of nonmelanoma skin cancer in the United States, 2006.

OBJECTIVES: To estimate the incidence of nonmelanoma skin cancer (NMSC) in the US population in 2006 and secondarily to indicate trends in numbers of procedures for skin cancer treatment. DESIGN: A descriptive analysis of population-based claims and US Census Bureau data combined with a population-based cross-sectional survey using multiple US government data sets, including the Centers for Medicare and Medicaid Services Fee-for-Service Physicians Claims databases, to calculate totals of skin cancer procedures performed for Medicare beneficiaries in 1992 and from 1996 to 2006 and related parameters. The National Ambulatory Medical Care Service database was used to estimate NMSC-related office visits. We combined these to estimate totals of new skin cancer diagnoses and affected individuals in the overall US population. RESULTS: The total number of procedures for skin cancer in the Medicare fee-for-service population increased by 76.9% from 1,158,298 in 1992 to 2,048,517 in 2006. The age-adjusted procedure rate per year per 100 000 beneficiaries increased from 3,514 in 1992 to 6,075 in 2006. From 2002 to 2006 (the years for which the databases allow procedure linkage to patient demographics and diagnoses), the number of procedures for NMSC in the Medicare population increased by 16.0%. In this period, the number of procedures per affected patient increased by 1.5%, and the number of persons with at least 1 procedure increased by 14.3%. We estimate the total number of NMSCs in the US population in 2006 at 3,507,693 and the total number of persons in the United States treated for NMSC at 2,152,500. CONCLUSIONS: The number of skin cancers in Medicare beneficiaries increased dramatically over the years 1992 to 2006, due mainly to an increase in the number of affected individuals. Using nationally representative databases, we provide evidence of much higher overall totals of skin cancer diagnoses and patients in the US population than previous estimates. These data give the most complete evaluation to date of the underrecognized epidemic of skin cancer in the United States.

Arch Dermatol. 2010 Mar;146(3):283-7

Photoprotective activity of oral polypodium leucotomos extract in 25 patients with idiopathic photodermatoses.

BACKGROUND: The incidences of idiopathic photodermatoses (IP) are increasing and the available therapeutic methods are often inadequate. AIM: To evaluate whether, in subjects affected by IP not responding to the usual available therapies, the oral administration of an extract of Polypodium leucotomos (PL) could provide an effective photoprotective activity. METHODS: 26 patients with polymorphic light eruption and two with solar urticaria were recruited to enter the study. The protocol excluded the use of ultraviolet protection filters or other drugs that could in some way interfere with exposure to light. All patients exposed themselves to sunlight while consuming 480 mg/day of PL orally. The response of the skin to sunlight exposure of 25 evaluable patients was compared with that occurring previously without administration of PL. RESULTS: With PL, we observed a relevant and statistically significant reduction of skin reaction and subjective symptoms. The tolerance of the drug has been excellent. CONCLUSION: PL extract administration has shown to be an effective and safe method, leading to a significant protection of skin in IP.

Photodermatol Photoimmunol Photomed. 2007 Feb;23(1):46-7

Beneficial regulation of matrixmetalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-beta by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells.

The extracellular matrix (ECM) that gives tissue its structural integrity is remodeled in skin aging/photoaging and cancer via the increased expression/activities of matrixmetalloproteinases (MMP), inhibition of the tissue inhibitors of matrix metalloproteinases (TIMP), or inhibition of collagen synthesis. Transforming growth factor-beta (TGF-beta), a predominant regulator of the ECM, is inhibited in aging/photoaging and stimulated in carcinogenesis. P. leucotomos (fern) extract has potential to counteract these alterations via its antioxidant, anti-inflammatory and photoprotective properties. The goal of this research was to determine the efficacy of P. leucotomos to (a) directly inhibit MMP-1, 2, 3, and 9 activities, (b) inhibit MMP-2, and stimulate TIMPs, fibrillar collagens and TGF-beta in non-irradiated or ultraviolet (UV) radiated fibroblasts, and (c) inhibit MMPs and TGF-beta, and stimulate TIMPs in melanoma cells. To this purpose, we examined the direct effect of P. leucotomos (0-1%) on MMPs’ activities, and its effects on the expression (protein and/or transcription levels) of (1) MMPs and TIMPs in dermal fibroblasts, and melanoma cells, (2) TGF-beta in non-irradiated, UVA (2.5 J/cm2) or UVB (2.5 mJ/cm2) irradiated fibroblasts, and melanoma cells, and (3) types I, III, and V collagen in non-irradiated or UV irradiated fibroblasts. P. leucotomos directly inhibited the activities of MMPs as well as the expression of MMPs in fibroblasts, and melanoma cells while stimulating the expression of TIMPs in these cells. P. leucotomos stimulated types I, III, and V collagen in non-irradiated fibroblasts, and types I and V collagen in UV radiated fibroblasts. P. leucotomos had predominant stimulatory effects on TGF-beta expression in non-irradiated or UV radiated fibroblasts, and inhibited TGF-beta expression in melanoma cells. The effects of P. leucotomos were largely similar to that of ascorbic acid. P. leucotomos demonstrated dual protective effects on the ECM via its inhibition of the ECM proteolytic enzymes and the stimulation of the structural ECM collagens. The effects of P. leucotomos on fibroblasts and melanoma cells may be partly via its cell-specific regulation of TGF-beta expression and partly via its antioxidant property. The intake or topical application of P. leucotomos may be beneficial to skin health, in aging and cancer prevention or treatment.

Arch Dermatol Res. 2009 Aug;301(7):487-95

Carotenoids and flavonoids contribute to nutritional protection against skin damage from sunlight.

The concept of photoprotection by dietary means is gaining momentum. Plant constituents such as carotenoids and flavonoids are involved in protection against excess light in plants and contribute to the prevention of UV damage in humans. As micronutrients, they are ingested with the diet and are distributed into light-exposed tissues, such as skin or the eye where they provide systemic photoprotection. beta-Carotene and lycopene prevent UV-induced erythema formation. Likewise, dietary flavanols exhibit photoprotection. After about 10-12 weeks of dietary intervention, a decrease in the sensitivity toward UV-induced erythema was observed in volunteers. Dietary micronutrients may contribute to life-long protection against harmful UV radiation.

Mol Biotechnol. 2007 Sep;37(1):26-30

Nutritional protection against skin damage from sunlight.

The concept of systemic photoprotection by dietary means is gaining momentum. Skin is continuously exposed to ultraviolet (UV) radiation, the major cause of skin disorders such as sunburn, photodamage, and nonmelanoma skin cancer. Most of the erythemal annual UV dose is encountered under nonvacation conditions, when no sunscreen is applied. In the absence of topically added compounds, skin protection depends solely on endogenous defense. Micronutrients can act as UV absorbers, as antioxidants, or can modulate signaling pathways elicited upon UV exposure. UV-induced erythema is a suitable parameter to assess photoprotection. Dietary protection is provided by carotenoids, tocopherols, ascorbate, flavonoids, or n-3 fatty acids, contributing to maintenance resistance as part of lifelong protection.

Annu Rev Nutr. 2004;24:173-200

Photoprotection of UV-irradiated human skin: an antioxidative combination of vitamins E and C, carotenoids, selenium and proanthocyanidins.

Endogenous antioxidants are decreased in skin and blood during UV exposure. Combined supplementation of beta-carotene, alpha-tocopherol and ascorbic acid in addition to topical sunscreens may help to lower the risk of sunburning. Acute UV erythema with sunburn reaction are the most important factors in conjunction with the cumulative life-long UV dose for inducing skin damage resulting in photoageing and precancerous and cancerous lesions. Therefore, a clinical, randomized, double-blind, parallel group, placebo-controlled study was conducted in healthy young female volunteers (skin type II) investigating the preventive, photoprotective effect of supplementation with Seresis, an antioxidative combination containing both lipid and water-soluble compounds: carotenoids (beta-carotene and lycopene), vitamins C and E, selenium and proanthocyanidins. In this study, the oral administration of Seresis appeared to be well tolerated. The preparation contains antioxidant compounds in quantities occurring at physiological levels and can therefore be used safely over a long period of time. Despite the fact that the assessment of the light sensitivity (minimal erythemal dose, chromametry) of the skin did not show any statistically significant differences between the Seresis and the placebo group, a clear statistical trend, however, could be demonstrated, i.e. Seresis was able to slow down the time of the development and grade of UVB-induced erythema. The primary efficacy parameter matrix metalloproteinases 1 (MMP-1) between treatment and placebo group following UV irradiation showed a significant difference (p < 0.05), which occurred due to the fact that after a 2-week UV irradiation, MMP-1 slightly increased (p < 0.03) in the placebo group and decreased (p < 0.044) in the treated group. The MMP-9 changes showed a clear tendency of decrease in the Seresis group (p < 1.393) and increase (p < 0.048) in the placebo group. These data emphasise that supplementation with Seresis decreases the UV-induced expression of MMP-1 and 9, which might be important in photoprotective processes. From our data, we thus finally draw the conclusion that by the combination of antioxidants, such as in the formulation of Seresis, a selective protection of the skin against irradiation can be achieved. This might be important for future recommendations for immediate suppression of the early phase of UV-induced erythema, that means pharmacological prevention of sunburn reaction as well as subsequent chronic skin damage.

Skin Pharmacol Appl Skin Physiol. 2002

Sep-Oct;15(5):307-15

Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced erythema in humans.

BACKGROUND: Carotenoids and tocopherols, known to be efficient antioxidants and capable of scavenging reactive oxygen species generated during photooxidative stress, may protect the skin from ultraviolet light-induced erythema. beta-Carotene is widely used as an oral sun protectant but studies on its protective effects are scarce. OBJECTIVE: The objective of this study was to investigate the protective effects of oral supplementation with carotenoids and a combination of carotenoids and vitamin E against the development of erythema in humans. DESIGN: A carotenoid supplement (25 mg total carotenoids/d) and a combination of the carotenoid supplement and vitamin E [335 mg (500 IU) RRR-alpha-tocopherol/d] were given for 12 wk to healthy volunteers. Erythema was induced by illumination with a blue-light solar simulator. Serum beta-carotene and alpha-tocopherol concentrations and skin carotenoid levels were assessed by HPLC and reflection photometry. RESULTS: Serum beta-carotene and alpha-tocopherol concentrations increased with supplementation. Erythema on dorsal skin (back) was significantly diminished (P < 0.01) after week 8, and erythema suppression was greater with the combination of carotenoids and vitamin E than with carotenoids alone. CONCLUSION: The antioxidants used in this study provided protection against erythema in humans and may be useful for diminishing sensitivity to ultraviolet light.

Am J Clin Nutr. 2000 Mar;71(3):795-8

Basic aspects of psychodermatology.

Psychodermatological or psychocutaneous disorders are conditions resulting from the interaction between the mind and the skin. There are three major groups of psychodermatological disorders; psychophysiologic disorders, psychiatric disorders with dermatologic symptoms, and dermatologic disorders with psychiatric symptoms. Along with the standard dermatological treatment, majority of these disorders can be treated with cognitive-bihevioral psychotherapy, psychoterapeutic stress-and-anxiety-management technicques and psychotropic drugs. Therefore, understanding of biopsychosocial approaches and liaison approach involving general practice, psychiatrist, dermatologist and psychologist treatment in this field is essential.

Psychiatr Danub. 2008 Sep;20(3):415-8

An extract of Polypodium leucotomos appears to minimize certain photoaging changes in a hairless albino mouse animal model. A pilot study.

Chronic ultraviolet B (UVB) exposure of human or murine skin is known to induce cutaneous photoaging and enhanced carcinogenic risk. An extract of Polypodium leucotomos (PL), a tropical fern plant, has been known to exhibit interesting antioxidant and photoprotective properties against acute exposure to ultraviolet radiation. The objective of this preliminary (or pilot) study was to determine the photoprotective role of topically applied Polypodium leucotomos extract in the prevention or amelioration of cutaneous changes of photoaging in hairless mice. PL-treated mice showed significant reduction of skinfold thickness than those observed in PL-untreated controls. Additionally, PL-treated mice showed a significantly lower degree of histologic parameters of photoaging damage, including dermal elastosis, compared with positive control mice. Interestingly, PL treatment also showed reduction in the number of mice showing skin tumors at 8 weeks after the cessation of the UVB exposure protocol. The results of this preliminary study illustrate that PL treatment helped to ameliorate and to partially inhibit some of the histologic damage associated with photoaging of skin and appeared to contribute to a decrease in the prevalence of UVB-induced skin tumors in mice.

Photodermatol Photoimmunol Photomed. 1999 Jun-Aug;15(3-4):120-6

Predominant effects of Polypodium leucotomos on membrane integrity, lipid peroxidation, and expression of elastin and matrixmetalloproteinase-1 in ultraviolet radiation exposed fibroblasts, and keratinocytes.

BACKGROUND: Polypodium leucotomos has been reported to have antioxidant, anti-inflammatory and photoprotective properties. Exposure of skin to ultraviolet (UV) radiation can lead to deposition of excessive elastotic material, reduction in collagen, and increased expression of matrix metalloproteinases (MMPs). OBJECTIVE: The goal of this research was to determine the effects of P. leucotomos in the absence or presence of UVA or UVB radiation on membrane damage, lipid peroxidation, and expression of elastin and MMP-1 in fibroblasts and keratinocytes, respectively. METHODS: Fibroblasts and keratinocytes, respectively, were irradiated by a single exposure to UVA (0.6, 1.8 or 3.6 J) or UVB radiation (0.75, 2.5 or 7.5 mJ), and then incubated with, or without, P. leucotomos (0.01, 0.1 and 1%) and examined for membrane damage, lipid peroxidation, expression of elastin (protein levels) and MMP-1 (protein levels or MMP-1 promoter activity). RESULTS: UV radiation did not significantly alter membrane integrity, lipid peroxidation or MMP-1 expression, but increased elastin expression. P. leucotomos significantly improved membrane integrity, inhibited lipid peroxidation, increased elastin expression, and inhibited MMP-1 expression in both fibroblasts, and keratinocytes. The effects of P. leucotomos predominated in the presence of UVA or UVB in both fibroblasts and keratinocytes, respectively, with the exception of inhibition of MMP-1 protein levels in fibroblasts only in combination with UV radiation. CONCLUSION: Lower concentration of P. leucotomos (lower than 0.1%), may be beneficial in preventing photoaging by improving membrane integrity and inhibiting MMP-1, without increasing elastin expression. Higher concentration (greater than 0.1%) of P. leucotomos may reverse the loss of normal elastic fibers associated with intrinsic aging.

J Dermatol Sci. 2003 Jun;32(1):1-9

Multiple primary melanoma: two-year results from a population-based study.

OBJECTIVE: To assess the frequency of occurrence and risk factors for multiple primary melanoma. DESIGN: Population-based, case-control study. SETTING: New Hampshire. PARTICIPANTS: Three-hundred fifty-four New Hampshire residents with a confirmed first diagnosis of cutaneous melanoma. MAIN OUTCOME MEASURE: Diagnosis of a subsequent primary cutaneous melanoma. RESULTS: An additional melanoma occurred in 27 individuals (8%) within 2 years of their initial diagnosis, including 20 (6%) within the first postdiagnosis year. In 9 (33%) of these 27 cases, at least 1 subsequent melanoma was deeper than the first tumor. The 27 individuals with a subsequent melanoma diagnosis were classified as “cases” and were compared on the basis of risk factors to the 327 “controls” with a single melanoma diagnosis. The data indicate an inverse relation of risk of multiple primary melanomas with multiple blistering sunburns (P = .01 for the trend); the odds ratio (OR) was 0.32 (95% confidence interval [CI], 0.11-0.93) for 2 or more sunburns compared with none. The number of atypical moles was significantly related to increased risk (P = .004 for the trend). The presence of 3 or more atypical moles compared with none was associated with more than a 4-fold risk of multiple primary melanomas (OR, 4.29; 95% CI, 1.51-12.16). CONCLUSIONS: Additional melanomas occur more frequently than previously shown. Our study confirms that atypical moles are strongly associated with risk of multiple primary melanomas but provides little evidence that risk is influenced by pigmentary characteristics, hours of sun exposure, or benign moles. The inverse association with blistering sunburn may reflect the influence of an unmeasured covariate.

Arch Dermatol. 2006 Apr;142(4):433-8

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