Molecular evidence that oral supplementation with lycopene or lutein protects human skin against ultraviolet radiation: results from a double-blinded, placebo-controlled, crossover study.

BACKGROUND: Increasing evidence suggests photoprotection by oral supplementation with ß-carotene and lycopene. OBJECTIVES: To examine the capacity of lycopene-rich tomato nutrient complex (TNC) and lutein, to protect against ultraviolet (UV)A/B and UVA1 radiation at a molecular level. METHODS: In a placebo-controlled, double-blinded, randomized, crossover study two active treatments containing either TNC or lutein were assessed for their capacity to decrease the expression of UVA1 the radiation-inducible genes HO1, ICAM1 and MMP1. Sixty-five healthy volunteers were allocated to four treatment groups and subjected to a 2-week washout phase, followed by two 12-week treatment phases separated by another 2 weeks of washout. Volunteers started either with active treatment and were then switched to placebo, or vice versa. At the beginning and at the end of each treatment phase skin was irradiated and 24 h later biopsies were taken from untreated, UVA/B- and UVA1-irradiated skin for subsequent reverse transcriptase polymerase chain reaction analysis of gene expression. Moreover, blood samples were taken after the washout and the treatment phases for assessment of carotenoids. RESULTS: TNC completely inhibited UVA1- and UVA/B-induced upregulation of heme-oxygenase 1, intercellular adhesion molecule 1 and matrix metallopeptidase 1 mRNA, no matter the sequence (anova, P < 0·05). In contrast, lutein provided complete protection if it was taken in the first period but showed significantly smaller effects in the second sequence compared with TNC. CONCLUSIONS: Assuming the role of these genes as indicators of oxidative stress, photodermatoses and photoageing, these results might indicate that TNC and lutein could protect against solar radiation-induced health damage.

Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women.

INTRODUCTION AND OBJECTIVES: In recent years there has been an increasing interest in the use of nutritional supplements to benefit human skin. Molecular evidence substantiating such effects, however, is scarce. In the present study we investigated whether nutritional supplementation of women with the standardized pine bark extract Pycnogenol® will improve their cosmetic appearance and relate these effects to expression of corresponding molecular markers of their skin. MATERIALS AND METHODS: For this purpose 20 healthy postmenopausal women were supplemented with Pycnogenol for 12 weeks. Before, during and after supplementation, their skin condition was assessed (i) by employing non-invasive, biophysical methods including corneometry, cutometry, visioscan and ultrasound analyses and (ii) by taking biopsies and subsequent PCR for gene expression analyses related to extracellular matrix homeostasis. RESULTS: Pycnogenol supplementation was well tolerated in all volunteers. Pycnogenol significantly improved hydration and elasticity of skin. These effects were most pronounced in women presenting with dry skin conditions prior to the start of supplementation. The skin-physiological improvement was accompanied by a significant increase in the mRNA expression of hyaluronic acid synthase-1 (HAS-1), an enzyme critically involved in the synthesis of hyaluronic acid, and a noticeable increase in gene expression involved in collagen de novo synthesis. CONCLUSIONS: This study provides skin-physiological and for the first time molecular evidence that Pycnogenol supplementation benefits human skin by increasing skin hydration and skin elasticity. These effects are most likely due to an increased synthesis of extracellular matrix molecules such as hyaluronic acid and possibly collagen. Pycnogenol supplementation may thus be useful to counteract the clinical signs of skin aging.

[Topical application of vitamins, phytosterols and ceramides. Protection against increased expression of interstital collagenase and reduced collagen-I expression after single exposure to UVA irradiation]. / Topische Applikation von Vitaminen, Phytosterolen und Ceramiden. Schutz vor vermehrter Expression der interstitiellen Kollagenase und verminderter Kollagen-I-Expression nach 1-maliger UVA-Bestrahlung.

Photoaged skin is characterized by a decrease of dermal collagen fibers, resulting from an increased breakdown and a diminished de novo synthesis. The increased breakdown results from an increased expression of matrix metalloproteinases (MMPs). The main building blocks involved in de novo synthesis of collagen fibers are collagen 1A1 and 1A2, the expression of which is reduced in photoaged skin. We studied the effect of topical application of vitamins, phytosterols and ceramides on UV-induced up-regulation of the expression of MMP-1 and on UV-induced down-regulation of COL1A1 and COL1A2. The study was conducted with 10 subjects with healthy skin who were comparatively treated for 10 days with (i) a basic preparation containing jojoba oil, (ii) the basic preparation supplemented with vitamins, (iii) the basic preparation supplemented with phytosterols and ceramides, and (iv) the basic preparation supplemented with vitamins, phytosterols and ceramides. All four preparations inhibited the UV induced up-regulation of MMP-1. Neither the basic product nor that supplemented with vitamins inhibited down-regulation of COL1A1 and COL1A2, but addition of phytosterols and ceramides caused a decreased down-regulation of the expression of these genes. Our results indicate that phytosterols and ceramides are effective in blocking the reduced collagen synthesis after UV irradiation and even stimulating synthesis. They may be useful additions to anti-aging products.

[Systemic photoprotection through carotenoids]. / Systemische Photoprotektion durch Karotinoide.

Nutritional supplements are increasingly used to protect human skin against environmentally-induced damage, most importantly as a consequence of ultraviolet radiation exposure. beta-carotene is a major constituent of comercially available products administered for systemic photoprotection. Studies on the systemic use of beta-carotene provide evidence that 15-30 mg/d over a period of about 10-12 wk produces a protective effect against UV-induced erythema. Similar effects have been attributed to mixtures of carotenoids or after long-term intake of dietary products rich in carotenoids. Supplementation with carotenoids contributes to basal protection of the skin but is not sufficent to obtain complete protection against severe UV irradiation.

[Sun protection during holidays]. / Sonnenschutz im Urlaub.

Ultraviolet radiation is causally involved in induction of skin cancer, premature skin aging and photodermatoses. The longing of our western society for a "healthy tanning" as well as the unbroken trend to spend the holidays in sunny regions lead to the fact that human skin is increasingly exposed to ultraviolet radiation and its detrimental effects. Because of the socio-political importance of the vacation period as the "most beautiful and most important time of the year", effective prevention of these unwanted UV effects has an enormous importance to the general population. In this article the most important methods for effective sun protection are critically discussed.

Successful treatment of solar urticaria by extracorporeal photochemotherapy (photopheresis)--a case report.

UNLABELLED: Solar urticaria is characterized by erythema and whealing immediately after exposure to ultraviolet radiation and/or visible light. We report about a patient with severe solar urticaria, who was highly sensitive to both UVA radiation and visible light with a Minimal Urticaria Dose (MUD) of 7 J/cm2 UVA. Management of this patient was extremely difficult because standard treatment with oral antihistamines, hardening with UVA, UVB, visible light or oral PUVA and even oral cyclosporin A were completely ineffective. We therefore decided to perform extracorporeal photochemotherapy (photopheresis, ECP). After nine treatment cycles with photopheresis the MUD increased from 7 J/cm2 UVA before treatment to 22 J/cm2 UVA. This hardening effect was associated with a significant decrease of the frequency and severity of whealing and the accompanying symptoms (pain, fatigue, pruritus). CONCLUSION: Photopheresis might be of some benefit in selected patients with otherwise intractable solar urticaria.

Phototherapy for atopic dermatitis.

The beneficial effects of ultraviolet (UV) radiation on atopic dermatitis has been appreciated for many years. While broadband UVB and psoralen UVA have been the mainstay of phototherapy for some time, the past 5 years have seen the introduction of phototherapeutic modalities, including UVA-1 and 311nm UVB. The best modality and mode of usage is dependent on the type of atopic dermatitis, severity and body site. T lymphocytes play an important role in disease pathogenesis and UV radiation has profound effects on skin and systemic immune responses.

Ultraviolet A1 (340-400 nm) phototherapy for scleroderma in systemic sclerosis.

BACKGROUND: The presence of an inflammatory infiltrate consisting of helper T cells and a dysregulated matrix metabolism leading to excessive deposition of collagen are two pathogenetic factors responsible for the developments of fibrosis and sclerosis in patients with systemic sclerosis. In previous studies, ultraviolet A1 (UVA1) radiation phototherapy was shown to deplete skin-infiltrating T cells through the induction of T-cell apoptosis and to up-regulate the expression of matrixmetalloproteinase-1 (collagenase-1) in dermal fibroblasts. OBJECTIVE: Our purpose was to determine whether UVA1 phototherapy is effective for systemic sclerosis. METHODS: Lesional skin on the forearms of patients with systemic sclerosis (diffuse type, n =3; limited type, n =1) was exposed to medium-dose UVA1 radiation (60 J/cm(2)) daily. RESULTS: In all patients studied, UVA1 phototherapy-treated skin lesions were markedly softened after 9 to 29 exposures. Clinical improvement was associated with an increase in (1) joint passive range of motion values (P <.05), (2) skin temperature (thermography, P <.05), and (3) cutaneous elasticity (cutaneous elastometry, P <.05). Histologic evaluation of skin specimens obtained before and after UVA1 phototherapy revealed loosening of collagen bundles and the appearance of small collagen fibers. CONCLUSION: These studies indicate that UVA1 phototherapy is effective for patients with systemic sclerosis.

[The UV record. Document for quality control, therapy planning and risk assessment in dermatologic photo- and photochemotherapy]. / Der UV-Pass. Instrument der Qualitätskontrolle, Therapieplanung und Risikoabschätzung bei dermatologischer Photo- und Photochemotherapie.

Ultraviolet (UV-) radiation therapy as a mono- or combination therapy (UV-A, UV-A1, UV-B, SUP, UV-B311) or as photochemotherapy with photosensitization (systemic PUVA-, bath PUVA-, topical PUVA-therapy) are successfully used for the treatment of several dermatological disorders. Long-term side effects of natural UV (sun light) include photoaging and induction of skin tumors. At present, the relevance of in-vitro findings of potential tumor induction in animals through therapeutic levels of UV radiation is a matter of debate. To assess these risks, information on treated location, kind of UV radiation and cumulative UV doses are required. Practically this information is barely accessible. This makes decisions on possible therapies difficult. To solve this problem we propose to use an "UV pass". At the end of each UV radiation cycle, the body location, the type of radiation and the cumulative dose are documented and this pass is given to the patient. This will improve the information transfer if the doctor is changed, as well as facilitating decisions about certain therapies and calculation of long-term risks of UV radiation. Finally it will improve the quality of UV photo- and photochemotherapy.

Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin.

Ultraviolet-B (UVB) (290-320 nm) radiation-induced cyclobutane pyrimidine dimers within the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotection by sunscreens is exclusively prophylactic in nature and of no value once DNA damage has occurred. In this paper, we have therefore assessed whether it is possible to repair UVB radiation-induced DNA damage through topical application of the DNA-repair enzyme photolyase, derived from Anacystis nidulans, that specifically converts cyclobutane dimers into their original DNA structure after exposure to photoreactivating light. When a dose of UVB radiation sufficient to induce erythema was administered to the skin of healthy subjects, significant numbers of dimers were formed within epidermal cells. Topical application of photolyase-containing liposomes to UVB-irradiated skin and subsequent exposure to photoreactivating light decreased the number of UVB radiation-induced dimers by 40-45%. No reduction was observed if the liposomes were not filled with photolyase or if photoreactivating exposure preceded the application of filled liposomes. The UVB dose administered resulted in suppression of intercellular adhesion molecule-1 (ICAM-1), a molecule required for immunity and inflammatory events in the epidermis. In addition, in subjects hypersensitive to nickel sulfate, elicitation of the hypersensitivity reaction in irradiated skin areas was prevented. Photolyase-induced dimer repair completely prevented these UVB radiation-induced immunosuppressive effects as well as erythema and sunburn-cell formation. These studies demonstrate that topical application of photolyase is effective in dimer reversal and thereby leads to immunoprotection.

Mechanisms of ultraviolet (UV) B and UVA phototherapy.

Ultraviolet (UV) radiation has been used for decades with great success and at a constantly increasing rate in the management of skin diseases, becoming an essential part of modern dermatologic therapy (Krutmann et al, 1999). For phototherapy, irradiation devices emitting either predominantly middlewave UV (UVB, 290-315 nm) or longwave UV (UVA, 315-400 nm) radiation are employed. In former years, patients were treated with broad-band UVB, broad-band UVA, or combination regimens. Broad-band UV phototherapy, however, is being replaced more frequently by the use of irradiation devices that allow treatment of patients' skin with selected emission spectra. Two such modalities which have their origin in European Photodermatology are 311 nm UVB phototherapy (which uses long-wave UVB radiation above 300 nm rather than broadband UVB) and high-dose UVA1 therapy (which selective employs long-wave UVA radiation above 340 nm). In Europe, 311 nm UVB phototherapy has almost replaced classical broad-band UVB phototherapy and has significantly improved therapeutic efficacy and safety of UVB phototherapy (van Welden et al, 1988; Krutmann et al, 1999). The constantly increasing use of UVA-1 phototherapy has not only improved UVA phototherapy for established indications such as atopic dermatitis (Krutmann et al, 1992a, 1998; Krutmann, 1996), but has also provided dermatologists with the opportunity to successfully treat previously untractable skin diseases, e.g., connective tissue diseases (Stege et al, 1997; Krutmann, 1997). These clinical developments have stimulated studies about the mechanisms by which UVB and UVA phototherapy work. The knowledge obtained from this work is an indispensable prerequisite to make treatment decisions on a rationale rather than an empirical basis. Modern dermatologic phototherapy has started to profit from this knowledge, and it is very likely that this development will continue and provide dermatologists with improved phototherapeutic modalities and regimens for established and new indications. This review aims to provide an overview about current concepts of the mode of action of dermatologic phototherapy. Special emphasis will be given on studies that have identified previously unrecognized immunosuppressive/anti-inflammatory principles of UV phototherapy.

Ultraviolet A1 (340-400 nm) phototherapy for cutaneous T-cell lymphoma.

BACKGROUND: The results of a recent study suggested that ultraviolet A1 radiation (UVA1R; 340-400 nm) phototherapy for atopic dermatitis works through induction of apoptosis in skin-infiltrating helper T cells, indicating the possibility that other helper T cell-mediated skin diseases may respond to UVA1R as well. OBJECTIVE: The purpose of this open pilot study was to assess the therapeutic effectiveness of UVA1 phototherapy for cutaneous T-cell lymphoma (CTCL). METHODS: UVA1 phototherapy was used as monotherapy in patients (n = 3) with histologically proven CTCL (stages IA and IB). For daily whole body UVA1 irradiations, either a high-dose (n = 2; 130 J/cm2 UVA1 per exposure) or medium-dose (n = 1; 60 J/cm2 UVA1) regimen was used. Therapeutic effectiveness was assessed clinically and histologically. RESULTS: In each of the 3 patients, skin lesions began to resolve after only a few UVA1 radiation exposures. Complete clearance was observed between 16 and 20 exposures, regardless of whether the high- or medium-dose regimen had been employed. CONCLUSION: These studies suggest that patients with CTCL stages IA and IB can be treated effectively with UVA1 phototherapy.

Successful monotherapy of severe and intractable atopic dermatitis by photopheresis.

BACKGROUND: Patients with chronic atopic dermatitis can become unresponsive to standard immunosuppressive therapy and thus pose a serious therapeutic problem. OBJECTIVE: Our purpose was to evaluate the therapeutic effectiveness of photopheresis in the management of patients with severe and intractable atopic dermatitis. METHODS: Photopheresis was used as monotherapy in patients (n = 3) who previously did not respond to treatment with glucocorticosteroids, cyclosporine, phototherapy, or photochemotherapy. Patients were treated at 2-week intervals (total number of treatments = 10). RESULTS: In all patients, photopheresis induced clinical improvement and reduction of elevated serum levels of eosinophil cationic protein and total IgE. Prolongation of the intervals between treatments from 2 to 4 weeks caused worsening in one patient, whereas shortening of treatment-free intervals improved both clinical and laboratory findings. CONCLUSION: These studies indicate that photopheresis may be used as monotherapy for the treatment of patients with severe atopic dermatitis that has become intractable to standard therapeutic modalities.

High-dose UVA1 therapy for atopic dermatitis: results of a multicenter trial.

BACKGROUND: The results of an open, single-center study suggested that phototherapy with high doses of UVA1 radiation (UVA1R; 340-400 nm) is effective for acute, severe exacerbations of atopic dermatitis (AD). OBJECTIVE: The purpose of this study was to assess the effectiveness of high-dose UVA1 phototherapy for acute, severe AD in a randomized multicenter trial in direct comparison with topical glucocorticoid therapy. METHODS: Patients were treated with high-dose UVA1R (10 days, 130 J/cm2/day; n = 20), topically with fluocortolone (10 days, 1 x daily; n = 17), or with UVA-UVB therapy (10 days, 1 x daily, minimal erythema dose-dependent; n = 16). RESULTS: With a clinical scoring system, significant differences in favor of high-dose UVA1R and fluocortolone therapy were observed (p < 0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was superior to fluocortolone (p < 0.002) therapy. Serum levels of eosinophil cationic protein and the blood eosinophil count were significantly reduced after high-dose UVA1 or fluocortolone, but not UVA-UVB therapy. CONCLUSION: This study confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for treatment of severe exacerbations of AD.

Evidence that singlet oxygen-induced human T helper cell apoptosis is the basic mechanism of ultraviolet-A radiation phototherapy.

Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.