Assessment of Natural Sunlight Protection Provided by 10 High-SPF Broad-Spectrum Sunscreens and Sun-Protective Fabrics.

In 1978, the FDA Advisory Panel proposed both indoor and natural sunlight SPF testing methods but reverted to indoor testing only in 1993. Today's sunscreen sun protection and broad-spectrum claims are based on mandated clinical tests using solar simulators and in vitro spectrophotometers. This research evaluated the protection of 10 high-SPF (30-110), broad-spectrum sunscreen products, as well as 6 sun-protective fabrics against natural sunlight in Arequipa, Peru. Each of the 17 subjects was exposed to natural sunlight for 1 h and 59 min under clear skies, with temperatures and humidity similar to those in an indoor clinical laboratory. Test sites were photographed 16-24 h later. Four dermatologists evaluated the photographs for erythema and persistent pigment darkening (PPD). Perceptible sun-induced skin injury (sunburn and/or pigmentation) was detected at 97% of the sunscreen-protected scores. The most sun-sensitive subjects obtained the least erythema protection. The higher the SPF was, the higher the erythema protection, but the intensity of PPD was also higher. The 2 sunscreens using only FDA-approved sunscreen filters rated 30 SPF and 45+ SPF performed poorly: Eighty-one percent of the 136 scores were graded 1 minimal erythema dose or higher erythema, achieving, at a maximum, SPF of 5-7 in natural sunlight. Sun-protective fabrics tested provided excellent sun protection. The erythema and PPD observed through the sunscreens in less than 2 h are incongruous with the broad-spectrum, high-SPF sunscreen claims. Reapplying these sunscreens and staying in the sun longer, as stated on the product labels, would have subjected the subjects to even more UV exposure. High-SPF, broad-spectrum sunscreen claims based on indoor solar simulator testing do not agree with the natural sunlight protection test results.

Green Tea Catechin Association with Ultraviolet Radiation-Induced Erythema: A Systematic Review and Meta-Analysis.

Catechins are a part of the chemical family of flavonoids, a naturally occurring antioxidant, and a secondary metabolite in certain plants. Green tea catechins are well recognized for their essential anti-inflammatory, photo-protective, antioxidant, and chemo-preventive functions. Ultraviolet radiation is a principal cause of damage to the skin. Studies observed that regular intake of green tea catechins increased the minimal dose of radiation required to induce erythema. The objectives of this systematic review and meta-analysis are to determine the effectiveness of green tea catechins in cutaneous erythema and elucidate whether green tea catechin consumption protects against erythema (sunburn) inflammation. A comprehensive literature search was conducted to identify the relevant studies. Two researchers carried out independent screening, data extraction, and quality assessment according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The pooled effect of green tea catechins on protection against erythema was assessed using approaches fixed-effects or random-effects model to quantify the effectiveness of green tea catechins in the erythema dose-response. Studies not be included in meta-analyses were summarized narratively. Six randomized controlled studies of enrolled studies regularly administrated green tea catechins orally for 6 to 12 weeks involving healthy volunteers comprising a total of 100 participants were included in the analysis. The results revealed green tea catechins have favorable protection against erythema inflammation even at increased minimal erythema dose (MED) of ultraviolet radiation. Meta-analysis results confirm oral supplementation of green tea catechins is highly effective at low-intensity ultraviolet radiation-induced erythema response (MED range; 1.25-1.30) compared to placebo, showing a significant pooling difference (p = 0.002) in erythema index (SMD: -0.35; 95% CI, -0.57 to -0.13; I2 = 4%, p = 0.40) in the random-effects model. The pro-inflammatory signaling pathways through oral supplementation with green tea catechins are an attractive strategy for photo-protection in healthy human subjects and could represent a complementary approach to topical sunscreens. Therefore, studies that involved green tea catechin in topical applications to human subjects were also evaluated separately, and their meta-analysis is presented as a reference. The evidence indicates that regular green tea catechin supplementation is associated with protection against UV-induced damage due to erythema inflammation.

Intense Pulsed Light: A Methodical Approach to Understanding Clinical Endpoints.

BACKGROUND: Intense Pulsed Light (IPL) is a non-coherent polychromatic broadband filtered flashlamp that emits light in the spectrum of approximately 400–1200 nm. Its effects on photorejuvenation are well documented. The goal of this study is to help practitioners better conceptualize and fine tune IPL device settings in order to produce the most effective and safest clinical outcome. MATERIALS/METHODS: This was a prospective study testing several filters (515 nm; 560 nm; 590 nm and 530–650; 900–1200 nm vascular filter), fluences, pulse durations, and pulse numbers (ie, multiple sequence pulsing or MSP) with a new IPL system. RESULTS: Post-procedure erythema response was more pronounced with increasing fluence, decreasing wavelength, fewer pulses and shorter pulse duration. The exception was the 515 nm filter with regard to pulse duration, which was observed to have a more pronounced response with longer pulse durations. The overall clinical outcome at the 4-week follow-up visit demonstrated greatest improvement in erythema and pigmentation using the 515 nm filter on a Fitzpatrick Skin Type III individual. CONCLUSION: Greatest clinical endpoint response at 4-week follow-up was observed with more robust initial responses. This was most apparent at higher fluence levels and fewer pulse counts. However, when the IPL is pushed to aggressive parameters, there is risk of hypopigmentation and hair loss as seen in this case study. Skin type is an important consideration when using IPL and MSP adds to its safety profile. J Drugs Dermatol. 2021;20(2):203-207. doi:10.36849/JDD.5638.

Orally administered mixed carotenoids protect human skin against ultraviolet A-induced skin pigmentation: A double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Photoprotection of human skin is determined as the capacity of sunscreens to prevent ultraviolet (UV) B radiation-induced erythema and UVA radiation-induced pigmentation. It is unequivocal that, in addition to sunscreens, oral supplementation with carotenoids can protect human skin against UVB radiation-induced erythema. It is not known if this is also the case for UVA radiation-induced pigmentation. OBJECTIVE: To clinically evaluate the photoprotective effects of daily supplementation with carotenoids against UVA radiation-induced pigmentation. METHODS: In this double-blind, placebo-controlled trial, 60 subjects (Fitzpatrick types II-IV) were randomized to receive Nutrilite™ Multi Carotene supplement or placebo for 12 weeks. UVB-induced minimal erythemal dose (MED), UVA-induced minimal persistent pigmentation dose (MPPD) and skin carotenoid levels were measured at baseline, 4, 8, and 12 weeks of intervention. Skin color was evaluated by expert clinical graders and by colorimetry. Carotenoid levels in the skin were measured by the Biozoom® device. RESULTS: In the intervention group, a significant increase in comparison with the placebo group was observed in (a) skin carotenoid levels, (b) UVB-induced MED, and (c) UVA-induced MPPD values obtained by colorimetry. CONCLUSION: Daily supplementation with carotenoids protects human skin against both UVB-induced erythema and UVA-induced pigmentation.

Pomegranate Juice and Extract Consumption Increases the Resistance to UVB-induced Erythema and Changes the Skin Microbiome in Healthy Women: a Randomized Controlled Trial.

In vitro and animal studies have demonstrated that topical application and oral consumption of pomegranate reduces UVB-induced skin damage. We therefore investigated if oral pomegranate consumption will reduce photodamage from UVB irradiation and alter the composition of the skin microbiota in a randomized controlled, parallel, three-arm, open label study. Seventy-four female participants (30-45 years) with Fitzpatrick skin type II-IV were randomly assigned (1:1:1) to 1000 mg of pomegranate extract (PomX), 8 oz of pomegranate juice (PomJ) or placebo for 12 weeks. Minimal erythema dose (MED) and melanin index were determined using a cutometer (mexameter probe). Skin microbiota was determined using 16S rRNA sequencing. The MED was significantly increased in the PomX and PomJ group compared to placebo. There was no significant difference on phylum, but on family and genus level bacterial composition of skin samples collected at baseline and after 12 week intervention showed significant differences between PomJ, PomX and placebo. Members of the Methylobacteriaceae family contain pigments absorbing UV irradiation and might contribute to UVB skin protection. However, we were not able to establish a direct correlation between increased MED and bacterial abundance. In summary daily oral pomegranate consumption may lead to enhanced protection from UV photodamage.

Effect of combination NSAID and NBUVB treatment in non-photoadapters-A pilot study.

BACKGROUND: Vitiligo is a disorder of dyspigmentation that can impact quality of life. While narrow-band ultraviolet B (NBUVB) is an effective treatment for vitiligo, a subset of patients are unable to respond to phototherapy as they cannot photoadapt. However, nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to increase the minimal erythema dose. PURPOSE: To determine whether ibuprofen allows non-photoadapters to respond to therapeutic doses of NBUVB and maintain photoadaptation. METHOD: Four patients unable to tolerate NBUVB or excimer past a dose of 1000 mJ/cm2 were enrolled in the study and given ibuprofen 400 mg prior to phototherapy, which was performed 2-3 times a week. Patients were followed up to 72 treatments to demonstrate photoadaptation and maintenance of response to phototherapy. Patients were clinically monitored by serial photographs approximately every 12 treatments. Response to phototherapy was monitored by tracking the dose of NBUVB received at each session. Maintenance of response was monitored for six treatments after discontinuing the ibuprofen. Percent change in pigmentation was also recorded. RESULTS: Three out of four subjects enrolled in the study were able to increase their doses of phototherapy to a therapeutic range, and subjects continued to photoadapt for six treatments after discontinuing ibuprofen. Two subjects achieved repigmentation during their course of phototherapy. CONCLUSION: Ibuprofen may be a safe alternative to corticosteroids for select patients with vitiligo that are unable to photoadapt. It appears that the ability to photoadapt continues once ibuprofen is discontinued, negating the need for chronic use. Enabling photoadaptation allows patients to achieve therapeutic doses of NBUVB phototherapy, leading to repigmentation and improved outcomes. TRIAL REGISTRATION: The trial was registered through Henry Ford Hospital IRB-No. 9744.

Tomato Phytonutrients Balance UV Response: Results from a Double-Blind, Randomized, Placebo-Controlled Study.

BACKGROUND: Our previous double-blinded, placebo-controlled cross-over study indicated that a nutritional supplement named lycopene-rich tomato nutrient complex (TNC) can protect from UVA1-induced (340-400 nm) and UVA- (320-400 nm)/UVB-induced (280-320 nm) upregulation of molecular markers associated with oxidative stress, inflammation, and ageing. OBJECTIVES: in the current double-blind, randomized, placebo-controlled multicenter study, we analyze whether a similar, synergistic carotenoid-rich TNC can protect from broadband UVB-induced threshold erythema formation assessed as increase in minimal erythemal dose (MED) reading, the intensity of erythema formation, and the upregulation of molecular markers associated with inflammation and immunosuppression, and whether this correlates with carotenoid blood levels. METHODS: One hundred and forty-nine healthy volunteers were randomized to two groups and subjected to a 5-week washout phase, followed by a 12-week treatment phase receiving either 15 mg lycopene, 5.8 mg phytoene and phytofluene, 0.8 mg ß-carotene, 5.6 mg tocopherols from tomato extract, and 4 mg carnosic acid from rosemary extract per day or placebo made from medium-chain triglycerides. At the end of each phase, MED determination, UVB irradiation, chromametry, biopsies, and blood samples were undertaken. RESULTS: The active supplement was well tolerated. Interestingly, no significant difference was seen in the MED between the active-supplement and placebo groups, as determined by visual grading by expert assessors. Of note, the carotenoid-containing supplement significantly protected against UVB-induced erythema formation measured as Δa* after the intervention minus Δa* after the washout phase as compared to the placebo. Moreover, intake of the active supplement significantly protected against UVB-induced upregulation of IL6 and TNFα as compared with the intake of placebo. Lastly, carotenoid plasma levels were significantly increased. CONCLUSION: This well-tolerated carotenoid-containing supplement significantly protected against UVB-induced erythema formation and upregulation of proinflammatory cytokines in healthy volunteers.

Efficacy of Autologous Platelet-Rich Plasma Combined With Ablative Fractional Carbon Dioxide Laser for Acne Scars: A Systematic Review and Meta-Analysis.

BACKGROUND: Acne scars are common and challenging clinical complications of acne vulgaris. Ablative fractional carbon dioxide (CO2) laser is a well-established treatment for acne scars; however, some postlaser adverse effects have been noted. Autologous platelet-rich plasma (PRP) can improve tissue regeneration. Several studies have investigated the efficacy of combination therapy of CO2 laser and PRP for acne scars. OBJECTIVES: The authors sought to conduct a meta-analysis of the efficacy of PRP combined with ablative fractional CO2 laser for treating acne scars by examining clinical trial results. METHODS: A systematic review was performed by searching PubMed, Embase, Cochrane Library, and Web of Science, and a meta-analysis was conducted to assess the clinical outcomes after combination therapy of PRP and ablative fractional CO2 laser compared with laser alone. RESULTS: We identified 4 eligible studies for the meta-analysis, including 3 randomized controlled trials. Our results demonstrated that clinical improvement after combination therapy was significantly higher than that after laser alone (odds ratio = 2.992, P = 0.001). Regarding major side effects, patients who underwent combination therapy experienced significantly shorter duration of crust compared with CO2 laser alone (standard mean difference = -1.140, P < 0.001); relatively shorter durations of erythema and edema were also noted after combination therapy. Furthermore, patient satisfaction rates were significantly higher after combination therapy than after laser alone (odds ratio = 3.169, P = 0.002). CONCLUSIONS: The combination of autologous PRP and ablative fractional CO2 laser has synergistic positive effects on the clinical outcomes for acne scars and can accelerate the recovery of laser-damaged skin.

Flavonol glycosides in Dyssodia tagetiflora and its temporal variation, chemoprotective and ameliorating activities.

Dyssodia tagetiflora is known as 'Tzaracata' and 'flor de muerto'. Recently, D. tagetiflora has been reported to have antioxidant activities in its polar extracts as well as insecticidal activities. Hyperoside (1), avicularin (2) and avicularin acetate (3) have been isolated previously. However, the temporary variation in glycoside flavonoids biosynthesis, as well as antibacterial and chemoprotective activities, have not been reported. The amount of 1, 2 and 3 in the different collections was characterized by HPLC-MS. Two new C-glycosides were characterized, quercetin-4'-methyl ether 6-C glucoside (A1) and quercetin-4'-methyl ether 8-C glucoside (A2), as well as [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl]3,4,5-trihydroxyoxane-2,6-dicarboxylate (A3). This is the first report of the presence of C-C flavonoid glycosides compounds in the genus Dyssodia. Hyperoside was the majority compound at all collections. The methanolic extracts of August 2016 and October 2017 were active against Micrococcus luteus and Bacillus subtillis. The methanolic extract has chemoprotective effects because, when applied topically in SKH-1 mice, it decreases the severity of epidermal damage induced by acute exposure to ultraviolet radiation. In addition, cutaneous photocarcinogenesis was decreased in mice treated with the extract. The methanolic extract of D. tagetiflora has chemoprotective properties by decreasing the damage caused by acute and chronic exposure to UV in mice.

Topical brimonidine-assisted laser treatment for the prevention of therapy-related erythema and hyperpigmentation.

Postinflammatory hyperpigmentation (PIH) and erythema are the most common adverse effects associated with laser treatment, particularly in dark-skinned individuals. Several methods have been used to prevent or minimize these adverse effects; however, to date, no definitive precautions/strategies are known to prevent post-laser PIH and erythema. We investigated whether the topical application of the α-adrenergic receptor agonist brimonidine could reduce laser treatment-related complications such as erythema and PIH.

A Comparative Split-Face Trial of Plant-Based Hypoallergenic Ointment vs Petroleum-Based Ointment Following Fractionated Carbon Dioxide Laser Resurfacing of the Face

Purpose: Fractionated carbon dioxide (CO2) laser resurfacing uses fractional photothermolysis with an ablative 10,600-nm wavelength for treatment of rhytides and photodamage. Although associated with reduced side effect profile from traditional ablative lasers, fractionated lasers can lead to significant erythema, edema, crusting, and exudation for 14 days. Post-care includes regular distilled water soaks and healing ointment. This study evaluated efficacy and patient satisfaction of a novel plant-based hypoallergenic ointment (Doctor Rogers RESTORE®Healing Balm; Product 1) compared to petroleum-based lanolin-containing ointment (Aquaphor® Healing Ointment; Product 2) to accelerate wound healing post-laser resurfacing of the face. Design: This was a single-center, prospective randomized, double-blinded, split-face comparative study of 10 subjects with photo-aging and rhytids who received treatment with fractionated CO2 laser between September 2017 and January 2018. Product 1 and Product 2 were randomized to each half of the face and applied from days 0 to 7 with an option to continue to day 14. The primary outcome measures were Investigator-rated degree of erythema, edema, crusting, exudation, and percentage healing, with follow-up evaluations performed at days 2, 4, 7, 14, and 30. The secondary outcome measure was patient satisfaction. Summary: Based on investigator post-resurfacing scores, day 4 showed improved erythema (50%), edema (50%), crusting (40%), and percentage healing (60%) on the Product 1-treated side compared to Product 2, with the majority of remaining patients scoring the same as Product 2. On day 14, Product 1 demonstrated improvement in erythema (50%), edema (30%), and percentage healing (30%) compared to Product 2, with all remaining patients scoring the same as Product 2. Crusting was the same between the two products on day 14. Ninety percent of patients preferred Product 1 over Product 2, found it easier to use, and were more likely to use it in the future. Conclusion: Product 1 is a plant-based hypoallergenic ointment that is safe and effective post-laser treatment and is associated with high patient satisfaction and preference.

The Protective Role of Astaxanthin for UV-Induced Skin Deterioration in Healthy People-A Randomized, Double-Blind, Placebo-Controlled Trial.

Skin is a major safeguard tissue in humans. Because biological barrier function is deteriorated by several kinds of stresses including exposure to ultra-violet (UV) rays, the protection and treatment of skin conditions by dietary supplements are important. We therefore evaluated the effects of dietary supplementation with an algal food-derived antioxidant, astaxanthin, on UV-induced skin deterioration. Twenty-three healthy Japanese participants were recruited to a 10-week double-blind placebo-controlled study. They were assigned to the astaxanthin group supplemented with a capsule containing 4 mg of astaxanthin or the placebo group. To assess the protective role of astaxanthin for UV-induced skin deterioration, we determined the minimal erythema dose (MED) and analyzed UV-induced changes of moisture and transepidermal water loss (TEWL) at baseline and after 9 weeks of supplementation. Subjective skin conditions were assessed by the visual analog scale. The astaxanthin group showed increased MED compared with placebo. In addition, the astaxanthin group had a reduced loss of skin moisture in the irradiated area compared with placebo. Subjective skin conditions for “improvement of rough skin” and “texture” in non-irradiated areas were significantly improved by astaxanthin. Astaxanthin seems protective against UV-induced skin deterioration and helps maintain healthy skin in healthy people.

An open-label clinical trial assessing the efficacy and safety of Bend Skincare Anti-Aging Formula on minimal erythema dose in skin.

BACKGROUND/PURPOSE: Sunburn and other health risks associated with excess sun exposure place huge economic burdens on societies, and create discomfort and disease within susceptible individuals. Oral supplements that reduce sunburn may be advantageous. This study evaluated the safety and efficacy of Bend Skincare Anti-Aging Formula to ameliorate sunburn induced with a solar simulator. METHODS: Subjects (n = 28) with Fitzpatrick skin phototypes I, II, or III took 4 capsules daily of the supplement providing 1400 mg of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), 120 mg of gamma-linolenic acid (GLA), 5 mg of lutein, 2.5 mg of zeaxanthin, and 1000 IU of vitamin D3 for 8 weeks. Skin on each subject's back was exposed to a progressive sequence of timed ultraviolet (UV) radiation exposure doses at baseline, and after 4- and 8-week treatment to determine their minimal erythema dose (MED). Results were compared before and after treatment using 3 paired t tests and subsequently 3 linear mixed models. RESULTS: Treatment significantly improved tolerance to UV exposure as evidenced by increased MED at 4 and 8 weeks compared with baseline (P < .001). This protection increased with prolonged use of Bend Skincare Anti-Aging Formula as demonstrated by progressively increased MED between baseline and 4 weeks, and again between 4 and 8 weeks (P < .001). Nearly 86% of patients responded to treatment within 4 weeks and 100% of patients responded by the end of the study, resulting in a 39% mean increase in MED at 4 weeks, and an 84% mean increase in MED at 8 weeks compared with baseline. Treatment was well tolerated with no product associated adverse events (AE) and only a few mild and expected side effects. CONCLUSION: Bend Skincare Anti-Aging Formula safely and effectively provides significant skin photoprotection that increases with continued use.

La psoriasis protege frente a una dosis eritemática mínima patológica / Psoriasis Protects Against a Low Minimal Erythema Dose

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¿Es útil la determinación de la dosis eritematógena mínima previa a la fototerapia ultravioleta B de banda estrecha? / Is it Useful to Calculate Minimal Erythema Dose Before Narrowband UV-B Phototherapy?

Introducción y objetivos: La dosis de inicio en la fototerapia UVB de banda estrecha (UVBBE) viene determinada por el fototipo o por la determinación de la dosis eritematógena mínima (DEM). El cálculo de la DEM identifica pacientes con fotosensibilidad no sospechada. El objetivo de nuestro estudio es conocer la influencia que puedan tener en una DEM disminuida los fármacos fotosensibilizantes concomitantes, el diagnóstico, la asociación con acitretina en pacientes con psoriasis y evidenciar si la DEM alterada provoca más reacciones adversas y más graves. Material y métodos: Se trata de un estudio observacional de una cohorte retrospectiva desde el período comprendido entre el 1 de febrero de 2009 al 31 de marzo de 2015. La determinación de la DEM se categorizó en DEM normal o patológica. Resultados: Trescientos dos pacientes con distintas dermatosis inician UVBBE en función de la DEM. No se han encontrado diferencias entre el grupo con DEM patológica respecto al normal, ni en el número de fármacos consumidos (p = 0,071), ni en el potencial fotosensibilizante (p = 0,806). El análisis multivariante ajustado por edad, sexo y fototipo reveló que la psoriasis es un factor protector de DEM patológica (OR = 0,31 [IC 95%: 0,16-0,58]). No se encontró riesgo significativo de eritema ni prurito en los pacientes con DEM alterada OR = 1,68 (IC 95%: 0,91-3,29) y OR = 2,04 (IC 95%: 0,99-4,22), respectivamente. Conclusiones: La psoriasis protege de tener una DEM patológica. Si bien el eritema y el prurito fueron más frecuentes en los pacientes con DEM patológica, las diferencias no fueron estadísticamente significativas (AU)

Introduction and objectives: The starting dose for narrowband UV-B phototherapy is determined by a patient's skin phototype or minimal erythema dose (MED). Calculation of MED identifies patients with unsuspected photosensitivity. The aim of this study was to investigate the influence of factors such as concomitant use of photosensitizing agents, diagnosis, and combination with acitretin in patients with psoriasis on the frequency and severity of adverse effects in patients with a low MED to narrowband UV-B phototherapy. Material and methods: We undertook a retrospective observational cohort study between February 1, 2009 and March 31, 2015. MED values were classified as normal or low. Results: In total, 302 patients with different skin conditions started narrowband UV-B phototherapy at a dose determined by their MED. No differences were found between patients with a low MED and those with a normal MED for number of drugs taken (P = .071) or use of photosensitizing agents (P = 0.806). Following adjustment for age, sex, and phototype, the multivariate analysis showed that psoriasis exerted a protective effect against a low MED (OR = 0.31 [95% CI, 0.16-0.58]). No significant risk of erythema or pruritus was detected in patients with a low MED (OR = 1.68; 95% CI, 0.91-3.29 and OR = 2.04; 95% CI, 0.99-4.22, respectively). Conclusions: Psoriasis protects against a low MED. Although erythema and pruritus were more common in patients with a low MED, the differences were not significant (AU)

Melatonin for prevention of erythema and oxidative stress in response to ultraviolet radiation.

Skin damage induced by UVR is an escalating problem in dermatology, and increasing incidence of skin cancer, especially for non-melanoma skin cancer, has been reported worldwide. UVR from sun exposure and the production of reactive oxygen species (ROS) is known to be a pivotal factor in the aetiology of skin cancer. The pineal hormone melatonin is recognized as the most potent endogenous antioxidant. Melatonin conducts its antioxidant effects acting directly as a radical scavenger and indirectly by up regulation of antioxidant enzymes. It has been proposed, that melatonin may have a protective effect against UVR-induced skin damage. The aim of this thesis was to: - Clarify melatonin's protective effect against UVR-induced skin damage in laboratory and clinical settings trough a systematic review of the literature. - To clinically assess the protective effect of topical treatment with melatonin against natural sun exposure, and determine the optimal concentration. - To clinically evaluate the degree of cognitive dysfunction with full body application of topical melatonin. Study 1: This was a systematic review using the databases Pubmed, EM-BASE and Cinahl. The databases were searched up to January 2013 to identify studies evaluating melatonin's protective effect against UVR-induced erythema in humans, and damage on a cellular level. Twenty studies were included, four human and 16 experimental. The results indicated that melatonin had a protective effect against UVR-induced erythema if applied before exposure, and this effect was probably obtained by melatonin acting directly as an antioxidant, and indirectly by regulating gene expression and inducing a DNA stabilizing effect. As these results were obtained using artificial UVR-sources and without investigating possible side effects, studies using natural sunlight and evaluating possible side effects of topical melatonin administration were warranted. Study 2: This study was a randomized, double-blind, placebo-controlled study. We evaluated the protective effect of three different doses of topical melatonin against erythema induced by natural sun-light. The primary outcome was reduction in erythema, evaluated by chromatography, after sun exposure, when treated with topi-cal melatonin (0.5%, 2.5%, 12.5%) versus placebo and no treatment. A significant difference in erythema formation was found between areas treated with melatonin 12.5% and areas receiving placebo or no treatment. However, this was only seen in participants with an erythema reaction to the sun exposure. Further-more, the treated skin areas were very small and studies assessing any potential adverse effects were necessary. Study 3: This also was a randomized, double-blind, placebo-controlled, cross-over study. We assessed the degree of cognitive dysfunction with full body application of topical melatonin 12.5%. Cognition was evaluated using a neuropsychological test battery consisting of Karolinska sleepiness scale (KSS), finger tapping test (FTT) and continuous reaction time (CRT). The impact on KSS was the primary outcome. We found no significant effect on cognition, however, large inter-individual variation was observed. These results support that melatonin is a safe drug for dermal application. The studies in this thesis may be valuable in the research field of melatonin's protective potential against UVR-induced oxidative skin damage. Increasing incidence of skin cancer is reported worldwide, and experts have suggested that the problem will only increase further, due to depletion of the ozone layer and the aging population. Furthermore, high-risk patient groups are emerging with the widely use of immunosuppressive medicine in various diseases, and this high-risk is in spite of use of protective measures known today. Therefore, development of new and more effective sun protective agents, with other qualities than simple chemical reflection of the UVR, is more important than ever. We have supported the suggestion of melatonin as a sun protective agent, and added the clinical relevant feature, that melatonin also has a protective effect against natural sunlight. Furthermore, we have supported the idea of melatonin being a safe drug for topical treatment, even in previous unknown high dosages. However, before any clinical implementation of melatonin as a sun protective agent can take place, further studies evaluating the long-term effects are warranted.

Skin reactions after photodynamic therapy are unaffected by 839 nm photobiomodulation therapy: A randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is associated with erythema and edema. Photobiomodulation (PBM) therapy may stimulate the skin recovery process. We investigated the potential of PBM to reduce PDT-induced skin reactions. STUDY DESIGN AND METHODS: Healthy volunteers (n = 20) were randomized to receive left- or right side PBM (near-infrared 839/595 nm) or placebo-PBM (595 nm) on their buttocks. Corresponding test areas were exposed to standardized PDT reactions, using ablative fractional laser-assisted PDT (AFXL-PDT) with methyl-aminolevulinate (MAL) incubated for 30, 90, and 180 minutes before red-light illumination. Each buttock received PBM and placebo-PBM for five consecutive days, starting one day before PDT interventions. Follow-up visits were performed 4 and 11 days after PDT. Outcome measure included blinded, observer-assessed skin reactions, substantiated by objectively measured erythema and pigment percentages and skin temperatures. RESULTS: PDT interventions induced a standardized range of erythema and edema in all subjects. Skin reactions were clinically unaffected by PBM throughout the active treatment period and at all subsequent follow-up visits (PBM vs. placebo-PBM, P = 1.000). Clinical results were supported by similar erythema intensities and skin temperatures in PBM and placebo-PBM treated skin: median erythema 28.1% versus 30.3% (AFXL-PDT with 30 minutes MAL-incubation), 36.1% versus 35.2% (90 minutes MAL-incubation) and 39.4% versus 40.9% (180 minutes MAL-incubation) (Day 4, P > 0.05). No differences in clinical hyperpigmentation or pigment percentages were observed between corresponding test areas in any subject on the final 11-day follow-up. CONCLUSION: Under the current study conditions, PDT-induced skin reactions were unaffected by PBM. Lasers Surg. Med. 49:810-818, 2017. © 2017 Wiley Periodicals, Inc.

Protective effects of a novel nutritional and phytonutrient blend on ultraviolet radiation-induced skin damage and inflammatory response through aging defense mechanisms.

BACKGROUND: The human body relies on several aging defense mechanisms (ADMs) to limit damage induced from pro-aging stressors (aging aggressors). However, such protective mechanisms can be compromised, leading to accelerated aging. The skin provides a model to probe the effects of an oral nutritional intervention on ADMs in response to ultraviolet radiation (UVR)-induced damage. OBJECTIVE: To determine whether supplementation with a novel nutritional and phytonutrient blend could protect against UVR-induced skin damage and positively influence facial skin attributes and characteristics by bolstering ADMs. METHODS: Thirty-six healthy, nonsmoking women (40-75 years) with Fitzpatrick skin types I and II were recruited. UVR-induced erythema and the number of apoptotic cells were determined before (pre-) and after 8-week (post-) supplementation. Other clinical variables included skin carotenoid concentrations, facial skin attributes and characteristics. RESULTS: Eight-week supplementation led to protection against UVR-induced skin damage as evidenced by reductions in erythema at all three minimal erythema doses (MEDs) (9.1 to 7.4 [P = 0.10]; 15.8 to 13.6 [P = 0.02]; and 19.6 to 17.3 [P = 0.01] for one, two, and three MEDs and a reduction in the average number of apoptotic cells [11.3 to 5.3, P < 0.0001] pre- and post-supplementation, respectively). Skin carotenoid concentrations increased from 28 111 Raman intensity units to 38 472 (P < 0.0001) along with noticeable improvements in facial skin attributes and characteristics: elasticity, transepidermal water loss, radiance, texture, and overall appearance (all P < 0.05) following supplementation. CONCLUSION: Eight weeks of oral supplementation positively impacted ADMs resulting in protection against UVR-induced skin damage and improvements in facial skin attributes and characteristics.