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      Beneficial Long-Term Effects of Combined Oral/Topical Antioxidant Treatment with the Carotenoids Lutein and Zeaxanthin on Human Skin: A Double-Blind, Placebo-Controlled Study

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          Abstract

          Background: The skin is exposed to numerous environmental assaults that can lead to premature aging. Of these agents, perhaps none is more ubiquitous than the ultraviolet (UV) wavelengths of sunlight. The primary immediate defense against environmental skin damage is the antioxidant capacity of the skin. However, this defense system can be compromised by moderate exposure to UV light. Therefore, bolstering the antioxidant defense system of the skin is a potentially important strategy for reducing environmentally induced skin damage. Aim of the Study: This clinical trial was designed to study the efficacy of lutein and zeaxanthin, two potentially important antioxidants found naturally in the skin, upon five skin physiology parameters (surface lipids, hydration, photoprotective activity, skin elasticity and skin lipid peroxidation – malondialdehyde) of human subjects. These xanthophyllic carotenoids were administered either orally, topically, or in combination (both oral and topical routes). Results: The results obtained indicate that the combined oral and topical administration of lutein and zeaxanthin provides the highest degree of antioxidant protection. However, oral and topical administration of these antioxidants individually also provides significant activity in the skin. In addition, oral administration of lutein may provide better protection than that afforded by topical application of this antioxidant when measured by changes in lipid peroxidation and photoprotective activity in the skin following UV light irradiation.

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          Most cited references39

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          The interaction of dietary carotenoids with radical species.

          Dietary carotenoids react with a wide range of radicals such as CCl3O2*, RSO2*, NO2*, and various arylperoxyl radicals via electron transfer producing the radical cation of the carotenoid. Less strongly oxidizing radicals, such as alkylperoxyl radicals, can lead to hydrogen atom transfer generating the neutral carotene radical. Other processes can also arise such as adduct formation with sulphur-centered radicals. The oxidation potentials have been established, showing that, in Triton X-100 micelles, lycopene is the easiest carotenoid to oxidize to its radical cation and astaxanthin is the most difficult. The interaction of carotenoids and carotenoid radicals with other antioxidants is of importance with respect to anti- and possibly pro-oxidative reactions of carotenoids. In polar environments the vitamin E (alpha-tocopherol) radical cation is deprotonated (TOH*+ --> TO* + H+) and TO* does not react with carotenoids, whereas in nonpolar environments such as hexane, TOH*+ is converted to TOH by hydrocarbon carotenoids. However, the nature of the reaction between the tocopherol and various carotenoids shows a marked variation depending on the specific tocopherol homologue. The radical cations of the carotenoids all react with vitamin C so as to "repair" the carotenoid.
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            Non-invasive raman spectroscopic detection of carotenoids in human skin.

            Carotenoids are thought to play a significant part in the skin's anti-oxidant defense system, and may help prevent malignancy. Inability to measure skin carotenoid content readily has, however, made it difficult to establish the relationship between carotenoid concentration and the occurrence of cutaneous malignancy. We have measured in vivo carotenoid concentration using a noninvasive optical method, Raman spectroscopy. To validate our instrumentation, abdominoplasty skin was evaluated by both Raman spectroscopy and high-performance liquid chromatography determination for carotenoid content. Evaluation of the Raman signal in specific carotenoid solutions was also performed. Precision of Raman measurements within skin sites, within subjects, and between subjects was measured. Sensitivity of the method was evaluated as a function of anatomical region and the distribution of carotenoids within the stratum corneum. Lastly, we evaluated the Raman signal in actinic keratosis and basal cell carcinoma lesions and perilesional skin and compared this with region-matched sites in healthy subjects. Our results indicate that the Raman scattering method reflects the presence of carotenoids in human skin and is highly reproducible. Evaluation of five anatomical regions demonstrated significant differences in carotenoid concentration by body region with the highest carotenoid concentration noted in the palm. Comparison of carotenoid concentrations in basal cell carcinomas, actinic keratosis, and their perilesional skin demonstrate a significantly lower carotenoid concentration than in region-matched skin of healthy subjects. These results represent the first evidence that carotenoid concentration in the skin correlate with the presence or absence of skin cancer and precancerous lesions.
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              Supplementation with Tomato-Based Products Increases Lycopene, Phytofluene, and Phytoene Levels in Human Serum and Protects Against UV-light-induced Erythema

              Carotenoids are suitable photoprotectants, and β-carotene supplements are used for protection against ultraviolet (UV) light-induced erythema. Protective effects are also observed when carotenoids are provided with the diet. Here, we investigated the photoprotective effects of synthetic lycopene in comparison with a tomato extract (Lyc-o-Mato®) and a drink containing solubilized Lyc-o-Mato® (Lyc-o-Guard-Drink). With these different sources, the volunteers ingested similar amounts of lycopene (about 10 mg/day). After 12 weeks of supplementation, significant increases in lycopene serum levels and total skin carotenoids were observed in all groups. Significant increases in the serum levels of phytofluene and phytoene occurred in the Lyc-o-Mato and the Lyc-o-Guard-Drink group. At weeks 0, 4, and 12 an erythema was induced with a solar light simulator. Dorsal skin of each subject was irradiated with 1.25 minimal erythemal dose (MED). Reddening of the skin was evaluated before and 24 hours after irradiation by chromametry and expressed as positive a-values (red/green-axis). Δ a-values (difference of a-value before irradiation and after 24 hours) were used as an index of erythema intensity. A decrease in the Δ a-value from week 0 to week 12, indicating prevention of erythema formation, was observed in all groups. Compared to week 0, the Δ a-value at week 12 was 25% lower in the synthetic lycopene group. The protective effect was more pronounced in the Lyc-o-Mato (38%) and Lyc-o-Guard-Drink (48%) groups. In the two latter groups, phytofluene and phytoene may have contributed to protection. Both of these carotenoids exhibit absorption maxima at wavelengths of UV light. Absorption of UV light protects skin from photodamage and might explain the differences observed between groups.
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                Author and article information

                Journal
                SPP
                Skin Pharmacol Physiol
                10.1159/issn.1660-5527
                Skin Pharmacology and Physiology
                S. Karger AG
                1660-5527
                1660-5535
                2007
                June 2007
                19 April 2007
                : 20
                : 4
                : 199-210
                Affiliations
                aDepartment of Plastic, Reconstructive and Aesthetic Surgery, Saint Eugenio Hospital, Rome, bDepartment of Dermatology, University of Molise, Campobasso, cDepartment of Dermatology, School of Medicine and Surgery, University of Naples II, Naples, dMavi Sud S.r.l., Aprilia, Italy; eKlinik für Dermatologie, Friedrich-Schiller-Universität Jena, Jena, Germany; fKemin Health, L.C., Des Moines, Iowa, USA
                Article
                101807 Skin Pharmacol Appl Skin Physiol 2007;20:199–210
                10.1159/000101807
                17446716
                93de2ba2-dc0f-43de-b381-d1f41e8e77ea
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 22 September 2006
                : 20 March 2007
                Page count
                Figures: 5, Tables: 3, References: 69, Pages: 12
                Categories
                Original Paper

                Oncology & Radiotherapy,Pathology,Surgery,Dermatology,Pharmacology & Pharmaceutical medicine
                Premature aging,Carotenoid,Zeaxanthin,Antioxidant,Lutein

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