{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:40:26Z","timestamp":1790286026069,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian Research and Innovation Agency, Research Programme","doi-asserted-by":"publisher","award":["P3-0395"],"award-info":[{"award-number":["P3-0395"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nutrition and Public Health and Tosla d.o.o.","award":["P3-0395"],"award-info":[{"award-number":["P3-0395"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Oral photoprotection is gaining attention as a complementary approach to conventional sun protection. This randomized double-blind placebo-controlled study evaluated the effects of an 8-week dietary intervention with a syrup supplement containing Polypodium leucotomos extract (PLE), Red Orange Extract (ROE), and vitamins A, C, D, and E on minimal erythema dose (MED), UVB-induced erythema (\u0394a*), and pigmentation changes (\u0394MI). Methods: In total, 54 fair-skinned participants (phototypes I\u2013III) were randomized into either the intervention (IP) or placebo group (n = 27 per group). MED, \u0394a*, and \u0394MI were assessed at baseline after 2 and 8 weeks of supplementation. Results: Throughout the intervention, MED gradually increased, while \u0394a* decreased in the IP group. While these changes were not statistically significant after 2 weeks, they reached significance after 8 weeks of intervention. By the end of the study, the IP group exhibited a significant 23.8% increase in MED (from 0.447 \u00b1 0.096 to 0.553 \u00b1 0.142 J\/cm2; p &lt; 0.05) and a 46.2% reduction in erythema intensity (from 2.40 \u00b1 0.94 to 1.29 \u00b1 1.04 au; p &lt; 0.0001). In contrast, \u0394MI in the IP group (from 0.67 \u00b1 0.81 to 0.82 \u00b1 0.96 au) were comparable to those observed in the placebo group, with no significant differences between groups. Conclusions: These findings suggest that supplementation with PLE, ROE, and vitamins A, C, D, and E provides systemic photoprotection by enhancing UV tolerance and reducing erythema without affecting tanning response. This study supports oral supplementation as an adjunct to topical photoprotection, with prolonged use potentially yielding cumulative benefits.<\/jats:p>","DOI":"10.3390\/nu17071240","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T05:43:33Z","timestamp":1743572613000},"page":"1240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Eight-Week Supplementation Containing Red Orange and Polypodium leucotomos Extracts on UVB-Induced Skin Responses: A Randomized Double-Blind Placebo-Controlled Trial"],"prefix":"10.3390","volume":"17","author":[{"given":"Petra","family":"Ker\u0161manc","sequence":"first","affiliation":[{"name":"VIST\u2014Faculty of Applied Sciences, Institute of Cosmetics, Gerbi\u010deva Ulica 53, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Poga\u010dnik","sequence":"additional","affiliation":[{"name":"VIST\u2014Faculty of Applied Sciences, Institute of Cosmetics, Gerbi\u010deva Ulica 53, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janko","family":"\u017dmitek","sequence":"additional","affiliation":[{"name":"VIST\u2014Faculty of Applied Sciences, Institute of Cosmetics, Gerbi\u010deva Ulica 53, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5088-9747","authenticated-orcid":false,"given":"Hristo","family":"Hristov","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Koprska Ulica 98, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"To\u010dkova","sequence":"additional","affiliation":[{"name":"VIST\u2014Faculty of Applied Sciences, Institute of Cosmetics, Gerbi\u010deva Ulica 53, 1000 Ljubljana, Slovenia"},{"name":"Department of Dermatovenerology, University Medical Centre Ljubljana, Gradi\u0161kova Ulica 10, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0032-318X","authenticated-orcid":false,"given":"Katja","family":"\u017dmitek","sequence":"additional","affiliation":[{"name":"VIST\u2014Faculty of Applied Sciences, Institute of Cosmetics, Gerbi\u010deva Ulica 53, 1000 Ljubljana, Slovenia"},{"name":"Institute of Nutrition, Koprska Ulica 98, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Farage, M.A., Miller, K.W., and Maibach, H.I. (2017). Influence of Exogenous Factors on Skin Aging. Textbook of Aging Skin, Springer.","DOI":"10.1007\/978-3-662-47398-6"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Farage, M.A., Miller, K.W., and Maibach, H.I. (2017). Textbook of Aging Skin, Springer.","DOI":"10.1007\/978-3-662-47398-6"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1111\/j.1751-1097.2012.01182.x","article-title":"Inflammasome Activation of IL-1 Family Mediators in Response to Cutaneous Photodamage","volume":"88","author":"Nasti","year":"2012","journal-title":"Photochem. Photobiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12222","DOI":"10.3390\/ijms140612222","article-title":"UV Radiation and the Skin","volume":"14","author":"Orazio","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s00011-022-01598-8","article-title":"Photoaging: UV radiation-induced inflammation and immunosuppression accelerate the aging process in the skin","volume":"71","author":"Salminen","year":"2022","journal-title":"Inflamm. Res."},{"key":"ref_6","first-page":"119","article-title":"Antioxidant defense systems in skin (Reprinted from Cosmeceuticals: Drugs vs. cosmetics, pg 145-187, 2000)","volume":"21","author":"Thiele","year":"2002","journal-title":"J. Toxicol.-Cutan. Ocul. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1016\/j.jaad.2016.09.040","article-title":"Current challenges in photoprotection","volume":"76","author":"Lim","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Parrado, C., Philips, N., Gilaberte, Y., Juarranz, A., and Gonz\u00e1lez, S. (2018). Oral Photoprotection: Effective Agents and Potential Candidates. Front. Med., 5.","DOI":"10.3389\/fmed.2018.00188"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/jdv.16030","article-title":"Photoprotection of the future: Challenges and opportunities","volume":"34","author":"Krutmann","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hyeraci, M., Papanikolau, E.S., Grimaldi, M., Ricci, F., Pallotta, S., Monetta, R., Minaf\u00f2, Y.A., Di Lella, G., Galdo, G., and Abeni, D. (2023). Systemic Photoprotection in Melanoma and Non-Melanoma Skin Cancer. Biomolecules, 13.","DOI":"10.3390\/biom13071067"},{"key":"ref_11","first-page":"540","article-title":"Determination of the minimal erythema dose and colorimetric measurements as indicators of skin sensitivity to UV-B radiation","volume":"79","author":"Dornelles","year":"2004","journal-title":"Photochem. Photobiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Anbualakan, K., Tajul Urus, N.Q., Makpol, S., Jamil, A., Mohd Ramli, E.S., Md Pauzi, S.H., and Muhammad, N. (2023). A Scoping Review on the Effects of Carotenoids and Flavonoids on Skin Damage Due to Ultraviolet Radiation. Nutrients, 15.","DOI":"10.3390\/nu15010092"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Luna, A., Zamarr\u00f3n, A., Juarranz, \u00c1., and Gonz\u00e1lez, S. (2023). Clinical Applications of Polypodium leucotomos (Fernblock\u00ae): An Update. Life, 13.","DOI":"10.20944\/preprints202306.1647.v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1039\/d0pp00124d","article-title":"The role of the aqueous extract Polypodium leucotomos in photoprotection","volume":"19","author":"Parrado","year":"2020","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1600-0781.1997.tb00108.x","article-title":"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","volume":"13","author":"Pathak","year":"1997","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.jaad.2004.06.027","article-title":"Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin","volume":"51","author":"Pathak","year":"2004","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/j.1600-0781.2007.00274.x","article-title":"Photoprotective activity of oral Polypodium leucotomos extract in 25 patients with idiopathic photodermatoses","volume":"23","author":"Caccialanza","year":"2007","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jaad.2010.09.773","article-title":"Oral administration of a hydrophilic extract of Polypodium leucotomos for the prevention of polymorphic light eruption","volume":"66","author":"Tanew","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_19","first-page":"85","article-title":"Oral Polypodium leucotomos extract photoprotective activity in 57 patients with idiopathic photodermatoses","volume":"146","author":"Caccialanza","year":"2011","journal-title":"G. Ital. Dermatol. E Venereol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jaad.2017.01.044","article-title":"The impact of oral Polypodium leucotomos extract on ultraviolet B response: A human clinical study","volume":"77","author":"Kohli","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1177\/026119290002800310","article-title":"Iron-induced Lipid Peroxidation in Human Skin-derived Cell Lines: Protection by a Red Orange Extract","volume":"28","author":"Morini","year":"2000","journal-title":"Altern. Lab. Anim. ATLA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/ptr.2973","article-title":"Antiinflammatory effects of a red orange extract in human keratinocytes treated with interferon-gamma and histamine","volume":"24","author":"Cardile","year":"2010","journal-title":"Phytother. Res. PTR"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/biof.5520300206","article-title":"Protective effects of a red orange extract on UVB-induced damage in human keratinocytes","volume":"30","author":"Cimino","year":"2007","journal-title":"BioFactors"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tomasello, B., Malfa, G.A., Acquaviva, R., La Mantia, A., and Di Giacomo, C. (2022). Phytocomplex of a Standardized Extract from Red Orange (Citrus sinensis L. Osbeck) against Photoaging. Cells, 11.","DOI":"10.3390\/cells11091447"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Nobile, V., Burioli, A., Yu, S., Zhifeng, S., Cestone, E., Insolia, V., Zaccaria, V., and Malfa, G.A. (2022). Photoprotective and Antiaging Effects of a Standardized Red Orange (Citrus sinensis (L.) Osbeck) Extract in Asian and Caucasian Subjects: A Randomized, Double-Blind, Controlled Study. Nutrients, 14.","DOI":"10.3390\/nu14112241"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/jocd.12083","article-title":"Protective effect of red orange extract supplementation against UV-induced skin damages: Photoaging and solar lentigines","volume":"13","author":"Puglia","year":"2014","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_27","unstructured":"(2025, March 01). Regulation (EC) No 1924\/2006 of the European Parliament and of the Council of 20 December 2006 on Nutrition and Health Claims Made on Foods. Available online: https:\/\/eur-lex.europa.eu\/eli\/reg\/2006\/1924\/oj\/eng."},{"key":"ref_28","unstructured":"(2025, March 01). Regulation (EU) No 1169\/2011 on the Provision of Food Information to Consumers. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX%3A32011R1169&qid=1742821286601."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1467-2494.1991.tb00561.x","article-title":"Skin colour typology and suntanning pathways","volume":"13","author":"Chardon","year":"1991","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/phpp.12592","article-title":"Global data of unprotected skin minimal erythema dose relationship to Individual Typology Angle","volume":"36","author":"Cole","year":"2020","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/bjd.12529","article-title":"Variations in skin colour and the biological consequences of ultraviolet radiation exposure","volume":"169","author":"Bernerd","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jid.2019.11.003","article-title":"Research Techniques Made Simple: Cutaneous Colorimetry: A Reliable Technique for Objective Skin Color Measurement","volume":"140","author":"Ly","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_33","unstructured":"(2019). Cosmetics\u2013Protection Test Methods\u2013In Vivo Determination of the Sun Protection Factor (SPF) (Standard No. ISO24444:2019)."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0926-9959(97)00183-9","article-title":"EEMCO guidance for the assessment of skin colour","volume":"10","year":"1998","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/srt.12109","article-title":"Discrimination between cutaneous pigmentation and erythema: Comparison of the skin colorimeters Dermacatch and Mexameter","volume":"20","author":"Kasraee","year":"2014","journal-title":"Ski. Res. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000497104","article-title":"Tomato Phytonutrients Balance UV Response: Results from a Double-Blind, Randomized, Placebo-Controlled Study","volume":"32","author":"Groten","year":"2019","journal-title":"Ski. Pharmacol. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Del Bino, S., Duval, C., and Bernerd, F. (2018). Clinical and Biological Characterization of Skin Pigmentation Diversity and Its Consequences on UV Impact. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092668"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s43856-024-00550-7","article-title":"Melanometry for objective evaluation of skin pigmentation in pulse oximetry studies","volume":"4","author":"Vasudevan","year":"2024","journal-title":"Commun. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.jaad.2013.11.004","article-title":"Update on tanning: More risks, fewer benefits","volume":"70","author":"Diehl","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_40","first-page":"19","article-title":"Safety and Efficacy of Oral Polypodium leucotomos Extract in Healthy Adult Subjects","volume":"8","author":"Nestor","year":"2015","journal-title":"J. Clin. Aesthetic Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Januszewski, J., Forma, A., Zembala, J., Flieger, M., Tyczy\u0144ska, M., Dring, J.C., Dudek, I., \u015awi\u0105tek, K., and Baj, J. (2024). Nutritional Supplements for Skin Health\u2014A Review of What Should Be Chosen and Why. Medicina, 60.","DOI":"10.3390\/medicina60010068"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Calniquer, G., Khanin, M., Ovadia, H., Linnewiel-Hermoni, K., Stepensky, D., Trachtenberg, A., Sedlov, T., Braverman, O., Levy, J., and Sharoni, Y. (2021). Combined Effects of Carotenoids and Polyphenols in Balancing the Response of Skin Cells to UV Irradiation. Molecules, 26.","DOI":"10.3390\/molecules26071931"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.3390\/ijms12128466","article-title":"Fernblock, a nutriceutical with photoprotective properties and potential preventive agent for skin photoaging and photoinduced skin cancers","volume":"12","author":"Gonzalez","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Parrado, C., Mascaraque, M., Gilaberte, Y., Juarranz, A., and Gonzalez, S. (2016). Fernblock (Polypodium leucotomos Extract): Molecular Mechanisms and Pleiotropic Effects in Light-Related Skin Conditions, Photoaging and Skin Cancers, a Review. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071026"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4606","DOI":"10.1080\/14786419.2019.1696329","article-title":"Blood orange (Citrus sinensis) as a rich source of nutraceuticals: Investigation of bioactive compounds in different parts of the fruit by HPLC-PDA\/MS","volume":"35","author":"Russo","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1046\/j.1467-2494.1998.177057.x","article-title":"In vitro antioxidant activity and in vivo photoprotective effect of a red orange extract","volume":"20","author":"Saija","year":"1998","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"641","DOI":"10.4162\/nrp.2023.17.4.641","article-title":"Protective effects of red orange (Citrus sinensis [L.] Osbeck [Rutaceae]) extract against UVA-B radiation-induced photoaging in Skh:HR-2 mice","volume":"17","author":"Kim","year":"2023","journal-title":"Nutr. Res. Pract."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1240\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:08:32Z","timestamp":1760029712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,2]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["nu17071240"],"URL":"https:\/\/doi.org\/10.3390\/nu17071240","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,2]]}}}