Citation: Tran, J.T.; Diaz, M.J.; Rodriguez, D.; Kleinberg, G.; Aflatooni, S.; Palreddy, S.; Abdi, P.; Taneja, K.; Batchu, S.; Forouzandeh, M. Evidence-Based Utility of Adjunct Antioxidant Supplementation for the Prevention and Treatment of Dermatologic Diseases: A Comprehensive Systematic Review. Antioxidants 2023, 12, 1503. https://doi.org/10.3390/ antiox12081503 Academic Editors: Ivana Beatrice Mânica Da Cruz and Fernanda Barbisan Received: 18 June 2023 Revised: 7 July 2023 Accepted: 14 July 2023 Published: 27 July 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). antioxidants Systematic Review Evidence-Based Utility of Adjunct Antioxidant Supplementation for the Prevention and Treatment of Dermatologic Diseases: A Comprehensive Systematic Review Jasmine Thuy Tran 1 , Michael Joseph Diaz 2 , Daphnee Rodriguez 3 , Giona Kleinberg 4 , Shaliz Aflatooni 5 , Siri Palreddy 6 , Parsa Abdi 7 , Kamil Taneja 8 , Sai Batchu 9, * and Mahtab Forouzandeh 10, * 1 School of Medicine, Indiana University, Indianapolis, IN 46202, USA 2 College of Medicine, University of Florida, Gainesville, FL 32610, USA 3 College of Medicine, University of Central Florida, Orlando, FL 32827, USA 4 College of Engineering, Northeastern University, Boston, MA 02115, USA 5 Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA 6 Department of Biology, Amherst College, Amherst, MA 01002, USA 7 Faculty of Medicine, Memorial University, St. Johns, NL A1B 3V6, Canada 8 Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; kamil.taneja@stonybrookmedicine.edu 9 Cooper Medical School, Rowan University, Camden, NJ 08103, USA 10 Department of Dermatology, University of Florida, Gainesville, FL 32606, USA * Correspondence: batchus1@tcnj.edu (S.B.); mforouzandeh@dermatology.med.ufl.edu (M.F.) Abstract: Skin conditions are a significant cause of fatal and nonfatal disease burdens globally, rang- ing from mild irritations to debilitating diseases. Oxidative stress, which is an imbalance between reactive oxygen species and the cells’ ability to repair damage, is implicated in various skin diseases. Antioxidants have been studied for their potential benefits in dermatologic health, but the evidence is limited and conflicting. Herein, we conducted a systematic review of controlled trials, meta-analyses, and Cochrane review articles to evaluate the current evidence on the utility of antioxidant supple- mentation for adjunct prevention and treatment of skin disease and to provide a comprehensive assessment of their role in promoting dermatologic health. The Cochrane Library, PubMed, EM- BASE, and Epistemonikos databases were queried. Eligibility criteria included (1) primary focus on nanoparticle utility for skin cancer; (2) includes measurable outcomes data with robust comparators; (3) includes a number of human subjects or cell-line types, where applicable; (4) English language; and (5) archived as full-text journal articles. A total of 56 articles met the eligibility criteria for the present review. Qualitative analysis revealed that topical and oral antioxidant supplementation has demonstrated preliminary efficacy in reducing sunburns, depigmentation, and photoaging. Dietary exogenous antioxidants (namely vitamins A, C, and E) have shown chemopreventive effects against skin cancer. Antioxidant supplementation has also shown efficacy in treating non-cancer dermatoses, including rosacea, psoriasis, atopic dermatitis, and acne vulgaris. While further studies are needed to validate these findings on a larger scale, antioxidant supplementation holds promise for improving skin health and preventing skin diseases. Keywords: antioxidant supplementation; vitamins; reactive oxygen species; skin cancer; dermatology 1. Introduction According to the Global Burden of Disease project, skin conditions are the fourth- leading source of nonfatal disease burden globally [1]. These conditions can range from mild irritations to chronic, debilitating diseases that significantly impact a person’s quality of life. Importantly, skin manifestations can give way to new diagnoses of otherwise occult systemic diseases, aiding in the timely initiation of important care and optimizing patient outcomes [2,3]. Antioxidants 2023, 12, 1503. https://doi.org/10.3390/antiox12081503 https://www.mdpi.com/journal/antioxidants