{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:29:15Z","timestamp":1787970555704,"version":"build-2784847793"},"reference-count":107,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007214","name":"VELUX Stiftung","doi-asserted-by":"publisher","award":["1156"],"award-info":[{"award-number":["1156"]}],"id":[{"id":"10.13039\/100007214","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007214","name":"VELUX Stiftung","doi-asserted-by":"publisher","award":["201808500155"],"award-info":[{"award-number":["201808500155"]}],"id":[{"id":"10.13039\/100007214","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China Scholarship Counsel","award":["1156"],"award-info":[{"award-number":["1156"]}]},{"name":"China Scholarship Counsel","award":["201808500155"],"award-info":[{"award-number":["201808500155"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Oxidative stress has been proposed as a key contributor to lifestyle- and age-related diseases. Because free radicals play an important role in various processes such as immune responses and cellular signaling, the body possesses an arsenal of different enzymatic and non-enzymatic antioxidant defense mechanisms. Oxidative stress is, among others, the result of an imbalance between the production of various reactive oxygen species (ROS) and antioxidant defense mechanisms including vitamin E (\u03b1-tocopherol) as a non-enzymatic antioxidant. Dietary vitamins, such as vitamin C and E, can also be taken in as supplements. It has been postulated that increasing antioxidant levels through supplementation may delay and\/or ameliorate outcomes of lifestyle- and age-related diseases that have been linked to oxidative stress. Although supported by many animal experiments and observational studies, randomized clinical trials in humans have failed to demonstrate any clinical benefit from antioxidant supplementation. Nevertheless, possible explanations for this discrepancy remain underreported. This review aims to provide an overview of recent developments and novel research techniques used to clarify the existing controversy on the benefits of antioxidant supplementation in health and disease, focusing on \u03b1-tocopherol as antioxidant. Based on the currently available literature, we propose that examining the difference between antioxidant activity and capacity, by considering the catabolism of antioxidants, will provide crucial knowledge on the preventative and therapeutical use of antioxidant supplementation in oxidative stress-related diseases.<\/jats:p>","DOI":"10.3390\/antiox11122322","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T02:25:36Z","timestamp":1669256736000},"page":"2322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Antioxidant Supplementation in Oxidative Stress-Related Diseases: What Have We Learned from Studies on Alpha-Tocopherol?"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8910-9795","authenticated-orcid":false,"given":"Fleur L.","family":"Meulmeester","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8511-8945","authenticated-orcid":false,"given":"Jiao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands"},{"name":"Department of Clinical Epidemiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon G.","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Mills","sequence":"additional","affiliation":[{"name":"NIHR Great Ormond Street Biomedical Research Centre, Great Ormond Street Hospital, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-7748","authenticated-orcid":false,"given":"Diana","family":"van Heemst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-809X","authenticated-orcid":false,"given":"Raymond","family":"Noordam","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1017\/S0029665113003881","article-title":"Nutrition and healthy ageing: The key ingredients","volume":"73","author":"Mathers","year":"2014","journal-title":"Proc. Nutr. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10522-021-09910-5","article-title":"Aging and age-related diseases: From mechanisms to therapeutic strategies","volume":"22","author":"Li","year":"2021","journal-title":"Biogerontology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/35041700","article-title":"Genetic pathways that regulate ageing in model organisms","volume":"408","author":"Guarente","year":"2000","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41576-019-0183-6","article-title":"The genetics of human ageing","volume":"21","author":"Melzer","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1038\/s41598-018-24146-z","article-title":"Calorie restriction is the most reasonable anti-ageing intervention: A meta-analysis of survival curves","volume":"8","author":"Liang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101228","DOI":"10.1016\/j.arr.2020.101228","article-title":"Effects of caloric restriction on the antagonistic and integrative hallmarks of aging","volume":"66","author":"Erbaba","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive oxygen species (ROS) as pleiotropic physiological signalling agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12291-014-0446-0","article-title":"Free radicals: Properties, sources, targets, and their implication in various diseases","volume":"30","author":"Phaniendra","year":"2015","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.redox.2015.01.002","article-title":"Oxidative stress: A concept in redox biology and medicine","volume":"4","author":"Sies","year":"2015","journal-title":"Redox Biol."},{"key":"ref_12","first-page":"e157","article-title":"The role of vitamin e in human health and some diseases","volume":"14","author":"Rizvi","year":"2014","journal-title":"Sultan Qaboos Univ. Med. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1093\/ajcn\/84.5.1200","article-title":"Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study","volume":"84","author":"Wright","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"584","DOI":"10.3945\/ajcn.2008.26423","article-title":"Vitamin E intake, alpha-tocopherol status, and pancreatic cancer in a cohort of male smokers","volume":"89","author":"Weinstein","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1161\/CIRCRESAHA.119.314944","article-title":"Relationship Between Serum Alpha-Tocopherol and Overall and Cause-Specific Mortality","volume":"125","author":"Huang","year":"2019","journal-title":"Circ. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"915","DOI":"10.3945\/ajcn.114.085480","article-title":"Vitamin E and C supplementation and risk of cancer in men: Posttrial follow-up in the Physicians\u2019 Health Study II randomized trial","volume":"100","author":"Wang","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1001\/jama.2008.600","article-title":"Vitamins E and C in the prevention of cardiovascular disease in men: The Physicians\u2019 Health Study II randomized controlled trial","volume":"300","author":"Sesso","year":"2008","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1001\/jama.294.1.56","article-title":"Vitamin E in the primary prevention of cardiovascular disease and cancer: The Women\u2019s Health Study: A randomized controlled trial","volume":"294","author":"Lee","year":"2005","journal-title":"JAMA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"f10","DOI":"10.1136\/bmj.f10","article-title":"Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: Systematic review and meta-analysis of randomised controlled trials","volume":"346","author":"Myung","year":"2013","journal-title":"Bmj"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1245049","DOI":"10.1155\/2016\/1245049","article-title":"Role of ROS and RNS Sources in Physiological and Pathological Conditions","volume":"2016","author":"Reed","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.redox.2017.12.012","article-title":"Teaching the basics of reactive oxygen species and their relevance to cancer biology: Mitochondrial reactive oxygen species detection, redox signaling, and targeted therapies","volume":"15","author":"Kalyanaraman","year":"2018","journal-title":"Redox Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100982","DOI":"10.1016\/j.arr.2019.100982","article-title":"Ageing, age-related diseases and oxidative stress: What to do next?","volume":"57","author":"Luo","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1042\/BJ20111752","article-title":"Cell signalling by reactive lipid species: New concepts and molecular mechanisms","volume":"442","author":"Higdon","year":"2012","journal-title":"Biochem. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101098","DOI":"10.1016\/j.mam.2022.101098","article-title":"The influence of the dietary exposome on oxidative stress in pregnancy complications","volume":"87","author":"Prins","year":"2022","journal-title":"Mol. Aspects Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118535","DOI":"10.1016\/j.bbamcr.2019.118535","article-title":"Iron homeostasis and oxidative stress: An intimate relationship","volume":"1866","author":"Galaris","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.bcp.2008.11.009","article-title":"Reactive oxygen species: Destroyers or messengers?","volume":"77","author":"Bartosz","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1021\/acs.chemrev.7b00568","article-title":"Biochemistry of Peroxynitrite and Protein Tyrosine Nitration","volume":"118","author":"Campolo","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101505","DOI":"10.1016\/j.redox.2020.101505","article-title":"Sexual hormones regulate the redox status and mitochondrial function in the brain. Pathological implications","volume":"31","author":"Pons","year":"2020","journal-title":"Redox Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/jn\/nxy306","article-title":"Redox Systems Biology of Nutrition and Oxidative Stress","volume":"149","author":"Dennis","year":"2019","journal-title":"J. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4350965","DOI":"10.1155\/2016\/4350965","article-title":"ROS and ROS-Mediated Cellular Signaling","volume":"2016","author":"Zhang","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/jcb.20202","article-title":"Thiol oxidation of cell signaling proteins: Controlling an apoptotic equilibrium","volume":"93","author":"Cross","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13086","DOI":"10.1073\/pnas.0603290103","article-title":"Dynamic redox control of NF-kappaB through glutaredoxin-regulated S-glutathionylation of inhibitory kappaB kinase beta","volume":"103","author":"Reynaert","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Courtois, G., and Fauvarque, M.O. (2018). The Many Roles of Ubiquitin in NF-\u03baB Signaling. Biomedicines, 6.","DOI":"10.3390\/biomedicines6020043"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.cr.7290105","article-title":"MAPK signal pathways in the regulation of cell proliferation in mammalian cells","volume":"12","author":"Zhang","year":"2002","journal-title":"Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41418-018-0062-2","article-title":"The tango of ROS and p53 in tissue stem cells","volume":"25","author":"Chen","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.freeradbiomed.2011.05.010","article-title":"Extending life span by increasing oxidative stress","volume":"51","author":"Ristow","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_37","first-page":"w13659","article-title":"Reactive oxygen species: From health to disease","volume":"142","author":"Brieger","year":"2012","journal-title":"Swiss Med. Wkly."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.molmed.2019.06.001","article-title":"Low Production of Reactive Oxygen Species Drives Systemic Lupus Erythematosus","volume":"25","author":"Urbonaviciute","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.redox.2015.07.009","article-title":"Genetic disorders coupled to ROS deficiency","volume":"6","author":"Brault","year":"2015","journal-title":"Redox Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Aggarwal, V., Tuli, H.S., Varol, A., Thakral, F., Yerer, M.B., Sak, K., Varol, M., Jain, A., Khan, M.A., and Sethi, G. (2019). Role of Reactive Oxygen Species in Cancer Progression: Molecular Mechanisms and Recent Advancements. Biomolecules, 9.","DOI":"10.3390\/biom9110735"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11010-019-03667-9","article-title":"ROS and diseases: Role in metabolism and energy supply","volume":"467","author":"Yang","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.cell.2008.04.041","article-title":"A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy","volume":"133","author":"Ago","year":"2008","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3236","DOI":"10.1161\/01.ATV.17.11.3236","article-title":"Prostaglandin F2-like compounds, F2-isoprostanes, are present in increased amounts in human atherosclerotic lesions","volume":"17","author":"Gniwotta","year":"1997","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1161\/CIRCRESAHA.110.232306","article-title":"Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Galphaq overexpression-induced heart failure","volume":"108","author":"Dai","year":"2011","journal-title":"Circ. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jacc.2015.05.020","article-title":"Contractile Function During Angiotensin-II Activation: Increased Nox2 Activity Modulates Cardiac Calcium Handling via Phospholamban Phosphorylation","volume":"66","author":"Zhang","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Cervantes Gracia, K., Llanas-Cornejo, D., and Husi, H. (2017). CVD and Oxidative Stress. J. Clin. Med., 6.","DOI":"10.3390\/jcm6020022"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"360438","DOI":"10.1155\/2014\/360438","article-title":"Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.bbadis.2015.01.015","article-title":"On the role of 4-hydroxynonenal in health and disease","volume":"1852","author":"Csala","year":"2015","journal-title":"Biochim. Biophys. Acta BBA Mol. Basis Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1152\/physrev.00047.2003","article-title":"Role of oxidative modifications in atherosclerosis","volume":"84","author":"Stocker","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s11883-017-0678-6","article-title":"Oxidative Stress in Atherosclerosis","volume":"19","author":"Kattoor","year":"2017","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/php.12969","article-title":"Cholesterol Peroxidation as a Special Type of Lipid Oxidation in Photodynamic Systems","volume":"95","author":"Girotti","year":"2019","journal-title":"Photochem. Photobiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3390\/biom2010076","article-title":"Oxysterols and their cellular effectors","volume":"2","author":"Olkkonen","year":"2012","journal-title":"Biomolecules"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.redox.2012.12.001","article-title":"Oxysterols in the pathogenesis of major chronic diseases","volume":"1","author":"Poli","year":"2013","journal-title":"Redox Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"101615","DOI":"10.1016\/j.arr.2022.101615","article-title":"Oxysterols are potential physiological regulators of ageing","volume":"77","author":"Poirot","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Luo, J., Noordam, R., Jukema, J.W., van Dijk, K.W., H\u00e4gg, S., Grassmann, F., le Cessie, S., and van Heemst, D. (2021). Low mitochondrial copy number drives atherogenic cardiovascular disease: Evidence from prospective cohort analyses in the UK Biobank combined with Mendelian Randomization. medRxiv.","DOI":"10.1101\/2021.07.01.21259854"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"325","DOI":"10.5607\/en.2015.24.4.325","article-title":"The Role of Oxidative Stress in Neurodegenerative Diseases","volume":"24","author":"Kim","year":"2015","journal-title":"Exp. Neurobiol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lee, K.H., Cha, M., and Lee, B.H. (2020). Neuroprotective Effect of Antioxidants in the Brain. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197152"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.bbadis.2013.10.015","article-title":"Oxidative stress and mitochondrial dysfunction in Alzheimer\u2019s disease","volume":"1842","author":"Wang","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40035-021-00261-2","article-title":"Mitochondrial links between brain aging and Alzheimer\u2019s disease","volume":"10","author":"Wilkins","year":"2021","journal-title":"Transl. Neurodegener."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41586-021-04059-0","article-title":"Disruption of mitochondrial complex I induces progressive parkinsonism","volume":"599","author":"Zampese","year":"2021","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcdb.2017.05.023","article-title":"ROS signalling in the biology of cancer","volume":"80","author":"Moloney","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e269","DOI":"10.1038\/emm.2016.119","article-title":"ROS homeostasis and metabolism: A critical liaison for cancer therapy","volume":"48","author":"Kim","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s13046-018-0909-x","article-title":"The role of cellular reactive oxygen species in cancer chemotherapy","volume":"37","author":"Yang","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"R646","DOI":"10.1152\/ajpregu.00247.2017","article-title":"The differential role of reactive oxygen species in early and late stages of cancer","volume":"313","author":"Assi","year":"2017","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1158\/1078-0432.CCR-18-3423","article-title":"Measurement of Tumor Antioxidant Capacity and Prediction of Chemotherapy Resistance in Preclinical Models of Ovarian Cancer by Positron Emission Tomography","volume":"25","author":"Greenwood","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6590","DOI":"10.1158\/1078-0432.CCR-19-0594","article-title":"First-in-Human Phase I Clinical Trial of Pharmacologic Ascorbate Combined with Radiation and Temozolomide for Newly Diagnosed Glioblastoma","volume":"25","author":"Allen","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.semradonc.2018.10.006","article-title":"Pharmacological Ascorbate as a Means of Sensitizing Cancer Cells to Radio-Chemotherapy While Protecting Normal Tissue","volume":"29","author":"Schoenfeld","year":"2019","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Flieger, J., Flieger, W., Baj, J., and Maciejewski, R. (2021). Antioxidants: Classification, Natural Sources, Activity\/Capacity Measurements, and Usefulness for the Synthesis of Nanoparticles. Materials, 14.","DOI":"10.3390\/ma14154135"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.freeradbiomed.2013.03.022","article-title":"Role of vitamin E as a lipid-soluble peroxyl radical scavenger: In vitro and in vivo evidence","volume":"66","author":"Niki","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1515\/BC.2002.048","article-title":"The 80th anniversary of vitamin E: Beyond its antioxidant properties","volume":"383","author":"Ricciarelli","year":"2002","journal-title":"Biol. Chem."},{"key":"ref_71","first-page":"287","article-title":"First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid","volume":"54","author":"Ighodaro","year":"2018","journal-title":"Alex. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1089\/ars.2010.3586","article-title":"Glutathione peroxidase-1 in health and disease: From molecular mechanisms to therapeutic opportunities","volume":"15","author":"Lubos","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/molehr\/gal080","article-title":"Age-dependent changes in the expression of superoxide dismutases and catalase are associated with ultrastructural modifications in human granulosa cells","volume":"12","author":"Tatone","year":"2006","journal-title":"Mol. Hum. Reprod."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"763","DOI":"10.2147\/CIA.S201250","article-title":"Changes in the blood antioxidant defense of advanced age people","volume":"14","author":"Kozakiewicz","year":"2019","journal-title":"Clin. Interv. Aging"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.vph.2015.03.005","article-title":"The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review)","volume":"71","author":"Siti","year":"2015","journal-title":"Vasc. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/HJR.0b013e3282f11f95","article-title":"Antioxidant vitamins intake and the risk of coronary heart disease: Meta-analysis of cohort studies","volume":"15","author":"Ye","year":"2008","journal-title":"Eur. J. Cardiovasc. Prev. Rehabil."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1161\/STROKEAHA.110.601526","article-title":"Dietary intakes of antioxidant vitamins and mortality from cardiovascular disease: The Japan Collaborative Cohort Study (JACC) study","volume":"42","author":"Kubota","year":"2011","journal-title":"Stroke"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1001\/jama.287.24.3223","article-title":"Dietary intake of antioxidants and risk of Alzheimer disease","volume":"287","author":"Engelhart","year":"2002","journal-title":"JAMA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1001\/archneur.61.1.82","article-title":"Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: The Cache County Study","volume":"61","author":"Zandi","year":"2004","journal-title":"Arch. Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/S1474-4422(05)70097-1","article-title":"Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson\u2019s disease: A meta-analysis","volume":"4","author":"Etminan","year":"2005","journal-title":"Lancet Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1093\/aje\/kwq416","article-title":"Vitamin E intake and risk of amyotrophic lateral sclerosis: A pooled analysis of data from 5 prospective cohort studies","volume":"173","author":"Wang","year":"2011","journal-title":"Am. J. Epidemiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1136\/jnnp.2005.083378","article-title":"Intake of polyunsaturated fatty acids and vitamin E reduces the risk of developing amyotrophic lateral sclerosis","volume":"78","author":"Veldink","year":"2007","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1001\/jama.2008.862","article-title":"Vitamins E and C in the prevention of prostate and total cancer in men: The Physicians\u2019 Health Study II randomized controlled trial","volume":"301","author":"Gaziano","year":"2009","journal-title":"JAMA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jacc.2020.10.048","article-title":"Diet-Derived Circulating Antioxidants and Risk of Coronary Heart Disease: A Mendelian Randomization Study","volume":"77","author":"Luo","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Martens, L.G., Luo, J., Dijk, K.W.V., Jukema, J.W., Noordam, R., and Heemst, D.V. (2021). Diet-derived antioxidants do not decrease the risk of ischemic stroke: A Mendelian Randomization Study in over 1 million participants. medRxiv.","DOI":"10.1101\/2021.03.19.21253362"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1093\/ajcn\/nqy225","article-title":"Circulating antioxidants and Alzheimer disease prevention: A Mendelian randomization study","volume":"109","author":"Williams","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/iub.1990","article-title":"Vitamin E\u2014The Next 100 Years","volume":"71","author":"Khadangi","year":"2019","journal-title":"IUBMB Life"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1046\/j.1468-1331.2001.00273.x","article-title":"Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency","volume":"8","author":"Gabsi","year":"2001","journal-title":"Eur. J. Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/ng0295-141","article-title":"Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein","volume":"9","author":"Ouahchi","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_90","unstructured":"Maxfield, L., and Crane, J.S. (2021, September 01). Vitamin C Deficiency, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK493187\/."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s10654-013-9801-3","article-title":"The Netherlands Epidemiology of Obesity (NEO) study: Study design and data collection","volume":"28","author":"Rabelink","year":"2013","journal-title":"Eur. J. Epidemiol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Martens, L.G., Luo, J., Meulmeester, F.L., Ashrafi, N., van Eekelen, E.W., de Mutsert, R., Mook-Kanamori, D.O., Rosendaal, F.R., van Dijk, K.W., and Mills, K. (2020). Associations between Lifestyle Factors and Vitamin E Metabolites in the General Population. Antioxidants, 9.","DOI":"10.3390\/antiox9121280"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4192","DOI":"10.1016\/j.clnu.2021.01.039","article-title":"Urinary oxidized, but not enzymatic vitamin E metabolites are inversely associated with measures of glucose homeostasis in middle-aged healthy individuals","volume":"40","author":"Luo","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1016\/j.numecd.2021.05.001","article-title":"Association of measures of body fat with serum alpha-tocopherol and its metabolites in middle-aged individuals","volume":"31","author":"Meulmeester","year":"2021","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"111440","DOI":"10.1016\/j.nut.2021.111440","article-title":"Associations of metabolomic profiles with circulating vitamin E and urinary vitamin E metabolites in middle-aged individuals","volume":"93","author":"Luo","year":"2022","journal-title":"Nutrition"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.jplph.2005.04.012","article-title":"Vitamin E bioavailability in humans","volume":"162","author":"Lodge","year":"2005","journal-title":"J. Plant Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Rubio, C.P., Hern\u00e1ndez-Ruiz, J., Martinez-Subiela, S., Tvarijonaviciute, A., and Ceron, J.J. (2016). Spectrophotometric assays for total antioxidant capacity (TAC) in dog serum: An update. BMC Vet. Res., 12.","DOI":"10.1186\/s12917-016-0792-7"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4331\/wjbc.v7.i1.14","article-title":"Complexity of vitamin E metabolism","volume":"7","author":"Birringer","year":"2016","journal-title":"World J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev-biochem-061516-045037","article-title":"Oxidative Stress","volume":"86","author":"Sies","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.archoralbio.2013.01.016","article-title":"Ascorbic acid and its pro-oxidant activity as a therapy for tumours of oral cavity\u2014A systematic review","volume":"58","author":"Putchala","year":"2013","journal-title":"Arch. Oral Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2165\/00063030-200620050-00002","article-title":"The pro-oxidant activity of high-dose vitamin E supplements in vivo","volume":"20","author":"Pearson","year":"2006","journal-title":"BioDrugs"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.freeradbiomed.2011.05.017","article-title":"Vitamins C and E: Beneficial effects from a mechanistic perspective","volume":"51","author":"Traber","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"635","DOI":"10.29252\/ijrm.15.10.6","article-title":"The effect of vitamin E and aspirin on the uterine artery blood flow in women with recurrent abortion: A single-blind randomized controlled trial","volume":"15","author":"Mesdaghinia","year":"2017","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1279250","DOI":"10.1155\/2019\/1279250","article-title":"Approaches and Methods to Measure Oxidative Stress in Clinical Samples: Research Applications in the Cancer Field","volume":"2019","author":"Katerji","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3196S","DOI":"10.1093\/jn\/134.11.3196S","article-title":"Efficacy of Dietary Antioxidants to Prevent Oxidative Damage and Inhibit Chronic Disease","volume":"134","author":"Frei","year":"2004","journal-title":"J. Nutr."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"75767","DOI":"10.18632\/oncotarget.20801","article-title":"Potential application of the oxidative nucleic acid damage biomarkers in detection of diseases","volume":"8","author":"Guo","year":"2017","journal-title":"Oncotarget"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0009-8981(03)00003-2","article-title":"Protein carbonyl groups as biomarkers of oxidative stress","volume":"329","author":"Rossi","year":"2003","journal-title":"Clin. Chim. Acta"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/12\/2322\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:25:32Z","timestamp":1760145932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/12\/2322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":107,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["antiox11122322"],"URL":"https:\/\/doi.org\/10.3390\/antiox11122322","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]}}}