{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:07Z","timestamp":1791521407706,"version":"4.3.4"},"reference-count":59,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Lodz","award":["503\/3-045-02\/503-31-001"],"award-info":[{"award-number":["503\/3-045-02\/503-31-001"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"crossref"}]},{"award":["503\/3-045-02\/503-31-001"],"award-info":[{"award-number":["503\/3-045-02\/503-31-001"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Riboflavin, i.e., vitamin B2, was first isolated by Kuhn and Gy\u0151rgy in 1933, who reported that it acts as a growth factor. Riboflavin has long been known to play a key role in energy metabolism and cellular respiration, and its deficiency negatively affects skin and mucous membrane health. More recent studies have found it to regulate mitochondrial metabolism and to serve as the core of flavin coenzymes (FAD, FMN), which enable the respiratory chain and \u03b2-oxidation. Riboflavin also plays a key role as an antioxidant. While it is not a classic free antioxidant, it supports the enzymatic antioxidant system by supporting glutathione reductase, thioredoxin reductase, and ROS neutralization. On the other hand, when exposed to light, riboflavin exhibits photosensitizing properties that generate reactive oxygen species. As a result, it can initiate oxidative processes involving lipids, proteins, and nucleic acids, thereby exhibiting a prooxidative effect. The aim of this review is to provide an overview of the current understanding of the role of riboflavin in cellular and human health.<\/jats:p>","DOI":"10.3390\/nu18193223","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:14:37Z","timestamp":1790694877000},"page":"3223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Riboflavin as a Regulator of Cellular Metabolism: From the Classic Vitamin B2 to a Key Redox Factor"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8560-5727","authenticated-orcid":false,"given":"Julia","family":"Ka\u017amierczak-Bara\u0144ska","sequence":"first","affiliation":[{"name":"DNA Damage Laboratory, Food Science Department, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1709-5897","authenticated-orcid":false,"given":"Krzysztof","family":"Halczuk","sequence":"additional","affiliation":[{"name":"DNA Damage Laboratory, Food Science Department, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6922-7834","authenticated-orcid":false,"given":"Boles\u0142aw T.","family":"Karwowski","sequence":"additional","affiliation":[{"name":"DNA Damage Laboratory, Food Science Department, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Overview of flavin-dependent enzymes","volume":"47","author":"Pimviriyakul","year":"2020","journal-title":"Enzymes"},{"key":"ref_2","unstructured":"Preedy, V.R. (2013). Riboflavin and B-Oxidation Flavoenzymes in B Vitamins and Folate: Chemistry, Analysis, Function and Effects, Royal Society of Chemistry."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1093\/ajcn\/77.6.1352","article-title":"Riboflavin (vitamin B-2) and health","volume":"77","author":"Powers","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1002\/jimd.12058","article-title":"Disorders of riboflavin metabolism","volume":"42","author":"Balasubramaniam","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1017\/S0007114514000178","article-title":"Riboflavin (vitamin B2) and oxidative stress: A review","volume":"111","author":"Ashoori","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.bbadis.2018.10.021","article-title":"Cofactors revisited\u2014Predicting the impact of flavoprotein-related diseases on a genome scale","volume":"1865","author":"Wegrzyn","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1960S","DOI":"10.3945\/ajcn.2009.27230B","article-title":"Studies of biomarker responses to intervention with riboflavin: A systematic review","volume":"89","author":"Hoey","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1146\/annurev-nutr-061121-084407","article-title":"Causes and Clinical Sequelae of Riboflavin Deficiency","volume":"43","author":"McNulty","year":"2023","journal-title":"Annu. Rev. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s12986-021-00630-8","article-title":"Effectiveness of a fortified drink in improving B vitamin biomarkers in older adults: A controlled intervention trial","volume":"18","author":"Heffernan","year":"2021","journal-title":"Nutr. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gibson, R.S. (2005). Assessment of the Status of Thiamin, Riboflavin, and Niacin. Principles of Nutritional Assessment, Oxford University Press. [2nd ed.].","DOI":"10.1093\/oso\/9780195171693.003.0020"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.3762\/bjoc.10.208","article-title":"Photo, thermal and chemical degradation of riboflavin","volume":"10","author":"Sheraz","year":"2014","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S0022-3476(77)80784-1","article-title":"Light (phototherapy)-induced riboflavin deficiency in the neonate","volume":"90","author":"Gromisch","year":"1977","journal-title":"J. Pediatr."},{"key":"ref_13","first-page":"76","article-title":"Significance of phototherapy-induced riboflavin deficiency in the full-term neonate","volume":"61","author":"Amin","year":"1992","journal-title":"Biol. Neonate"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4919","DOI":"10.1017\/S0029665118000708","article-title":"Intake, status and dietary sources of riboflavin in a representative sample of Irish adults aged 18\u201390 years","volume":"77","author":"Kehoe","year":"2018","journal-title":"Proc. Nutr. Soc."},{"key":"ref_15","unstructured":"World Health Organization, and Food and Agriculture Organization of the United Nations (2004). Vitamin and Mineral Requirements in Human Nutrition, World Health Organization. [2nd ed.]."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mosegaard, S., Dipace, G., Bross, P., Carlsen, J., Gregersen, N., and Olsen, R.K.J. (2020). Riboflavin Deficiency-Implications for General Human Health and Inborn Errors of Metabolism. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113847"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1093\/ajcn\/63.1.54","article-title":"Pharmacokinetics of orally intravenously administered riboflavin in healthy humans","volume":"63","author":"Zempleni","year":"1996","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tao, Z., Huo, J., Hao, X., and Liang, J. (2025). Riboflavin in neurological diseases: Therapeutic advances, metabolic insights, and emerging genetic strategies. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1663136"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"681","DOI":"10.2147\/JIR.S501652","article-title":"Flavins and Flavoproteins in the Neuroimmune Landscape of Stress Sensitization and Major Depressive Disorder","volume":"18","author":"Schrier","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4078","DOI":"10.1038\/s41467-025-59255-7","article-title":"Structure and transport mechanism of human riboflavin transporters","volume":"16","author":"Wang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_21","first-page":"2659","article-title":"The Expression of Riboflavin Transporters in Human Colorectal Cancer","volume":"38","author":"Tutino","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bartmann, L., Schumacher, D., von Stillfried, S., Sternkopf, M., Alampour-Rajabi, S., van Zandvoort, M.A.M.J., Kiessling, F., and Wu, Z. (2019). Evaluation of Riboflavin Transporters as Targets for Drug Delivery and Theranostics. Front. Pharmacol., 10, Erratum in Front. Pharmacol. 2020, 11, 617329. https:\/\/doi.org\/10.3389\/fphar.2020.617329.","DOI":"10.3389\/fphar.2020.617329"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41586-025-09018-7","article-title":"Taurine from tumour niche drives glycolysis to promote leukaemogenesis","volume":"644","author":"Sharma","year":"2025","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1002\/fft2.70084","article-title":"Dietary Riboflavin Supplementation Suppresses Colorectal Cancer Progression by Restoring the Function Effector of CD8+ T Cells","volume":"6","author":"Chen","year":"2025","journal-title":"Food Front."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102342","DOI":"10.1016\/j.canep.2023.102342","article-title":"High serum riboflavin is associated with the risk of sporadic colorectal cancer","volume":"83","author":"Ma","year":"2023","journal-title":"Cancer Epidemiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41556-025-01856-x","article-title":"Riboflavin metabolism shapes FSP1-driven ferroptosis resistance","volume":"28","author":"Skafar","year":"2026","journal-title":"Nat. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/s41431-026-02106-w","article-title":"SLC52A3-related Brown-Vialetto-Van Laere syndrome: A large cohort from the Arabian Peninsula","volume":"34","year":"2026","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_28","first-page":"285","article-title":"Riboflavin metabolism: Role in mitochondrial function","volume":"4","author":"Balasubramaniam","year":"2020","journal-title":"J. Transl. Genet. Genom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"118103","DOI":"10.1016\/j.foodres.2025.118103","article-title":"High-dose neonatal riboflavin remodels energy metabolism and brain mitochondrial ultrastructure in rats exposed to maternal high-fat diet","volume":"226","author":"Toscano","year":"2026","journal-title":"Food Res. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1039\/c2fo10246c","article-title":"Riboflavin as a photosensitizer. Effects on human health and food quality","volume":"3","author":"Cardoso","year":"2012","journal-title":"Food Funct."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1039\/D5CP03884G","article-title":"Riboflavin\u2014Understanding the dynamics and interactions of the triplet state","volume":"28","author":"Scholz","year":"2026","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ionita, G., and Matei, I. (2019). Application of Riboflavin Photochemical Properties in Hydrogel Synthesis. Biophysical Chemistry: Advance Applications, IntechOpen.","DOI":"10.5772\/intechopen.88855"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1039\/D2RA07379J","article-title":"Investigating the photosensitization activities of flavins irradiated by blue LEDs","volume":"13","author":"Ribes","year":"2023","journal-title":"RSC Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9720","DOI":"10.1021\/acs.chemrev.2c00787","article-title":"Endogenous Photosensitizers in Human Skin","volume":"123","author":"Bastos","year":"2023","journal-title":"Chem. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5580","DOI":"10.1021\/acs.jcim.4c01104","article-title":"Riboflavin-Induced DNA Damage and Anticancer Activity in Breast Cancer Cells under Visible Light: A TD-DFT and In Vitro Study","volume":"64","author":"Majumder","year":"2024","journal-title":"J. Chem. Inf. Model."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jphotobiol.2018.02.006","article-title":"Investigating the scavenging of reactive oxygen species by antioxidants via theoretical and experimental methods","volume":"180","author":"Jabeen","year":"2018","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.redox.2015.07.008","article-title":"Antioxidant responses and cellular adjustments to oxidative stress","volume":"6","author":"Miguel","year":"2015","journal-title":"Redox Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Udhayabanu, T., Manole, A., Rajeshwari, M., Varalakshmi, P., Houlden, H., and Ashokkumar, B. (2017). Riboflavin Responsive Mitochondrial Dysfunction in Neurodegenerative Diseases. J. Clin. Med., 6.","DOI":"10.3390\/jcm6050052"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"608","DOI":"10.3892\/etm.2022.11545","article-title":"Riboflavin ameliorates mitochondrial dysfunction via the AMPK\/PGC1\u03b1\/HO-1 signaling pathway and attenuates carbon tetrachloride-induced liver fibrosis in rats","volume":"24","author":"Tang","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1093\/brain\/aws161","article-title":"Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease","volume":"135","author":"Johnson","year":"2012","journal-title":"Brain"},{"key":"ref_41","first-page":"e84491","article-title":"Long-Term Survival in Brown-Vialetto-Van Laere Syndrome: A Case Report Highlighting Respiratory Care","volume":"17","author":"Moreira","year":"2025","journal-title":"Cureus"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Colasuonno, F., Bertini, E., Tartaglia, M., Compagnucci, C., and Moreno, S. (2020). Mitochondrial Abnormalities in Induced Pluripotent Stem Cells-Derived Motor Neurons from Patients with Riboflavin Transporter Deficiency. Antioxidants, 9.","DOI":"10.20944\/preprints202011.0360.v1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s11064-025-04552-2","article-title":"Riboflavin (Vitamin B2) Accumulation Modulates Neuronal Cellular Homeostasis in Typical Brain Development and Cerebral Palsy","volume":"50","author":"Toscano","year":"2025","journal-title":"Neurochem. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Suwannasom, N., Kao, I., Pru\u00df, A., Georgieva, R., and B\u00e4umler, H. (2020). Riboflavin: The Health Benefits of a Forgotten Natural Vitamin. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030950"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Maccio, A., Sanna, E., Neri, M., Oppi, S., and Madeddu, C. (2021). Cachexia as Evidence of the Mechanisms of Resistance and Tolerance during the Evolution of Cancer Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062890"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1079\/BJN20051439","article-title":"Energy-modulating vitamins\u2014A new combinatorial therapy prevents cancer cachexia in rat mammary carcinoma","volume":"93","author":"Perumal","year":"2005","journal-title":"Br. J. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/1476-511X-10-177","article-title":"Suppression of nitric oxide induction and pro-inflammatory cytokines by novel proteasome inhibitors in various experimental models","volume":"10","author":"Qureshi","year":"2011","journal-title":"Lipids Health Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12950-016-0145-0","article-title":"Riboflavin along with antibiotics balances reactive oxygen species and inflammatory cytokines and controls Staphylococcus aureus infection by boosting murine macrophage function and regulates inflammation","volume":"13","author":"Dey","year":"2016","journal-title":"J. Inflamm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.ajcnut.2022.11.014","article-title":"Pregnancy thiamine and riboflavin intake and the risk of gestational diabetes mellitus: A prospective cohort study","volume":"117","author":"Ge","year":"2023","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8609213","DOI":"10.1155\/2020\/8609213","article-title":"Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus","volume":"2020","author":"Yaribeygi","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"117","DOI":"10.13005\/bbra\/3484","article-title":"Redox Imbalance and Oxidative Stress in Diabetes Mellitus: Mechanistic Insights into Complications and Antioxidant-Based Therapeutic Perspectives","volume":"23","author":"Reddy","year":"2026","journal-title":"Biotechnol. Res. Asia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.abb.2015.08.013","article-title":"Ameliorative effect of riboflavin on hyperglycemia, oxidative stress and DNA damage in type-2 diabetic mice: Mechanistic and therapeutic strategies","volume":"584","author":"Alam","year":"2015","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1158\/1055-9965.EPI-09-1052","article-title":"Antioxidant micronutrients and biomarkers of oxidative stress and inflammation in colorectal adenoma patients: Results from a randomized, controlled clinical trial","volume":"19","author":"Hopkins","year":"2010","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1093\/ecco-jcc\/jjz208","article-title":"Riboflavin Supplementation in Patients with Crohn\u2019s Disease [the RISE-UP study]","volume":"14","author":"Bourgonje","year":"2020","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e08246","DOI":"10.1016\/j.heliyon.2021.e08246","article-title":"Physicochemical properties of and volatile compounds in riboflavin fortified cloudy apple juice; study of its effect on job fatigue among Egyptian construction workers","volume":"7","author":"Fouad","year":"2021","journal-title":"Heliyon"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hill, M.H., Mushtaq, S., Williams, E.A., Dainty, J.R., and Powers, H.J. (2009). Study Protocol: Randomised controlled trial to investigate the functional significance of marginal riboflavin status in young women in the UK (RIBOFEM). BMC Public Health, 9.","DOI":"10.1186\/1471-2458-9-90"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.3945\/ajcn.110.008409","article-title":"Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM)","volume":"93","author":"Powers","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.freeradbiomed.2022.08.008","article-title":"The effect of riboflavin supplementation on the systemic redox status in healthy volunteers: A post-hoc analysis of the RIBOGUT trial","volume":"190","author":"Bourgonje","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6082613","DOI":"10.1155\/2019\/6082613","article-title":"A Randomized Pilot Trial to Evaluate the Bioavailability of Natural versus Synthetic Vitamin B Complexes in Healthy Humans and Their Effects on Homocysteine, Oxidative Stress, and Antioxidant Levels","volume":"2019","author":"Lindschinger","year":"2019","journal-title":"Oxidative Med. Cell. Longev."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3223\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:18:26Z","timestamp":1791519506000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":59,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["nu18193223"],"URL":"https:\/\/doi.org\/10.3390\/nu18193223","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]}}}