{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:58:31Z","timestamp":1786597111646,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Sepsis remains one of the major challenges in modern intensive care, characterized by high mortality and complex metabolic and immunological disturbances. Given the limited effectiveness of current therapeutic strategies, increasing attention has been directed toward supportive interventions aimed at restoring metabolic homeostasis. Particular interest has been focused on selected vitamins that exhibit pleiotropic biological effects. Thus, we summarized the current evidence on the role of selected vitamins (C, D, B1, B9, B12) in the treatment and supportive management of sepsis, highlighting their mechanisms of action, potential clinical benefits, and limitations derived from available studies. A comprehensive analysis of the literature was performed, including clinical trials and meta-analyses evaluating the efficacy of vitamin supplementation in sepsis, with particular emphasis on combined interventions and randomized controlled trials in severe sepsis and septic shock. Vitamin D might demonstrate the greatest therapeutic potential, particularly in patients with severe sepsis and respiratory failure, with benefits associated with achieving appropriate therapeutic concentrations. Thiamine (vitamin B1) appears to provide potential advantages primarily in deficient patients, improving mitochondrial function and reducing the risk of renal failure. Evidence regarding folic acid (vitamin B9) and cobalamin (vitamin B12) remains inconclusive, as both deficiency and elevated serum levels have been linked to adverse outcomes. Vitamin C, despite its well-documented antioxidant and microcirculatory effects, has not yet shown consistent evidence of mortality reduction. In conclusion, current evidence suggests that vitamin supplementation might represent an adjunct to standard sepsis therapy, particularly within a personalized approach that considers nutritional status and metabolic phenotype. The development of standardized dosing protocols and well-designed clinical trials is essential to determine the efficacy and safety of phenotype-driven individualized approaches in sepsis management.<\/jats:p>","DOI":"10.3390\/nu17213330","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T09:44:30Z","timestamp":1761212670000},"page":"3330","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Role of Vitamins in Sepsis: A Narrative Review"],"prefix":"10.3390","volume":"17","author":[{"given":"Pawe\u0142","family":"Radkowski","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-719 Olsztyn, Poland"},{"name":"Clinical Department of Anesthesiology and Intensive Care, Regional Specialist Hospital, 10-561 Olsztyn, Poland"},{"name":"Klinika-Hospital Zum Heiligen Geist, 34560 Fritzlar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2569-5529","authenticated-orcid":false,"given":"Anna","family":"Gogojewicz","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Poznan University of Physical Education, 61-871 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9833-2958","authenticated-orcid":false,"given":"Joanna","family":"Charasna","sequence":"additional","affiliation":[{"name":"Emergency Medical Services Training Center in Kalisz, 62-800 Kalisz, Poland"},{"name":"Faculty of Finance and Management, WSB University Merito in Wroc\u0142aw, 53-609 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ucja","family":"Pilaczy\u0144ska-Szcze\u015bniak","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy, Faculty of Medicine and Health Sciences, University of Kalisz, 62-800 Kalisz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0022-2741","authenticated-orcid":false,"given":"\u0141ukasz","family":"Grabarczyk","sequence":"additional","affiliation":[{"name":"Alarm Clock Clinic, Coma Recovery and Neurorehabilitation Center, Kondratowicza 8, 03-242 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, October 21). Sepsis. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/sepsis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1001\/jama.2016.0288","article-title":"Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Seymour","year":"2016","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1001\/jama.2017.17687","article-title":"Enhancing Recovery From Sepsis: A Review","volume":"319","author":"Prescott","year":"2018","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e194900","DOI":"10.1001\/jamanetworkopen.2019.4900","article-title":"Risk Factors at Index Hospitalization Associated With Longer-term Mortality in Adult Sepsis Survivors","volume":"2","author":"Harrison","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.chest.2016.11.036","article-title":"Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study","volume":"151","author":"Marik","year":"2017","journal-title":"Chest"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1001\/jama.2019.11825","article-title":"Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial","volume":"322","author":"Fowler","year":"2019","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1001\/jama.2019.22176","article-title":"Effect of Vitamin C, Hydrocortisone, and Thiamine vs. Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial","volume":"323","author":"Fujii","year":"2020","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1056\/NEJMoa2200644","article-title":"Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit","volume":"386","author":"Lamontagne","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s13054-019-2538-y","article-title":"Vitamin C administration in the critically ill: A summary of recent meta-analyses","volume":"23","author":"Carr","year":"2019","journal-title":"Crit. Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s13054-025-05383-x","article-title":"Early administration of vitamin C in patients with sepsis or septic shock in emergency departments: A multicenter, double-blind, randomized controlled trial: The C-EASIE trial","volume":"29","author":"Vandervelden","year":"2025","journal-title":"Crit. Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s00134-024-07733-9","article-title":"Sepsis subtypes and differential treatment response to vitamin C: Biological sub-study of the LOVIT trial","volume":"51","author":"Rynne","year":"2025","journal-title":"Intensive Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1600224","DOI":"10.3389\/fnut.2025.1600224","article-title":"Vitamin C improves 28-day survival in patients with sepsis-associated acute kidney injury in the intensive care unit: A retrospective study","volume":"12","author":"He","year":"2025","journal-title":"Front. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1001\/jama.2020.24505","article-title":"Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial","volume":"325","author":"Sevransky","year":"2021","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s44231-024-00066-7","article-title":"Clinical Efficacy of Megadose Vitamin C in Sepsis: Protocol for a Multicenter Randomized Single\u2014Blind Placebo\u2014Controlled Clinical Trial","volume":"4","author":"Wang","year":"2024","journal-title":"Intensive Care Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13054-024-04818-1","article-title":"Thiamine administration in septic shock: A post hoc analysis of two randomized trials","volume":"28","author":"Vine","year":"2024","journal-title":"Crit. Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1223862","DOI":"10.3389\/fmed.2023.1223862","article-title":"Thiamine as a metabolic resuscitator in septic shock: A meta-analysis of randomized controlled trials with trial sequential analysis","volume":"10","author":"Sangla","year":"2023","journal-title":"Front. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1186\/s12871-020-01195-4","article-title":"Effects of thiamine on vasopressor requirements in patients with septic shock: A prospective randomized controlled trial","volume":"20","author":"Petsakul","year":"2020","journal-title":"BMC Anesthesiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"86","DOI":"10.4103\/IJCIIS.IJCIIS_159_20","article-title":"Effectiveness of thiamine therapy in mortality rate in patients with septic shock: A systematic review and meta-analysis","volume":"11","author":"Kanchanasurakit","year":"2021","journal-title":"Int. J. Crit. Illn. Inj. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kim, W.Y., Jung, J.W., Choi, J.C., Shin, J.W., and Kim, J.Y. (2019). Subphenotypes in Patients with Septic Shock Receiving Vitamin C, Hydrocortisone, and Thiamine: A Retrospective Cohort Analysis. Nutrients, 11.","DOI":"10.3390\/nu11122976"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Delrue, C., Speeckaert, R., Delanghe, J.R., and Speeckaert, M.M. (2023). Vitamin D Deficiency: An Underestimated Factor in Sepsis?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032924"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1177\/08850666241250319","article-title":"Outcomes of High-Dose Versus Low-Dose Vitamin D on Prognosis of Sepsis Requiring Mechanical Ventilation: A Randomized Controlled Trial","volume":"39","author":"Ashoor","year":"2024","journal-title":"J. Intensive Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1485554","DOI":"10.3389\/fcimb.2024.1485554","article-title":"Vitamin D supplementation during intensive care unit stay is associated with improved outcomes in critically Ill patients with sepsis: A cohort study","volume":"14","author":"Li","year":"2025","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s44158-024-00139-5","article-title":"Update on vitamin D role in severe infections and sepsis","volume":"4","author":"Cutuli","year":"2024","journal-title":"J. Anesth. Analg. Crit. Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"816","DOI":"10.3390\/nu17050816","article-title":"Evaluation of Vitamin D Supplementation in Critically Ill Patients-A Narrative Review of Randomized Controlled Trials Published in the Last 5 Years","volume":"17","author":"Wang","year":"2025","journal-title":"Nutrients"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yang, B., Zhu, Y., Zheng, X., Li, T., Niu, K., Wang, Z., Lu, X., Zhang, Y., and Shen, C. (2023). Vitamin D Supplementation during Intensive Care Unit Stay Is Associated with Improved Outcomes in Critically Ill Patients with Sepsis: A Cohort Study. Nutrients, 15.","DOI":"10.3390\/nu15132924"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Shang, S., Chen, D., Wei, Y., Zou, S., Chang, Q., Zhou, H., and Yu, A. (2025). The Role of Vitamin D and Vitamin D Receptor in Sepsis. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47070500"},{"key":"ref_29","first-page":"1221","article-title":"Research progress on B vitamins in the treatment of sepsis","volume":"36","author":"Xu","year":"2024","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1159\/000538959","article-title":"Efficacy and Safety of Hydrocortisone, Ascorbic Acid, and Thiamine Combination Therapy for the Management of Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","volume":"185","author":"Deng","year":"2024","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_31","first-page":"247","article-title":"Folic acid and vitamin B12 as biomarkers of morbidity and mortality in patients with septic shock","volume":"39","author":"Planells","year":"2022","journal-title":"Nutr. Hosp."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.clnesp.2022.05.008","article-title":"Micronutrient deficiencies in critically ill patients receiving continuous renal replacement therapy","volume":"50","author":"Fah","year":"2022","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.clnu.2022.02.015","article-title":"ESPEN micronutrient guideline","volume":"41","author":"Berger","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mucha, P., Kus, F., Cysewski, D., Smolenski, R.T., and Tomczyk, M. (2024). Vitamin B(12) Metabolism: A Network of Multi-Protein Mediated Processes. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202406.1262.v1"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s12916-024-03552-3","article-title":"Vitamin B12 status and the risk of developing sepsis in patients with bacterial infection: A prospective observational cohort study","volume":"22","author":"Pregernig","year":"2024","journal-title":"BMC Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Toscano, A., Bellone, F., Maggio, N., Cinquegrani, M., Spadaro, F., Bueti, F.M., Lorello, G., Marini, H.R., Lo Gullo, A., and Basile, G. (2025). Unlocking the Predictive Power of Nutritional Scores in Septic Patients. Nutrients, 17.","DOI":"10.3390\/nu17030545"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Piccioni, A., Spagnuolo, F., Candelli, M., Voza, A., Covino, M., Gasbarrini, A., and Franceschi, F. (2024). The Gut Microbiome in Sepsis: From Dysbiosis to Personalized Therapy. J. Clin. Med., 13.","DOI":"10.3390\/jcm13206082"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/21\/3330\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T09:54:26Z","timestamp":1761213266000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/21\/3330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":37,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["nu17213330"],"URL":"https:\/\/doi.org\/10.3390\/nu17213330","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}