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Sepsis is described as infection-triggered dysregulated inflammation and oxidative stress causing endothelial glycocalyx disruption, microcirculatory failure, and organ dysfunction. The review highlights widespread vitamin C insufficiency in ICU patients, concentration-dependent redox effects, and mixed clinical trial outcomes. It evaluates limitations in existing studies and outlines future research directions for individualized dosing.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/vitamin-c-for-sepsis-from-mechanisms-to-individualized-therapy/412728/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/vitamin-c-for-sepsis-from-mechanisms-to-individualized-therapy/412728.png","ImageObject",300,407,{"name":92,"@type":93},"pop out","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role does vitamin C insufficiency play in sepsis patients?","Question",{"text":113,"@type":114},"Many sepsis patients have insufficient vitamin C, attributed largely to metabolic consumption. Reported studies link lower vitamin C levels with worse outcomes such as increased mortality risk in septic shock and more severe disease in children.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why is vitamin C dosage considered critical in sepsis treatment?",{"text":118,"@type":114},"Vitamin C’s pharmacological effects are concentration-dependent. Moderate concentrations support endothelial and microcirculatory function, while very high levels may shift to pro-oxidant effects and disrupt key redox pathways.",{"name":120,"@type":111,"acceptedAnswer":121},"How do clinical outcomes of vitamin C in sepsis compare with preclinical findings?",{"text":122,"@type":114},"Preclinical studies suggest benefit in reducing organ damage, but clinical trials have produced mixed results. 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M. Vissers, University of Otago, New Zealand Yuchang Wang,  \nHuazhong University of Science and Technology, China  \n*CORRESPONDENCE  \nChunmei Gui  \n [g19936865822@outlook.com](g19936865822@outlook.com)  \nRECEIVED 06 September 2025  \nREVISED 18 November 2025  \nACCEPTED 27 November 2025  \nPUBLISHED 18 December 2025  \nCITATION  \nXiao Y, Gong F, Zhang L and Gui C (2025) Vitamin C for sepsis: from mechanisms to individualized therapy.  \nFront. Med. 12:1700351 .  \ndoi: 10.3389/fmed.2025.1700351  \nCOPYRIGHT  \n© 2025 Xiao, Gong, Zhang and Gui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nVitamin C for sepsis: from mechanisms to individualized therapy  \nYang Xiao1 , Fang Gong1 , Lina Zhang2 and Chunmei Gui1*  \n1 Department of Intensive Care Unit, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, China, 2 Department of Intensive Care Unit, Xiangya Hospital of Central South University, Changsha, China  \nSepsis is a critical illness initiated by infection and characterized by a dysregulated inflammatory and oxidative stress response, leading to high mortality ratesand impaired long-term quality of life. It is noteworthy that many sepsis patients have insufficient levels of vitamin C, an essential micronutrient. Due to its diverse physiological roles, including antioxidant, anti-inflammatory, immunomodulatory, and antimicrobial-enhancing effects, vitamin C has gained significant attention as a potential adjunctive therapy for sepsis. However, the specific mechanisms by which vitamin C acts in sepsis are still not fully understood. Recent preclinical studies have shown that it can help reduce sepsis-induced organ damage, but clinical trials assessing its effectiveness have produced mixed results. Importantly, vitamin C’s pharmacological effects depend on its concentration, and it has complex pharmacokinetics, which makes establishing an appropriate dosage regimen critical for achieving therapeutic outcomes in patients. This review aims to synthesize the current evidence regarding the therapeutic mechanisms of vitamin C in sepsis, identify limitations in the existing clinical research, and highlight future directions for investigation.  \nKEYWORDS  \nsepsis, septic shock, vitamin C, ascorbic acid, mechanism  \n1 Introduction  \nSepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, represents a major global public health concern, with an incidence of 677.5 cases per 100,000 people and a mortality rate of 148.1 per 100,000—accounting for 19.7% of global deaths ( 1) . The primary pathological mechanism of sepsisinduced organ injury involves microcirculatory dysfunction, in which the endothelialglycocalyx—a critical layer of negatively charged polysaccharides and proteins essential for maintaining microvascular homeostasis—plays an important role. This structure regulates vascular tone and permeability while inhibiting leukocyte and platelet adhesion to the endothelium. During sepsis, activation of Toll-like receptors by pathogen-and damageassociated molecular patterns triggers dysregulated inflammation and oxidative stress. This cascade disrupts glycocalyx structural integrity and induces endothelial damage, exacerbating capillary leakage, microvascular immunothrombosis, and microcirculatory failure, ultimately leading to multiorgan dysfunction (2–5) .","cbCaiuVSYvHmeOaP","https://ap.wps.com/l/cbCaiuVSYvHmeOaP","pdf",1595927,12,"English","# Introduction\n# Vitamin C in sepsis: deficiency and clinical relevance\n# Mechanistic rationale: concentration-dependent redox and endothelial effects\n# Evidence synthesis and clinical controversies\n# Future directions","[{\"question\":\"What role does vitamin C insufficiency play in sepsis patients?\",\"answer\":\"Many sepsis patients have insufficient vitamin C, attributed largely to metabolic consumption. Reported studies link lower vitamin C levels with worse outcomes such as increased mortality risk in septic shock and more severe disease in children.\"},{\"question\":\"Why is vitamin C dosage considered critical in sepsis treatment?\",\"answer\":\"Vitamin C’s pharmacological effects are concentration-dependent. Moderate concentrations support endothelial and microcirculatory function, while very high levels may shift to pro-oxidant effects and disrupt key redox pathways.\"},{\"question\":\"How do clinical outcomes of vitamin C in sepsis compare with preclinical findings?\",\"answer\":\"Preclinical studies suggest benefit in reducing organ damage, but clinical trials have produced mixed results. Some cohort data indicate that moderatedose, longer-duration regimens may reduce mortality, yet controversies remain.\"}]","Vitamin C for sepsis: from mechanisms to individualized therapy | PDF",1790592656]