[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-416647-105":59,"doc-detail-416647-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","postoperative-delirium-and-vitamin-c-rethinking-unfavorable-outcomes-through-the-lens-of-underdosing","Postoperative Delirium and Vitamin C: Rethinking Unfavorable Outcomes Through the Lens of Underdosing","","Letter to the editor addressing a pilot study on perioperative ascorbic acid for preventing postoperative delirium (POD) in older cardiovascular surgery patients. It argues that POD mechanisms involve multifactorial neuroinflammation, including surgery- and anesthetic-driven blood-brain barrier disruption that permits peripheral inflammatory mediators. The letter emphasizes that vitamin C’s therapeutic effects are dose- and time-dependent, highlights cross-species dose translation limits, and notes that post-cardiac surgery vitamin C levels fall substantially, potentially making 2 g/day subtherapeutic and limiting conclusions due to small sample size and lack of controls.",{"@graph":69,"@context":122},[70,84,105],{"@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/postoperative-delirium-and-vitamin-c-rethinking-unfavorable-outcomes-through-the-lens-of-underdosing/416647/",{"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/postoperative-delirium-and-vitamin-c-rethinking-unfavorable-outcomes-through-the-lens-of-underdosing/416647.png","ImageObject",300,407,{"name":92,"@type":93},"Well Done","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does the pilot study conclude about ascorbic acid for preventing postoperative delirium?","Question",{"text":112,"@type":113},"The authors concluded that ascorbic acid administration may not be effective in reducing the incidence of POD, despite observing a 33% POD incidence.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why does the letter connect postoperative delirium with blood-brain barrier disruption and neuroinflammation?",{"text":117,"@type":113},"It explains that surgical trauma triggers inflammatory cascades and that surgery and anesthetics can disrupt the blood-brain barrier, allowing peripheral inflammatory mediators to enter the CNS and amplify neuroinflammation.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the letter argue vitamin C could have been ineffective in the pilot regimen?",{"text":121,"@type":113},"It suggests the 2 g/day dosing may be subtherapeutic relative to neuroprotective thresholds, because vitamin C activity is dose- and time-dependent and concentrations can decline markedly after cardiac surgery.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},416647,1791171697,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":39,"preview_page_count":4},5909892210082,"https://ap-avatar.wpscdn.com/avatar/56001069da27c9f41e8?x-image-process=image/resize,m_fixed,w_180,h_180&k=1789614185077863061","Letter to the Editor J Clin Med Res. 2025;17(12):740-742   \nPostoperative Delirium and Vitamin C: Rethinking Unfavorable Outcomes Through the Lens of Underdosing  \nChia-Yu Kuoa, Shu-Wei Liaob, c, I-Chia Tengb, Jen-Yin Chenb, d, e  \nTo the Editor  \nWe read with great interest in the pilot study examining the effects of perioperative ascorbic acid (2 g/day for 2 days) in preventing postoperative delirium (POD) among older cardiovascular surgery patients [1] . In that study, a 33% incidence of POD was observed, aligning with previous observational findings [2] . The authors concluded that ascorbic acid administration may not be effective in reducing the incidence of POD [1] .  \nThe pathophysiological mechanisms underlying POD are multifactorial and complex. Neuroinflammation has emerged as one of the most widely recognized contributors [3] . Surgical trauma initiates an inflammatory cascade characterized by significant elevations in circulating pro-inflammatory cytokines. Moreover, both surgery and anesthetic agents-whether volatile anesthetics or propofol-can disrupt the blood-brain barrier [4] . Disruption of the blood-brain barrier facilitates the entry of peripheral inflammatory mediators into the central nervous system, thereby amplifying neuroinflammation within the brain parenchyma. Age-related disruption of the blood-brain barrier increases susceptibility to delirium in elderly individuals, especially in the presence of systemic inflammation [5] . Consequently, older patients are particularly vulnerable to developing POD, notably following cardiac surgery.  \nVitamin C (ascorbic acid) is well known for its antioxidant and anti-inflammatory properties, as well as for its potential to stabilize the blood-brain barrier [6] . Importantly,  \nManuscript submitted September 6, 2025, accepted December 20, 2025 Published online December 24, 2025  \naDepartment of Medical Education, Chi Mei Medical Center, Tainan City 71004, Republic of China  \nbDepartment of Anesthesiology, Chi Mei Medical Center, Tainan City 71004, Republic of China  \ncCenter of General Education, Chia Nan University of Pharmacy and Science, Tainan 71710, Republic of China  \ndSchool of Medicine, National SunYat-Sen University, Kaohsiung 80424, Republic of China  \neCorresponding Author: Jen-Yin Chen, Department of Anesthesiology, Chi Mei Medical Center, Tainan City 71004, Republic of China.  \nEmail: [chenjenyin@gmail.com](chenjenyin@gmail.com)  \ndoi: [https://doi.org/10.14740/jocmr6376](https://doi.org/10.14740/jocmr6376)  \nthe potential therapeutic activity of vitamin C is dose- and time-dependent [7] . In animal studies, high-dose vitamin C (400-2,000 mg/kg/day) significantly improved cognitive or neurological outcomes through attenuation of neuroinflammation and preservation of the blood-brain barrier [8-10] . Based on the Nair-Jacob dose conversion principles, which account for interspecies differences in metabolic rate [11], the translated equivalents range from 4 to 20 g/day for a 60-kg adult-far exceeding the dose used in the pilot study, which employed the maximum permitted dose of ascorbic acid in Japan (2 g/day) [1] . Direct extrapolation to human dosing should be approached with caution due to species-specific differences in absorption and plasma saturation kinetics. Due to active transport via sodium-dependent vitamin C transporters, vitamin C concentrations in cerebrospinal fluid and neurons substantially exceed plasma levels, thereby enhancing neuroprotection against oxidative stress [12-14] . According to the study by Padayatty et al, the predicted peak plasma vitamin C concentrations after intravenous administration at a rate of 1 g/min were approximately 1,000 µmol/L for 1.25 g, 2,870 µmol/L for 5 g, 5,580 µmol/L for 10 g, and 13,350 µmol/L for 50 g. The pharmacokinetics of intravenous vitamin C are nonlinear with a short plasma half-life (about 2 h) although 100% bioavailability of intravenous vitamin C is assumed [14] . Therapeutic targets in huma","cbCaijF3xDZRVbf0","https://ap.wps.com/l/cbCaijF3xDZRVbf0","pdf",234799,"English","# To the Editor\n## Background and results of the pilot study\n## Neuroinflammation and blood-brain barrier disruption\n## Dose- and time-dependence of vitamin C and underdosing hypothesis\n## Study limitations and need for rigorous trials","[{\"question\":\"What does the pilot study conclude about ascorbic acid for preventing postoperative delirium?\",\"answer\":\"The authors concluded that ascorbic acid administration may not be effective in reducing the incidence of POD, despite observing a 33% POD incidence.\"},{\"question\":\"Why does the letter connect postoperative delirium with blood-brain barrier disruption and neuroinflammation?\",\"answer\":\"It explains that surgical trauma triggers inflammatory cascades and that surgery and anesthetics can disrupt the blood-brain barrier, allowing peripheral inflammatory mediators to enter the CNS and amplify neuroinflammation.\"},{\"question\":\"How does the letter argue vitamin C could have been ineffective in the pilot regimen?\",\"answer\":\"It suggests the 2 g/day dosing may be subtherapeutic relative to neuroprotective thresholds, because vitamin C activity is dose- and time-dependent and concentrations can decline markedly after cardiac surgery.\"}]","Postoperative Delirium and Vitamin C: Rethinking Unfavorable Outcomes Through the Lens of Underdosing | PDF",1790606167]