METABOLIC SUPPORT: Edited by Marianne ChapmanUpdate on vitamin C administration in critical illnessFujii, Tomokoa,b,c; Lankadeva, Yugeesh R.d,e; Bellomo, Rinaldob,d,f Author Information aIntensive Care Unit, Jikei University Hospital, Tokyo, Japan bAustralian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia cDepartment of Health Promotion and Human Behaviour, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan dDepartment of Critical Care, University of Melbourne ePreclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, Melbourne fIntensive Care Unit, Austin Hospital, Heidelberg, Victoria, Australia Correspondence to Rinaldo Bellomo, AO, Heidelberg, Australia. Tel: +61 3 9496 5992; fax: +61 3 9496 3932; e-mail: [email protected] Current Opinion in Critical Care: August 2022 - Volume 28 - Issue 4 - p 374-380 doi: 10.1097/MCC.0000000000000951 Buy Metrics Abstract Purpose of review Several studies have recently explored the effects of intravenous vitamin C in sepsis. We aimed to summarize their findings to provide perspectives for future research. Recent findings Sepsis trials examined 6 g/day of intravenous vitamin C with or without the thiamine and/or hydrocortisone compared with placebo or hydrocortisone. Network meta-analysis reported that intravenous vitamin C, thiamine, hydrocortisone, or combinations of these drugs was not proven to reduce long-term mortality. However, the component network meta-analysis suggested an association of high-dose (>6 g/day) and very-high dose vitamin C (>12 g/day) and decreased mortality but with low certainty. The preclinical investigations have, however, advanced to much higher doses of intravenous vitamin C therapy since a scoping review on harm reported that mega-doses of intravenous vitamin C (50–100 g/day) had been administered without any conclusive adverse effects. In a Gram-negative sheep model, renal tissue hypoperfusion was reversed, followed by improvements in kidney function when a mega-dose of vitamin C (150 g/day equivalent) was administered. Summary The effect of intravenous vitamin C in critically ill patients has yet to be determined and might be dose-dependent. Clinical studies of very high or mega doses of vitamin C are justified by preclinical data. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.