{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:01:24Z","timestamp":1782928884043,"version":"3.54.5"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Intravenous (IV) vitamin C has been proposed as an adjuvant therapy in sepsis\/septic shock due to its biological plausibility and safety profile, but the proliferation of reviews has not resolved its clinical utility. To synthesize the evidence on IV vitamin C (monotherapy, HAT\u2014hydrocortisone+vitamin C+thiamine\u2014and vitamin C+thiamine) in adults with sepsis\/septic shock, prioritizing 28\u201330-day mortality. Umbrella review of systematic reviews and meta-analyses (MEDLINE\/PubMed, Embase, Scopus, and Web of Science, without language restriction). Quality was assessed with AMSTAR 2, overlap with CCA, and when available, TSA and component\/network meta-analysis (CINeMA). Certainty of evidence was graded using GRADE with an anchor estimator per outcome and regimen. Thirty-one reviews were included (30 quantitative: 28 SR\/MA and 2 component\/network MA; 1 qualitative). Combinations (HAT and vitamin C+thiamine) did not reduce mortality; hemodynamic improvements (small decreases in \u0394SOFA and vasopressor hours) were modest, did not translate into survival benefits, and were primarily attributable to the corticosteroid. Monotherapy showed a possible mortality benefit signal under specific conditions (initiation \u226424\u2009h, intermediate dose 25\u2013100\u2009mg\/kg\/day, 3\u20134-day courses; more pronounced in sepsis than shock), but with low-to-moderate certainty due to heterogeneity, imprecision, publication bias, and very high overlap among reviews. Combination regimens (HAT and vitamin C plus thiamine) did not reduce mortality; hemodynamic improvements were modest, did not translate into survival benefits, and were primarily attributable to the corticosteroid component. For monotherapy, a possible mortality benefit signal was identified under specific conditions (initiation within 24\u2009h, intermediate dose 25\u2013100\u2009mg\/kg\/day, 3\u20134-day courses, more pronounced in sepsis than shock), but overall certainty remains low-to-moderate due to heterogeneity, imprecision, publication bias, and very high overlap among reviews. These findings do not support routine use of IV vitamin C in any regimen; for monotherapy, the identified signal warrants rigorous multicenter trials in well-defined clinical scenarios before any recommendation can be made.<\/jats:p>","DOI":"10.1371\/journal.pone.0351072","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:25:31Z","timestamp":1782926731000},"page":"e0351072","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Monotherapy or combinations? Intravenous vitamin C in sepsis and septic shock: An umbrella review of 31 systematic reviews"],"prefix":"10.1371","volume":"21","author":[{"given":"V\u00edctor Juan","family":"Vera-Ponce","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhosmer","family":"Ballena-Caicedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lupita Ana Maria","family":"Valladolid-Sandoval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella 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