High-Dose Intravenous Ascorbate in Sepsis, a Pro-Oxidant Enhanced Microbicidal Activity and the Effect on Neutrophil Functions.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic reasoning and prior trial literature without new human data
PubMed 36672559 · doi:10.3390/biomedicines11010051
What was done
This narrative review synthesized mechanistic and clinical literature regarding high-dose intravenous vitamin C (HDIVC) administration in sepsis, specifically evaluating its concentration-dependent antioxidant versus pro-oxidant actions, impacts on neutrophil functions, and neutrophil extracellular trap (NET) formation.
What was found
The review reports that supraphysiologic plasma vitamin C levels (>5 mM) achieved after 4 days of HDIVC induce extracellular pro-oxidant effects that directly damage microbial membranes. Vitamin C modulates NET formation in a concentration-dependent manner: it inhibits NETs at concentrations of 1 mM or less, but facilitates NETs at concentrations of 5 mM or higher. The abstract notes that several randomized controlled trials of HDIVC in sepsis have yielded negative results, and it reports no primary statistical effect sizes or patient numbers.
Why it matters
It provides a mechanistic framework explaining how high-dose vitamin C can act as a pro-oxidant and modulate neutrophil responses, offering biological context for why broad clinical trials have failed.
Limits
This is a narrative review with no original clinical data, meta-analysis, or systematic search methodology. The proposed pro-oxidant microbicidal benefits are theoretical and must be weighed against the potential harm from enhanced NET-mediated tissue injury in sepsis.
Cited by
- supports High doses of vitamin C taken continuously can act as a pro-oxidant rather than an antioxidant.