Hydrocortisone, ascorbic acid and thiamine for sepsis: Is the jury out?

Table 1 Summary of key roles of vitamin C in sepsis

Key role	Mechanism
Antioxidant	Scavenges extracellular, intracellular and mitochondrial ROS; limits oxidation of mitochondrial proteins, enzymes, lipoproteins, cell membrane, etc.
Anti-inflammatory	Inhibits activation of NFκB, decreases HMGB1, inhibits histamine, prevents NETosis, inactivates HIF-1α
Microcirculation	Increases eNOS, decreases iNOS, preserves tight junctions
Immune function	Supports lymphocyte proliferation, increases neutrophil bactericidal action, improves chemotaxis, stimulates interferon production, decreases T regulatory cells (Tregs), prevents lymphocyte apoptosis
Anti-thrombotic	Decreases platelet activation and tissue factor expression, increases thrombomodulin
Synthesis of catecholamines	Acts cofactor in synthesis of epinephrine, dopamine and vasopressin. Increases adrenergic sensitivity
Wound healing	Hydroxylation of procollagen, increased expression of collagen mRNA

Reproduced with permission from Nutrients[4]. ROS: Reactive oxygen species; NFκB: Nuclear factor κB; HIF-1α: Hypoxia-inducible transcription factor-1α; HMGB1: High mobility group box 1; eNOS: Endothelial nitric oxide synthetase; iNOS: Inducible nitroc oxide synthetase; HO-1: Heme oxygenase-1; HIF-1α: Hypoxia-inducible transcription factor-1α.