Evaluation of Vitamin C for Adjuvant Sepsis Therapy

Abstract

Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis.

Impact of Intravenous Ascorbic Acid Infusion on Novel Biomarkers in Patients with Severe Sepsis

“…Further, microvascular dysfunction characterized by refractory vasodilation, loss of endothelial barrier function, disseminated intravascular coagulation, edema, multi-organ failure and death in animal models of sepsis are effectively treated with ascorbic acid [5].…”

Emerging Therapeutic Targets of Sepsis-Associated Acute Kidney Injury

“…These include: heparin 138,139 , statins 140,141 , pentoxifylline 142 , beta-blockade 143 , dexmedetomidine 144 , acetaminophen 145 , selenium 146,147 , L-citrulline 148 , L-carnitine 149 , zinc 118 , hydrocortisone 150,151 , melatonin 152 , vitamin D 153 , thiamine 154 , and vitamin C 155 . Several of these trials test the concept as to whether pharmaconutrients given in large doses can improve outcomes in sepsis through anti-oxidant and anti-inflammatory mechanisms 147 .…”

Adjuvant vitamin C treatment in sepsis—how many oranges a day keep (vasopressor-dependent) septic shock away?

“…In animal models of sepsis, intravenous ascorbate rapidly and persistently improved capillary and microcirculatory blood flow, decreased microvascular permeability, and attenuated inflammation. Vitamin C also restored endothelial barrier function, prevented apoptosis, and exerted antibacterial effects (3,8). Additionally, vitamin C acts as a cofactor to optimize activity of the enzymes dopamine β-hydroxylase and peptidylglycine α-amidating monooxygenase which synthesise respectively norepinephrine and vasopressin (9,10).…”