Vitamin C for Sepsis and Septic Shock

Abstract

Background: Sepsis remains a leading cause of death in the critically ill. The combination of thiamine, vitamin C, and hydrocortisone has recently emerged as a potential adjunctive therapy and supportive care for patients with sepsis and septic shock. Areas of Uncertainty: Several randomized and observational controlled trials evaluated the role of vitamin C in sepsis and septic shock. However, there are variabilities in the findings of these studies that led to a substantial global debate on incorporating vitamin C therapy in clinical practice. Data Sources: A PubMed and Embase English language literature search through April 2021 was performed using the following terms: ascorbic acid, vitamin C, corticosteroid, hydrocortisone, thiamine, HAT, sepsis, and shock. Citations, including controlled trials, observational studies, review articles, guidelines, and consensus statements, were reviewed. The risk of bias for each clinical study was systematically evaluated. Relevant clinical data focusing on efficacy, safety, and special considerations regarding the use of vitamin C with and without thiamine and hydrocortisone in sepsis and septic shock were narratively summarized. Results: The most commonly used vitamin C dosing in sepsis and septic shock is 1.5 g every 6 hours with and without thiamine and hydrocortisone. Current literature is limited because of heterogeneity in vitamin C regimen used, initiation time, and duration of treatment. This limitation led to variability in outcomes evaluated. Vitamin C decreases proinflammatory mediators and slows the progression of endothelial injury in severe sepsis. There is an inconsistency between randomized controlled trials and observational controlled trials regarding mortality, resolution in organ failure, hospital and intensive care unit length of stay findings with the use of vitamin C in septic shock. Vitamin C seems to be safe in comparison with placebo. Conclusions: Future studies with consistent end points, initiation time with an emphasis on early initiation, and standard vitamin C dosing regimen are needed to determine the overall benefit of vitamin C in sepsis.

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

“…Vitamin C or ascorbic acid (AA) is a powerful antioxidant that can have beneficial effects on delaying the aging process and age-related diseases thorough its action on redox oxidative and mitochondrial pathways, on the immune system, on inflamm-aging, on endothelial integrity, and on lipoprotein metabolism [ 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 ]. Supplementation of AA also appears to prevent OS, immunosenescence, telomere attrition, disorganization of chromatin, and excessive secretion of inflammatory factors, and to prolong life [ 122 ].…”

CD3D and CD247 are the molecular targets of septic shock

“…[22] Antioxidants such as vitamin C, vitamin E, and glutathione can alleviate the damage of oxygen free radicals to cells and tissues and protect cells from oxidative stress. [23] Vasoactive drugs such as nitrates and dihydroergotamine can modulate vascular tone, improve circulation and tissue perfusion, and attenuate organ dysfunction and tissue damage. [24] β-Antimicrobials such as lactams and macrolides can directly kill bacteria, prevent further spread and exacerbation of infection, and protect the organism from damage due to infection.…”

Research progress on therapeutic effect and mechanism of hydrocortisone on sepsis

“…It was suggested a synergistic effect of hydrocortisone and vitamin C in the treatment of sepsis [5,26]. Vitamin C and HAT scavenge superoxide radicals (O 2-) and inhibit the activation of xanthine oxidase and NADPH oxidase.…”

“…Vitamin C protects mitochondria from oxidative stress, and restores the eNOS activity and improves the eNOS bioavailability. Vitamin C clears peroxynitrite (ONOO -), preventing endothelial tight junction loosening [5,26].…”