Vitamin therapy in sepsis

Abstract

Vitamins are essential micronutrients with key roles in many biological pathways relevant to sepsis. Some of these relevant biological mechanisms include antioxidant and anti-inflammatory effects, protein and hormone synthesis, energy generation, and regulation of gene transcription. Moreover, relative vitamin deficiencies in plasma are common during sepsis and vitamin therapy has been associated with improved outcomes in some adult and pediatric studies. High-dose intravenous vitamin C has been the vitamin therapy most extensively studied in adult patients with sepsis and septic shock. This includes three randomized control trials (RCTs) as monotherapy with a total of 219 patients showing significant reduction in organ dysfunction and lower mortality when compared to placebo, and five RCTs as a combination therapy with thiamine and hydrocortisone with a total of 1134 patients showing no difference in clinical outcomes. Likewise, the evidence for the role of other vitamins in sepsis remains mixed. In this narrative review, we present the preclinical, clinical, and safety evidence of the most studied vitamins in sepsis, including vitamin C, thiamine (i.e., vitamin B 1 ), and vitamin D. We also present the relevant evidence of the other vitamins that have been studied in sepsis and critical illness in both children and adults, including vitamins A, B 2 , B 6 , B 12 , and E. Impact Vitamins are key effectors in many biological processes relevant to sepsis. We present the preclinical, clinical, and safety evidence of the most studied vitamins in pediatric sepsis. Designing response-adaptive platform trials may help fill in knowledge gaps regarding vitamin use for critical illness and association with clinical outcomes.

The effect of intravenous vitamin C on clinical outcomes in patients with sepsis or septic shock: A meta-analysis of randomized controlled trials

“…It is well-established that patients with sepsis have decreased levels of vitamin C (also known as ascorbic acid), and this depletion has a dose-dependent association with increased organ dysfunction and mortality ( 7 ). The beneficial effects and associated mechanisms of vitamin C in sepsis including its anti-inflammatory and anti-oxidant properties ( 8 , 9 ), acting as an enzymatic cofactor in the synthesis of vasopressin, cortisol, and catecholamine ( 10 , 11 ), inhibiting the nitric oxide synthase and regulating the clearance of alveolar fluid ( 12 , 13 ).…”

Construction of gene network database, and identification of key genes for diagnosis, prognosis, and treatment in sepsis

“…Interestingly, monocyte counts were independently associated with mortality in patients with sepsis [53]. Serum vitamin B 12 levels have been positively correlated with increased mortality in critically ill patients [54]. Thus, our analysis generated novel hypotheses that merit future validation.…”

The Effects of Vitamins and Micronutrients on Helicobacter pylori Pathogenicity, Survival, and Eradication: A Crosstalk between Micronutrients and Immune System

“…The most common forms of food-derived vitamin A are retinol (vitamin A1) and carotenoids (provitamin A) which are transferred to hepatic stellate cells (HSCs) and then stored as retinyl ester [ 113 ]. Retinol, especially found in animal foods including dairy, fish, egg yolks, and meat, is converted to retinal by retinyl ester and thereby plays a key role in low-light and color vision and mitochondrial oxidative phosphorylation [ 114 , 115 ]. By being converted to retinoic acid (RA), a hormone-like growth factor, retinol stimulates the differentiation and growth of epithelial cells and maintains the homeostasis of the skin and bone [ 116 , 117 ].…”