Effect of vitamin C in critically ill patients with sepsis and septic shock: A meta-analysis

Feng, Fang; Yang, Heiko; Yang, Weiwei; Chang, Xue-Ni; Chen, Yu

doi:10.1177/0036850421998175

Cited by 11 publications

(13 citation statements)

References 28 publications

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“…However, the ICU length of stay did not differ between the two groups. Therefore, multicenter and randomized controlled trials are needed to further clarify the safety and effectiveness of using vitamin C to treat patients with sepsis and septic shock [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model

et al. 2021

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Sepsis is an extremely complex clinical syndrome, usually involving an excessive inflammatory response including an overshooting cytokine release that damages tissue and organs of the patient. Due to the severity of this condition, it is estimated that over 11 million people die from sepsis each year. Despite intensive research in the field, there is still no specific therapy for sepsis. Many sepsis patients show a marked deficiency of vitamin C. 9 out of 10 sepsis patients have a hypovitaminosis C, and every third patient even shows a clinical deficiency in the scurvy range. In addition, low vitamin C levels of intensive care sepsis patients correlate with a higher need for vasopressors, higher Sequential Organ Failure Assessment (SOFA) scores, and increased mortality. Based on this observation and the conducted clinical trials using vitamin C as sepsis therapy in intensive care patients, the aim of the present ex vivo study was to evaluate the effects of high-dose vitamin C alone and in a triple combination supplemented with vitamin B1 (thiamine) and hydrocortisone on the lipopolysaccharide (LPS)-induced cytokine response in peripheral blood mononuclear cells (PBMCs) from healthy human donors. We found that all corticosteroid combinations strongly reduced the cytokine response on RNA- and protein levels, while high-dose vitamin C alone significantly diminished the PBMC mediated secretion of the cytokines interleukin (IL)-10, IL-23, and monocyte chemo-attractant protein (MCP-1), which mediate the inflammatory response. However, vitamin C showed no enhancing effect on the secretion of further cytokines studied. This data provides important insights into the possible immunomodulatory function of vitamin C in an ex vivo setting of human PBMCs and the modulation of their cytokine profile in the context of sepsis. Since vitamin C is a vital micronutrient, the restoration of physiologically adequate concentrations should be integrated into routine sepsis therapy, and the therapeutic effects of supraphysiological concentrations of vitamin C in sepsis patients should be further investigated in clinical trials.

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Section: Discussionmentioning

confidence: 99%

Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model

et al. 2021

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“…117,118 Neither found a significant difference in the primary endpoint of mortality (28-day mortality, or long-term mortality). Of three published meta-analyses limited to RCTs, [119][120][121] two showed a reduction in 72-hour SOFA scores among patients in the intervention groups, but no difference in mortality. 119,120 One, which was limited to RCTs of vitamin C infusion only, shows a significant reduction in 28-day mortality (odds ratio: 0.60, with 95% CI: 0.42-0.85).…”

Section: Clinical Studies Of Vitamin C In Sepsismentioning

confidence: 96%

“…Multiple systematic reviews with meta-analyses evaluating vitamin C in the critically ill and in sepsis have been published. 3,56,[114][115][116][117][118][119][120][121][122] Two of the five meta-analyses of vitamin C in sepsis and/or septic shock included all study types (i.e., RCTs, before/after, cohort studies), and included studies of vitamin C alone or in combination with thiamine and/or hydrocortisone. 117,118 Neither found a significant difference in the primary endpoint of mortality (28-day mortality, or long-term mortality).…”

Section: Clinical Studies Of Vitamin C In Sepsismentioning

confidence: 99%

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Any Role of High-Dose Vitamin C for Septic Shock in 2021?

Agarwal

Hager

Sevransky

2021

Semin Respir Crit Care Med

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While the use of vitamin C as a therapeutic agent has been investigated since the 1950s, there has been substantial recent interest in the role of vitamin C supplementation in critical illness and particularly, sepsis and septic shock. Humans cannot synthesize vitamin C and rely on exogenous intake to maintain a plasma concentration of approximately 70 to 80 μmol/L. Vitamin C, in healthy humans, is involved with antioxidant function, wound healing, endothelial function, and catecholamine synthesis. Its function in the human body informs the theoretical basis for why vitamin C supplementation may be beneficial in sepsis/septic shock.Critically ill patients can be vitamin C deficient due to low dietary intake, increased metabolic demands, inefficient recycling of vitamin C metabolites, and loss due to renal replacement therapy. Intravenous supplementation is required to achieve supraphysiologic serum levels of vitamin C. While some clinical studies of intravenous vitamin C supplementation in sepsis have shown improvements in secondary outcome measures, none of the randomized clinical trials have shown differences between vitamin C supplementation and standard of care and/or placebo in the primary outcome measures of the trials. There are some ongoing studies of high-dose vitamin C administration in patients with sepsis and coronavirus disease 2019; the majority of evidence so far does not support the routine supplementation of vitamin C in patients with sepsis or septic shock.

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“…Pooled data using a random effect model showed a 19% reduction in odds for hospital mortality, while among the 15 RCTs, this effect could not be observed. Feng et al [30] included nine RCTs with a 584 septic patients and revealed no significant differences between the vitamin C and control group on the primary endpoint 28-day mortality or secondary endpoints including vasopressor dose and length of stay. Lastly, the SRMA by Xing et al [35], including 18 RCTs with N = 2001 critically ill patients, reported reduced ICU and hospital length of stay without significant effects on the longest follow-up mortality, hospital or ICU mortality and change in SOFA scores.…”

Section: Metaanalysesmentioning

confidence: 99%

Vitamin C in critical illness: end of the story or still a place?

Radke

Homayr

Stoppe

et al. 2023

Current Opinion in Critical Care

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Purpose of review Critical illness is associated with decreased micronutrient levels, including vitamin C, an essential antioxidant for systemic inflammation. This review discusses the most recent evidence of high-dose vitamin C monotherapy in critically ill adults. Recent findings Three randomized-controlled trials (RCTs) were published in 2022. A pilot study including 40 patients with septic shock could not detect significant differences in outcome parameters after administering vitamin C. A multicenter study with 124 septic patients showed no significant difference in 28-day mortality, while vitamin C was associated with an increased risk of acute kidney dysfunction. The LOVIT trial, an international prospective RCT in 872 septic patients, revealed an increased risk of the composite endpoint persistent organ dysfunction plus death at day 28 in the high-dose vitamin C group. Six systematic reviews and meta-analyses (SRMA), including up to 4740 patients published before and 2 SRMA publications including these RCTs showed divergent results on clinical endpoints including mortality. Summary The use of high-dose intravenous vitamin C cannot be recommended for the septic critically ill in clinical practice since the LOVIT trial. Further research is needed to evaluate its potential role in other critically ill patients.

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Effect of vitamin C in critically ill patients with sepsis and septic shock: A meta-analysis

Cited by 11 publications

References 28 publications

Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model

Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model

Any Role of High-Dose Vitamin C for Septic Shock in 2021?

Vitamin C in critical illness: end of the story or still a place?

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