Vitamin C and Sepsis: Data becomes sour, suggesting damage

Vitamin C was associated with significant damage when used in patients with sepsis in the intensive care unit (ICU), the LOVIT trial found.

For patients receiving vasopressor therapy in the ICU, the endpoint of death or persistent organic dysfunction on the 28th was more common in those who had been randomized to IV vitamin C therapy instead of placebo (44.5% vs 38.5%, risk ratio). [RR] 1.21, 95% CI 1.04-1.40), according to Francois Lamontagne, MD, of the University of Sherbrooke in Quebec, and colleagues, writing in the New England Journal of Medicine.

Individual mortality outcomes (35.4% vs. 31.6%, respectively) and persistent organic dysfunction (9.1% vs. 6.9%) had an unfavorable trend for the vitamin C group, but were not significantly different:

  • Mortality: RR 1.17 (95% CI 0.98-1.40)
  • Persistent organic dysfunction: RR 1.30 (95% CI 0.83-2.05)

And a secondary analysis of the primary outcome that fit the pre-specified initial characteristics was also not significant (RR 1.15, 95% CI 0.90-1.47).

In addition, vitamin C receptors were no longer at risk for tissue dysoxia, inflammation, or endothelial injury, making it impossible for researchers to determine the mechanism of potential vitamin C damage, the group reported.

The study’s findings were also presented at the 2022 Critical Care Reviews meeting.

The researchers acknowledged that there may have been confusion in the study, given the lack of information on specific pathogens, antimicrobial therapy, and the presence of acute respiratory distress syndrome in trial participants.

Further data are expected from ongoing vitamin C trials. These include REMAP-CAP in the context of pneumonia, LOVIT-COVID in hospitalized patients with COVID, and a European study on sepsis complicated by acute respiratory distress syndrome.

Interest in vitamin C IV as a potential treatment for sepsis is based on the belief that its antioxidant properties could reduce tissue damage caused by oxidative stress.

However, the evidence for the effectiveness of vitamin C in sepsis has not been strong, as shown by a recent meta-analysis. The 2017 paper that sparked interest in vitamin C in this environment has been criticized as potentially “too good to be true” and the underlying data has also been questioned.

Meanwhile, sepsis remains a common cause of death, albeit soon. It is responsible for more than a third of all hospital deaths and kills 11 million people worldwide each year, the Lamontagne group said.

The Phase III LOVIT trial was conducted in France, Canada, and New Zealand. Eligible patients were adults with sepsis who were receiving vasopressor therapy and had been in the ICU for no more than 24 hours. All had proven or suspected infections as the primary diagnosis. Patients with contraindications for vitamin C therapy, those receiving vitamin C in the open, and those with abstinence or expected deaths within 48 hours were excluded.

From November 2018 to July 2021, the researchers had 872 patients randomized 1: 1 to vitamin C or placebo. The experimental group received a bolus of vitamin C, while the controls obtained equal dextrose or saline. Assigned treatments were administered for 30 to 60 minutes every 6 hours for up to 96 hours. All other treatments were performed at the discretion of the treatment team.

The mean age was 65 years and less than 40% of patients were women. The initial characteristics were similar between the vitamin C and placebo groups, as well as the use of co-interventions and life support therapies during the course of their stays in the ICU.

Lamontagne and colleagues warned that their study was conducted in high-income countries and therefore may not be widespread in lower-income countries where the sepsis rate can be very high. taller.

  • James Lopilato is a writer for Medpage Today. It covers a variety of topics that are being explored in current medical science research.

Disclosures

The trial was funded by the Lotte and John Hecht Memorial Foundation, and New Biomedical Canada provided materials for the study.

Lamontagne received an institutional grant from the Lotte and John Hecht Memorial Foundation. He is also involved in other vitamin C trials. The co-authors reported relationships with the Lotte and John Hecht Memorial Foundation, and with Bayer, Baxter Healthcare Corporation, Bristol Myers Squibb, Fisher and Paykel Healthcare NZ, the French Ministry of Health, Leadiant Biosciences , Pfizer and Roche Diagnostics.

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