Vitamin C in sepsis – More harm than good

Vitamin C in sepsis – More harm than good / Attempts to use high-dose vitamin C infusions to prevent death or organ failure in sepsis patients failed, according to a larger study.

On the contrary: after 28 days, patients in the verum group had a higher risk of death than patients in the placebo group.

Sepsis is a life-threatening organ dysfunction caused by an overwhelmed immune system and a dysregulated host response to infection. According to one hypothesis, the resulting tissue-damaging oxidative stress could be alleviated by vitamin C. Furthermore, vitamin C could contribute to the immune system. A potentially beneficial effect of vitamin C administration is also based on the observation that sepsis patients often have low vitamin C levels.

Unclear data situation

Since studies on vitamin C administration in sepsis led to divergent results, a possible benefit of this approach was re-examined in a multi-centre, randomized, controlled phase III study. A clarification is also important for health economics, since not all countries have a broad arsenal of therapeutic options and vitamin C would be a cost-effective alternative.

The LOVIT study

The phase III study LOVIT (Lessening Organ Dysfunction With VITamin C) investigated whether high-dose vitamin C administration in sepsis patients within 28 days reduces the risk of mortality or the risk of persistent organ damage.

The study enrolled 872 patients with sepsis from a confirmed or suspected infection who had been in an ICU for less than a day and were already requiring vasopressor circulatory support. 435 of them (verum group) received high-dose vitamin C infusions (50 mg/kg body weight every six hours for a maximum of four days); 437 (placebo group) patients received corresponding placebo infusions. The primary study endpoint consisted of patient death or permanent organ damage within the first 28 days after the illness.

Increased risk of mortality

The primary endpoint of the study occurred in 191 of 429 patients (44.5%) in the verum group compared to 167 of 434 patients (38.5%) in the placebo group.

Vitamin C therapy was associated with a 21% increased risk of mortality or persistent organ damage (risk ratio [RR] = 1.21; 95% confidence interval 1.04 to 1.40; p = 0.01 ). Looking at the individual components of the composite endpoint, the risk of mortality in the verum group was 35.4% versus 31.6% in the placebo group (RR = 1.17), and the risk of suffering a persistent organ disorder was 35.4% 9.1% in the verum group versus 6.9% in the placebo group (RR = 1.30).

There were no notable differences between the two groups for secondary endpoints, such as certain biomarkers for inflammation or endothelial damage, survival at six months, quality of life and acute kidney injury. The only abnormality was a tendency towards an increase in hypoglycaemia (6.1% versus 5.1%; RR = 1.25) and an anaphylactic reaction in the verum group.

Unexpected result

The authors of the study had not expected this result. Secondary analyzes of biomarkers quantifying the extent of inflammation, oxygen deprivation and endothelial damage also offered no explanation.

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