Vitamin C: abrupt termination may increase mortality of sepsis patients

What is it about?

The LOVIT trial of vitamin C for sepsis patients found that mortality was increased in patients randomized to the vitamin C group. We show that mortality was increased only after vitamin C was terminated, but not during the vitamin C administration.

Featured Image

Photo by Alexander Grey on Unsplash

Photo by Alexander Grey on Unsplash

Why is it important?

In animal models of sepsis, vitamin C prevented hypotension and lung injury, improved capillary blood flow, and prolonged survival. Two randomized trials reported that vitamin C significantly decreased mortality for patients with sepsis. The recent LOVIT (2022) trial further examined the potential effects of vitamin C on sepsis patients. Unexpectedly, those in the vitamin C group had 1.17 times the risk of dying within 28 days than those in the placebo group. The LOVIT authors concluded that “those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo”. We found that there was no difference between the vitamin C and placebo groups during the 4-day vitamin C administration, indicating that vitamin C itself was not harmful. Immediately after the termination of vitamin C, on days 5 to 7, there was a 2.3-fold increase in mortality in the vitamin C group when compared to the placebo group. This indicates that it was the termination of vitamin C which caused the harm to the vitamin C group. Hence the conclusion of the LOVIT trial authors that the “receiving” of vitamin C explained the observed harm seems unjustified. Further research on vitamin C for critically ill patients should not be discouraged by the increased mortality caused by the abrupt termination of short-term vitamin C in the LOVIT trial.

Perspectives