Megadose Vitamin C Failed to Lower Sepsis Mortality

Megadose intravenous vitamin C did not reduce 28-day mortality compared with placebo among adults with sepsis in the CEMVIS randomized clinical trial, published in Critical Care. Investigators said the results do not support routine use of the regimen in the sepsis population.

CEMVIS was a multicenter, randomized, single-blind, placebo-controlled trial at four hospitals in China. Of 234 patients, 231 were included in the modified intention-to-treat population: 114 assigned to vitamin C and 117 to placebo. Participants received intravenous vitamin C 12g every 12 hours or an equivalent volume of 5% glucose for 4 days or until transfer out of the intensive care unit. The primary outcome was 28-day all-cause mortality.

By day 28, 35 of 114 patients (30.7%) in the vitamin C group and 36 of 116 patients (31.0%) in the placebo group had died (odds ratio, 0.99; 95% CI, 0.56-1.74; P=.97). No significant between-group differences were observed in intensive care unit length of stay, weaning from mechanical ventilation or vasopressors, duration of organ-support therapies, or change in Sequential Organ Failure Assessment scores through 96 hours.

A prespecified subgroup analysis found an interaction according to septic shock status (P for interaction=.026). Mortality numerically favored vitamin C without septic shock (15.4% vs 34.0%) but numerically favored placebo with septic shock (38.7% vs 29.0%). Investigators called these findings exploratory and hypothesis-generating. Hypernatremia was more frequent with vitamin C (35.1% vs 20.5%; P=.02). Two vitamin C recipients developed hemolysis; both carried a heterozygous glucose-6-phosphate dehydrogenase (G6PD) c.1376G>T variant, and a treatment contribution could not be excluded.

Limitations included the single-blind design, modified intention-to-treat analysis, conduct exclusively in China, exclusion of adults older than 80 years, and the small subgroup without septic shock. 

Source: Guan J, Wang G, Liang Z, et al. Effect of megadose vitamin C in patients with sepsis: the CEMVIS randomized clinical trial. Crit Care. Published online August 24, 2026. doi:10.1186/s13054-026-06280-7