Harm after abrupt termination of vitamin C
death, critically ill, organ dysfunction, sepsis, diabetes
PHYSIOLOGICAL STRESS, CRITICALLY ILL, EVENTS, SEPSIS, DIABETES
The LOVIT authors concluded that “in adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo” [This conclusion is misleading as it implies that it was the “receiving” of intravenous vitamin C that explains the increased risk of death by day 28 in the participants randomized to vitamin C. We demonstrate that there is no evidence of difference in mortality between the trial groups The published survival curves comparing the vitamin C and placebo groups of the LOVIT trial cover a period of 180 days [Similar time-modification was previously observed in the CITRIS-ALI trial, which also examined the effect of 4-day vitamin C on sepsis. The groups differed significantly during the 4-day vitamin C administration, but not thereafter [Some medical treatments are events at a point in time, or within a narrow time period, such as vaccination and surgery. In such cases we expect long-term benefits from the short treatment and the effects can be estimated over a long follow-up period. On the other hand, many treatments require compliance over a long period of time. For example, antihypertensive and diabetes drugs are taken regularly for years before effects are seen on clinically relevant outcomes. Similarly, when vitamin C is administered for critically ill patients, it should be administered over a long period for benefits to be seen.There is evidence that vitamin C is depleted during severe physiological stress, indicated by decreases in vitamin C levels, and parallel increases in the oxidized forms of the vitamin, i.e., dehydroascorbate and ascorbate free radical [For decades, there has been concern about the possibility of a rebound effect from abrupt termination of vitamin C [In the LOVIT trial, the median length of ICU stay was 6 days, that is, 2 days longer than the 4-day vitamin C administration. Furthermore, 25% of patients stayed in ICU for ≥12 days, that is ≥8 days beyond the termination of vitamin C. The LOVIT trial reported baseline vitamin C levels, but not levels thereafter. Excess mortality was pronounced in patients with the lowest baseline vitamin C levels [