March 2019
Harri Hemilä, and Elizabeth Chalker
Abstract
A number of controlled trials have previously found that in some contexts, vitamin C can have beneficial effects on blood pressure, infections, bronchoconstriction, atrial fibrillation, and acute kidney injury. However, the practical significance of these effects is not clear. The purpose of this meta-analysis was to evaluate whether vitamin C has an effect on the practical outcomes: length of stay in the intensive care unit (ICU) and duration of mechanical ventilation.
We identified 18 relevant controlled trials with a total of 2004 patients, 13 of which investigated patients undergoing elective cardiac surgery. We carried out the meta-analysis using the inverse variance, fixed effect options, using the ratio of means scale. In 12 trials with 1766 patients, vitamin C reduced the length of ICU stay on average by 7.8% (95% CI: 4.2% to 11.2%; p = 0.00003). In six trials, orally administered vitamin C in doses of 1–3 g/day (weighted mean 2.0 g/day) reduced the length of ICU stay by 8.6% (p = 0.003). In three trials in which patients needed mechanical ventilation for over 24 hours, vitamin C shortened the duration of mechanical ventilation by 18.2% (95% CI 7.7% to 27%; p = 0.001).
Given the insignificant cost of vitamin C, even an 8% reduction in ICU stay is worth exploring. The effects of vitamin C on ICU patients should be investigated in more detail.
Conclusions: The Way Forward
We found statistically highly significant evidence that vitamin C can shorten the length of ICU stay. We consider that our finding is a proof of concept, strongly encouraging further research, rather than justifying recommendations for change in practice. In further studies, the dose-response relationship should be carefully investigated, and oral and intravenous administration should be compared directly. Given that some common cold studies found the benefit of vitamin C to be greater in males than females, the effects of vitamin C in the ICU context should be compared between sexes. ICU patients are a highly heterogeneous group, and evidently, one estimate of vitamin C effect should not be expected to apply to all patient groups. Our analysis on mechanical ventilation indicated that the benefits of vitamin C may be greater for patients with more severe illness.
Studies of arbitrary combinations of antioxidants teach us little, since they cannot be compared or pooled and drawing conclusions about a specific antioxidant is impossible. Instead, factorial trials such as the one shown in Table 3 are informative regarding individual effects and possible interactions. Although the dose of vitamin C may influence the size of effect, it is likely that the baseline level of vitamin C also has an impact on the benefits of vitamin C administration and should therefore be measured. In addition, it is important that any further studies are sufficiently powered to be able to detect a reasonable effect and the required sample size should be calculated accordingly.
Vitamin C costs only pennies per gram, whereas one day in the ICU may cost thousands of dollars; therefore, an 8% decrease in ICU stay from the administration of 2 g/day of vitamin C warrants further research.
