Clinical randomized trial of vitamin D and C supplementation in critically ill patients with respiratory failure

Acute respiratory failure (ARF) is the most common organ failure, affecting up to 30% of all intensive care unit (ICU) admissions. Since vitamin deficiencies are frequent in critically ill patients, and considering that the two primary mechanisms involved in ARF are inflammation and oxidative stress, this study aims to investigate the effects of co-supplementation of vitamins D and C on inflammatory parameters, oxidative stress, and clinical outcomes in critically ill ARF patients. In this double-blind, randomized, placebo-controlled trial, ARF patients admitted to the ICU were randomly assigned to either the intervention group (daily 2000 mg of intravenous vitamin C plus 5000 IU of oral vitamin D) or the control group (placebo). The intervention lasted 10 days, and patients were followed for 90 days, assessing inflammation, oxidative stress parameters, and clinical outcomes. Thirty-four patients in the intervention group and 33 in the control group completed the trial. At the end of the intervention, High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and malondialdehyde (MDA) were significantly reduced, while total antioxidant capacity (TAC) increased significantly in the intervention group compared to both the baseline and the control group (p < 0.001). Among the clinical outcomes, only the duration of ICU stay was shorter in the intervention group (0.028). However, 90-day survival (HR 0.55; 95% CI 0.21–1.41; P = 0.22) did not show a significant difference between the two groups. Our study concluded that vitamin D and C supplementation may improve inflammation and oxidative status in critically ill ARF patients, reducing ICU stays but not affecting 90-day mortality. The study has been registered at https://irct.behdasht.gov.ir/ . Number: IRCT20090822002365N29.Registered on 2023-08-05 and it was ethically approved by the Committee of Iran University of Medical Sciences (registration IR.IUMS.REC.1402.210).