Effect of Early High-Dose Vitamin D3 Repletion on Cognitive Outcomes in Critically Ill Adults

Vitamin D to Improve Outcomes by Leveraging Early Treatment Network Investigators

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. Research Question: Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function? Study Design and Methods: This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group. Results: Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42). Interpretation: In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function. Trial Registry: ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov

Original languageEnglish (US)
Pages (from-to)909-918
Number of pages10
Issue number3
StatePublished - Sep 2021


  • ICU
  • executive function
  • global cognition
  • vitamin D

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine


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