Critical illnesses are significant public health issues because of adverse outcomes including the high mortality rate and substantial health care costs. Critical illness survivors suffer significant long-term morbidity and mortality. Biologic daa suggests a relationship between vitamin D and important outcomes in critically ill patients. The recently published VITdAL-ICU trial a randomized controlled trial demonstrates that high dose vitamin D supplementation in critically ill patients with severe vitamin D deficiency appears to improve mortality. How vitamin D supplementation impacts critical care outcomes and which patients may benefit from vitamin D supplementation is not clear. We propose to examine the mechanism of protection of vitamin D and identify biologically plausible biomarkers through examination of the pharmacokinetics of high dose vitamin D supplementation and the modification of circulating metabolites with vitamin D supplementation using human blood samples from the completed VITdAL-ICU trial. Morbidity and mortality related to critical illness remain unacceptably high and novel therapeutic approaches to improve outcomes are urgently needed. Vitamin D is an inexpensive and innovative therapy that has significant potential to improve outcomes in critically ill patients with vitamin D deficiency.

Public Health Relevance

Patients admitted to the Intensive Care Unit (ICU) are at very high risk for mortality. Mortality in the hospital is 12% for patients who receive ICU care and mortality approaches 30% for those with sepsis. Few therapeutic options other than antibiotics and supportive care have been shown to improve outcomes in the ICU. Recently in the VITdAL-ICU trial, vitamin D supplementation was shown to improve mortality in critically ill patients when given to those with severe vitamin D deficiency. An effective therapeutic agent such as vitamin D, which may be able to alter one of the key pathways leading to uncontrolled inflammation, has significant potential to improve outcomes for critically ill patients. We propose to examine blood samples from the VITdAL-ICU trial to determine if inflammation and metabolism pathways improve with vitamin D and identify blood markers of patients likely to benefit from vitamin D.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Somers, Scott D
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Brigham and Women's Hospital
United States
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Christopher, Kenneth B (2018) Nutritional metabolomics in critical illness. Curr Opin Clin Nutr Metab Care 21:121-125
Purtle, Steven W; Horkan, Clare M; Moromizato, Takuhiro et al. (2017) Nucleated red blood cells, critical illness survivors and postdischarge outcomes: a cohort study. Crit Care 21:154
Lasky-Su, Jessica; Dahlin, Amber; Litonjua, Augusto A et al. (2017) Metabolome alterations in severe critical illness and vitamin D status. Crit Care 21:193
Mogensen, Kris M; Horkan, Clare M; Purtle, Steven W et al. (2017) Malnutrition, Critical Illness Survivors, and Postdischarge Outcomes: A Cohort Study. JPEN J Parenter Enteral Nutr :148607117709766