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Updated: May 5, 2026

A Data-Driven Approach to Quantifying Immune States in Sepsis
Published on: February 7, 2025
Impact of Vitamin D3 Supplementation on 28-Day ICU Mortality in Sepsis Patients: A Retrospective Study with
Xiaofei Huang1,2, Anqiang Zhang3, Dalin Wen3
1Department of Emergency Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
Abstract:
Reduced levels of vitamin D are associated with increased incidence and mortality of sepsis. Nonetheless, the effectiveness of vitamin D supplementation in improving sepsis patients' outcomes continues to be debated. In this research, which was conducted as a retrospective cohort analysis, data obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV 3.0) were used. The focus of the study was on vitamin D3 administration to sepsis patients while in the ICU. The primary outcome measurement was 28-day ICU mortality, with secondary outcomes of mechanical ventilation duration, percentage of patients receiving mechanical ventilation, and ICU stay length. The Kaplan-Meier curve analysis, Cox regression analysis, and subgroup analyses were performed to explore the link between vitamin D3 supplementation and sepsis prognosis. A 1:1 propensity score matching (PSM) approach was used to strengthen the reliability of the results. Before matching, the cohort comprised 28,524 patients, which was reduced to 4,856 after PSM. The analysis revealed that vitamin D3 supplementation was associated with a lower 28-day ICU mortality rate (HR = 0.71, 95% CI: 0.64-0.78, p < 0.001). Kaplan-Meier curve analysis revealed significantly greater survival probabilities in the group receiving vitamin D3 than in the group not receiving vitamin D3 (p < 0.001). Subgroup analysis showed that total cumulative exposure to vitamin D3 was more strongly associated with 28-day ICU mortality (p < 0.001), whereas daily dose and dosing frequency showed no significant association. The results after PSM and subgroup analysis were consistent with those of the original cohort study, further confirming the robustness of the results. Overall, vitamin D3 supplementation is associated with lower 28-day ICU mortality and better outcomes in patients with sepsis. However, given the retrospective observational design, large-scale prospective randomized controlled trials are warranted to validate these observational associations and establish causal effects.
Insights
Vitamin D3 supplementation may reduce 28-day mortality in sepsis patients. This study found lower ICU mortality and better outcomes with vitamin D3, but more research is needed.
Area of Science:
- Critical Care Medicine
- Nutritional Science
- Epidemiology
Background:
- Vitamin D deficiency is linked to increased sepsis incidence and mortality.
- The role of vitamin D supplementation in sepsis patient outcomes remains controversial.
Purpose of the Study:
- To investigate the association between vitamin D3 supplementation and outcomes in intensive care unit (ICU) sepsis patients.
- To analyze the impact of vitamin D3 on 28-day ICU mortality, mechanical ventilation duration, and ICU stay length.
Main Methods:
- Retrospective cohort analysis using the MIMIC-IV 3.0 database.
- Propensity score matching (PSM) to create comparable groups (4,856 patients post-PSM).
- Kaplan-Meier curves, Cox regression, and subgroup analyses were employed.
Main Results:
- Vitamin D3 supplementation was associated with significantly lower 28-day ICU mortality (HR=0.71, p<0.001).
- Kaplan-Meier analysis showed improved survival probabilities in the vitamin D3 group (p<0.001).
- Total cumulative vitamin D3 exposure, not daily dose or frequency, correlated with reduced mortality.
Conclusions:
- Vitamin D3 supplementation appears linked to improved outcomes and reduced mortality in sepsis patients.
- Further large-scale prospective randomized controlled trials are necessary to confirm these findings and establish causality.
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