Vitamin D Status and Sepsis Outcomes: A PRISMA-Compliant Umbrella Review and Meta-Analysis

Area of Science:

• Critical Care Medicine
• Nutritional Immunology
• Genetics

Background:

• Vitamin D is crucial for immune function.
• Deficiency is linked to infection susceptibility and poor outcomes in critical illness.
• Existing research on vitamin D, VDR gene polymorphisms, and sepsis is fragmented.

Purpose of the Study:

• To conduct an umbrella review of high-level evidence on vitamin D status, VDR gene polymorphisms, supplementation, and sepsis.
• To synthesize evidence on sepsis incidence, mortality, severity, and genetic associations.
• To adhere to PRISMA 2020 guidelines for systematic reviews.

Main Methods:

• Umbrella review of systematic reviews and meta-analyses (2014-2025).
• Searches in PubMed, PubMed Central, and journal archives.
• Inclusion of adult, pediatric, and neonatal populations; qualitative synthesis of data.

Main Results:

• Vitamin D deficiency strongly correlates with increased sepsis risk, mortality, and severity.
• Associations are more pronounced in pediatric and neonatal populations.
• Vitamin D supplementation showed no consistent benefit for sepsis risk or mortality.

Conclusions:

• Vitamin D deficiency is a significant indicator of sepsis risk, severity, and prognosis.
• Current evidence does not support vitamin D supplementation for treating established sepsis.
• Further research may clarify the role of VDR gene polymorphisms in sepsis susceptibility.