25-Hydroxyvitamin D and the Inflammation–Nutrition Axis in Critically Ill Adults: Associations with Neutrophil-to-Lymphocyte Ratio and Prognostic Nutritional Index

Abstract

Vitamin D deficiency is common in critical illness, but its relationship with integrated inflammatory and immunonutritional markers remains incompletely characterized. This cross-sectional study evaluated associations of serum 25-hydroxyvitamin D [25(OH)D] with the neutrophil-to-lymphocyte ratio (NLR) and Prognostic Nutritional Index (PNI) in 81 critically ill adults admitted to a tertiary intensive care unit in Indonesia. Total lymphocyte count, serum albumin, and C-reactive protein (CRP) were examined as complementary biomarkers. Associations were assessed using Spearman correlation and multivariable linear regression adjusted for age, sex, APACHE II score, and systemic corticosteroid use; bootstrap analyses with 5,000 resamples assessed robustness. Median 25(OH)D was 20.00 ng/mL, and 90.1% of participants had concentrations ≤30 ng/mL. Serum 25(OH)D correlated inversely with NLR (rₛ = −0.266, p = 0.016), although this association did not remain significant after false-discovery-rate correction. In adjusted analysis, each 10-ng/mL increase in 25(OH)D was associated with a 2.74-unit lower NLR (95% CI, −5.55 to 0.06; p = 0.055) and a 2.07-point higher PNI (95% CI, 0.19 to 3.96; p = 0.032). The PNI association remained supported by bootstrap analysis (BCa 95% CI, 0.34–4.46; p = 0.043). No significant unadjusted associations were observed with total lymphocyte count, albumin, or CRP. Higher 25(OH)D may therefore be selectively associated with immunonutritional status in critically ill adults, warranting prospective confirmation.