Elevated baseline vitamin B12 level and all-cause mortality risk in patients with sepsis: a cohort analysis

Elevated serum vitamin B12 levels have been associated with adverse outcomes in various clinical settings; however, the prognostic significance of pre-existing vitamin B12 elevation measured before sepsis onset remains unclear. This study examined the association between pre-sepsis vitamin B12 levels and clinical outcomes in adults with sepsis.

This retrospective cohort study utilized the TriNetX database to identify adults diagnosed with sepsis between 2010 and 2024. Patients with elevated vitamin B12 levels (≥1,000 pg./mL) measured within 3 months before sepsis diagnosis were compared with those having normal levels (300-900 pg./mL) using 1:1 propensity score matching. The primary outcome was 90-day all-cause mortality. The secondary outcomes included major adverse cardiovascular events, organ failure, intensive care unit (ICU) admission, and progression to severe sepsis.

After propensity score matching, 18,830 patients per group (37,660 patients in total) were included in this cohort. Elevated pre-sepsis vitamin B12 levels were associated with increased 90-day mortality [26.3% vs. 21.8%; hazard ratio (HR): 1.29, 95% confidence interval (CI): 1.24-1.35, p < 0.001] and progression to severe sepsis (17.3% vs. 15.3%; HR 1.18, 95% CI 1.12-1.24, p < 0.001). Organ failure (HR 1.09, p < 0.001) and ICU admission showed a marginal association (HR 1.05, p = 0.031), while major adverse cardiovascular events showed no significant association. During the 90-365-day follow-up period, the associations were attenuated (mortality: HR 1.07, 95% CI 0.99-1.15, p = 0.077). Dose-response analysis revealed stronger associations at vitamin B12 levels >1,200 pg./mL (HR 1.35 for mortality). Younger patients (18-65 years) exhibited more pronounced associations.

Elevated pre-sepsis vitamin B12 levels are associated with increased short-term mortality and adverse outcomes in patients with sepsis, suggesting that elevated pre-sepsis vitamin B12 levels may serve as a risk-associated biomarker, although its independent prognostic utility requires further validation.