Associations of Vitamin B12 and Methylmalonic Acid Levels with Mortality Risk in Patients with Preexisting Stroke: A Prospective Cohort Study

Purpose : The relationship between vitamin B12, methylmalonic acid (MMA, a marker of B12 deficiency), and mortality among stroke survivors remains unclear. This study investigates the association between serum vitamin B12 and MMA levels with mortality in stroke survivors. Methods: This prospective cohort study, part of the NHANES, included adults who experienced a stroke between 1999-2004 and 2011-2014, followed until December 31, 2019. We analyzed serum B12 and MMA levels, dietary B12 intake, and supplement use. Three weighted Cox proportional hazards regression models estimated the association between these biomarkers and mortality risk, presented as hazard ratios (HR) with 95% confidence intervals (CI). Restricted cubic spline (RCS) analysis explored potential nonlinear relationships between MMA, serum B12, dietary intake, and supplement use with mortality risk. Results: A total of 820 stroke survivors were followed for a median of 7.17 years. Elevated MMA levels were significantly associated with all-cause mortality, with multivariate-adjusted HRs for MMA quartiles being 1.00 (reference), 1.471 (95% CI: 1.034-2.094), 1.647 (95% CI: 1.123-2.416), and 2.277 (95% CI: 1.512-3.430), P trend ≤ 0.001. The study revealed that participants with the highest levels of MMA and B12 had a multivariable-adjusted HR of 2.390 (95% CI: 1.317-4.337, P = 0.004). Conversely, no significant associations were observed between serum B12 concentration, dietary B12 intake, or supplement use and mortality risk. Conclusion: Among stroke survivors, elevated MMA levels are significantly linked to increased all-cause mortality, while serum B12 levels and intake do not significantly affect mortality risk, potentially due to reduced responsiveness to vitamin B12.