Vitamin B12, Methylmalonic Acid, and Mortality Risk in Stroke Survivors: A Prospective Cohort Study

Abstract Purpose This study aims to explore the relationship between serum vitamin B12, methylmalonic acid (MMA, a marker of B12 deficiency), and mortality among stroke survivors. Methods Utilizing data from NHANES, this prospective cohort study included adult patients diagnosed with stroke between 1999–2004 and 2011–2014, with follow-up until December 31, 2019. The study focused on analyzing serum vitamin B12, MMA levels, dietary B12 intake, and supplement use. Weighted Cox proportional hazards regression models were employed to assess the association between these biomarkers and mortality risk, with results expressed as hazard ratios (HR) and 95% confidence intervals (CI). Additionally, restricted cubic spline (RCS) analysis was used to investigate potential nonlinear relationships between MMA, serum B12, dietary intake, supplement use, and mortality risk. Results The study included 820 stroke survivors, with a median follow-up period of 7.17 years. Higher MMA levels were strongly linked to an increase in all-cause mortality. After adjusting for multiple variables, the HRs for MMA quartiles were 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. Additionally, individuals in the highest quartiles for both MMA and B12 levels exhibited a multivariable-adjusted HR of 2.390 (95% CI: 1.317–4.337, P = 0.004). In contrast, no meaningful connections were found between mortality risk and serum B12 levels, dietary B12 intake, or the use of supplements. Conclusion For stroke survivors, increased MMA levels are strongly correlated with higher all-cause mortality.