Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands

This population-based cohort study examines the association of plasma concentrations of vitamin B-12 with all-cause mortality among adults in the Netherlands. Importance Higher plasma concentrations of vitamin B-12 have been associated with mortality in elderly and hospitalized populations, including patients with chronic kidney disease, but the association of plasma concentrations of vitamin B-12 with mortality in the general population remains unclear. Objective To investigate the association of plasma concentrations of vitamin B-12 with all-cause mortality. Design, Setting, and Participants This longitudinal cohort study used post hoc analysis to examine data from participants of the Prevention of Renal and Vascular End-stage Disease Study in Groningen, the Netherlands. Participants included individuals who completed the second screening visit beginning January 1, 2001, excluding those who were missing values of vitamin B-12 plasma concentrations or used vitamin B-12 supplementation. Follow-up time was defined between the beginning of the second screening round to end of follow-up on January 1, 2011. Data analysis was conducted from October 2, 2018, to February 22, 2019. Exposures Plasma vitamin B-12 concentration level. Main Outcomes and Measures Death as recorded by the Central Bureau of Statistics of Groningen, the Netherlands. Results A total of 5571 participants (mean [SD] age, 53.5 [12.0] years; 2830 [50.8%] men) were included in analyses. Median (interquartile range) plasma concentration of vitamin B-12 was 394.42 (310.38-497.42) pg/mL. During the median (interquartile range) of 8.2 (7.7-8.9) years of follow-up, 226 participants (4.1%) died. According to quartiles of the distribution of plasma vitamin B-12 concentration levels, mortality rates were 33.8 deaths per 10000 person-years for the quartile with the lowest plasma concentration of vitamin B-12 and 65.7 deaths per 10000 person-years for the quartile with the highest plasma concentration of vitamin B-12. After adjustment for multiple clinical and laboratory variables, Cox regression analyses found a significant association between higher vitamin B-12 plasma concentration level and increased risk of all-cause mortality (hazard ratio per 1-SD increase, 1.25 [95% CI, 1.06-1.47]; P = .006). Conclusions and Relevance These findings suggest that higher levels of plasma concentrations of vitamin B-12 were associated with increased risk of all-cause mortality after adjusting for age, sex, renal function, and other clinical and laboratory variables. The mechanisms underlying this association remain to be established. Question Are plasma concentrations of vitamin B-12 associated with risk of all-cause mortality among adults from the general population of the Netherlands? Findings In this population-based cohort study including 5571 adults, higher plasma concentrations of vitamin B-12 were associated with a 25% increased adjusted risk of all-cause mortality per 1-SD increase. Meaning These findings suggest that higher plasma concentrations of vitamin B-12 are associated with all-cause mortality, independent of traditional risk factors.