Association of Plasma Concentration of Vitamin B(12) With All-Cause Mortality in the General Population 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 10 000 person-years for the quartile with the lowest plasma concentration of vitamin B(12) and 65.7 deaths per 10 000 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.