The origin of vitamin B12 levels and risk of all-cause, cardiovascular and cancer specific mortality: A systematic review and dose-response meta-analysis

Abstract

Background: Vitamin B12 is essential to human but the implications of serum vitamin B12 level for mortality in clinical practice remain unclear. We conducted a systematic review and dose-response meta-analysis to quantify the relationship between vitamin B12 levels and the risk of all-cause, cardiovascular, and cancer mortality.

Methods: Electronic databases of PubMed, Embase, and the Cochrane Library Central Register of Controlled Trials were searched from inception through May 2023. Two reviewers independently extracted individual study data and evaluated the risk of bias among the studies using the Newcastle‒Ottawa Scale. To examine a potential nonlinear relationship between the vitamin B12 levels and all-cause mortality, we performed a two-stage random effects dose‒response meta-analysis.

Results: Twenty-two cohort studies (92,346 individuals with 10,704 all-cause deaths) were included. A linear trend dose-response analysis showed that each 100 pmol/L increase in serum vitamin B12 concentration was associated with a 4 % higher risk of all-cause mortality in the general population (adjusted HR 1.04, 95 % confidence interval CI 1.01 to 1.08; n = 8; P non-linearity = 0.11) and a 6 % higher risk for all-cause mortality in older adults (adjusted HR 1.06, 95 % CI 1.01 to 1.13; n = 4; P non-linearity = 0.78). Current evidence was mixed for the association between serum vitamin B12 concentration and cardiovascular mortality and was limited for cancer mortality. The meta-analysis of cohort studies showed a positive association between a high serum vitamin B12 concentration (>600 pmol/L) and all-cause mortality (adjusted HR 1.50, 95 % CI 1.29 to 1.74; n = 10; p < 0.01), CVD mortality (adjusted HR 2.04, 95 % CI 0.99 to 4.19; n = 2; p = 0.02), except cancer mortality (adjusted HR 1.56, 95 % CI 0.82 to 2.95; n = 3). Similarly, serum vitamin B12 concentrations (400-600 pmol/L) were associated with increased all-cause mortality (adjusted HR 1.34, 95 % CI 1.10 to 1.64; n = 9; p < 0.01).

Conclusions: Serum vitamin B12 concentration was positively associated with the risk of all-cause mortality, especially among older adults, with a linear increasing trend. These findings suggested the primary cause of elevated level of serum vitamin B12 concentration should be timely identified and effectively managed in clinical practice.

Keywords: All-cause mortality; CVD; Cancer; Dose-response meta-analysis; Vitamin B12.