Low Serum Vitamin B-12 Concentrations Are Prevalent in a Cohort of Pregnant Canadian Women

ABSTRACT Background Folate and vitamin B-12 are essential nutrients for normal cell growth and replication, but the association of serum folate and vitamin B-12 concentrations with mortality risk remains uncertain. Objective This study was performed to investigate the associations of serum folate and vitamin B-12 concentrations with mortality risk and test whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism modifies these associations. Methods A total of 3050 Japanese community residents aged ≥40 y were prospectively followed-up for mortality between 2002 and 2012. Cox proportional hazards models and restricted cubic splines were used to estimate HRs and 95% CIs of mortality. Results During a median follow-up period of 10.2 y, 336 participants died. Higher serum folate concentrations were associated with lower risks of all-cause mortality [multivariable-adjusted HR: 0.73; 95% CI: 0.56, 0.96 for the second tertile (8.8–12.2 nmol/L; median 10.4 nmol/L) and HR: 0.61; 95% CI: 0.46, 0.80 for the third tertile (≥12.5 nmol/L; median 15.6 nmol/L) serum folate concentrations compared with the first tertile (≤8.6 nmol/L; median 7.0 nmol/L)]. This association remained significant in all sensitivity analyses. Spline analyses showed a steady decline in all-cause mortality risk with increasing serum folate concentrations up to 20–25 nmol/L. This association persisted regardless of the MTHFR C677T genotypes. For serum vitamin B-12, the multivariable-adjusted HR of 1.32 (95% CI: 0.97, 1.79) of all-cause mortality was marginally significantly greater in the first tertile compared with the second tertile. This association was attenuated and nonsignificant after the exclusion of participants with a history of cardiovascular disease or cancer, or participants aged ≥85 y at baseline, or deaths in the first 3 y of follow-up. Conclusions Serum folate concentrations were inversely associated with the risk of all-cause mortality in Japanese adults. Serum vitamin B-12 concentrations were not consistently associated with all-cause mortality risk after accounting for reverse-causation bias.

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Interpretation of vitamin B-12 and folate concentrations in population-based surveys does not require adjustment for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz303 ◽

2020 ◽

Vol 111 (4) ◽

pp. 919-926 ◽

Cited By ~ 2

Author(s):

Melissa F Young ◽

Junjie Guo ◽

Anne Williams ◽

Kyly C Whitfield ◽

Sabiha Nasrin ◽

...

Keyword(s):

Survey Design ◽

Serum Vitamin ◽

Correlation Coefficients ◽

Population Based ◽

Reproductive Age ◽

Serum Folate ◽

Vitamin B ◽

Cross Sectional ◽

Population Prevalence ◽

Vitamin B 12

ABSTRACT Background Vitamin B-12 and folate deficiencies in women and children have important public health implications. However, the evidence is conflicting and limited on whether the influence of inflammation on biomarker concentrations may be sufficiently and consistently influenced by inflammation to require adjustment for interpreting concentrations or estimating population prevalence of deficiencies. Objective We examined correlations between concentrations of the inflammation biomarkers C-reactive protein (CRP) and α1-acid glycoprotein (AGP) and serum vitamin B-12 and serum and RBC folate among nonpregnant women of reproductive age (WRA; 15–49 yr) and preschool children (PSC; 6–59 mo). Methods We analyzed cross-sectional data from 16 nationally representative nutrition surveys conducted in WRA (n = 32,588) and PSC (n = 8,256) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project. Spearman correlations between CRP or AGP and vitamin B-12 or folate concentrations were examined, taking into account complex survey design effects. Results Correlations between inflammation and vitamin B-12 or folate were weak, with no clear pattern of association in either WRA or PSC. Correlation coefficients between CRP and vitamin B-12 for WRA and PSC ranged from −0.25 to 0.16, and correlations between AGP and vitamin B-12 ranged between −0.07 and 0.14. Similarly, correlations between CRP and serum folate ranged from −0.13 to 0.08, and correlations between AGP and serum folate between −0.21 and 0.02. Only 3 surveys measured RBC folate, and among them, correlations for WRA ranged from −0.07 to 0.08 for CRP and −0.04 for AGP (1 country). Conclusions Based on the weak and inconsistent correlations between CRP or AGP and vitamin B-12 or folate biomarkers, there is no rationale to adjust for inflammation when estimating population prevalence of vitamin B-12 or folate deficiencies in WRA or PSC.

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