Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Nutr. 2021 Mar 11;151(3):657-665. doi: 10.1093/jn/nxaa382.
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.
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.
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.
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.
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.
叶酸和维生素 B-12 是细胞正常生长和复制所必需的营养物质，但血清叶酸和维生素 B-12 浓度与死亡风险的关系仍不确定。
本研究旨在探讨血清叶酸和维生素 B-12 浓度与死亡风险的关系，并检验亚甲基四氢叶酸还原酶（MTHFR）C677T 多态性是否会改变这些关系。
共纳入 3050 名年龄≥40 岁的日本社区居民，前瞻性随访 2002 年至 2012 年期间的死亡情况。使用 Cox 比例风险模型和限制三次样条估计死亡率的 HR 和 95%CI。
在中位随访 10.2 年期间，336 名参与者死亡。较高的血清叶酸浓度与全因死亡率降低相关[多变量校正 HR：0.73；95%CI：第二三分位（8.8-12.2 nmol/L；中位数 10.4 nmol/L）为 0.56，95%CI：0.46，0.80；第三三分位（≥12.5 nmol/L；中位数 15.6 nmol/L）与第一三分位（≤8.6 nmol/L；中位数 7.0 nmol/L）相比]。这种关联在所有敏感性分析中仍然显著。样条分析显示，随着血清叶酸浓度的升高，全因死亡率呈稳定下降趋势，直至 20-25 nmol/L 时达到平台期。这种关联在不考虑 MTHFR C677T 基因型的情况下仍然存在。对于血清维生素 B-12，第一三分位的全因死亡率 HR 为 1.32（95%CI：0.97，1.79），与第二三分位相比略有显著增加。在排除了心血管疾病或癌症病史、基线年龄≥85 岁的参与者或随访前 3 年内死亡的参与者后，这种关联减弱且无统计学意义。
在日本成年人中，血清叶酸浓度与全因死亡率呈负相关。在考虑到反向因果关系偏倚后，血清维生素 B-12 浓度与全因死亡率风险之间的关系并不一致。
