High Serum Folate Concentrations Are Associated with Decreased Risk of Mortality among Japanese Adults

• Published in: The Journal of nutrition Vol. 151; no. 3; pp. 657 - 665
• Main Authors: Chen, Sanmei, Honda, Takanori, Hata, Jun, Sakata, Satoko, Furuta, Yoshihiko, Yoshida, Daigo, Shibata, Mao, Ohara, Tomoyuki, Hirakawa, Yoichiro, Oishi, Emi, Kitazono, Takanari, Ninomiya, Toshiharu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2021; Oxford University Press; American Institute of Nutrition
• Subjects: Adults; Aged; Cardiovascular diseases; Causation; Cohort Studies; Cyanocobalamin; Essential nutrients; Female; folate; Folic acid; Folic Acid - blood; Gene polymorphism; Genotypes; Humans; Japan; Japanese; Male; Methylenetetrahydrofolate reductase; Middle Aged; Mortality; Nutrients; nutritional biomarkers; Polymorphism; prospective cohort; Prospective Studies; Reductases; Risk; Risk Factors; Sensitivity analysis; serum; Statistical models; Vitamin B; vitamin B-12; Japan; CVD; eGFR; folate; prospective cohort; vitamin B-12; nutritional biomarkers; mortality; ALT; MTHFR; serum; Japanese; SFA
• ISSN: 0022-3166; 1541-6100
• 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.