Associations of Dietary, Serum, and Red Blood Cell Folate With Frailty: A Cross-Sectional Study

This study examines the associations between different forms of dietary, serum, and red blood cell folate and frailty in US NHANES participants using two frailty assessment tools: the frailty index (FI) and phenotype.Folate levels in various forms were assessed using 24-h dietary recalls and fasting blood sample. Frailty status was determined using a FI based on 36 frailty items or the five criteria of the frailty phenotype. Logistic regression and restricted cubic splines were used to analyze the associations between folate levels and frailty.Among 31 719 participants (mean age 50.4 [SD, 17.9] years, 51.2% female), 8340 (26.3%) were classified as frailty by the FI. Penalized spline logistic models revealed significant L-shaped associations between natural food folate and frailty, and U-shaped associations for fortified foods folic acid with frailty (p-nonlinear < 0.05). Compared to the second intake quartile, participants in the lowest quartiles of natural food folate had a higher prevalence of frailty (OR, 1.17; 95% CI, 1.07-1.28), while those in the third (OR, 0.90; 95% CI, 0.82-0.99) and fourth quartiles (OR, 0.83; 95% CI, 0.75-0.92) had lower prevalence. U-shaped associations were also observed for serum total folate, 5-methylTHF, non-methyl folate, and RBC folate with frailty (p-nonlinear < 0.001), along with positive associations for serum UMFA and Mefox with frailty. Higher frailty prevalence was found in participants in the lowest quartile of serum total folate, 5-methylTHF, and non-methyl folate (ORs ranging from 1.16 to 1.29) and in the fourth quartile of non-methyl folate and RBC folate (ORs 1.18-1.31).U-shaped associations were observed for fortified foods folic acid and blood folate (serum total folate, 5-methylTHF, non-methyl folate, and RBC folate), an L-shaped association for natural food folate, and positive associations for serum UMFA and Mefox with frailty.