Association of dietary intake of folate, serum folate, and red blood cell folate with mortality risk in patients with depression: a population-based longitudinal cohort study

BackgroundFolate level is associated with depression, yet prospective evidence is lacking on the relationship of dietary intake, serum, and red blood cell (RBC) folate levels with mortality risk in patients with depression.MethodsDietary intake, serum, and RBC folate data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 were included. Depression was diagnosed using the PHQ-9 with a cutoff value of 5. Additionally, all-cause and cause-specific mortality data up to December 31, 2019, were determined from the National Death Index. Weighted multivariable Cox regression and restricted cubic spline (RCS) analysis were used to determine the relationship between folate and outcomes.ResultsA total of 4843 adult patients with depression were included, with a mean age of 45.16 years, and females accounted for 61.59%. Over a mean follow-up of 7.2 years, 544 participants died. Weighted Cox regression showed that, after adjustment, only RBC folate among nine folate indicators significantly predicted all-cause mortality in patients with depression. A per standard deviation (SD) increase in RBC folate increased the all-cause mortality risk by 12% (HR: 1.12, 95% CI: 1.04-1.21, p = 0.003). RCS analysis revealed a U-shaped association of RBC folate with all-cause, CVD, and cancer mortality, with inflection points at 540.5 ng/ml, 575.2 ng/ml, and 624.1 ng/ml, respectively. Further segmented regression showed that an increase in RBC folate reduced only cancer mortality risk to the left of the inflection points. To the right of these points, RBC folate was significantly positively associated with all-cause, CVD, and cancer mortality risks.HighlightsRBC folate exhibited a U-shaped association with all-cause, cardiovascular-specific, and cancer-specific mortality risks in patients with depression.ConclusionDietary and serum folate were not associated with overall mortality rates in patients with depression. However, RBC folate exhibited a U-shaped association with all-cause, cardiovascular-specific, and cancer-specific mortality risks in patients with depression.