Red blood cell folate and depression risk in U.S. women: A dose–response analysis from a nationwide cross-sectional study (2009–2018)

In contemporary society, the prevalence of depression among women is worsening and rising annually, influenced by numerous intricate factors. Folate, a B vitamin, is vital for overall human health. This study aimed to investigate the association between red blood cell (RBC) folate levels and depression within a nationally representative group of women in the U.S. We conducted a cross-sectional study to examine the association between depression and RBC folate levels among women in the U.S., using data from the National Health and Nutrition Examination Survey from 2009 to 2018. Participants were stratified by depressive status and categorized into 4 quartiles (Q1-Q4) based on their RBC folate levels. We built both univariate and multivariate regression models to conduct a comprehensive threshold effect analysis on the correlation between RBC folate levels and depression. We analyzed data from 9409 women in the U.S. In the fully adjusted model, when RBC folate was sorted into 4 quartiles, both the lowest (Q1: odds ratio [OR] = 1.396, 95% confidence interval [CI]: 1.135-1.717, P = .0027) and highest (Q4: OR = 1.425, 95% CI: 1.160-1.749, P = .0014) quartiles showed significantly higher odds of depression compared to the reference Q2. Threshold effect analysis identified a breakpoint at 985 nmol/L, indicating a U-shaped association between RBC folate level and depression. Below 985 nmol/L, the risk of depression significantly decreased by 6% per 100 nmol/L increase in RBC folate (OR = 0.9994, 95% CI: 0.9989-0.9999, P = .0099). Above this inflection point, the risk significantly increased by 3% per 100 nmol/L increase (OR = 1.0003, 95% CI: 1.0002-1.0005, P < .0001). A U-shaped association was observed between RBC folate and depression among women in the U.S. Maintaining appropriate RBC folate levels may help reduce depression in women. However, the mechanisms behind both RBC folate and depression still require further in-depth research.