Xu Ying, Huang Caijuan, Yang Haiping
Department of Hematology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
J Health Popul Nutr. 2025 May 29;44(1):174. doi: 10.1186/s41043-025-00898-z.
Folate 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.
Dietary 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.
A 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.
RBC folate exhibited a U-shaped association with all-cause, cardiovascular-specific, and cancer-specific mortality risks in patients with depression.
Dietary 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.
叶酸水平与抑郁症相关，但关于抑郁症患者饮食摄入、血清和红细胞（RBC）叶酸水平与死亡风险之间关系的前瞻性证据尚缺乏。
纳入了2007年至2018年美国国家健康与营养检查调查（NHANES）中的饮食摄入、血清和RBC叶酸数据。使用PHQ-9诊断抑郁症，临界值为5。此外，从国家死亡指数确定截至2019年12月31日的全因和特定病因死亡率数据。采用加权多变量Cox回归和受限立方样条（RCS）分析来确定叶酸与结局之间的关系。
共纳入4843例成年抑郁症患者，平均年龄45.16岁，女性占61.59%。平均随访7.2年，544名参与者死亡。加权Cox回归显示，调整后，九个叶酸指标中只有RBC叶酸显著预测抑郁症患者的全因死亡率。RBC叶酸每增加一个标准差（SD），全因死亡风险增加12%（HR：1.12，95%CI：1.04-1.21，p = 0.003）。RCS分析显示RBC叶酸与全因、心血管疾病和癌症死亡率呈U形关联，拐点分别为540.5 ng/ml、575.2 ng/ml和624.1 ng/ml。进一步的分段回归显示，在拐点左侧，RBC叶酸增加仅降低癌症死亡风险。在这些点右侧，RBC叶酸与全因、心血管疾病和癌症死亡风险显著正相关。
在抑郁症患者中，RBC叶酸与全因、心血管疾病特异性和癌症特异性死亡风险呈U形关联。
饮食和血清叶酸与抑郁症患者的总体死亡率无关。然而，在抑郁症患者中，RBC叶酸与全因、心血管疾病特异性和癌症特异性死亡风险呈U形关联。
