Liao Xin, Yu Song, Wang Lin, Zhang Ruyue, Yu Ke
Department of General Medicine, The General Hospital of Western Theater Command, Chengdu, Sichuan, China.
Department of General Medicine, the Third Affiliated Hospital of Chengdu Medical College, Chengdu Pidu District People's Hospital, Chengdu, Sichuan, China.
Front Physiol. 2025 Mar 20;16:1494863. doi: 10.3389/fphys.2025.1494863. eCollection 2025.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. However, the role of folate in MASLD remains controversial. This study aimed to investigate the association between two folate indicators [serum folate and red blood cell (RBC) folate] and MASLD prevalence using data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES).
A total of 3,879 participants without liver disease or significant alcohol consumption were included in the final analysis. Hepatic steatosis was assessed via transient elastography, with MASLD defined as a controlled attenuation parameter (CAP) ≥285 dB/m and the presence of at least one cardiometabolic risk factor. Logistic regression and generalized additive models (GAMs) were used to evaluate associations between folate levels and MASLD, with subgroup analyses stratified by age, gender, and body mass index (BMI).
After full adjustment for confounders, RBC folate exhibited a significant positive association with MASLD (OR = 1.111 and 95% CI: 1.015-1.216 per 1-unit increase). In contrast, serum folate showed a transient negative association in minimally adjusted models (OR = 0.869 and 95% CI: 0.802-0.941), which disappeared after further adjustments. Subgroup analyses confirmed that age, gender, and BMI did not modify the RBC folate-MASLD relationship.
These findings suggest that elevated RBC folate levels are independently associated with MASLD prevalence, whereas serum folate may lack clinical relevance due to susceptibility to confounding factors. RBC folate, as a stable biomarker of long-term folate status, may serve as a superior indicator for investigating folate-MASLD associations.
代谢功能障碍相关脂肪性肝病（MASLD）是全球最常见的慢性肝病。然而，叶酸在MASLD中的作用仍存在争议。本研究旨在利用2017 - 2020年美国国家健康与营养检查调查（NHANES）的数据，调查两种叶酸指标[血清叶酸和红细胞（RBC）叶酸]与MASLD患病率之间的关联。
共有3879名无肝病或大量饮酒的参与者纳入最终分析。通过瞬时弹性成像评估肝脂肪变性，MASLD定义为受控衰减参数（CAP）≥285 dB/m且存在至少一种心血管代谢危险因素。采用逻辑回归和广义相加模型（GAM）评估叶酸水平与MASLD之间的关联，并按年龄、性别和体重指数（BMI）进行亚组分析。
在对混杂因素进行充分调整后，RBC叶酸与MASLD呈显著正相关（每增加1个单位，OR = 1.111，95% CI：1.015 - 1.216）。相比之下，血清叶酸在最小调整模型中呈短暂负相关（OR = 0.869，95% CI：0.802 - 0.941），在进一步调整后消失。亚组分析证实，年龄、性别和BMI并未改变RBC叶酸与MASLD的关系。
这些发现表明，RBC叶酸水平升高与MASLD患病率独立相关，而血清叶酸可能因易受混杂因素影响而缺乏临床相关性。RBC叶酸作为长期叶酸状态的稳定生物标志物，可能是研究叶酸与MASLD关联的更佳指标。
