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ORIGINAL RESEARCH article

Front. Nutr.
Sec. Nutrition and Metabolism
Volume 11 - 2024 | doi: 10.3389/fnut.2024.1437183

Serum folate levels and risk of metabolic dysfunction-associated steatotic liver disease: results from a crosssectional study and Mendelian randomization analysis

Provisionally accepted
Lan Y. Chen Lan Y. Chen Jie Gao Jie Gao Bin X. Wang Bin X. Wang Hong Lu Hong Lu Ya Zheng Ya Zheng Qian Ren Qian Ren *
  • Lanzhou University, Lanzhou, China

The final, formatted version of the article will be published soon.

    Evidence from observational studies on the association between folate and metabolic dysfunction-associated steatotic liver disease (MASLD) is conflicting.Aims: This study aimed to investigate the association between serum folate concentration and MASLD and further assess the causal relationship using Mendelian randomization (MR) analysis.To investigate the causal relationship between serum folate and MASLD, we conducted a cross-sectional study that selected 1117 participants from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). The association between serum folate level and the risk of MASLD was evaluated under a multivariate logistic regression model.In addition, we conducted a two-sample MR Study using genetic data from a large genome-wide association study (GWAS) to compare serum folate level (37465 individuals) and MASLD (primary analysis: 8434 cases/770180 controls; Secondary analysis:1483 cases/17781 controls) were performed to infer causal relationships between them. Inverse variance weighted (IVW) was used as the primary method of MR Analysis.The results from the NHANES database showed that Tertile 3 group (Tertile 3: ≥ 48.6 nmol/L) had a significantl y lower risk (OR=0.58, 95% CI: 0.38 ~ 0.88, P=0.010) of MASLD than Tertile 1 group (Tertile 1: < 22.3 nmol/L) after co mplete adjustments. However, in the IVW of MR Analysis, there was no causal relationship between serum folate level a nd MASLD risk in the primary analysis (OR=0.75, 95% CI:0.55~1.02, P=0.065) and secondary analysis (OR=0.83, 95% CI: 0.39~1.74, P=0.618).In observational analyses, we observed an inverse association between higher serum folate concentrations and a reduced risk of MASLD. Our MR study generated similar results, but the association failed to reach the significance threshold of P<0.05, suggesting that our MR study does not support a causal relationship between serum folate levels and MASLD risk. Additional research involving a larger number of cases would contribute to enhancing the confirmation of our preliminary findings.

    Keywords: Folate, Mendelian randomization, NHANES, MASLD, Cross-sectional study

    Received: 23 May 2024; Accepted: 26 Aug 2024.

    Copyright: © 2024 Chen, Gao, Wang, Lu, Zheng and Ren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Qian Ren, Lanzhou University, Lanzhou, China

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