ORIGINAL RESEARCH article

Front. Nutr.

Sec. Clinical Nutrition

Volume 12 - 2025 | doi: 10.3389/fnut.2025.1504441

Association between Red blood cell folate and Accelerated Aging in American Adults: A Cross-Sectional Study from the National Health and Nutrition Examination Survey

Provisionally accepted
  • 1Nanjing University of Chinese Medicine, Nanjing, China
  • 2Binhai Hospital of Traditional Chinese Medicine, Yancheng, China

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

Objective: The study aims to explore the relationship between red blood cell (RBC) folate concentrations and accelerated aging.Methods: Data were derived from the National Health and Nutrition Examination Survey (NHANES) cycles of 2007-2010, including 8,944 participants aged ≥20 years. Phenotypic Age Acceleration (PhenoAgeAccel) was calculated using chronological age and 9 aging-related biomarkers. Multivariate linear regression and generalized additive models were used to analyze the relationship between RBC folate levels and PhenoAgeAccel. Smooth curve fitting was used to explore the potential nonlinear relationship and threshold effect analysis was applied to examine inflection point.Results: The analysis revealed a U-shaped relationship between RBC folate levels and PhenoAgeAccel, with the inflection point at 732.9 ng/mL. The PhenoAgeAccel decreased by 0.0027 years per 1 ng/mL increase in RBC folate when RBC folate ≤ 732.9 ng/mL (β: -0.0027, 95%CI: -0.0051, -0.0002), and increased by 0.0058 years per 1 ng/mL increase in RBC folate when RBC folate > 732.9 ng/mL (β: 0.0058, 95%CI: 0.0026, 0.0090). Subgroup analyses indicated consistent associations across most demographic and health categories, except for a positive correlation in participants with cardiovascular diseases.Conclusion: There was a U-shaped association between RBC folate and accelerated aging among U.S. adults.

Keywords: RBC folate, Phenotypic age acceleration, biological aging, NHANES, U-shaped relationship

Received: 15 Oct 2024; Accepted: 26 May 2025.

Copyright: © 2025 Wang, Song, Li and Xu. 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:
Chong-chao Li, Nanjing University of Chinese Medicine, Nanjing, China
Cheng Xu, Nanjing University of Chinese Medicine, Nanjing, China

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