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The causal relationships between iron status and sarcopenia in Europeans: a bidirectional two-sample Mendelian randomization study

European Journal of Clinical Nutrition volume 79, pages 207–213 (2025)Cite this article

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Abstract

Background

Previous studies have indicated potential associations between metals, lifestyle factors, and sarcopenia. However, the specific causal relationships between iron status, lifestyle factors, and sarcopenia remain unclear. Therefore, we conducted a bidirectional two-sample Mendelian Randomization (MR) approach to investigate these relationships.

Methods

The exposure variables included iron status, living alone, coffee intake, alcohol taken with meals, and moderate physical activity, while the outcome variable was sarcopenia, assessed by grip strength in both hands and usual walking pace. We employed the Weighted Median (WM), the Inverse Variance-Weighted (IVW), and other MR methods to explore these problems for analysis. Simultaneously, we conducted a bidirectional MR analysis to assess whether sarcopenia has a reverse causal relationship with internal iron status.

Results

In our present research, we found serum iron (P = 0.033), ferritin (P = 0.001), transferrin saturation (P = 0.029) and coffee intake (P = 0.002) revealed a negative trend for sarcopenia, living alone (P = 0.022) and alcohol taken with meal (P = 0.006) showed a opposite trend for sarcopenia. Whereas sarcopenia showed negative trend for ferritin (P = 0.041) and transferrin saturation (P = 0.043), showed the opposite trend for transferrin (P = 0.021).

Conclusion

Our study suggested that higher serum iron levels might reduce the risk of sarcopenia. Moreover, living alone and alcohol consumption might increase the sarcopenia risk, while coffee intake and moderate physical activity could reduce the sarcopenia risk.

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Fig. 1
Fig. 2: Forest plot for Bidirectional MR analysis of the causal effect of serum iron status on sarcopenia.
Fig. 3: Forest plot for Bidirectional MR analysis of the causal effect of sarcopenia on serum iron status.
Fig. 4: Forest plot for Two-Sample MR analysis of the causal effect of lifestyles on sarcopenia.

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Data availability

The datasets presented in this study can be found in online repositories. The websites for these datasets have been provided in the article. Further inquiries can be directed to the corresponding author.

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Acknowledgements

Everyone who contributed significantly to the work has been listed.

Funding

Shandong First Medical University Science and Education Integration talents academic promotion plan funds (922/001003088002), Beijing Municipal Talent Work Leading Group - Young Beijing Scholars Talent Program (Youth Beijing Scholar 2020, No.25), Beijing Hospital Management Center Summit Talent Program (DFL20220401). The article was supported by the visiting research fund for teachers of ordinary undergraduate universities in Shandong Province.

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Author notes

  1. These authors contributed equally: Zhanhui Qiu, Chenyang Hou.

Authors and Affiliations

  1. School of Public Health, Shandong First Medical University, Shandong Academy of Medical Science, Shandong, 250117, PR China

    Zhanhui Qiu, Xiangsheng Xue, Yuchen Zhang, Jiujing Lin, Jia Li, Haoran Zhang & Qingzhi Hou

  2. Affiliated Tumor Hospital, Shandong First Medical University, Shandong, 250117, PR China

    Chenyang Hou

  3. Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, No. 31 Xinjiekou East Road, Xicheng District, 100035, Beijing, PR China

    Yingyu Zhang & Yajun Liu

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Contributions

QZH and YJL conceived the study, QZH and YJL obtained the funding, ZHQ wrote the first draft, QZH and CYH critically revised the manuscript. QZH, CYH and ZHQ made substantial contributions to the design of the protocol. YCZ, XSX, HRZ, JJL, JL and YYZ prepared the figure and table. All authors critically reviewed the draft and approved the final version for publication.

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Correspondence to Yajun Liu or Qingzhi Hou.

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Qiu, Z., Hou, C., Xue, X. et al. The causal relationships between iron status and sarcopenia in Europeans: a bidirectional two-sample Mendelian randomization study. Eur J Clin Nutr 79, 207–213 (2025). https://doi.org/10.1038/s41430-024-01531-8

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