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Sex-Specific Associations of Dietary Iron Intake with Brain Iron Deposition on Imaging and Incident Dementia: A Prospective Cohort Study

  • Original Research
  • Published:
The journal of nutrition, health & aging

Abstract

Objectives

The study aimed to evaluate the association of dietary iron intake with incident dementia and brain iron deposition.

Design/Setting/Participants

We included dementia-free participants from the UK Biobank who completed at least one 24-hour dietary recall at study baseline (2009–2012) and were followed up to 2021. Incident dementia was determined through linkage to medical records and death registries. Brain MRI was conducted in a subgroup of participants since 2014, with T2* measurements being used as indicators of brain iron deposition.

Measurements

Cox proportional hazard models were used to assess the associations of high (top quintile) and low (bottom quintile) versus medium (quintile 2 to 4) level of dietary iron intake with incident dementia, respectively. Linear regression was applied to assess the relations between dietary iron intake and brain T2* measurements.

Results

During follow-up (mean = 9.5 years), a total of 1,454 participants (650 women and 804 men) developed dementia among 191,694 participants (55.0% female; mean age, 56.2 years). When adjusted for sociodemographic, lifestyle, and other dietary factors, participants with low dietary iron intake (< 10.05 mg/day) had a significantly higher dementia risk (hazard ratio [HR], 1.50, 95% confidence interval [CI], 1.19–1.89), while the relation for high intake (>16.92 mg/day) was non-significant (HR, 1.16, 95% CI, 0.92–1.46). A significant gender difference (P-interaction < 0.001) was observed, with a U-shaped association in male participants (HR for low vs. medium, 1.56, 95% CI, 1.14–2.13; HR for high vs. medium, 1.39, 95% CI, 1.03–1.88; P-nonlinearity < 0.001) and no significant association in females, regardless of their menopause status. In general, dietary iron intake was not related to T2* measurements of iron deposition in most brain regions.

Conclusion

Our findings suggested a U-shape relationship between dietary iron intake and risk of dementia among males, but not females.

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Data Availability Statement

The UK Biobank is an open-access resource that all bona fide researchers can use for approved research by registering and applying at http://www.ukbiobank.ac.uk/register-apply/. Data used in this study are accessible by request to the UK Biobank. Application ID was 55005.

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Acknowledgement

This research uses data from the UK Biobank and we appreciate the UK Biobank participants. We thank Anahid Pinchis from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the English text of a draft of this manuscript.

Funding

The current study was supported by the Fundamental Research Fund for the Zhejiang Provincial Universities (grant number 2021XZZX029), the Zhejiang University Education Foundation Global Partnership Fund (granted to CY), the National Science Fund for Excellent Young Scholars (81922060), and the Talent Introduction Programme of Chinese Academy of Sciences (granted to GZ). The UK Biobank received the support of the Wellcome Trust, Medical Research Council, Department of Health, Scottish government, and Northwest Regional Development Agency. The research was designed, conducted, analyzed, and interpreted by the authors entirely independently of the funding sources.

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Author notes

  1. Contributed equally as co-first authors

Authors and Affiliations

  1. School of Public Health, Zhejiang University School of Medicine, 866 Yu-hang-tang RD, Hangzhou, China

    W. Pan, H. Chen, C. Ni, Changzheng Yuan & Min Yang

  2. CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

    G. Zong

  3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Changzheng Yuan

  4. Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Min Yang

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  1. W. Pan
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Contributions

Min Yang and Changzheng Yuan contributed to the conception and design of the study. Hui Chen contributed to the acquisition of data and data analysis. Wenfei Pan, Hui Chen, and Chunxiao Ni wrote the original draft. Min Yang, Geng Zong, and Changzheng Yuan contributed to revising the manuscript. Geng Zong acquired the data and provided the storage and computing resources. All authors reviewed and edited the draft, and approved the final manuscript.

Corresponding authors

Correspondence to Changzheng Yuan or Min Yang.

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Ethical approval was obtained from the North West-Haydock Research Ethics Committee (reference: 16/NW/0274).

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Pan, W., Chen, H., Ni, C. et al. Sex-Specific Associations of Dietary Iron Intake with Brain Iron Deposition on Imaging and Incident Dementia: A Prospective Cohort Study. J Nutr Health Aging 26, 954–961 (2022). https://doi.org/10.1007/s12603-022-1852-2

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