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Dietary intake of folate, vitamin B6, vitamin B12, and riboflavin and the risk of incident dementia

European Journal of Clinical Nutrition (2025)Cite this article

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Abstract

Background/Objectives

Low intake of B vitamins may increase dementia; However, epidemiological evidence, particularly for riboflavin (vitamin B₂), remains sparse. This study aimed to examine the association between dietary intakes of B vitamins (riboflavin, vitamin B6, vitamin B12, and folate) and the incidence of disabling dementia necessitating care under Japan’s national insurance over a 15-year observation period.

Methods

As part of the Circulatory Risk in Communities Study, a prospective study involving a community-based cohort of 4171 Japanese individuals aged 40–69 years was conducted. Dietary intakes of B vitamins were estimated through a single 24-h dietary recall method. Disabling dementia was defined by the daily living disability status related to dementia based on the long-term care insurance system of Japan. Hazard ratios of disabling dementia were estimated using area-stratified Cox proportional hazard models.

Results

Over a median follow-up of 15.4 years, 887 cases of disabling dementia were identified. Riboflavin intake was inversely associated with the risk of disabling dementia; the multivariable hazard ratio for the highest versus lowest quartiles was 0.51 (95% CI 0.42–0.63; P for trend <0.001). A similar inverse association was observed for vitamin B6 and folate intakes, with multivariable hazard ratios of 0.80 (0.66–0.97; P for trend = 0.01) and 0.79 (0.65–0.96; P for trend <0.001), respectively.

Conclusions

Our findings suggest that dietary intake of B vitamins, especially riboflavin, vitamin B6, and folate, is associated with a reduced risk of disabling dementia in Japanese individuals.

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Fig. 1: Study design for the timing of exposure and outcome.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request and with the permission of the cohort committee.

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Acknowledgements

The authors thank the healthcare staff of Ikawa, Yao, and Kyowa. The authors would also like to thank Thomas Mayers of the Medical English Communication Center, University of Tsukuba, for language revision.

Funding

This study was partly supported by Health and Labour Science Research Grants for Dementia grant numbers H21-Ninchisho-Wakate-007 and H24-Ninchisho-Wakate-003, and for Comprehensive Research on Cardiovascular Disease and Life–Related Disease grant numbers 20FA1002 and 23FA1006, Ministry of Health, Labour and Welfare, Japan; JSPS KAKENHI grant numbers 26253043, 17H04121, 18H04077, 18K10097, 21H03194, 23K21515 and 25H01090; and Japan FULLHAPP.

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Authors and Affiliations

  1. Department of Public Health Medicine, Institute of Medicine, and Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan

    Rie Kishida, Kazumasa Yamagishi, Isao Muraki, Mitsumasa Umesawa & Tomoko Sankai

  2. Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore

    Rie Kishida

  3. Department of Public Health, Graduate School of Medicine, Juntendo University, Tokyo, Japan

    Kazumasa Yamagishi & Ai Ikeda

  4. Department of Bioscience, Graduate School of Agriculture, Ehime University, Matsuyama, Japan

    Koutatsu Maruyama

  5. Department of Preventive Medicine and Public Health, Keio University, Tokyo, Japan

    Mizuki Sata

  6. Clinical Epidemiology and Biostatistics, Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden

    Mizuki Sata

  7. Department of Public Health, Faculty of Medicine, Kindai University, Osakasayama, Japan

    Mari Tanaka, Chika Okada & Hironori Imano

  8. Center for Nutritional Epidemiology and Policy Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

    Chika Okada

  9. Osaka Center for Cancer and Cardiovascular Disease Prevention, Osaka, Japan

    Yasuhiko Kubota, Takeo Okada & Masahiko Kiyama

  10. Yao City Public Health Center, Yao, Japan

    Mina Hayama-Terada & Akihiko Kitamura

  11. Epidemiology Section, Division of Public Health, Osaka Institute of Public Health, Osaka, Japan

    Yuji Shimizu

  12. Ibaraki Western Medical Center, Chikusei, Japan

    Isao Muraki

  13. Dokkyo Medical University School of Medicine, Mibu, Japan

    Mitsumasa Umesawa

  14. Institute of Global Health Policy Research, Bureau of Global Health Cooperation, Japan Institute for Health Security, Tokyo, Japan

    Hiroyasu Iso

Authors
  1. Rie Kishida
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Contributions

Conception and design of the study: RK, KY, and H Iso; Analysis of data: RK; Drafting the article: RK, KY, and H Iso; Involved in data collection, interpretation of the data, and critical revision of the manuscript: RK, KY, KM, AI, MS, MT, CO, YK, MH, YS, IM, MU, H Imano, TS, TO, AK, MK, H Iso.

Corresponding author

Correspondence to Kazumasa Yamagishi.

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The authors declare no competing interests.

Ethics approval and consent to participate

The institutional review boards of the Osaka Institute of Public Health (No. 2409-02), Kindai University (No. R04-255), Osaka University (No. 14285-13), and University of Tsukuba (No. 2047-1) approved the study procedure. This study conformed to the principles of the Declaration of Helsinki. Informed consent was obtained from community leaders. Based on the nature of the study as a secondary use of data initially obtained for public health practice on cardiovascular disease prevention within the local community, individual consent was not required for the analysis. In compliance with relevant guidelines and regulations, the participants were retrospectively allowed to opt out of the analysis. If participants did not decline participation in this study, their consent for data usage was assumed.

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Kishida, R., Yamagishi, K., Maruyama, K. et al. Dietary intake of folate, vitamin B6, vitamin B12, and riboflavin and the risk of incident dementia. Eur J Clin Nutr (2025). https://doi.org/10.1038/s41430-025-01663-5

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  • DOI: https://doi.org/10.1038/s41430-025-01663-5

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