Abstract

Introduction: Dietary nitrate, through conversion to nitric oxide, which supports vascular and nervous system function, may lower dementia risk but may also form neurodegenerative N-nitrosamines, depending on the nitrate source. Methods: We investigated associations between source-specific nitrate and nitrite intake and incident and early-onset dementia (< 65 years) in 54,804 dementia-free participants from the Danish Diet, Cancer and Health Cohort Study over ∼27 years. Nitrate and nitrite intakes were derived from food frequency questionnaires and nitrate and nitrite databases. Results: Higher plant-sourced nitrate intake was non-linearly associated with lower rates of incident dementia (fifth vs first quintile hazard ratio 95% confidence interval: 0.90 [0.83, 0.98]), while increased risk was seen for higher intakes of animal-sourced, additive-permitted meat-sourced, and tap water-sourced nitrate. Similar associations were seen for source-specific nitrite intake and were more pronounced for early-onset dementia. No clear effect modification was observed. Discussion: These findings highlight the importance of nitrate source in dementia risk and warrant further investigation. Highlights: Plant nitrate is associated with a lower risk of incident and early-onset dementia. Animal and tap water nitrate are associated with an increased risk of dementia. Encouraging consumption of plant-based nitrate sources may lower risk of dementia.

Keywords

Cohort study, early-onset dementia, incident dementia, nitrate, nitrite

Document Type

Journal Article

Date of Publication

12-1-2025

Article Number

e70995

Volume

21

Issue

12

PubMed ID

41416568

Publication Title

Alzheimer's & Dementia

Publisher

Wiley

School

Centre of Excellence for Alzheimer's Disease Research and Care / School of Medical and Health Sciences

Funding Information

The Danish Diet, Cancer and Health Study was funded by the Danish Cancer Society, Denmark. This study was supported by grants from the World Cancer Research Fund (IIG_FULL_2020_020) and Independent Research Fund Denmark (1030-00307B). The study was supported by BERTHA – the Danish Big Data Centre for Environment and Health funded by the Novo Nordisk Foundation Challenge Programme (Grant NNF17OC0027864). Catherine P. Bondonno is funded by a National Health and Medical Research Council Ideas Grant (Grant APP2030071) and Western Australian Future Health Research and Innovation Fund (Grant WANMA/EL2023-24/2). Liezhou Zhong is supported by an Emerging Leader Fellowship from the Western Australian Future Health Research and Innovation Fund (ID: WANMA/EL2022/8) and a National Health and Medical Research Council of Australia (NHMRC) Ideas Grant (ID: 2028286). Lauren C. Blekkenhorst is supported by a NHMRC of Australia Emerging Leadership Investigator Grant (ID: 1172987) and a National Heart Foundation of Australia Post-Doctoral Research Fellowship (ID: 102498). Stephanie R. Rainey-Smith is supported by a NHMRC Investigator Grant (GNT1197315). Nicola P. Bondonno is funded by a National Health and Medical Research Council Early Career Fellowship (Grant APP1159914), Australia.

Funding received from the National Health and Medical Research Council (NHMRC)

APP2030071, 2028286, 1172987, GNT1197315, APP1159914

Administering Institution

Edith Cowan University

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Content Type

Full object

Recommended Citation

Bondonno, C. P., Pokharel, P., Erichsen, D. W., Zhong, L., Schullehner, J., Kyrø, C., Frederiksen, K., Hendriksen, P. F., Dalgaard, F., Blekkenhorst, L. C., Rainey‐Smith, S. R., Gardener, S. L., Sigsgaard, T., Raaschou‐Nielsen, O., Tjønneland, A., Hodgson, J. M., Dahm, C. C., Olsen, A., & Bondonno, N. P. (2025). Source‐specific nitrate intake and incident dementia in the Danish Diet, Cancer and Health Study. Alzheimer’s & Dementia, 21(12), Article e70995. https://doi.org/10.1002/alz.70995

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Link to publisher version (DOI)

10.1002/alz.70995