Plant but not animal sourced nitrate intake is associated with lower dementia-related mortality in the Australian Diabetes, Obesity, and Lifestyle Study

Anjana Rajendra; Nicola P Bondonno; Liezhou Zhong; Simone Radavelli-Bagatini; Kevin Murray; Stephanie R Rainey-Smith; Samantha L Gardener; Lauren C Blekkenhorst; Dianna J Magliano; Jonathan E Shaw; Robin M Daly; Kaarin J Anstey; Joshua R Lewis; Jonathan M Hodgson; Catherine P Bondonno

doi:10.3389/fnut.2024.1327042

Plant but not animal sourced nitrate intake is associated with lower dementia-related mortality in the Australian Diabetes, Obesity, and Lifestyle Study

Front Nutr. 2024 Aug 21:11:1327042. doi: 10.3389/fnut.2024.1327042. eCollection 2024.

Authors

Anjana Rajendra¹, Nicola P Bondonno^{1

2}, Liezhou Zhong¹, Simone Radavelli-Bagatini¹, Kevin Murray³, Stephanie R Rainey-Smith^{4

5

6

7

8}, Samantha L Gardener^{5

6

8}, Lauren C Blekkenhorst^{1

9}, Dianna J Magliano^{10

11}, Jonathan E Shaw^{10

12}, Robin M Daly¹³, Kaarin J Anstey^{14

15

16}, Joshua R Lewis^{1

9

17}, Jonathan M Hodgson^{1

9}, Catherine P Bondonno^{1

9}

Affiliations

¹ Nutrition and Health Innovation Research Institute, School of Medical and Health Sciences, Royal Perth Hospital Research Foundation, Edith Cowan University, Perth, WA, Australia.
² The Danish Cancer Society Research Centre, Copenhagen, Denmark.
³ School of Population and Global Health, University of Western Australia, Perth, WA, Australia.
⁴ Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Murdoch, WA, Australia.
⁵ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
⁶ Australian Alzheimer's Research Foundation, Perth, WA, Australia.
⁷ School of Psychological Science, University of Western Australia, Perth, WA, Australia.
⁸ Lifestyle Approaches Towards Cognitive Health Research Group, Murdoch University, Murdoch, WA, Australia.
⁹ Medical School, The University of Western Australia, Royal Perth Hospital, Perth, WA, Australia.
¹⁰ Diabetes and Population Health, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
¹¹ Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
¹² School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
¹³ Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia.
¹⁴ School of Psychology, The University of New South Wales, Sydney, NSW, Australia.
¹⁵ Neuroscience Research Australia (NeuRA), Randwick, NSW, Australia.
¹⁶ UNSW Ageing Futures Institute, Kensington, NSW, Australia.
¹⁷ Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.

Abstract

Introduction: Dietary nitrate is potentially beneficial for cardiovascular, cerebrovascular, and nervous systems due to its role as a nitric oxide (NO) precursor. Increased nitrate intake improves cardiovascular health and therefore could protect against dementia, given the cardiovascular-dementia link.

Objective: To investigate the association between source-dependent nitrate intake and dementia-related mortality. As individuals with diabetes are at higher risk of dementia, a secondary aim was to investigate if the associations between nitrate and dementia varied by diabetes mellitus (DM) and pre-diabetes status.

Methods: This study involved 9,149 participants aged ≥25 years from the well-characterised Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study followed over a period of 17 years. Intakes of plant-sourced, vegetable-sourced, naturally occurring animal-sourced nitrate, and processed meat (where nitrate is an allowed additive)-sourced nitrate were assessed from a 74-item food frequency questionnaire completed by participants at baseline and nitrate databases were used to estimate nitrate from these different dietary sources. Associations between source-dependent nitrate intake and dementia-related mortality were assessed using multivariable-adjusted Cox proportional hazards models adjusted for demographics, lifestyle, and dietary factors.

Results: Over 17 years of follow-up, 93 (1.0%) dementia-related deaths occurred of 1,237 (13.5%) total deaths. In multivariable-adjusted models, participants with the highest intakes of plant-sourced nitrate (median intake 98 mg/day) had a 57% lower risk of dementia-related mortality [HR (95% CI): 0.43 (0.22, 0.87)] compared to participants with lowest intakes of plant-sourced nitrate (median intake 35 mg/day). A 66% lower risk was also seen for higher intakes of vegetable-sourced nitrate [HR (95% CI): 0.34 (0.17, 0.66)]. No association was observed for animal-sourced nitrate, but the risk was two times higher amongst those who consumed the most processed meat-sourced nitrate intake [HR (95%): 2.10 (1.07, 4.12)]. The highest intake of vegetable-sourced nitrate was associated with a lower risk of dementia-related mortality for those with and without DM and pre-diabetes.

Conclusion: Encouraging the intake of nitrate-rich vegetables, such as green leafy vegetables and beetroot, may lower the risk of dementia-related mortality, particularly in individuals with (pre-) diabetes who are at a higher dementia risk.

Keywords: cohort; dementia; diabetes; diet; dietary nitrate.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. For funding or logistical support, we are grateful to: National Health and Medical Research Council (NHMRC grant 233200), Australian Government Department of Health and Ageing. Abbott Australasia Pty Ltd., Alphapharm Pty Ltd., AstraZeneca, Bristol-Myers Squibb, City Health Centre-Diabetes Service-Canberra, Department of Health and Community Services—Northern Territory, Department of Health and Human Services—Tasmania, Department of Health—New South Wales, Department of Health—Western Australia, Department of Health—South Australia, Department of Human Services—Victoria, Diabetes Australia, Diabetes Australia Northern Territory, Eli Lilly Australia, Estate of the Late Edward Wilson, GlaxoSmithKline, Jack Brockhoff Foundation, Janssen-Cilag, Kidney Health Australia, Marian & FH Flack Trust, Menzies Research Institute, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk Pharmaceuticals, Pfizer Pty Ltd., Pratt Foundation, Queensland Health, Roche Diagnostics Australia, Royal Prince Alfred Hospital, Sydney, Sanofi Aventis, Sanofi-Synthelabo, and the Victorian Government’s OIS Programme. AR is grateful for support provided by the Australian Government Research Training Programme (AGRTP) to pursue doctoral studies at Edith Cowan University, Australia. NB is funded by a National Health and Medical Research Council Early Career Fellowship (Grant number APP1159914). SR-S is supported by an NHMRC Investigator Grant (GNT1197315). LB is supported by an NHMRC of Australia Emerging Leadership Investigator Grant (ID: 1172987) and a National Heart Foundation of Australia Post-Doctoral Research Fellowship (ID: 102498). The salary of DM is supported by an NHMRC Investigator Grant (APP 2016668). The salary of JS is supported by an NHMRC Investigator Grant (APP 1173952). KA is supported by ARC Laureate Fellowship (FL190100011). The salary of JL is supported by a National Heart Foundation Future Leader Fellowship (ID: 102817). The salary of CB is supported by a Royal Perth Hospital Research Foundation ‘Lawrie Beilin’ Career Advancement Fellowship (ID: CAF 127/2020) and the Western Australian Future Health Research and Innovation Fund.