Dietary nitrate supplementation and cognitive health: the nitric oxide-dependent neurovascular coupling hypothesis
Abstract
Diet is currently recognized as a major modifiable agent of human health. In particular, dietary nitrate has been increasingly explored as a strategy to modulate different physiological mechanisms with demonstrated benefits in multiple organs, including gastrointestinal, cardiovascular, metabolic, and endocrine systems. An intriguing exception in this scenario has been the brain, for which the evidence of the nitrate benefits remains controversial. Upon consumption, nitrate can undergo sequential reduction reactions in vivo to produce nitric oxide (•NO), a ubiquitous paracrine messenger that supports multiple physiological events such as vasodilation and neuromodulation. In the brain, •NO plays a key role in neurovascular coupling, a fine process associated with the dynamic regulation of cerebral blood flow matching the metabolic needs of neurons and crucial for sustaining brain function. Neurovascular coupling dysregulation has been associated with neurodegeneration and cognitive dysfunction during different pathological conditions and aging. We discuss the potential biological action of nitrate on brain health, concerning the molecular mechanisms underpinning this association, particularly via modulation of •NO-dependent neurovascular coupling. The impact of nitrate supplementation on cognitive performance was scrutinized through preclinical and clinical data, suggesting that intervention length and the health condition of the participants are determinants of the outcome. Also, it stresses the need for multimodal quantitative studies relating cellular and mechanistic approaches to function coupled with behavior clinical outputs to understand whether a mechanistic relationship between dietary nitrate and cognitive health is operative in the brain. If proven, it supports the exciting hypothesis of cognitive enhancement via diet.
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NO-mediated improvements in microvascular function could facilitate cognitive processes that depend on white matter integrity.
“These results imply that NO-mediated improvements in microvascular function could facilitate cognitive processes that depend on white matter integrity [176,177].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [177]
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- Authors
- Gonçalves, J. S., Marçal, A. L., Marques, B. S., Costa, F. D., Laranjinha, J., Rocha, B. S., & Lourenço, C. F.
- Affiliations
- Centro de Neurociências e Biologia Celular (PT)
- University of Coimbra (PT)
- Corresponding author
- Rocha, Bárbara S.
- Lourenço, Cátia F.
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2024-02-22
- Volume
- 52
- Issue
- 1
- Pages
- 279-289
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- OpenAlex
- W4392088472
- Cited by
- 6
- References
- 22
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- dietary nitrate, nitric oxide, neurovascular coupling, cognitive function, cerebral blood flow, nitrate supplementation, brain health, neurodegeneration, cognitive aging, cognitive enhancement, vasodilation, neuromodulation
- MeSH terms
- Neurovascular Coupling, Cognition, Humans, Nitrates, Nitric Oxide, Dietary Supplements
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