Dietary nitrate supplementation and cognitive health: the nitric oxide-dependent neurovascular coupling hypothesis.

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.

LDL isolated from plasma-loaded red wine procyanidins resist lipid oxidation and tocopherol depletion.

Dietary phenolic compounds may act as antioxidants in vitro, but because of structural modifications during absorption, its role based on concentrations high enough to afford an antioxidant protection needs to be re-evaluated. We have explored the hypothesis that red wine procyanidins interact with low density lipoproteins (LDL) and that, at this location, the phenolic compounds efficiently protect LDL from oxidation and maintain LDL alpha-tocopherol at a high steady state concentration by recycling it back from the alpha-tocopheroxyl radical. To this end, human plasma was supplemented with wine procyanidins and isolated LDL were challenged with a constant flux of peroxyl radicals. As compared with LDL from plasma-free procyanidins, those LDL better resisted lipid oxidation and exhibited longer lag-phases of alpha-tocopherol consumption. The procyanidins, depending on their structure, were able to reduce the UV-induced alpha-tocopherol radical in a micellar system, as evidenced by electron paramagnetic ressonance. Mechanistically, the protection of LDL was interpreted in terms of quenching of peroxyl radicals and the recycling of alpha-tocopherol by the procyanidins bound to the lipoproteins. These results support the notion that, in human plasma, the procyanidins, via binding to LDL, may act as efficient local antioxidants.