Does dietary nitrate boost the effects of caloric restriction on brain health? Potential physiological mechanisms and implications for future research

Mushari Alharbi, Blossom Cm Stephan, Oliver M Shannon, Mario Siervo, Mushari Alharbi, Blossom Cm Stephan, Oliver M Shannon, Mario Siervo

Abstract

Dementia is a highly prevalent and costly disease characterised by deterioration of cognitive and physical capacity due to changes in brain function and structure. Given the absence of effective treatment options for dementia, dietary and other lifestyle approaches have been advocated as potential strategies to reduce the burden of this condition. Maintaining an optimal nutritional status is vital for the preservation of brain function and structure. Several studies have recognised the significant role of nutritional factors to protect and enhance metabolic, cerebrovascular, and neurocognitive functions. Caloric restriction (CR) positively impacts on brain function via a modulation of mitochondrial efficiency, endothelial function, neuro-inflammatory, antioxidant and autophagy responses. Dietary nitrate, which serves as a substrate for the ubiquitous gasotransmitter nitric oxide (NO), has been identified as a promising nutritional intervention that could have an important role in improving vascular and metabolic brain regulation by affecting oxidative metabolism, ROS production, and endothelial and neuronal integrity. Only one study has recently tested the combined effects of both interventions and showed preliminary, positive outcomes cognitive function. This paper explores the potential synergistic effects of a nutritional strategy based on the co-administration of CR and a high-nitrate diet as a potential and more effective (than either intervention alone) strategy to protect brain health and reduce dementia risk.

Keywords: Brain health; Caloric restriction; Cognitive function; Dementia; Dietary nitrate; Endothelial function; Nitric oxide.

Conflict of interest statement

The authors declare no conflict of interest.

Not applicable.

© 2023. BioMed Central Ltd., part of Springer Nature.

Figures

Fig. 1
Fig. 1
Synergistic effects of dietary nitrate and caloric restriction on brain health. Both interventions could induce NO bioavailability through the nitrate/nitrite/NO pathway or Akt, AMPK and SIRT1 pathways. NO would increase mitochondrial efficiency by reducing ROS and inducing ATP from oxygen and ADP. In addition, NO would improve the endothelial function by interacting with sGC to convert GTP into cGMP, which activates PKG leading to MLCP (smooth muscle relaxation) and VASP (platelet aggregation inhibitor) activation. Moreover, NO could modulate inflammation that acts as pro-inflammatory when it reacts with O2- (from uncoupled mitochondria) to form ONOO-. Furthermore, NO could enhance neurotransmission through activation of the antero-and retrograding signalling, which facilitates Ca + transferal. CR and dietary nitrate have several pathways that could increase the autophagy process by mTOR inhibition, Akt, AMPK, and SIRT activation. Key: AMPK, adenosine monophosphate-activated protein kinase; Akt, protein kinase B; cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate; MLCP, myosin light-chain phosphatase; mTOR, mechanistic target of rapamycin; PKG, protein kinase G; sGC, soluble guanylate cyclase; SIRT1 and SIRT3, sirtuin; VASP, vasodilator-stimulated phosphoprotein; XOR, xanthine-oxidoreductase

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