Acute Effect of a High Nitrate Diet on Brain Perfusion in Older Adults

Department of Physics, Wake Forest University, Winston-Salem, NC 27109, USA.
Nitric Oxide (Impact Factor: 3.52). 10/2010; 24(1):34-42. DOI: 10.1016/j.niox.2010.10.002
Source: PubMed


Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults.
In this investigation we administered a high vs. low nitrate diet to older adults (74.7±6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex.
These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning.

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Available from: Janine M Jennings, Sep 24, 2014
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    • "Nitrate, abundant in green leaf vegetables, is stepwise reduced to nitrite in the oral cavity and • NO in the stomach [5]. The postprandial burst of gastric • NO has been shown to be involved in several physiological mechanisms in the gastrointestinal tract (mucus production, increase in vascular tone, antimicrobial action, immune modulation [6] [7] [8]) and systemically (preventing ischemia– reperfusion injury, modulating mitochondrial respiration, and increasing cerebral blood flow [9] [10] [11]). However, by acting as a bioreactor, the gastric lumen affords chemical and mechanical conditions for the reaction between dietary components and nitrogen oxides, including • NO [12] [13] [14] [15]. "
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    ABSTRACT: Background. Nitric oxide (•NO), a ubiquitous molecule involved in a plethora of signaling pathways, is produced from dietary nitrate in the gut through the so-called nitrate-nitrite-NO pathway. In the stomach, nitrite derived from dietary nitrate triggers a network of chemical reactions targeting endogenous and exogenous biomolecules, thereby producing new compounds with physiological activity. Objective. The aim of this study was to ascertain whether compounds with physiological relevance are produced in the stomach upon consumption of nitrate- and ethanol-rich foods. Design. Human volunteers consumed a serving of lettuce (source of nitrate) and alcoholic beverages (source of ethanol). After 15 min, samples of the gastric headspace were collected and ethyl nitrite was identified by GC-MS. Wistar rats were used to study the impact of ethyl nitrite on gastric smooth muscle relaxation at physiological pH. Result. Nitrogen oxides, produced from nitrite in the stomach, induce nitrosation of ethanol from alcoholic beverages in the human stomach yielding ethyl nitrite. Ethyl nitrite, a potent vasodilator, is produced in vivo upon the consumption of lettuce with either red wine or whisky. Moreover, at physiological pH, ethyl nitrite induces gastric smooth muscle relaxation through a cGMP-dependent pathway. Overall, these results suggest that ethyl nitrite is produced in the gastric lumen and releases •NO at physiological pH, which ultimately may have an impact on gastric motility. Systemic effects may also be expected if ethyl nitrite diffuses through the gastric mucosa reaching blood vessels, therefore operating as a •NO carrier throughout the body. Conclusion. These data pinpoint posttranslational modifications as an underappreciated mechanism for the production of novel molecules with physiological impact locally in the gut and highlight the notion that diet may fuel compounds with the potential to modulate gastrointestinal welfare.
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    • "Given recent suggestions that changes in cerebral blood flow during high-intensity exercise might be related to the fatigue process (Nybo, 2008; Rooks et al., 2010; Rupp and Perrey, 2008) it is pertinent to note that dietary nitrate supplementation has been reported to enhance cerebral perfusion in brain areas associated with executive functioning in older adults at rest (Presley et al., 2011). Specifically, a nitrate-rich diet increased regional cerebral perfusion in frontal lobe white matter, particularly between the anterior cingulated cortex (ACC) and dorso-lateral prefrontal cortex (Presley et al., 2011). The ACC is purported to be affected by mental fatigue (Cook et al., 2007) and its activity has been shown to be related to the perception of effort during exercise (Williamson et al., 2001, 2002, 2006). "
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    ABSTRACT: Dietary inorganic nitrate supplementation causes physiological effects which may enhance exercise tolerance. However it is not known whether nitrate might alter cognitive function during exercise. In a double-blind, cross-over study, sixteen subjects ingested either nitrate-rich beetroot juice or a placebo and completed a continuous cycle exercise test involving 20 minute stages at 50% and 70% V˙O2peak and a final stage at 90% V˙O2peak until volitional exhaustion. Cognitive tasks were completed before, during and after exercise. In the dietary nitrate condition: plasma [nitrite] increased (p < 0.01), systolic blood pressure decreased (p < 0.05) and there was a trend for a reduced oxygen uptake at 50% V˙O2peak. Tissue oxygenation improved across exercise intensities and exercise tolerance was greater at 90% V˙O2peak (p < 0.05). Rating of perceived exertion, energy levels and cognitive performance were similar between conditions with mental fatigue being evident from 70% V˙O2peak onwards (P < 0.05). Dietary nitrate supplementation enhanced short-term endurance exercise performance with concomitant mental fatigue but did not improve cognitive performance post-fatigue.
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    • "However, uncertainties about the safety of nitrites limit clinical interventions. To our knowledge, there is just one report showing an association between high nitrite consumption and increased regional brain perfusion in elderly subjects (Presley et al., 2011). Since cerebral hypoperfusion precedes and contributes to the onset of clinical dementia, this finding has clinical relevance. "
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    ABSTRACT: Vascular aging is the term that describes the structural and functional disturbances of the vasculature with advancing aging. The molecular mechanisms of aging-associated endothelial dysfunction are complex, but reduced nitric oxide (NO) bioavailability and altered vascular expression and activity of NO synthase (NOS) enzymes have been implicated as major players. Impaired vascular relaxation in aging has been attributed to reduced endothelial NOS (eNOS)-derived NO, while increased inducible NOS (iNOS) expression seems to account for nitrosative stress and disrupted vascular homeostasis. Although eNOS is considered the main source of NO in the vascular endothelium, neuronal NOS (nNOS) also contributes to endothelial cells-derived NO, a mechanism that is reduced in aging. Pharmacological modulation of NO generation and expression/activity of NOS isoforms may represent a therapeutic alternative to prevent the progression of cardiovascular diseases. Accordingly, this review will focus on drugs that modulate NO bioavailability, such as nitrite anions and NO-releasing non-steroidal anti-inflammatory drugs, hormones (dehydroepiandrosterone and estrogen), statins, resveratrol, and folic acid, since they may be useful to treat/to prevent aging-associated vascular dysfunction. The impact of these therapies on life quality in elderly and longevity will be discussed.
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