Improving cognition via vegetable derived NO? Polyphenols?

Intravenous sodium nitroprusside (acting as a NO donor) shows impressive antipsychotic potential. I wonder if dietary nitrate supplementation (vegetables rich in nitrate include spinach, lettuce, broccoli and beetroot) can provide both antipsychotic and cognitive benefits for people with schizophrenia via improved function of the PFC?

Here’s an interesting article:

Dietary nitrate modulates cerebral blood flow parameters and cognitive performance in humans: A double-blind, placebo-controlled, crossover investigation.

Nitrate derived from vegetables is consumed as part of a normal diet and is reduced endogenously via nitrite to nitric oxide. It has been shown to improve endothelial function, reduce blood pressure and the oxygen cost of sub-maximal exercise, and increase regional perfusion in the brain. The current study assessed the effects of dietary nitrate on cognitive performance and prefrontal cortex cerebral blood-flow (CBF) parameters in healthy adults. In this randomised, double-blind, placebo-controlled, parallel-groups study, 40 healthy adults received either placebo or 450ml beetroot juice (~5.5mmol nitrate). Following a 90minute drink/absorption period, participants performed a selection of cognitive tasks that activate the frontal cortex for 54min. Near-Infrared Spectroscopy (NIRS) was used to monitor CBF and hemodynamics, as indexed by concentration changes in oxygenated and deoxygenated-haemoglobin, in the frontal cortex throughout. The bioconversion of nitrate to nitrite was confirmed in plasma by ozone-based chemi-luminescence. Dietary nitrate modulated the hemodynamic response to task performance, with an initial increase in CBF at the start of the task period, followed by consistent reductions during the least demanding of the three tasks utilised. Cognitive performance was improved on the serial 3s subtraction task. These results show that single doses of dietary nitrate can modulate the CBF response to task performance and potentially improve cognitive performance, and suggest one possible mechanism by which vegetable consumption may have beneficial effects on brain function.

•Dietary nitrate is reduced endogenously via nitrite to nitric oxide.
•The effects of nitrate rich beetroot juice on frontal cerebral blood-flow were tested.
•Nitrate modulated the hemodynamic response to task performance in the frontal cortex.
•Performance on one of three tasks (serial 3s subtractions) was improved.
•Plasma nitrite was increased.

“The ingestion of nitrate, including from dietary sources, is associated with a number of effects consistent with increased levels of endogenous NO synthesis, including reductions in blood pressure. This effect has been demonstrated as early as 3 h after a single dose of nitrate rich beetroot juice, with a concomitant protection of forearm endothelial function and in vitro inhibition of platelet aggregation. Dietary nitrate has also been shown to reduce the overall oxygen cost of sub-maximal exercise 2.5 h after ingestion and after three or more days of administration. Similarly, an increase in peak power and work-rate, a speeding of VO2 mean response time in healthy 60–70 year olds and delayed time to task failure during severe exercise have also been reported following the consumption of nitrate rich beetroot juice consumed daily for 4 to 15 days. Nitrate related reductions have also been demonstrated with regard to the rate of adenosine-5′-triphosphate (ATP) turnover using magnetic resonance spectroscopy, whilst improved oxygenation has been confirmed directly in the muscle during exercise using Near-Infrared Spectroscopy (NIRS).

NO plays a pivotal role in cerebral vasodilation and the neurovascular coupling of local neural activity and blood-flow. Several studies have probed the effects of dietary nitrate derived from beetroot or spinach on brain function, including three studies that have included some form of cognitive testing either as an additional measure, or as the primary focus of the project. Whilst these studies demonstrated modulation of a number of physiological parameters they did not provide evidence of cognitive improvements, possibly due to comparatively small sample sizes and other methodological factors. Two studies have also investigated the effects of dietary nitrate on cerebral blood-flow parameters. In the first of these, Presley et al. demonstrated, using arterial spin labelling magnetic resonance imaging (MRI), that a diet high in nitrate consumed for 24 h increased regional white matter perfusion in elderly humans, but with this effect restricted to areas of the frontal cortex. More recently, Aamand et al., investigated the effects of 3 days of administration of dietary nitrate (sodium nitrate) on the haemodynamic response in the visual cortex elicited by visual stimuli, as assessed by functional MRI (fMRI). They demonstrated a faster, smaller and less variable blood-oxygen-level dependent (BOLD) response following nitrate, which they interpreted as indicating an enhanced neurovascular coupling of local CBF to neuronal activity. As the BOLD response simply reflects the contrasting magnetic signals of oxygenated and deoxygenated haemoglobin (with increased activity imputed from an assumed relative decrease in deoxyhemoglobin as local activation engenders a greater influx of blood borne oxygenated -Hb), it cannot disentangle the contributions of changes in blood-flow and changes in oxygen consumption to the overall signal. The current study therefore utilised Near-Infrared Spectroscopy (NIRS), a brain imaging technique that has the advantage over fMRI BOLD in that it measures both concentration changes in deoxy-Hb and overall local CBF (changes in oxy-Hb and deoxy-Hb combined).”

  • Previous research suggests that NO exerts a number of effects that might also impact on overall cellular energy consumption in the brain. These include the inhibition of mitochondrial respiration and therefore oxygen consumption, including via inhibition of cytochrome c oxidase, and enhancement of the efficiency of oxidative phosphorylation by decreasing slipping of the proton pumps

“It is important to note that beetroot contains a plethora of other, potentially bioactive, phytochemicals including the nitrogenous betalains, a range of phenolics, including multiple flavonoids and flavonols and folates. Given the ability of similar phytochemicals to modulate peripheral endothelial function, CBF parameters and cognitive function the possibility that any effects are related to high levels of these other compounds cannot be ruled out. It is also notable that the NO3/NO2/NO pathway is reported to be most prevalent during hypoxic conditions and in the presence of reducing agents such as vitamin C and polyphenols. Having said this, recent evidence from a study directly comparing nitrate rich beetroot juice to nitrate depleted (but otherwise identical) beetroot juice suggests that the effects seen on blood pressure and the O2 cost of exercise are directly attributable to the nitrate content of the juice rather than to any other bioactive components (although synergies cannot be ruled out). Given the potential for multifarious phytochemicals to impact on CBF, an extension of the current study using these nitrate rich and depleted interventions may be able to resolve the question of the direct contribution of nitrate to the cognitive and CBF effects seen here.”

To conclude:

“…the findings here suggest that supplementation with dietary nitrate can directly modulate important physiological aspects of brain function and improve performance on a cognitive task that is intrinsically related to prefrontal cortex function. Taken alongside a previous demonstration of increased prefrontal cortex perfusion in elderly humans following consumption of a high nitrate diet for ~ 36 h, the results here suggest both a specific food component and physiological mechanisms that may contribute to epidemiological observations of relationships between the consumption of a diet rich in vegetables and polyphenols (which naturally co-occur with nitrate in vegetables) and preserved cognitive function in later life. Of particular importance, the results here were demonstrated in young humans, who can be assumed to be close to their optimum in terms of brain function, and hint at the potential benefits of a healthy, vegetable rich diet across the lifespan.

In summary, dietary nitrate, administered as beetroot juice, modulated CBF in the prefrontal cortex during the performance of cognitive tasks that activate this brain region, with this effect most consistently seen as reduced CBF during the easiest of three tasks (RVIP). Cognitive performance was improved on a further task, serial 3s subtractions. These results suggest that a single dose of dietary nitrate can modify brain function, and that this is likely to be as a result of increased NO synthesis leading to an exaggerated neurovascular response to activity or improved efficiency of cellular metabolism”

Dietary intake of cocoa flavanols is also associated with benefits for cognitive performance [1].

See also:

Novel aspects of dietary nitrate

Psychiatric Disorders and Polyphenols: Can They Be Helpful in Therapy?

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