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Nitrate rich vegetables - a healthy cognitive enhancer?

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Here's an interesting article on nitrate rich vegetables...

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.
  • 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
  • Vegetables rich in nitrate include spinach, lettuce, broccoli and beetroot

"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)."



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

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I'm going to expand on this a bit.

Basically, my PFC needs all the help it can get. I have quite annoying cognitive deficits that are preventing me from doing the things that I want to. I've tried conventional medications but they don't really offer any improvements. Cognitive remediation is promising but until I have the ability to concentrate, that is itself a challenge. I'm hesitant to use experimental cognitive enhancers these days and don't have many available prescription options for pharmacological treatment of cognitive symptoms.

I'm sort of inspired by intravenous sodium nitroprusside (acting as a NO donor) which shows impressive potential as a novel antipsychotic. I'm not quite crazy enough to slam some nitroprusside myself, so safer options were explored.

My hypothesis is that dietary nitrate supplementation in combination with polyphenol-rich raw cacao can safely provide cognitive benefits for my schizophrenia via improved function of the PFC.

I'm using subjective changes in sustained attention as a crude proxy of PFC function, as one of my main impairments is in sustained attention. I've also got baseline Cambridge Brain Science results which I'll also compare.

I'm on day three of 5.5mmol dietary nitrate twice daily (in 15g raw cacao powder) added to my usual regime of supplements and vitamins. I've been starting to be able to concentrate on a monotonous task better but will continue to see how things go. With regard to residual positive symptoms, there hasn't been any noticeable change.

If anyone else decides to try enriching their diet with nitrate rich foods, I'd be keen to hear your experiences :)

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i'm keen to hear how you go alchemica, somehow i think your results will be more conclusive than mine. i'll try your two tablespoons of cocoa powder daily for a while but is there any other way to reach the mark beside a half liter of beetroot juice? eg actual beetroot, spinach, other?

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If ingesting the required amounts of beetroot etc wasn't feasible, I'd be inclined to consider something similar to the study by Aamand et al. where they used a supplemental form dietary nitrate (sodium nitrate). I think exploiting potential synergies by the inclusion of polyphenols etc is worth doing, so I'd personally avoid any supplementation without those added.

Not sure my results will be more conclusive ;)

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beetroot is 10% sugar that's all, it would be handy to know how much spinach, what type and it should be prepared, but chocolate will be fine. then i'll pray that my days somehow provide a measure stick for my cognition.

everything with me is very smooth and level these days, but i do supplement with fairly random amounts of nootropics.

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The mean contents of nitrates are summarized as follows (mg kg-1): Cabbage, 510; leek, 91; lettuce, 1439; parsley, 1070; spinach, 1132; radish, 3428. The content of nitrates can vary from 1-10000 mg kg-1, depending not only on genetic factors such as kinds or strains of the vegetables but also on environmental factors including the places or conditions of cultivation and storage [1]

Those results are for plants grown in Turkey. If Australian ones are similar:

5.5 mmol of nitrate = 340mg. ~300g of spinach might provide that if if my calculations are correct. ~240g of lettuce might work, too.

I haven't seen the nitrate content of raw cacao alone. I'm simply exploring the synergy, or perhaps potential antagonism (if plasma nitrite plays an important role in any cognitive benefits): cocoa flavanols "attenuated the increase in plasma nitrite after nitrate intake" [2].

Might be easier to test these things without the full moon :wink:

Edit: Here's a better table (from this review)

post-5043-0-21070000-1438564180_thumb.jp

Edited by Alchemica
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that full moon was something alright, a blinding light.

i'm probably coming very close to the mark most days already due to my leafy green intake.

and how hard is it to eat 100-150g of radish? not hard at all.

Edited by ThunderIdeal

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I found this in the health food shop today guys. I'm really interested in what's being said here. I picked up a bottle and will try it with the cacao like suggested! Works out at $2 a dose, fairly convenient.

post-9832-0-45378200-1438414877_thumb.jp

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Dunno, you guys seem to have the grasp here. But..

Wiki States "a 65 kg person would likely have to consume at least 4.6 g to result in death". For this particular product you'd have to drink 189 bottles or 91L.

Edited by theuserformallyknownasd00d

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Here's an interesting article that covers dietary nitrates/nitrites:

Novel aspects of dietary nitrate

The circulation of nitrogen in nature is a prerequisite for life on earth. In the nitrogen cycle atmospheric nitrogen is fixated by bacteria into forms that can be utilized by plants and mammals. Nitrate and nitrite are obligate intermediates in this cycle, and for more than half a century these anions have interested nutritional scientists, mostly in relation to cancer, because of their ability to form nitrosamines. However, after the discovery of mammalian endogenous nitric oxide (NO) generation and later that its oxidation products nitrate and nitrite can be recycled back to bioactive NO, a novel field of research has emerged that explores a potentially beneficial role of these anions in physiology, nutrition, and therapeutics. In our diet, vegetables are the major source of nitrate that can fuel a nitrate-nitrite-NO pathway. Herein we discuss the nutritional aspects of this pathway and what is presently known about the implications for human health.

For a different review of nitrite and potential formation of N-nitroso compounds see here

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Thanks alchemica, hears a few other articles which helped me get my head around nitrite/nitrate. The whole bodily/saliva conversion is bloody interesting

http://chriskresser.com/the-nitrate-and-nitrite-myth-another-reason-not-to-fear-bacon/

http://www.anabolicmen.com/5-nitrate-rich-foods/

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Could we just eat some slow cooked bacon to avoid converting too much of the nitrate content to nitrosamines and then scoff a piece of dark chocolate ?

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After 4 days of 5.5 mmol dietary nitrate and 15g raw cacao twice daily, I scored above my average on Feature match (activating the mid-ventrolateral frontal cortex) but had no change in Digit span.

I can't say my attention span on monotonous tasks has subjectively improved but I do feel slightly more focused and clear headed to some extent. There hasn't been a change in positive symptoms but they are stress-dependent and my stress levels have been higher recently. This dietary intervention has been well tolerated.

I'll now try 4 days of 5.5 mmol dietary nitrate (twice daily) without the flavanol-rich cacao.

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I love your work!

I have sampled numerous plants from the garden that I have found to have a similar effect as described by the ingestion of nitrarte's above. These include memory plant, gotu kola, and comfrey.

Don't forget that if you require the plant to grow specifically for your chemistry then the seed will need to be imbued with your DNA and regular communications with that plant ensure your biological updates. A plant that grows just for you!

It is s simple, natural process to imbue your DNA with a plant, more can be found on this in The Ringing Cedars Series.

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Angiotensin II receptor inhibitors like Losartan can profoundly increase nitric oxide synthesis both eNOS and nNOS. Maritime Pine bark also can do this.

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