Eating greens and nitric oxide production

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Eating greens and nitric oxide production

Postby Jumpstart » Mon Sep 01, 2014 9:58 am

Jeff,

Have you run across any actual studies that show eating greens six times a day increases nitric oxide production. I've found studies for many types of food that show this result but I can't seem to find even one involving greens. What I have found is stuff that talks about what should happen in the body in theory but no actual studies that test that theory. I started this tread in the lounge but I haven't had anyone come up with an actual result. You're my last hope.
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Re: nitric oxide production

Postby JeffN » Mon Sep 01, 2014 12:06 pm

Jumpstart wrote:Jeff,

Have you run across any actual studies that show eating greens six times a day increases nitric oxide production. I've found studies for many types of food that show this result but I can't seem to find even one involving greens. What I have found is stuff that talks about what should happen in the body in theory but no actual studies that test that theory. I started this tread in the lounge but I haven't had anyone come up with an actual result. You're my last hope.


Thanks.

I appreciate this question as it gives me the opportunity to once again reinforce the notion of *wholism* over *reductionism*, something that seems to becoming more prevalent even in the WFPB world.

Before I give my direct response, a few things to put it in perspective...

First, let's remember the principle I explained in the thread on "When No Risk Means High Risk and High Benefit Means No Benefit."

viewtopic.php?f=22&t=43681

And this one on High Quality Foods

viewtopic.php?f=22&t=28413

If you have not read them lately, I would really recommend reading them in their entirety again.

Many of these studies are being done on populations and subjects who are not consuming a healthy low fat diet based on a predominance of minimally processed plants so the results need to be put in proper perspective and context and/or do not directly apply. Few Americans eat minimally processed plants so their current intake of plant nitrates is very low where as anyone following the principles we recommend here, already has a much higher intake, some even higher than the amounts used therapeutically in these studies.

This report helps make that point and I recommend reading the full paper. As you can see, anyone including lots of plants as we recommend is already easily consuming quite a bit or plant nitrates *throughout the day*, and many can easily surpass the therapeutic dose used in some studies.

http://www.efsa.europa.eu/en/scdocs/doc/689.pdf

It will also highlight that greens are not the only plant food high in nitrate and even some plants thought of as low quality (i.e., iceberg lettuce) is actually higher in nitrate content then kale.

From the link on High Quality Foods

the average nitrate level in curly kale was 537 mg/kg -- but iceberg lettuce was 875 mg/kg, leaving kale in the dust!


Second, while I think the intake of green leafy veggies and especially cruciferous veggies is important, and should be a regular part of our diet, I am not as enthusiastic in insisting it has to be 6x a day. :) I tried to clarify this here, with a recent interview with Dr Esselstyn on the subject...

http://www.jeffnovick.com/RD/Q_%26_As/E ... ponds.html

In regard to eating "kale" 6x a day.

"I recommend greens (which includes broccoli, cauliflower, bok-choy, Swiss chard, kale, collards, beet greens, mustard greens, turnip greens, Napa cabbage, Brussels, sprouts, broccoli, cauliflower, cilantro, parsley, spinach, arugula, etc) 6 times a day for those specific people who have significant cardiovascular issues, especially angina. I have never said "kale" itself 6 times a day but "greens," as in the jingle. Six times a day is not for everyone though it would be good for everyone to include greens in their diets as much as possible. Not just a few spinach leaves."


And in regard to the study in Okinawa on the impact of eating greens, which Dr Esselstyn will often reference in regard to his "mantra:, I analyzed that here so we can see what they actually ate and how much to get the benefit

viewtopic.php?f=22&t=28413#p377385

The difference in the intervention was 129 grams (169-40), which is 4.5 ounces and the difference in the total was 155 grams (356-201), which is 5.5 ounces. These amounts are the equivalent of about 2 servings.


Lastly, in regard to the "6x a day" principle...

While I understand why Dr Esselstyn uses it as a "mantra," (like with the cholesterol of 150) we also have to put it in proper perspective.

While some pharmacological treatments must be given multiple times a day, (insulin, etc), many are not, as their impact is much longer term than a few hours. Some actually last days. So, is the impact of nitrates on our endothelium, blood flow, BP, etc, short term or long term.

As we can see in these studies, when given as a "treatment," the effect last for many hours, in some of these studies, 4-6 hours or more and the overall impact may last for days.

http://www.atherosclerosis-journal.com/article/S0021-9150(13)00517-0/abstract

http://jap.physiology.org/content/107/4/1144

And one of the main companies who is selling a supplement created from all the above studies, has just 420 mg in a a dose, which is recommended once per day.

http://www.neogenis.com/neo40-daily.html

Remember, as I said above, "anyone including lots of plants as we recommend is already easily consuming quite a bit or plant nitrates *throughout the day.*"

So, let's put this together.

If you were on the standard American diet with little to no whole plant foods with virtually no dietary plant nitrate intake, and were suffering from high BP, poor blood flow and impaired endothelium health, might a "dose" of kale show improvement? Of course. If the subject refused to make any other change to their diet and lifestyle, might it be of some benefit to *dose* with it 3x a day or 6x a day? Maybe.

But that is not our scenario. Wouldn't it be better just to switch over to our recommendations?

Now take someone following the principles of the program as we recommend, who is already on a healthy lower fat, minimally processed, calorie adequate, nutrient sufficient, diet from a variety of minimally processed plant foods with already has a much higher, if not substantially higher content of dietary plant nitrates in it and getting them at every meal, who is also following a healthy lifestyle and exercising and getting some sun (both of which also raise nitric oxide production). Will adding in 6 servings a day be of even more benefit? Will it have to be 6x a day to be of benefit?

My answer to both questions is no.

However, make sure you *are* following the principles of the program. :)

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Re: nitric oxide production

Postby JeffN » Tue Sep 02, 2014 8:36 am

JeffN wrote:As we can see in these studies, when given as a "treatment," the effect last for many hours, in some of these studies, 4-6 hours or more and the overall impact may last for days.

http://www.atherosclerosis-journal.com/article/S0021-9150(13)00517-0/abstract

http://jap.physiology.org/content/107/4/1144


In checking back at these today, it seems I posted the wrong links. My apologies. I guess having multiple windows with multiple studies open can result in this. However, the first one does show plasma levels were significantly higher at 4 hours (T240), "Following beetroot juice consumption, plasma concentrations of the circulating NO pool were higher at T60, T120, and T240 (P < 0.001 at all time points)."

Here are the correct links. They do test greens specifically and do try & explain the mechanism in several of them.

http://m.hyper.ahajournals.org/content/ ... 4.full.pdf

"After ingestion of KNO3 capsules (24 mmol), there was a rapid (within 30 minutes) increase in circulating plasma nitrate concentration, peaking at 3 hours and remaining significantly elevated at 24 hours (Figure 1A)."

"Plasma cGMP concentration was significantly raised compared with baseline at 3 and 24 hours after ingestion of KNO3 capsules (24 mmol; Figure 1E).

"KNO3 capsule ingestion substantially lowered SBP and DBP over 24 hours,"


http://m.hyper.ahajournals.org/content/ ... 4.full.pdf

"Nitrate levels showed a trend to remain elevated at 24 hours after beetroot juice compared to water (P 0.05). Plasma nitrite also increased significantly (2-fold) after beetroot juice ingestion, an effect that reached a peak at 3 hours and remaining at this raised level up until 5 hours after juice ingestion."

"However, systolic BP was significantly reduced by 6 mm Hg at 24 hours after beetroot juice ingestion compared to 1 hour (106.2, 2.8 and 112.4, 3.4 mm Hg, respectively, P0.01; Figure 2). "




http://rivm.openrepository.com/rivm/bit ... 802014.pdf

Peak concentrations are reached at about 2-3 hours, half life is about 6-7 hours and levels can be elevated up to 15 hours or more.



http://hyper.ahajournals.org/content/61/5/1091.long

" At 24 hours, clinic SBP was still significantly lower than the control limb (difference between nitrate versus water, 8.5±1.3 mm Hg; P<0.01) and reduced from baseline (7.2±2.1 mm Hg; P<0.05; Figure 5A). DBP remained lower in the dietary nitrate-treated limb up to 6 hours,"

"After dietary nitrate ingestion, plasma [nitrate] increased rapidly above baseline with significant elevations evident at 30 minutes. Levels peaked at 2 hours (peak increase from baseline, 156.8±22.9×10−6 mol/L; P<0.001) and remained elevated for the first 6 hours of measurement, returning to baseline at 24 hours"

"Finally, to confirm that the effects of nitrite in the patients related to NO bioactivity, we measured the circulating levels of cGMP. At 24 hours, postdietary nitrate (a time point at which BP had been sustained at lower levels for several hours) [cGMP] was significantly elevated above placebo control "

"Interestingly, the BP-lowering effects persisted at the 24-hour time point when circulating levels of nitrate and nitrite had returned almost to baseline. It has been demonstrated that nitrite within the circulation is rapidly taken up into tissues57 where it may be stored. It is possible that, despite diminution of circulating nitrite levels, tissue levels remain elevated providing a continued supply of NO,"

(NOTE: Those of us already following a WFPB diet rich in dietary nitrate rich plants, already have levels way above the baselines used in this/these study(ies) and, if we follow the program on a regular basis, maintain a higher level in our tissue throughout the day, which would be available as a continued supply of NO. The first quote below shows the average vegetarian, who eats better but nowhere as healthy as recommended here, already has almost 4x the level of intake)


http://www.ncbi.nlm.nih.gov/pmc/article ... 5-0677.pdf
(this is an excellent review article)

"The vegetarian diet has been demonstrated to contain ~4.3 mmol nitrate day-1, close to the ADI, almost four times greater than a ‘normal’ diet, which contains ~1.2 mmol nitrate (49)"

"A study of 3 days’ supplementation with ~120 g of round green lettuce (NOTE: about 2 servings) demonstrated that ~70% of the nitrate load was excreted and the total amount of urinary nitrate excretion in a 24 h period increased from 53 mg (~0.9 mmol) on the normal diet to 223, 241 and 243 mg on days 2, 3 and 4 respectively; equivalent to ~4 mmol nitrate."

"Plasma tmax of 1.5–1.8 h." "Plasma half-life of 5–8 h"


As you can see here, even every day vegans have higher intake of nitrates from vegetables.

http://www.pzh.gov.pl/page/fileadmin/us ... 2-2013.pdf


While clearly, more work in this area can be done, and maybe on day we will learn something valuable from all of it they may have me and all those others I mentioned, reconsider our recommendations, as of now, several points are clear...

1) A healthy WFPB already has many times the amount of dietary nitrates in it then a typical diet and even more then in a typical vegetarian diet. (NOTE - Studies on the DASH diet, which is a little healthier than the typical SAD but not as healthy as our recommendations, show that nitrate intake can easily go over 1000 mg/day)

2) The impact of a single dosing of nitrates appears to peak at around 2-3 hours and last till 5-6 hours and the overall impact can last upwards of 24 hours depending on the markers used to evaluate the impact.

3) While plasma levels are important, when following this diet, our tissues will maintain higher levels throughout the day, and capable of producing NO as needed.

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Re: nitric oxide production

Postby Jumpstart » Tue Sep 02, 2014 9:05 am

Jeff,

Thanks so much for all the hard work it took to answer my question. I knew if anyone would be able to provide the best answer that person would be you.

I'm very grateful

Barbara
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Re: nitric oxide production

Postby JeffN » Tue Sep 02, 2014 9:25 am

Thank you.

Ironically, or coincidentally, I just got off the phone with Ann and Dr. Esseslstyn. She is preparing for her book tour and had a few questions and we also discussed the above issue. :)

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Re: Eating greens and nitric oxide production

Postby JeffN » Thu Aug 06, 2015 9:05 am

An excellent review on this topic was published just this week.

Review: Inorganic nitrite and nitrate: evidence to support consideration as dietary nutrients
Nutrition Research. Volume 35, Issue 8, August 2015, Pages 643–654
Nathan S. Bryana, John L. Ivy

http://www.sciencedirect.com/science/ar ... 1715001359

Abstract
There are now indisputable health benefits of nitrite and nitrate derived from food sources or when administered in a clinical setting for specific diseases. Most of the published reports identify the production of nitric oxide (NO) as the mechanism of action for nitrite and nitrate. Basic science as well as clinical studies demonstrates that nitrite and/or nitrate can restore NO homeostasis as an endothelium-independent source of NO that may be a redundant system for endogenous NO production. Nitrate must first be reduced to nitrite by oral commensal bacteria and then nitrite must be further reduced to NO along the physiological oxygen gradient. The purpose of this review is to define their role as indispensable nutrients needed for maintaining NO homeostasis and describe the daily intake required to achieve a threshold of activation as well as define the upper tolerable limits based on published literature in PubMed databases. Optimal ranges of intake will be discussed to maximize the benefits while mitigating any potential risks of overexposure to these naturally occurring anions. This information will allow for future research using safe and effective doses of nitrite and nitrate in long-term clinical trials to effectively test their roles in disease prevention or treatment.

The full text is not available for free yet, but I read it this morning.

I think it is an excellent review of the data in both humans and animals, and its conclusions and recommendations are not much different than what I have posted above.

The range of dose of nitrate used in the human studies that showed specific health-promoting outcomes including Reduced blood pressure, Improved performance, Enhance performance, Reduce diastolic pressure, Enhance performance in PAD, Reverse vascular dysfunction was 6.15 to 19.8 mg/kg. The average was 9.52 gm/kg. Most of the range of the dose used was between 7-10. For someone 150 lbs, the average is 649 mg and the range is 477 to 680 mg.

The range of dose of nitrite used in the human studies that showed specific health-promoting outcomes including Reduction in systolic pressure, Modify cardiovascular risk, and Reduce blood pressure, was less than 1 mg/kg.

Since the research demonstrated benefits with a huge margin between the level needed for benefit and the one that may be toxic, the author recommends that that we call this Vitamin N and that an RDA/DRI and UL be set for it.

As already discussed in this thread (and in the follow up thread (viewtopic.php?f=22&t=44556), and as one can see in the EFSA Report posted above, this is easily attainable in our regular diet and/or by the addition of a few servings of vegetables, especially green leafy vegetables.

Keep in mind, the above results were done on subjects consuming the typical diet so the dose and impact used on them, may not directly apply to someone already following our recommendations and as such, may be somewhat blunted on someone following our recommendations as they are already consuming a healthy diet and consuming, which includes nitrates/nitrites.

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Re: Eating greens and nitric oxide production

Postby JeffN » Thu Sep 03, 2015 9:28 am

This review is from a friend & colleague and is also excellent, though a few years old. It is also a continuing education credit course



Reap the Benefits of Beetroot Juice —
Evidence Suggests It Improves Heart Health and Athletic Performance
By Ellen Coleman, MA, MPH, RD, CSSD
Today’s Dietitian
Vol. 14 No. 2 P. 48
February 2012 Issue

http://www.todaysdietitian.com/newarchi ... 2p48.shtml

From the article

Sources of Dietary Nitrate
Beetroot juice is an easy way to quickly ingest a substantial amount of dietary nitrate. However, some individuals may find the taste of beetroot juice unpleasant. Furthermore, it can cause red urine and stools. Fortunately, beetroots are just one of many vegetables that are high in nitrate. Leafy green vegetables tend to be the top sources.

The dose of dietary nitrate used in the research to reduce the oxygen cost of exercise, improve athletic performance, and lower blood pressure ranges from 300 to 500 mg.11 Clients can readily obtain these amounts through their diet. For instance, foods such as celery, cress, chervil, lettuce, red beetroot, spinach, and arugula (rocket or rucola) contain very high nitrate levels (more than 250 mg/100 g), and celeriac, Chinese cabbage, endive, fennel, kohlrabi, leeks, and parsley are among those with high nitrate levels (approximately 100 to 250 mg/100 g).14 More specifically, 1 cup of raw spinach contains approximately 900 mg of nitrate; 1/2 cup cooked collard greens, approximately 200 mg; 1 cup raw leaf lettuce, approximately 100 mg; and 1/2 cup vegetable juice, approximately 40 mg.14
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Re: Eating greens and nitric oxide production

Postby JeffN » Sat Sep 12, 2015 7:03 pm

The median level in the highest terrible was 427.


Consumption of nitrate-containing vegetables is inversely associated with hypertension in adults: a prospective investigation from the Tehran Lipid and Glucose Study.
Golzarand M, Bahadoran Z, Mirmiran P, Zadeh-Vakili A, Azizi F.
J Nephrol. 2015 Sep 3. [Epub ahead of print]
PMID:26335410

http://www.ncbi.nlm.nih.gov/pubmed/26335410

Abstract

BACKGROUND: There is growing evidence of the potential properties of nitrate-rich foods against development of hypertension (HTN) and vascular disease. In this study, we investigated the association of nitrate-containing vegetables (NCVs) with risk of HTN after 3 years of follow-up.

METHODS: This prospective study was conducted on 1546 non-hypertensive subjects, aged 20-70 years. Blood pressure was measured at baseline and after 3 years and HTN was defined by the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure criteria. Dietary intake was collected using a validated semi-quantitative food frequency questionnaire (FFQ). NCVs and high-, medium- and low-NCV subcategories were defined, and the odds of HTN after 3 years according to tertiles of NCV and NCV-category intake were estimated by logistic regression and adjusted for potential variables.

RESULTS: Mean age of participants was 38.0±12.0 years at baseline and 57.0 % were women. Mean dietary intake of energy-adjusted NCV was 298.0±177.3 g/day. After adjustment for total energy intake, fiber, sodium, potassium and processed meat, a significant inverse association was observed between NCV and the risk of HTN in the highest tertile category (odds ratio 0.63, 95 % confidence interval: 0.41-0.98, p for trend = 0.05). There was no significant association of 3 year risk of HTN across tertiles of low nitrate-, medium nitrate- and high-nitrate vegetables.

CONCLUSION: Higher dietary nitrate intake from vegetables sources may have a protective effect against development of HTN.
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Re: Eating greens and nitric oxide production

Postby JeffN » Sun Sep 13, 2015 2:30 pm

Here is a chart from the following study that shows how long to peak nitric oxide concentration and how long the impact lasted. Peak levels arrive about 2-3 hours after ingestion, and are approaching baseline again by 12 hours later

Image

Beetroot juice and exercise: pharmacodynamic and dose-response relationships
Journal of Applied Physiology Published 1 August 2013 Vol. 115 no. 3, 325-336
DOI: 10.1152/japplphysiol.00372.2013

http://jap.physiology.org/content/115/3/325

Abstract

Dietary supplementation with beetroot juice (BR), containing approximately 5–8 mmol inorganic nitrate (NO3−), increases plasma nitrite concentration ([NO2−]), reduces blood pressure, and may positively influence the physiological responses to exercise. However, the dose-response relationship between the volume of BR ingested and the physiological effects invoked has not been investigated. In a balanced crossover design, 10 healthy men ingested 70, 140, or 280 ml concentrated BR (containing 4.2, 8.4, and 16.8 mmol NO3−, respectively) or no supplement to establish the effects of BR on resting plasma [NO3−] and [NO2−] over 24 h. Subsequently, on six separate occasions, 10 subjects completed moderate-intensity and severe-intensity cycle exercise tests, 2.5 h postingestion of 70, 140, and 280 ml BR or NO3−-depleted BR as placebo (PL). Following acute BR ingestion, plasma [NO2−] increased in a dose-dependent manner, with the peak changes occurring at approximately 2–3 h. Compared with PL, 70 ml BR did not alter the physiological responses to exercise. However, 140 and 280 ml BR reduced the steady-state oxygen (O2) uptake during moderate-intensity exercise by 1.7% (P = 0.06) and 3.0% (P < 0.05), whereas time-to-task failure was extended by 14% and 12% (both P < 0.05), respectively, compared with PL. The results indicate that whereas plasma [NO2−] and the O2 cost of moderate-intensity exercise are altered dose dependently with NO3−-rich BR, there is no additional improvement in exercise tolerance after ingesting BR containing 16.8 compared with 8.4 mmol NO3−. These findings have important implications for the use of BR to enhance cardiovascular health and exercise performance in young adults.
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Re: Eating greens and nitric oxide production

Postby JeffN » Thu Apr 20, 2017 8:28 am

While this study is not about eating greens, it is about the ingestion of nitrates and their impact on blood flow and oxygenation. The same product has been used in several other studies as it has a standardizes amount of nitrates in it.

What they have found from their studies is that their is no additional benefit to taking the product, which contains 560 mg of nitrate, more then 1x a day and in this study, it was only 3x a week.

This is inline with everything I said above.

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Beet Root Juice: An Ergogenic Aid for Exercise and the Aging Brain
J Gerontol A Biol Sci Med Sci glw219.
DOI: https://doi.org/10.1093/gerona/glw219

http://news.wfu.edu/2017/04/19/beetroot ... k-younger/

Abstract

Background:
Exercise has positive neuroplastic effects on the aging brain. It has also been shown that ingestion of beet root juice (BRJ) increases blood flow to the brain and enhances exercise performance. Here, we examined whether there are synergistic effects of BRJ and exercise on neuroplasticity in the aging brain.

Methods:
Peak metabolic equivalent (MET) capacity and resting-state magnetic resonance imaging functional brain network organization are reported on 26 older (mean age = 65.4 years) participants randomly assigned to 6 weeks of exercise + BRJ or exercise + placebo.

Results:
Somatomotor community structure consistency was significantly enhanced in the exercise + BRJ group following the intervention (MBRJ = −2.27, SE = 0.145, MPlacebo = −2.89, SE = 0.156, p = .007). Differences in second-order connections between the somatomotor cortex and insular cortex were also significant; the exercise + BRJ group (M = 3.28, SE = 0.167) had a significantly lower number of connections than exercise + placebo (M = 3.91, SE = 0.18, p = .017) following the intervention. Evaluation of peak MET capacity revealed a trend for the exercise + BRJ group to have higher MET capacity following the intervention.

Conclusions:
Older adults who exercised and consumed BRJ demonstrated greater consistency within the motor community and fewer secondary connections with the insular cortex compared with those who exercised without BRJ. The exercise + BRJ group had brain networks that more closely resembled those of younger adults, showing the potential enhanced neuroplasticity conferred by combining exercise and BRJ consumption.

"Three times a week for six weeks, they drank a beetroot juice supplement called Beet-It Sport Shot one hour before a moderately intense, 50-minute walk on a treadmill."


Article

With beetroot juice before exercise, aging brains look ‘younger’
http://news.wfu.edu/2017/04/19/beetroot ... k-younger/
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