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That is from 2004.
It proved effective during SARS Cov-1 outbreak. Critical patients were treated using Nitric Oxide which not only improved lungs health but also improved immunity. Now clinical trials are being conducted to treat SARS Cov-2. Hopefully it will be effective in treating novel coronavirus patients. https://www.webmd.com/lung/news/20200409/nitric-oxide-invest...
Remember it is also important to control O2-(superoxides) since NO + O2- = ONO−2 (perixoynitrite)

And that can lead to higher cytokine levels https://www.jbc.org/content/277/3/2330

which are helpful to a certain extent...

NOS baby! Granny shifting, not double-clutching like you should.
Viagra as covfefe-19 antagonist?
I understand this is just a snarky remark, but IIRC sildenafil is actually being tested.
This was literally the first thing that came to my mind, and I'm being serious.
That will have.... unintended consequences.

"Are you afraid of COVID-19 or are you just happy to see me?" :')

But seriously, it can't be good to walk around with a boner all day every day. Could be intimidating for women too. And embarrassing for men. Maybe if it's effective to people already infected and in hospital anyway. But I couldn't see this socially feasible as a preventative drug.

From what I understand, this is important for people who show (severe) symptoms of Covid-19, not as a preventive drug. So no reason to take it until clear symptoms show up.
>But seriously, it can't be good to walk around with a boner all day every day. Could be intimidating for women too. And embarrassing for men. Maybe if it's effective to people already infected and in hospital anyway. But I couldn't see this socially feasible as a preventative drug.

That's not how viagra works. It makes an erection possible, it doesn't cause one.

it inhibits an enzyme responsible for constricting bloodflow, as far as I know.

the whole viagra causes boners thing is really just a convenient gimmick for comedians.

if you want something that causes a boner, look at percutaneous perineal electrostimulation[0].

when THAT becomes the treatment for covid19 we're in trouble.

[0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435023/

Climbers in Himalayas use sildenafil all the time to cope with altitude sickness/High Altitude Pulmonary Edema. That could also align with the theory from some NYC doctor that COVID-19 requires the same approach as altitude sickness and not ventilators (too much lung damage). Also, Chinese doctors reported that people in "prone positioning" recovered faster.

https://www.webmd.com/lung/news/20200407/doctors-puzzle-over...

I'm just a little disappointed its not nitrous oxide...
I too read nitrous and pictured large event halls converted to temporary corona wards filled with thousands of people wearing masks and giggling.
Even better, doctors would be prescribing cans of whipped cream.
Does it mean we will need to eat raw crushed garlic daily alongside wearing masks now?
I have already increased my garlic intake quite a lot. Social distancing makes stinky breath less of a concern.
And stinky breath makes social distancing easier.
Added benefit to keep vampires away.
I wonder if we're in danger of p hacking here. Suppose in the scramble to contain the outbreak, everything is tested for efficacy against the disease. There will surely be some positive studies just due to luck.
Absolutely correct. This is a small part of why observational evidence is not very strong evidence. People should take each observation with a grain of salt.
Perhaps that's true with some observations. I'm no expert on the subject here, but this does seem like a scientific study that wouldn't really involve luck.
All scientific studies, including this one, involve uncertainty, which also Involves luck. Wed need to see a lot more data (and human data as well) before prescribing NO or viagra for coronavirus treatment. You also have the ability to select runs with faster or lower replication rates, confounding variables like the temperature that could have changed with each run or across the plate, etc.
This is from 2004. Here's a quick search for papers which cite this one: https://scholar.google.com/scholar?cites=3174486874880036805...

Edit: "Role of epithelial nitric oxide in airway viral infection" https://www.sciencedirect.com/science/article/pii/S089158490... says NO inhibits both virus replication and latency of viruses, including coxsackievirus, influenza A and B, rhinovirus, cytomegalovirus, vaccinia virus, ectromelia virus, human herpesvirus-1, and HPIV3 and cites 10 papers for these claims.

Easy solution is to run the trial again with 2-3x the sample size. If you think there are a lot of lot of studies we are searching, use 5x the sample size.
Exactly. That seems to be what happened with the chloroquine kerfuffle too, where the original paper got picked up and pushed irresponsibly in the media and policy world, but no one in the scientific community has been able to replicate it.

To some extent this is self-healing, though, in that in a giant outbreak like this someone's going to try every promising-looking technique in practice and return good data on real world results.

That wouldn’t be p hacking, it would just be false positives from multiple tests. But yeah that seems a possibility
Random fact of the day: you produce nitric oxide in your paranasal sinuses, and concentrations increase while humming.
That's one reason to breathe through your nose if you're not doing it.
"WHO and CDC advise everyone to start humming all day long." I like it.
So nutritionally we should be looking at things needed to stimulate the NOS gene (NOS1, NOS2, NOS3):

NOS2 cofactors are; Heme, FAD, FMN, and BH4

Zinc - It helps make BH4 through the GCH1 and PTS enzymes from GTP.

Riboflavin - it is the precursor for FMN and FAD. Notably zinc is needed to turn riboflavin into FMD and FAD.

B6 (P5P) - Needed for Heme synthesis.

Beets - The nitrates are turned into NO in the gut.

Black Tea - Shown to increase NO. And shown to inhibit SARS: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142193/

Vitamin C - Helps protect BH4

But it is for certain another reason to examine zinc in health outcomes from SARS infection. The metal binding site of NOS is zinc also so...

How about l-Citrulline (watermelon) and alliin/allicin (garlic)?
Neither will help create NO without the cofactors that help the enzymes that make NO. It is like trying to stuff a clogged pipe with more water.
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A varied diet to get all the minerals and vitamins is certainly good in general, but is that really what's being looked at here? Another comment posted a link about inhaled nitric oxide being used with SARS-1. People probably shouldn't be inhaling beets.
We know now that genetics and lifestyle can alter someones needs for nutrients. So what is good "in general" might not be good for me.

https://ghr.nlm.nih.gov/condition/riboflavin-transporter-def...

It is not about inhaling beets, it is trying to figure out a possible environmental cause for the wide discrepancy of outcomes of SARS infection. We make NO in our body, some need more help than others and it might be genetic.

https://www.sciencedirect.com/science/article/pii/S037811191... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485952/

Well, I don't think there's any harm in eating a lot of beets, but if people thought that would cure them, or prevent them from becoming ill 100% of the time, that could lead to grim possibilities.
Getting sunlight on your skin is probably the best option.

https://www.mdpi.com/1422-0067/14/1/191/htm#b4-ijms-14-00191

Although a study from China shows that higher UV exposure doesn't seem to slow down infection rates.

But that depends on the amount of oxidative stress you have...

" UVA-induced decomposition of the NODs, like nitrite, leads not only to non-enzymatic formation of nitric oxide (NO), but also to toxic reactive nitrogen species (RNS), like peroxynitrite. Whereas under antioxidative conditions the generation of protective amounts of NO is favored, under oxidative conditions, less injurious reactive nitrogen species are generated, which may enhance UVA-induced cell death. "

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Zinc (intracellular) is also well known to inhibit viral RNA replication: https://journals.plos.org/plospathogens/article?id=10.1371/j...
I could go on and on about zinc. ACE2 is a zinc metalloproteinase, contains two zinc ions and uses zinc as a cofactor. Hey, you know, maybe that is why it is good becasue SAARS-CoV-2 happens to drag ACE2 INTO the cell so maybe the zinc it drags in helps inhibit the virus? Just a thought.

But zinc is also a cofactor for ADAM17 which is responsible for shedding ACE2 from the cell. It is a possible route to lower cellular replication of the virus if the ACE2 cannot enter the cell.

L-Arginine
Yeah, that is fine, but if you are deficient in, or not taking zinc and B2 with it, it is useless. NOS2 needs the cofactors I listed above to function and taking more arginine will just lead to nutrient depletion of those cofactors.
Since this stuff is still poorly understood, rather than taking narrowly targeted supplements my strategy is to just eat a lot of everything. That way I cover all the bases and I'm unlikely to be deficient in anything. And then get enough exercise to burn off the excess calories that come along with essential nutrients.
This and your few previous posts have been a frantically whirled-up word salad of technical stuff including lots about zinc and nitrous oxide. And NOD, ACE2, FAD, BH4, ADAM17...

Do you have any background in this, or any understanding of it?

> Do you have any background in this, or any understanding of it?

Yes, I do.

If you want help understanding it just keep asking me questions about instead of trying to tease out my credentials. I am not stating theories, I am only throwing out some hypotheses.

OK, where does it say black tea increases NO in vivo? I did look at your paper saying black tea inhibits sars, but where actually does it say extracts of it do other than in vitro? (I bet bleach does even better but that doesn't help in reality except for wiping down surfaces).

Reference for beets being linked to NO isn't given. Wiki says "eNOS synthesizes NO from the terminal guanidine-nitrogen of L-arginine and oxygen and yields citrulline as a byproduct", how does that link to beets?

Thanks

>where does it say black tea increases NO in vivo?

Activation of Endothelial Nitric-oxide Synthase by the p38 MAPK in Response to Black Tea Polyphenols* https://www.jbc.org/content/279/45/46637.short

>Reference for beets being linked to NO isn't given.

Beetroot juice increase nitric oxide metabolites in both men and women regardless of body mass https://www.tandfonline.com/doi/abs/10.3109/09637486.2015.11...

Nitrates in vegetal foods are turned into nitric oxide in the GI tract.

Or you could just provide your credentials. Hi my name is XXXX, and I'm certified _______. Here's why I believe NO could be a useful thing to study in the fight against the coronavirus. Otherwise, you're just some random person on the internet contributing to the FUD.
There are plenty of credentialed people who do not know much or use their credentials to scam people, so it really does not matter. If I posted my credentials everyone would just believe me because of my credentials. I want the ideas to stand on their own.

If you do not understand nutritional science you should not believe anyone, and I am not advising anyone take anything and I am not writing for the lay person.

> If I posted my credentials everyone would just believe me because of my credentials

Credentials count for something, not everything, as you pointed out. But they suggest a good starting point. So please do post yours.

> If you do not understand nutritional science you should not believe anyone

That completely defeats the point of having experts, so I disagree. Experts exist so I don't have to spend 1/4 of my life becoming one in their area (so I become one in mine instead).

> and I am not writing for the lay person

Yes you are, this is a forum of lay people when it comes to nutritional science (although it's not nutritional science you're talking about, more biochemistry or something like that. Difference being 'eat 5 a day and cut down the salt' and knowing the details of serotonin denaturing by MAOI-B (or is it -A?))

I'll follow yer other stuff up tomorrow, when I'm sober. Alcohol dehydrogenase FTW.

I am writing here, where there are lay people, but I am still not writing for lay people. And I am not giving up credentials because if you worked in academia you would know why.

No one is an expert on the nutrigenomics of COVID19, not even me. Again, I am talking hypothesis, not theory or practice. No one needs to be credentialed to have a hypothesis but just be prepared to have it questioned.

Old nutritional science was "cut out the salt", but it is going in a different direction.

Keep writing. Layperson here and I doubt taking in more black tea, zinc, and eating beetroot will harm anyway. Also it appears to make sense that increasing the amount of a molecule that allows for better circulation, and thus more oxygen flowing, could potentially help.
Actually it could be bad. I AM JUST TALKING. It could be that increasing NOS at the wrong time might make it harder to get oxygen. It might be beneficial at the begining of the infection but bad if you already have pulmonary vasodilation.

There is a huge blood pressure drop when things get bad so more NO might make it worse.

But thanks.

> It could be that increasing NOS at the wrong time might make it harder to get oxygen

Then FFS STOP TALKING! Useful advice is only useful if it's useful. If it's not useful (AKA 'just talking') it's useless. Unless it has another purpose, which I am starting to suspect is to make you feel good.

I don't mind informed speculation but this is not how you are presenting it.

If you admit you don't know if it could be beneficial or harmful, why are you spouting it here?

I was not giving advice. You are taking it as advice. That is stupid. Talking is by no means useless, what an odd thing to say!
Gotcha - well either way I am not going to experiment on myself with the gas, but as i said, drink black tea instead of coffee and add beetroot to my diet. I think presenting both pros and cons of an idea is a must in any debate.
A doctor told me this when i relayed your comments:

They noticed: “oxygen does not enter molecules because of virus toxins, and instead of capturing 4 molecules the hemoglobin only captures one”. He did not have an opinion on wether nox can have a benefit but indeed it appears that people can breathe but the oxygen is not delivered. Very interesting.

Citrulline Mallate, Argenine also increases nitrogen in the body and so do green leafy vegetables
I appreciate your enthusiasm but without any credentials this feels like a mania induced posting that's hard to filter through for quality
So just ignore it if you do not have time. You are obviously not my target audience.

But how do credentials help you other than to make you gullible when someone shows you their credentials? I am not saying I am correct and you should take a bunch of supplements, it is just some hypothesis.

I have time because it is my work and there is a pandemic that has given me the free time. I am sorry you do not have the interest in something that gives you passion so it looks like "mania" to you.

I think you’ve posted enough on a sensitive health topic in a difficult time that you should either post credentials, not comment so frequently as if an authority, or end your comments either saying you are or are not a doctor. It’s to a point where I think admins should nuke these threads. I’m an MD anesthesiologist at an academic center where we have been trialing NO for about a month on these patients - see that wasn’t that hard.

Edit: and just to add, credentials are to make the audience aware of the context and bias of the presenter, not to validate them. A virologist, biochemist, infectious disease specialist, nutritionist, epidemiologist, public health employee, and undergrad aspiring biology major have different perspectives and understanding of the domains involved. Witholding that context (with hostility) should always be suspect.

Anyone else with "credentials" will understand the metabolic pathways enough to have a conversation with me.

Sorry, I just do not want to post my credentials for privacy reasons.

Asking you now, are you concerned about peroxynitrite formation and are you doing anything to control it? Like IV Vitamin C?

https://ccforum.biomedcentral.com/articles/10.1186/s13054-01...

IV Sodium Ascorbate?

Talking to an MD about IV Sodium Ascorbate, now he's really going to think that you are crack pot. I trust Linus Pauling more than I trust anyone else, but still.... :-)

But you haven't given us any information, or helped to educated anyone, other than to tell us that you have a degree.

My wife's oncologist has a degree, but I had spend 2 hours arguing with her before she realized that she was making a fundamental error in diagnosing my wife's cancer, a fundamental error she had been making for the last 10 years.

My wife has a PhD in Biochemistry, the Oncologist was a well known and highly respected physician, and I was just a guy with a Computer Science degree, but I was the only one to figure it out.

> should always be suspect.

Suspect of what? What bias? I am just talking about science. Bu this is why I am here, to get away from all the credential posturing in academia. You are an MD, are you telling me you cannot commiserate with me on that point?

I stopped looking at credentials the first time I was awed by a new student. It was less about what he knew and more about how he thought. I will treat you with the same respect. I do not care if you have an MD.

This is the last time I will respond to this topic of credentials. If I was saying something stupid you would be attacking me on the science, but instead you are looking to qualify credentials, and that is my problem with health sciences and why there has been such poor progress in the field over the last 30 years.

What does telling someone in the ICU because they can't breathe to eat beets have to do with medical science? That's the problem with trying to cure something with supplements, it's not a reliable delivery method…
Where the bleep did I say that?

It might be BAD if they are on a vent to increase NO. I am talking about before or at the beginning of infection so they never have to get on a vent.

Can you comment on Heme and the reported heart distress associated with Covid19?
I do not see Heme being directly involved. I feel the mechanism of damage might be mediated through oxidative stress. Possibly through Zinc deficiency and failure of the SOD1 or SOD3 enzymes.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418422/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774793/

Thank you for your reply.

So my general impression is that red blood cells are failing to get adequate oxygen, even in cases where the lungs aren't, per se, filled up with fluid to interfere with oxygenation of the blood. I saw a comment somewhere, and I can't find it at the moment, comparing this to altitude sickness, which is a thing I have read up on and which makes some sense to me in terms of my impression of the pathology here.

So what specific pathway would inhibit uptake of oxygen, even in the absence of pneumonia? Typically, that's a side effect of anemia, which can be caused by either lack of B vitamins or lack of iron (which I understand to be also called Heme -- correct me if I'm wrong as I am a lay person here, not a medical professional).

So I'm trying to envision a specific chemical process that disrupts uptake of oxygen or binding of oxygen to the red blood cell and which is not anemia.

This sounds an awful lot like how carbon monoxide poisoning works. So maybe that's a mechanism to look at. The body can be fooled, either by viruses or chemicals of various sorts, to lock up those pathways with things that interfere with what we need.

This is, as I understand it, how Zithromax causes magnesium deficiency: The drug binds to the same receptors as magnesium, so they compete for uptake in the body. You cannot successfully take them together. Taking them together both makes the antibiotic less effective (it should be taken, in fact, with something acid, not something alkaline) and it also prevents the body from adequately absorbing the magnesium.

In practice, the way around this is to time your use of Zithromax and magnesium so that uptake occurs at different hours of the day and they don't compete. This is possible because of the relatively long half life of Zithromax, which means you don't need frequent dosing.

So this is the kind of mental model I'm trying to wrap my mind around. I know some of these types of antagonistic processes exist and if we can figure out what the mechanism is here for how people are basically suffocating, it should cast light on a solution.

>So my general impression is that red blood cells are failing to get adequate oxygen

There does not seem to be evidence of this.

The trouble breathing and O2 exchange is happening because the aveoli are collapsing in bad cases. This occurs when pulmonary vasodilation causes fluid to get in between the aveoli and capillaries.

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I've been taking beet root powder for tough workouts for a while, no harm in taking it daily now.
What's a good brand? Really hard to find a trustworthy brand on amazon. Thanks!
Isn't it easier to just buy beetroots?
No, and not especially in the current situation.

It’s far too convenient to have a distilled source of nutrients/flavor as opposed to shopping, cleaning, preparing it and then storing it such that it is available without a lot of thought/planning.

Of course, this is not a general statement, it only applies to some stuff. I enjoy “regular” food too much for that!

Exposure to NOx can also permanently reduce lung function. This is one of those “in vitrio” things that’s kind of interesting but probably ultimately unhelpful (at least for the current situation.)
NOx? NO is a naturally occurring cardiovascular signalling molecule of enormous importance in the body so its actions may well be of significance in disease events.
Nitric oxide in this context is the result of dietary processes of foods rich in certain types of nitrates.

They are not referring to the direct inhalation of nitric oxide gas.

There have been a bunch of posts about this, including this paper, on https://www.reddit.com/r/covid19stack. E.g. here is an interesting post with a bunch of natural breathing techniques for boosting nitric oxide production:

https://www.reddit.com/r/covid19stack/comments/fp3i6l/natura...

There are a bunch of YouTube videos demonstrating how to do it if you search for them. The FDA also recently granted compassionate use authorization to a device that produces inhaled nitric oxide:

https://www.fiercebiotech.com/medtech/fda-expands-access-to-...

This is a great example of why people don't trust mainstream medicine. You have the WHO very publicly "debunking" the idea that garlic could prevent Covid-19, and then the FDA approves use of some multi-million dollar device with the same mechanism of action and the company's stock increases 5x in a day.

Remember that not trusting mainstream medicine is no reason at all to trust non-mainstream medicine.

Non-mainstream medicine advises us to eat garlic with alcohol, wash with saline solution, take antibiotics, and burn down a mobile phone mast.

I wonder if it's a mistake to treat all "non-mainstream medicine" as a single group here.

I'm not a physician, but I find some elements of non-mainstream medicine (e.g. certain teas can ease certain symptoms) more plausible than others (e.g. burning down a mobile phone mast helps with prevent covid19 spread).

Absolutely, but it can be difficult for non-specialists to tell them apart.

The anti-5G nonsense is spread with a similar anti-government spin to the original post by Alex3917.

The herbal tea market includes everything from making your own ginger tea, to a box costing $20 and promoting some idea of ancient Indian spiritualism and vitality.

Pharisee much? Jesus.

This kind of gate keeping is EXACTLY why citizens are disenfranchised from the healthcare system - at least, in the US.

It is a mistake. One that is made by both proponents and opponents of non-mainstream medicine.
Here's a nice quote from the (admittedly strawman-laden, but imo still nice) Poem "Storm" by Tim Minchin (https://youtu.be/HhGuXCuDb1U):

Do you know what they call alternative medicine that's been proved to work? Medicine.

Of course the provedness of medical treatments can vary, but statements on a random online shop don't really cut it for me.

Many natural remedies have studies backing them up, yet the mainstream medicine outright refuses to use any kind of nstural medicine, simply because there is no money in it. You can’t make lots of money selling garlic.
Remember "mainstream medicine" includes countries outside the USA, where the profit motive is reduced, sometimes to zero.

In light of this, your claim makes much less sense.

I was going to ask what country with mainstream medicine has no profit motive, but then I saw your strawman where you equate herbal tea with chopping down phone masts.

Word of advice - pull your head out yer arse.

I expect you can make lots of money selling garlic, otherwise nobody would grow it.
There is a huge jump to make from cells in a dish to people.
Arginine vasopressin supplements flying off the shelves yet?
Also, nitric oxdide is necessary for erections, and is what all the "boner drugs" increase when used.

https://www.mayoclinic.org/diseases-conditions/erectile-dysf...

    Sildenafil (Viagra)
    Tadalafil (Adcirca, Cialis)
    Vardenafil (Levitra, Staxyn)
    Avanafil (Stendra)
Just wait for the spammers to get word of this. The emails should be entertaining: "Huge boner and kill COVID! BUY HERE!!!1!!"
Came here for the boner pill comments and was not disappointed. I believe watermelon also helps with nitric oxide.
Okay I’m safe then.
... which is heavily found in leafy green vegetables. Eat healthy folks.
So, does use of nicotine cause nitric oxide to be released in the body?

Was there some anecdotal data related to smoking and infection rate?

I know very little about biology.

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This isn't exactly surprising since NO is one of the main chemicals lymphocytes and granulocytes use to kill pathogenic cells.
I've read that ACE and ARB inhibitors promote the generation of nitric oxide.
the hypothesis about ACE inhibitors and ARBs promoting covid-19 severity has never been proven in any human study and in fact ARBs have been shown to reduce mortality in one of the few covid studies which have been done:

Anti-hypertensive Angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients https://www.medrxiv.org/content/10.1101/2020.03.20.20039586v...

If true this N.O. theory could explain some of the dramatic differences in Covid 19 outcomes based on age.

"...production of NO declines steadily with increasing age..." (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390088/)

It could also explain why heart disease, diabetes, and high blood pressure are comorbid for Covid 19 as they are all associated with lower N.O.

I am not stating fact here, just hypothesis. There are both diets and genetics that can tie all these comorbidities together.

Just look at zinc and heart disease. I am just posting one study but the evidence is plentiful. https://care.diabetesjournals.org/content/30/3/523.short

So if one has heart disease they may also be low in zinc. So zinc might be the common denominator to both CVD and COVID19. It is not that heart disease is a risk factor for COVID19, but that zinc deficiency is a risk factor for both.

And they find some odd effects in NO synthesis from zinc deficiency. It lowers NOS activity but has other bad effects as well:

https://journals.lww.com/co-clinicalnutrition/Abstract/2000/...

On the other hand, total nitric oxide synthase activity in the intestine of zinc-deficient animals is significantly lower than that in controls, indicating that zinc deficiency may induce a potential vulnerability to nitric oxide rather than an absolute increase of nitric oxide synthase activities.