6 ms·

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 hel

by podgaj 7y ago

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/ 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...

bitL 7y ago
How about l-Citrulline (watermelon) and alliin/allicin (garlic)?
- podgaj 7y ago
  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.
deleted 7y ago
[deleted]
goda90 7y ago
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.
- podgaj 7y ago
  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-deficiency-neuronopathy#genes 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/S0378111917310752 https://www.sciencedirect.com/science/article/pii/S037811191... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485952/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485952/
- blacksmith_tb 7y ago
  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.
atrilumen 7y ago
Noni?
cpncrunch 7y ago
Getting sunlight on your skin is probably the best option. https://www.mdpi.com/1422-0067/14/1/191/htm#b4-ijms-14-00191 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.
- podgaj 7y ago
  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. "
- deleted 7y ago
  [deleted]
- selimthegrim 7y ago
  Where was this study published?
  - cpncrunch 7y ago
    No idea. Just saw it referenced in media
    - selimthegrim 7y ago
      Found it - https://erj.ersjournals.com/content/early/2020/04/01/13993003.00517-2020 https://erj.ersjournals.com/content/early/2020/04/01/1399300...
ekianjo 7y ago
Zinc (intracellular) is also well known to inhibit viral RNA replication: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1001176 https://journals.plos.org/plospathogens/article?id=10.1371/j...
- podgaj 7y ago
  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.
aznumeric 7y ago
L-Arginine
- podgaj 7y ago
  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.
nradov 7y ago
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.
throwaway_pdp09 7y ago
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?
- podgaj 7y ago
  > 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.
  - throwaway_pdp09 7y ago
    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
    - podgaj 7y ago
      >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 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/10.3109/09637486.2015.1121469 https://www.tandfonline.com/doi/abs/10.3109/09637486.2015.11... Nitrates in vegetal foods are turned into nitric oxide in the GI tract.
  - dylan604 7y ago
    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.
econcon 7y ago
Citrulline Mallate, Argenine also increases nitrogen in the body and so do green leafy vegetables
mgcross 7y ago
And avoid using mouthwash: https://www.ncbi.nlm.nih.gov/pubmed/31709856 https://www.ncbi.nlm.nih.gov/pubmed/31709856
robk 7y ago
I appreciate your enthusiasm but without any credentials this feels like a mania induced posting that's hard to filter through for quality
- podgaj 7y ago
  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.
  - hashmymustache 7y ago
    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.
    - podgaj 7y ago
      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/s13054-014-0460-x https://ccforum.biomedcentral.com/articles/10.1186/s13054-01...
DoreenMichele 7y ago
Can you comment on Heme and the reported heart distress associated with Covid19?
- podgaj 7y ago
  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/PMC5418422/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774793/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774793/
  - DoreenMichele 7y ago
    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.

by podgaj 7y ago

bitL 7y ago

How about l-Citrulline (watermelon) and alliin/allicin (garlic)?

podgaj 7y ago
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.

deleted 7y ago

[deleted]

goda90 7y ago

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.

podgaj 7y ago
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-deficiency-neuronopathy#genes 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/S0378111917310752 https://www.sciencedirect.com/science/article/pii/S037811191... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485952/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485952/
blacksmith_tb 7y ago
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.

atrilumen 7y ago

Noni?

cpncrunch 7y ago

Getting sunlight on your skin is probably the best option. https://www.mdpi.com/1422-0067/14/1/191/htm#b4-ijms-14-00191 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.

podgaj 7y ago
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. "
deleted 7y ago
[deleted]
selimthegrim 7y ago
Where was this study published?
- cpncrunch 7y ago
  No idea. Just saw it referenced in media
  - selimthegrim 7y ago
    Found it - https://erj.ersjournals.com/content/early/2020/04/01/13993003.00517-2020 https://erj.ersjournals.com/content/early/2020/04/01/1399300...

ekianjo 7y ago

Zinc (intracellular) is also well known to inhibit viral RNA replication: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1001176 https://journals.plos.org/plospathogens/article?id=10.1371/j...

podgaj 7y ago
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.

aznumeric 7y ago

L-Arginine

podgaj 7y ago
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.

nradov 7y ago

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.

throwaway_pdp09 7y ago

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?

podgaj 7y ago
> 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.
- throwaway_pdp09 7y ago
  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
  - podgaj 7y ago
    >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 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/10.3109/09637486.2015.1121469 https://www.tandfonline.com/doi/abs/10.3109/09637486.2015.11... Nitrates in vegetal foods are turned into nitric oxide in the GI tract.
- dylan604 7y ago
  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.

econcon 7y ago

Citrulline Mallate, Argenine also increases nitrogen in the body and so do green leafy vegetables

mgcross 7y ago

And avoid using mouthwash: https://www.ncbi.nlm.nih.gov/pubmed/31709856 https://www.ncbi.nlm.nih.gov/pubmed/31709856

robk 7y ago

I appreciate your enthusiasm but without any credentials this feels like a mania induced posting that's hard to filter through for quality

podgaj 7y ago
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.
- hashmymustache 7y ago
  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.
  - podgaj 7y ago
    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/s13054-014-0460-x https://ccforum.biomedcentral.com/articles/10.1186/s13054-01...

DoreenMichele 7y ago

Can you comment on Heme and the reported heart distress associated with Covid19?

podgaj 7y ago
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/PMC5418422/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774793/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774793/
- DoreenMichele 7y ago
  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.