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Endothelial Nitric Oxide Synthase and POTS

Discussion in 'Other Health News and Research' started by adreno, Apr 13, 2016.

  1. adreno

    adreno PR activist

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    Not sure if this was ever posted. It certainly fits with my experience that supplements which increase eNOS activity worsens my OI.

    Full text here:
    http://hyper.ahajournals.org/content/46/5/1103.long
     
    Last edited: Apr 13, 2016
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  2. adreno

    adreno PR activist

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    This study also drew the conclusion that eNOS and nNOS are increased in POTS.

    Full text:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191087/
     
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  3. adreno

    adreno PR activist

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    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC311308/

    So eNOS and nNOS are activated after an increase in intracellular calcium concentration. Links to channelopathy?
     
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  4. Sidereal

    Sidereal Senior Member

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    Personally, calcium channel blockers make my OI vastly worse. High nitrate foods like beets raise my BP (paradoxically) and improve OI but the effect is short-lived and rapid tolerance develops (couple of weeks).
     
  5. Crux

    Crux Senior Member

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  6. adreno

    adreno PR activist

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    Interesting. I am not eating a whole lot of nitrite foods, though. It would seem, as suggested in the studies above, that eNOS is over expressed. I wish I knew how to reduce this expression. Barring that, hydroxocobalamin seems to help a little by mopping up excess NO.
     
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  7. Crux

    Crux Senior Member

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    If we can find the source of Oxidative Stress that's causing the overexpression of eNOS, et al., good.

    The eNOS becomes uncoupled, and the production of toxic NO products ensues.
     
  8. adreno

    adreno PR activist

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    Interesting, again @Crux . I've never heard of eNOS uncoupling before. That would indicate that ROS leads to more ROS in a vicious circle. Or as they put here:

    eNOS uncoupling in cardiovascular diseases--the role of oxidative stress and inflammation.

    But wouldn't this uncoupling lead to less NO being produced, not more?

    Pharmacological prevention of eNOS uncoupling.
     
  9. adreno

    adreno PR activist

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    Also, I do not suffer from hypertension, or any other symptom associated with eNOS uncoupling and low NO. In this abstract, things are explained more clearly:

     
  10. Crux

    Crux Senior Member

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    @adreno , I used those terms even though they are more involved with reduced NO bioavailability rather than overexpression.

    I ran across an article that compared a type of eNOS overexpression and uncoupling as,' trying to peddle a bicycle with a broken chain'. Couldn't find it again.

    I'm more concerned with overproduction of NO itself and its pathology.

    Here's a small study that used a general NOS inhibitor demonstrating that excessive NO was causing autonomic failure in a small group : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2497433/

    This article discusses the role of NO in immune response. It discusses the pro and anti inflammatory effects of NO.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100761/

     
    Last edited: Apr 16, 2016
  11. DeGenesis

    DeGenesis Senior Member

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    This reminds me of Dr. Pall's OH/ONOO theory.
     
  12. Lolinda

    Lolinda after meals, I need to lay in bed for hours

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    Thanks @adreno for posting all this research! When I read such papers, I always ask myself: does it apply to me? Can I get a test done? I would like to get tested first for nitric oxide, to see if I have elevated levels at all, before entering all the details of so many possible causes. Now, all testing methods have advantages and disadvantages, but most often nitrate and nitrite are estimated in blood or urine. I would be already glad with a rough estimate if there is sthg grossly wrong in me.

    Question to all researchers and research enthusiasts on PR: Do you give the following home test method a chance to deliver at least a very rough estimate?

    - Use these nitrate & nitrite test stripes with serum or urine. In case of urine, divide by creatinine.
    - Avoid sports and eat low nitrate for 3 days before the test (PM me if you need fulltext access, the 3 days are mentioned only in the fulltext)

    The test stripes use the same reaction as is most often used in published research, that is, the Griess reaction. They are for complex biological substances ranging from aquarium water to soil.
     
    Last edited: Sep 18, 2016
  13. Mor

    Mor

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    Very interesting.

    Indeed it does.

    Quote below from Dr Myhill, which is fitting after reading that study:
     
  14. Mor

    Mor

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    "Astaxanthin inhibits nitric oxide"
    http://www.ncbi.nlm.nih.gov/pubmed/14503852

    Also:
    http://www.ncbi.nlm.nih.gov/pubmed/23100599

    So alleviating oxidative damage improves mitochondrial function? Isn't that the goal of Dr Pall?
     
  15. Lolinda

    Lolinda after meals, I need to lay in bed for hours

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    I was very interested in Pall's approach, so I got tested. Fortunately, these tests are relatively easy to obtain, labs usually offer them under names such as "nitrosative stress". Nitrosative stress is exactly the free radical damage (=oxidative stress) brought about by NO/ONOO. Here are two entirely different testing approaches, offered in Europe by Redlabs.be and by ganzimmun.de and some others. In the US, there is a subsidiary of Redlabs, you find them over their homepage. The Ganzimmun-style test should be really easy to find in the US or UK or wherever you are from. I did far too much readings on these things, just lost my time, should have got tested immediately, so I had known earlier that I do not have any nitrosative stress at all....

    While nitrosative stress is easy to test, nitric oxide is a topic in its own right and is not easy to test at all. I directly asked the labs if any of these tests shown below allow any conclusions about nitric oxide. No, they dont. It works like this: Free radical damage, that is, nitrosative stress, occurs only if there is a process called NO uncoupling. Elevated NO may deplete BH4 and make uncoupling more likely to happen, but doesn't cause nitrosative stress in itself.
    -> These tests below are fine to rule out the NO/ONOO issue, but are not ruling out elevated NO in itself. I would be so glad to find a good test for NO! Testing would be really important as NO (without nitrosative stress) is actually very useful and supporting health. I do not like so much the idea of lowering it without knowing if I have too much. In fact, most people woud be glad to increase their NO (cardiovascular diseases, athletes, etc).

    redlabs.be:
    IMG_20160919_092606.jpg

    ganzimmun.de in Germany and labor team W in Switzerland:
    IMG_20160919_092223.jpg
     
    Last edited: Sep 19, 2016
  16. Mor

    Mor

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    I tested 8mg of Astaxanthin, and I see no difference in my POTS. Who knows, it was just one day and I don't plan to keep taking it.

    Stuff that seems awesome on paper often doesn't match the same awesomeness in actuality.
     
    Last edited: Sep 19, 2016
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  17. JES

    JES Senior Member

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    NO has a blood half-life of a couple of seconds, so I assume it would be impossible to measure it in a standard blood test, at least not reliably. Nitrite and nitrate levels would be easier to measure since they have a longer half life, and since they participate in the NO cycle they are some kind of indicators for NO activity.
    Exactly. Astaxanthin is a super antioxidant, no doubt, but I don't see much other specific benefits in it for CFS/ME. I responded to it in similar way as to most other antioxidants, in short term it improved my symptoms, in long term it worsened my fatigue. It doesn't seem much different as alpha-lipoic acid etc.
     
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  18. Lolinda

    Lolinda after meals, I need to lay in bed for hours

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    Exactly! That is what I mean by "NO testing". I cited studies in my post above, most of their measurement methods relying on nitrate/nitrite. But I have found so far only a bogus lab (ELN in the Netherlands) that offers a test commercially (and they tell you to send in the sample unfrozen, it will be fine... not only that NO has a half-life of seconds, but nitrate and nitrite arent that stable either).

    You are the first person whom I see writing this. I have that too, very similar! I always wondered that so many people are enthusiastic about ALA... But in me it is first improvement, then worsening. It was like that when I had ME (meanwhile resolved). Now, where "only" POTS and neuropathy is left, the nature of improvement and worsening is a bit different, but the pattern is the same. Currently it is that in the first wave of improvement (few days), a "heavenly peace" comes upon me. And the best part of it is that I feel like doing everything with minimal effort and big effect. And a peaceful wisdom in my mind. Really wow, so good! But at the same time sleeping issues increase day by day until I better stop ALA after a few more days. Btw on the first day with ALA, my neuropathy got better too (less stinging pains).

    I wonder, what was your ALA dose? (Mine: 2 x 200mg)
    Did you try ALA in low doses to see if it is better?
    Do you have any explanation for all this up and down?
     
    Last edited: Sep 19, 2016
  19. JES

    JES Senior Member

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    I trialed ALA a couple of times in 2014, it somehow gave me hypogylacemia which was the primary reason I stopped taking it, I reckon I never did more than 200mg.

    But yeah, I do have this worsening reaction to almost every antioxidant I've tried, my CFS symptoms go from mild to moderate while on them in a matter of less than a week. I don't have POTS diagnosed, but I notice that my standing heart rate is much increased after being a couple of days on a strong antioxidant, it even causes some skipped beats. My chronically cold hands also tend to get worse. I wouldn't be surprised if all this is related to the NO cycle, as antioxidants tend to lower NO levels, which seems to result in worsening for me.
     
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  20. Lolinda

    Lolinda after meals, I need to lay in bed for hours

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    Thank you!! That fully answers the issue!! I just double-checked and yes, ALA lowers blood sugar:
    http://umm.edu/health/medical/altmed/supplement/alphalipoic-acid
    "Several studies suggest alpha-lipoic acid helps lower blood sugar levels."

    And this fully explains my sleeping issues: if blood sugar goes down -> cortisol goes up -> no sleep.
    I add that my blood sugar is just barely enough as I am on a very low carb diet. I need that, because that is what got me out of bad ME and what keeps me out of it. Lowering blood sugar further is no good. Thanks a lot for your post, which helped me to discover why ALA causes bad sleep in me!!

    But then there are the good things, which I want:
    "Its ability to kill free radicals may help people with diabetic peripheral neuropathy, who have pain, burning, itching, tingling, and numbness in arms and legs from nerve damage."
    (I dont have any diabetes, but do have axonal neuropathy)

    --> I will take next a small dose, maybe 100mg in the early morning, so that the effect fades off till night.

    And for your case: if you think of hypoglycaemia, there is an easy way to combat that: eat more healthy fats (olive oil, lard, butter, coconut oil). This sounds paradox but it works, because fat is a long lasting continuous source of energy and does not cause blood sugar fluctuations, insulin spikes, etc.
    (Remark: The situation I describe for myself, i.e. barely enough blood sugar, occurs only if you are on a very low carb diet, that is, in ketosis. - I am and I profit greatly. )
    - But this is just a minor side comment. More importantl comment:

    Regarding antioxidants and NO: Have you checked for all sorts of infections? Antioxidants are bad if you have an infection, because it is oxidants, that is free radicals, how your body fights the infections! Equally, nitric oxide should not at all be lowered but increased in infections, it fights them well!
    - OK I guess much of this you already know... You seem really well-informed from your comments. But if there is only a single new idea I could give, then I am glad.
    The only "antioxidant" I would take when fighting Infections is vitamin C... It is just as much a pro-oxidant...

    btw cold limbs sounds to me like too little NO, to start with....
    And you could try for that:
    - eat lots of grean leaves (parsley, cilantro,spinach,...)
    - here sbdy makes the point that thebacteria in AOmist convert ammonia to nitrite. Which is exactly what ammonia oxidising bacteria should do
     
    Last edited: Sep 19, 2016

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