Potential linking RBC, glycolysis, air hunger, thyroid, ATP dumping, pregnancy improvement and...

Not dead yet!

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I know you said don't change anything. But I have a question. Is this saying that we need more phosphate? Or do we need to increase our ability to make this 2,3-BPG? Because traditionally the food that contains the most phosphate (without looking it up, just relying on cultural tradition) is milk. And I"m not a milk drinker, but I get into these moods where I have to have cheese or other dairy products. Would it be reasonable to do something harmless like increase milk products (if you're not lactose intolerant, of course)?

There are other sources, as well as the insight that Vitamin D is also required for dietary absorption, here: https://ods.od.nih.gov/factsheets/Phosphorus-HealthProfessional/#h3 In case someone is vegan, lentils with sundried mushrooms, would be the go to, it looks like.

But I don't want to get carried away, it may not help to have more dietary phosphorous. This is very exciting but I"m having a hard day, so I will read more later. Thanks so much though! :happy:
 

dejurgen

Well-Known Member
There may be a concentration thing going on here because if I got an IV of just fluids and electrolytes, this went away.
I was not aware of this. I don't know if it is common.

But there may be logic to it.

One of the ways I see this 2,3-Bisphosphoglycerate supply going low in ME/FM/... is by RBC being "hampered and temporary unable to move on" in the finer capillaries. So they are stuck for a longer then normal time there. That wouldn't be that surprising as we appear to have inflexible RBC, who can flow poorly through smaller capillaries.

There are also (mixed) reports on these smallest capillaries being narrowed quite a bit in ME/FM/...
Also, having low blood volume "hits" the smallest capillaries more then the bigger blood vessels. That is, when the speed of blood flow decreases, blood becomes increasingly viscous (meaning it flows worse and worse and becomes more thick). In that aspect it's worse then water. I've written on that before.

So IV saline does possibly three things here:
1) It increases (temporary) the blood volume. That makes the smallest capillaries being "less hit" by very poor blood flow.
2) It (temporary) decreases the ratio of RBC to total blood volume quite a bit. Higher RBC content per volume makes blood flow worse so diluting it should make it flow better. With it, sort of an anemic condition is created but if "somehow" this would up 2,3-Bisphosphoglycerate then this may more then compensate for it. Remember: our bodies are already "tuned" to live under low oxygen conditions and hibernating to save oxygen.
3) The (temporary) increased blood volumes may increase blood pressure or pressure fall over the capillaries. That could "push them a bit open" although this may be a minor effect.

Getting back to the "somehow" in 2):
If RBC get stuck too long in the smallest capillaries then they will block the blood flow near completely over there. Unflexible round RBC are often bigger then the diameter of these vessels so if one is stuck you have a sort of a stuck traffic jam.

But the tissue still needs oxygen. So these RBC will slowly give away their oxygen. Remember: 2,3-Bisphosphoglycerate is mainly stored in the RBC themselves. Having more of this chemical does increase the release speed of oxygen. Having less of this chemical does decrease the release speed of oxygen.

So when RBC can take the "quick" route through broad blood vessels, our RBC with according to me few of this chemical will have released few oxygen. But if the RBC take the very slow route through our very narrow RBC then they still will have released a (very) high percentage of their oxygen.

Compare it a bit with a truck spraying salt on icy roads to deice them. Compare the RBC of healthy people to a salt truck with a spraying arm with big holes in it. Compare the RBC of ME/FM/... people to a salt truck with a spraying arm with small holes in it.

When both drive at high speed over the highway spraying salt, the first one will release enough salt and have few left at the end of the highway. The "ill" one will release few salt along the road and return near full at the end of the highway.

Now let them drive really slowly along an equal length "slow speed" road with the exact same "spraying settings". The "healthy" one will completely run out of salt before being halfway as it releases salt per minute, not per kilometer driven (in the case the spray arm is noting more then a hole at the end of the truck). The "ill" one on the other hand will be able to deice the entire small road properly. And it likely will still have some salt left at the end of the road.

You could oversimplify this in a way and say that our RBC are "chemically tuned" by decreasing the 2,3-Bisphosphoglycerate content in them for "poor road conditions allowing only slow travel".

Translated to ME: the RBC may be tuned to remain somewhat more functional for operating under conditions of high oxidative stress (unflexible RBC that have trouble squeezing themselves through the smallest capillaries) and plenty of "rubble on the road" like inflammatory damage, lesions, NETs for trapping pathogens, broken down pathogens and body cells...

So this mechanism may tell something about the underlying problem. Constant IV saline supply unlikely solves this problem long term, at least not in random doses and intervals.

I hope it's a bit more clear what I try to explain. Keep in mind it is quite a big oversimplification. But it gives an overview of how things might work out here.
;)

For example, when the RBC "get stuck in this traffic jam", they'll likely easily run out of energy. And this 2,3-Bisphosphoglycerate buffer in the RBC offers some extra fuel for glycolysis for them to produce ATP for the RBC themselves. So "traffic jams" sort of self regulate the adequate amount of 2,3-Bisphosphoglycerate in the RBC to an extend. But this is a fairly crude mechanism so things like pregnancy and hyperthyroidism may affect it *sometimes* for the better (with regards to breathing).

BTW: we both appreciate the appreciation
 

Issie

Well-Known Member
Yes, we do appreciate the appreciation. Makes our efforts feel of value.

With POTS people, IV's have been given over the years to help increase low blood volume. It is really only a temporary help, as dejurgen indicated. It can give that added boost, but is short lived. Some docs are no longer advising them now. We need a better way to help this. I've had POTS friends with ports put in for several IV's a week......it hasn't made them well. But for a few hours, they feel better.
 
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sb4

Member
@dejurgen I am interested in the recent links with O2 in the blood just not getting used. I used to experience this where I would need to take deep breathes but still I felt like I was lacking air, it is a different sensation to hyperventilation. Anyway I haven't experienced this in a couple of years (I have improved fairly significantly in this time) however last night was day 2 on progesterone. I got up to pee and when I layed back down I was hit by this exact sensation that I hadn't had for years. I tried doing buteyko breathing but it didn't help, I tried mild hyperventilation but it didn't seem to help. I was breathing deeply but it felt like the room had barely any O2. Anyway it decreased after 20-30 mins and I managed to sleep.

I have stopped progesterone now (last time I tried I had messed up sleep after 1 day). I did a quick search for links between 2,3 BPG and estrogen and progesterone but didn't find anything. I should imagine there is something out there as you said 2,3 BPG increases in pregnancy.

Was this just random? Possibly although I am leaning towards the progesterone causing it since it has been a couple of years since I last experienced it.
 

Issie

Well-Known Member
@sb4 , I have issues with progesterone too. It gives me horrible hot flashes and what seems to be mast cell issues. (Though it is said to help some with mast cell, it did the complete opposite with me. Here is a link where others have mast cell symptoms with it too.)


I've given dejurgen some links of threads I participated in years ago with progesterone being not so good for many of us with POTS. Hopefully he will post what may help you. There are scientific reasons some don't do well with progesterone. Methylation mutations being one. Also issues with vasoconstriction and vasodilation. Then there is the balance between the sex hormones, for both women and men. Balance being key point here.

Issie
 
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dejurgen

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@dejurgen I am interested in the recent links with O2 in the blood just not getting used. I used to experience this where I would need to take deep breathes but still I felt like I was lacking air, it is a different sensation to hyperventilation. Anyway I haven't experienced this in a couple of years (I have improved fairly significantly in this time) however last night was day 2 on progesterone. I got up to pee and when I layed back down I was hit by this exact sensation that I hadn't had for years. I tried doing buteyko breathing but it didn't help, I tried mild hyperventilation but it didn't seem to help. I was breathing deeply but it felt like the room had barely any O2. Anyway it decreased after 20-30 mins and I managed to sleep...
I would suspect that what happened works by increasing progesterone as a precursor to many other hormones including aldosterone.

"Progesterone in turn is the precursor of the mineralocorticoid aldosterone, and after conversion to ... ... testosterone, estrone, and estradiol.
https://en.wikipedia.org/wiki/Aldosterone"

"It is essential for sodium conservation in the kidney, salivary glands, sweat glands and colon.[3] It plays a central role in the homeostatic regulation of blood pressure"
"It influences the reabsorption of sodium and excretion of potassium (from and into the tubular fluids, respectively) of the kidney, thereby indirectly influencing water retention or loss, blood pressure and blood volume."
"Aldosterone tends to promote Na+ and water retention, and lower plasma K+ concentration by the following mechanisms:"

More water retention leading to higher blood volume seems a good thing in ME/FM/... but there is another side of it.

"Orthopnea or orthopnoea[1] is shortness of breath (dyspnea) that occurs when lying flat"
"...resulting from fluid redistribution into the central circulation, causing an increase in pulmonary capillary pressure."
"Orthopnea is due to increased distribution of blood to the pulmonary circulation when a person lies flat or closer to a horizontal position. Lying flat decreases the inhibitory effect that the gravity usually has on the blood that is coming back to the heart from the lower extremities of the body... ...The increased intra-parenchymal pulmonary intravascular pressure can also result in hydrostatic pressure related fluid exudation into the alveoli, thus causing pulmonary edema and further worsening shortness of breath."

I have this a lot. The idea is that, when someone has "plenty of inflammatory things going on" including in the lungs, that blood flow is hampered.

But not all parts of it are necessarily equally hampered. The blood coming from the heart to the tissue is under fairly high pressure from the heart's pumping action. If blood outflow is not enough and it can be done safely, blood pressure can be increased to increase blood flow towards the tissues. The returning part is more difficult to control however. That depends largely on pressure on the tissue to push the blood back. If due to inflammation the resistance to blood flow is increased, this part can IMO be prone to get enough blood back to the heart. Blood reflow problems are common in ME, especially in the form of heart prefill problems. Did you by chance happen to observe significantly increased heart during these episodes?

Now if there is an insufficient removal of blood from the lungs to the heart either water can accumulate in the lungs or lung capillaries can expand and push the lung pockets more closed. Both will hamper breathing a lot.

Note that trying to do the reverse, decreasing aldosterone and blood volume has its own set of serious problems. So in many cases a good balance is needed to minimize total symptoms IMO.

The best thing that works for me is getting up a few times at night, walking around, sit like 15 minutes on a chair and or do some circulation exercises (basically some very light warm up). That seems to help "drain" the excess fluid from places it shouldn't be. Also not abruptly getting up or going back to lay down helps me.
 
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Issie

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You may appreciate this thread that we had years ago on progesterone and aldosterone. Some good links from different ones in the post. I personally have near no aldosterone and renin. My subset type of POTS seems to contribute to it. And the usual treatment for that us very large amounts of diuretics. Which we could NOT do because of low blood volume with my POTS.

 
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Issie

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Here is some research I did on it back then. NOTE: these are old threads and science has advanced. More research needed on these earlier post.


 
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sb4

Member
@dejurgen @Issie Yeah, my main symptoms are heart pounding (different to elevated heart rate) and other POTS related stuff. I have no PEM.

Yes my heart was pounding during the event but then again it always is, this is my worst symptom.

Interesting you noticed this upon abruptley getting up and down. This is most likely what happened to me as it hit as soon as I lay back down.

Thanks for the info and links on aldosterone / renin etc. I shall have a look at them tomorrow.
 

Issie

Well-Known Member
You may look closer into MCAS (Mast Cell Activation Syndrome) as that for sure causes heart pounding. And since progesterone gives me MCAS symptoms, could be a connection. I'm doing a new thing for it though and don't have it quite tweaked enough to talk about yet. Though I have spoken of it on another thread on this forum. And that thread is very interesting and worth a visit to.

May I ask why you were attempting progesterone again?
 
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Issie

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sb4

Member
@Issie I was just mainly trying it to see if it helped, I previously noticed a decrease on POTS with pregnenolone DHEA, and on top of that there is pregnancy remission in women and lower rates in men so I thought Id see what happens.

As for the Renin Aldosterone stuff. I do have POTS but my symptoms seem to be different from most. I am at a level now where my heart rate doesn't go above 100 even if I have been standing/walking for perhaps 30-60mins. However I still get lots of over heart symptoms, the main one being heart pounding, which apparently isn't that common.

I have developed a weird aversion to salt. This is a new thing as a couple years ago when I was still ill, I could eat all my days calories as salami without much issue. Now even a little salt kills the meal for me and I can't eat it. On top of that I have never noticed any benefit to my POTS from fluid nor salt intake, even at very high doses.

The latest bloods I have access to show sodium and calcium in range, yet potassium above range, and phosphorus below range. Of course I wasn't informed of this by my doctor, I was just lucky enough to obtain a copy of the results. This does not explain my salt aversion. If potassium is high relative to salt shouldn't my body wan't more salt to compensate? Also I think I have the same problem with calcium judging by I get a similar response to having a moderate amount of cheese which I absolutely did not get a few years ago.

I do have a genetic kidney disease however this generally doesn't kick in until late in life and I have had my kidney bloods done and they have come back normal. I am 29 BTW so I don't see how this is causing issue.
 

Issie

Well-Known Member
I have questioned salt use with POTS from nearly day one. I don't salt load and wonder how smart that is long term. I wrote an article on salt on the DINET forum too. I use little salt myself and then only Himylian or Sea Salt. I think we need all the minerals found in both of those salts.

I too have kidney issues from a young age and have to be very careful what I do. I did need to cut out animal protein for my kidneys at one time and reversed CKD from stage 3 to stage 1. Of course there is also this matter of low renin and aldosterone. But, over time, realized adding salt or Florinef (which is basically a type of aldosterone)
was flat wrong for me.

Back then it was thought possibly high angiotensin 2 was an issue with POTS. But with low renin and aldosterone- the way the kidneys work and how things are broken down.....that was an impossible thing for me. Unless it was from a different source in the body. That basically proved to be a dead end for many of us.

I don't know your subset type. But I'm HyperPOTS with high standing NE levels and tend to have higher blood pressures instead of low. The way I treat/manage my POTS is different from how those with lower pressures do. Which category do you fall into?

Have you looked into MCAS? For sure that can give the pounding heart, even when lying. Even strong emotion or moving your arm over your head, getting too hot. All can cause MCAS. It is common with POTS.

The other thing common is EDS (Ehlers Danlos). I also have this.

Another thing I discovered with me, is I have too thick blood. And thinning my blood with herbs and enzymes and slightly vasodilating my veins, helps me.

Dejurgen and I, both, are experimenting with another possible help. But we don't have it completely tweaked to where we want to share. It has side effects and we don't have it worked out yet. But, we are hopeful.

As for the pounding heart and that anxiety feeling it brings.....one thing I have found helpful is Motherwort. I get alcohol free tincture and put in water and drink. It seems to calm the sympathetic system down. Also Lemon Balm seems to help me. Some have found Blackstrap molasses to help. But you with high potassium, I would NOT suggest that. As it is high in potassium.

But if its MCAS there will be other suggestions for that.

I had wondered if you were trying progesterone for hormonal issues. For me, I have found I was estrogen dominant. (And I question that of guys too. Many of my guy POTS friends are.) One thing I have found to help balance my hormones is DIM. I plan to add more information about this later.

Issie
 
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Issie

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I looked up those old threads. Note this first one.....low aldosterone can cause high potassium.


 
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Issie

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I found this article by Cort interesting. I had also found with myself that I thought too high Co2 was an issue for me and breathing.

 
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Issie

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I need to take another look at all the science on this as it is always advancing. All those post were many years ago and things may have more science/knowledge that could help this be sorted better and with more detail.

That being said.......I think a lot of the things we think are "illness" because of the "symptoms" are in fact......COMPENSATIONS........to try and right a worse wrong. There could be a very good reason the body has lowered things or upped things.

Right now, I'm working on a hypothesis as to there actually being a benefit to having more histamine in the body. It's just the receptors are not working properly to moderate that response and keep homeostasis/balance. Still being refined. But, I'm no longer blocking my mast cell with antihistamines. And my pain has improved, cognitive function and energy. BUT......still having issues with balance and that makes one a bit miserable. Still tweaking.
 
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sb4

Member
@Issie I have looked into MCAS but I don't seem to fit any of the symptoms although I didn't know pounding heart was one.

Interestingly enough my mum and brother both have very flexible thumb joints which is a sign of EDS. I do not, however I may have TMJ. I have got from as far as I can remember, this thing that happens only a couple of time a year where I feel like I dislocate my jaw during eating / yawning. My jaw also can get quite achy fairly regularly. This is probably conective tissue related.

It is possible that I am genetically susceptable to connective tissue issues without overt symptoms and then I have aquired further connect tissue issues through this disease.

I recently had an MRI done and upon extention(?) bending my head backwards. My head bent far above the upper normal range. Also my gums massively receded during the first months of this illness. I made a poll over on phoenixrising and as you can see over 75% report connective tissue deterioration and 30% of those rapid onset.

I understand what you are saying re salt but did you experience initial benefits in POTS to doing it. I have noticed nothing in regards to symptoms either before or after this weird salt aversion onset.

As for my POTS subset I don't really know. I am not hyper pots via tilt table test I had done in london but I think my norepinephrine was near top of the range. I don't have low BP nor light headedness / fainting. I barely even get racing heart anymore. I absolutely do get heart thumping though and it is my worst symptom by far. I had some lightheadedness and a lot of heart racing when i was at my worst and I also get this when I go into ketosis which I speculate is due to adrenal issues (adrenal needs more glucose).

What I think is happening is my sympathetic nervous system is compensating for poor blood flow. I have dry mouth, gastroparesis, and I never feel relaxed. I rarely feel anxious though despite doctors telling me over and over that I am anxious. What confirms this for me is that I got acupuncture a few years back. Afterwards I was hit by a wave of relaxation that I hadn't felt in years. This is how I felt before I was ill. Anyway when I got up to catch the bus my heart rate absolutely exploded. I felt like I was going to die, I tried counting my pulse but it was going too fast, I speculate that it was around 200. At the time I didn't know I had POTS.

I have tried aspirin for blood thinning but didn't notice much difference aside from perhaps increased bruising.
 

Issie

Well-Known Member
No I never got any good benefit from salt and Florinef was most horrible for me. As was any other POTS medicine they tried. Beta Blockers were awful!!! They can up mast cell issues too. If they have ever given it for POTS, I have tried it. My best prescription medicines for POTS were Tramadol and Bentyl. One works on all the neurotransmitters the other a muscle relaxer. I took super low doses and cycled off and on to keep a very low dose effective. I've NOT been on them regularly for about 4 months now. But I am having more issues with POTS and I can get some pretty high heart rates. Still trying to stay off them and give the experiments we are working on a chance and to see if things will regulate out with time. It's not intolerable, but I've had some real lows.

Are you using compression garments? I find abdominal compression better for me than on my legs. Though I wear them both when I travel.

Sounds like there may be some Hypermobility in your family. Also, a bad tooth bite/alignment can cause TMJ. I had to wear braces because of that. It sure made a difference. And can be covered by medical when it's not just a cosmetic thing. But, I do have EDS, so was more than just my bite.

That sudden burst when you stand is normal but not to the degree us POTS people have. Most all peoples heart rate increases with an initial stand but then balances out. With us, it is a compensation to get our blood to our heart and head. Our heart is trying to do this. If you can activate your leg muscles to assist, it will help. Fidget all the time with your legs. I have one of those exercise balls I use when I sit in a chair and I bounce my legs on it and pick it up with my legs. The leg muscles assist the heart pumping and it doesn't have to do it all. Also, when standing, flex and release your leg muscles and also do a bit of a dance while standing. That helps keep things moving and will bring down your upright POTS issues. You will see us POTS people moving a good bit, as we subconsciously are doing it to help blood flow.

If Dejurgen and I can get this worked out, it will cover a broad range of illnesses and different subset types. His symptoms are different than mine and we deal with different levels of endurance and energy. And with us being different genders, some things may work differently for the two of us. But, both and all are so similar they may have the same "cause". We will see.......
 
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sb4

Member
@Issie Yeah I know that the calf acts almost like a second heart to pump blood back up the leg. The problem I have is I get lots of lactic acid buildup from minimal exertion. This then leads to heart symptoms getting worse. I wonder why most ME people don't get instant lactic acid build up but then get hit later on with PEM yet I do not.

I have tried compression socks but there is not much use for them for me. I spend most of the day sitting down cross legged and my heart is generally okay on standing / walking for moderate amounts of time.

I am interested in this theory you and @dejurgen are working on but there are somethings that I don't understand. Such as why is carb metabolism worse than fat if 2,3 BPG and high ROS is true? I know burning fat saves about 5% O2 but the difference in symptoms between carbs and fat is a lot more than 5% symptoms wise. Perhaps the glucose in blood is more susceptible to ROS damage than (saturated) fats?

I have tried beta blockers and ivabridine for POTS through the NHS. Neither helped. I am on mirtazapine which did help my POTS. I speculate this is because mirt increases adrenaline levels causing more vasoconstriction. I have tried mestinon and bethanchol from online pharmacies but they didn't help. I tried licorice root and similar that made my symptoms worse. I tried aGPC and felt like I was almost in remision for around 30mins. Could never repeats this though.
 

Issie

Well-Known Member
I'll let dejurgen talk more about the science of things. His brain is more "on" than mine, right now. He has a knack at making things easier to understand.

Good the heart rate part of your POTS is mostly under control. That's a positive step forward.
 
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