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

[sb4]

@dejurgen Another thing I have thought, some people report improvement with HBOT, some notice nothing. However, if high ROS in blood was an issue shouldn't everyone get significantly worse on HBOT? As far as I understand it, HBOT cannot increase oxygen saturation beyond 100% but some of the O2 does get in to the blood, unbound to hemaglobin.

 

[dejurgen]

As for the Renin Aldosterone stuff... ...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... ...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.

By chance, is you heart rate confined in a very small range? When close to being worse, my heart rate varied between 90 (resting) and 95 (almost falling down from exhaustion when "exercising" or better said trying to walk 10 meters)? It doesn't need to be that narrow, but if it is I could answer quite a bit more precise on certain of these topics.

 

[dejurgen]

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.

I think there are two common inflammatory sources "masked" here:

* Carb rich food has a whole different influence on gut microbiome then fat metabolism. One of the common problems with keto-diets is that people get constipated. That is mainly attributed to lack of sufficient fiber. But much of that fiber is a rich source of food for gut bacteria.
Good gut bacteria are supposed to be good, but give me any pre- or pro-biotics or give me any fructose rich food (or any FODMAP food, look this up if you don't know yet about it) makes my gut go haywire.
Feed me one big apple ("an apple a day keeps the doctor away they say) in the morning and nothing else as breakfast and I get plenty of blood in my stool, as bad that it had caused the stool plus water in the toilet to be colored blood red. Sorry for the visuals. I takes months to many months for me to recover from such single assault on my gut.
In my case, I believe I have a sizable case of fructose intolerance so that too much "quick rocket fuel" reaches my large bowel and creates an explosive growth in all sorts of unbalanced bacteria creating a massive gut immune reaction. Over time, FODMAPs (being semi-fast carbs) triggered the same problem I believe.
Note that the small bowel is supposed to be (nearly) bacteria free so any food taken up there will not feed the bacterial growth.

=> So huge difference number one: fat has a different effect on the gut microbiome then carbs and the microbiome going wrong can be very inflammatory.

* Blood glucose levels need to be controlled in very tight margins for not to have either too few blood glucose (fainting or dying) nor too much (too sticky blood and limb necrosis like in untreated diabetes).
So eating carb rich food, especially food rich in "quick" carbs causes the total (glucose + fructose + lactose +...) blood sugar level to rise that rapidly that it easily becomes very inflammatory. Plenty of insulin has to be mobilized to reduce this dangerous excess as quickly as possible.
Several options are available. The easiest one is converting glucose to glycogen and store this as a reserve fuel in the liver and muscle tissue. But the body can only have a limited reserve of glycogen before it is maxed out. Also, the conversion speed is limited and largely depends on the liver working well. Our livers however are likely already overloaded by fighting all the toxins and ROS our sick bodies produce so they may be slow at reducing excess blood sugar levels.
Another option is to produce fat reserves out of glucose. Here again, the liver is an important converter of excess blood sugar to fat. And our livers likely...
A last option is to entice/force the cells to take up as much fat as possible and burn it like the mob burns evidence just before a raid by the police.

That extra energy production may sound like heaven for an ME patient, but just think of burning wood with too few oxygen: you get a very dirty burning with plenty of thick toxic smoke. Do that with a wood burner and it "eats" through piles of wood but it only produces modest amounts of heat and expels plenty of very dirty smoke and creates a thick tar-like layer of chemicals on the inside of the chimney. These waste products have so much energy in them that risk on chimney fires is high.

Now get back to the body: plenty of glucose to burn very fast but the RBC providing the "fire" with very few oxygen. Result: still not that much usable energy and plenty of ROS and dirty waste products. (That could also explain the quick lactate build-up that some patients see).
Fat has this problem to a far lesser extend. The capacity of the body to store extra fat far exceeds what a person can eat in one day.

=> So huge difference number two: feeding on mainly carbs requires a far better control between supply and demand of energy up to the several hours by several hours basis compared to feeding fat rich food. Some health issues like we have may further constrain this balancing. Breaking this balance too much can be very inflammatory. High insulin levels all by itself can be very inflammatory.

IMO living on a carb dominant diet as an ME patient requires a low caloric diet and sufficient spreading of caloric intake. Some other variants can work too but non is really easy to get right.
A mixed carb / fat diet IMO still requires a moderate caloric intake to not be too inflammatory but may be a bit more tolerant to variation.
A dominantly fat rich diet has IMO the highest tolerance for variation and creates a more balanced hormonal state when it comes to caloric intake. Fat (in a low carb diet) has a far higher satisfying factor limiting caloric intake. A high fat diet has its own challenges however.

Note that all of above suggest modest caloric intake or a "leave the table with a slight hunger" approach. Just don't switch dietary habits very fast whatever you change. We're not that good with going in full reverse in an instant.

 

[dejurgen]

My jaw also can get quite achy fairly regularly.

I mainly get this when I have a cold. It seems to be infection related in my case. Yours likely differs.

However, if high ROS in blood was an issue shouldn't everyone get significantly worse on HBOT? As far as I understand it, HBOT cannot increase oxygen saturation beyond 100% but some of the O2 does get in to the blood, unbound to hemaglobin.

As you said, it cannot increase oxygen saturation beyond 100%. But a part of the patients has difficulty to reach 90+% a lot of the time.

Also, increased pressure does increase the amount of oxygen that is in the supplied. air. That in technical terms increases the partial pressure of oxygen in the supplied air. That makes oxygen take-up easier. For people with inflamed lung tissue or lung edema or air way obstruction or... this may ease breathing and get oxygen saturation above 90%. For all this should lower mechanical effort and energy needed to breath. As any effort taxes us...

Now getting this oxygen saturation very high is a good thing for damaged RBC. Having energy/ATP starved RBC too long at partial oxygenation does let the (heme of) the RBC create plenty of ROS damaging the RBC themselves. So squeezing oxygen saturation from 95 to 97% may only provide a bit more oxygen, but is provides more then a bit more margin against this highly destructive event (RBC getting damaged rapidly by own produced ROS). Even then, notice that it if for example the RBC still return with 80% of their oxygen to the lungs that releasing 17 versus 15% of oxygen makes (17-15)/15*100% = 13.3% more oxygen provided to the tissues. That IMO is saying quite a bit more then a mere few percent of more oxygen carried!

For those with sufficiently high normal oxygen saturation there are however other sides to it:

While oxygen uptake by the lungs increase with higher oxygen partial pressure (and thus higher air pressure), CO2 release from the lungs is dependent on the CO2 partial pressure of the blood. In more plain speak:
Extra oxygen in the air will allow us to breath in less air. But breathing in and out smaller volumes of air will make expelling CO2 more difficult. Because of that CO2 content in the blood has to rise. That will allow the RBC to release yet more oxygen. Consider it a sort of "free" Buteyko breathing.

Note however that increased blood CO2 levels and oxygen release can result in increased problems with ROS if it is too much. Things get IMO quite a bit worse when this increase in oxygen provision to the cells leads to the patient doing more and over exerting while his cells have more access to oxygen.

Now in most HBOT setups, the patient is actually resting and has few ability to exert himself. So IMO the biggest "risk" of increased oxygen supply, (ab)using it to do to much, is taken away in this setup reducing its risk of producing excessive ROS levels (directly when being supplied with plenty of oxygen).

That is one thing I believe: if one succeeds to increase oxygen release (with breathing techniques or by some other way) that still pacing as much as before for many months is necessary for the body to have a decent chance to heal itself a bit. You IMO don't want to squander this improvement to immediately start and do more things.

@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

If this 2,3 BPG thing would be the main cause of it, then know that it is the placenta producing a lot more of it during pregnancy. No placenta no extra 2,3 BPG.

I tried aGPC and felt like I was almost in remision for around 30mins.

That's thirty minutes right? I'd very much like you to confirm this. It could help us further. I can imagine Issie would like to know how much delay there was between intake (oral?) and this effect. Thanks in advance for trying your best effort to fill in the details here.

 

[sb4]

@dejurgen Thanks for the response. Some real good stuff there that I hadn't thought about.

As for the heart rate, it is usually between say 80-95 but can go a fair bit higher so I wouldn't say I am locked in this range just that a couple years back when I was much worse my HR would be frequently 100+ and much higher if I gad to stand.

For the aGPC I wish I could remember better, it was around 5yrs ago now when I had no idea what was going on. I am pretty sure it was plain aGPC I took although there was a small chance it was parasymPlus although I am pretty sure I only started experimenting with it afterwards. As for dosage and time after I noticed response I couldn't say. It was probably less than an hour after dosage.
When I say I went into remmision for thirty minutes, I cannot say for sure as I spent those 30mins in a chair at my computer. All I know is my constant heart pounding that has been with me for 9yrs (at that point 4/5yrs) stopped, and I felt relaxed, not overly so, just like a normal person would, instead of wired and unrelaxed that I feel all the time. So for those 30mins (or so, I can't remember exactly how long it lasted) sitting in my chair playing video games I had no symptoms and thought to myself I had cracked it. I had being reading Dr Diana Driscoll at the time and I didn't even know I had POTS I was just looking at the gastroparesis angle.
Of course subsequent doses never worked, I tried high and low. Even recently I started taking it again with piracetam but stopped after a few days after getting massive headache.

For the carb thing your explanation makes a lot of sense to me. The gut one I am not so sure it is a problem in me but it would be super hard to tell as the gut can cause many non gut symptoms. I don't get blood in my stool after carbs. My symptoms appear to be more inline with my BG. I took regular measurements when I was experimenting with high carb and my symptom severity more or less followed my postprandial BG. Symptoms elevate and reach a peak around 1-1.5hrs in then slowly decrease to baseline over the few hrs.

Overloading with energy after a meal, of which the cell / mitochondria cannot utilize due to low O2 makes a lot of sense especially considering that glucose cannot be as easily dealt with as fat and also various insulin responses.

One thing I have noticed is when I get into ketosis, certain POTS symptoms get significantly worse, particularly rapid heart rate and weakness, poorer tolerance to standing. I have interpreted this to be due to adrenal gland stuggling without carbs. I figure my adrenals are working hard to keep me in sympathetic dominance to help blood flow. As far as I am aware adrenals need high carbs/vit C. Without them I produce less adrenaline and this causes vasodialation poor blood flow, and rapid heart.

Anyway, I have noticed though I am not 100% certain that when I cant take this anymore and eat some carbs (say 100g chocolate bar 50g carbs) these symptoms go away however I don't notice the usual response I get to carbs. This suggests in me it is not a gut issue but like you say, energy overload as if my liver is depleted in carbs due to ketosis, taking in 50 or so grams would go straight to filling up glycogen reserves and the fat of the meal can be dealt with easily.

I had the perfect opportunity to test this last night as I had hit the ketosis adrenal problem again so I ate a bunch of chocolate (over 100g carbs) and unfortunately this just lead to the usual post carb symptoms which died down after 3hrs, however after those 3hrs no more ketosis adrenal problem. Perhaps the energy intake was just too high.

One thing that is puzzling me though is that I have previously found improvement in things that boost Pyruvate Dehydrogenase activity. I noticed a significant improvement after taking thiamine with meal a couple of years ago. I seem to have maintained that improvement with need for thiamine anymore (perhaps correcting a deficiency as my diet 6 months before I go very bad was very low B1).
I have also noticed improvement in carbs tolerance when taking MCT oil with carbs. The logic was that if PDH is problematic then I could skirt the issue by providing acetyl CoA to the liver in the presence of carbs via fat. If LCT are used they bypass the liver and insulin shoves them in fat however MCTs are metabolised with glucose in the liver.
I intend to try MCT + Carbs again today. I noticed an improvement doing this but that goes against your energy overload theory does it not. The only thing I can think how it would go with your theory is that the MCT provides NAD+ to help mop up problematic NADH/lactate accumulation. Perhaps forcing PDH activiy increase mito affenity for O2?
I should note that on day one of doing this I felt great post meal (it took about an hour to kick in). Whilst I continued to do it afterwards and experienced improved tolerance to carbs, I never reclaimed that great feeling. I have since learnt that this has happened in over people and it is though that you give your (brain?) cells a ton of energy as your body doesn't expect both high ketones and high glucose at the same time however it quickly adjusts for this. Still, shouldn't energy overload be a problem? Perhaps it is different in the brain as I do not get many brain symptoms.

This post is super long but I will just quickly say that the HBOT idea does make a lot of sense however I thing that @Hip posted that it is possible that O2 gets into the blood beyond 100% saturation. I guess free O2. Which should cause big problems with ROS. I think this is the supossed anti pathogen effect of HBOT.

 

[Issie]

I found your post interesting and have experimented with fasting and MCT oil myself. I still intermittent fast daily and allow about an 8 hour eating window and have found that helpful to me. I however did not do well on the added MCT oil and found it distressing to my gut and it causing more digestive issues. I thankfully don't have gastroparesis, though I was checked for it. At one time I used a lot of coconut products (oil, milk) and thought it was helping. If nothing else changed gut ecology (microbiome) and possibly helped with yeast and pathogens. But have since felt it not so good to continue and have done much better off them. (Same with stevia. Stevia has been used to eliminate pathogens and can kill Lyme.....which I've also battled with. It will however change gut microbiome and I am better off it, at this point in time.)

The one product you used with GPC and Huperzine looks interesting. However, not everyone does well with Carnitine and certain concentrated aminos. Huperzine can also give the headache you speak of. And give a bit of that hyped feeling.....turns the brain on. One of the supplements I use now, Clari T, has that in it. It has helped me with severe brain fog and cognitive functioning and possibly helped energy levels. Many of us with POTS, EDS, MCAS, ME/CFS, FMS have this dreaded brain fog thing and it comes and goes in severity. Mine got worse with exposure to mold and need of extensive treatments for CIRS and Lyme. That direction gave significant improvements. I have taken GPC before and did think it was beneficial. Not sure why I didn't continue it. Maybe was just on to the next experiment and didn't think it was enough improvement by itself. Maybe, time to revisit that. Some of these brain things not only help blood flow but they increase and decrease dopamine and that can improve mood and energy too. For us with POTS, blood flow to the brain is of utmost importance.

However, not all of us POTS people need to vasoconstrict. I don't. In fact, anything I tried that did that made me so much worse. I do much better vasodilating to a small degree. Too much and POTS gets worse. But definitely herbs and supplements that vasodilate and improve blood flow and slightly thin the blood helps me. More people with HyperPOTS, my subset, are finding this to be true for them too. I may have been the "rebel" who initiated this line of thinking. As when I was DX, was before they even started separating us into subsets, and I figured out their approach was all wrong for me and got pretty verbal about it. Thankfully, I listened to my body and talked about it. Now doctors are finding what I've been saying to be true and there is published articles on it now.

I also found compression socks to be damaging to small fiber nerves with us EDS people and make neuropathy worse. But, still necessary when we aren't able to move our legs enough and we need our leg muscles helping our heart. Though I only wear them if I will need to stand longer or I'm traveling. I also stopped crossing my legs, as anything that can cut or slow blood flow can potentially increase issues to the upper body. One reason why us POTS people do better to elevate our legs while sitting. (I love my bouncy, exercise ball for this. It helps to bounce my legs and get them up.)

I don't subscribe to the ketosis idea. I think some of us do need more sugars for our brains. Not talking refined sugars nor fruits. But vegetable carbs that can provide that. I'm like dejurgen and find I can't eat fruits very well as fructose sugars seem to give me issues. And, as him, forget the apples. Do horrible with them. I had been a very strict vegan for 3 1/2 years.....no animal products at all. It did initially help and I reversed CKD from stage 3 to now stage 1. I have to still be careful with animal protein as it's very hard on the kidneys. But I did need to add them back as I got weaker and weaker without them. I should had been okay being vegan going by blood type (I'm an A.) But discovered grains, nightshades, lectin and fructose to be a huge issue for me. So that sort of takes the ability to be a strict vegan and have what is necessary to be healthy. So, there again, gut issues rear its head.

We are making progress......got to keep moving forward and find that "Purple Bandaid ".

 

[Issie]

Oh, forgot to comment on B1 - Thiamine. Many POTS people have found this helpful. I do think getting dosage correct and not imbalancing all the Bs is important. Many of our symptoms can appear to be deficiency of this vitamin. However, I have found it hard to tolerate in any of the 3 forms. Not sure why this is. Even got some without fillers, thinking it may have been that as the cause. Still not the best thing for me. I intend to try to sort this to see if there could be a compensation going on here and reason for maybe lowish levels with us. But, that one is on the shelf for now. I did/do however, find when I take it.....mosquitoes leave me alone.

 

[sb4]

@Issie On the B1 tolerance issue, have you heard of Dr Lonsdale? He advocates very high dose B1 to get over paradoxical effects. As for balancing, that is an issue to be wary of. I have gone through periods of high B1 + other Bs.

I found that even at 1tbsp MCT I would start to see digestive issues but I found that if I emulsified it in fat I could take 4tbsp+ quite easy. In fact this is what they do with the MCT formulas they give kids with epilepsy. The problem with these formulas is the emulsifier they use. With regular MCT (C8) I get diarrhea, with formula no diarrhea but massive gut pain, with eggs (+ cheese probably helps) I don't notice anything.

I too went a few months eating 100g+ unscented coconut oil per day but didn't notice much. It is important to note the C Oil actually contains a very small amount of MCTs that are available for ketone production.

Yeah for the Huperize A product I found no effect at small dose and very bad effect at high dose that took a week to recover from. Caution definitely wise here.

@dejurgen I may do a little experiment soon where I consume a modest amount of low GI carbs and watch for a reaction. If the carbs are slowly absorbed into my liver/blood at low levels then my cells shouldn't be dealing with too much more energy than when fasting. This will also cause insulin levels to be low. If I tolerate this fairly well then that further hints that low O2 is the problem and not PDH inhibition.

Ideally I would have the glucose drip in at a rate that almost fully inhibits lipolysis in fat cells without increasing overall blood glucose into high energy range. It is my understanding that insulin acts to inhibit lipolysis at low levels and only at high levels (energy excess) does it push glucose into cells. So low levels of glucose dripping in would act to merely replace the fat the cell is oxidizing with glucose without supply the cell with more energy. If my issue is with glucose oxidation, in this scenario my symptoms should get noticeably worse. If my issue is poor O2 usage, my symptoms should remain more or less the same.

The problem is using the right amount of food to not spike BG to high causing high insulin response and cell energy overload, and not too small amount that no effect would be noticed. I will probably have to measure BG levels throughout.

 

[Issie]

Yes, in fact I just started reading his book on B1 and Dysautonomia. I do seem to be deficient in it, yet not tolerating it. Will you give me the fast run down on why mega dose is better and why there is a paradox response? Will take me a bit to get through the book as I'm in a flare at the moment.

Also why you caution as to balance of B's. I don't do well with methyl B's, that's for sure. Despite having methylation mutations.

 

[sb4]

@Issie I wish I could remember but I cannot. I read a few posts of his years ago.

I just say it as a precaution. For example if someone took B1, felt better, then a few weeks down the line feels worse, they could have depleted something with the B1. Indeed there is a thread on phoenixrising on refeeding syndrome induced by B1. One member found B1 reduced here phoshpate, perhaps something similar is happening in you. Here is the thread.

 

[Issie]

Thanks for the thread link and also for including our thread here for others to read and add to. I found the refeeding link interesting as well. I wonder if she just added too much B1 to start with and her body didn't adjust as it had been deficient for awhile. I've found with myself to go super low initially and let the body slowly adjust and come on line. Massive amounts of anything could be too much of a surge. Introduction of low and slow, probably best. Maybe her phosphorus levels were low to start with and adding the B1 made it come to light. The Lonsdale book is also saying that magnesium should be used with B1 to help balance things and get mitrochondria to working again if they have gone off line. (Mine are off line, all 5 mitochondria complexes are not working properly. And I did have a vaccine as a child that I feel was the start of dysfunction for my sis, a male friend and I, as is also spoken of as showing up a B1 deficiency and causing dysautonomia in the Lonsdale book.)

So you found Vit D and sunlight to have given you benefit. Both dejurgen and I have had low D levels and upping even with high supplements have not gotten us to the range we desire. You said you will go shirtless and that has helped. With me, being a girl, I'm not going to do that.....plus I have vitiligo and can burn super easy. Am very fair skinned and blue eyed to start with.

It's all a work in progress, isn't it. As we collect and put the puzzle pieces together and compare notes to get it all sorted. I think it will take a community of us to do this as we have a good reason in our favor to find the answers. Docs can't possibly look at all the complexities we have, and be able to devote enough time to get all the pieces. But as a collective, maybe we will piece it together and get our "Purple Bandaid ".

 

[sb4]

@Issie I cannot say if Vitamin D helped or not. All I can say is my levels where good after lots of time in the sun. Regarding sunlight, the heat KILLS ME. It makes my heart pounding and POTS signficantly worse. However if it is a coolish day or something then I feel better outside. This is mainly mood/mental effects and not so much POTS/CFS.

I spend most of my time indoors now but my computer is by my window and the sun is directly facing it. I also get up and walk around outside multiple times through the day such that my circadian rhythm is kept inline. Before I got ill I experienced great health effects via managing circadian rhythm and I have kept them up ever since. Perhaps this is way I get to sleep on time and wake up around sun rise where as others with this illness become night owls.

I recently made a thread over there trying to come with a way to test out dejurgens theory on low O2 being responsible for poor carb tolerance however half way through I realized my experiment probably won't yield very good results. I may try it anyway at some point.

 

[Issie]

I don't knowwwww......with gastroparesis and you probably being gluten intolerant.....that test sounds like it would "kill" you. Talk about gut issues. That would be too many carbs and especially for someone used to going into ketosis. I'd rethink that one.........

 

[sb4]

@Issie I have had bread recently. I causes some gut irritation but nothing severe. I have also been experimenting with high /' moderate carb for a few years on and off so for me this isn't really an issue. The issue is I don't think this "experement" will yield useful results either way.

If my symptoms increase a small but noticable amount, that could be from error in glucose oxidation, or it could be from more energy used in digestion, more gut irritation, or BG spikes causing energy overload from low O2. It would be very hard to differentiaite bettween them.

I decided to start up MCT oil again. I mixed 6 tbsps egg yolk powder with 6 tbsp MCT oil and so far the next day no diarhea and only mild gut irritation.

 

[Issie]

Wow, a true risk taker. That's a lot of oil if you haven't been doing it regularly. With a possible keto flu in sight. Guessing you may need to stay close to the porcelain throne. Hope it isn't too painful of an experiment. Let us know how it goes and what conclusion you drew from it.

 

[sb4]

@Issie Yeah I spoke to soon. Not much stomach pain but my BM over 1 day after consuming MCT oil + yolk powder was diarhea type. I guess the delayed onset is just an effect of gastroparesis.

 

[Issie]

No, that's what happens with too much ketosis and MCT oil will do that. I was fearful for you.