Glucose Intolerance. PDH inhibition or low O2?

[sb4]

I am interested an idea dejurgen posted about on health rising. It is tied to a study which found O2 wasn't being released from blood as much as it should. I asked him to explain how this accounts for carbs intolerance. He gave an interesting explanation which made me think that PDH might not be a problem. So with that in mind I think glucose intolerance due to dejurgens low O2 theory goes something like this.

Cells have low O2, this means they have low energy production. If they are forced to produce more energy they struggle and lactic acid is produced in increasing amounts, this all leads to negative symptoms. When you eat a carb containing meal, those carbs have to be dealt with to prevent BG going to high, so they are shoved into cells however these cells have low O2 so cannot deal with them correctly so lactic acid is produced, etc and symptoms are increased. This doesn't happen with fats as they can easily be dealt with by putting them into fat cells.

So I figure that if I supplied enough glucose for a significant period of time (via low GI foods) to inhibit lipolysis yet not so much that glucose is actively pushed into cells to be dealt with, I could see whether errors in glucose metabolism are the issue in me or whether. Getting those levels right would be very tricky though. I would need to have a small blood glucose peak followed by a slow lowering to baseline. I would need to provide the same level of calories as are utilized during fasting such that the cell isn't forced to use more calories than it was before.

"In other terms, in a rested state, an average person consumes about 3.5 ml of O2 per kilogram body weight per minute or expends about 1 kcal* per kg body weight per hour. This rate of energy expenditure is expressed as 1 metabolic equivalent (MET) (4). Using these common values, it can be calculated that a resting 70 kg man expends around 1680 kcal per day."

If those numbers are correct then I would be consuming about 90kcal per hour in a fasted state. So I need to eat enough low GI starch that would provide roughly this amount per hour in a long drawn out fashon. This is 22g Carbs per hour.

This suggests that fasting RER 0.77-0.78. If I have got this correct, 1 is complete glucose oxidation, 0.7 if fat. So this means that 1/4 of kcals consumed in a fasting state are glucose and 3/4 fatty acids. Fasting BG is around 5 mmol/L and 5L of blood = 25mmol. I can't seem to find anything stating how quickly it is utilized so I will work it out, although this could have already gone wrong in many places. 90kcal * 0.25 glucose = 22kcal glucose used per hour. Glucose 180 g/mol * 0.025 mol = 4.5g of glucose in blood at any moment or 18kcals.

So we use up just over the total amount of glucose in our blood in 1hr. That's pretty convenient. So if I where to replace my fasting calories used from fat with glucose my BG would be 20 mmol/L which is full on diabetes. So if someone has a RER of 1 meaning they are fully oxidizing glucose, why don't they have 20 mmol/L BG? Perhaps in this case glucose is taken out of the blood (and put in) at an enhanced rate to compensate for lack of blood FFA. If this is the case it will be difficult to use BG readings to track how much glucose my tissues are using. Using this logic would it be possible to have a RER of 1 with BG of 5mmol/L?

So I guess if I consumed 20g of low GI carbs per hour I would have some spikes in BG every 30 mins but wouldn't be pushing my cells too my over normal fasting metabolism. If I did this over the course of 6hrs that is 120g carbs total. If I ate this in one meal I would definitely notice an effect however spread out over 6 hrs the effect would be much reduced so I do not think this is a good test of the idea. I would need a steady glucose infusion to provide 90kcals per hour.

This is after 50g of carbs for each source. A slice of brown bread is around 15g. So if I where to attempt this I could do one slice per hr for 6hrs. My gastroparesis is also a factor which makes this idea kind of bust. I will still post the thread anyway in case I decide to try something similar.

 

[sb4]

I have just reread this post and realize it is not clear at all what it is about.

Basically, I wish to test the theory that my poor tolerance to carb meals is not due to direct problems in glucose oxidation (PDH), but due to low O2 leading to cells stuck in low metabolism state.

In this theory when the BG raises after a carb meal, the cells get a message from insulin to accept more glucose. In a healthy cell they would just take it up and send it to the mito, in a low O2 cell they would take it up and be forced in to over producing lactic acid with it resulting in problem and possibly negative symptoms that I experience.

Fat doesn't have this problem as it is easily taken up into fat cells and therefor if the cell cannot use the fats due to low O2 it is not a problem, it is not forced to turn it into potentially toxic compounds.

So a perfect test would be if I was under glucose IV where I was supplied a rate of 90kcals per hour or so for a few hours. This dose would fully inhibit lipolysis and replace the fat calories burnt during fasting without supplying so much to force cells to increase metabolism.

If there was a problem with glucose oxidation (PDH inhibition) then during this time I would feel shitty. However if the problem was low O2 then I shouldn't feel much different since this does isn't pushing metabolism further nor requiring much increase in O2.

Of course this test isn't possible but I would be interested if anyone else has any ideas how to test this theory.

 

[Frunobulax]

I have just reread this post and realize it is not clear at all what it is about.

Basically, I wish to test the theory that my poor tolerance to carb meals is not due to direct problems in glucose oxidation (PDH), but due to low O2 leading to cells stuck in low metabolism state.

I feel like I should read that theory you're referring to. Where can I find it?

I might be stating the obvious (I don't know your background), but ockhams razor says we should start working with the most probable theory, which would be insulin resistance. Did you do a Kraft test? Do you have metabolic syndrome? What is your fasting glucose/insulin (HOMA-IR) and HbA1c? (Insulin resistance means the glucose might not get into the cells in sufficient quantity.)

Second most likely is inhibition of PDH due to oxidative and nitrosative stress. (Glucose does get into the cells but can't be metabolized because complex I of the Krebs cycle is blocked.)

Once these options are checked, we can look further

so they are shoved into cells however these cells have low O2 so cannot deal with them correctly so lactic acid is produced
[...]
In this theory when the BG raises after a carb meal, the cells get a message from insulin to accept more glucose. In a healthy cell they would just take it up and send it to the mito, in a low O2 cell they would take it up and be forced in to over producing lactic acid with it resulting in problem and possibly negative symptoms that I experience.

That's an oversimplification, unfortunately. Cells have glycogen stores, excess glucose pushed into muscle cells is converted to glycogen and will be converted back to glucose and metabolized when needed. Glycogen stores are sufficient to give energy for a couple of days on a high carb diet. So there is a significant decoupling between glucose intake and energy expenditure. If glycogen stores are full, the excess glucose is converted to triglycerides in the liver, and that's the reason why your blood glucose will return to baseline eventually.

You could fast for 3+ days and then start your experiment. Glycogen stores should be empty at that point, yet cells would immediately switch to glucose metabolism because that's what they do. But again I haven't fully understood what you're trying to prove.

In any case, what's the therapeuthic consequence? The obvious thing to do would be to switch to a ketogenic diet, wouldn't it?

My gastroparesis is also a factor which makes this idea kind of bust.

Couldn't you eat small amounts of whatever carb you want every 30 minute or so? Eventually there should be a tight balance between carbs eaten and carbs released into the bloodstream. There is also a low glycemic mush that they use in experiments to compare to sugar, so you can mix shakes that are either high glycemic or low glycemic but have the same structure. I think David Ludwig mentioned in one of his talks, I could dig it out if you like.

 

[sb4]

Hey @Frunobulax , the hypothesis I am referring to is in the comments of this blog on O2 extraction by user dejurgen.

Did you do a Kraft test?

I haven't heard of it until now. I does seem interesting especially considering high insulin normal BG however on a quick look it seemed to require blood being taken which makes it inconvienient.

Do you have metabolic syndrome?

Over the past 3 years I have gone from 65kg to 92(?). Before that my wieght was relatively stable. The wieght gain is mainly correlated with carb intake I think although it did start when I started on mirtazapine which does cause weight gain however I take a low dose.

hat is your fasting glucose/insulin (HOMA-IR) and HbA1c? (Insulin resistance means the glucose might not get into the cells in sufficient quantity.)

Don't know my HbA1c however when I was experimenting with high carb a year or 2 ago I measured my BG. Here is a sample of my readings from my notes:
BG = 4.2mmol/L.
Rice, OJ, bananas. B1(100)/2/3/6, Mirt (Med reich), DG. Roughly 1200kcal 250g+ carbs. Right arm bone pain, from b-vitamin changes? Some palps, not much though.
9:15, 1hr postprandial. BG 9.8mmol/L.
Xylitol multiple times throughout the day, miswak, mouthwash; Trying to get rid of mouth bacteria infection.
10:15, 2hr postprandial. BG 6.2mmol/L. Seems I am able to get large amounts of glucose (assuming it's getting absorbed at a reasonable rate) out of my blood pretty quick.

It did fairly regularly go up to 11mmol and stay there for a couple of hrs if I remember right but I was eating very high carb. More so than what whould be used for testing. If I was healthy I think my BG wouldn't have gotten that high despite VHC.

That's an oversimplification, unfortunately. Cells have glycogen stores, excess glucose pushed into muscle cells is converted to glycogen and will be converted back to glucose and metabolized when needed. Glycogen stores are sufficient to give energy for a couple of days on a high carb diet. So there is a significant decoupling between glucose intake and energy expenditure. If glycogen stores are full, the excess glucose is converted to triglycerides in the liver, and that's the reason why your blood glucose will return to baseline eventually.

Right but this is in a healthy person. If low O2 is true then a healthy person would be able to burn off excess carbs through O2 and get rid of the excess through the systems you mention. Perhaps these systems get overwhelmed and the result is lactic acid buildup.

If not low O2 then why wouldn't PDH inhibition be able to deal with excess glucose in the ways you have stated?

For me I get a lot of lactic acid build up (burning muscles) from minimal activity that is unrelated to deconditioning. I also get quite bad heart pounding. I suspect that the heart pounding is worse when lactic acid problems are worse as generally all my symptoms are worse with heart pounding. Something is stopping the glucose from being oxidised.

You could fast for 3+ days and then start your experiment. Glycogen stores should be empty at that point, yet cells would immediately switch to glucose metabolism because that's what they do. But again I haven't fully understood what you're trying to prove.

Yeah I have a problem where my POTS symptoms worsen noticably when I enter ketosis. Usually around the 3 day mark on a keto diet. I speculate that this is adrenals based. Adrenals need carbs as far as I am aware. I feel like I am constantly in sympathetic mode. I am unable to relax. When entering ketosis my heart rate climbs significantly and I feel weak. I figure my body is in sympathetic tone to vasoconstrict my blood vessels to help POTS symptoms, and when I enter ketosis it struggles to do this.

I had a salivary cortisol test done when I was in ketosis and my morning cortisol and overal cortisol where very low. I have done it 2 over times when not keto and my cortisol has been more or less normal.

I figured that if I replaced my fasting FFA with glucose without going over the amount of energy my cells would use during fasting, I could see if there was a direct problem with glucose oxidation or if it was a general energy metabolism problem, like O2.

In any case, what's the therapeuthic consequence? The obvious thing to do would be to switch to a ketogenic diet, wouldn't it?

The therapeuthic consequence isn't immidiately obvious but I have been operating under the assumption that my poor carb tolerance was due to PDH inhibtion for a couple of years now. If this turns out to be wrong and it is instead low O2 then this would mean that forcing on PDH wouldn't get me very far. Indeed I noticed no effect from dichloroacetate.

I figure I could then focus my energy on the O2 issue.

Couldn't you eat small amounts of whatever carb you want every 30 minute or so? Eventually there should be a tight balance between carbs eaten and carbs released into the bloodstream. There is also a low glycemic mush that they use in experiments to compare to sugar, so you can mix shakes that are either high glycemic or low glycemic but have the same structure. I think David Ludwig mentioned in one of his talks, I could dig it out if you like.

That mush is interesting. I figure that if I wanted to do this I would need to drink a small amount of glucose every 15mins or so for something like 6hrs. I may still do this yet but currently I am still messing around with my diet.

Do you also experience poor carb tolerance?

 

[percyval577]

@sb4 I have no answere to the theory here, though an observation.

In the early summer I figured out that that VitC, Citrate from lemon juice, and Acetate from vinegar have - in very small amounts, and in this order taken - a nice effect. After some months the effect of acetate vanished.

Recently I happened to have eaten a lot of sugar from cake, and the effect of acetate reappeared. (I take only a drop in 0.8 liter water.)

 

[Frunobulax]

I haven't heard of it until now. I does seem interesting especially considering high insulin normal BG however on a quick look it seemed to require blood being taken which makes it inconvienient.
Over the past 3 years I have gone from 65kg to 92(?).

IMHO it's well worth your time to check it out in detail. I can only give you cliff notes because it's a complex issue. There are some excellent youtube videos out there and some good books, but I don't know any website that explains it all. (You'll find more information in the ketogenic forums over here: https://www.ketogenicforums.com/).

I had MetS too, and treating it with low carb diet has improved my symptoms a lot, to the point that I can work again (from being nearly bedridden). Along the way I got rid of several symptoms (gout, heartburn, high trigycerides, psoriasis, hypertension), drugs (allopurinol, omeprazole) and dropped 30 pounds in the last year. So I'm a believer

The basic theory is that we develop tolerance to insulin over the decades, so our pancreas must produce more and more insulin to digest carbs, up to 5-10 times as much as a healthy person would need for the same amount. High insulin can cause a variety of diseases including diabetes, obesity, artherosclerosis, high blood pressure, fatty liver and gout (you may get some or even all). It increases the risk for depressions, cancer and other diseasees.
This is the carbohydrate-insulin-model, excellent introductions are from Robert Lustig (

) and Gary Taubes (

). Both have written good books on the subject, if you are more interested in biochemistry then you should check out Richard Feinman (https://www.amazon.com/-/de/dp/1603588191).

Main drivers are a high-carb diet, sugar, processed food (emulsifiers and such) and vegetable oils high in omega-6 fatty acids. The only way to reverse it is to avoid all these stuff and go on a ketogenic diet, which is safe and efficient (

,

).

The connection to ME/CFS is that metabolic syndrome causes silent inflammation, and I believe inflammation to be a root cause of ME/CFS (https://forums.phoenixrising.me/threads/causes-for-me-cci-vs-inflammation.78586/). The connection between MetS and inflammation is sketched by Gary Fettke (

) and others (https://www.youtube.com/watch?v=-ltCa513yZs). I should point out that there may be many causes of inflammation, so metabolic syndrome is most probably one piece in an orchestra. But it's a loud one and getting rid of it can help a lot. Leaky gut is closely related to metabolic syndrome, Steven Gundry has written some good books on that subject ("The longevity paradox") and Paul Mason talks about it https://www.youtube.com/watch?v=mjQZCCiV6iA.

Sten Ekberg has a very good series of videos on youtube covering specific questions (https://www.youtube.com/user/drekberg).

Over the past 3 years I have gone from 65kg to 92(?). Before that my wieght was relatively stable. The wieght gain is mainly correlated with carb intake I think although it did start when I started on mirtazapine which does cause weight gain however I take a low dose.


Don't know my HbA1c however when I was experimenting with high carb a year or 2 ago I measured my BG. Here is a sample of my readings from my notes:

Metabolic syndrome is not boolean, it's a continuous development that starts at "healthy" and ends at "diabetic". Glucose control may be normal until the very end, that's the problem -- you can have VERY high insulin and yet still normal glucose, and the insulin is the hormone that causes the damage. Looking at your weight gain and glucose it's very likely that you have MetS and may be prediabetic. (Kraft patterns are abnormal for 85% of all adult americans, so almost everybody in a western civilization is well on this trajectory. The question is if we're closer to healthy or to diabetic though.)

Mirtazapine, well, do you absolutely need it? There are much better remedies (less side effects) to treat mood issues IMO, including tryptophane/5-HTP and rhodelia rosea. (I was on several antidepressants, and none of them helped in any way. 3 months on rhodelia rosea and the depression was gone.) If sleep is the issue, maybe check out melatonin and gaba. But antidepressants have some very unfavorable long term side effects, and I have beef with mirtazapine specifically because it can cause restless legs, a disease that has impacted my life almost as much as ME/CFS.

I will look at the O2 theory when I have more time. But I firmly believe that there are several reasons causing ME/CFS, and the way to go is to find and eliminate them one by one. If you have MetS (which I consider likely) then fixing it should reduce oxidative stress, which should in turn improve complex 1 of the Krebs cycle, normalizing lactate production. So basically my approach would be to fix MetS first, and it's quite possible that other issues including lactate production disappear.

Unfortunately that's not the root cause of ME/CFS, it's only a symptom -- I know many people who have normalized their lactate/pyruvate ratio or went ketogenic and still have PENE.

 

[sb4]

@percyval577 That is interesting, when you say it has a very nice effect, what effect does it have? Are you saying your carb tolerance improves? Are you thinking the Acetate / Citrate are providing substrate to Krebs?

@Frunobulax Thanks for the videos although the problem I see with this in my case is that I got ill in 2011 however I have experimented with low carb and ketosis before that time and indeed during and for long after when I got originally ill I was doing low carb / paleo. Over the last 10 years I have spent the overwhelming majority of time low carb occasionally trying keto or higher carb. Only the last couple of years have I tried high carb.

I think I could well have low grade metabolic syndrome but the problem there is what is the solution? I am currently doing carnivore again and I have had diarhea all 4 days I have been on it so far. Usually I don't get this issue. I am getting around 150g protein which should keep me out of ketosis yet I have started to experience keto like heart symptoms at night again.

My body cannot tolerate keto anymore. I tried high dose vit C + keto to test my adrenals idea a month or so ago, I noticed the vit c helped a little but not much and then I peed out a kidney stone.

This just leaves me at low carb but not keto which is where I am at most of the time.

I agree with what you say with carbs and omega 6 fatty acids. Peter @ hyperlipid has a blog series on protons which explains this at the mitochondrial level and I think his explanation is by far the best I have read. I would encourage you to check it out if you are interested.

Interestingly Peter also speculates on "carbosis" basically super low fat very high carb and how it works at the mito level basically the same as low carb does with reducing insulin. It may interest you.

 

[Frunobulax]

@Frunobulax Thanks for the videos although the problem I see with this in my case is that I got ill in 2011 however I have experimented with low carb and ketosis before that time and indeed during and for long after when I got originally ill I was doing low carb / paleo. Over the last 10 years I have spent the overwhelming majority of time low carb occasionally trying keto or higher carb. Only the last couple of years have I tried high carb.

I think I could well have low grade metabolic syndrome but the problem there is what is the solution? I am currently doing carnivore again and I have had diarhea all 4 days I have been on it so far. Usually I don't get this issue. I am getting around 150g protein which should keep me out of ketosis yet I have started to experience keto like heart symptoms at night again.

[...]
I agree with what you say with carbs and omega 6 fatty acids. Peter @ hyperlipid has a blog series on protons which explains this at the mitochondrial level and I think his explanation is by far the best I have read. I would encourage you to check it out if you are interested.

It's impossible to do a remote diagnosis Weight gain is a fairly reliable indicator that you have high insulin. Years of low carb should have resolved metabolic syndrome, but then where does the insulin come from? It's possible that the antidepressant or other medication is responsible
You may be the exception to the rule, but (again ockhams razor) let's check the most probable cause (metabolic syndrome) first, and if we can rule it out then move to the next explaination. Maybe the easiest test for MetS is insulin resistance, or checking HOMA-IR (fasting glucose and fasting insulin). If it's below 1 you're fine, if it's higher then you may want to do something about it.

Keto is not carnivore. I was on a low-meat ketogenic diet for half a year, eating lots of salad, vegetables, coconut oil and olive oil. Steven Gundry is a proponent of that. Most ME/CFS sufferers have a lot of intolerances so you need to find out what you can eat. However, you have to give the diet a bit more time, it takes about a month to adapt to a fat metabolism (especially overcome the keto flu), and it may be longer for us. One way around it is a gradual change of the diet, slowly reduce carb content and up the fat and protein over the course of a few months.

It may take longer for general health effects. Gundry did a study with his autoimmune disease patients and checked symptoms after 9 months, and someting like 95% of them had significant improvement or even complete resolution of symptoms. Also you have to make sure to eat the right meat on carnivore -- not lean muscle (which is 99% of the meat in stores) but fatty meat and organs (liver, brain etc.), otherwise the fat content is too low and the protein overwhelms your kidneys. And of course beef is better than pork and poultry.

Meat will not kick you out of ketosis btw. The body converts only very little protein to glucose, and once you're keto the insulin spike disappears (

). But a problem with meat may be industrial fodder: If you feed corn and soy to animals their meat will contain lectins and their fat will contain a lot of omega-6. So you may get exactly the bad stuff that you want to avoid, and the only way around it is to buy organic, grass fed beef (which is very expensive unfortunately). That was one of the reasons why I went low meat at first, I simply couldn't afford organic meat but I could afford organic coconut oil and vegetables.

I love hyperlipid, btw

 

[percyval577]

@percyval577 That is interesting, when you say it has a very nice effect, what effect does it have? Are you saying your carb tolerance improves? Are you thinking the Acetate / Citrate are providing substrate to Krebs?

I finally became aware of this possibility, but I didn´t start with this consideration.

Acetate I started originally because I thought to very slightly influence acid sensing ion channels in the accumbens (... as acetate is an acid). And it had an effect which could be interpreted like so, I would report.

Then I forgot about it, as the effect was tiny enough and didn´t lead to an improvement. Only in summer I rediscovered it as described, and now I thought it would serve for the acetylation of proteins and histones.

(I didn´t think anymore on the accumbens, probably b/c it fits into the VitC/Citrate thing, which I interprete as silencing stem cells and metal chelation, so actions which are not specifically localized.)


I have to say that these three are part of a bunch of influences, but especially VitC and Citrate (in this order and only sipwise) are indeed constantly nice and probably important. I would describe it as a release of tension. Sometimes my vision gets clearer.

After this interpretation, it might work only when one is in any phase of getting better, be it long termed or short termed, say some time after a meal, because it would say that stem cells are readjusted and metals are reconfigurated.

So after all, yes, it might also or additionally be an effect via the Krebs cycle, or only this effect, although it indeed feels like a release of tension, with concomitantly some ability to focus, mentally and in vision sometimes.

 

[percyval577]

I forgot, I don´t seem to have a special carb issue, but it might help me with bad effects from carbs, difficult to say, I don´t eat them too much. Until now I had only this very pronounced effect, and a second tiny one after three fruits the next day.

I will try to test it and skipping acetate for a while completely, but I might not manage to do so.

 

[Frunobulax]

I forgot, I don´t seem to have a special carb issue, but it might help me with bad effects from carbs, difficult to say, I don´t eat them too much. Until now I had only this very pronounced effect, and a second tiny one after three fruits the next day.

The thing is, insulin resistance has no symptoms itself. It causes all those other diseases, possibly through NO (nitric oxide) inhibition (see Gary Fettkes talk about inflammation). The only way to be sure is to do a Kraft test, or (less reliable) look at HOMA-IR. You are here in this forum so I'll assume that you have ME, which means it's probably a good idea to check on all common issues that are just a bit out of the average GPs eye (like MetS). I'm not saying you have it, but I do say that it's a good idea to rule it out. And at least over here in Europe the check on insulin and glucose (=HOMA-IR) is covered by insurance, so all it takes is to ask the doctor to do these two values (glucose will be checked anyway) whenever you're due for your next visit. See, I'm not suggesting anything outlandish

Of course if you eat few carbs or at least no refined carbs you may be safe. (Carbs from legumes and fruit come with fiber and antioxidants. Nature supplies the remedies to the problems caused by the carbs, the problem is that we remove these remedies through refining.) People who avoid sugar and white flour may never get metabolic syndrome. But the further you are on that axis (from health to diabetes), the faster you'll progress. Or in other words: If you have moderately elevated insulin, a low carb approach (less than ~100g carbs per day) may very well be sufficient to reverse any damage. If you have severely elevated insulin you'll have to go keto (less than 25g) for a long time, perhaps with regular fasting periods as I do (I eat one meal a day only, and plan a switch to alternate day fasting).

 

[sb4]

Keto is not carnivore. I was on a low-meat ketogenic diet for half a year, eating lots of salad, vegetables, coconut oil and olive oil.

Yeah, I should have been clearer but I have done carnivore twice and keto a dozen times. I am actually hoping the higher protein intake will prevent the usual keto heart symptoms. I should also say that I have tried pushing through the worsening heart keto symptoms for 3 weeks without much change before quiting. I don't think it is an adaption issue. I would speculate that being in ketosis is a stressor on my body in its current state. Maybe through knackered adrenals.

Weight gain is a fairly reliable indicator that you have high insulin. Years of low carb should have resolved metabolic syndrome, but then where does the insulin come from? It's possible that the antidepressant or other medication is responsible
You may be the exception to the rule, but (again ockhams razor) let's check the most probable cause (metabolic syndrome) first, and if we can rule it out then move to the next explaination.

Yeah it isn't clear to me either but what if it is the glucose intolerance that is causing this apparent metabolic syndrome. Cells cannot accept the normal amount of glucose as they are converting it to lactic acid, therefore stronger insulin signal, cells forced to accept, more lactic acid is generated.

I should note that all my significant gains in fat came when I was experimenting with higher carbs. I went a good few months having potatoes and butter as the majority of my cals and by the end I was significantly fatter.

The test does sound interesting but would be a pain to get. I think I might have more luck getting something like HOMA-IR test through the GP though I need to ask GP other stuff and hate going there.

Meat will not kick you out of ketosis btw. The body converts only very little protein to glucose, and once you're keto the insulin spike disappears

I have heard this but both me and my brother have done high meat paleo and keto and both notice a significant diference between them. So I think high meat is providing enough oxaloacetate / whatever to keep the krebs moving without much ketones.

I love hyperlipid, btw

Yeah his stuff is really good. In fact it was a recent post from hyperlipid that made me give carnivore another bash.

I will finally say this. When I first got ill with this I was 6 pack lean, with decent muscle mass. I still experienced symptoms of lactic acid build up in muscles from minimal activity as well as heart and other issues back then. The symptoms just weren't as bad and declined over the following years.
If, and it is a big if, if the lactic acid build up was from poor glucose tolerance then (I actually think it is due to poor blood flow / POTS but what is causing this???) it is unlikely this glucose intolerance was caused by metSyn, unless metS can be induced rapidly by tonsilitis / stomach ulcer.

 

[sb4]

(I didn´t think anymore on the accumbens, probably b/c it fits into the VitC/Citrate thing, which I interprete as silencing stem cells and metal chelation, so actions which are not specifically localized.)

Got to say I don't know much about accumbens / stem cells so not sure what is happening there.

Then I forgot about it, as the effect was tiny enough and didn´t lead to an improvement. Only in summer I rediscovered it as described, and now I thought it would serve for the acetylation of proteins and histones.

I came up with several ideas for supplying acetate / actylCoA precursors. I think I came up with an idea of an aCoA bomb that would contain:
10g Sodium Acetate
10g K Acetate
Ethyl AcetoAcetate
MCT oil

Was hopping this would bypass a potential PDH dificiency and provide the need acetyl CoA and stuff to be used in krebs and histone acetylation etc. Never did try it but I have all the ingredients.

So after all, yes, it might also or additionally be an effect via the Krebs cycle, or only this effect, although it indeed feels like a release of tension, with concomitantly some ability to focus, mentally and in vision sometimes.

I am suprised at the effects from such a small dose of vinegar. I have tried all three compounds you mentioned before all in high dose but haven't noticed too much.

 

[percyval577]

I am suprised at the effects from such a small dose of vinegar. I have tried all three compounds you mentioned before all in high dose but haven't noticed too much.

There might be two parameters (and btw, I am surprized, too):

• It is an additional "negative" influence (release of bad actions) on top of inducing ones, mainly some metals and my low manganese diet, and some vitamin B´s (which I also take seperately).
• in high doses the target cells might refuse to act at all, b/c it might be too much action. I tested VitC for long, but it never gave this effect like it now does in small doses.

The first good effect from acetate I got by accident from a salat with vinegar (I then was wondering what it might have been). Interesting here is also that it was not in isolation.


Another experience I had with acetate might have been alcohol, I had - symptomatically only - very good effects from beer for quite a while (only during the cold seasons). I think it was that there gets some acetate formed, wasn´t it? So now I think that this may have been one of the influences (also on top of an other main influence).

Finally I had good effects from alkaloids (very very small doses, it´s rather a strong poison), which would inhibit acetylcholinesterase. I got the whole thing theoretically wrong, I am even now confused, but the latest input I took was, that from one of the involved molecules some acetate would be derived (hope not to confuse here).


So, maybe there is some little chance to get some good effect from a small dose?

 

[percyval577]

The thing is, insulin resistance has no symptoms itself. It causes all those other diseases, possibly through NO (nitric oxide) inhibition (see Gary Fettkes talk about inflammation).

I got tested long time ago, maybe in the third year of my symptoms, but everything was ok.

Now I sometimes wonder a bit if in some brain areas might be an insulin resistance, if this is possible. I indeed have good effects from chromium (picolinat) which is known to help with insulin resistance if I am not wrong, but this is only one influence along with others, might though be that it´s an energy coding issue. I also have good effects from some VitB´s, and they too (well not B9 and B12) are used in the mitochondria for energy production.

Thank you you for Fettkes, I will look at him (interesting name, btw). I think in my brain there is a tendency of too much NO, at least from the iNOS. (Here my biggest discovery is that manganese in the presence of LPS upregulates the iNOS.)

 

[Frunobulax]

I got tested long time ago, maybe in the third year of my symptoms, but everything was ok.

Now I sometimes wonder a bit if in some brain areas might be an insulin resistance, if this is possible. I indeed have good effects from chromium (picolinat) which is known to help with insulin resistance if I am not wrong, but this is only one influence along with others, might though be that it´s an energy coding issue. I also have good effects from some VitB´s, and they too (well not B9 and B12) are used in the mitochondria for energy production.

Thank you you for Fettkes, I will look at him (interesting name, btw). I think in my brain there is a tendency of too much NO, at least from the iNOS. (Here my biggest discovery is that manganese in the presence of LPS upregulates the iNOS.)

High insulin causes inflammation. ME may be moderated by inflammation.
What kind of test did you do? Most tests (oral glucose tolerance, HbA1c) are notoriously unreliable, as evidenced by the Kraft research (https://www.ncbi.nlm.nih.gov/pubmed/27344544). Half of the patients with normal glucose tolerance have hyperinsulinemia and should be considered prediabetic.

I have wondered about NO production and nitrosative stress. I'm not sure that I have an answer yet.

 

[sb4]

A way I could somewhat test this is drinking 2L fat free milk over the course of 7hrs. That would be around 90kcals and 15g carbs per hour. Since fasting state burns 90kcals per hour and 5g carbs, I would be tripling the amount of carbs with minimal increase of energy. Protein is a confounding variable though, also assuming my body absorbs the milk uniformly over that time is.

 

[Frunobulax]

A way I could somewhat test this is drinking 2L fat free milk over the course of 7hrs. That would be around 90kcals and 15g carbs per hour. Since fasting state burns 90kcals per hour and 5g carbs, I would be tripling the amount of carbs with minimal increase of energy. Protein is a confounding variable though, also assuming my body absorbs the milk uniformly over that time is.

Another major coufounder is that that lactose is metabolized differently than glucose (as is fructose). I guess it would be better to use something that provides mainly glucose, perhaps something like a soluble starch drink.

 

[Jwarrior77]

@sb4
I think you hit the nail on the head with this one. It always perplexed me to why after developing this illness I suddenly could not tolerate sugar or carbs at all. It would always put me in a coma like state after eating it even in low amounts. I would get extreme muscle fatigue and tiredness, extreme cognitive difficulty, and have practically no energy to even get up off the couch or bed. Doing the keto diet helped me a lot and then I went off of it after doctors said there was no reason I should be on it. Going off the keto diet put me in a very bad place. I believe after months of eating carbs and consuming sugar I developed a severe case of D-lactic acidosis. In an act of desperation I went carnivore and it single handedly saved me. It took a couple months but I am now able to get up, walk around, and think clearly for the first time in what feels like forever. Im still very disabled but at least many symptoms improved. I also rarely get the extreme muscle soreness anymore. I usually only get it when I wake up but goes away halfway through the day.

I heard that people have issues with heart symptoms and the "keto flu" while on carnivore and keto. What fixes this is that you have to increase your salt and electrolytes especially while fasting. If you don't that's when you get the undesired symptoms. Your kidneys don't hold onto extra electrolytes when on carnivore. Many people recommend this brand: https://drinklmnt.com/products/lmnt-recharge-electrolyte-drink I put one pack in a liter of water. It truly does help and I also take some extra magnesium. Another thing is, is that you have to play around with how much fat you need. I needed lots of fat initially where I was eating half a jar of tallow a day. It also immensely helped my energy levels. Now I am eating mainly high protein.

Anyways back to the topic. I think the low O2 in the cells is what contributes immensely to the mitochondrial dysfunction. It explains why people like myself cant tolerate sugar and the increase in lactic acid production. But I always wondered what causes the low O2 in the first place. I recently found out that I have extreme neck instability. I have C1 instability, AAI, and suspected CCI. I also have many symptoms of tethered cord with one of the biggest being urinary issues. There seems to be a huge correlation for people to have undiagnosed tethered cord for years then developing into neck issues because of the constant stress and stretching of the spinal cord. If you haven't seen this thread by Jen Brea I highly recommend it:

https://twitter.com/i/web/status/1201429588556959744

Also: https://medium.com/@jenbrea/pathology-part-ii-could-pem-be-a-symptom-of-neural-strain-f5be69175e1

It turns out tethered cord impairs glucose metabolism and causes metabolic failure of intracelluar mitochondria. I know people get annoyed but I think a huge percentage of ME/CFS is caused by undiagnosed structural issues. I never realized anything was super wrong with my neck until I got a digital motion x-ray on it.

 

[sb4]

@Jwarrior77 I am currently doing more or less carnivore aswell. For me its a toss up between low O2, and PDH inhibition. Probably both contribute.

The electrolytes have minimal effect on my heart symptoms and I no longer tolerate salt.

As for CCI etc, I don't know if I have tethered cord however I had an upright MRI of the neck down and posted a thread on here about it with pics. It is still ambiguis to me as I do have a below normal CXA (?) and my brain stem clearly bends on the way out. However, Dr Gillete and the doc at Medsera both didn't dx me with anything, Gillete said he needed another scan to rule out atlantoaxial instability but I can't afford it, plus he has a very high rate of positive dx.

Recently me jaw has been dislocating more and my neck has been aching / uncomfortable more but applying upwards traction to my head does nothing.