@S-Holmes said in Glucose loading cures everything?:
Have you noticed any retracing?
I can't say I have! Every time I've had severe symptoms it's been because I've taken too much glucose.
All that said I think I'm "set up" to heal well/smoothly on glucose. If I had started this before I changed the way I eat I'm sure it would have been much more rough. All my systems were in shambles.
Now many of them already work relatively well, despite the incredible fatigue. It's like all my parts work better, except the motor. In that sense I may experience less "detox" symptoms, because when the motor is working, the pathways for elimination are ready to be ramped up. Any “detox” symptoms I’ve had have been incredibly gentle though.
I haven't seen a convincing argument from Dr Stephens about the value of retracing symptoms, or even why a high dose is necessary to heal. I've continued to wake up refreshed, and don’t experience crashing or a lactate buildup which is common in ME, so even though the glucose hasn't fully removed my fatigue overnight, I feel incredibly hopeful about this approach.
Alan Franklin talks about three stages of ME/CFS: The unstable or toxic stage, the stabilising stage, and remission. I think that in 2021, after eating PM for about a year, I got to the stabilizing stage. The following fall I got covid again, and since November '22 I've been back in the toxic stage. I have hardly been able to do anything before crashing.
Now, two weeks in, now taking 12-14 tbsp a day, approximately 1 every hour, I am at least in the stabilizing stage, if not remission. I think it will take time, and only time will tell how much I can recover, but with reading the science I feel “logically hopeful” for the first time.
@T-3 said in Glucose loading cures everything?:
More information, even speculative, about the mechanisms that make glucose special would be good to read here -- and whether there are reasonable food-based approaches to "glucose maxing" that might work (e.g. foods with more cofactors that help the breakdown process from all carbohydrates to blood-glucose).
NOW FOR SOME EDUCATED SPECULATION:
This is long, so take breaks and have some glucose if necessary! 
First I want to say how I've approached this. In 2020 I realised low blood sugar activate the "stress hormones", and had a sense that my "stress" would be best "managed" through food.
Since 2021 I’ve been reading about the metabolic system, in part RP’s articles and learning from this community, and about the ME/CFS research, feeling like I am only surface level understanding a lot of it, but with this idea that if I get to know the patterns, it will make it easier to recognize what interventions to try, and how to tweak them to fit my specific needs. My approach has always been that the body and brain is smart, and not doing anything dumb, like “limit glucose because it’s afraid of a future episode of hyperglycolosis”.
For a long time now a leading hypothesis for ME/CFS has been that there is something in the metabolic system that isn’t optimal, and that it has to do with the body's ability to break down carbohydrates. With time the research has been able to pinpoint more and more where in the metabolism this issue is occurring.
The Itaconate shunt
Now we know this much:
Something is happening in the Krebs cycle that could explain why carbohydrates are not broken down, and that is called the Itaconate shunt.
I think what the glucose is allowing is a positive shift in the Krebs cycle (which is “the center of carbon metabolism in the human body” - a quote from the last video I am gonna post), away from the Itaconate shunt; and downstream from that positive shift, recovery can begin/resume, and healing can occur.
I'm so deep into the research about ME/CFS now that it's hard to know how available it is to other people. But this is a very short video explaining the Itaconate shunt, that happens (or can happen) in the Krebs cycle after injuries (infection, TBI, vaccine induced, etc), and when it does it could be said to "limit glucose".
Or rather, the Krebs cycle is not able to prioritize the breaking down of carbs and fat, when the Itaconate shunt is happening.
I wasn't able to embed the videos, so just gonna post links:
https://youtu.be/7inKF32vtl8?si=-WlofDsDiUCn9JX2
My thoughts about Stephens hypothesis
I’ll say more about the Itaconate shunt, but first I want to say something about Stephens hypothesis, and why I think he’s onto something with glucose, but I don’t think he understands at all why it’s working - and I am not recommending anyone to trust that high doses are necessary for recovery. I don’t think it is.
Stephen's describe it this way in this talk, from around 28 minutes. From this talk: https://youtu.be/AiyoNM7OT7Y?si=gqthd-LKJkG94ZnX
“that isn't exactly what happens after an injury, but it's close. The brain kind of opens up the valve from your body to let more glucose in, so there's enough fuel to respond to that situation. So you have enough energy in your brain to fight or flee or even to just freeze and pay attention to what is going on around you.
When that happens the brain gets too much glucose, it comes in too fast, and that causes a condition called hyperglycolosis, meaning your brain is getting too much glucose, too fast. If that continuous for any length of time that becomes dangerous, so what the brain will do is like it turns the valve down to limit the amount of glucose coming in. It does it in the moment, and that turns off the hyperglycolosis, but it also does this permanently, because the brain wants to prevent a future episode of hyperglycolosis.”
His hypothesis is this idea that the brain “let’s glucose in”, and with every glucose limiting events will “let in” less and less. In my opinion he has created a hypothesis that is just educational speculation (a lot of it is correct, but a lot of it is not), and I think his hypothesis shows that he doesn’t understand the metabolic system very well.
It’s a hypothesis that is very “brain alone”, and it seems to miss that hypoglycemia is very common in all of the diagnosis he is treating - which is important because too much glucose can make that worse.
Hypoglycemia
If you’re not (or have at no point been) testing blood glucose levels, it’s important to know if that’s a likely issue for you. Do a search about your diagnosis and/or your symptoms! And if you have hypoglycemia and you’re not finding relief or having more symptoms on high doses, I would warmly recommend you explore lower doses, or at least test your BG to see what's going on.
The Itaconate shunt is not mentioned on Stephens homepage. A lot of the references and research is old or very old, and describes things that will happen downstream from the Itaconate shunt. I think he's done a good effort, but not quite found the mechanism he was looking for.
Which isn't super surprising, as I think ME/CFS researchers are closer to understanding this than most, and I get that he’s not updated on ME/CFS research, because ME/CFS has been psycologized for so long and isn't thought of as a neurological disorder. I think for that reason the amazing research that is happening isn’t given attention in any mainstream publications. It’s also not being funded enough; if it was, I think these researchers would already know more about how to treat the Itaconate shunt.
The ME hypothesis
The ME hypothesis about Itaconate shunt is similar, but still very different.
I’ll repeat it, in case people are still trying to wrap their head around this: The hypothesis is that there is something happening in the Krebs cycle that doesn’t allow the breakdown of fat and carbohydrates to occur as it should. That includes disaccharides like sucrose, but that’s likely better than complex carbs, with lots of fiber; meaning you might be able to have a similar result with something other than glucose, but why would you? You would likely need to supplement something to support the system, like B1. But, why would you.
When the Krebs cycle doesn't work as intended the production of ATP is also severely stunted. In fact, the Itaconate shunt uses ATP. You will also end up with a lot of lactate; which explain why ME/CFS patients have very high levels of lactate in the blood.
As long as we’re alive the Itaconate shunt isn’t complete/the Krebs cycle still works a little, and from what I understand it can fluctuate, which explain why many of us can have better or even really good weeks, days and moments, even if the Itaconate shunt is happening most of the time.
In case it isn't clear:
My hypothesis is that when you supplement with pure glucose, Itaconate shunt doesn’t happen anymore, and the Krebs cycle can function appropriately again!
My experience is you don't need a high dose for that to happen, you need a sufficient dose, consistently - but consistently just means quite often, or even "when your blood sugar starts to fall". Most of us will know when that happens.
Some of my guesses as to why glucose hasn’t been tested large scale (or small scale) is
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That most of the research I’ve read about TBI’s (traumatic brain injuries) the bigger fear is hyperglycemia.
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Who will fund it? It's food, not a patented medication.
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Because PUFA and fear of sugar means most people’s metabolism doesn’t work great to begin with, and more glucose alone can make their bodies more deficient, faster.
Someone who hasn’t started healing their metabolism will likely have a very different reaction to trying glucose than I have had. The reason I stopped having sugar, the first time I did was in 2011, was because sugar was exacerbating my symptoms. It could have been because of the way I was eating, but it could have been because I was still in the unstable/toxic stage after an injury.
A more detailed look at the Itaconate shunt
For anyone interested in a deeper explanation about the hypothesis, here’s is a more detailed video.
https://youtu.be/RiVDNhg4l48?si=jPHmXSc940nYMh03
If you start watching this one, and then start to think it’s too confusing, there’s some clarifications around 30 minutes that are helpful. I still haven’t watched the last 20 minutes or so, but my sense is you can jump to 30minutes if the first 30 is too detailed.
This video talks more about the Itaconate shunt, the how and why the brain is limiting fuel after an accident. I don't think anyone knows yet why it gets stuck in this shunt. I have some hypothesis' about what can happen downstream to make the it increasingly harder to get out of the loop though. My sense is these loops may vary between us, and be dependent on, or affected by, the imbalances already active in our specific body.
One hypothesis is that digestion is not prioritized during the shunt. When digestion is shut down, the gut won’t break down carbohydrates as much, and when that happens most people are recommended to eat more complex carbs, and avoid white sugar. With this, even less glucose will be available for the Krebs cycle.
The Ray Peat of it all
I’ve already said I don’t think Peat understood ME/CFS. But I hope he would be excited to learn about the Itaconate shunt, because it clarifies things he knew (the GABA system he mentions might be the Krebs cycle?), and personally I think the ME/CFS research goes well with a RP approach to the metabolism.
I looked up some of the things that can be an issue when the Itaconate shun happens. Some of the search words/key ideas I used was B1/Thiamine deficency, GABA, glutamate, ammonia. And on glutamate I found this, from Peat: https://bioenergetic.life/?q=Glutamate: (I’ve added some comments, that may help clarify why I think this is relevant.)
This one: kmud-190315-viruses, from 00.35:
00:35:04.160 --> 00:35:06.160
Listener:
Hi, I'm from Arizona.
Thanks for the show, Andrew and Dr. Peat.
Dr. Peat, your article on immunodeficiency mentions the autoantibodies several times.
Glutamate is an excitatory amino acid and glutamate decarboxylates the enzyme that turns glutamate into GABA which is associated with relaxation somehow.
My question is about how some people have autoantibodies to this enzyme and these are associated with type 1 diabetes and stiff man syndrome.
I was wondering if you had any comments on the system and how does gamma hydroxybutyrate and/or passion fruit juice influence the autoantibodies in GABA?
Ray Peat:
I think the energy system should be able to use the antibodies to clean out the defective enzymes and not continue to be produced.
I think supporting the GABA system with magnesium, glucose, carbon dioxide, anti-inflammatory things,
the pro-GABA steroids derived from progesterone in particular, and the anti-immune steroid DHEA which helps to redirect the antibody production.
Estrogen tends to make us overproduce antibodies but not be able to guide the correction process.
So things that shift the whole physiology towards oxidation and the relaxed, highly energized state of the cell.
I think that's the route out of all of those autoimmune diseases.
Listener:
Do you have any comments on people who have adverse childhood experiences and physical injuries?
I had a head injury 20 years ago.
Ray Peat:
Those same things, the things that increase stability and energy production and carbon dioxide production, all of those are constantly causing cells to be born and differentiate in the right direction.
Listener:
Last question, is there any use for GABA supplementation?
Ray Peat:
Normally it doesn't get into the brain because of the so-called blood-brain barrier,
but when the brain is very injured it is taken up because basically the brain needs it.
But ordinarily I think it's enough just to eat a pro-oxidative diet, avoid the excess of phosphate, lactic acid, iron and so on.
I’ll dissect this more if anyone is interested, because I think we’re finding signs of an Itaconcate shunt here (or seeing stuff that will be an issue downstream, when the Itaconate shunt is happening).
I am already supplementing some of the things he’s suggestion: magnesium, glucose. I also think B1 is helpful here, in the recovery phase, but I only take a normal dose. The other stuff I think falls into place when the Krebs cycle is functioning as intended.
The HPA Axis
I've already posted this hypothesis research, but I want to say something more about it, so here it is again.
Hypocortisolemic ASIA: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1422940/full?fbclid=IwZXh0bgNhZW0CMTAAAR1C5hdVFRydpUViXaHE4EZUGwIAZzeoKvpIBz-3UyI9i4hNcVNFVjlP1CM_aem_98genhg2EQxnqVdoeUCZ9w
Then don't mention the Itaconate shunt, which is especially surprising, because it could explain something they do mention: "A developmental model is postulated that involves the interaction between immune hyperactivation, autoimmune hypophysitis or pituitary hypophysitis, and immune depletion."
Antibodies are also mentioned. This theory can probably be used for other neurological diagnosis, as there are overlapping findings in the HPA axis. I am thinking the things mentioned in this article may be a side effect of the shunt, and/or autoimmune symptoms that are just coming from not enough fuel to the HPA axis. That will leave us with a lot of hormonal imbalances, that can explain a long list of symptoms.
If you think you have a “glucose limitation” look up the hormones produces in the hypothalamus, pituitary gland and adrenals, and you might find the explanation for your weird symptoms.
The importance of enough nutrient dense food, while supplementing
I’m gonna end by saying that I think it’s very important to eat enough while supplementing glucose. Like sucrose, glucose is empty calories, meaning they don't contain any nutrients. If you are gaining weight on glucose you are likely not having enough nutrient dense food, or not enough calories overall. (Or too much glucose.)
I notice it myself, but even my very healthy best friend, who is doing 3x4 tbsp a day because he has some small stuff he would like to heal, notices that he needs more/more nutrient dense food to avoid “crashing” after activity. When he eats enough though, the small stuff is healed and he feels great.
My thinking is that when the Krebs cycle works better, having more carbs with nutrients will be better than having loads of glucose, and I can already have more starches!
I am guessing that with hypoglycemia there’s often less ability to store glucose. I think maybe the liver (and body overall) will store fat instead, when it’s not able to store glycogen (or doesn't have any extra glucose to store?
Which is another reason I think taking big doses won’t be helpful: I don’t think the body is able to store the extra glucose well - yet. That will change with time I think, because if the liver is storing fat it will start to release it and store glucose instead.
All in all I think with time both my bestie and I will become more resilient, and have more flexibility around this; like being able to skip a meal with no problems, because the body’s ability to store glycogen will get better when the Krebs cycle works as intended. But I consider the next many months (at least 6) as a recovery period, where I will prioritize rest and gradually build strength, when I feel the body is ready. Already seeing some nice improvements, so I am hopeful!
Just to repeat, in case someone is wondering, so you don't have to go looking: I take 12-14 tbsp a day, approximately every hour. I might need less over time? I take it with salt, and I take cream of tartar for potassium. I mostly go on gut feeling for both.
I also take oyster powder and liver capsules, because I can't get that fresh and good quality. I also supplement magnesium bisglycinate, b1, vitamin d and k2. All of these I supplement because of symptoms, but I might not need to continue if the Krebs cycle work better.
