Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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Significant improvement in quality of life by hacking glucose metabolism

Discussion in 'General Treatment' started by sb4, Nov 20, 2018.

  1. sb4

    sb4 Senior Member

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    For the longest time I have been in a bit of a catch22. If I eat high carbs my heart pounding (my worst symptom) and POTS in general increases significantly yet my gastroparesis doesn't cause much issue. If I eat low carb high fat my post meal POTS / heart pounding is fairly minimal however my gastroparesis flares up significantly.

    I have, for the longest time, been trying things to improve my glucose tolerance or improve my gut motility, to make one of these diets work, with only modest success. Methylation/b-vits helped, as did other things but nothing to write home about until now.

    For the last 4 days now I have been taking 1/2-1tbsp of MCT oil (C8) with my morning high carb meal. I have been having this meal for a couple of months now every morning and it is around 150g carbs (potatoes) with a little butter and cheese. For the longest time, like clockwork, after eating carbs I experience heart pounding and other pots symptoms starting soon after finishing the meal and climbing until about 1hr postprandial where it reaches its peak, stays there until 1.5/2hrs post and slowly climbs back down to base line over the next couple of hours.

    With MCT oil however, I experience heart pounding etc after meal finished up to 1hr increasing, however it is noticeably more mild than before. When it gets to roughly 1hr my heart symptoms decline to near baseline and stay that way. I have only been doing this for 4 days at breakfast only and the result has been the same every day, giving me the confidence to post this thread this early in.

    The theory is that something is going wrong with my glucose metabolism. MCTs are oxidized preferentially over glucose. So what I think could be happening is say I have a problem with pyruvate dehydrogenase. When I eat carbs, glucose is delivered to the cell, it goes down the glycolytic pathways to get to PDH where it should be providing the acetyl CoA for TCA to make the energy the cell needs. However, only some gets through so now the cell doesn't have enough energy entering the mito as insulin is suppressing the fat getting to the cell and so it has to make lactic acid to provide the energy. This causes cells / organs / heart to struggle with even basic at rest energy demands and causes the negative symptoms I experience.

    With MCTs however, the liver receives glucose and the medium chain triglycerides at the same time. The liver will always give preference to mcts over glucose. So the liver breaks down the 8 carbon fat into a bunch of acetyl CoA. Which then enters the TCA cycle instead of glucose (through PDH). Now the liver has an oversupply of acetyl CoA and a deficit of oxaloacetate, so all the glucose theoretically should go into providing oxaloacetate to allow the TCA cycle to keep spinning. This avoids PDH having to be used.

    I am not entirely sure that this is the mechanism at play as I have tried sodium dichloroacetate which should activate PDH without success, as well as PDH cofactors (ALA, Mg, NAD/FAD, Allithiamine) with only mild success.

    The video below looks at a study where people ate 300g pasta, 100g tomato sauce with 3tbsps of MCT and they achieved a blood level of beta hydroxybutyrate of 0.3. Mild to moderate ketosis is 0.5-1.5, after a normal glucose meal it is near 0, and normal overnight fast is something like 0.02. So it is providing much more ketones than does overnight fast and is having the oposite effect on ketones as does a glucose based meal.

    To enter ketogenesis you most have low oxaloacetate compared to high acetyl CoA. Then the liver sticks 2 acetylcoa together to make ketone bodies that can be used by the brain. Since MCTs can only provide acetyl CoA, this means that once liver glycogen is full, all the ingested carbs alongside MCTs, provided you are making bHB, most be going to oxaloacetate, right? This would completely bypass the need to use PDH.

    Here is the video in question. Note that high doses of MCT along with carbohdrate meals are given to epilectic kids, who have to be in ketosis all the time, and it proforms very similar to a keto diet. This could be useful for those of you who have found keto helps @leokitten if you wanted to add more viarety to your diet or just to test if it works.



    Any thoughs anyone? @Hip @nanonug @Learner1
     
  2. ryan31337

    ryan31337 Senior Member

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    Hi @sb4,

    I think we might have discussed this before, but another much simpler explanation is that you experience rapid gastric emptying, which is slowed by consuming fat. Your postprandial symptoms seem compatible with that and your experience of gastroparesis when taking it to the extremes of VLCHF would seem to fit a gastric dysmotility picture too.

    Adding oils to every meal is one of the interventions for rapid emptying that was recommended by a neurogastroenterology prof that I've seen. He recognises this dumping in POTS/hypermobile community as a frequent issue.

    Perhaps he has an overly simple view of the mechanisms at play, but Occam's razor and all...

    Ryan
     
  3. sb4

    sb4 Senior Member

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    Yeah I still don't think it's that @ryan31337 although I could be wrong. If I eat fat and carbs I still get the same heart pounding symptoms. They maybe more drawn out as fat slows the stomach emptying but they are definitely there and significant.
     
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  4. Learner1

    Learner1 Forum Support Assistant

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    Random things that come to mind are:
    • High fat + high carbs does not seem to be beneficial over the long haul. You can choose high fat or high carb, but not both together. I understand the experimentation you're doing to figure out how to make one or the other work. If I were in your shoes I'd be targeting a lower carb high fiber antinflammatory diet. But how to get there...
    • Have you tried digestive enzymes? If so, have you tried different blends to optimize digestion of carbs or fat?
    • Do you have "leaky gut" which is promoting food intolerances/allergies as partially digested food makes it into your bloodstream? Supporting gut lining with glycine and/or glutamine may help, and an elimination diet or complete food allergy testing from US Biotek or Cyrex Labs may help you determine what you may be reacting to. The Food Intolerance Bible by Anthony Hayne is a wonderful resource.
    • Have you had free and total carnitine checked? It's needed to help with fats in mitochondria?
    • Have you tried pantothenic acid, biotin thiamine or riboflavin? https://lpi.oregonstate.edu/mic/vitamins/pantothenic-acid https://www.slideshare.net/sihamgritly/7-vitamins-and-cofactors
    Best wishes...
     
  5. sb4

    sb4 Senior Member

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    I am definitely in agreement that picking either high carb or high fat is the way to go in most cases but my case is very unique. I think if a high fat high carb diet allows me to avoid my 2 worst symptoms which no doubt were causing my body considerable stress, then it is the lesser of 2 evils. Although having said that this doesn't necessarily need to be a high fat diet. If I can 200g carbs 3tbsp mct (40g fat) x2 a day then I will be at 800kcal fat 1600 carbs.

    Yeah I have tried a bunch of different brands and they do help a bit. This was only really notiacable when I was really bad though.

    I suspect I do to some extent but I am saving my pounds sterling for other potential things. Will keep it in mind for the future though.

    I see where you are coming from here but I am not sure it is an issue. I seem to be able to burn fats without too much trouble and have tried both acetyl carnitine and fumarate versions without noticing anything.

    Yeah I am taking all of them currently and have taken biotin in the past. The definitely do help but not as much as MCT has so far!
     
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  6. Learner1

    Learner1 Forum Support Assistant

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    How much pantothenic acid, biotin, thiamine or riboflavin are you taking? My doctor has me on 1.5-2g of Thorne Pantethine, 500mg benfotiamine, and 250mg R5P.

    Food intolerances might be a worthwhile investigation. The book I recommended is cheap...

    Glycine might be useful.

    Keep us posted, ok? And good luck.
     
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  7. sb4

    sb4 Senior Member

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    Thanks Learner1.

    I am on 50mg Allithiamine although I have in the past gone up to 800mg. Riboflavin 25mg sublingual as FMN. The others in activated B-Complex.

    I am taking glycine at various doses throughout the day though have found it makes me very sleepy. It does seem to help glucose tolerance.
     
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  8. Learner1

    Learner1 Forum Support Assistant

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    The vitamins all work together. If you are short of one, it bottlenecks the whole process.

    I take 4.5g glycine before bed each night. Great for sleep!
     
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  9. gregh286

    gregh286 Senior Member

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    Boom.....what a post and another leap forward understanding of poor glucose burn and the oxidative stress it putting on our body.
    I had an episode a few weeks ago of quite a few baileys cream (a highly sugary alcoholihc drink). I worked out I had about 100g of sugar in about 90 mins.
    Hard started to pump real hard...normally I'm 60 bpm. Rise to 130 or so for about 2 hours. Wasnt adrenaline or anything I was sat there calm as you like. Dropped about 1200mg ala with 500mg thiamine brought it down pretty rapidly then. I know the pdh was partially blocked for it to happen and returned to baseline quickly.
    I wrote a post I'm outta here a few back and still maintain excellent function but sugar is so demonic to us its unbelievable and still I need go use ala and.glutamine lots to control my cfs.
    Can you not just little carb with each meal? Will avoid heart pounding and gastro?
    The MCT oil is great idea....did you try upping dose?
     
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  10. sb4

    sb4 Senior Member

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    @gregh286 Thanks, yeah the carbs I eat and the heart/POTS symptoms I recieve are proportional. Although I think even a little sets me over a bit of a tipping point.

    That is what I was doing before, lowish carb high fat and just dealing with the gastroparesis and heart stuff.

    I have tried upping the dose but got slight diarrhea so I have backed off a little. The situation I am in now is I still recieve heart stuff up to an hr after the meal but then I feel good. I am currently trying a small dose before meal to try to eliminate the remaining symptoms. I also plan on trying emulsified MCT in hopes for quicker absorption and less chance of diarrhea, and exogenous ketones although I don't think these will work as well as MCT for multiple reasons.
     
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  11. gregh286

    gregh286 Senior Member

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    Yea I noticed in the video they got 43g of MCT over the pasta. Thought that was quite a lot actually.
    Yea my diet has changed quite a lot and I have a strong palette so can mix and mash pretty well. Breakfast is eggs...smoked salmon and olives. Yoghurt for lunch with nuts and dinner is meat and veg...
    Gets a little repetitive unless you're a flamboyant cook with lots of to time creating recipes. Must get MCT oil see how the reaction is.

    Quite a lot of people come across CFs with different triggers but outcome same...poor glucose burn. Lot of.theories around blood cell shapes...CNS...HPA....sticky blood......lipid rafts but are they enough to put people in bed for decades? Doubt it. A broken kerbs cycle however is a different story
     
  12. sb4

    sb4 Senior Member

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    Yeah, 43g sounds is a lot but it's probably achievable. It's 3TBSPs. Highest I have gone is 2tbsps with minimal GI effects although I am eating a larger meal than in the study.
     
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  13. sb4

    sb4 Senior Member

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    I am looking into what sort of FADH2/NADH ratio I will be generating with this sort of diet as I believe it is very important in terms of insulin sensitivity and allowing for clear signalling in terms of metabolism based on Peter@hyperlipids work.

    Basically, when it comes to insulin resistance, a ratio of 0.48 FADH2/NADH and above seems to produce significant insulin resistance. This means C16 (palmitic acid) and above saturate fatty acids produce insulin resistance and lots of ROS. This is good as if you are eating a high saturated fat diet you want your cells to be relatively insulin resistant so only minimal glucose will be up taken and it will go to the tissues that need it the most. The ROS signals insulin resistance. You will be burning fat and producing little insulin which probably is why lots of people have success with ketogenic diet and weight loss; through good signaling of cells energy levels.

    If you are eating very high glucose (not fructose) on the other hand, then I think glucose has a FADH2/NADH ratio of around 0.2. Either way it is a lot smaller meaning a lot less ROS generation and thus a lot more insulin sensitivity, meaning you need a lot less insulin to take up glucose and thus low insulin means good cell signalling according to the theory.

    If you eat a mixed meal however then your FADH2/NADH ratio will be somewhere in the middle and you will be generating significant reverse electron flow causing significant ROS meaning you cells will be somewhat insulin resistant in the face of high BG meaning more insulin needs to be released meaning poor cell signalling if your metabolism is compromised for whatever reason. This is why people can do really well, metabolism wise, on a very high carb very low fat diet, or very low carb very high fat diet, but not on a mixed one.

    Now if we look at exogenous ketones, if I have got this right then bHB generates 1 NADH in it's conversion to 2 acetylCoA. The 2 acetyl CoA then go on to produce 6 NADH and 2 FADH. So bHB has a ratio of 0.28. This would explain why the brains can use ketones for energy but not fatty acids. The brain needs to keep ROS very low as the brain cells are a lot more important than regular cells and cannot be regenerated. If it used fats it's mitochondria would produce a lot of reverse electron flow generating a lot of ROS. As ketones produce a low amount of reverse electron flow due to a lot more NADH entering complex 1, and a lot less FADH2 entering complex 2, then the brain can use ketones with minimal ROS generation.

    Now if there is high blood ketones and high blood glucose at the same time, how does the cell signal it has enough energy? If I remember right excess glucose in a cell eventually starts getting in at complex 2 generating REF. Perhaps the mechanism is same here.

    Now if we look at MCTs are specifically Caprylic Acid (C8). If peter is to be believed then this has a ratio of 0.47 and does not trigger high RET whereas palmitic at 0.48 does. Lets see where that ratio of .47 came from. The 8 carbons of Caprylic acid need to be shortened down to 4, 2 carbon actyl CoAs. This means it needs to be "cut" 3 times and each time it is cut it generates 1 FADH2 and 1 NADH. Each of the 4 acetyl CoAs generated 1 FADH2 and 3 NADH in the TCA cycle. So per C8 we get 7 FADH2 and 15 NADH which is a ratio of 0.4666 which rounded up is 4.7.

    So if I eat 3 high carb meals I would probably need to have MCT as my only fat and have it lower than 15-20% of calories to keep my cells fairly insulin sensitive based on what I have learned from other sources. For an 800kcal meal this would be 120-160kcal from C8 so 1 to 1 and 1/3tbsps. This would need to balance out up to 150g carbs. I don't think that would be enough to appreciably reduce symptoms however if exogenous ketones can also reduce symptoms then perhaps this could be enough due to bHB low ratio.

    I am not sure if exogenous ketones will work as I think a big part of this is the fact the C8 is supplying lots of acetyl Coa to my liver meaning glucose has to go through oxaloacetate instead. With exogenous ketones however, the liver doesn't use them at all and I am not sure how willing cells other than the brain are to use them. So I suspect exogenous bHB alone will still give me symptoms as my cells will still be using PDH. In combination however...
     
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  14. SherDa

    SherDa

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    I thought medium chain fats weren't stored but instead are burned right away and that's why it's okay to have them at the same time as carbohydrates?
     
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  15. sb4

    sb4 Senior Member

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    Yeah thats pretty much right. What happens when you eat normal long chain fats is they absorb through your intestines into the lymphatic vein that runs to your heart where they enter the bloodstream. If your insulin is high because you also ate carbs then the fat goes from the blood into your fat cells where it is stored.
    If you eat MCTs however they get absorbed through your stomach into your portal vein which goes straight to the liver. The liver then starts metabolising the MCTs and in doing so turns them into ketones which then go out into the blood to be used for energy. However, if the cell in question is "full" of energy it can take the ketones/acetyl CoA and change it back into fat for storage.
    The difference here is that long chain fat gets stored instantly (obviously simplifying a lot here) wheres mcts get used for energy first and only if the cell has too much energy would it be stored as fat.
     
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  16. sb4

    sb4 Senior Member

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    Does anyone know how readily tissues other than the brain take up and use ketones. I have heard it's mainly the brain and other tissues are fairly resistant to them. This would make sense as ketones are somewhat expensive to make and will probably be only used by tissues that can't survive without glucose.
     
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  17. leokitten

    leokitten Senior Member

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    From my past readings on the subject and personal experience (with blood measurements) all bodily tissues will readily switch and are happy to solely use ketones, except the brain, which can meet approx 70% energy requirements from ketones.

    Homo sapiens evolved going days between meals all the time, so we have very highly evolved mechanisms to fully function only on body fat.
     
    Last edited: Dec 1, 2018
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  18. leokitten

    leokitten Senior Member

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    That being said like you mentioned if your blood glucose is high enough then insulin will prevent fats from being made into ketones.

    I’ve found that even having a ketone level of 1.5 mmol/L is not enough energy for me, I will feel somewhat better but not until it gets > 2 or a GKI < 2.5 does my metabolism start working well again and the broken aerobic glycolysis pathway get circumvented enough to make me feel significantly better.
     
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  19. leokitten

    leokitten Senior Member

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  20. sb4

    sb4 Senior Member

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    Yeah I have heard that you should eat vegetables with high long chain fat as like you say, the high fat increases inflammatory effects of the immune system and short chains (created by bacteria for veg) reduce that inflammation.

    In my reading I found that MCTs can potentially cause allergies and increase Th2 although I think this is from oral consumption as the effects happen in the intestines. It was recommended to take away from food but that obviously can cause GI issues.

    If I were you @leokitten I would purchase some regular MCT oil and use it transdermally with your normal keto meals and see what effects. If no or minimal sides then progress to using it with some carbs. I would cup my hand and poor some in my hand then apply it to my skin 3/4 times, which is probably equal to 6-7tbsps. I apply it to my torso and face and sit shirtless for a good 6hrs. Apply it 15-30mins before eating. I would also buy some C8 (in my very limited experience C6/8/10/12 containing ones cause worse GI response) and take 1/2tbsp at first but see how far you can build up to over the coming weeks, assuming of course, that it has helped you.

    I am still tinkering with this at the moment as I am experiencing a little too fast GI. I think the thing with MCT is, even small amounts can cause big symptoms. You may not need as much as me however as I am eating like 200g carbs in my morning meal, with some butter and cheese, and then a fairly low carb evening meal.

    If you just do 100g carbs +MCT like once or twice a week you may be filling up some nutritional deficiencies that you might be encountering on the keto diet. Hopefully if this is true it will stop your urge for carbs followed by a crash, but there is a lot of if's and but's before then. I choose potatoes because they are nutrient dense, particularly in magnesium and potassium which I find hard to get on keto. Also I have a weird thing going on with me where I have an aversion to salt despite having POTS and high salt does me no favours. I seem to crave foods with higher Mg and K.
     
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