Choline on the Brain? A Guide to Choline in Chronic Fatigue Syndrome
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Why is ME energy-related symptomatology so different from diabetes?

Discussion in 'General ME/CFS Discussion' started by leokitten, Dec 3, 2018.

  1. leokitten

    leokitten Senior Member

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    I want to open a discussion related to a question I’ve asked myself recently and been too exhausted to research and dig deeper:

    If ME involves a block, or major reduction, of aerobic glycolysis in the mitochondria (via PDH inhibition or related), and diabetes involves resistance to insulin outside the cell reducing glucose from entering the cell, then why don’t PwME have high blood glucose**? Why do people with diabetes not have even close to the symptoms and immense disability we get very quickly with this disease?

    From my understanding, most people with diabetes do not even know they’ve been living with it for years until they see a doctor and find blood glucose levels well above 200, or they go because they get their first diabetes related symptom. So you can see it’s very different from ME because you don’t really have any clinical symptoms for a long time yet your body is completely resistant to glucose.

    ** I believe one Aussie ME research group found that PwME have elevated fasting blood glucose compared to healthy controls, though we are still at the top end of the normal range.

    It’s also consistent with my own blood glucose tests over the ME years and more recent home blood measurements (when not doing keto), elevated but doctor never thought abnormal because usually below, and sometimes at, 100.

    Its been this way since my first doctors appointment and blood work 1 1/2 months after getting ME (and not knowing what it was or what was going on). I was still very much in great athletic shape at the time and was at ideal weight, so can definitely rule out other causes.

    I also think this might put PwME at slightly higher risk of eventually getting diabetes in the future compared to healthy controls.
     
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  2. Art Vandelay

    Art Vandelay Senior Member

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    A specialist I saw a very long time ago believed that insulin resistance was common in ME/CFS.

    Did you have your insulin levels tested as well? He argued you needed to test insulin levels tested alongside glucose levels with glucose tolerance tests to get a better idea as to what was going on.

    My results showed that while my glucose levels weren't too bad, I had to produce a lot insulin (well above the normal range expected in a GTT) in order to keep my blood glucose under control. He told me he found this often in the ME patients he tested.

    It was on this evidence that he diagnosed me with insulin resistance. I've been on a very low carb diet ever since and it has helped a lot (although it's not the magic bullet for me unfortunately).

    For what it's worth, this is his website but he hasn't updated it in a very long time: http://www.agale.com.au/IR.htm
     
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  3. leokitten

    leokitten Senior Member

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    @Art Vandelay thanks for the info, one of my OP questions is though, why do we get so many symptoms that are so intense and these symptoms are so disabling pretty much from the get go? A little insulin resistance will not cause such life devastating energy production problems, not even full blown diabetes will do that even after having it for a few years.

    I believe there is this ME disease process inhibiting aerobic glycolysis that eventually, as a side effect, will cause some insulin resistance. At first with ME you aren’t resistant, you just can’t use glucose in mito, and your body starts eventually pumping out more insulin thinking it’s having trouble gettting glucose into cell when in fact it’s jusf not getting used well.. Then after a couple years of that as a side effect your cells do start becoming insulin resistant.

    While your doctor saw that and told you to go low carb to treat it which is a good thing, he or she didn’t further examine the possible causes. If you were healthy and changed your diet to low carb, after doing it a year let’s say you should be able to start eating regular amount of carbs again for a short while before the test, then do that test again and it would show that your insulin resistance would be gone or far reduced. I don’t think that would happen with a PwME even after a year or more of low carb, and it shows it’s not our lifestyle that got us insulin resistant, but something else.
     
    Last edited: Dec 4, 2018
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  4. Art Vandelay

    Art Vandelay Senior Member

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    I agree! Whatever that 'something else' is is the million dollar question I guess.

    My money's on the 'smouldering infection' theory (I can't recall which researcher was using this expression most recently but it was most likely someone from Monash/Melbourne. It might be Mark Guthridge perhaps).
     
    Last edited: Dec 4, 2018
  5. Crux

    Crux Senior Member

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    My belief is that iron dyshomeostasis is at least an aspect of ME/CFS, as well as other neurodegenerative diseases. I also believe that ME/CFS is a neurodegenerative disease.

    Unfortunately, blood tests and iron panels may not predict where iron is accumulating, and where it may be deficient in tissues and organs.

    Pathogens have a particular affinity for iron, so much of the fatigue experienced may also be from infections, and the body's efforts to inhibit them.

    Iron dyshomeostasis is also associated with insulin resistance and diabetes.

    Here's an article about iron, diabetes, and Alzheimer's disease:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133192/
     
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  6. alex3619

    alex3619 Senior Member

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    There was a paper recently, I cannot recall its name, that indicated type two diabetes was at least five different diseases.

    I think it possible ME is a sixth type, with vastly different initiating chemistry. There are probably more types. Type 2 diabetes is most likely a hodgepodge of many things with similar final stage glucose chemistry.

    Our shunt of glucose metabolism away from mitochondria into lactate metabolism is similar to what the popular diabetes drug, Metformin, does.

    We also have an energy metabolism ceiling. The problem with us is that an extra glucose will be shunted off to the liver, as lactate, for processing. I am still unclear what this will lead to, but suspect this includes fatty liver. Our one thing that has been shown as glucose absorption resistance during exercise, is really about our ceiling effect.
     
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  7. Learner1

    Learner1 Forum Support Assistant

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    I don't have a glucose problem now that the infrctions I'd had were treated. I've also been on a lower carb, high fat, high protein diet for several years.

    I do have heriditary hemochromatosis which had been missed for quite awhile as everyone thought my elevated serum ferritin was as an acute phase reactant due to my multiple infections. I am heterozygous for 2 of the HFE SNPs and not homozygous for the main one so my serum ferritin wasn't over 1,000 as some patients are, but 605 before treating the infections, but still 275 after treating them. Curious, I dug up.5 years worth of iron panels and found It had the same weird pattern of low TIBC and UIBC and high serum iron and iron saturation - my saturation was 74% at one point.

    The conventional books will give stories of eventual multiple organ failure. From what I've gleaned, I believe this is because there are Fenton reactions going on in the mitochondria, damaging them, and it seems to be contributing to my poor mitochondrial function, in addition to the peroxynitrites which were already damaging them.

    So, for me, part of the answer is to get iron panels done regularly and have blood and the extra iron removed at certain intervals (between 3 weeks and 3 months). My doctors try to keep my serum ferritin between 60 and 100, over 60 is needed for mitichondria to work properly.

    The other part is to repair the damage by discouraging peroxynitrite formation, then replenishing mitochondrial membranes with phospholipids, while providong the nutrients needed for the mitochondria to work. These include carnitine, MitoQ, riboflavin, and other nutrients like folate, B12, and branched chain amino acids.

    Increased aerobic glycolysis has only been found in subsets of ME/CFS patients, not all. As a cancer survivor, this worries me, as glycolysis feeds cancer, and in cancer, it is helpful to increase OXPHOS, which helps the good cells, but damaged the cancer cells. Hypoxia has been found in chronic diseases, particularly if we have thick, viscous blood, which is why oxygen therapies like hyperbaric oxygen can be helpful.

    And then there are strategies to increase numbers of mitochondria, like exercise to one's tolerance and PQQ. I've found my ability to exercise has increased through these strategies, taking replacement hydro cortisone as well as glutathione, BCAAs and NAD+ (not nicotinamide riboside).
     
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  8. Crux

    Crux Senior Member

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    It's great @Learner1 , that you are managing hemochromatosis, and finding ways to regulate iron metabolism.

    Unfortunately, most people with neurodegenerative diseases don't present with elevated iron in serum, elevated ferritin,elevated transferrin saturation, and low TIBC,UIBC. Not everyone with hemochromatosis has increased brain iron deposition either.

    There are also iron loading conditions, such as aceruloplasminemia that present with anemia. These patients have accumulation of iron in the brain.

    Excess brain iron is also found in Parkinson's disease and MS. Most of these patients also experience fatigue. Susceptibility to infections has been noted.

    Researchers are only beginning to find more iron loading genes, but meanwhile, it seems to me that it's really important to research iron metabolism and regulation, especially with this epidemic of dementia we're having.

    Also, since iron dyshomeostasis is a suspect in a multitude of diseases, I question the safety of mandated iron fortification of flour.

    I just wish that some of this excess brain iron deposition would be searched in ME/CFS, but it's expensive, requires certain types of MRI specialists, and more that I don't really know about.
     
  9. jesse's mom

    jesse's mom Senior Member

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    Right?!
     
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  10. Learner1

    Learner1 Forum Support Assistant

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    Flour can be problematic for many reasons...:depressed:
     
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  11. Kenshin

    Kenshin Senior Member

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    My Ferritin was over 1000 when I was malnourished. It was not due to infection, it eventually went normal after regaining weight, I don't have both genes to be susceptable to hemochromatosis, but it is interesting that there are other iron disorders.
     
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  12. Wishful

    Wishful Senior Member

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    As Learner1 mentioned, not all PWME have reduced aerobic glycosis. My guess is that it's a common secondary effect of ME. The mitochondria in my muscles seem to be doing just fine. Cerebral ones, not so sure...
     
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  13. Crux

    Crux Senior Member

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    I also believe this is happening, and causing fatigue. With the Fenton reaction, iron reacts with peroxides, forming free radicals and inflammation, basically.

    Lately I've been rinsing my mouth with hydrogen peroxide because it seems to inhibit infection better than anything. However, the side effect is a bit of neuropathy in my feet.

    I suspect peroxynitrites are being formed. In diabetes there looks to be an elevated state of this free radical.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321249/
     
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  14. Learner1

    Learner1 Forum Support Assistant

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    I had tried this too, before I learned there is an oral microbiome, and just like with the gut microbiome, an imbalance or deficit or overgrowth of certain strains have been linked to a wide range of diseases, like preeclampsia in pregnancy, cardiovascular problems, non-alcoholic fatty liver disease, etc.

    I switched to a tea tree oil non-fluoride toothpaste a while back and use a natural mouthwash. Its still a new science, so there are no prescriptive answers, but something worth considering...
     
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  15. kangaSue

    kangaSue Senior Member

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  16. Hip

    Hip Senior Member

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    I should think ME/CFS patients don't in general have high blood glucose because blood glucose is regulated by sensors that keep blood sugar levels within certain bounds, irrespective of glucose supply and demand:
    So even if there might be less demand for glucose in ME/CFS due to blockages in glycolysis, unless something actually goes amiss with the blood glucose level regulating system itself (the beta cells of the pancreas), you will not see glucose abnormalities in ME/CFS.



    As we know, the hormone insulin, secreted by beta cells, controls blood glucose levels by sending a message to the muscles (and the liver) to absorb glucose from the blood and to store it within the muscles. That then removes some glucose from the blood. So when blood glucose goes up, insulin is secreted, and that brings blood glucose levels back down.

    Type 1 diabetes involves too little insulin being produced when it is needed (due to loss of beta cells), so when blood glucose levels go up, the system struggles to bring it down.

    Type 2 diabetes involves the muscles themselves not properly responding to insulin to absorb glucose from the blood (the muscles do not "hear" the message conveyed by insulin), so again the system struggles to bring glucose levels down.

    In either case, the problem is have too much glucose in the blood, rather than a shortage of glucose.


    Diabetic patients can get low blood sugar though if they take too much insulin by mistake: in which case, this shortage of insulin does produce a series of symptoms which includes brain fog:
    However, these symptoms (when mild) are rectified just by consuming additional sugar, such as a sugary chocolate bar or drink.
     
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  17. Wishful

    Wishful Senior Member

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    For those concerned about elevated peroxynitrite, several spices and herbs are strong peroxynitrite scavengers. Cinnamon is one. Google should find the full list. They make my ME symptoms worse.
     
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  18. ljimbo423

    ljimbo423 Senior Member

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    A major difference could be low grade brain inflammation in ME/CFS from activated microglia as Jarred Younger has found.

    I think it's possible that activated microglia are causing fatigue, flu-like symptoms, brain fog etc. in ME/CFS but not diabetes.

    Ron Davis said in one of his videos that the brain is most certainly involved in ME/CFS and I agree.
     
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  19. leokitten

    leokitten Senior Member

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    No offense to @Learner1 but where is the evidence that there are PwME that have normal aerobic glycolysis or more broadly no metabolic abnormalities?

    If I’m not mistaken, the Norwegian study showing impaired aerobic glycolysis and other findings was one of the largest ME cohorts ever studied. Their findings were also more or less corroborated by studies published by Australian and US research groups.

    No one has shown yet that there is a subgroup of people with ME who have no cellular metabolic abnormalities.
     
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  20. Wishful

    Wishful Senior Member

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    I did ask here sometime ago, and a couple of people replied that they lack the muscle impairment, but had other common ME symptoms, so it's not just me. It does sound like a very small subgroup.

    Like me, others have reported being able to lift weights, ride bikes, etc, at the same level as pre-ME. That qualifies as evidence. In proper scientific studies, there may be a bias against people who don't show the muscle impairment (disqualify for the study), or perhaps we're just so rare that we haven't showed up in studies. Maybe in a large study, there's a graph with one point way out from the others, and it just gets dismissed as a measurement error or whatever.

    Just because we haven't been covered in a published paper doesn't mean that we don't exist.
     

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