MS Tied To Glucose Deficiency Due To Endotoxin And Fat, Extra Glucose May Treat It

Discussion in 'Scientific Studies' started by haidut, Jul 16, 2019.

  1. haidut

    haidut Member

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    Just a few days ago I posted the groundbreaking study on metabolic derangement in ALS - i.e. it is a diseased characterized by increased FAO, which wastes glucose. Simply increasing dietary glucose was able to greatly restrain the pathology.
    https://raypeatforum.com/community/threads/als-tied-to-increased-fat-oxidation-fao-increasing-glucose-may-treat-it.29852/
    Well, hot on the heels of that study is the study below, which found very similar pathology in Multiple Sclerosis (MS). According to the study, MS is a state of perceived glucose deficiency, which causes neuronal mitochondria to fuse and become unable to produce energy. The trigger for the fusion and the cause of the energetic blockade are the fatty acid derivatives known as ceramides. The cerebro-spinal fluid (CSF) of MS patients was found to contain very high levels of ceramides. Ceramide synthesis is known to be triggered by activation of the endotoxin receptor TLR4, and ceramides are known to block the oxidation of glucose as well as overall mitochondrial function.

    Ceramide - Wikipedia
    "...Ceramides induce skeletal muscle insulin resistance when synthesized as a result of fatty acid activation of TLR4 receptors.[6] Ceramides induce insulin resistance in many tissues by inhibition of Akt/PKB signaling.[7]Aggregation of LDL cholesterol by ceramide causes LDL retention in arterial walls, leading to atherosclerosis.[8] Ceramides cause endothelial dysfunction by activating protein phosphatase 2 (PP2A).[9] In mitochondria, ceramide suppresses the electron transport chain and induces production of reactive oxygen species."

    So, the cascade of causes for the pathology of MS suddenly seems rather simple when examined from an energetic point of view. No need for Epstein-Barr viral infection, genetic predispositions, or other mysterious unknown causes. What's even more shocking is that the solution to this pathology was also rather simple - simply increase the supply of glucose, the Randle cycle swings in favor of glucose and health is rapidly restored. And for those that prefer more direct interventions, TLR4 antagonists, antibiotics, or even aspirin may target more specific pathways and thus reduce the synthesis of those pesky ceramides.

    metabolic perspective on CSF-mediated neurodegeneration in multiple sclerosis

    "...Treatment of neurons with medium supplemented with ceramides, induced a time-dependent increase of the transcripts levels of specific glucose and lactate transporters, which functionally resulted in progressively increased glucose uptake from the medium. Thus ceramide levels in the CSF of patients with progressive multiple sclerosis not only impaired mitochondrial respiration but also decreased the bioavailability of glucose by increasing its uptake. Importantly the neurotoxic effect of CSF treatment could be rescued by exogenous supplementation with glucose or lactate, presumably to compensate the inefficient fuel utilization. Together these data suggest a condition of ‘virtual hypoglycosis’ induced by the CSF of progressive [MS] patients in cultured neurons and suggest a critical temporal window of intervention for the rescue of the metabolic impairment of neuronal bioenergetics underlying neurodegeneration in multiple sclerosis patients."

    Differences in MS patients' cerebrospinal fluid may be key to drugs that halt progression

    "...The research team delved deeper to determine what was present in the CSF of progressive MS patients that could be causing these mitochondrial changes and, possibly, an increased energy demand. Previous research has indicated that mitochondria elongate in an effort to generate more energy for cells when there is enhanced energetic demand or a decrease in available glucose. The researchers' lipid profiling of the CSF samples revealed that CSF from progressive MS patients had increased levels of ceramides."

    "When we exposed cultured neurons to ceramides, we elicited the same changes caused by exposure to CSF from progressive MS patients, and we further discovered that ceramides induced neuronal damage by acting on two cellular mechanisms," said Maureen Wentling, a research associate in the Casaccia lab and the study's first author. "On one end, ceramides impaired the ability of neurons to make energy by directly damaging the mitochondria. On the other end, they also forced neurons to more rapidly uptake glucose in an attempt to provide energy for the cell." The researchers were able to prevent the neurotoxic effect of CSF on cultured neurons by supplementing glucose. Supplementation isn't a sustainable approach in the diseased brain, however, so a different approach will ultimately be needed for developing therapies that improve mitochondrial function in patients with progressive MS."
     
  2. tca300

    tca300 Member

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    So this might explain why Roy Swank had so much success treating MS with a diet low in Saturated fat. Interesting.
     
  3. kitback

    kitback Member

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    Can someone help me understand how to “simply increase the supply of glucose”? What actual changes can I make in my diet to best accomplish this? More sucrose?

    I have many symptoms of MS and believe this is what I am dealing with. It has been going on for about two years. I have vision loss with blurry vision, double vision, grayed out vision. I have muscle weakness in my legs, balance issues, extreme fatigue and lack of stamina. I was suffering from burning nerve pain in my torso but after reading a study posted by Haidut on the benefits of combining Taurine with T3, that completely eliminated the burning nerve pain.

    Since the conversion of T4 into T3 requires glucose, I suspect this study explains what has been going on with my thyroid. Over the course of the past year, I have seen my temperatures drop from 98.6°F down to the low 97’s and recently 96.2°F. During this period, I have continued taking my thyroid supplements at the same dosage as I have for years, T3 in the morning and T3/T4 at bedtime. I could not understand what was causing this slow but steady decrease in my temperature since there was no change in my thyroid dosage or diet. After reading the above information, I now believe it is due to a glucose deficiency. (And as an unwelcome but not too surprising “side effect” of the decreased thyroid function and slower metabolism, I have slowly gained 13 pounds with no change in diet over the past year.)
     
  4. OP
    haidut

    haidut Member

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    I think this is what the study suggests - i.e. increasing dietary carbs should be beneficial, just as the study on ALS, and the study on ALS did mention a human clinical trial with increased glucose/sugar diet. I think this is the trial they are referring to, so if you Google around you may be able to find exactly how much extra glucose the patients were getting.
    Diet high in calories and carbs could slow ALS progression
     
  5. Kartoffel

    Kartoffel Member

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    Why might this explain his success? Is there any evidence that he had any success?
     
  6. kitback

    kitback Member

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    Thanks Haidut! I found a list of foods highest in glucose on Nutrition Data so that should help. I will check out the other study. I’ll give it a try and report back on my results!
     
  7. Kartoffel

    Kartoffel Member

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    A list of foods high in glucose :D?
     
  8. tca300

    tca300 Member

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    Because ceramides are made from saturated fat.
    In Defense of Low Fat: A Call for Some Evolution of Thought (Part 1)
    She goes heavily into it, I dont really care too. I also think Tyw talked about it somewhere. I think that maybe in a given context ( hormonal, nitric oxide, endotoxin) saturated fats could make MS worse. Not that they are the cause by any means though. Also seems like countries who dont eat much saturated fat have virtually no MS deaths. MULTIPLE SCLEROSIS DEATH RATE BY COUNTRY

    But I'm probably wrong because I am not putting really any effort into researching it thoroughly. Just a few observations.
    Also I remember reading a study on using saturated fat as a carrier for hormones ( testosterone therapy ) as the saturated fat allows testosterone to get into the cell better than various other carriers used, but I also noticed that the saturated fat also allows estrogen into the cell much easier. Ray has mentioned estrogen as a potential issue regarding MS, so if estrogen is high, eating saturated fat might make things worse. Of course this is all contextual.
     
  9. Kartoffel

    Kartoffel Member

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    Ceramides are mostly made from (or rather with) PUFA, and not saturated fat. I searched for "ceramides" in that Minger article, and it doesn't appear once.
    What essentially all of those countries have in common is that they are "third world" or developing countries with low total fat and calorie intake, I don't understand how that can lead to the conclusion that saturated fat has anything to do with MS. It's safe to assume that a low fat diet is generally a good idea, given the fats that people normally eat.
     
  10. tca300

    tca300 Member

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    Japan, Singapore, South Korea, and China are third world, developing countries? Her article had an area about Swank and how he had success treating MS with a diet low in saturated fat. Can you please share some proof that ceramides are made from PUFA? I have only seen information about how Palmitic Acid is the fat they are synthesized from. Thanks.

    Ceramide is a structural and signaling molecule. It is made up of a fatty acid called sphingosine and is located within the membrane of cells, in great concentrations. Sphingosine is synthesized from palmitoyl coa and serine in a condensation required to yield dehydrosphingosine.
     
  11. Amazoniac

    Amazoniac Member

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    - Review of Two Popular Eating Plans within the Multiple Sclerosis Community: Low Saturated Fat and Modified Paleolithic

    "Swank’s studies have been criticized for not being randomized controlled trials; his comparison of ‘good’ and ‘poor’ responders may also be biased towards a positive result because patients who are feeling well are more likely to adhere to the ≤20 g saturated fat restriction while those who are declining may abandon it [63]. His reports were also criticized for not using blinded assessors [64,65]. Additional weaknesses include the risk of missing data that is not missing at random but missing as part of the disease process, selection bias, exclusion of patients who were following the diet ‘poorly,’ absence of brain MRI data and the lack of standardized validated dietary assessment measures. The strength of the Swank cohort study is long duration of the follow up period and size of the cohort."​
     
  12. tca300

    tca300 Member

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    Thanks!
     
  13. Kartoffel

    Kartoffel Member

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    I said essentially all of them, and, yes, China is a developing country, and tens of millions of rural inhabitants eat very little fat. Swank used a low saturated fat diet because he used a low fat diet, and his success is rather badly documented, which is why nobody acknowledges his "results". The Burr studies already showed that EFA "deficiency" caused a drastic reduction of skin ceramides, and that feeding them n-6 restored their levels. Mind you, the "saturated" fat in the study below is lard.

    Saturated- and n-6 Polyunsaturated-Fat Diets Each Induce Ceramide Accumulation in Mouse Skeletal Muscle: Reversal and Improvement of Glucose Tolerance by Lipid Metabolism Inhibitors
     
  14. tca300

    tca300 Member

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    Awesome, thanks!
     
  15. Amazoniac

    Amazoniac Member

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    His brief speculation (I believe it was already posted elsewhere):

    [25] How saturated fats may be a causative factor in multiple sclerosis and other diseases

    "During digestion all fats are first reduced to small globules of fat and then to chylomicra in the blood. These chylomicra collect in the small arteries from which feeding capillaries arise. After a large fatty meal, the chylomicra are crowded together and form aggregates. When formed from unsaturated fats (oils), aggregates are relatively small and loosely held together. The aggregates are small enough to enter and pass through the capillaries and nourish the tissue. Conversely, saturated fat aggregates are much larger and tightly bound together. They may or may not enter the capillaries and, due to their size, may get lodged in the capillaries or very slowly pass through. The rigidity of the aggregates makes them less easy to deform by the shear forces than the softer aggregates formed from the lower molecular weight droplets from vegetable oils. As a result the tissues to be nourished by the large aggregates fail to receive adequate nourishment and may starve or function poorly."​
     
  16. Tarmander

    Tarmander Member

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    This is cool. I have seen some astounding results for MS from the Coimbra protocol.
     
  17. Kartoffel

    Kartoffel Member

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    This is basically the same as pointing to a block of coconut fat and then saying "see how hard it is? that will happen in your arteries!1!!"

    No problem. I think that there is nothing wrong with low fat diets, quite the opposite. Even saturated fat will interfere with CHO oxidation at a certain concentration, but there is nothing inherently toxic about it, and moderate quantities of it, as opposed to PUFA, have been shown not to interfere with crucial glucose enzymes such as PDH
     
  18. Amazoniac

    Amazoniac Member

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    For whatever reason the oils weren't detrimental, contrary to fats.

    ↳ [23] Multiple sclerosis: Twenty years on low fat diet

    "We have defined fats as lipids solid at room temperature (70 °F). In addition to butter and animal fat (lard), this includes all the margarines, hydrogenated oils other than margarine, ie, vegetable shortening (Crisco), chocolate, and hydrogenated peanut oil in peanut butter. Oils are fluid at room temperature, both those of vegetable and of fish (cod liver oil) origin. To avoid confusion due to labeling of many processed foods, patients were instructed not to use cake and other prepared mixes, nor other processed foods, unless we were first consulted, since hydrogenated oils are often labeled as 'vegetable oil.'"

    "Because low fat consumers were also the high oil consumers, it is not possible to conclude that a high oil intake improves the patient, although this may be true. It is clear, however, that a high oil intake was not harmful."​
     
  19. Kartoffel

    Kartoffel Member

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    I think the things you posted above regarding his methodological shortcoming show some of the reasons why it might be a waste of time to debate why what happened in his "trials" or whatever you want to call it.
     
  20. Amazoniac

    Amazoniac Member

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    I bet that if was the opposite you wouldn't mind entertaining the idea.

    <Table: Fatty acids rank'd according to their propensity to do a competition with dextrose>
     
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