Restoring Metabolism Prevents / Reverses "permanent" Nerve Damage

Discussion in 'Scientific Studies' started by haidut, Apr 16, 2020.

  1. haidut

    haidut Member

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    Yet another study demonstrating the crucial role cellular metabolism plays in pathological processes. While most of my posts deal with beneficial effects of improving OXPHOS on various chronic diseases, the study below demonstrates that the same may be true in acute pathologies such as traumatic injury, especially in tissues with high energy demands such as the nervous system. More importantly, the study may help overthrow an old dogma, which even the general populations seems to be strongly indoctrinated in - i.e. that once injured, nerve cells cannot recover, and as such nerve damage is permanent. Well, according to this new study, there is nothing permanent about nerve injury and the lack of regeneration is nothing but a sign of depleted energy reserves (as a result of the injury) and/or malfunctioning mitochondria. Simply improving energy production in the nerve cells (axons) prevented most of the "permanent" damage caused by the injury as well as the subsequent paralysis. And how was the energy production improved? The scientists gave the animals creatine, in an HED of about 10g-15g daily for a period of 8 weeks. The mechanism of action of creatine was through increasing ATP levels. I wonder what the results would have been if instead of only creatine the scientists had given a combination of substances all proven to enhance recovery from traumatic nerve injury - creatine, inosine, progesterone, pregnenolone, niacinamide, thyroid, magnesium, etc. There may have been no nerve damage at all, and thus full recovery.

    Restoring Cellular Energetics Promotes Axonal Regeneration and Functional Recovery after Spinal Cord Injury - ScienceDirect
    "...Nerve fibers or axons of the central nervous system (CNS) in adult mammals regenerate poorly after injury, often leading to permanent neurological impairments. Axonal regeneration is a highly energetic process, suggesting that enhancing energy metabolism could be a way to facilitate axonal regrowth after injury. By using three CNS injury mouse models, this collaborative study by the Xu and Sheng groups reveals that enhancing the transport of mitochondria, the power supply of the cell, by deleting one of its protein anchors rescues injury-induced cellular damage and facilitates axonal regeneration and its connections while restoring motor functions. Administration of the bioenergetic compound creatine also facilitates regeneration. This study establishes that mitochondrial dysfunction and energy deficits contribute to poor CNS axonal regeneration and that supplementing the energy supply can be ameliorative."

    "...We aimed to directly target energy metabolism with creatine, an FDA approved blood-brain-barrier permeable ergogenic compound that rapidly regenerates ATP from ADP independent of mitochondrial transport (Tarnopolsky and Beal, 2001). Creatine monohydrate (2 g/kg) was administered to mice via gavage twice per day up to 8 wpi (Figure 7A). In vertebrates, creatine is converted into phosphocreatine for rapid ATP generation by creatine kinase (CK); CK activity correlates with creatine content and energy demands in tissue (Wyss and Kaddurah-Daouk, 2000)."

    Boosting energy levels within damaged nerves may help them heal
    "...When the spinal cord is injured, the damaged nerve fibers — called axons — are normally incapable of regrowth, leading to permanent loss of function. Considerable research has been done to find ways to promote the regeneration of axons following injury. Results of a study performed in mice and published in Cell Metabolism suggests that increasing energy supply within these injured spinal cord nerves could help promote axon regrowth and restore some motor functions. The study was a collaboration between the National Institutes of Health and the Indiana University School of Medicine in Indianapolis."

    “...We are the first to show that spinal cord injury results in an energy crisis that is intrinsically linked to the limited ability of damaged axons to regenerate,” said Zu-Hang Sheng, Ph.D., senior principal investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and a co-senior author of the study. Like gasoline for a car engine, the cells of the body use a chemical compound called adenosine triphosphate (ATP) for fuel. Much of this ATP is made by cellular power plants called mitochondria. In spinal cord nerves, mitochondria can be found along the axons. When axons are injured, the nearby mitochondria are often damaged as well, impairing ATP production in injured nerves. “Nerve repair requires a significant amount of energy,” said Dr. Sheng. “Our hypothesis is that damage to mitochondria following injury severely limits the available ATP, and this energy crisis is what prevents the regrowth and repair of injured axons.” Adding to the problem is the fact that, in adult nerves, mitochondria are anchored in place within axons. This forces damaged mitochondria to remain in place while making it difficult to replace them, thus accelerating a local energy crisis in injured axons."

    "...To test the energy crisis model further, mice were given creatine, a bioenergetic compound that enhances the formation of ATP. Both control and knockout mice that were fed creatine showed increased axon regrowth following injury compared to mice fed saline instead. More robust nerve regrowth was seen in the knockout mice that got the creatine. “We were very encouraged by these results,” said Dr. Sheng. “The regeneration that we see in our knockout mice is very significant, and these findings support our hypothesis that an energy deficiency is holding back the ability of both central and peripheral nervous systems to repair after injury.”"
     
  2. retroactive

    retroactive Member

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    What do you think of creatine supplementation?
     
  3. shine

    shine Member

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    Isn't the daily HED more like 20-30g instead of 10-15g because they gave the dose twice daily?
     
  4. orewashin

    orewashin Member

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    If thyroid can reverse nerve damage, then why do injured tissues reduce T4's conversion to T3 and increase its conversion to reverse-T3?

    While I think vitamins and other nutrients can help in healing, I'm skeptical about thyroid be able to do the same.

    I have CFS, which is linked to deep brain damage, and any amount of T4, even with T3, produces brain fog. I have doubts that the brain would evolve such a mechanism unless it helped the nerves regenerate.
     
  5. james2388

    james2388 Guest

    I'm sure if CFS Chronic Fatigue Syndrome was linked to 'deep brain damage' they would see it on an MRI and with endocrine hormone blood work as well. I think many people should stop relying on thyroid as their one magically trick. Try eating more protein 150grams a day for albumin production to actually circulate thyroid, protein, and other hormones.
     
  6. orewashin

    orewashin Member

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    I eat more protein than that and tried many things. My albumin is slightly above normal and has been that way for years. You're making assumptions and seem to believe that CFS isn't a legitimate disease.

    There were many studies done that showed CFS is related to variable regressions in the deep brain regions. Feel free to debate the topic with the people in this thread, who have CFS and have read about it and tried treating it for years.

    Healing Midbrain Damage (chronic Fatigue Syndrome)
     
  7. james2388

    james2388 Guest

    If it's not on MRI, if it's not on blood work, if it's not on autopsy, if it's not genetic/enzyme related, or damage caused by drug use- it doesn't exist. Syndromes are just symptoms of other established conditions. Some people want to persuade others they have a disease, some people want to actually solve it, instead of going with something ridiculous like mid brain damage? Are you proposing you have a tumor, or had a stroke? Do you have seizures? Idk what to tell alcoholics, heroin, cocaine, obesity, anorexia, porn, gambling addicts, concussion patients all have some different or damage to the brain. Depression and schizo have different brain readings. Neuroscience is all the hype...

    If all your lab values look okay, your digestion is good, your getting dense diet, it's most likely an enzyme/mineral cofactor deficiency in catecholamine production. Vitamin C / MOAI / MTHFR - methylation issue. I just made a post about coffee/caffeine catecholamine urinary excretion.
     
  8. james2388

    james2388 Guest

     
  9. orewashin

    orewashin Member

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    CFS is diagnosed when all other potential causes of fatigue are ruled out.

    CFS often develops as a result of viral infections.

    CFS is linked to differences in deep brain areas on MRI. Areas that are linked to autonomic regulation.

    CFS has been researched for years and a treatment has not been found.
     
  10. james2388

    james2388 Guest

    So i guess all your lab values look okay. I mean if I was you had to go by a diagnosis of exclusion, I would have a file with all my lab work in pdf's with information blacked out ready to share to people to get ideas. And I gave you mine which is a more evolved theory, that it's a neurotransmitter / catecholamine issue from a unique vitamin/mineral/enzyme/ - cofactor relationship like MAOI activity, like MTHFR activity.

    What viral infection are you talking about? What antibody markers have you been tested for?
    As I said Neuroscience is all hype right now. Put in any condition, I listed several ' it's all linked to the brain'.
    Are you proposing you have autonomic dysreflexia? Because that is just a chronic symptom of a Spinal Cord Injury - A neurological condition.
    Quite the difference between Neuroscience, & Neurology/Neurosurgeons.
    Have you seen a Neurologist?
    You sure you don't have MS?
     
  11. Recoen

    Recoen Member

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    I agree with a lot of this. People want to hold onto their syndromes and diseases. Almost to the point that they don’t “really” want to get better. I think chasing genetics is worse. I think it’s all in a hope to be different and unique vs looking for other creative outlets because so many have no energy to do so. For example, when I was really sick I spent a lot of time on my phone, etc because it’s easier in many ways to do that than to be with others, or even yourself. I like the Pareto principle and think focusing on the mitochondria, so a bioenergetic view if you like, is the 20% cause that gives the 80% effect. Research is starting to show that those mutations are restored once you fix the mitochondria. Also, if you aren’t expressing those snps, cnv, etc from over methylating, oncometabolites, etc then they aren’t a problem.
     
  12. S-VV

    S-VV Member

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    Its been some time since I read something as ridiculous as this. If you know anything about medicine, which evidently you do not, it would become evident that blood tests in the usual sense cover only a very small amount of the existing metabolome.
     
  13. james2388

    james2388 Guest

    Typical response for someone detached from a practical reality. To bad they don't have you to help them with their CFS. I gave my theory, that if all his lab values look okay, it's most likely a catecholamine issue, MAOI or MTHFR/ methlyation some unique vitamin/mineral relationship not expressing that well.... OH wait... Tell me how catecholamine issues are measured with lab values... Let's get him in some special lab to measure brain values of dopamine, serotonin, noradrenalin. LOL you make me laugh guy.

    Please enlighten us on what your profound intellect can share with us...

    I'd like to share a second thing to look into. Is for Owishwashy to get a sleep study done to make sure he doesn't have any pallet abnormalities and has sleep apnea... That's up there for causes of 'Chronic Fatigue Syndrome' .....
     
  14. orewashin

    orewashin Member

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    Of course I've seen a neurologist. I've also seen a rheumatologist and an endocrinologist.

    I've gotten most of the blood work done, apart from a specialized thyroid blood test that's yet to come. I'm going to get EMG, nerve conductance, and neurocognitive testing done, as well as possibly muscle biopsy and table tilt testing. There's no indication that I should get an MRI and CFS isn't diagnosable by MRI because the aberrations aren't consistent.

    I had postural orthostatic hypotension since I was in middle school. Childhood CFS is a recognized condition despite CFS most commonly occurring in older populations.

    I had a couple of bad flus, and felt worse in the long run after contracting them. I'm sure you'll hear CFS in the context of COVID-19. However, they seemed to merely worsen my condition.

    I didn't have CFS since early childhood, rather, it got progressively worse over time, even while I was living a lifestyle that can be considered almost ideal health-wise.

    Why do I think it's a CNS issue? While I do have neuropathy in my feet, that's an issue that appeared about a year ago. I was already dysfunctional a decade ago.

    What it feels like is this: You can sometimes move normally, and possibly be quite energetic, but there's this thing called "post-exertional malaise". It isn't that you lack energy to begin with, but rather, something tires easily.

    A person with mitochondrial disease was misdiagnosed with CFS, and a paper was written about it, but mitochondrial diseases are very rare and run in families. The person was successfully treated with megadoses of B1 and B2.

    I won't rule out that I have a co-enzyme deficiency, but that has less proof than CFS being caused by deepbrain damage from viruses. It also doesn't explain orthostatic intolerance in people with CFS.

    Or why I get brain fog from a single small dose of T4, and feel more alert not taking thyroid at all than a combination of T3 and T4. So far, brain injury converting T4 to reverse-T3 in an attempt to promote healing the best theory.
     
  15. Inaut

    Inaut Member

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    @haidut really enjoyed this post
     
  16. james2388

    james2388 Guest

    You've seen a neurologist but you have neuropathy in your feet? Assuming you are at an appropriate bmi.. And you have yet to have an MRI of your spine to look for MS lesions, or spinal stenosis? Which very much are significantly connected to autonomic dysreflexia as I have previously mentioned in spinal cord injuries or degrading disc disease, that can effect muscle tone, blood pressure etc.

    You've seen an endocrinologist and all your blood labs must have been fine and you're taking t4 and t3 aimlessly and feel better not taking thyroid hormone? You understand that by chasing such a vague syndrome, you are literally not getting anywhere. Emg = nerve conductance, Table tilt test, lol omg how much money are you going to waste? & neurocognitive testing??? You seem like you'll be able to pass:

    :Neurocognitive testing is a way to measure brain function non invasively. It uses paper-and-pencil tests or computerized tests to assess important aspects of cognition: attention, memory, language, reaction time, perception, and so on.

    Keep barking up the thyroid tree, when your labs are fine.... You know that B vitamins assist in methylation, and various enzymatic processes right? Which you are directly saying some people get healed from CFS from b1 and b2. b2 - Riboflavin being extremely important for MTHFR variant carriers.

    I'd get into into counseling, they do more than just help people with emotional problems. They are familiar with the ins and outs of healthcare and can direct you to the help you need. Seriously I'd get a spinal MRI, a gene test so you can now definitely if you are a MTHFR carrier and can supplement riboflavin and folate. But ultimately this shouldn't even be a problem if you are eating several ounces of liver a week...
     
  17. Kram

    Kram Member

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    Did you do anything in particular to fix your mitochondria when you were ill? I am familiar with vitamin K2, selenium, CO2, b vitamins, COQ10, methylene blue, T3 etc. but just curious if there was anything else
     
  18. orewashin

    orewashin Member

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    I get brain fog from natural and synthetic T4, meaning I also get it from the T4 produced in my own body. I can increase my alertness by taking T3, which suppresses T4 production.

    Most people with CFS don't have a localized thyroid problem (Hashimoto's in my case), and so, they never discover that T4 causes brain fog because they never go on it and it's with them all along.

    So brain fog is seen as an inseperable part of CFS, although it's probably a consequence of localized injury and a tendency for the brain to convert T4 into reverse-T3 to slow metabolism and promote healing.

    So while your theories may hold water, this is an important clue you fail to take into account. Why would I get brain fog from 10 mcg of T4 if T4 is already low and T3 is normal? It doesn't make sense unless the brain was locally converting the T4 to reverse-T3. Unfortunately, blood tests do not measure T3 and reverse-T3 of specific areas.

    So my speculation was that if the brain reduces thyroid activity in response to local injury, then wouldn't thyroid slow nerve regeneration in the brain?
     
  19. Recoen

    Recoen Member

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    I’m still not 100% recovered, but am close to 80%. B vitamins have been crucial for me - especially B1. I had to use singles and start low and build slow with them. I also needed some low dose I, Mo, Se, Mn, and B for a while ~RDA. Now oysters, shrimp, and liverwurst seem to give me what I need. K2 and E have also been helpful. Ancestral supplements thyroid was a game changer for me. Then the usual Peat things like enough protein, Ca (I basically never ate dairy after I stopped breastfeeding at 8mos), carbs that work for me, carrot salad, getting enough sun, limiting exercise, and collagen; sleep and changing my priorities. Finding God again was also huge for me too - my stress, etc.
     
  20. james2388

    james2388 Guest

    Recoen is following her instincts. "Zinc is also an essential part of the enzyme deiodinase, which converts T4 into functional T3."
    Orewashin stop taking T4, your body does not need it. Humble yourself it's far more complex than adding in x and saying I have brain fog right after.... Again what I've been saying this whole time, and I don't even think your understand Peat because you're not getting the relationship of minerals in enzyme cofactors to facilitate natural production and conversion. All this talk about brain fog, post exercise fatigue, chronic fatigue syndrome, neurocognitive testing

    Have you tried incorporating more Zinc? Eating Muscle Meat? You understand why so many people are regaining their lives on The Vertical Diet??? Zinc from Beef Muscle Meat!!!!!
     
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