Alcohol Brain Damage Due To Iron Accumulation; Vitamin B1 To The Rescue

Discussion in 'Scientific Studies' started by haidut, Sep 14, 2020 at 11:56 AM.

  1. haidut

    haidut Member

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    Chronic alcohol abuse is highly detrimental to health and especially to the brain. Alcohol puts the body in a reductive state and depletes vitamin B1 (thiamine) stores. If the B1 deficiency becomes severe enough it manifests through what is clinically known as Wernicke-Korsakoff syndrome (WKS), characterized by dementia and other severe neurological symptoms. It is treatable by administering B1 and most hospitals have the so-called "banana bags", which are IV solutions containing glucose and B vitamins, including high-dose B1. However, mainstream medicine claims that B1 therapy can only help in early stages of that syndrome and that all other stages are incurable and progressive. The main reason for these claims is that mainstream medicine does not know what the mechanism through which alcohol damages the brain is. Well, the study below serves to both corroborate Peat's views on the "synergy" between alcohol, iron and PUFA while also possibly refuting the mainstream medical claim that B1 cannot treat chronic cases of WKS. As it turns out, alcohol stimulates the release of iron in the blood and its subsequent accumulation in the brain. B1 not only supports the energy production in this extremely energy-sensitive organ but also prevents the iron accumulation in the brain by restoring the blood-brain-barrier. The study also mentions the potential therapeutic role of iron chelators, which suggests that aspirin, vitamin E, tetracycline antibiotics, milk, etc all have potential therapeutic roles. Actually, B1 may itself have iron chelation effects, which may explain why in animal models of WKS the administration of B1 has been shown to fully reverse it on its own. Considering the toxic iron deposits in various organs are not in the form of free iron but in the form of lipofuscin (PUFA+iron), it would be an amazing result if the clinical trial planned by the study authors below discovers that B1 can prevent / reverse lipofuscin accumulation. The accumulation of the latter is a hallmark not only of chronic diseases but of the aging process in general and multiple studies have demonstrated that removing lipofuscin from the cell restores mitochondrial function to youthful levels.

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    Vitamin B1 deficiency a key factor in the development of alcohol-related dementia: Hypothesis describes the role of iron deposits in the brain as the cause of dementia in alcoholics

    "...Researchers Stephan Listabarth, Daniel König and Benjamin Vyssoki from the Department of Psychiatry and Psychotherapy, Division of Social Psychiatry at MedUni Vienna and Simon Hametner from MedUni Vienna's Department of Neurology, Division of Neuropathology and Neurochemistry, have now advanced a plausible hypothesis to explain alcohol-induced brain damage: the cognitive deterioration is caused by iron deposits in the brain but the administration of vitamin B1 could protect the brain from these deposits. We know from various neurodegenerative diseases that iron deposits in the brain are responsible for nerve tissue damage. These deposits can also be detected in specific regions of the brain (including the basal ganglia) in people who drink a lot of alcohol. The hypothesis advanced by the study authors now also offers an explanation as to why iron deposits are so prevalent in this patient group: high alcohol consumption results in elevated iron levels in the blood and also to vitamin B1 (thiamine) deficiency, which, among other things, is important for maintaining the blood-brain barrier. If these two situations coincide, more iron will be deposited inside the brain, ultimately leading to oxidative tissue damage. This newly described role of vitamin B1 in this process could represent a huge step forward in our understanding of the development of alcohol-related neurological damage and, in particular, could offer a new point of attack for preventive and therapeutic approaches. It would then be conceivable to give continuous vitamin B1 substitution in the future, as a preventive measure. The researchers believe it would also be useful to evaluate the use of drugs to reduce iron levels (e.g. chelators), as is already done in other neurodegenerative diseases. The authors of the current work have already started planning a prospective clinical study to validate the above-mentioned relationship between alcohol dependency, vitamin B1 deficiency and cerebral iron deposits and to provide a basis for further research in the field of alcohol-related dementia in the future.
     
  2. Recoen

    Recoen Member

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    Copied from the pregnenolone thread.

    On another note your recent review of the paper on B1 and lipofuscin was a great find! You remarked about the possibility of B1 not allowing lipofuscin to accumulate in the first place, this paper might interest you:
    https://www.researchgate.net/profil...oxicity-in-rats.pdf?origin=publication_detail

    This of course all makes sense given Gilbert Lings work. If you look at the hydrated vs unhydrated diameters, Fe+2, Co+2, Ni+2, Cu+2, Zn+2, and Sn+2, all have the same hydrated diameter as Ca+2 = 600pm. Which means they also use the “Ca ion channels” (https://electrobionics.org/ionic_radii.pdf).Here is a recent paper showing that Fe does: L-type Ca 2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy | Nature Medicine

    This also shows why potassium is desired over Na, 300pm and 450pm respectively. And when the cytoplasm structure changes Na will substitute for K (100pm vs 160pm unhydrated diameters). And why all of the above (Ca, etc) become “stuck” in the cell in a low ATP/ CO2 state. Dr Ling discusses this in terms of c-values.

    Back to your article, if B1 and alcohol both help to get the Fe back in circulation I wonder if a therapeutic amount of alcohol + B1 would be an effective strategy for excess Fe removal. The problem obviously being excretion once it’s in circulation- I believe this is where albumin would come in. One could of course do a blood donation but for those who can’t.
     
  3. OP
    haidut

    haidut Member

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    Thanks, very interesting! What do you think may be the mechanism behind high-calcium intake's propensity to lower intracellular iron? Would it be related to sharing the calcium channel among the several metal ions?
    As far as the alcohol effects - I think you are spot on. In a recent podcast with Peat I brought up some old studies that showed lower doses of alcohol (equivalent to 1-2 drinks daily in humans) actually dissolved lipofuscin and helped clear it up from the cell. Combined with B1, this process is probably synergistic in light of the new study. Reduction of lipofuscin is known to reliable extend both average and maximum lifespan in animals and (non)-coincidentally low-dose alcohol was recently found to double lifespan in worms. So does cholesterol (in the same study), which makes me wonder if cholesterol helps solubilize lipofuscin (as it is known to do with other lipophilic chemicals) and somehow make it more excretable...
    Alcohol DOUBLES LIFESPAN, helps resist stress
    Tiny amounts of alcohol dramatically extend a worm's life, but why?
    Caenorhabditis elegans Battling Starvation Stress: Low Levels of Ethanol Prolong Lifespan in L1 Larvae

    "...Addition of 13 µM cholesterol to starving L1 larvae incubated in M9 medium was previously reported to significantly increase their survival [17]. However, since the cholesterol was dissolved in ethanol, resulting in a final solvent concentration of 17 mM (0.1%), we wanted to ask if ethanol itself might be responsible for some or all of the lifespan extension. We thus repeated the previous experiments with an additional control of ethanol alone. We found that starved wild-type L1 larvae incubated in M9 medium live about 15 days (Fig. 1, panel A), while larvae incubated in M9 medium supplemented with cholesterol dissolved in ethanol live about 30 days, or about twice as long (panel C). These results are similar to those previously reported [17]. However, the lifespan of N2 L1 larvae was also extended to about 30 days when only ethanol was added to the M9 medium (panel B), suggesting that the observed effect of cholesterol can be attributed to the ethanol solvent. We also repeated these experiments in the protein repair deficient pcm-1 strain. Here, we observed similar starvation survival in the presence and absence of 17 mM ethanol as the wild-type N2 strain (Fig. 1, panels A and B). But significantly, the survival with 13 µM cholesterol/17 mM ethanol was greatly reduced in the pcm-1 mutant compared to 17 mM ethanol alone (panel C). These experiments are summarized in Table S1. These results suggest that cholesterol may be toxic to pcm-1 mutants, rather than leading to a partial extension of lifespan as originally reported [17]."

    "...To characterize the lifespan extension due to ethanol, we first investigated the concentration dependence of the effect. We found that ethanol concentrations ranging from 4 mM to 68 mM (0.024% to 0.4%) result in similar lifespan extensions to the one obtained with 17 mM (0.1%) ethanol (compare Fig. 1, panels A and B, with Fig. 2, panels A and B). Interestingly, we noted no large differences in survival at the higher (or lower) ethanol concentrations. We have summarized these data in terms of 75%, 50%, and 25% survival in Table S1 and show the statistics for replicate experiments in Table S2. To determine the lowest ethanol concentration that would extend lifespan, we incubated L1 larvae in ethanol concentrations ranging from 0.001 to 1 mM (Fig. 2, panel C). Ethanol concentrations below 1 mM (0.1, 0.01 and 0.001 mM) did not result in the clear lifespan extension (Fig. 2, panel C) that we observed with concentrations ranging from 4 to 68 mM (Fig. 2, panels A and B). These results suggest that very low (1 mM) ethanol concentrations are effective in prolonging the starvation survival of L1 larvae."
     
  4. Recoen

    Recoen Member

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    From a purely physics standpoint, I think Ca+2 relative priority in the “VGCCs” has to do with the electron configuration. The nucleus and unpaired electrons creating a “dipole”. The dipole moments will be different for the ions listed above. These dipoles will create an electric field. There’s always the possibility of magnetic dipoles and resulting magnetic fields too- the fact that you have charge moving shows there will be one. I think these interactions with the local cytoplasm is what dictates the ion preference. This would be pretty simple to model if we knew more about the cytoplasm structure at the boundary between the cell and extracellular space. What proteins are there, etc.

    Because Ca, etc uptake depends on the changing structure of the cytoplasm I think experiments will show “Ca channels” move. This having to do with the protein folding and unfolding caused by the interaction with CO2 and ATP, etc.

    Of course the relative amounts of the different ions will play a role too.

    Thats really interesting about cholesterol! So do you think cholesterol and other fats vs albumin and other proteins will help excrete unneeded Fe?

    I wonder if the alcohol is becoming triglycerides and this is how it breaks down lipofuscin.
     
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