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Boosting Mitochondria Increases Energy, Leads To Viral Clearance

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by Hip, Nov 29, 2011.

  1. Hip

    Hip Senior Member

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    Boosting Mitochondria May Not Only Increase Energy, But Also Lead To Complete Viral Clearance

    New study: The mitochondrial respiratory chain has a critical role in the antiviral process in Coxsackievirus B3-induced myocarditis.

    The above study compared mice strains that were able to completely clear coxsackievirus B (CVB) infection, to mice strains that could not clear this virus and had lingering infection with immune activation.

    The study was in the context of coxsackievirus B3-induced myocarditis, but I think CVB myocarditis may be an excellent viral model for studying chronic fatigue syndrome, since chronic lingering CVB infection is strongly associated with CFS.

    After 90 days, the study authors found that the non-clearing mice showed permanently restricted mitochondrial complex I activity, whereas the mice that cleared the virus normalized all four mitochondrial complexes.

    In general, the authors found that reduced CVB3 titers correlated with increased complex I and III activity.

    So mitochondrial complexes I and III are possibly the ones you want to boost the most, to try to get viral clearance, if you have enterovirus / coxsackievirus B associated chronic fatigue syndrome.

    Supplements that boost mitochondrial complexes I and III include: pyrroloquinoline quinone, gingko biloba, and melatonin (at night).

    The paper concluded: "the regulation of energy metabolism appears crucial for an effective virus elimination and may be of prognostic and therapeutic significance."

    So intriguingly, it seems that low energy output from mitochondria not only likely cause fatigue, but worse still, it seems to prevent the clearance of enterovirus from the tissues.

    So boosting mitochondria, particularly complexes I and III, may not only provide a welcome increase in energy, but may also help clear viral infections.


    Boosters of Mitochondrial Complexes:

    Pyrroloquinoline quinone stimulates complex I.
    Gingko biloba stimulates complexes I and III.
    Melatonin stimulates complexes I and IV.
    Methylene blue stimulates complex IV.
    Methylphenidate (Ritalin) stimulates complexes II and IV (refs: 1, 2).
    Deprenyl stimulates complex IV.
    Bezafibrate stimulates complex IV.


    Inhibitors of Mitochondrial Complexes:

    Metformin partially inhibits complex I.
    MDMA (ecstasy) inhibits complex I in mice.
    Cocaine inhibits complex I .
    Rotenone (an insecticide, pesticide and piscicide) inhibits complex I.
    Pyrethroid pesticides like permethrin, often used as pet flea killer, is a potent inhibitor of complex I.
    Poliovirus inhibits complex II.
    Organophosphate pesticide malathion inhibits complex IV.


    Supplements That Boost Mitochondrial Function:

    Creatine.
    Glutamine protects mitochondrial structure and function in oxygen toxicity.
    High doses of nicotinamide prevent oxidative mitochondrial dysfunction in a cellular model and improve motor deficit in a Drosophila model of Parkinson's.
    Piracetam improves mitochondrial dysfunction following oxidative stress.
    Q10 Take co-enzyme Q10 with food! Q10 facilitates the conversion of nutrients into energy in the mitochondria. So take with meals.
    Alpha lipoic acid + acetyl-L-carnitine.
    Magnesium.
    Malic acid.
    Coconut oil / MCT oil.
    Taurine.
    D-ribose.


    Supplements That Boost Mitochondrial Biogenesis:

    Mitochondrial biogenesis = birth of new mitochondria. There are around a few hundred to a few thousand mitochondria in each cell. Some people think that CFS may not just be linked to reduced mitochondrial function, but also to reduced mitochondrial numbers. So generating new mitochondria may be a good idea.

    Quercetin promotes mitochondrial biogenesis.
    Resveratrol.
    Leucine (and Branched Chain Amino Acids).
    R-alpha-lipoic acid and acetyl-L-carnitine.
    Isoflavones (daidzein, genistein, biochanin A).
    Caffeine.
    Hydroxytyrosol (from olive oil, and olive leaf extract). Commercial name: Hidrox.
    Pioglitazone (Actos), an antihyperglycemic, antidiabetic drug.
    Estradiol (hormone).
    Pyrroloquinoline quinone (possibly a new vitamin).
    Caloric Restriction (fasting) promotes mitochondrial biogenesis.
    Erythropoietin.
    Cold exposure.
    Hypoxia.
    SRT1720 (new drug from Sirtris Pharmaceuticals).
    Telmisartan enhances mitochondrial biogenesis in human endothelial cell.
    Triiodothyronine (T3).
    DHEA.
    Pyruvate.
    Lactate.
    Lithium.



    Also of interest: Wikipedia's article on complex III says: "mutations in complex III cause exercise intolerance".

    Given this, I wonder if virally induced restrictions in complex III might explain the post exertional malaise (PEM) in CFS, which is an exercise intolerance?

    It possibly adds weight to the idea of boosting complex I and III as a CFS treatment.
    Last edited: May 20, 2014
    heapsreal, beaverfury, amaru7 and 4 others like this.
  2. Artstu

    Artstu Senior Member

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    That would explain why I feel better when it is cold.
  3. richvank

    richvank Senior Member

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    Hi, Hip.

    I suggest that the reason for the mito dysfunction in ME/CFS is the vicious circle associated with glutathione depletion and the partial methylation cycle block. Unless this vicious circle is broken, I think that improvement in mito function in this disorder is likely to be limited, though some of the things you listed will help to some degree.

    Best regards,

    Rich
    amaru7 likes this.
  4. MDL

    MDL

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    Followi the H2S Trail...

    I have written about hydrogen sulfide as an underlying mechanism in ME/CFS. Mitochondria are organelles descended from ancient eukaryotic sufur-utilizing microbes and, believe it or not, mitochondria have retained this ancient ability to utilize H2S as a substrate to oxygen. I believe this gas plays a fundamental role in our mitochondria and in this disease.

    There are several enzymes associated with H2S production. Many of you are familiar with cystathionine beta synthase (CBS) because you have the up-regulated CBS polyorphism. Another enzyme is cystathionine gamma lyase, otherwise known as CSE.

    In China, where interest in H2S is high, scientists recently infected mice with coxsackievirus B-3 virus and looked at CSE: In the myocarditis group, the serum H2S content and H2S production rates in cardiac tissues were significantly higher than those in the control group 4 and 10 days after injection (P<0.05). The expression of CSE protein in the heart in the myocarditis group was also significantly higher than that in the control group The authors concluded that CBS and its downstream production of H2S increase in mice with acute viral myocarditis. From this, they postulated that the increased expression of CSE/H2S pathway might be involved in the pathogenesis of viral myocarditis. http://www.ncbi.nlm.nih.gov/pubmed/20849728

    It would seem to me that this is worthy of further exploration.

    Further, as far as glutathione in the mitochondria is concerned, hydrogen sulfide again comes into play. In fact, Hydrogen sulfide increases glutathione production and suppresses oxidative stress in mitochondria.
    http://www.ncbi.nlm.nih.gov/pubmed/19852698

    This seems pretty significant to me.

    Marian
  5. MDL

    MDL

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    Follow the H2S Trail...

    I have written about hydrogen sulfide as an underlying mechanism in ME/CFS. Mitochondria are organelles descended from ancient eukaryotic sufur-utilizing microbes and, believe it or not, mitochondria have retained this ancient ability to utilize H2S as a substrate to oxygen. I believe this gas plays a fundamental role in our mitochondria and in this disease.

    There are several enzymes associated with H2S production. Many of you are familiar with cystathionine beta synthase (CBS) because you have the up-regulated CBS polyorphism. Another enzyme is cystathionine gamma lyase, otherwise known as CSE.

    In China, where interest in H2S is high, scientists recently infected mice with coxsackievirus B-3 virus and looked at CSE: In the myocarditis group, the serum H2S content and H2S production rates in cardiac tissues were significantly higher than those in the control group 4 and 10 days after injection (P<0.05). The expression of CSE protein in the heart in the myocarditis group was also significantly higher than that in the control group The authors concluded that CBS and its downstream production of H2S increase in mice with acute viral myocarditis. From this, they postulated that the increased expression of CSE/H2S pathway might be involved in the pathogenesis of viral myocarditis. http://www.ncbi.nlm.nih.gov/pubmed/20849728

    It would seem to me that this is worthy of further exploration.

    Further, as far as glutathione in the mitochondria is concerned, hydrogen sulfide again comes into play. In fact, Hydrogen sulfide increases glutathione production and suppresses oxidative stress in mitochondria.
    http://www.ncbi.nlm.nih.gov/pubmed/19852698

    This seems pretty significant to me.

    Marian
  6. Navid

    Navid Senior Member

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    Hi:

    non-scientist here; but very sick, so interested in your posts.....can you tell us what this may mean for patient treatment....is there something we should be taking to icrease mito function?

    thank you





  7. MDL

    MDL

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    Hi Navid,

    I am so sorry that you are very sick. I wish I could give you some advice, but unfortunately, I am not a doctor. The best advice is to find a good integrative doctor who can test you for allergies and pathogens, advise on your diet, and look at your genetics. On the question of what might increase mito function, I know that some people like the Xymogen Mitochondrial Renewal Pak.

    I hope tomorrow is a better day for you.
    Marian
  8. globalpilot

    globalpilot Senior Member

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    "Note that these authors say that replicating viruses were no longer detectable after 90 days in both mice strains, but in fact, it is known form the work of Dr Nora Chapman et al, and Dr Chia, that non-cytolytic Coxsackie B viruses can remain indefinitely in cells, even when replicating virus particles are no longer detectable. This likely explaining the lingering immune activation observed in chronic myocarditis, as well as in chronic fatigue syndrome, even when replicating viruses cannot been seen anymore."

    I'm confused by this ... cells eventually die so if the virus is not cytolytic wouldn't the infection die out eventually as the cells die ?
  9. richvank

    richvank Senior Member

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    Hi, globalpilot.

    Some of the cells in our bodies last for our entire lifetimes. This includes neurons in the brain, heart muscle cells and cells in the lens of the eye. As I understand it, memory B cells can be immortalized, too. If the virus resides in one of these cell types, it can be there in the latent state for our lifetimes. Herpes simplex 1 and Herpes zoster reside in neurons. EBV resides in immortalized B cells. I guess Coxsackie can reside in heart muscle cells. I don't know about other viruses.

    Best regards,

    Rich
  10. Waverunner

    Waverunner Senior Member

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    While I do think that Mitochondria have their role in this disease, I don't think that the treatment recommendations here will help us. PWME and people on this board tried these supplements over and over again and none got cured. Posts about mitochondria appear on a regular basis, they all blame the mitochondria as cause of ME and they all recommend some supplements and all the treatment recommendations don't work for most people.
  11. Hip

    Hip Senior Member

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    Hi Marian

    Thanks very much for those links.

    I find your H2S theory very thought provoking, especially since the H2S neurotoxic metabolite test I took a couple of years ago came out a strong positive. I did some experiments at that time with taking orally some H2S absorbers such as zinc acetate, hydroxocobalamin, zeolite, and even small amounts of sodium nitrite (which you have to be very careful with, as a fatal dose of sodium nitrite can be as a little as 1 gram).

    However, even after a few weeks on this anti-H2S regimen, I did not get much in the way of results, in terms of improved CFS symptoms. Since in experiments, mice emerged very quickly from their H2S-induced low energy "suspended animation" state, I assume the same thing would happen to CFS patients once the H2S has been removed: ie, you'd return to normal health within hours or days, rather than weeks or months.

    It's also interesting that some perfectly healthy people can have digestions that regularly produce odorous flatulence (which generally means they are producing H2S in their gut), but experience no ill effects. I myself occasionally have this odorous H2S flatus (usually, like many people, when I have a meal with lots of beans); however I don't feel any worse on those days; in fact, I usually feel noticeably better when my digestion is more odorous, for some reason.

    This could of course be a paradoxical result, and this is something I did think about: ie, it may be that increased H2S in the gut spurs some H2S detoxification system into action in the body, thus actually lowering overall bodily H2S (in which case, an experimental treatment for CFS might be a very low level exposure to H2S - though that's not easy to do, given that breathing H2S can be fatal).



    It may be that the source of the H2S is as intracellular one, in which case, perhaps a different strategy may be needed to absorb or to block its production. It says in the above link you gave on CVB viral myocarditis that cystathionine gamma-lyase is the enzyme involved in manufacturing H2S in coxsackievirus B infection. I am not sure if this is an intracellular enzyme, but if so, then perhaps the impact of H2S in CFS patients is indeed confined to within the cells.

    I am not sure how easily H2S can diffuse in and out of cells across the plasma membrane. If it can diffuse very easily, then perhaps this distinction made here between intracellular and extracellular H2S is not really correct.


    Do you know if there are intracellular enzymes that break down H2S? If so, could the it be that CFS patients have a lack of these enzymes, thus leading to H2S toxicity?
  12. Hip

    Hip Senior Member

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    I often take your methylation protocol, and I think it does help me. I tend to test out so many different protocol though (often ones of my own design), that it can be a problem working out which ones are providing the benefits. If I could duplicate myself 10 times, and use these self copies as guineas pigs for testing various protocols, it would be much easier!
  13. Hip

    Hip Senior Member

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    Me too. I find the mitochondrial supplements boost energy, which is great, but they do not cure. I bet, though, that nobody has tried all of the above supplements at the same time....

    However, it is intriguing that in these mice experiments, viral clearance and normalization of the immune response corresponded to high complex I and III activity; whereas the chronic viral infection state corresponded to low complex I activity.

    This suggests that you don't want to take any old mitochondrial boosters, but rather you want ones that boost complex I and III activity.

    Supplements that boost or protect mitochondrial complexes I and III include: pyrroloquinoline quinone, gingko biloba, and melatonin (at night).

    Here is a thread about someone with CFS getting good results from pyrroloquinoline quinone.
  14. globalpilot

    globalpilot Senior Member

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    Thanks Rich. Dr Chia is talkign about enterovirus in the gut and says it can be non-cytolytic so I'm not sure then why the infection would persist. I would understand it if it were cytolytic.

  15. richvank

    richvank Senior Member

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    Hi, globalpilot.

    Maybe the virus can spread from one cell to another without killing the cells.

    Best regards,

    Rich
  16. Hip

    Hip Senior Member

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    Chia's research focused on enteroviruses in the gut (both the cytolytic and non-cytolytic subsets) because the gut is a main reservoir of enteroviruses in the body, and because it is relatively easy to take tissue sample from the gut. However, the mental symptoms of CFS are probably underpinned by these same cytolytic and non-cytolytic infection in the brain (but of course nobody living with CFS is going to donate a part of their brain in order to test this...).

    It is known that enteroviruses can ascend the vagus nerve that runs from the gut to brain in three days. So this is one route of entry that enteroviruses have into the brain.

    Coxsackievirus B seems able to infect the astrocyte cells in the brain (an astrocyte is a type of glial cell), according to this recent paper from China. And a postmortem examination of the brain, performed on a deceased CFS patient of the late Dr John Richardson (who had studied enteroviruses in CFS for 50 years), found lots of enterovirus infection in the outer (exterior) lining of the blood vessels in the brain, and some enterovirus infection in the glial cells.

    The difference between a cytolytic and a non-cytolytic enterovirus is simply that the non-cytolytic version has had a tiny part of its genome deleted and removed the part that encodes for the shell of the virus (capsid). Thus the non-cytolytic version is identical, except that it has no shell. The analogy think of for this is that a non-cytolytic enterovirus is like a snail without its shell.

    In essence, the non-cytolytic enterovirus is just a naked RNA genome.

    I am not sure whether this shell-less non-cytolytic enterovirus can jump into new cells or not (I have not seen any research that confirms or refutes this possibility). However, since there are likely thousands of copies of this naked RNA an infected cell, presumably if that cell divides to create daughter cells (mitosis), the daughters will also carry the infection.

    Refs:

    Coxsackievirus Infection Induced Cytopathy and Cytokine Secretion in Astrocyte.
    J. Richardson. (2001). Viral Isolation from Brain in Myalgic Encephalomyelitis (A Case Report).
  17. snowathlete

    snowathlete

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    I thought I read somewhere that infected cells are supposed to let off some kind of marker when they get infected with disease, for T cells to come along and clear them up?

    If not, how can we even hope to get rid of the blighters?
  18. Hip

    Hip Senior Member

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    One of the cunning little tricks that coxsackievirus B deploys is removing this marker from the surface of our cells, so that when the immune system's killer-T-cells (CD8 T cells) come along, they don't notice anything wrong, even though the cell is infected.

    This is like smashing the burglar alarm off the wall before you rob a house.

    The marker of cellular infection the cell's burglar alarm is called the major histocompatibility complex (MHC). Remove this MHC marker from the outer surface of a cell, as coxsackievirus B attempts to do, and an infected cell then becomes invisible to these killer-T-cells.


    This type of trick is known as immune evasion. All pathogens that survive as chronic infections in the body do so by using various immune evasion tactics. If it were not for these immune evasion tactics, our immune system would have no trouble in fighting off infections.

    Refs:
    Coxsackievirus B3 Proteins Directionally Complement Each Other To Downregulate Surface Major Histocompatibility Complex Class I
  19. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Interesting! I read somewhere that Bond Uni in Australia are not only look into nk cells but also cd8 tcells and finding their dysfunctional, could it be coxsackievirus??
  20. Hip

    Hip Senior Member

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    I have not seen this, but if you have a link, I'd like to read it.

    At the moment I have just started a new antiviral strategy that involves boosting the killer T-cell (CD8 T cell) response. I managed to find several supplements that boost killer T-cells, namely:

    CD8 Boosting:
    Siberian ginseng
    Echinacea
    Licorice
    B12 methylcobalamin
    Ecklonia Cava
    Astragalus
    Proboost (thymic protein A)

    So I thought, why not take them all simultaneously, and see what happens?

    This should increase killer T-cell surveillance, which may make up for the down-reulation of the number of MHC infection markers.

    The only problem is that killer T-cell are involved in autoimmunity, so these CD8 boosting supplements are probably not be a good strategy for people with autoimmune tendencies; and these supplements might even precipitate autoimmunity in some people.

    See here: Activation of Autoimmunity Following Use of Immunostimulatory Herbal Supplements.

    I have also experimented in boosting natural killer cell function, using a different set supplements, and this does seem to give me more energy.

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