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The Tetracycline Antibiotics Inhibit Mitochondrial Respiration

Discussion in 'Scientific Studies' started by haidut, Mar 14, 2015.

  1. haidut

    haidut Member

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    I posted a study about a month ago showing that the tetracycline class of antibiotics are potent inhibitors for a large number of cancer types. The proposed mechanism of action in that study was the fact that the tetracyclines were very toxic to the tumor mitochondria.
    This study found that the tetracyclines inhibit mitochondrial respiration in normal cells too. I wonder what would Ray say about that and what the impact is for people using those antibiotics on a regular basis for gut issues.
    Perhaps more interestingly (and in support of Peat's endorsement of the tetracyclines), despite the decrease in mitochondrial respiration organisms treated with a tetracycline antibiotic were more agile as they aged - i.e. they did not exhibit decline in physical/mental fitness with age.
    So, what's going on here - tetracyclines cause lower respiration/metabolism but improved fitness??

    http://www.the-scientist.com//?articles ... ochondria/

    "... Two years ago, study coauthor Johan Auwerx, an energy metabolism researcher at the École Polytechnique Fédérale in Lausanne, Switzerland, and his colleagues observed that the tetracycline class of antibiotics, which target mitochondrial translation, led to an imbalance between mitochondrial and nuclear protein translation in both worms and mammalian cell lines. Expanding on this observation, the researchers have now shown that even low concentrations of tetracyclines can inhibit mitochondrial function and lead to changes in both mitochondrial and nuclear protein expression. Across four commonly used human cell lines, as little as 1 microgram of the drug per milliliter resulted in a decrease in cellular respiration, signaling impaired mitochondrial activity. Treatment with amoxicillin, an antibiotic that does not target protein synthesis in the mitochondria, did not lead to these effects. Further, genome-wide expression data showed global repression of mitochondrial protein synthesis in the presence of the tetracycline doxycycline.
    In C. elegans and D. melanogaster, doxycycline exposure during development resulted in developmental delays as well as decreased oxygen consumption when the animals reached adulthood. However, both the doxycycline-treated worms and the fruit flies were more agile throughout their lives compared to those not exposed to the antibiotic, Auwerx and his colleagues found. This observation was consistent with the authors’ previous findings that blocking mitochondrial translation can partly prevent a decline in physical fitness with age."
     
  2. Such_Saturation

    Such_Saturation Member

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    Well if it's the same as methylene blue it should skip electron chain steps, so of course less yield but a secure yield that can maintain function. Or perhaps it increases selective pressure for healthier mitochondria like lithium does.
     
  3. OP
    haidut

    haidut Member

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    Good points. I was also thinking about the mechanism similar to lithium - i.e. kill cells with defective mitochondria. Here are some studies discussing that tetracyclines and lithium have similar biochemical properties.

    http://www.ncbi.nlm.nih.gov/pubmed/8413842
    http://www.ncbi.nlm.nih.gov/pubmed/1965041
    http://www.ncbi.nlm.nih.gov/pubmed/6310696
     
  4. Such_Saturation

    Such_Saturation Member

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    And lithium also is antibacterial and also messes with ribosomes.
     
  5. michael94

    michael94 Member

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    fascinating
     
  6. Above&Beyond

    Above&Beyond New Member

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    So what if you took doxycycline and lithium orotate at the same time?
     
  7. Sucrates

    Sucrates Member

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    Has anyone any further insight on this?
     
  8. kiran

    kiran Member

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    I take minocycline on and off. Taking it for a longer time makes me loopy and my balance gets affected. Ended up taking it in 3 day bursts.
     
  9. OP
    haidut

    haidut Member

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    Interesting, thanks. Have you asked Peat about the balance effects from minocycline? It sounds like something gut irritation or ear toxicity would do. Or hypoglycemia of course.
     
  10. Joeyd

    Joeyd Member

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    is it better to take tetracycline over minocycline or doxycycline? (i know theyre all tetracyclines)
     
  11. OP
    haidut

    haidut Member

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    I think any one of these is OK. Minocycline seems to target the nervous system more than the other two, hence why it is commonly used in studies for animal models of ALS, AD, MS, Parkinson, etc.
     
  12. churchmouth

    churchmouth Member

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    I am on minocycline for over a month to improve skin.

    Side effect is inflammation is down significantly and bowels are a lot more bullet proof too.

    The effect on my mitochondria (this study) does worry me though.

    @haidut do you think there is any concerns taking methylene blue as well as minocycline? I geuss we dont understand what is going on yet.
     
  13. jitsmonkey

    jitsmonkey Member

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    I get the most marked mood improvement from doxy.

    I've tested doxy, mino, tetra & penicillin
     
  14. jb116

    jb116 Member

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    Couldn't there be s biological complexity at play here where even though it has this negative property there is still a greater net effect. Like with RU486
     
  15. churchmouth

    churchmouth Member

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    Haidut on Danny Roddy's patreon crowdcast mentioned that he isn't concerned about mitochondrial respiration inhibition at the dosages used for acne (50-100mg a day).
     
  16. dfspcc20

    dfspcc20 Member

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    What are signs that the nervous system needs "targeting" by antibiotics, other than overt ALS, AD, MS, Parkinson symptoms?
     
  17. Vinero

    Vinero Member

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    Maybe the decrease in respiration/metabolism is simply that metabolism becomes more efficient with fewer calories.
    Ray mentioned in one of his interviews that when he was younger he worked in the woods and he needed like 5000 calories a day or something, while still being skinny and having many hypothyroid symptoms.
    When he took a thyroid supplement his body didn't need such as massive amount of calories anymore, his metabolism decreased (became more efficient).
    He could eat 2500 calories or something while gaining bodyweight. Maybe the decrease in metabolism seen with tetracycline antibiotics is similar to taking thyroid in the sense that it makes your metabolism more efficient instead of wasteful.
     
  18. Blossom

    Blossom Moderator

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    Interesting perspective.
     
  19. OP
    haidut

    haidut Member

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    I think it is difference of thyroid-driven vs. adrenal-driven metabolism. People with high adrenaline/cortisol also have high metabolism but of the wrong kind. Strenuous exercise also raises metabolism through this bad method. So, taking thyroid lowers the stress hormones, which increases progesterone/DHEA and restores the oxidative metabolism. It is better to have higher RMR and do fine on 2,500 calories daily then stress yourself to death and need 5,000 daily. It is not just high metabolism that matters, but high resting metabolism (RMR). People running on stress hormones have low RMR but higher daily average MR. Only RMR has been positively associated with health and protective against CVD, cancer, etc. High metabolic rate driven by adrenals is actually quite unhealthy and that has been confirmed in so many human studies. So I keep wondering if all the doctors recommending regular exercise even read medical journals any more. I guess, old myths (and industries) die hard...
     
  20. krosser

    krosser New Member

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    I was reading on tetracyclines and came across a side effect of minocycline, which is hair loss. Although it is indicated as rare but if you google, you find several cases of people experiencing hair loss when taking minocycline.
    I was considering trying it in 50mg dose, but I don't want to lose even more hair :)
     
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