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Drugs linked to mitochondrial toxicity (eg: tetracycline, minocycline, metformin)

Discussion in 'General ME/CFS Discussion' started by Hip, May 19, 2017.

  1. Hip

    Hip Senior Member

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    Since ME/CFS may involve some form of mitochondrial or energy metabolism dysfunction, it might be an idea to post a list of drugs that are reported to have mitochondrial toxicity effects (see the list below).

    Perhaps mitochondrial toxicity might be behind some of the adverse effects that ME/CFS patients experience from certain drugs.


    Here is a list of drugs that may have damaging effects on mitochondria:


    I am not sure how reliable this list is, as there are no references given. The above list come from the website www.mitoaction.org. Further info from that website here: Mitochondrial Toxicity.

    Not in the above list is fluoroquinolone antibiotics, but this paper indicates that the fluoroquinolone antibiotic ciprofloxacin can cause a "selective loss of mitochondrial DNA (mtDNA)".

    As far as supplements go, berberine has been shown to have toxic effects on mitochondria.


    Chemicals in the environment can also cause mitochondrial toxicity:


    Evidence of mitochondrial DNA (mtDNA) damage has been found in Gulf War Illness (GWI), a condition symptomatically similar to ME/CFS; this may have come from organophosphate exposure during the Gulf War. (Interestingly enough, tumor protein p53 can help repair damaged mitochondrial DNA — see this post). But there is not much evidence for mtDNA damage in ME/CFS itself.
     
    Last edited: May 25, 2017
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  2. Diwi9

    Diwi9 Senior Member

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    @Hip - I'm curious about minocycline (took it for two years as a teen for acne). Cort has 2014 post on HealthRising discussing that it is potentially neuroprotective and also potentially protective of mitochondria: article.
     
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  3. gabriella17

    gabriella17 Senior Member

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    I feel pretty depressed reading this list. I take a lot of Tylenol (3k - 4k mg daily) as well as Aleve 2x daily.
     
  4. Hip

    Hip Senior Member

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    I would not get too concerned. Lots of people use these drugs on a long term basis without any apparent issues. These drugs might be more of an issue for people with known mitochondrial diseases (the website the list comes from is about inherited genetic mitochondrial diseases, which does not include ME/CFS).

    For ME/CFS patients, however, any mitochondria toxicity from these drugs may have little or no impact. The list is put up just for awareness, but it does not imply that you should avoid these drugs if you have ME/CFS.



    It's quite possible that minocycline has both benefits and negative aspects. There are no studies cited in that list of drugs with reported mitochondrial toxicity, so you'd have to look up the studies on minocycline mitochondrial toxicity, and get the fine details.
     
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  5. drob31

    drob31 Senior Member

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    I used tamoxifen before for non-cancer related things...
     
  6. Alvin2

    Alvin2 If humans were rational...

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    Pretty much, if these drugs were causing widespread mitochondrial damage it would be very apparent quite quickly with the number of people using them
     
  7. Hip

    Hip Senior Member

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    Indeed, I don't think anyone with ME/CFS should be worried about taking these drugs from the mitochondrial perspective. Maybe if you have Gulf War Illness, or if you had a major exposure to mitochondria-damaging environmental chemicals, you might be slightly more cautious.

    But even for people with known mitochondrial diseases, the www.mitoaction.org webpage on these drugs concludes that:
    So for those with mitochondrial diseases, they say that you should only avoid the drugs which are clearly toxic to the mitochondria; but for the drugs that are only potentially toxic, these can be used, but with some care.

    On that webpage it says that the antidepressant, antipsychotic, barbituate, anti-anxiety, cholesterol, analgesic/anti-inflammatory, beta blocker, anti-arrhythmic, antiviral, antiretroviral and cancer drugs in the list are only potentially toxic to mitochondria. So these perhaps are the least to be concerned about.

    But they say that the antibiotics tetracycline, minocycline, chloramphenicol and aminoglycosides can be harmful to the mitochondria (because they inhibit mtDNA translation and protein synthesis). And metformin, used for diabetes, is also considered toxic to mitochondria. So perhaps a bit more caution may be required with these.
     
    Last edited: May 21, 2017
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  8. pamojja

    pamojja Senior Member

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    Of this list I only seriously tested aspirin and metformin.

    Even a baby aspirin makes the next bowel movement mingled with blood. Tried one baby aspirin repeatedly with long periods between. But to no avail.
    Metformin I tried really hard on each of my yearly vacations in a high-carbing country because of my ridiculous carb-sensitivity. For the first 2 years I went through diarhea, nausea, vomiting, weiht-loss. Then I started to tolerate it increasingly better. However, after each vacation my serum B9 and B12 are tanked, and homocysteine at all time highs. Even depletes CoQ10 in my case. And that are all effects before considering mitochondrial.
     
  9. Valentijn

    Valentijn WE ARE KINA

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    The mitochondrial disease clinician I saw on Monday thought that non-genetic mitochondrial diseases could provoke the same reaction that I had to metformin.

    I'm not sure it's that easy to notice that the drug is doing damage to the mitochondria. Metformin is a hugely popular drug for Type 2 diabetes, yet of the 10-12 patients on this forum who mentioned trying it, none are still taking it. All but one stopped it due to it making them feel worse.

    And a large majority of patients who have tried amitriptyline or statins report a very bad experience with them, from what I've seen on this forum.
     
  10. eljefe19

    eljefe19

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    Metformin inhibits Akt and mTorC1 so it makes sense to me that it made pwme worse
     
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  11. eljefe19

    eljefe19

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  12. Skycloud

    Skycloud Senior Member

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    Interesting. I'm slowly coming off citalopram taken for anxiety which started in the autumn. I didn't feel anything that I considered untoward whilst going on it, but I did notice that this last winter I was worse than I think I should have been with many of my symptoms. (And this year not due to christmas) I wasn't expecting to relapse the way I did. I've dropped down from 20mgs to 15mgs 3 weeks ago and now feel noticeably better. Don't know hether it's down to this or not but shan't be going back on this again.
     
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  13. Gingergrrl

    Gingergrrl Senior Member

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    The Fluoroquinolone Antibiotics now have an FDA blackbox warning for Mito damage (Levaquin, Cipro etc). At least in the US-not that most doctors pay attention or alert patients to it.
     
  14. Hip

    Hip Senior Member

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    That interesting, and that's really the rationale for creating this thread: just for ME/CFS patients who are taking one or more of the above drugs on a long term basis to be on the lookout for any general worsening of their ME/CFS symptoms, which might potentially be due to a mitochondrial toxicity effect of the drugs.

    It does not necessarily mean that you have to avoid these drugs, but it's probably a good idea to monitor any worsening your ME/CFS symptoms while you are taking them.

    There was recently a post by ME/CFS patient @Vojta who became profoundly (and permanently) worse after taking a long term course minocycline and azithromycin.



    Would you have a link for that black box warning indicating mitochondrial damage as a side effect, as I cannot find any info on it. Possibly it was suggested, but has not yet been implemented?

    A few more studies on possible mitochondrial damage due to fluoroquinolones and other antibiotics:

    This study links quinolones, aminoglycosides, and beta-lactams to mitochondrial dysfunction.

    This study found that MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage.
     
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  15. Silence

    Silence

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    https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm513183.htm

    Direct quotes from the FDA:

    The FDA first added a Boxed Warning to fluoroquinolones in July 2008 for the increased risk of tendinitis and tendon rupture. In February 2011, the risk of worsening symptoms for those with myasthenia gravis was added to the Boxed Warning. In August 2013, the agency required updates to the labels to describe the potential for irreversible peripheral neuropathy (serious nerve damage).

    In November 2015, an FDA Advisory Committee discussed the risks and benefits of fluoroquinolones for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections based on new safety information. The new information focused on two or more side effects occurring at the same time and causing the potential for irreversible impairment. The advisory committee concluded that the serious risks associated with the use of fluoroquinolones for these types of uncomplicated infections generally outweighed the benefits for patients with other treatment options.

    Today’s action also follows a May 12, 2016, drug safety communication advising that fluoroquinolones should be reserved for these conditions only when there are no other options available due to potentially permanent, disabling side effects occurring together. The drug safety communication also announced the required labeling updates to reflect this new safety information.

    Couldn't find any info on specific mitochondrial damage except this:

    FDA Response to Citizen Petition: Southern Network on Adverse Reactions (SONAR), Docket No. FDA-2014-P-0856. The Petition requests that FDA require changes in the professional labeling of Levaquin (levofloxacin) regarding “Potential Mitochondrial Toxicity”.
     
    Last edited: May 20, 2017
  16. Gingergrrl

    Gingergrrl Senior Member

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    Will look later for a link and unable to right now b/c at my IVIG. I remember when two new warnings were added re: potential Mito damage, and psychiatric side affects like psychosis, to FQ antibiotics but now wondering if they were proposed but did not yet become black boxed?
     
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  17. Rvanson

    Rvanson Senior Member

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    Interesting. I will have to study this some more. That is quite a few medications, from many manner different classes of medications.

    Thanks for posting this!
     
  18. Learner1

    Learner1 Professional Patient

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    At last year's United Mitochondrial Disease Foundation conference, there were a couple of sessions on toxicity.

    There's a group at a university in the US building a database of drugs that are toxic to mitochondria. 75% of the drugs they tested proved toxic to mitochondria. They were warning the doctors of prescribing drugs that could inadvertently damage their patients.

    The conference also went through repair mechanisms for mitochondria. Good that they have them, but it was clear that there's a tipping point where you have so much damage its unfixable. Most diseases of aging are in some way related to mitochondrial damage.

    The list on Mito action is not comprehensive and is out of date. I was put on a 4 month course of ciprofloxacin, then later carboplatin and paclitaxel. None were on the list, but all are known to damage mitochondria, but my doctors never explained the risks, and now my mitochondria are damaged. And the doctors just say "Gee, so sorry... "

    From the presentations I saw, it would be wise to investigate any drug before taking it. And, they may not affect everyone equally. Some of us have genetics that make us more prone to damage... the proverbial canaries in the coal mine...
     
  19. Alvin2

    Alvin2 If humans were rational...

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    How do you know?
     
  20. Gingergrrl

    Gingergrrl Senior Member

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    http://www.myquinstory.info/fda-makes-label-changes-to-the-fluoroquinolones/

    I thought that the Citizen Petition had led to official changes in the FDA label of FQ antibiotics re: mitochondrial toxicity but apparently this has not gone through yet. I believe that it will one day.

    In researching this to find a link for this thread, I just learned that Dr. Jay Cohen passed away in Dec 2015. I am shocked and had no idea. I consulted with him in 2010 when I had a neurotoxic reaction to Levaquin and he was a very kind man and smart doctor.

    I am posting a link to what I think was his most powerful letter (to the US Senate) re: the overall toxicity of FQ antibiotics:

    http://www.medicationsense.com/articles/2014/letter.php

    Quotes from that letter:

    Edit: "FTS" is Fluoroquinolone Toxicity Syndrome

     
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