Fluoroquinolone Toxicity Article – Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications

I’m so excited to share this article, “Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications” by Krzysztof Michalak, Aleksandra Sobolewska-Wlodarczyk, Marcin Włodarczyk, Justyna Sobolewska, Piotr Woźniak, and Bogusław Sobolewski, with you! It is the first article of its kind that I’ve seen. While there are thousands of articles about fluoroquinolones, many of which focus on the damaging effects of fluoroquinolones, and many case-studies that note the adverse-effects of fluoroquinolones (hundreds of articles about fluoroquinolones are linked HERE), this is the first article that acknowledges that fluoroquinolone toxicity (referred to as both Fluoroquinolone Associated Disability (FQAD) and fluoroquinolone toxicity throughout the article) is a disabling syndrome, that also goes over the mechanisms by which fluoroquinolones can cause fluoroquinolone toxicity/FQAD, and even gives recommendations on how to treat fluoroquinolone toxicity/FQAD (while also acknowledging that there are no cures or verified treatments). The article even calls for more extensive research to be done into fluoroquinolone toxicity, and the various mechanisms through which fluoroquinolones hurt people.

It is an enlightening article, and I encourage you to print it out and give it to your doctors, family members, and anyone else who is interested in what fluoroquinolones do and how they hurt people. In this post, I’m going to go over some highlights from the article, but I recommend that you read it yourself (you can access it through THIS LINK, after clicking on the “provisional pdf” link).

The first paragraph of the abstract to the article states:

“Long term Fluoroquinolone Associated Disability (FQAD) after fluoroquinolone (FQ) antibiotic therapy appears in recent years a significant medical and social problem, because patients suffer for many years after prescribed antimicrobial FQ-treatment from tiredness, concentration problems, neuropathies, tendinopathies and other symptoms. The knowledge about the molecular activity of FQs in the cells remains unclear in many details. The effective treatment of this chronic state remains difficult and not effective. The current paper reviews the pathobiochemical properties of FQs, hints the directions for further research and reviews the research concerning the proposed treatment of patients.”

To see that in writing, in an academic article, is incredibly validating.

Adverse Effects of Fluoroquinolones

Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications, goes over the documented effects of fluoroquinolones. For tendinopathies and tendon ruptures, researchers have found that:

“FQs are associated with an increased risk of tendinitis and tendon rupture. This risk is further increased in those over age 60, in kidney, heart, and lung transplant recipients, and with use of concomitant steroid therapy.”

Fluoroquinolones cause neurotoxicity, as well as central and peripheral nervous system ailments:

“Taking FQs is associated with their neurotoxicity, as well [5-8]. The main symptoms being correlated to FQ treatment include insomnia, restlessness, and rarely, seizure, convulsions, and psychosis [9-11]. Many reports point to chronic persistent peripheral neuropathy to be generated by FQs [12-18]. Cohen et al. [19] showed that a possible association between FQ and severe, long-term adverse effects involving the peripheral nervous system as well as other organ systems are observed.

Fluoroquinolones also cause cardiotoxicity and an elongation of the QT interval, as well as hepatotoxicity and nephrotoxicity. Fluoroquinolone use has even been linked to type-2 diabetes onset.

Fluoroquinolone toxicity / FQAD is a multi-symptom, chronic illness that affects all body systems. Fluoroquinolones deleteriously affect every muscle, tendon, ligament, nerve, and even bone, in the body. They damage every cell in the body.

Fluoroquinolone Damage Mechanisms

Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications, notes the various mechanisms by which fluoroquinolones cause cellular (mitochondrial) damage, including oxidative stress, and the downstream effects of oxidative stress, including disruptions in the mitochondrial Permeability Transition Pore (PTP) (and the article authors state, “The influence of FQs on the detailed regulation of PTP is the urgent topic for further research.”), Calcium and magnesium homeostasis, lowered ATP production, and more.

Here is a diagram of the mechanisms of fluoroquinolone toxicity (published in the article):

Figure 2. The main ways of FQ toxicity. The positive regulatory loops magnifying the toxicity of FQs are marked with ‘+’. The ‘?’ signs denote the possible but not confirmed effects of FQ toxicity.

The article also notes the epigenetic effects of fluoroquinolones and oxidative stress:

“Beside OS (oxidative stress), epigenetic effects of FQs are of high importance, as well. The epigenetic effects may depend on the methylation of DNA and/or histones, however, ROS contribute also to epigenetic changes [42]. Some authors point also to the similarity of bacterial and mitochondrial DNA, both existing in circular super-twisted helices and gyrase-like enzymes being postulated to be responsible for the organization of mitochondrial DNA, suggesting the possible direct effect of FQs to mitochondrial DNA leading to the disturbed mitochondria regeneration and division [43, 44]. The changes in the cytoskeleton were observed also after FQ treatment [45] and cytoskeleton has been demonstrated to be strictly connected with energy dissipation and organization in mitochondria [46-49].”

Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications, also notes that fluoroquinolones chelate various minerals and metals. The article notes that, “Seedher’s results indicate that chelation formation with bivalent metals can cause significant alterations in the human serum-FQ binding affinity.” The article also describes how fluoroquinolones chelate iron, zinc, magnesium, and other minerals, and how this chelation can have enzymatic and even epigenetic adverse effects.

Fluoroquinolones are GABA antagonists, and the effects of fluoroquinolones are similar to those of benzodiazepine withdrawal. The authors of Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications, describe a potential mechanism through which GABA is depleted by fluoroquinolones:

“One of the proteins which can support PTP opening is Translator Protein (TSPO), called also peripheral-type benzodiazepine receptor or isoquinoline binding protein. TSPO is predominantly located on the surface of the mitochondria where it is postulated to physically associate with VDAC-ANT. It has been suggested that TSPO may activate PTP opening, causing ∆Ψm reduction and leading to apoptosis [80, 81]. Some authors suggest that epileptogenic activity of FQs possibly relates to GABA-like structure of some FQs which may allow them to act as GABA antagonists [82, 83]. Since TSPO is also a benzodiazepine receptor, similar interaction may maybe also take place between FQs and TSPO leading to opening PTP.”

I have always wondered how GABA inhibition is connected to mitochondrial destruction. The article excerpt above answers that question for me.

Fluoroquinolones can lead to chronic illness and permanent disability, which has led many people to question whether or not they remain in the body for an extended period of time (or, if they do damage while they’re in the body that continues long after the drug has left the body). The authors of Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications note that:

“The other important feature of FQs has been presented by V.T. Andrioleet al. [55]. Namely, they estimated the minimum solubility of FQs in neutral pH. They pointed that this class of molecules is characterized by very high melting point, generally >200°C, which indicates that the crystal forms are very stable. All these FQ features strongly support the thesis that FQs can survive in the cell for a long time contributing to chronic, long-term adverse reaction in patients treated with FQs. The question, to what extent takes this phenomenon place and if it contributes to chronic symptoms of FQAD, remains unclear.”

It is acknowledged throughout the article that it is unknown whether or not fluoroquinolones stay in the body for an extended period of time. It is possible, through the mechanism noted above, but no hypotheses about fluoroquinolones remaining in the body after they “should” have been metabolized and fully excreted, have been explored. It’s both possible that they remain in cells, and that they don’t – no one really knows.

The article authors repeatedly call for additional research into the various mechanisms by which fluoroquinolones lead to pain, disability, and chronic illness:

“Summing up, the number of enzymes possessing reduced activity due to their ion-cofactor chelation is probably long and it is the important topic for further research. The separate problem consists the chronicity of ion-chelation by FQs. The presented research does not describe the chronic state of FQAD but the phenomena taking place during FQ application. It must be analyzed, to which degree persistent ion chelation takes place at FQAD patients.”

Fluoroquinolone Toxicity Treatment

Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications is the first article I’ve seen that discusses the treatment of fluoroquinolone toxicity as a multi-symptom, chronic illness. The authors note that the first step in approaching a treatment is to discover why fluoroquinolones are causing chronic illness in the first place. Effective treatment, of course, depends on effective identification of the problem. With that noted, the article authors have enough knowledge to make a few suggestions:

“Until detailed knowledge concerning FQ toxicity would be recognized, the following directions in supporting FQAD patients are proposed according to the known and probable mechanisms of FQ toxicity: A. reduction of the oxidative stress; B. restoring reduced mitochondrial potential ∆Ψm; C. supplementation of uni- and bivalent cations that are chelated by FQs;D. supporting the mitochondrial replication in the cell – pulling the more destroyed to apoptosis and proliferation of the more healthy ones; E. removing FQs permanently accumulated in the cells (if this phenomenon takes place); F. regulating the disturbed epigenetics and enzyme activities”

The article authors note that antioxidant supplementation is a broad topic and that fixing the damage done by fluoroquinolones and oxidative stress is not as simple as just ingesting an antioxidant pill. However, antioxidant supplements that specifically target the mitochondria have shown some promising results:

“The antioxidants which enter easily the mitochondria are the most interesting ones. Lowes et al. [79] shows that the mitochondria targeted antioxidant MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells. In cells treated with MitoQ the oxidative stress was lower and mitochondrial membrane potential was maintained.”

Other antioxidants have also had promising results in repairing fluoroquinolone treated cells. Some of the antioxidants with promising results include N-acetylcysteine, resveratrol, as well as Vitamins C and E. Supplementation of the trace minerals that are important cofactors for antioxidants is also important.

Conclusion

I greatly appreciate the authors of Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications. They approach fluoroquinolone toxicity/FQAD as a complex and multifaceted illness. It IS a complex and multifaceted illness, and it is refreshing to read an article that doesn’t over-simplify or downplay the illness. I also appreciate the exploration of what is currently known about fluoroquinolone toxicity/FQAD, and the assertions that more research into fluoroquinolone toxicity is needed (it is!). I think that everyone who is going through fluoroquinolone toxicity/FQAD should read it, and share it as widely as possible.

 

 

 

Tagged: , , , , , , , ,

16 thoughts on “Fluoroquinolone Toxicity Article – Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications

  1. L September 6, 2017 at 9:23 am Reply

    Sorry, all I could think of reading this was…”yes, we already know that.” You know who doesn’t? The doctors who keep prescribing it.

    • Lisa September 6, 2017 at 9:28 am Reply

      I appreciate that they’re listening.

      • L September 6, 2017 at 9:52 am Reply

        I know. I didn’t mean to sound so cynical. Just frustrated that this info never seems to get to the people who most need to hear it. Thanks for all you do Lisa. xo

  2. Chris September 6, 2017 at 12:09 pm Reply

    Good info here. Like I said before, I have one of the best gastroenterologists in the state of California and he recommended these things and for me it’s a cute.

    1) Staying active, even if by simple walking in the evenings or at the beach.
    2) Taking 2 capsules of VSL3 daily. Every 12 hours to be precise.
    3) Drinking at least 3 bottles of water a day. (We should be doing this anyway)
    4) Getting a good night sleep with plenty of air or even fans.
    5) Avoid Motrin, Naproxen, Endocin, NSAIDS
    6) Avoid steroids

    The key is time. Time has shown to also greatly decrease symptoms.
    I am also one of many that has taken over 60 tablets in a 30 day period.

    Looking back now I believe the toxicity starts not with just with the antibiotic, but the mixing of an NSAID or steroid with the Cipro. That to me is what’s started everything.

    • Chris September 6, 2017 at 12:11 pm Reply

      Wow, this site is horrible. This sites spellcheck doesn’t work via new iPhone.

  3. Jeremy September 6, 2017 at 1:39 pm Reply

    Bravo, we now that, but still very important step in recognising the problem of Fluoroquinolone Associated Disability (FQAD).

    I’m proud that team from Poland, my homeland, wrote this article!

  4. Alex September 6, 2017 at 5:10 pm Reply

    Considering the duration that fluoroquinolones have been on the market, it’s baffling that it took so long for medical professionals to publish this journal. Let’s see how much time it takes for doctors to become educated with this information.

    I’m turning 30 later this year. I’ve suffered from Crohn’s disease since I was 11. Lived with depression since my youth as well. Nothing that I’ve experienced in my life is worse than the symptoms of FQAD. It hurts me to say this, but I may be dead by the time effective treatment is provided for this systemic toxicity.

    Thank you for actively running this site and continuing to post updates, Lisa. You’ve contributed to prolonging my life. My parents are the primary reason that I haven’t put myself out of my misery. The secondary reason is the hope that you’ve instilled and your positive influence in general. I can’t express how much I appreciate the time and effort that you dedicate to helping others who are afflicted with this condition.

    • Lisa September 7, 2017 at 2:42 pm Reply

      Hi Alex,

      Your comment took my breath away and brought tears to my eyes. I’m struggling to find appropriate words in response. Everything feels so trite – I’m sorry for what you’re going through, hang in there, have hope, keep going, and I really hope that a cure and healing are found in time for you. I hope for those things for you, but the words don’t feel adequate. Virtual hugs, thoughts, and prayers aren’t adequate either, but they’re being sent your way.

      Thank you for your kind and generous words. I’m glad, and honored, to have helped.

      All my best,
      Lisa

      • L September 7, 2017 at 4:19 pm Reply

        💜💜💜💜

  5. Thomas Sealy September 6, 2017 at 8:00 pm Reply

    Mahalo Lisa for this very important information! Will be adding some MitoQ to my diet.

    Sent from my iPhone

    >

  6. Don September 9, 2017 at 12:07 pm Reply

    This is very exciting news, thank you for sharing Lisa. I’m interested in how the authors came to study this topic and if they are planning on studying any further or trying some of the possible treatments on patients. Do you think it would be possible to have them on the podcast to pick their brains some more Lisa? I noticed they list the author’s email address, we should all be writing to thank him!

  7. Julie Anderson September 9, 2017 at 4:11 pm Reply

    I am new to this group and actually unsure if I have issues from taking Cipro as it was many, many years ago and I was diagnosed with Lupus after taking the Cipro… anyhow I do have a variety of joint problems and severe body aches etc. But for now I don’t get the lingo being used in some of these posts and I am wondering what ‘MitoQ’ is as well as ‘capsules of VSL3’ ??? I do find it all very interesting and helpful… I had no idea that others had suffered after taking these antibiotics! Thank you very much!

    • Lisa September 9, 2017 at 8:15 pm Reply

      Hi Julie,

      I’m glad to hear that you’re exploring the Cipro connection! Knowledge is power, and it can even be helpful for healing.

      MitoQ and VSL3 are both supplements. MitoQ is an antioxidant supplement, and VSL3 is a probiotic supplement. I believe that both are available on Amazon and info on both can be found through searching for them on this page and on google. Ruth’s Story and Brett’s story both have a lot of great information about MitoQ in them.

      Regards,
      Lisa

  8. Renan September 23, 2017 at 5:07 pm Reply

    I don’t know how much I can take this situation anymore.

    Just 25 y.o.
    My health is destroyed and my family thinks I am crazy. Sometimes I think I should just end my own life. Suicide seems the only choice.

    • L September 23, 2017 at 5:34 pm Reply

      Renan, I was suicidal for months. I had over 30 side effects, including vision loss, gasping for every breath, olfactory nerve damage to where everything in the world asphyxiated me making me a shut in. I dropped 1/4 of my weight and needed help to move and I experienced the most excruciating pain I have ever know. I wanted “out” more than anything. Somehow I got through and I am so glad today that I didn’t do anything to remove myself. I know it may seem hopeless now but please hang in there. I had horrific damage and lost more than a year of my life. I am now 2 1/2 years out and while I still have side effects I am light years from where I was, and back to doing most of what I did before.

      I am so so sorry your family doesn’t believe you. It just adds insult to injury. You might want to show them the FDA’s FQAD (fluoroquinolone associated disability) information. You can also direct them to Dr Jay Cohen’s book: “How We Can Halt the Cipro and Levaquin Catastrophe: The Worst Medication Disaster in U.S. History.”

      Do you have an integrative doctor or naturopath? If not I urge you to see one. They will likely believe you, when regular allopathic (western) doctors do not. And they can help you heal. Please stay with us.

    • Lisa September 24, 2017 at 9:17 am Reply

      I’m so sorry for all that you are going through, Renan! Please stay with us, and with all your loved ones. I know that this journey is difficult and painful. Please try to have faith that the pain will shift, and hopefully even end. I know that L, who commented above, has come far in her healing. I am hopeful that you will too. Please stay around to see.

      Hugs,
      Lisa

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: