Persistent Fluoroquinolones in the Body and Delayed Adverse Reactions

This is a guest post written by Gary. You can read Gary’s story HERE. It contains a wonderful wealth of knowledge, insight, and advice. 

Fluoroquinolone side effects are often multisymptom affecting a wide range of bodily functions, ie: CNS, Muscles, Tendons, Brain, etc (Halkin, 1988l Mattappalil and Mergenhagen, 2014; Menzies et al., 1999; Moorthy et al., 2008; Thomas and Reagan, 1996; etc)

The chronic, often multisymptom, effects are not well documented and are normally assigned (often multiple) different diagnosis by doctors, such as clinical depression, fibromyalgia, etc/ (Strauchman and Morningstar, 2012)

I argue the reason for the chronic effects is because the Fluoroquinolones are not metabolized correctly, or the are metabolized and the normal biological enzymes that are responsible for detoxification of xenobiotic substrates is impared. A xenobiotic is a synthetic chemical such as Levaquin, Cipro, pestacides, etc. It’s also likely that FQ exposure changes gene expressions relating to various cytochrome P-450s (which is responsible for metabolizing and detoxification) causing your body to accumulate toxic chemicals, being unable to remove them.

For example, According to Liang et al., (2015), Fish that were exposed to a specific FQ had changes to cytochrome P450 1A (CYP1A), cytochrome P-450 3A (CYP3A), glutathione S-transferase (GST), P-glycoprotein (P-gp), which are all responsible for metabolizing and/or removal of xenobiotics. Other animals exposed to FQs were shown to have changes in cytochrome P-450 sites – For example, Dogs exposed to FQs showed inhibiting only cytochrome P-450 3A (Regmi et al., 2005; 2007), Chickens (Shlosberg et al., 1997; Granfors et al., 2004). To be fair, this might not affect humans completely, but this would likely explain the delayed toxicity to the CNS and other parts of the body – Delayed toxicity for FQ patients are likely a result of impared detoxification pathways due to FQ exposure overall which means the body has a high level of xenobiotics that cannot be removed.

There are even a few case studies on /people/ to support this article. In a paper (Strauchman and Morningstar, 2012), a patient was prescribed Moxifloxacin in 2005 and developed a worsening set of symptoms (after inclusion of medication), such as episodic tachycardia, episodic dizziness, episodic shortness of breath, and chronically swollen glands. Additional symptoms included daily episodes of nausea, sweating, tremors, brain fog, blurred vision, panic attacks, and phonophobia. Over the course of 3 years, after Moxifloxacin treatment, her condition improved, modestly.

In 2011, the PCP diagnosed the patient with diverticulitis and prescribed her ciprofloxacin 500 mg – Over the course of the treatment, she started to experience all the previous symptoms from 2005 – including panic attacks, insomnia, blurred vision, tachycardia, and nausea. This episode additionally included diffuse musculoskeletal joint pain. The patient also reported that her elbows, wrists, and knees seemed to crack too easily and too often. (p.3). Full workup was ordered, including genetic testing which showed the following:

– Genetic polymorphism in the cytochrome P-450 pathway

– Genetic variations in the catechol-o-methyl transferase enzyme, the Nacetyl transferase enzyme, and the glutathione-s-transferase enzyme necessary for glutathione conjugation and phase II detoxification.

The patient was also tested for polychlorinated biphenyls and other volatile solvents. They found the patient to have elevated levels of ethylbenzene, xylene, and the pesticide dichlorodiphenyldichloroethylene. Although these levels could indicate environmental accumulation, impaired detoxification pathways may make this accumulation more of a contributing factor.

Fluoroquinolone treatment seems to affect enzymes possesses, causing reduced activity due to chelation of ions, such as Se2 [Selenium], Mg2 [Magnesium], Fe2/3+ [Iron] (Badal et al., 2015; Uivarosi, 2013; Seedher and Agarwal, 2010) which explains the chronic issues, as well as delayed toxicity (due in part to impaired detoxification)

Even more evidence that either FQs remain in the body, impairing detoxification of xenobiotics (or they contribute to impairment) is from a journal (Cohen, 2008) where a patient was on a 14 day course of Moxifloxacin and became disabled, for many years; His symptoms were Brain Fog, Cognitive Defects/memory loss, tingling and numbness in his legs, joint pains, Achilles pain, Chronic Fatigue, Weakness, to a degree that he could barely stand or walk; The patient began IV Based Antioxidant therapy, and his condition improved considerably (95%+ recovery within a month). It’s highly likely that the IV Antioxidant therapy activated/modulated cytochrome P-450 to allow the patients body to excrete the excessive, normal environmental xenobiotics (and including Moxifloxican) and the patient recovered.

Fluoroquinolones have a very high melting point, over 200C, which means the crystals they form are very stable in neutral pH. (Andriole et al., 2000). If FQs are stuck within the cells, then that means they are responsible with mitochondrial ETC leakage, causing depressed health effects (ie: Brain Fog from FQ exposure is likely caused by FQs interfering with ATP energy output, which affects the Brain’s homeostasis).

What causes the delayed toxicity? There are only 3 possible explanations.

– You have pre-existing genetic polymorphisms in cytochrome P450s (and others) that prevent you from metabolizing and/or excreting FQs – Which leads to various normal systems in the body to suffer for a long period of time. (FQ crystals are ‘stuck’ in your body)

– FQs /cause/ the polymorphisms because they chelate heavy metals that enzymes require for proper biological function, such as phase II detoxification. Once this happens, your body begins to accumulate xenobiotics and you develop delayed toxicity.

– FQs cause mitochrondia dysfunction with organs responsible for generting glutathione, causing your body to have extremely low levels of glutathione, leading to increased amounts of xenobiotics that you cannot remove.

If this behavior takes place, how do we prove it?

– Genetic testing is the only way to be sure you have these Genetic polymorphisms/Genetic Variations – Some sites out there do provide this.

– Liquid Chromatography-tandem mass spectrometry will need to be performed on blood samples from people currently damaged by FQs to see if any concentrations of it exist in plasma.

– Total GSH testing would likely show lower-than-expected glutathione levels in the body with someone that is disabled, because if FQs are embedded in the cells, they are likly decreasing ATP output of various organs.

How would we remove the FQs that are ‘stuck’ in the body?

– Ozone is able to remove FQs from water (Feng et al., 2016). Therefor, Ozone therapy might be an idea If this behavior of FQs takes place.

– Fluoroquinolones have a Michael acceptor in them, making them very electrophilic. The non-aromatic double bond could potentially be subject to nucleophilic attack via a Michael addition, so one removal strategy could be allowing ligating the fluoroquinolone/associated polymorphs to something that is readily transported across cell membranes and excreted. However, this would need to be drawn up on a computer simulation to see if this could be done, cost effectively.

– Prolonged IV Antioxidant therapy, as shown above, seems to reverse FQ toxicity in some patients but further testing will need to be done (A heavy metal toxscreen via blood to be tested for chemical insult will likely need to be ordered)

Pharmacogenomics is going to likely show who is compatible with FQs and who isn’t, down the road–once we identify specific SNP’s that are broken with us floxies, the /good/ news is, with CRISPR technology, those of us with pre-existing polymorphisms (pre/post-FQ) will likely be able to have them corrected with little to no side effects.

Data from the following:

Strauchman M, Morningstar MW. Fluoroquinolone toxicity symptoms in a patient presenting with low back pain. Clinics and Practice. 2012;2(4):e87. doi:10.4081/cp.2012.e87.

N. L. Regmi, A. M. Abd El-Aty, R. Kubota, S. S. Shah, and M. Shimoda, “Lack of inhibitory effects of several fluoroquinolones on cytochrome P-450 3A activities at clinical dosage in dogs,” Journal of Veterinary Pharmacology and Therapeutics, vol. 30, no. 1, pp. 37–42, 2007.  ·  ·

N. L. Regmi, A. M. Abd El-Aty, M. Kuroha, M. Nakamura, and M. Shimoda, “Inhibitory effect of several fluoroquinolones on hepatic microsomal cytochrome P-450 1A activities in dogs,” Journal of Veterinary Pharmacology and Therapeutics, vol. 28, no. 6, pp. 553–557, 2005.  ·  ·

M. D. Brand, R. L. Goncalves, A. L. Orr et al., “Suppressors of superoxide-H2O2 production at site IQ of mitochondrial complex I protect against stem cell hyperplasia and ischemia-reperfusion injury,” Cell Metabolism, vol. 24, no. 4, pp. 582–592, 2016.  ·  ·

M. A. Simonin, P. Gegout-Pottie, A. Minn, P. Gillet, P. Netter, and B. Terlain, “Pefloxacin-induced Achilles tendon toxicity in rodents: biochemical changes in proteoglycan synthesis and oxidative damage to collagen,” Antimicrobial Agents and Chemotherapy, vol. 44, no. 4, pp. 867–872, 2000.  ·  ·

Krzysztof Michalak, Aleksandra Sobolewska-Włodarczyk, Marcin Włodarczyk, Justyna Sobolewska, Piotr Woźniak, and Bogusław Sobolewski, “Treatment of the Fluoroquinolone-Associated Disability: The Pathobiochemical Implications,” Oxidative Medicine and Cellular Longevity, vol. 2017, Article ID 8023935, 15 pages, 2017. doi:10.1155/2017/8023935

J. M. Radandt, C. R. Marchbanks, and M. N. Dudley, “Interactions of fluoroquinolones with other drugs: mechanisms, variability, clinical significance, and management,” Clinical Infectious Diseases, vol. 14, no. 1, pp. 272–284, 1992.

H. H. M. Ma, F. C. K. Chiu, and R. C. Li, “Mechanistic investigation of the reduction in antimicrobial activity of ciprofloxacin by metal cations,” Pharmaceutical Research, vol. 14, no. 3, pp. 366–370, 1997.

N. Seedher and P. Agarwal, “Effect of metal ions on some pharmacologically relevant interactions involving fluoroquinolone antibiotics,” Drug Metabolism and Drug Interactions, vol. 25, no. 1–4, pp. 17–24, 2010.

H. Koga, “High-performance liquid chromatography measurement of antimicrobial concentrations in polymorphonuclear leukocytes,” Antimicrobial Agents and Chemotherapy, vol. 31, no. 12, pp. 1904–1908, 1987.

A. Pascual, I. García, S. Ballesta, and E. J. Perea, “Uptake and intracellular activity of trovafloxacin in human phagocytes and tissue-cultured epithelial cells,” Antimicrobial Agents and Chemotherapy, vol. 41, no. 2, pp. 274–277, 1997.

V. T. Andriole, The Quinolones – Third Edition, Acedemic Press, San Diego California, 2000.

S. Badal, Y. F. Her, and L. J. Maher 3rd, “Nonantibiotic effects of fluoroquinolones in mammalian cells,” The Journal of Biological Chemistry, vol. 290, no. 36, pp. 22287–22297, 2015.

J. Y. Lee, S. H. Lee, J. W. Chang, J. J. Song, H. H. Jung, and G. J. Im, “Protective effect of metformin on gentamicin-induced vestibulotoxicity in rat primary cell culture,” Clinical and Experimental Otorhinolaryngology, vol. 7, no. 4, pp. 286–294, 2014.  ·  ·

Z. K. Salman, R. Refaat, E. Selima, A. El Sarha, and M. A. Ismail, “The combined effect of metformin and L-cysteine on inflammation, oxidative stress and insulin resistance in streptozotocin-induced type 2 diabetes in rats,” European Journal of Pharmacology, vol. 714, no. 1–3, pp. 448–455, 2013.  ·  ·

A. I. Morales, D. Detaille, M. Prieto et al., “Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway,” Kidney International, vol. 77, no. 10, pp. 861–869, 2010.  ·  ·

W. Chowanadisai, K. A. Bauerly, E. Tchaparian, A. Wong, G. A. Cortopassi, and R. B. Rucker, “Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression,” The Journal of Biological Chemistry, vol. 285, no. 1, pp. 142–152, 2010.  ·  ·

T. Stites, D. Storms, K. Bauerly et al., “Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice,” The Journal of Nutrition, vol. 136, no. 2, pp. 390–396, 2006.

Y. Huang, N. Chen, and D. Miao, “Biological effects of pyrroloquinoline quinone on liver damage in Bmi-1 knockout mice,” Experimental and Therapeutic Medicine, vol. 10, no. 2, pp. 451–458, 2015.  ·  ·

M. Feng, L. Yan, X. Zhang et al., “Fast removal of the antibiotic flumequine from aqueous solution by ozonation: influencing factors, reaction pathways, and toxicity evaluation,” Science of The Total Environment, vol. 541, pp. 167–175, 2016

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21 thoughts on “Persistent Fluoroquinolones in the Body and Delayed Adverse Reactions

  1. Don February 12, 2018 at 11:08 am Reply

    Does anyone know of a DNA site that would show if someone has the cytochrome p-450 variant?

  2. Gary February 12, 2018 at 3:18 pm Reply

    23andme can save your data, and geneticgenie.org has a ‘detoxification’ page you can upload your results to.

    • Don February 12, 2018 at 3:27 pm Reply

      Thanks Gary!

      • Don February 13, 2018 at 12:25 pm Reply

        Gary have you tried ozone therapy or researched it much? Also are you aware of a way to repair chromosome p450 if it is not functioning? I’m going to check mine because I i already have my 23 data. Have you checked yours yet?

        • Gary February 16, 2018 at 8:15 pm

          Don

          I have not tried Ozone therapy, but there are some people here who have tried it. I vaguely remember someone in Atlanta who tried it for about 2 months and it reversed their symptoms.

          To be fair, this might be placebo overall. But something is certain – Genetic issues are responsible for our side effects (as demonstrated in the above papers)

          I really wish we could get a Mass Spec performed on some floxies to see if the metabolites from FQs are in the cells.

        • Don February 17, 2018 at 6:00 pm

          Thanks for the response Gary. It’s been my personal belief that the FQ ‘s are still in our cells.

  3. Gérard February 12, 2018 at 3:43 pm Reply

    Thank you for the article, ozone therapy is really recommended in our case? I see several story of war that speaks positively! do we have any other info on the subject? a big thank-you
    sorry for english i’m belgian and the translation is from Google
    Gérard

  4. Gary February 12, 2018 at 11:22 pm Reply

    Hello Gérard

    I really wish I could say this would remove FQs from the body, but there is some anecdotal evidence from people that say it worked for them.

  5. Gerard February 13, 2018 at 3:48 am Reply
    • T February 13, 2018 at 6:44 pm Reply

      Gerard thanks for that article. Very interesting , I will give it a try !

  6. Gérard February 14, 2018 at 5:11 am Reply

    do not go too fast, I read more information not to hurt … interresant but we must be careful

  7. Gary February 26, 2018 at 2:38 pm Reply

    I’d be very very careful reading over ‘detoxification’ articles on various websites. You can’t detoxify yourself with a specific food, or diet; biological enzymes like CYP450’s and your kidneys are responsible for such detoxification of xenobiotics.

  8. Anna October 19, 2018 at 7:39 am Reply

    Can anyone tell me more about delayed effects? I wonder how long effects can be delayed. For example if someone took Cipro, and did not have symptoms for 3 months after, could they then develop symptoms that late? I just wonder if Floxies see the extent of the damage within the first 3 months.

    • Debs January 13, 2019 at 5:03 am Reply

      Yes, the first symptoms of FQ toxicity can be delayed for many months.symptoms can also, when they do arise whether immediately or months later, then often will multiply, & accumulate for varying amounts of time, Ie it was around18 months out before I had original symptoms stop popping up & accumulating in my most damaging floxing
      Another scenario, is that people can develop symptoms of FQ toxicity early on , these symptoms then sometimes will disappear, & people think they have been very lucky & dodged that FQ bullet , only for those delayed symptoms to then show up many months, or even later on, even after later prescriptions of FQs down the line.
      Symptoms for example in regards to the damage caused to connective tissue may perhaps not be noticeably FELT at all in a first floxing, & then the damage can accumulate over subsequent prescriptions of FQs, ‘ under the radar ‘ until it reaches a tipping point unique to the person where it becomes noticeable / visible.

      Nobody, bottom line, imo whether they are noticeably floxed or not, gets out of taking a FQ ‘ antibiotic’ completely unscathed at a DNA/mitochondrial level, the mechanism of action of the drug sees to that. The FQs cause damage to the DNA/mitochondria from the very first dose we take, its how the drugs ‘ work ‘. its just for some people, the damage caused by them is never seen, nor is it or felt, as in that particular person it is imperceptible, thus will be never noticed, never realised.
      This scenario is of course how industry gets away with disabling & murdering countless people with their mitochondrial damaging drugs, & one way of many they collect new customers, & how our Drs end up thinking Fluoroquinolone Iatrogenic injury is ‘ rare’, as If then a person develops symptoms/ health conditions later down the line, this situation of course will never be connected or reported on, by either the Dr or the patient to that harmless sounding FQ ‘antibiotic’ they may have taken many moons ago .

      http://www.myquinstory.info/fq-faq/

  9. Vanessa October 23, 2018 at 3:36 pm Reply

    I was floxed in February 2018. It was living a nightmare that no doctor understand or help. I went in desperation to a functional doctor whom I believe saved me. She did organic acids testing which revealed and prove what you are saying in this article. All mitochondrial markers were off and disfunctioning and glutathione was depleted. So at that time I was given NAC to rebuild glutathione. I also nutritionally built all the missing depleted back in over months. My diet is non inflammatory and very healthy. I take a lot of supplements still at 8 months, but am so much better. I think a big key is the NAC but also fixing other deficiencies. The mitochondria need acetyl l carnitine of which we just recently increased and my eyes are now working more normally for the first time since floxing. I suggest organic acids testing to any floxie so you can repair exactly whats depleted. A functional doctor is really the best.

    • Anna October 23, 2018 at 3:54 pm Reply

      I will buy some NAC and look into acetyl l carnitine. Thanks, Vanessa!

  10. Don January 30, 2019 at 3:56 pm Reply

    Debs says: “Nobody, bottom line, imo whether they are noticeably floxed or not, gets out of taking a FQ ‘ antibiotic’ completely unscathed at a DNA/mitochondrial level, the mechanism of action of the drug sees to that. I agree with that 100%. Once a Fluoriquinolone is ingested in my opinion it is with you for life. The level it can impair you can vary widely but I think once a Fluoroquinolone is in your body it is never completely eliminated.

    • Mike June 28, 2019 at 6:01 am Reply

      I don’t believe that one bit. The body has so many repair mechanisms, and through proper diet and exercise, whatever free radicals are in your body can be flushed out and excreted. I think people try to find a way to explain delayed onset of symptoms. Lifestyle and other environmental factors contribute to this.

      Based on the logic above, if everyone took a FQ, they would experience these side effects immediately and tissue turnover through normal exercise would do nothing – even with mitochondrial repair and excretion of toxins, free radicals, etc. Some even assume it gets stored in fat cells, which with exercise would burn that out and allow the body to flush the free radicals out of one’s system. People’s metabolic rates and body chemistries are different and the symptoms show up at different times for different folks. It’s very rare to see someone exhibit signs and symptoms of FQ toxicity more than three months after taking a final dose.

      Once the pill is in your system, the damage is done. But it is excreted, and sometimes it just takes time for the symptoms to show up. Free radicals are neutralized by antioxidants and other key vitamins and minerals.

      The key is and always will be exercise. That’s how you repair mitochondria and that’s how you burn fat cells – which is where FQs are – theoretically – stored. But no – it does not “stay in your system forever.”

  11. Debs September 29, 2019 at 1:44 am Reply

    The FQ does not remain in your body for the damage to be continually accruing/ showing up even many years down the line, mitochondrial turnover is important here . I personally have an open mind on this ‘ FQ remaining in the body’ aspect, until it is proven one way or the other., if this is ever possible.
    I have quite an open mind on this subject like I have on all others .ie my opinions are fluid and they change with the new information received. this is how science works, science is never ‘settled ‘. What I meant by that statement is that everyone has DNA / mitochondrial / cellular disturbances/changes on taking a FQ, nobody is excepted from this, as this how the drugs ‘work’. in the human body.

    It is actually not rare at all for people to exhibit new signs and symptoms of FQ toxicity more than 3 months down the line Mike, In my own case I had new symptoms showing up even 18 months after the event after my most damaging floxing, and after existing in this weird world for over 30 years and having been a member in our various groups for quite a few years I can confirm that I’m by far not the only one.
    I tend to share this view on the ‘ do the this FQs remain in the body ‘ question due to the research I have carried out myself.

    http://www.myquinstory.info/faq/fqs-remain-body/

  12. Debs September 29, 2019 at 1:45 am Reply

    That should be ‘ does not have to remain in the body ‘ , floxiefog strikes again

    • Remus Piricsi October 30, 2019 at 11:55 am Reply

      I think they do remain in the body i know in my case because everytime i do a detox symptoms come back just like when i took the antibiotic , maybe it’s not the case with everybody , first time i was having with gut issues, was prescribed Nacetylcistein for detox few days into it symptoms came back exactly like first time i took it, mind you when i took the first pil li had an immediate reaction like in an hour . So i had a panic attack after finishing my detox wich only happened when i took the pill then all the symptoms from the cracking to the headaches and fatigue came back but to a lesser extent over time they diminished, third time was 2 weeks ago when i was prescribed another natural treatement for my gut, i was having some gut issues not as severe as before but i wanted to get rid of them ,at this point most things were normal still had some cracking in knees but i could exercise energy was on point no pain ,floaters still present but everything else was my old self, a week into the treatement after taking my last dose again panic attack ,cracking in both knees , fatigue sleeping longer hours , severe cracking in both knees ,peripheral neuropathy wich was completely gone , even muscle twitching ,although again less severe than in prevous cases so i don’t know. I’m just going to start ozone therapy i’ll report back but personally at least in my case these events did not happen randomly just by chance it was everytime i tried to detox and these weren’t new symptoms just the same old. Mind you i had them from the start in my case they didn’t appear months after taking the drug but everytime i had a flare up was when i tried to detox my body through Glutathione or its precursor Nacetylcistein .

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