Tag Archives: mitochondria

Fluoroquinolone Toxicity Featured in NATURE

Fluoroquinolone toxicity is highlighted and featured in NATURE – one of the oldest, most reputable, journals in the world. This is so exciting!!

You can read the article, When antibiotics turn toxic, that was published in Nature on March 21, 2018 HERE.

Here are some highlights from the Nature article:

First, thank you to Dr. Miriam van Staveren whose story was told in the Nature article. She is a physician and a fellow “floxie.” Even as a physician, she had trouble getting her experience of being poisoned by Levofloxacin acknowledged:

“Since then, she has seen a variety of medical specialists. Some dismissed her symptoms as psychosomatic. Others suggested diagnoses of fibromyalgia or chronic fatigue syndrome. Van Staveren is in no doubt, however. She’s convinced that the antibiotic poisoned her.”

Second, the article mentions Fluoroquinolone Toxicity and Fluoroquinolone Associated Disability (FQAD) by name. This is huge! Rather than calling what we are experiencing something like, “a rare adverse reaction,” it is referred to as fluoroquinolone toxicity or FQAD. This is subtle acknowledgement that what we are going through is a syndrome–a thing in itself–not just a “side-effect” to be dismissed.

Third, even though the word “rare” is used throughout the article, and I know that this is annoying and off-putting for all of us who see that fluoroquinolone toxicity is NOT RARE, the article also notes that the frequency of fluoroquinolone toxicity is higher than many assume:

“From the 1980s to the end of 2015, the FDA received reports from more than 60,000 patients detailing hundreds of thousands of ‘serious adverse events’ associated with the 5 fluoroquinolones still on the market (most commonly tendon rupture, as well as neurological and psychiatric symptoms), including 6,575 reports of deaths. The FDA says that the reports of adverse events it receives — sent in by drug manufacturers, by doctors and directly by consumers — cannot be used to reach conclusions about the severity of problems associated with drugs. Still, the fluoroquinolones have attracted more complaints than other more widely used antibiotics. And only 1–10% of adverse events are estimated to be reported to the FDA, suggesting that fluoroquinolones might have harmed hundreds of thousands of people in the United States alone, says Charles Bennett, a haematologist at the University of South Carolina’s College of Pharmacy in Columbia. Bennett is also director of the Southern Network on Adverse Reactions, a state-funded pharmaceutical-safety watchdog, which has been working with people affected by fluoroquinolones since 2010.”

Fourth, mitochondrial damage is noted as a cause of fluoroquinolone toxicity:

“Accumulating evidence, Golomb says, suggests that fluoroquinolones are damaging mitochondria, the power packs inside human cells that evolved from symbiotic, bacteria-like cells billions of years ago. This kind of harm can affect every cell in the body, explaining why a wide range of symptoms can appear and get worse over time.”

Fifth, the article noted that Dr. Charles Bennett, may have found some genes shared by people who are hurt by fluoroquinolones:

“At a conference last September, Bennett reported preliminary data that might hint at why only some people develop serious side effects from fluoroquinolones. He took saliva samples from 24 people who reported neuropsychiatric side effects — such as memory loss, panic attacks and depression — and found that 13 of them (57%) shared a gene variant usually seen in only 9% of the population.”

If there are genes that make people more succeptible to disabling fluoroquinolone toxicity, perhaps those can be tested for before fluoroquinolone prescriptions are written.

Sixth, the article notes the obstacles that scientists, researchers, and doctors face when they question and investigate adverse drug reactions. It is noted that little support or funding for adverse drug reaction research is available, and that many scientists face push-back from pharmaceutical companies when they attempt to research fluoroquinolone toxicity.

Last, Floxie Hope was mentioned in the article. Squeee! What an honor and a privilege to be mentioned in an article in Nature!

“On websites and Facebook groups with names such as Floxie Hope and My Quin Story, thousands of people who have fallen ill after fluoroquinolone treatment gather to share experiences. Many of them describe a devastating and progressive condition, encompassing symptoms ranging from psychiatric and sensory disturbances to problems with muscles, tendons and nerves that continue after people have stopped taking the drugs. They call it being ‘floxed’.”

Those seven points are the highlights of the article, in my opinion, but I suggest that each of you read the article yourself. It’s currently (03/25/18) on the home-page of nature.com. Squee!



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


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.


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.




NSAIDs and FQs Damage Mitochondria, Increase Oxidative Stress, and Cause Cell Death

As I noted in the post, Why NSAIDs Suck for Floxies (and Probably Everyone Else Too), NSAIDs often exacerbate fluoroquinolone toxicity symptoms, and there are several mechanisms through which NSAIDs can interact with fluoroquinolones. The results of a recent article published in the Journal of Molecular and Cellular Cardiology by researchers at UC Davis, Different effects of the nonsteroidal anti-inflammatory drugs meclofenamate sodium and naproxen sodium on proteasome activity in cardiac cells, help to further explain why NSAIDs trigger fluoroquinolone toxicity symptoms, and why they are a horrible combination.

NSAIDs and Fluoroquinolones Damage Mitochondria

The study showed that NSAIDs “Attack mitochondria, reducing the cardiac cell’s ability to produce energy” (source).

Likewise, fluoroquinolones have been shown to attack mitochondria. The studies, Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells and Delayed cytotoxicity and cleavage of mitochondrial DNA in ciprofloxacin-treated mammalian cells show that fluoroquinolones damage mitochondria, deplete mitochondrial DNA, and cause oxidative stress.  Also, the FDA admits that mitochondrial damage is the likely mechanism through which fluoroquinolones cause peripheral neuropathy.

Healthy mitochondria are vital for cellular energy and health. Unhealthy mitochondria have been linked to many diseases, including M.S., fibromyalgia, M.E./C.F.S., P.O.T.S., diabetes, cancer, aging, and more. Do NSAIDs and fluoroquinolones increase one’s chances of getting those diseases that are related to mitochondrial dysfunction? It’s certainly reasonable to think so – via the mitochondrial damage link – but studies have not shown a direct connection (mainly because neither have been researched).

NSAIDs and Fluoroquinolones Increase Reactive Oxygen Species (ROS)

NSAIDs also “Cause the production of reactive oxygen species, which stresses heart cells and is associated with many diseases, including heart disease” (source).

Fluoroquinolones have also been shown to increase production of reactive oxygen species (ROS – aka oxidative stress). The article, Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients notes that, “Several in vitro and in vivo study using animals revealed that fluoroquinolones induced oxidative stress by producing reactive oxygen species (ROS)” and that in vivo human studies show that, “ciprofloxacin and levofloxacin induce more reactive oxygen species that lead to cell damage than gatifloxacin.

ROS are described as follows:

Without oxygen, we could not exist. However, in the process of generating energy by “burning” nutrients with oxygen, certain “rogue” oxygen molecules are created as inevitable byproducts. Known as free radicals and reactive oxygen species, these unstable, highly reactive molecules play a role in cell signaling and other beneficial processes when they exist in benign concentrations.  But when their numbers climb, as may occur as a result of aging and other conditions, they may wreak havoc with other molecules with which they come into contact, such as DNA, proteins, and lipids. As such, these “pro-oxidant” molecules become especially toxic.

In fact, a prevailing theory of disease and aging states that the gradual accumulation of pro-oxidant molecules, and the harm they incur, is responsible for many of the adverse changes that eventually cause various diseases. These include cancer (possibly triggered by free radical-induced damage to cellular DNA) and inflammatory and degenerative diseases such as Alzheimer’s, arthritis, atherosclerosis, and diabetes. While scientists have not yet reached consensus on the topic, accumulated evidence overwhelmingly identifies increased oxidative stress with age as a source of damage to cellular structure and function. (source)

To drastically over-simplify things, ROS are the opposite of antioxidants. If you’ve ever read about the benefits of antioxidants like vitamin C or glutathione, ROS have the opposite effects. In excess, ROS are harmful and damaging to cells.

NSAIDs and Fluoroquinolones Cause Cell Death

NSAIDs were found to “Impair the cardiac cell’s proteasome, the mechanism for degrading harmful proteins. This leads to toxic buildup and eventually to the death of cardiac cells” (source).


Fluoroquinolones have also been found to cause cell death (apoptosis). This has been shown in many articles that note that fluoroquinolones are useful as chemotherapeutic agents specifically because they kill cells. Unfortunately, they don’t just kill cancer cells, they also kill healthy cells. The following articles note that fluoroquinolones are chemotherapeutic drugs that damage and kill cells:

  1. In an article published in the journal Urology, it was noted that, “Ciprofloxacin and ofloxacin exhibit significant time and dose-dependent cytotoxicity against transitional carcinoma cells.” That’s great – excellent, actually – if you happen to have carcinoma cells in your bladder. But if you just happen to have a bladder infection, chemo drugs that exhibit toxicity toward human cells – cancer or otherwise – are inappropriate for use (1).
  2. The mechanism for action for fluoroquinolones is that they are topoisomerase interrupters (2).Topoisomerases are enzymes that are necessary for DNA replication and reproduction. All of the other drugs that are topoisomerase interrupters are approved only for use as chemotherapeutic agents. It is only appropriate to use drugs that disrupt the process of DNA replication and reproduction when someone’s cells are already so messed up that they have cancer.
  3. Fluoroquinolones have been found to interfere with the DNA replication process for human mitochondria (3, 4, 5). Mitochondria are vital parts of our cells, (cellular energy is produced in our mitochondria), and disrupting the process through which mitochondrial DNA replicates causes cellular destruction, oxidative stress and disease.
  4. Fluoroquinolones have been shown to be genotoxic and to lead to chromosomal abnormalities in immune system cells (6).
  5. Fluoroquinolones disrupt cellular tubulin assembly (7). All of the other drugs that disrupt tubulin assembly are chemotherapeutic drugs.
  6. Fluoroquinolones disrupt enzymes, including CYP1A2 enzymes, which are necessary for detoxification.

Avoid NSAIDs and Fluoroquinolones

Dr. Aldrin V. Gomes, one of the authors of Different effects of the nonsteroidal anti-inflammatory drugs meclofenamate sodium and naproxen sodium on proteasome activity in cardiac cells, “advised caution when using NSAIDs either topically or orally” (source). Likewise, caution is warranted when using fluoroquinolones, as one can gather from reading any of the stories of pain and suffering caused by fluoroquinolones. Personally, I will do everything in my power to avoid both NSAIDs and fluoroquinolones for the rest of my life. Mitochondrial destruction, oxidative stress, and cell death aren’t things I want.

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Loss of Faith in the Healthcare System

After getting “floxed,” I lost a lot of faith in the medical system.

I used to think that the medical system, as a whole, was trustworthy. I knew that the system was imperfect, but I thought that most of the problems had to do with cost and insurance, and that drugs generally were well understood and regulated, and that they did more good than harm.

Getting hurt by a prescription drug, an antibiotic no less, shook my faith in the medical system. Researching fluoroquinolones and other drugs made me realize how little anyone knows about how drugs work, and why they sometimes don’t work, and I further lost faith in the system.

As I witnessed a prescription drug causing people to be chronically ill, I started to wonder if many of the chronic illnesses (autoimmune diseases, neurodegenerative diseases, mysterious diseases like ME/CFS and fibromyalgia, diabetes, etc.) were due to the cellular destruction inflicted by prescription drugs. Many prescription drugs, not just fluoroquinolones, wreak havoc on the microbiome, mitochondria, neurotransmitters, and more–and problems with those systems have been linked to many of the chronic diseases of modernity.

I saw that the only thing that the FDA is inclined to do about adverse drug reactions is to increase the size of the warning labels–as if anyone reads the warning labels and as if this is actually a solution. I noted that thousands of people are killed by prescription drugs each year, and I lost faith in the FDA’s ability to regulate the pharmaceutical industry.

The 21st Century Cures Act, a piece of legislation that is going through Congress right now, is a thinly-veiled give-away to the pharmaceutical industry that decreases drug regulation at a time when it needs to be increased. Congress is not only failing to recognize the problem of prescription drugs hurting and killing people, it is actively encouraging the pharmaceutical industry to do more of the same. I didn’t have a lot of faith in the U.S. Congress before I got “floxed,” but I have even less faith in them now. (If you want to read my take on the 21st Century Cures Act, I wrote about it in the post, “The 21st Century Cures Act” Is On Its Way – Here’s Why You Haven’t Heard About It that was published on Collective Evolution on 7/7/15.)

I wonder how many other people there are like me–who no longer trust the medical system after being hurt by it. I suspect that most (but certainly not all) people who get hurt by prescription drugs no longer view the system as a whole as trustworthy or credible.

Once a system loses credibility, many people opt out of it and seek alternatives. If the healthcare system loses credibility in the minds of most people, and most people opt out of it, it will, eventually, collapse. I have no idea when this will happen, or even if there are enough people who think like me that it will happen. We shall see.

Unfortunately, a lot of people are currently being hurt by adverse drug reactions, and more people will have to get hurt for a crash to happen. I don’t hope for a crash. I hope that the regulators (the FDA) start doing their jobs and that the pharmaceutical companies start upholding their credos and start having morals. I wish I saw that happening, but I don’t. Maybe we will reach a tipping point where it will happen–to be determined.

The healthcare industry is immense, and it is much more complicated than the sub-prime housing market that crashed in 2007-2008. However, I see some similarities between the sub-prime housing market crash and my assertion that the healthcare industry is going to crash (at some point–maybe). Those similarities are described in the post, The Healthcare System Collapse: Lessons from the Housing Market Crash and “The Big Short” that was published on Hormones Matter yesterday – 2/4/16. (This post started as an intro to the Hormones Matter post, and it just morphed into its own post. Please read and share The Healthcare System Collapse: Lessons from the Housing Market Crash and “The Big Short” – Thanks!)

I foresee a crash in the medical system because I’ve lost faith in it. Maybe I’m wrong and other people will respond differently from how I have after getting hurt by the medical system. Maybe I really am “rare” and other people won’t get hurt by the medical system. Or, maybe drugs will get more and more dangerous because of lack of regulation, and more and more people will get hurt by pharmaceuticals and they will lose faith in the system just like I did, and the demise of the system as we know it will arrive. To be determined, and we shall see. Hopefully I’m just being too pessimistic and the FDA will start doing a better job at protecting people from dangerous drugs. I really do hope that occurs.

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Bulletproof Radio Interview

I had the honor of being interviewed by Dave Asprey for Bulletproof Radio, one of the best, and most popular, health podcasts in the world.

Check it out!

Bulletproof fluoroquinolone antibiotics



Please subscribe to Bulletproof Radio, download episode #263, “Know Your Antibiotics & Restore Your Mitochondria” and tell all your friends to do the same. Thank you!

Bulletproof Radio has more than 1,000,000 subscribers, and to be able to reach that many people with information about fluoroquinolone toxicity is, potentially, a very, very, very big opportunity, and a very big deal for the “floxie” community.

Where do I even begin describing what an honor it is to have the opportunity to be featured on Bulletproof Radio, Dave Asprey’s popular and influential podcast?

Dave Asprey is the ultimate Bio-Hacker. (You can read about his biohacking endeavors in this article – http://www.mensfitness.com/life/entertainment/inside-personal-health-laboratory-bulletproof-coffees-dave-asprey-worlds-most.) He has sought to optimize his health and performance in all areas, and he has shared his optimal diet, as well as supplement tips, on his web site, https://www.bulletproofexec.com/, and in his excellent book, The Bulletproof Diet: Lose up to a Pound a Day, Reclaim Energy and Focus, Upgrade Your Life.

According to his bio on facebook, “Dave Asprey is a, biohacker, Silicon Valley investor, entrepreneur and the man behind Bulletproof® Coffee. He is the founder of Bulletproof Nutrition, which reaches more than 1.5 million visitors monthly. His top-ranked podcast, Bulletproof Radio, has 9+ million downloads. He has also been featured on the Today show, Nightline, CNN, and in Financial Times, Rolling Stone, Men’s Health, Vogue, Marie Claire, Slate, Forbes, and more. He lives with his family in Victoria, British Columbia.”

And, according to the iTunes summary of Bulletproof Radio, “Bulletproof Executive Radio was born out of a fifteen-year single-minded crusade to upgrade the human being using every available technology. It distills the knowledge of world-class MDs, biochemists, Olympic nutritionists, meditation experts, and more than $250,000 spent on personal self-experiments. From private brain EEG facilities hidden in a Canadian forest to remote monasteries in Tibet, from Silicon Valley to the Andes, high tech entrepreneur Dave Asprey used hacking techniques and tried everything himself, obsessively focused on discovering: What are the simplest things you can do to be better at everything? Welcome to being Bulletproof, the State of High Performance where you take control and improve your biochemistry, your body, and your mind so they work in unison, helping you execute at levels far beyond what you’d expect, without burning out, getting sick, or just acting like a stressed-out a*****e. It used to take a lifetime to radically rewire the human body and mind this way. Technology has changed the rules. Follow along as Dave Asprey and guests provide you with everything you need to upgrade your mind, body, and life.”

It is truly an honor to have the opportunity to share information about fluoroquinolone toxicity on Bulletproof Radio. Thank you for listening!


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Floxie Hope Podcast Episode 14 – Dr. Terry Wahls

It was an absolute HONOR to interview Dr. Terry Wahls for episode 14 of The Floxie Hope Podcast. Dr. Wahls has inspired millions of people with her personal story of putting progressive multiple sclerosis (M.S) into remission through diet and lifestyle changes. She is the author of The Wahls Protocol: A Radical New Way to Treat all Chronic Autoimmune Conditions Using Paleo Principles. In addition to reversing the course of various autoimmune diseases, the Wahls Protocol has helped thousands of people to recover from mysterious chronic illnesses like Lyme Disease, fibromyalgia, chronic fatigue syndrome / M.E, and fluoroquinolone toxicity.

In this interview, Dr. Wahls and I discuss how mitochondria can be repaired through diet and lifestyle changes. We go over the basics of The Wahls Protocol diet, and we discuss how everyone who has been hurt by a mitochondrial poison can nourish their cells. Information about Dr. Wahls can be found on http://terrywahls.com/.

You can listen to the podcast through these links:



Please accept my sincere apologies for the horrible sound quality in the first 5 minutes of the podcast. It is better after the 5 minute mark, so please hang in there and listen past the fuzziness at the beginning.

Renee’s story illustrates how helpful The Wahls Protocol is for those suffering from fluoroquinolone toxicity – https://floxiehope.com/renees-story-cipro-reaction/.

Dr. Wahls’ TED talk has been viewed more than 2.2 million times and has inspired and touched every person who has viewed it. I encourage you to listen to the podcast, buy the book, and watch Dr. Wahls’ inspirational TED talk


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