Tag Archives: ciprofloxacin

Ciprofloxacin Depletes Exosomal DNA

Journal of Extracellular Vesicles, “Biological properties of extracellular vesicles and their physiological functions”

The study, “Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA” published in Nature, found that, “ciprofloxacin induced the release of both DNA (mitochondrial and chromosomal sequences) and DNA-binding proteins on the exofacial surfaces of small extracellular vesicles referred to in this paper as exosomes.” And, “Our results reveal for the first time that prolonged low-dose ciprofloxacin exposure leads to the release of DNA associated with the external surface of exosomes.”

In the discussion section of “Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA” the authors expand on their findings:

“Exposure of Jurkat cells to ciprofloxacin has been shown to induce oxidative stress, production of reactive oxygen species, mitochondrial dysfunction, inhibition of the respiratory chain and decrease of mitochondrial membrane potential leading to mitophagy47. Our MS analysis has also confirmed the above biological processes in Jurkat cells. Importantly, the presence of ciprofloxacin has been reported to lead to the loss of mtDNA28, 29 and an aneuploidy caused by the genotoxic stress of Jurkat cells30, 48. Genotoxic stress response has been shown to induce the release of nucleosomes by leukemic myeloid cells49. In the present study, mitochondrial damage of ciprofloxacin-exposed Jurkat cells has been evidenced by the abundance of mtDNA, and the nucleoid protein FEN1, as well as numerous other mitochondrial proteins in the secreted vesicles. Ciprofloxacin inhibits both the bacterial DNA gyrase and the mammalian topoisomerase II enzymes responsible for proper DNA replication50. Given that ciprofloxacin mainly inhibits the mitochondrial isoform of mammalian topoisomerase II29, its presence induces mtDNA fragmentation as well as subsequent gradual decrease in mtDNA content29.”

And also note that:

“We found that the exosomal DNA release-inducing effect was not solely observed in the case of Jurkat cells as we also detected ciprofloxacin-induced release of exofacial EV DNA in the case of the pancreatic cancer cell line MiaPaCa. These results demonstrate that DNA-associated EVs may be released from various types of cells after long-term ciprofloxacin exposure.”

These findings are interesting, and I think consequential and explanatory.

But, I am guessing that most people reading this need some more information about what the excerpts above mean. I know I did (and I had to read it about five times).

First, understanding “Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA” requires a little knowledge of what extracellular vesicles and exosomes are.

Extracellular vesicles (EVs) are “lipid bilayer-delimited particles that are naturally released from a cell and, unlike a cell, cannot replicate. EVs range in diameter from near the size of the smallest physically possible unilamellar liposome (around 20-30 nanometers) to as large as 10 microns or more, although the vast majority of EVs are smaller than 200 nm. They carry a cargo of proteins, nucleic acids, lipids, metabolites, and even organelles from the parent cell. Most cells that have been studied to date are thought to release EVs, including some bacterial, fungal, and plant cells that are surrounded by cell walls. A wide variety of EV subtypes have been proposed, defined variously by size, biogenesis pathway, cargo, cellular source, and function, leading to a historically heterogenous nomenclature including terms like exosomes and ectosomes.” (Source)

Exosomes are a subtype of extracellular vesicles. “Exosomes are best defined as extracellular vesicles that are released from cells upon fusion of an intermediate endocytic compartment, the multivesicular body (MVB), with the plasma membrane.” (Source) More information (that’s only basic if you have a heavy science background) about exosomes can be found in “Q&A: What are exosomes, exactly?

Basically, they’re molecules secreted from cells that affect other cells (sometimes positively, sometimes negatively).

Here’s a series of videos that give a really high-level, shiny and high-production-value explanation of exosomes and extracellular vesicles:

Additionally, here are some interesting tidbits about extracellular vesicles (EVs) and exosomes gathered from various articles:

“In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored.” (Source)

“EVs alone regulated the expression of numerous genes related to inflammation and signaling.” (Source)

“EVs are carriers of pathogen-associated and damage-associated molecular patterns, cytokines, autoantigens and tissue-degrading enzymes. In addition to a possible role in the pathogenesis of a number of inflammatory conditions, such as infections and autoimmune diseases, EVs, including microvesicles (also known as microparticles), exosomes and apoptotic vesicles, have therapeutic potential and might be used as biomarkers for inflammatory diseases.” (Source)

“another significant role of EVs has emerged in the removal of unwanted molecular material as a means for cell maintenance.” (Source)

“This report is the first show that numbers of blood-derived EVs are elevated in patients suffering from CFS/ME, indicating their potential involvement in disease pathogenesis. This promising finding may not only provide insights into the mechanisms involved in the disease but also shows that EVs may be useful for early diagnosis of illness. Moreover, isolation of circulating EVs coupled to our prototype for their detection by LFIA may constitute a powerful diagnostic tool, which can be performed in a single step and in minutes. We concluded that EVs may play a critical role in CFS/ME. Studies with larger sample size, outcome measures and different study designs (i.e. cross-sectional vs. longitudinal cohorts) are now urgently needed. These studies should stratify subgroups according to illness onset and progression, and assess patients at baseline and following induction of post-exertional malaise (PEM), using the 2-day cardiopulmonary exercise test (CPET).” (Source)

“Mast cells, being capable of both degranulation and subsequent recovery, have recently attracted substantial attention as also being rich sources of secreted extracellular vesicles (including exosomes and microvesicles).” (Source)

Both extracellular vesicles and exosomes contribute to processes that are related to many illnesses (including multi-symptom chronic illnesses like ME/CFS and autoimmune diseases, as well as cancer), as well as some of the processes behind those diseases such as inflammation, mast cell activation, cellular signaling and communication, etc. Neither extracellular vessicles nor exosomes are bad though – they are neither good nor bad. They are a natural function, and their relationship to these disease processes may be to spread the disease or prevent the disease, depending on many more factors than I can even begin to fathom.

I surmise and assume though, that removal and depletion of DNA from exosomes, is not a healthy or productive thing to do. And as this study showed, ciprofloxacin, and probably other fluoroquinolones, remove/deplete DNA from exosomes.

Can the removal of DNA from exosomes trigger inflammation? Can the depletion of DNA from exosomes change the inter-cellular communication in ways that trigger illnesses? Extracellular vesicles and exosomes are involved with the immune system, so can depletion of DNA from exosomes trigger immune dysregulation or autoimmune diseases? In depleting DNA from exosomes, does ciprofloxacin trigger disease? We know that ciprofloxacin can trigger multi-symptom chronic illness – is the depletion of exosomal DNA the mechanism through which it “floxes” people?

I don’t know the answers to those questions, and I doubt that the scientists who know much more about cellular processes than I do know those answers either. But “Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA” raises some really interesting questions, and provides some interesting and insightful links for those of us who are exploring what occurs in the body of a “floxed” person.

Sources*:

Nature, “Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA

BMC Biology, “Q&A: What are exosomes, exactly?

Journal of Extracellular Vesicles, “Biological properties of extracellular vesicles and their physiological functions

Cellular and Molecular Life Sciences, “Critical role of extracellular vesicles in modulating the cellular effects of cytokines.

Nature Reviews. Rheumatology., “Emerging role of extracellular vesicles in inflammatory diseases.

Journal of Extracellular Vesicles, “Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study

Seminars in Cell and Developmental Biology, “Mast cell secretome: Soluble and vesicular components.

*I found these sources through the post “Nature’s Quinolones: The 4Qs” on FluoroquinoloneThyroid.com – you should check it out – it’s great.

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New Study Finds that Ciprofloxacin Depletes Mitochondrial DNA

An excellent article about the effects of ciprofloxacin (a fluoroquinolone antibiotic) on mitochondrial DNA was recently published in the journal, Nucleic Acids Research. The article, Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2, by Anu Hangas, Koit Aasumets, Nina J Kekäläinen, Mika Paloheinä, Jaakko L Pohjoismäki, Joachim M Gerhold, and Steffi Goffart, gives a great amount of insight into the damage that ciprofloxacin does to mitochondria, and I recommend that you read it (linked through the article title). I’m going to go over the article in this post, and point out some of the more interesting findings.

First, a bit of background information to help readers to understand the article.

Mitochondria are the energy centers of our cells. There are over ten million billion mitochondria in the human body (Lane p. 1). Each cell (with a few exceptions) contains an average of 300-400 mitochondria that are responsible for generating cellular energy through a process called ATP (Adenosine Triphosphate). Mitochondria regulate energy production, aging, epigenetic signaling between and within cells and many other important functions. Proper functioning of mitochondria is vital, and when mitochondria are not operating properly, a wide range of disease states can ensue (2).

Mitochondria have their own DNA (mtDNA) that is separate from (though it interacts with) nuclear DNA. The structure of mtDNA is similar to that of bacterial DNA, and it is widely thought that mitochondria descended from ancient bacteria. The similarities between bacteria and mitochondria should make everyone take pause to think about how antibiotics of all kinds are affecting mitochondrial health. This post, and the article that it is based on, only focuses on the effects of ciprofloxacin, a fluoroquinolone antibiotic, on mitochondrial health, but if you want to read about the effects of other antibiotics on mitochondria, the article “Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells” is a great place to start.

There are enzymes in our cells called topoisomerases. According to the wikipedia article for topoisomerase:

Topoisomerases are enzymes that participate in the overwinding or underwinding of DNA. The winding problem of DNA arises due to the intertwined nature of its double-helical structure. During DNA replication and transcription, DNA becomes overwound ahead of a replication fork. If left unabated, this torsion would eventually stop the ability of DNA or RNA polymerases involved in these processes to continue down the DNA strand.

In order to prevent and correct these types of topological problems caused by the double helix, topoisomerases bind to DNA and cut the phosphate backbone of either one or both the DNA strands. This intermediate break allows the DNA to be untangled or unwound, and, at the end of these processes, the DNA backbone is resealed again. Since the overall chemical composition and connectivity of the DNA do not change, the DNA substrate and product are chemical isomers, differing only in their global topology, resulting in the name for these enzymes. Topoisomerases are isomerase enzymes that act on the topology of DNA.[1]

Bacterial topoisomerases and human topoisomerases proceed via similar mechanisms for managing DNA supercoils.

The mechanism of action for all fuoroquinolones is that they are topoisomerase interruptors. The FDA warning label for ciprofloxacin states that the mechanism of action for ciprofloxacin is, “The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.”

Here is a video that describes how fluoroquinolones work, and how they interrupt topoisomerase and thus interrupt the process of bacterial (and mitochondrial, as we shall discuss below) DNA replication.

I have argued, and I believe, that EVERY drug that is a topoisomerase interruptor, should be thought of as a chemotherapy drug. All other topoisomerase interrupting drugs ARE chemo drugs. But fluoroquinolones are thought of as antibiotics, and handed out as if they are inconsequential. They are extremely consequential though, and they are hurting too many people. More information on fluoroquinolones being chemo drugs can be found in the post, “Cipro, Levaquin and Avelox are Chemo Drugs.”

Now to highlight some of the important parts of Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2.

The abstract of the article, Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2, notes that:

“Loss of Top2β or its inhibition by ciprofloxacin results in accumulation of positively supercoiled mtDNA, followed by cessation of mitochondrial transcription and replication initiation, causing depletion of mtDNA copy number. These mitochondrial effects block both cell proliferation and differentiation, possibly explaining some of the side effects associated with fluoroquinolone antibiotics.”

When you look into the multiple roles of mitochondria–from controlling cellular energy production to aging, and the links between mitochondrial damage and various multi-symptom chronic illnesses (from ME/CFS to autism to autoimmune diseases), yes, most definitely, the damaging effects of fluoroquinolones on mitochondria can certainly explain many, if not all, of the side effects associated with fluoroquinolone antibiotics.

The study found that, “In agreement with the in vitro assay, also HeLa cells treated with ciprofloxacin or doxorubicin rapidly accumulated supercoiled mtDNA (Figure 3A).”

This accumulation of supercoiled mtDNA led to a “change in topology” of the mitochondria, and a depletion of the mitochondrial DNA. Per the article:

“The change in topology caused by the inhibition of mitochondrial Top2 was connected with an impairment of mtDNA replication. 7S DNA, the 650bp ssDNA strand incorporated at the D-loop region of mtDNA, was rapidly depleted upon ciprofloxacin, ethidium bromide and doxorubicin treatment.”

Ciprofloxacin treatment not only depleted mtDNA, it also inhibited mtDNA synthesis:

“ciprofloxacin treatment reduced mtDNA copy number by 18% within 3 days (Figure 3C). As at the same time the growth rate of ciprofloxacin-treated cells was strongly reduced doubling time 170.2 h versus 22.7 h in untreated controls (Supplementary Figure S4), the observed depletion reflects a nearly complete inhibition of mtDNA synthesis.”

Ciprofloxacin treatment, and the resulting supercoiled mtDNA, also stalled mtDNA replication.

“Ciprofloxacin caused a strong reduction in these intermediates already after 2 h treatment (Figure 3E). After 20 h, this effect was clearly enhanced, with the strand-asynchronous intermediates being replaced by strand-coupled replication intermediates, a hallmark of mtDNA replication stalling (25,31–33).”

It was also found that ciprofloxacin inhibited the increase of mtDNA that typically comes with building muscle. It was found that:

“The impairment of mtDNA maintenance by ciprofloxacin not only disturbed cellular proliferation and the physiological increase of mtDNA copy number during muscle maturation, it also effectively impaired the fusion of confluent myoblasts to multinuclear myotubes (Figure 4E) and cell differentiation as indicated by the reduced expression of the heavy chain of Myosin II, a marker of differentiated skeletal muscle (Figure 4F).”

In the paragraph that the above quote was taken from, it was stated that “This increase (of mtDNA when muscle matures) was completely abolished by ciprofloxacin.” I’ve said it multiple times before, but, again, fluoroquinolones should NEVER be given to athletes (or anyone who values their ability to move, or have their heart beat).

In the article’s discussion section, this summary of the demonstrated damage done by ciprofloxacin was given:

“Ciprofloxacin caused a dramatic effect on mtDNA topology, blocking replication initiation, reducing copy number and inhibiting mitochondrial transcription (Figures 2B3AE and 4A). Ciprofloxacin, the third most commonly used antibacterial antibiotic, stops the cleavage/re-ligation reaction of type II topoisomerases midway, generating double-strand breaks, persistent protein–DNA adducts and reduces also the overall enzyme activity (30). Its toxicity to mitochondria has been reported in various studies, suggesting a broad range of mechanisms including topoisomerase inhibition, oxidative stress, altered calcium handling and photosensitization (38–40). In our study, we observed ciprofloxacin to clearly reduce Top2 topoisomerase activity both in vitro and in vivo, but did not find any indication of increased mtDNA double-strand breaks (Figure 3AC). However, ciprofloxacin did impair the overall mtDNA integrity in post-mitotic cells (Figure 4D). As our detection method (long-range PCR) does not distinguish between strand-breaks, abasic sites or base alterations inhibiting Taq polymerase, the observed effect might be caused by oxidative damage, which fluoroquinolones have been reported to induce in a variety of cell types (41,42).”

And the study’s authors also surmise that many of the severe adverse effects of fluoroquinolones are due to the depletion of mtDNA caused by the drugs:

“The severe side effects of ciprofloxacin and other fluoroquinolones include tendinopathies such as tendon rupture, joint inflammation, muscle weakness, central and peripheral neuropathies, epilepsy and psychological symptoms such as depression. These symptoms have been proposed to be connected to enhanced oxidative stress (42,54,55), but the molecular mechanism remained unclear. The reduction of mtDNA copy number and mitochondrial transcription caused by the altered topology of mtDNA might result in severe dysregulation of the electron transport chain complexes, as known to occur under ciprofloxacin treatment (56), lead to respiratory chain dysfunction and cause the observed enhanced oxidative stress.

Ciprofloxacin has also been reported to interfere with physiologically significant cell differentiation processes, such as spermatogenesis (57), brain development (41), bone mineralization (58), as well as to induce renal toxicity and heart arrhythmia (59). While the molecular mechanisms of these adverse effects are yet unclear, mitochondria play a central role in all of these physiological processes, making mitochondrial impairment a likely culprit for the disturbed cellular physiology.”

Throughout the article, the effects of ciprofloxacin are compared to the effects of another topoisomerase interrupting drug, doxorubicin. Per its wikipedia post, Doxorubicin “is a chemotherapy medication used to treat cancer.[3] This includes breast cancer, bladder cancer, Kaposi’s sarcoma, lymphoma, and acute lymphocytic leukemia.” The authors of Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2 noted that, “Interestingly, doxorubicin had a similar, but milder inhibitory effect on mtDNA replication than ciprofloxacin.” Why, yes, it is interesting that a drug that is marketed and dispensed as an antibiotic is more damaging than a similar drug that is marketed and dispensed as a chemotherapy drug. It’s very interesting indeed. It is also interesting that another topoisomerase interrupting chemotherapeutic drug, topotecan, was found to increase the expression of genes related to autism (“Topoisomerases facilitate transcription of long genes linked to autism“).

The Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2, authors conclude their article with two points. First, that very little is known about the consequences of mtDNA supercoiling. “Although central in bacterial genome maintenance, the whole phenomena of DNA supercoiling and its functional implications are virtually unstudied in mitochondria and calls for future research.” Yes, future research is needed, and better late than never. But nalidixic acid, the backbone of all fluoroquinolone antibiotics, was first used clinically in 1967. Shame on the medical and scientific communities for not studying the effects of fluoroquinolones on mtDNA earlier. We should have known more about the consequences of these drugs long before millions of prescriptions had been doled out, and millions of people affected.

Second, the authors of Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2 conclude by stating, “As fluoroquinolone antibiotics are widely used and effective drugs against a number of important bacterial pathogens, their dosage, systemic enrichment and side-effects should be reviewed in the mitochondrial context, and their clinical use should be considered with great care.” Yes, indeed, the effects of fluoroquinolones on mitochondria should be given long, hard, thoughtful consideration by every doctor, pharmacist, scientist, and every relevant person in the FDA and other regulatory agencies.

Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2 is an eye-opening article with groundbreaking research. Yes, more research needs to be done. But the research that has been done, that is described in the article, is greatly appreciated. Thank you to all the authors – Anu Hangas, Koit Aasumets, Nina J Kekäläinen, Mika Paloheinä, Jaakko L Pohjoismäki, Joachim M Gerhold, and Steffi Goffart.

 

Floxie Hope Podcast Episode 26 – Tamara

I had the pleasure of interviewing Tamara for Episode 26 of The Floxie Hope Podcast.

Please check out the podcast through this link:

https://itunes.apple.com/us/podcast/floxie-hope-podcast/id945226010

You can also read about Tamara’s journey:

https://floxiehope.com/tamaras-story-cipro-toxicity/

Tamara wrote her recovery story back in 2014. She has since had a beautiful, healthy, vivacious little girl, and her life has changed significantly in the last 4 years.

She speaks about her journey through fluoroquinolone toxicity, and how her life has changed in the last 4+ years since she was hurt by Cipro in this episode of The Floxie Hope Podcast.

Thank you for sharing your journey, Tamara!

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Subscriptions, reviews, and shares of The Floxie Hope Podcast are greatly appreciated! Please let me know if you have questions about how to do any of those things.

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EMA Hearing on Fluoroquinolone Toxicity Part 1

The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) held a hearing regarding the risks of permanent and disabling effects of fluoroquinolones (i.e. Fluoroquinolone Toxicity) on Wednesday June 13, 8018. More than 100 patient testimonials were submitted to the PRAC, and several dozen people who suffered from fluoroquinolone toxicity testified before the PRAC in-person.

The patients who testified were asked to answer three questions:

  1. What is your view on the role of quinolones and fluoroquinolones in the treatment of infections?
  2. What is your view of the risks associated with quinolone and fluoroquinolone use?
  3. In your opinion, what further measures could be taken to optimize the safe use of quinolones and fluoroquinolones?

You can watch the hearing, and listen to the patient testimonials, through this video:

All of the patient testimonials were moving, thought-provoking, and insightful. Thank you to all who testified – many of whom traveled hundreds of miles/kilometers to get to the hearing. It is because of the people who testified (including those who testified in writing) that the PRAC now knows how truly devastating fluoroquinolones are. Hopefully they will be moved to action by the testimonials provided.

A transcript of the hearing will be published, and I will link to it when it is available. In the meantime, I will highlight some of the testimonials given during the hearing. I highly recommend that you watch the video, as the words directly from the victims’ mouths are much more powerful than my synopsis.

Elizabeth Carmouche testified that she was given ciprofloxacin as a prophylactic “in case” she got a urinary tract infection or travelers’ diarrhea while on holiday. She only took two of the prescribed pills, and has been suffering from the devastating effects of those pills for more than two years. She went from being an active to a woman with no pain, to suffering from severe joint, muscle, tendon, and bone pain, as well as peripheral neuropathy. She testified that doctors were unable to help her, and many dismissed the connection between ciprofloxacin and her ill health. She asserted that the following measures need to be taken:

  1. There needs to be official recognition of fluoroquinolone toxicity syndrome, and doctors need to be made fully aware of what the syndrome entails.
  2. Bayer, and the other pharma companies that produce fluoroquinolones, need to identify the precise mechanism of damage done by fluoroquinolones, and those companies need to establish a protocol for healing those who have been hurt by fluoroquinolones.
  3. Patients damaged by fluoroquinolones should be treated and guided by medical professionals.
  4. A red-flag system needs to be put in patient records so that those who have experienced an adverse reaction to a fluoroquinolone are never given fluoroquinolones again.

In closing, Elizabeth notes that fluoroquinolones are linked to mitochondrial damage, and that mitochondrial damage is linked to many diseases including Parkinson’s, Alzheimer’s, and other serious and severe diseases.

The next presenter was a pharmacist from Northern Spain named Manex Bettan Arguinzoniz (Bettan). He was just 37 years old when ciprofoxacin destroyed his body, mind, and health. He went from being athletic and able to play with his children, to being unable to do many of the activities that he loves. Despite being a pharmacist, he was unaware of the debilitating, disabling, and devastating effects of ciprofloxacin. He also found that his doctors and other specialists were unaware of the extent of the damage done by fluoroquinolones. His doctor (who is also his father in law) was only convinced of the link between Bettan’s health problems and ciprofloxacin when another doctor who had studied at the Mayo Clinic noted the reality of the link. Bettan suggests that fluoroquinolones be restricted so that they are only used in life-or-death situations in hospitals. He suggests that a stronger, possibly black-box, warning be added so that patients are aware of the dangers of fluoroquinolones.

One of the EMA PRAC members asked Bettan if he got his information about fluoroquinolone toxicity from patient testimonials or scientific papers. He answered that he read many papers about fluorouinolones. There are hundreds of research papers about fluoroquinolones and the damage they do listed on https://floxiehope.com/fluoroquinolones-links-resources/.

The next presenter was Richard Cooknell. Richard was a firefighter before he was poisoned by quinolones. He is still unable to work, and suffers from many ill effects. He asserts that quinolones are used too widely, and that their use should be restricted to life-or-death situations. Richard points out that fluoroquinolones are often inappropriately prescribed for non-bacterial chronic prostatitis. He also points out that there is no information in the warning label about the effects of fluoroquinolones being permanently disabling, or that adverse reactions can be delayed. Richard was able to gain a diagnosis of fluoroquinolone toxicity by a rheumatologist, and he asked that fluoroquinolone toxicity be more officialy recognized and diagnosed by more doctors.

Richard points out that his prostatitis was non-bacterial, as many cases of prostatitis are, and that he never should have been given fluoroquinolones for a non-bacterial ailment. The post, “Cipro is no better than a PLACEBO at treating chronic prostatitis / chronic pelvic pain syndrome” goes over some information about this.

Richard also points out that NSAIDs and steroids have caused set-backs for him and many other victims of fluoroquinolones toxicity.

The next speaker was Markus Hamedinger. Markus suffers from tendon and joint pain, and has received a confirmed diagnosis of fluoroquinolone toxicity. Fluoroquinolone toxicity has severely affected Markus’s life, and he is unable to do many of the activities that he used to enjoy. His symptoms have not improved in the 2+ years that he has been sick.

Markus asserts that fluoroquinolones are used too often, and that they are inappropriately used when other, safer, antibiotics could be used. He notes the delayed adverse reactions to fluoroquinolones are a factor in keeping the effects of fluoroquinolones under-recognized. He says that doctors need to be made aware of exactly which infections need to be treated by fluoroquinolones, and which infections can be treated with other antibiotics. He also states that fluoroquinolone use should be banned in agriculture, to prevent exposure to fluoroquinolones from occurring through meat consumption.

The PRAC Chairwoman asked a question about repeated exposure making the reaction worse, and Markus noted that his reactions got worse and worse with each fluoquinolone exposure.

The next presenter was Miriam Knight. Miriam also presented on behalf of Raymond Miller and Geoffrey Robinson. Miriam is the co-founder of Quinolone Toxicity Support UK, and is also an administrator for Fluoroquinolone Toxicity Victims in Europe.

Miriam asserts that there is no role of quinolones/fluoroquinolones in the treatment of disease. She notes that mitochondrial DNA wasn’t known, studied, or acknowledged when quinolones were developed, and that they are chemotherapeutic agents.

Miriam points out that despite the official death toll from quinolones being low, there are many people who are hurt by these drugs in fatal ways – including aortic aneurysm.

Miriam notes the damage done by quinolones to mitochondrial DNA, and how mitochondrial DNA damage effects individuals differently depending on a variety of factors.

Miriam asserts, “There will never be a safe use of quinolones. They will always cause damage, observed or not.” And she also states that if removing them from the market is impossible, they should at least be severely restricted.

Miriam also asserts that quinolone toxicity should be a diagnosable illness with a diagnosis code. This is incredibly important in getting it acknowledged and quantifying the damage done by quinolones.

Miriam connects the dots between chronic pain, fibromyalgia, ME/CFS and fluoroquinolone toxicity.

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There are several dozen other testimonials. In the interest of the attention-spans of those reading this, I am going to split my notes about the hearing into several posts. This is the first of __ (tbd) posts about the hearing.

THANK YOU to all who testified. The testimony provided is wonderful, thoughtful, passionately delivered, and those who provided it represented themselves and the “floxie” community wonderfully!

End note – To those who testified, if I misspelled your name, please let me know. Also, if anyone would like me to publish their testimony directly, please send it over. Thank you!

 

 

 

Can Floxies Drink Alcohol?

Many people have asked me if they can/should drink alcohol post-flox.

As with most things, the answer is – it depends, and everyone is different.

Some Floxies tolerate alcohol fine, while others don’t.

Alcohol is, of course, bad for you. It’s hard on the liver, and can lead to cirrhosis and alcoholic hepatitis. It burdens your liver’s detoxification abilities and hinders your ability to get rid of other toxins. Alcohol wreaks havoc on the gut microbiome, and can encourage candida growth. Alcohol weakens the immune system, and can make you more succeptible to other illnesses. I could go on and on because there are hundreds of articles about the harm that alcohol inflicts on the human body. No matter how many videos come out about tequila being a probiotic, or articles there are about wine containing resveritrol, alcohol is not a health elixir. It is not good for you.

HOWEVER, it is quite fun (IMO), and it even has some health benefits–it’s a painkiller and it reduces feelings of stress and anxiety. Alcohol has enough redeeming qualities that billions of people around the world, most of whom are aware of the negative effects of alcohol, consume it. I do, and so do many other floxies.

When I first got floxed, I stopped drinking for a while. My body was going hay-wire in every conceivable way, and I didn’t want to contribute to my problems by knowingly consuming a substance that is bad for me. I think that abstaining from alcohol during the acute phase of fluoroquinolone toxicity was the right thing for me to do.

Once my body stabilized (i.e. it stopped feeling like a bomb was going off in my body, and I even had some improved/normal days) I started having a drink every once in a while. Even though I could drink, I found that my tolerance for alcohol was greatly diminished. Before I got floxed I could handle three-ish drinks in an evening (and I thoroughly enjoyed drinking them). After getting floxed, my tolerance was one drink a night (that was barely enjoyable). I didn’t even want to drink more than that–I struggle to explain why, but I just felt done after 3/4 of a drink. Over time (I am now a bit over 5 years post-flox) my tolerance increased, and I can now comfortably have two alcoholic beverages in an evening. That’s plenty for me, in my personal opinion of how much I should/shouldn’t drink.

I never experienced a relapse in fluoroquinolone toxicity symptoms as a direct result of drinking alcohol, but other people have, and I encourage everyone who wants to drink post-flox to be very careful and cautious with alcohol consumption. Comments such as this one, from Bob (and the comment just above it when you click on the link, from Ann), are examples of alcohol triggering an increase in, or relapse of, fluoroquinolone toxicity symptoms:

After getting floxed I had relapses to alcohol which I only drank on vacation. I suspect this is due to severe kill off of gut flora. I am afraid to drink anymore.

This comment from Mark also notes that alcohol consumption can lead to fluoroquinolone toxicity symptom flares:

I cheated this weekend and drank alcohol/ate dairy. You know what? It flared up my cipro symptoms full force. Knee joints started cracking like crazy, achilles heal flare, etc. I’m convinced that we are all suffering an overgrowth of yeast and the faster we can get that under control, the healthier we will be.

Some people have a more moderate reaction to alcohol post-flox. This comment, from Ruth, is really interesting and insightful. Though she can drink alcohol without issue, she typically abstains:

I am able to drink again but my tolerance is greatly reduced. It won’t actually harm your gaba receptors because alcohol acts on gaba-b instead of gaba-a. I think it promotes healing.

When the alcohol downgrades the gaba-b subunit, I think the body makes repairs to some of the a subunits in order to put things back in balance.

I think when the FQ took out some of your gaba-a receptors your body gave you extra gaba-b receptors. This can make you a lot more receptive to the effects of alcohol. The b unit seems to be able to replace itself faster. That’s why alcohol withdrawal lasts a lot less long than benzodiazepine withdrawal. This is all just my theory. I have nothing to back it up with except my own experience.

Last year I got drunk at the Racine Zoo by accident. They hosted a teacher’s night and served spiked punches with no indication that they were alcoholic. I had what they had labeled as “Lesson Learned Lemonade.” I was thirsty so I slammed a big cup. At first I felt super relaxed and I thought that my nervous system must really be healing. Maybe it was that walk on the beach… and then I felt it. I knew it had been alcoholic. I ended up drunk off my ass, but not so bad that I couldn’t say “gamma amino butyric acid,” ha, ha. I got a brief relapse from that experience, of symptoms I had not had in a long time. After that ended my base line seemed higher.

So I think alcohol is not completely bad. However, it can devastate your gut microbiome, so I am very careful about it. I had a tiny tiny bit of Bailey’s at Christmas. I enjoyed it. Other than the holidays I abstain from alcohol for the sake of my healthy flora.

Although it won’t stop your nervous system from healing, remember that psych symptoms can also stem from an imbalance of healthy vs. unhealthy microbes. Alcohol can worsen that situation considerably so for the foreseeable future it is better to abstain. Farther down the road you will probably be able to have a beer now and then with no ill effects.

Some people have even found that alcohol has helped them. It is a pain reliever and relaxant. It reduces anxiety and stress – even the anxiety and stress that comes with getting poisoned by a pharmaceutical. Stress and anxiety reduction are crucial for healing from fluoroquinolone toxicity. Both Bronwen and Barbara noted that they felt better with moderate alcohol consumption.

Bronwen’s Comment:

As far as booze goes, I actually found one drink helped lessen my symptoms a bit when they were getting overwhelming in the evening – much to my surprise, but I have only ever read one other person that found the same thing – most find the opposite. Again, test yourself! I certainly could not have more than one drink. The liver is struggling along with the other organs, as the clearing house for toxins, so alcohol puts another burden on it.

Barbara’s Comment:

My saving grace is I am allowed wine 😁😁 hallelujah .I have been able to drink alcohol from the begining and in certain times when the pain was bad I swear it helped.

As you can see, reactions to alcohol post-flox vary considerably. So, what should your take-away from this post be? Should you drink alcohol, or not? I can’t answer that for you, because I have no idea how you respond to alcohol, or how much you enjoy consuming it. If alcohol isn’t your drug of choice, and you don’t particularly like it, don’t start drinking because some people have responded positively to its benefits. If you want to drink alcohol, it is, of course, best to do it in moderation. If you want to avoid all things that may trigger a relapse, or that are generally bad for the body, by all means, don’t drink. As with all advice for my floxie friends – it depends, everyone is different, and be careful.

 

Fluoroquinolone Antibiotics Increase Risk of Birth Defects

A few years ago, a friend from high school who was in her second trimester of pregnancy with her second child, reached out to me to ask me what antibiotics she should avoid. She had pneumonia, and was on her way to the doctor’s office. I told her that she should steer clear fluoroquinolones (Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, and Floxin/ofloxacin).

Being an empowered and skeptical person, my friend didn’t just take my word for it that fluoroquinolones were dangerous, she did her own research and noted that the warning label for Cipro/ciprofloxacin stated:

Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. CIPRO should not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother. An expert review of published data on experiences with ciprofloxacin use during pregnancy by TERIS–the Teratogen Information System–concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (quantity and quality of data=fair), but the data are insufficient to state that there is no risk.2

With that information in-hand, she was empowered to adamantly refuse the prescription for Cipro that her doctor wanted to give her, and instead insisted that she get a prescription for a safer antibiotic (a pregnancy category B antibiotic).

I was relieved beyond words when she told me that she had refused the Cipro prescription. She wasn’t going to get floxed, and whatever effects the Cipro may have had on her baby were avoided.

Study Indicates that Fluoroquinolones May Increase Risk of Birth Defects

A recent study in the British Journal of Pharmacology, “Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study” has shown that, “antibiotics in the class called quinolones — ciprofloxacin, levofloxacin and others — are particularly dangerous and should be avoided in pregnancy.”

The study, which “followed 139,938 mothers of babies born in Quebec from 1998 to 2008, tracking their antibiotic use in the first trimester, and their babies’ birth defects through the first year of life” found that:

Moxifloxacin exposure was associated with a 5-fold increased risk of respiratory system malformations and ofloxacin use with an 8-fold increased risk of MCMs. However, these results should be interpreted with caution given the small number of exposed cases.

Teratogenicity of quinolone has been reported in the literature in animal and experimental studies [50, 51]. Indeed, quinolones can act as DNA gyrase inhibitors and also as mitotic inhibitors [52]. This may partially damage DNA and induce fetal malformation, which supports our findings [52].

The other antibiotics examined were also more dangerous during pregnancy than I think any pregnant woman should feel comfortable with, but fluoroquinolones were found to be particularly dangerous.

Too Many Pregnant Women are Prescribed Fluoroquinolone Antibiotics

My friend had a healthy son, and he is now a happy and healthy toddler. She took antibiotics (but not fluoroquinolone antibiotics) during pregnancy, but her son was not negatively affected.

My friend was fortunate. However, most pregnant women don’t have a high school friend who incessantly posts about the dangers of fluoroquinolones, and many of them take fluoroquinolones during pregnancy without being aware of the risks these drugs pose to them or their babies. Doctors who prescribe fluoroquinolones to pregnant women, when there are safer alternative antibiotics, are endangering women and children, and there is nothing okay about that.

***

New York Times, “Certain Antibiotics May Increase Risk of Birth Defects

British Journal of Clinical Pharmacology, “Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study

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Fluoroquinolones and Statins: A Recipe for Rhabdomyolysis

In May, 2017, WSB-TV 2 Atlanta aired the story, “Clark Howard says near-fatal disease possibly caused by popular antibiotic,” in which the story of how Clark Howard, a popular consumer expert and host of the nationally syndicated Clark Howard Show, was hurt by a combination of ciprofloxacin (a fluoroquinolone antibiotic) and generic Lipitor (a statin). Mr. Howard had a severe and life-threatening reaction to these drugs, and he is quoted in the story as saying, “I felt like death,” and “It was a struggle to walk five steps.” Mr. Howard was admitted to the hospital where he was diagnosed with rhabdomyolysis–a condition where muscles break down rapidly, causing severe strain on the kidneys and, potentially, death.

Both fluoroquinolones alone, and fluoroquinolones combined with statins, have been documented to cause rhabdomyolysis.

Here are some articles about fluoroquinolone-induced rhabdomyolysis:

Here is a news story about Chris Dannelly, who was killed after levofloxacin-induced rhabdomyolysis:

Additionally, here are some articles about fluoroquinolone plus statin induced rhabdomyolysis:

Both fluoroquinolones and statins are known to damage mitochondria, and they are both fluorinated drugs. They are also both widely prescribed–to millions of people annually–often concurrently.

In the article “Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the Athletic Population” a description of the basic science behind fluoroquinolone-induced muscle damage (and rhabdomyolysis) is described. The following is a quote from “Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the Athletic Population“:

Muscle: Basic Science

Although the etiology of fluoroquinolone-associated muscle disorders has yet to be fully elucidated, evidence supports a relationship with both latent myopathic disorders and the fluorine atom in fluoroquinolones. Despite no history of myopathy, an electromyogram (EMG) performed on a 54- year old woman with apparent ofloxacin-induced rhabdomyolysis demonstrated evidence of myopathy [85]. The patient’s myalgias and muscle weakness resolved upon discontinuation of ofloxacin. It is unknown whether the myopathic findings on EMG were related to the acute rhabdomyolysis or an underlying myopathy. In another case, a 33-year-old man thought to have norfloxacin-induced rhabdomyolysis was found to be susceptible to malignant hyperthermia by in vitro contracture tests [86], which raises the question of a possible link between the 2 conditions. His clinical complaints of myalgia and weakness and laboratory abnormalities resolved 6 months after discontinuing the norfloxacin. The researchers hypothesized that a similar muscle deficit may have accounted for the patient’s susceptibility to malignant hyperthermia and rhabdomyolysis induced by fluoroquinolones. Both malignant hyperthermia and fluoroquinolone-associated muscle disorders are thought to be triggered by a fluorine-containing compound [86]. To further investigate this possible connection, the same French investigators studied muscle function in 3 patients who presented with myalgia, tendinopathy, and arthralgia associated with fluoroquinolone exposure [87]. These results were compared with 3 patients exposed to fluoroquinolones who had no adverse events and 9 subjects with no known muscle disease who had not taken fluoroquinolones. Muscle contraction and metabolism were investigated through the use of histology, in vitro contracture tests, and 31P magnetic resonance spectroscopy (31P MRS). The 3 patients with fluoroquinolone-associated myalgia and weakness displayed similar metabolic abnormalities, whereas the 3 subjects exposed to fluoroquinolones with no adverse effects displayed normal metabolic profiles. These findings led the researchers to conclude that the adverse effects recorded in the 3 patients were related to a pre-existing muscular anomaly revealed by fluoroquinolone treatment. Further support for the hypothesis that fluorine may be the trigger for fluoroquinolone associated myopathy comes from the fact that no adverse muscular events have been reported with unfluorinated quinolones. In addition, steroid myopathy is thought to occur more frequently with fluorinated steroids (ie, dexamethasone and triamcinolone) than with nonfluorinated steroids (ie, prednisone or hydrocortisone) [88-90]. The researchers recommended that any patient experiencing myalgias associated with fluoroquinolone exposure should undergo noninvasive muscle metabolic testing with 31P MRS along with a subsequent muscle biopsy for histoenzymology and contracture tests if a metabolic disorder is found.

Muscle: Clinical Manifestations

A variety of muscle syndromes have been reported in association with fluoroquinolone use, ranging from mild myalgias to life-threatening rhabdomyolysis[78,85-87,91-95]. In fact, some investigators have proposed that myalgias may be the most common adverse effect of fluoroquinolone use [78]. Symptoms, which typically consist of diffuse muscle pain with or without weakness [86,87,91] and perhaps a predilection for proximal muscle groups [85,92], appear to manifest within 1 week after initiation of fluoroquinolone treatment [94] and often resolve within 1-4 weeks after discontinuation of the medication [78,86,91,92], although symptoms that persisted up to 6 months have been reported [86]. Statins may potentiate fluoroquinolone-associated myopathy (emphasis added) [91,92]. Furthermore, an association may exist between an underlying myopathic process and the development of myalgias and/or rhabdomyolysis after fluoroquinolone exposure, as previously discussed.

It is interesting that the authors of “Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the Athletic Population” attribute myalgia and rhabdomyolysis to the fluorine atom that is added to quinolones to form fluoroquinolones. The toxicity of fluorine is often overlooked by researchers and “floxies” alike, in part because of the politics associated with assertions that fluorine and fluoride are toxic (they are). As the first sentence in the quote (“Although the etiology of fluoroquinolone-associated muscle disorders has yet to be fully elucidated”) notes though, the exact mechanism through which fluoroquinolones, statins, and fluoroquinolones and statins together, cause adverse reactions is not fully known.

What is known is that fluoroquinolones, and fluoroquinolones combined with statins, can cause rhabdomyolysis, and that rhabdomyolysis can be deadly.

If you are a “floxie” that is on statins, I highly recommend that you talk to your doctor about the case reports linked above and the possibility of rhabdomyolysis and other myalgias being induced by fluoroquinolones, statins, or both.

If you have existing myalgias, including fibromyalgia, I suggest that you take the quote above to your doctor and get off of all fluorinated drugs–as they have been shown to exacerbate myalgias.

I hope that the millions of people on statins, and their doctors, recognize that fluoroquinolones should not be given to people on statins because the two drugs combined can increase the likelihood of rhabdomyolysis and other myalgias.

I’m sorry that Mr. Howard was hurt by ciprofloxacin and generic Lipitor, but hopefully the publicity that his story is getting will serve as a warning for others.