Tag Archives: fluoroquinolone antibiotics

Fluoroquinolone Antibiotics Associated with Carpal Tunnel Syndrome

It is well-known and well-documented that fluoroquinolones weaken and destroy musculoskeletal tissues–especially, but not limited to, tendons. 

Additionally, it is known that fluoroquinolones cause neurological problems, and can lead to painful and debilitating peripheral neuropathy. (In 2013, fluoroquinolone warning labels were updated to note that Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, and Floxin/ofloxacin can cause permanent and disabling peripheral neuropathy.)

Given that fluoroquinolones disproportionately affect the tissues in joints, and that they also adversely affect nerves (causing painful neuropathy), it’s not surprising that fluoroquinolone antibiotic use is associated with Carpal Tunnel Syndrome (CTS)–a medical condition that includes “pain, numbness, and tingling, in the thumb, index finger, middle finger, and the thumb side of the ring fingers,” as well as weakness and muscle wasting.

Both CTS and fluoroquinolone-use are common in America, and researchers Jasmine Z. Cheng, Mohit Sodhi, Mahyar Etminan, and Bruce C. Carleton, examined how they are related in “Fluoroquinolone Use and Risk of Carpal Tunnel Syndrome: A Pharmacoepidemiologic Study” published in the journal Clinical Infectious Diseases in August, 2017.

In “Fluoroquinolone Use and Risk of Carpal Tunnel Syndrome: A Pharmacoepidemiologic Study” the researchers found that, “Any use of FQ within the year prior to CTS diagnosis was associated with a 34% and 36% increased risk of CTS in the primary and sensitivity analyses, respectively” and that:

“The results of our study are consistent with an increase in the risk of CTS with FQs. The risk was consistent among all risk periods with a slight increase among past users, which may be due to the longer period elapsed for CTS to manifest itself. FQ-related neurotoxicity can persist cumulatively in relation to exposure levels [8, 9]. The exact mechanism by which this occurs is unknown [9], but proposed models include direct nerve inflammation and ischemia from toxic metabolite and free radical formation [10], and FQ-induced tendonitis/tendinopathy causing mechanical compression upon the adjacent nerves (eg, median nerve) that share the carpal tunnel [11]. Reports of nerve biopsy studies on patients who have experienced FQ adverse events have revealed significantly reduced nerve fiber density consistent with small fiber neuropathy, which may be a potential mechanism of CTS [12]. Although neurotoxicity is the second most commonly reported adverse event, with several studies documenting FQ association with central and peripheral nerve damage [8, 9], this is the first large-scale study exploring the relationship between FQs and CTS.”

CTS is a malady that affects thousands of people and has societal costs in the millions of dollars. In “Fluoroquinolone Use and Risk of Carpal Tunnel Syndrome: A Pharmacoepidemiologic Study” the researchers note that:

“CTS is a disease of significant societal burden with a prevalence of 5% and incidence of up to 2.3 per 1000 person-years [4, 5]. CTS causes loss of function and decreased quality of life for individual patients, and also comprises a large cumulative drain on healthcare and socioeconomic resources from loss of productivity and worker’s compensation claims [6]. One study of 4443 CTS claimants in Washington State estimated a cumulative socioeconomic cost of US$197–$382 million over 6 years for this cohort alone [6].”

Fluoroquinolones are increasing the risk of CTS in millions of people (20+ million prescriptions for fluoroquinolones are written each year). Are doctors or patients aware that they are increasing the patient’s chances of CTS–a painful, debilitating, and costly condition–when fluoroquinolone antibiotics are taken? I doubt it, but they should be.

Please spread the word about how dangerous fluoroquinolones are by sharing posts, news articles, and research articles that connect fluoroquinolones with other illnesses. It wouldn’t occur to most people that a commonly prescribed class of antibiotics could be connected with CTS, psychiatric illness, pain, pseudotumor cerebri, tendon damage and ruptures, or multi-symptom chronic illnesses. But fluoroquinolones ARE connected with those, and other, diseases and syndromes. Articles like “Fluoroquinolone Use and Risk of Carpal Tunnel Syndrome: A Pharmacoepidemiologic Study” help to provide evidence of the extensive damage that fluoroquinolones do, and I am grateful to the researchers who examined the connections. Please spread the word so that doctors and patients alike are informed. Thank you.

 

 

Fluoroquinolone Warning Labels to be Updated in Canada

Health Canada, the department of the government of Canada with responsibility for national public health (like the U.S. Food and Drug Administration) has “carried out a review of the potential risk of persistent and disabling side effects linked to the use of fluoroquinolones. The review was triggered by a benefit and safety review done by the United States Food and Drug Administration (FDA) on systemic (taken by mouth or by injection) fluoroquinolone drugs.”

The Canadian Review of fluoroquinolones concluded that (SOURCE):

  • Health Canada’s review concluded that some of the known side effects, specifically tendonitis/tendinopathy, peripheral neuropathy and central nervous system disorders, already linked to the use of fluoroquinolones, may be persistent and/or disabling. Given the high use of fluoroquinolones in Canada and the information reviewed, these side effects are considered rare.
  • Health Canada recommended that the safety information for all fluoroquinolone products be updated to include information about this rare but serious risk. Health Canada is working with manufacturers to update the safety information of all systemic (taken by mouth or by injection) fluoroquinolone products marketed in Canada. In addition, an Information Update and a Health Care Professional Letter will be published and distributed to further inform Canadians and healthcare professionals about this risk.
  • Health Canada is working with the Drug Safety and Effectiveness Network (DSEN) and the Canadian Agency for Drugs and Technologies in Health (CADTH) to conduct additional studies to better understand the use of fluoroquinolones in Canada.
  • On October 6, 2016, Health Canada brought together a Scientific Advisory Panel on Anti-Infective Therapies to discuss the risks associated with the use of fluoroquinolones. The panel recommended that the safety information for fluoroquinolones be updated, and risk communications be published and distributed to further inform Canadians and healthcare professionals about the potential risk that some of the known side effects, specifically tendonitis/tendinopathy, peripheral neuropathy and central nervous system disorders may be persistent and/or disabling.
  • Health Canada will continue to monitor safety information involving fluoroquinolones, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified.

As a result of its safety review, Health Canada is working on updating fluoroquinolone warning labels.

Additionally, above and beyond what the U.S. F.D.A. has done, Health Canada has agreed to publish and distribute a Healthcare Professional Letter regarding fluoroquinolone risks. The Healthcare Professional Letter includes the following points:

  • It is recommended that the potential for disabling and persistent serious adverse events be considered when choosing to prescribe a fluoroquinolone.
  • Fluoroquinolones should not be prescribed to patients who have experienced serious adverse reactions during or after prior treatments.
  • Healthcare professionals are advised to stop systemic fluoroquinolone treatment if a patient reports a serious adverse reaction. The patient’s treatment should be switched to an alternative treatment with a non-fluoroquinolone antibacterial drug if needed to complete the treatment course.
  • Healthcare professionals should be aware that some adverse reactions associated with the use of fluoroquinolones can occur within hours to weeks after exposure to the treatment.

This acknowledgement from Health Canada that fluoroquinolones may have permanent and/or disabling effects is a huge step in the right direction for Canadian “floxies.”

All Canadians who have experienced adverse reactions to fluoroquinolones are encouraged to report their reactions to Health Canada through the Canada Vigilance Adverse Reaction Online Database.

This acknowledgement from Health Canada is a huge step in the direction of safety and informed consent for all Canadians. It is appreciated!

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Vision Problems from Fluoroquinolones

A few years ago, I was chatting with a work associate about fluoroquinolone toxicity, and she mentioned that a friend of hers had lost her vision after taking ciprofloxacin. Yes, you read that correctly–her friend LOST HER VISION as a result of getting floxed. I was shocked and appalled. Losing my energy was bad enough, I can’t even fathom going blind, even temporarily, from taking an antibiotic. My associate’s friend had to take more than a month off of work, and several months off from driving, in order for her eyes to heal and her vision to return to a level at which she could return to doing those things. Her vision did return, and I believe that this was her only side-effect, but still, losing one’s vision is a pretty serious and severe side-effect. I’d be pretty upset if I COULDN’T SEE as a result of taking an antibiotic.

I have heard from many other people who have suffered from vision problems, including blurred vision, floaters, dry eyes, “visual snow,” and a loss of comprehension of visual information, post-flox.

In a comment on this site, Joyce described her vision problems as follows:

“Could Levaquin caused my visionroblem that happened sudden? Yes, I can type but onlyk because I’ve done years and years of 12-18 hour days of typing so as long as I know where the keyboard is, I can type — can barely see the letters so errors elude me.

Sunday, October 9, 2016, myvision went from being okay to not there in the blink of an eye — literally. My husband and I were eating lunch in a restaurant, someone sat down at a table near us, I glanced over, when I glanced back at my husband, my vision was gone except for a narrow bright white area to the right and bottom of my vision field. Called optometrist, he initially diagnosed a pin stroke and told me to go to ER, so I did. CT at ER showed nothing but as precaution, was given TPA and flown to major hospital. Three CT scans there showed nothing. Ultrasound of heart showed it to be in good shape. Cholsterol loa, blood sugar low, BP kept dropping on its own so docs happy with all that. MRI showed “shadow” in right temporal lobe — docs didn’t know if it was bleeding or what, nor how long it had been ther enor if it would go away.

Upper left quadrant of visual field seems as if I’m looking through a dense brown fog. Rest of visual field is useable — can get around on my own, do housework, walk, etc., but can’t see to drive, read nor do my job which is thypesetting and graphic design. Dark area has decreased by about 70% since initial onset but isn’t improving past that.”

In “Painful Dry Eyes” on www.fluoroquinolonethyroid.com, JMR describes her post-flox dry eyes as follows:

“The severely dry eyes affected everything: my ability to read, to watch TV, to use the computer, to write, to look out on the world; to be athletic, to be outside in the wind or cold night air; to blink the 23,000 -30,000 times a day the average person blinks without feeling the dry, gritty pain with each one of those blinks; to sleep at night without waking up constantly in pain just from my dry eyes alone. There’s “dry eyes”, and then there’s “Bone-Dry eyes” – zero moisture what so ever – and I simply couldn’t live a life worth living with that.”

The warning label for Cipro/ciprofloxacin notes that, “blurred vision, disturbed vision (change in color perception, overbrightness of lights), decreased visual acuity, diplopia, eye pain, tinnitus, hearing loss, bad taste, chromatopsia” are special sense related adverse-effects that have been reported. The warning label text feels so flippant–as if decreased visual acuity and/or eye pain aren’t serious, life-altering, horrible side-effects for a drug to have. Did anyone’s doctor warn them that they may have long-term vision problems as a result of taking Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, or Floxin/ofloxacin? No? I didn’t think so.

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If you read the full “Painful Dry Eyes” post on www.fluoroquinolonethyroid.com you will note the connections that the author makes between thyroid hormone (and iodine) levels and the severity of her eye-related fluoroquinolone toxicity symptoms. If you read through more posts on www.fluoroquinolonethyroid.com you will see that there are many connections between fluoroquinolone toxicity symptoms and thyroid hormones. A summary of the connection can be seen in the post “Fluoroquinolone Antibiotics and Thyroid Problems: Is there a Connection?” on www.hormonesmatter.com.

It is clear from patient reports that fluoroquinolones badly affect hormonal stability and balance. The site, www.fluoroquinolonethyroid.com, goes over how thyroid hormones are adversely-affected by fluoroquinolones. Patient stories such as Andrew’s Story and Gary’s Story go over how fluoroquinolones deplete testosterone. Many women have reported that their fluoroquinolone toxicity symptoms are greatly affected by hormonal fluctuations that correspond with their menstrual cycles. Additionally, in the article “Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the Athletic Population” several endocrine-system disorders are listed as risk factors for fluoroquinolone-related musculoskeletal problems.

Hormones also greatly affect vision and eye health. In “Blinded By Side Effects: Vision and Hormonal Birth Control,” Kerry Gretchen states:

“Hormones affect every system of the body so perhaps it should come as no surprise that they can greatly impact your vision. In fact, it is the fluctuation in hormones that is the primary reason for worsening eyesight with age. So of course, manipulating the body’s natural chemistry by using hormonal birth control can cause a variety of vision problems.”

Blinded By Side Effects: Vision and Hormonal Birth Control is an interesting and insightful post that I recommend you read for more information about the hormone-vision connections. Though it focuses on how hormonal birth control affects vision–not on connections between fluoroquinolones, hormones, and vision problems–the connections just between hormonal disturbances and vision problems are interesting and relevant to “floxies” of both sexes.

I believe that post-flox vision problems are related to hormone imbalances. Working with a good doctor to help get your hormones back in balance (or, at least to run some tests) seems like an appropriate course of action for any “floxies” who are suffering from severe, life-altering, vision/eye related side-effects. Hormones are notoriously difficult to balance though, and caution is warranted. “Balancing your hormones” may be easier said than done, but working on it, and getting information from a doctor who works with patients with hormonal problems, seems like a good path to start down.

Time may also help. My peripheral vision floaters went away less than a year after getting floxed, and my eye moisture returned a few years after that. (My eyes were never dry to the point that they were painful, but I didn’t wear contact lenses for a while post-flox. I can wear them again.) I can’t pinpoint anything specific that helped other than time and maybe acupuncture. My vision problems weren’t near as bad as those of my work associate’s friend, Joyce, or JMR though. If my symptoms had been that severe, I probably would have been willing to try pharmaceutical and/or supplemental hormonal adjustments.

As is the case with most fluoroquinolone toxicity symptoms, there is no cure for vision-related fluoroquinolone toxicity issues, and even getting recognition of the reality of the multifaceted adverse-effects of these drugs is difficult.

Fluoroquinolone toxicity symptoms are severe, fluoroquinolones adversely affect multiple bodily systems including vision, and the symptoms of fluoroquinolone toxicity are often not reversible through medical interventions. Therefore, fluoroquinolones should not be prescribed unless absolutely medically necessary. This isn’t that difficult a concept–it should be reality.

 

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Be Warned: FDA Issues New Stronger Warnings About Risks Of Fluoroquinolone Antibiotics

I wrote “Be Warned: FDA Issues New Stronger Warnings About Risks Of Fluoroquinolone Antibiotics” for Collective Evolution. It was published on May 17, 2016. It’s about the harm that fluoroquinolones inflict, as well as the FDA announcement that fluoroquinolone warning labels are to be updated to note that the risks outweigh the benefits for many conditions.

Please read and share “Be Warned: FDA Issues New Stronger Warnings About Risks Of Fluoroquinolone Antibiotics” – THANK YOU!

Collective Evolution has millions of views each month and over 4 million facebook “likes.” Please spread this article far and wide to maximize it’s reach. Thank you!!!

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Serious Psychiatric Reactions from Fluoroquinolones

Heather McCarthy News Story

Please read and share post, “Psychiatric Adverse Reactions to Pharmaceuticals Ignored” that was published on Hormones Matter. It highlights the tragic story of Shea McCarthy, a young man who lost his life after suffering from a severe psychiatric adverse reaction to Levaquin.

The severe psychiatric adverse reactions to fluoroquinolones need to be recognized and acknowledged. No one is choosing to have a severe psychiatric adverse reaction to a drug, yet people with psychiatric adverse reactions are often ignored and disregarded. As you can see from Shea’s tragic story, not listening to people who have psychiatric adverse reactions to drugs can have tragic consequences.

Here is the video of the news story, “CALL 6: Mother blames antibiotic for son’s death – Purdue University student took Levaquin:”

There are several possible mechanisms through which fluoroquinolones can cause anxiety, depression, insomnia, psychosis, and other severe psychiatric adverse-effects. Oxidative stress may be the mechanism through which fluoroquinolones cause severe psychiatric problems, as I described in “Can Antibiotics Induce Psychiatric Reactions?” Maybe gut microbiome destruction by fluoroquinolones leads to the psychiatric adverse effects. The Psychology Today article, “The Gut-Brain Connection, Mental Illness, and Disease” goes over evidence that our gut microbiome is intricately linked to our mental health. Obviously, fluoroquinolones are powerful antibiotics that destroy the gut microbiome. Another possibility, one that I have not previously explored, is that fluoroquinolones cause severe psychiatric reactions because they have a piperazine attachment to the quinolone core. In the picture below, the quinolone core is zone 4 and the piperazine attachment is zone 3.

Cipro Molecular Structure

Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid.

Piperazine blocks GABA activity. GABA is gamma-Aminobutyric acid, “the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays the principal role in reducing neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone.” (wiki) When GABA is blocked, people feel edgy, agitated, excited (not in a good way), anxious, and can suffer from insomnia, muscle spasms, seizures, and more.

Piperazine is often used “for making fake ecstasy because of the similarity in taste, and at certain doses, a user may experience favorable side effects and feel ‘high.’” (source) It is also often mixed with MDMA in ecstasy.

Additionally, it is noted in “Acetylcholine (ACh) – Related Damage” on http://fluoroquinolonethyroid.com/ that:

“Piperazines (anti-parasiticals which kill parasites by paralyzing them) have neuromuscular effects which are thought to be caused by blocking acetylcholine at the myoneural junction. (Plenty of pets have been poisoned with over the counter piperazine toxicity from wormers – so no, it’s not just helminths they affect). Among the numerous properties of Piperazine derivatives, they are not only muscarinic antagonists, but also are the basis for recreational drugs with euphoria and stimulant properties, such as amphetamines, BZP, MDMA [rather, ecstasy, as noted above], and TFMPP, along with all the negative side effects of these drugs (no wonder I was hallucinating during my acute reaction). So now we have a toxic neuromuscular agent with amphetamine/ecstasy-like effects (piperazine), along with a toxic iodine displacer (fluorine), attached to a chemotherapeutic agent with an intracellular, intranuclear, and intra-mitochondrial genotoxic mechanism of action (quinolone) – a synthetic, fluoridated, neurotoxic, genotoxic chemotherapeutic poison masquerading as an antibiotic and being given en masse to the human and animal population.”

Fluoroquinolones “are known to non-competitively inhibit the activity of the neurotransmitter, GABA, thus decreasing the activation threshold needed for that neuron to generate an impulse.” (source, source, source) Fluoroquinolones have also been shown to have similar effects on GABA neurotransmitters as benzodiazepine withdrawal (source).

The inhibition of GABA by the piperazine part of fluoroquinolones is a plausible, even likely, mechanism for the many horrible psychiatric effects that people suffer from after taking fluoroquinolones.

In a survey of 94 people who experienced adverse reactions to Levaquin/levofloxacin, a fluoroquinolone antibiotic, 72% reported experiencing anxiety, 62% reported depression, 48% reported insomnia, 37% reported panic attacks, 33% reported brain fog and/or cognitive impairment, 29% reported depersonalization and/or derealization, 24% reported thoughts of suicide and 22% reported psychosis. (source, source)

More than 20 million prescriptions for fluoroquinolones are given out in the U.S. each year. If even only 1% of the people who take fluoroquinolones experience a psychiatric adverse-reaction, that’s still a lot of people whose minds aren’t their own, who are suffering from depression, anxiety, insomnia and worse, because of an antibiotic that is made with a chemical that has amphetamine/ecstasy-like effects.

These effects can have tragic consequences, as can be seen in the video and article mentioned above about Shea McCarthy.

Psychiatric adverse effects of prescription drugs are serious, and they should be taken seriously. They are not a choice. No one would choose to feel psychotic, or even anxious.

There are many plausible mechanisms through which fluoroquinolones can cause psychiatric problems. Perhaps it is time that the psychiatric effects of fluoroquinolones become more widely recognized.

 

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Why Athletes Should Never Take Fluoroquinolone Antibiotics

chris-fqwall

No one should take fluorouqinolone antibiotics unless there is no other alternative and one is in a life-or-death situation. Athletes in particular should be aware of the harm that fluoroquinolones can do, and they should avoid them if at all possible. Athletes should know that their athletic abilities, and even their lives, can be taken from them by fluoroquinolone antibiotics.

Please read, and share, this post:

Why Athletes Should Never Take Fluoroquinolone Antibiotics

Thank you!

 

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Fluoroquinolone Toxicity Video of News Stories

Chris Jones made this WONDERFUL video –

https://www.youtube.com/watch?v=XgTiGhFrBgc

He posted it with the following instructions:

Over the last year there have been many news stories about fluoroquinolones. I made a video to highlight these stories. I am asking you all to please help me do a few things.

1. Watch it many times to get the view count up.

2. Like the video.

3. Leave a comment on it in YouTube. ( the news stories comments helped a lot, but once the story is gone it is a lot harder for new people to see them). These comments will help people who get floxed years from now.

4. Share as many time as possible.

After the comments and views are high. I will be emailing it to major news stations, talk shows, politicians, the FDA, and I recommend you send it to the doctor who rx you this poison.

Thank you everyone who had the courage to do a news story. I know how hard it was. And thank you to everyone behind the scenes who put them together.

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Fluoroquinolones Deplete Iron and Lead to Epigenetic Changes

In my ciprofloxacin toxicity recovery story I note that:

I take a low dose iron supplement – only 5 mg. – daily. The brand of iron supplement that I use is Pur Absorb, but I’m guessing that other low-dose iron supplements will work equally well. Within just a couple days of starting taking the iron supplement, my energy levels increased dramatically. I could walk a mile without being exhausted afterward. In addition to improving my energy level, the iron supplement seems to make my muscles and tendons more supple and malleable. When my tendons are feeling tight, a dose of iron helps to loosen them up – within just a couple hours. Too much iron is really bad for you, so please be careful with supplementing it (ask your doctor, yada yada), but it helps me immensely.”

I’ve always wondered why iron helped me to recover from fluoroquinolone toxicity. In some ways, it didn’t make sense – iron is an oxidant (according to a doctor friend, it’s a bit more complicated than that, and in some situations iron can be an antioxidant and in others it can be an oxidant), and antioxidant supplements are what help most floxies. Also, iron is a component of the Fenton Reaction, and the Fenton Reaction is where, “Iron(II) is oxidized by hydrogen peroxide to iron(III), forming a hydroxyl radical and a hydroxide ion in the process. Iron(III) is then reduced back to iron(II) by another molecule of hydrogen peroxide, forming a hydroperoxyl radical and a proton. The net effect is a disproportionation of hydrogen peroxide to create two different oxygen-radical species, with water (H+ + OH–) as a byproduct.” Basically, iron can “donate or accept free electrons via intracellular reactions and help in creating free radicals.” Free radicals are ROS. Some of the nastiest ROS are created in the Fenton Reaction – hydroxyl radicals and hydroperoxyl radicals. According to “Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients,” fluoroqinolones increase the production of ROS, and it has been postulated (by myself and others) that the mechanism for fluoroquinolone toxicity is an excess of ROS wreaking havoc on all systems of the body.

So, why did iron make me feel so much better?

It’s a question that has perplexed me for years.

Answers to that question can be found in the article, “Non-antibiotic effects of fluoroquinolones in mammalian cells” which was published in the July, 2015 issue of The Journal of Biological Chemistry. In this post I will highlight some of the more interesting findings from “Non-antibiotic effects of fluoroquinolones in mammalian cells.” All excerpts from the article are quoted and italicized.

Here we show that the FQ drugs Norfloxacin, Ciprofloxacin, and Enrofloxacin are powerful iron chelators comparable to Deferoxamine, a clinically-useful iron chelating agent.”

Fluoroquinolones suck iron out of (chelate) cells just as well as drugs that are meant to suck the iron out of cells (Deferoxamine). Iron is an essential mineral that is critical for transporting oxygen throughout the body. Chelation of iron from cells can be detrimental to health in multiple ways including, “delayed cognitive function, poor exercise performance and lowered immune function. In children, iron deficiency anemia can cause psychomotor and cognitive abnormalities resulting in future learning difficulties.

We show that iron chelation by FQ leads to epigenetic effects through inhibition of α-ketoglutarate-dependent dioxygenases that require iron as a co-factor.”

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Iron depletion leads to adverse epigenetic effects through inhibition of iron-dependent enzymes. This is a very big deal – Fluoroquinolones can change genetic expression (epigenetics) in human cells. Later in the article it is noted that, “This is the first study to show global epigenetic changes induced by FQ antibiotics.” It had been previously postulated in “Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology” (2009) that all fluoroquinolone adverse effects were the result of epigenetic changes, but “Non-antibiotic effects of fluoroquinolones in mammalian cells” describes the first study of human cells that shows epigenetic changes caused by fluoroquinolones. Epigenetics wasn’t even a notion, much less a field of study, when the FDA approved fluoroquinolones, drugs whose mechanism of action is, “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.” Think about that next time you pick up a drug from the pharmacy and assume that it’s safe because the FDA approved it.

Dioxygenases are enzymes that are necessary for aerobic life. Fluoroquinolones inhibit α-ketoglutarate-dependent dioxygenases, which require iron as a co-factor.  Depletion of α-ketoglutarate-dependent dioxygenases leads to changes in how genes are expressed.

Fluoroquinolones were also found to inhibit several demethylases, “enzymes that remove methyl (CH3-) groups from nucleic acids, proteins (in particular histones), and other molecules. Demethylase enzymes are important in epigenetic modification mechanisms. The demethylase proteins alter transcriptional regulation of the genome by controlling the methylation levels that occur on DNA and histones and, in turn, regulate the chromatin state at specific gene loci within organisms.” FQs were found to inhibit “Jumonji domain histone demethylases, TET DNA demethylases, and collagen prolyl 4-hydroxylases, leading to accumulation of methylated histones and DNA, and inhibition of proline hydroxylation in collagen, respectively. These effects may explain FQ-induced nephrotoxicity and tendinopathy.” (emphasis added).

Many possible mechanisms for the tendinopathy and compromised collagen integrity caused by fluoroquinolones have been proposed. It has been suggested that fluoroquinolone caused destruction of connective tissues are due to metalloprotease (MMP) malfunctions, magnesium depletion, and the NO/ONOO cycle. In “Non-antibiotic effects of fluoroquinolones in mammalian cells” it is asserted that iron chelation, and the inhibition of enzymes that utilize iron, are behind the fluoroquinolone-caused musculoskeletal adverse effects:

These results suggest, for the first time, that FQ treatment can cause unanticipated epigenetic effects. Moreover, we suggest that the well-established linkage between FQ treatment and tendinopathy reflects impairment of collagen maturation by FQ. We suggest that it is the inhibition of collagen 4 prolylhydroxylases by FQ mediated iron chelation, and repression of collagen P4H1 and LH1 transcription that underlies the peculiar tendinopathy side effects of FQ antibiotics.”

And:

FQ are potent iron chelators capable of inhibiting 2-KG dependent dioxygenases because of the crucial role of iron in the active site. We show that FQ treatment inhibits collagen maturation. Prolyl 4- hydroxylase and lysyl hydroxylase are iron dependent enzymes essential for the post-translational modification of collagen. Both play central roles in collagen maturation through hydroxylation of proline and lysine residues to mediate collagen cross-linking. Covalent crosslinks are required for the tensile strength of collagen fibers (64). We suggest that it is iron chelation by FQ that accounts for suppressed collagen hydroxylation, giving rise to tendinopathies.”

And:

Additionally, suppression of HIF-1α can have drastic effects on vascularization and energy metabolism in connective tissues, contributing to decreased blood flow in an already hypoxic and avascular tissue. We suggest that these three insults – inhibition of prolyl and lysyl dioxygenases, reduction of P4HA1 and LH1 mRNA levels, and reduced tendon vascularization upon HIF-1α depletion – together account for FQ induced tendinopathies.”

To sum up the excerpts, fluoroquinolones chelate iron from cells, this leads to inhibition of iron-dependent enzymes, which lead to epigenetic changes that result in collagen malformation and tendinopathies. It should also be noted that fluoroquinolones chelate other minerals, including magnesium, from cells, and magnesium-dependent enzymes are inhibited by fluoroquinolones as well.

All doctors and researchers, and the FDA, should note that in chelating necessary minerals from the body, fluoroquinolones are not only inhibiting necessary enzymatic reactions, they’re also changing genetic expression, and that the long list of severe adverse effects of fluoroquinolones may be due to adverse expression of genes. Neither long-term, nor intergenerational effects of fluoroquinolones are currently known.

So… what should floxies do with this information? Personally, I supplement iron and I find that it helps me immensely. Not everyone can, or should, supplement iron though. Too little iron is bad, but too much is also harmful. The prudent thing to do is to get your iron levels tested and to supplement if necessary under the care of your doctor.

When I corresponded with Dr. Maher, one of the authors of “Non-antibiotic effects of fluoroquinolones in mammalian cells,” he noted that, “I would simply emphasize that what we demonstrate in this work involves human cells grown in culture, and lab conditions, and we want to make it clear that these are findings of potential mechanisms of fluoroquinolone antibiotics that could be relevant for patients, but we provide no direct data related to human patients or treatments. Further studies will be required to understand if these or related effects actually occur in people.”

I am thankful to Doctors Badal, Her and Maher for their work on “Non-antibiotic effects of fluoroquinolones in mammalian cells!” Of course, caution should be used when drawing conclusions from their results. Though I shouldn’t draw conclusions about how FQs react in a complex human body from how human kidney cells react in a petri dish, I don’t think that it’s completely out of line to say that the potential implications of this research are huge. The chelation of minerals from cells by fluoroquinolones may be leading to epigenetic changes in the people who take fluoroquinolones. What this means for their health is not currently known.

The epigenetic adverse effects of fluoroquinolones were found to be reversible by exposing the floxed cells to iron, and studies have shown that magnesium, vitamin E, MitoQ and NAC can reverse some of the effects of fluoroquinolones, so please have hope, hang in there, and take your mineral supplements (under the supervision of your doctor, yada, yada).

 

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Letter to Congress Re the 21st Century Cures Act

The 21st Century Cures Act is going through the Energy & Commerce Committee now. You can read more about the Act here – http://energycommerce.house.gov/cures. The 21st Century Cures Act is a thinly veiled corporate give-away for the pharmaceutical companies. There are many things that I object to in the Act, but I think that its momentum is unstoppable so I’m recommending changes to it, rather than killing it. I am going to send the following letter to the bill’s sponsors, Fred Upton and Diana DeGette. I will also send this letter to my Congressional representatives. I encourage everyone reading this to send a letter to Congressman Upton, Congresswoman DeGette and other Congressional representatives. Please feel free to use my letter as a template, or to customize it as you see fit.

Also, please “tweet” your letters, stories, and anything else that you want to say about the 21st Century Cures Act to the Energy & Commerce Committee @HouseCommerce, Representative Upton @RepFredUpton, Representative DeGette @RepDianaDeGette and use the hashtags #Cures2015 and #Path2Cures. Thanks!

May 16, 2015

Re: Inclusion of Consumer Protection against Adverse Drug Reactions in the 21st Century Cures Act

Dear Chairman Upton and Representative DeGette:

I am writing because I have suffered from an adverse reaction to a popular pharmaceutical, and I would like to see more consumer protection and safety measures added to the 21st Century Cures Act.

At the age of 32, I went from doing crossfit regularly to barely being able to walk because I suffered from an adverse reaction to ciprofloxacin, a powerful fluoroquinolone antibiotic that can permanently damage all the nerves and connective tissues in one’s body. In addition to loss of mobility, I suffered from memory loss, loss of reading comprehension, loss of energy, and pain. There are many people who have significantly worse reactions than I did.

Because adverse reactions to fluoroquinolone antibiotics (and other pharmaceuticals) can be delayed, they are bizarre in nature (who would think that a prescription antibiotic could cause multi-symptom, chronic illness that resembles an autoimmune disease?), and adverse reactions can occur after previously tolerating the drug well, they are thought to be “rare.” I would argue that they are actually under-recognized.

However, since The 21st Century Cures Act focuses on “rare” conditions, I encourage you to focus some attention in the bill to “rare” adverse reactions to prescription drugs.

When people are hurt by a prescription drug they are often unable to gain help from the medical establishment (doctors can’t put your cells back together – the tv ads are misleading), and they are often unable to gain justice through the legal system (if a devastating adverse effect is listed on the warning label, you cannot sue because “you were warned”).

The pharmaceutical companies need to take more responsibility for the damage that the drugs that they create and manufacture do. Warning labels are not enough. They simply shift the blame from the maker of the drug to the victim of the drug. Enclosed is a plan to make pharmaceutical companies take responsibility for the harm done by the drugs that they discover, produce and put into the market.

The 21st Century Cures Act is proposing to get rid of many safeguards that are currently in place that keep dangerous drugs from entering the market. This is the wrong thing to do. More consumer safeguards need to be put in place, not fewer. If you are going to get rid of phase III clinical trials for potentially dangerous drugs, there MUST be systems in place to gather information about adverse reactions that occur in the general public that is consuming the drugs. I encourage you to put systems in place that require long-term and intergenerational studies to be performed on all drugs that are on the market.

The 21st Century Cures Act has a section that focuses on encouraging the development of new antibiotics. While it should be acknowledged that antibiotic resistance is a problem, the solution should be focused on prudent use of antibiotics, not the development of stronger antibiotics. Antibiotic drugs are not benign. I was hurt by an antibiotic drug—ciprofloxacin. It caused a multi-symptom syndrome that looked and felt like an autoimmune disease. Fluoroquinolone antibiotics have been found to have deleterious effects on mitochondria, neurotransmitters, the microbiome, the endocrine system, and more. Long-term studies to see if they are causally related to the many chronic diseases of modernity that are affected by mitochondria, neurotransmitter, microbiome and hormonal health, have not been conducted. Long-term studies on dangerous drugs like fluoroquinolones, that work by disrupting the DNA and RNA replication process for bacteria and mitochondria, should be conducted before the production of more drugs in their class is encouraged.

More attention should be paid to causes of the chronic diseases that plague our society. A major cause of chronic disease is ongoing cellular damage caused by pharmaceuticals.

Please balance out the 21st Century Cures Initiative so that it takes into consideration that pharmaceuticals are inherently dangerous and have multiple, often unacceptable, adverse effects. Moves toward greater drug safety are necessary and appropriate.

Thank you,

Lisa Bloomquist

Lakewood, Colorado

Enclosed: “A Public Policy Plan to utilize the Pharmaceutical Industry and Pharmacogenomics to reduce serious Adverse Drug Reactions, develop Personalized and Individualized Therapy, and provide a Functional Map of the Human Genome” by JMR on http://fluoroquinolonethyroid.com/

 

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Are Dangerous Antibiotics Causing Chronic Illness?

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I wrote the following post about fluoroquinolone toxicity for Fearless Parent:

ARE DANGEROUS ANTIBIOTICS CAUSING CHRONIC ILLNESS?

Please check it out and share it.  Thank you!

Fearless Parent is a great organization with lots of interesting articles on their web site, and many interesting podcasts.

I was interviewed on the Fearless Parent Podcast a few weeks ago.  You can get more information about the podcast, and listen to it, HERE.

For those who are parents, or who want to spread the word about the dangers of fluoroquinolones to parents, this post on Hormones Matter is a good one to share too – DON’T LET YOUR BABIES GROW UP TO BE FLOXIES.

Thank you for spreading the word about the dangers of fluoroquinolones!  I HATE that children are getting floxed.  HATE IT.  Perhaps, with awareness, we can keep some kids safe.

 

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Fluoroquinolones and Dental Problems

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This post, “Can Fluoroquinolone Antibiotics Cause Dental Problems?” published on Hormones Matter, is not very hopeful.  In fact, it’s quite frightening.  Many patient reports have been coming in lately about fluoroquinolone induced dental problems and teeth falling out.  Christopher’s story, on The Fluoroquinolone Wall of Pain is one of the stories highlighted.  Having all of your teeth fall out is a hefty price to pay for using an antibiotic – especially an antibiotic that is regularly prescribed for urinary tract and sinus infections.

I couldn’t find much in the way of journal articles about fluoroquinolone toxicity and dental problems.  If any of you find journal articles with dental problems listed as an effect of fluoroquinolones, please let me know.

The patient reports are quite compelling though – and frightening.

A couple people have mentioned that magnesium supplementation helps their post-flox teeth.  It’s probably a good thing to keep up.

On a personal note, I love my teeth.  Vanity is certainly at play, but I have really good teeth and I’d like to keep them.  I lost a tooth to internal resorbtion – basically, the root disintegrated for no reason – a long time before I took a FQ.  That stunk, for sure.  I can only imagine the horror of losing all of one’s teeth.  Hugs to those who are having post-FQ dental problems!

 

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Lyme Disease and Fluoroquinolone Antibiotics

To my dear friends with chronic Lyme Disease,

I am so sorry for all that you are going through!  The pain, the exhaustion, the fear, the frustration – all of it.  My heart goes out to all of you!

I know that treatment options are a touchy topic, and that antibiotics are often a necessary part of dealing with Lyme Disease.  However, I’m going to jump right into a volatile sea and say, PLEASE, please, please be careful with antibiotics, and know that they are not all created equally.  Fluoroquinolone antibiotics – Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin and Floxin/ofloxacin – are chemo drugs that can do absurd amounts of harm.  I would hate for you to have to deal with two chronic illnesses at once – chronic Lyme and Fluoroquinolone Toxicity Syndrome.  Both are horrible.

Words of Wisdom from a Floxie with Lyme

A few comments on this site, from people who are dealing with both chronic Lyme Disease and Fluoroquinolone Toxicity, are more illustrative than anything I can say.  Here is a comment from my dear friend Catherine, who has been dealing with Lyme Disease for 18 years and Fluoroquinolone Toxicity for 2 years:

My situation is complicated, because I have been wheelchair bound with lyme and co infections for 18 years. I have had about 400 doses of Cipro and 12 days of avelox. I actually got quite a lot better on the cipro for about 4 years, before deteriorating again. Unfortunately, I didn’t realize it was the cipro – because I had done well on it before, it never occurred to me that it was now harming me – and carried on taking it for a year or two after I was first floxed. I then took nearly two weeks of avelox which finished me off, and I have now been bedbound for the last 18 months. I only made the connection between FQs and my health 12 months ago, when I took my last avelox.

I have had massive CNS and PN symptoms.  Over 100 symptoms in all. Some digestive issues too. By Christmas last year I felt that I had stabilized, but have recently developed new symptoms of dry eyes and receding gums.

Other aspects have improved – anxiety and panic attacks have lessened somewhat, and most nights I get 6 or 7 hours solid sleep.

Obviously, I’ve got a lot of damage to repair, and a long road ahead. This summer I have managed a few trips out in the car, which is more than I could do last summer. I have two young children, so I have to keep going for them!

She added, in a different comment on another conversation:

I had chronic borrelia and rickettsia for years before I began antibiotics. I then took FQs for years, and did well for a while. But at some point (I can’t be sure exactly when) I stopped doing so well and felt I was no longer responding – not just to FQs but to all the other antibiotics I was taking. And so the doctor gave me different and stronger FQs until eventually I became totally incapacitated and finally made the connection between FQs and floxing etc. I still don’t understand why the rickettsia/lyme now seems untouchable by any antibiotic. I would have thought after nearly 10 years of FQs I would have no infection left, but it’s worse and more virulent than ever. I can only guess that the FQs have effected a change in the rickettsia bugs themselves.

Tolerance Thresholds for Fluoroquinolones

Many people have suggested that fluoroquinolones bring out latent Lyme Disease.  I don’t know if this theory is true or not, as there haven’t been any studies (that I know of) trying to prove that hypothesis.

What has been shown to be true, however, is that fluoroquinolone antibiotics severely damage cells.  The parts of cells that are most damaged by fluoroquinolones are the mitochondria.  Mitochondrial damage is tricky in that both delayed adverse reactions, and tolerance thresholds are features of drug induced mitochondrial damage.  Thus, as Catherine’s comments illustrate, a drug that was once well tolerated can harm you the next time you have it.  (More info about tolerance thresholds for mitochondria damaging drugs can be found here – http://www.hormonesmatter.com/fluoroquinolone-time-bomb-mitochondria-damage/.)

Everyone’s tolerance threshold for fluoroquinolones is different.  Some people develop Fluoroquinolone Toxicity Syndrome after taking one pill.  Other people can handle hundreds of pills before their lifetime threshold is reached.  After an individual’s threshold is crossed though – the multi-symptom, chronic illness of Fluoroquinolone Toxicity results.

Delayed adverse reactions make it so that, often, people don’t even realize that they’ve crossed their tolerance threshold for fluoroquinolones until they have taken too many pills and the bomb in their body has gone off.  It’s Russian Roulette – but you can pull the trigger and release more and more bullets after the one that starts the reaction goes off – and each additional bullet does additional damage.

The symptoms of Fluoroquinolone Toxicity Syndrome are very similar to the symptoms of chronic Lyme Disease – pain, fatigue (um… bedridden exhaustion is more apt), insomnia, aching joints and muscles, decreased cognitive abilities, anxiety, depression and other psychiatric problems, etc.  The similarities between the two make it difficult to distinguish one from another.  They’re both real and they’re not mutually exclusive.  Some people even surmise that they’re related (but, like I mentioned above, I’m not sure about that).

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We’re in This Together

Humans like to break things into categories.  It helps us to understand them.  But, rather than attempting to convince you that your symptoms are from FQ toxicity, or listening to arguments that I might have latent Lyme, may I suggest that we all listen to Rene’s words of wisdom (also from a comment on www.floxiehope.com – Rene has also dealt with both Lyme and fluoroquinolone toxicity) :

Be careful about getting married to the disease label: “Look at the systems involved.” The massive amounts of data that I have combed through, during the years of illness, (before I was retested & given the diagnosis of Lyme), unveiled the commonality of all these illness or chronic conditions. If you have Lyme, MS, Fibromyalgia, Chemical Sensitives, Flouroquinolone injuries, Cancer it is a cellular issue of detoxification and efficiently utilizing the bio nutrients, the raw material we are made up of that send those signals & then receive the messages. The terrain is everything, which is why everything we eat and absorb is signally the terrain. The beliefs we have, what we covet and worship. How to improve the terrain and the function of these systems. Send the right signals and receive the right signals.

She also wrote:

the most beneficial & healing things you can do for Lyme are tantamount to doing much of what Fluoroquinolone injured do.

I know that for FQ toxicity, there is no one single “magic bullet” cure, but that many different things help people.  Some people are helped by a clean and healthy diet full of vitamins and minerals (Douglas recovered with the help of a healthy diet), some are helped by glutathione injections and liver cleanses (Richard was), Some are helped by antioxidant and mineral supplements (Ruth has some excellent antioxidant supplement advice), some are helped by alternative medicine (my acupuncturist helped me a lot) and most are helped by a combination of approaches.  All of the approaches are holistic and affect multiple systems.  Multiple systems with multiple negative feedback loops are broken by fluoroquinolones, and by Lyme spirochetes.  Systems break down with both diseases – and those broken systems break other systems.  The negative feedback loops are complex and difficult to fix.  But I thoroughly believe that the innate positive feedback loops are stronger than the negative feedback loops.  I hope that this belief is true.

All of us “spoonies” with under-recognized, systemic, often chronic illnesses have more in common than we don’t.  I hope that the stories of hope and healing on this page resonate with anyone with Lyme or any other chronic disease who reads this.

Back to Lyme and Fluoroquinolones

Perhaps I’m biased because fluoroquinolones hurt me, but I can’t believe that a drug that depletes mitochondrial DNA, leads to a massive amount of oxidative stress, depletes intracellular magnesium and decimates the microbiome is helpful to people who are already suffering from a chronic illness.  I understand that the Lyme bacteria need to be fought, but destroying your cells seems like a lousy way to do it.  (Interestingly, it has been suggested that tetracyclines, including doxycycline, are supportive of mitochondria whereas FQs are destructive.)  You need healthy cells in order to fight.  How to improve the health of your cells is a really difficult question and I don’t know the right answer.  I’m pretty sure that fluoroquinolones aren’t the answer to much though – certainly not for chronic Lyme Disease.

The main thing that I can ask of my friends with Lyme is this – please be careful.  Don’t think that the side-effects of drugs are “rare” or that they won’t happen to you.  Know the potential for chronic multi-symptom illness that comes with each fluoroquinolone pill, and if you choose to take Cipro, Levaquin or Avelox, do so with your eyes wide open.  Informed consent is, after all, quite important.

May you all find healing.

Best regards,

Lisa

 

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Fluoroquinolones Linked to Type 2 Diabetes

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Fluoroquinolone antibiotics and type 2 diabetes mellitus Telfer, Stephen J. Medical Hypotheses , Volume 83 , Issue 3 , 263 – 269

Please read Fluoroquinolone Antibiotics Linked to Diabetes on Hormones Matter.

http://www.hormonesmatter.com/fluoroquinolone-antibiotics-diabetes-risk/

And here is the source article, “Fluoroquinolone antibiotics and type 2 diabetes mellitus” – http://www.medical-hypotheses.com/article/S0306-9877(14)00217-5/fulltext

The thought that fluoroquinolones cause cellular damage and magnesium depletion to the point that they increase the risk of type 2 diabetes is frightening, for sure.  There is quite a bit of evidence that dietary adjustments can influence type 2 diabetes significantly though.  So, that’s a reason for some hope.

The role of magnesium depletion in FQ toxicity described in “Fluoroquinolone antibiotics and type 2 diabetes mellitus” helps to explain why magnesium is the supplement that seems to help floxies almost across the board.  Magnesium is necessary for hundreds of enzymatic reactions.

A hopeful thing about the article, “Fluoroquinolone antibiotics and type 2 diabetes mellitus” is that it is a huge help in building a case against the makers of fluoroquinolones.

Smart, resourceful, intelligent people are working on this.  Change will happen.  It will.  It must.

 

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Cellular Oxidative Damage from Fluoroquinolones

Here are some thoughts about what is/was going on in our floxed bodies.

First, here’s my typical disclaimer.  I’m not a doctor or scientist.  I’m doing my best to put together this information, but I could be wrong.  I do my best to be right and I back up my assertions with peer-reviewed journal articles.

As I mentioned in Article Breakdown – “Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria,” I believe that this paragraph describes much of what occurs in floxed cells:

“Increased steady-state levels of mitochondrial superoxide, arising from reduction of Sod2 activity in the Sod+/−mice (i.e., approximately half the wild-type activity), may be exacerbated by drugs that directly target the ETC [e.g., the complex I inhibitors flutamide and troglitazone (122)]. The increased amount of superoxide raises two considerations. First, superoxide that escapes dismutation to hydrogen peroxide cannot cross the inner mitochondrial membrane and can oxidize [Fe-S]-containing enzymes (e.g., aconitase and complex I/III subunits). Alternatively, superoxide can rapidly react with mitochondrial nitric oxide (NO) to form peroxynitrite (ONOO−). For example, the fluoroquinolone antibiotic trovafloxacin (TVX), a typical DILI (drug induced liver injury) associated drug, raises steady-state levels of NO in hepatocellular mitochondria (unpublished data). The mechanisms are not known, but TVX also increases cytosolic (non-ferritin-bound) Ca2+, likely activating the Ca2+-dependent mitochondrial NO synthase (123) to produce ONOO−. Peroxynitrite is dangerous for a number of reasons: i) under acidic conditions, it can be degraded to form the extremely reactive hydroxyl radical; ii) it may directly cause the nitration of aconitase, Sod2, and the [Fe-S]-containing subunits of ETC complexes; and iii) it can induce mitochondrial permeabilization (Figure 4B) (124). This superimposed oxidative/nitrative stress could ultimately push the cell across the threshold to observable injury.”

SUPEROXIDE DAMAGE OF MITOCHONDRIAL DNA

Superoxide is a powerful oxidant that is quite toxic.  Per “Mitochondrial matrix reactive oxygen species production is very sensitive to mild uncoupling,” “ROS are produced continuously as a by-product of aerobic metabolism.  Superoxide can be produced as a result of the one-electron reduction system within the mitochondrial electron transport chain.  Superoxide can then be converted into hydrogen peroxide (H2O2) by superoxide dismutase (the Mn isoform in the matrix and cu, Zn-superoxide dismutase in the cytosol).  H2O2 can be converted into highly reactive hydroxyl radicals (OH-) by the Fenton reaction, and can cause lipid peroxidation.” More info about superoxide can be found here – http://en.wikipedia.org/wiki/Superoxide

In properly functioning cells, superoxide dismutase (SOD) converts superoxide into hydrogen peroxide (H2O2) and water.  Unfortunately, fluoroquinolones deplete cellular SOD.  In “Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients” it was found that, for human patients with urinary tract infections and treated with various fluoroquinolones, “There was substantial depletion in both SOD and glutathione levels particularly with ciprofloxacin.”

Without sufficient SOD, as noted above, superoxide “cannot cross the inner mitochondrial membrane and can oxidize.”  Oxidization within the mitochondrial membrane is harmful because it damages mitochondrial DNA (mtDNA) and starts the vicious cycle of oxidative damage to mitochondria.  (This “vicious cycle” theory is described in “Oxidative stress induces degradation of mitochondrial DNA” – “According to this theory, the production of ROS by mitochondria leads to mtDNA damage and mutations which in turn lead to progressive respiratory chain dysfunction and to a further increase in ROS production as a consequence of this dysfunction. The exponential escalation of these processes is commonly referred to as a ‘vicious cycle’, and the theory predicts that the rise in mtDNA mutations and ROS eventually reach levels that are incompatible with life.”  It should be noted that whether or not this theory is true for how aging works is contentious.  The vicious cycle of damage done by ROS does occur in mitochondria though.)

THE NITRIC OXIDE / PEROXYNITRITE (NO/ONOO-) CYCLE

Additionally, “superoxide can rapidly react with mitochondrial nitric oxide (NO) to form peroxynitrite (ONOO−).”  The ways in which peroxynitrite are dangerous are noted in the paragraph from “Mechanisms of Pathogenesis” at the beginning of this post.

Dr. Martin L. Pall, Professor Emeritus of Biochemistry and Basic Medical Sciences at Washington State University describes the NO/ONOO- (nitric oxide / peroxynitrite) cycle in his web site, http://www.thetenthparadigm.org/index.html.  Here is a diagram from The Tenth Paradigm describing the NO/ONOO- cycle –

ONOO cycle

Here is Dr. Pall’s description of the above diagram:

“Fig. 1 legend.  Vicious (NO/ONOO-) cycle diagram.  Each arrow represents one or more mechanisms by which the variable at the foot of the arrow can stimulate the level of the variable at the head of the arrow.  It can be seen that these arrows form a series of loops that can potentially continue to stimulate each other.  An example of this would be that nitric oxide can increase peroxynitrite which can stimulate oxidative stress which can stimulate NF-kappaB which can increase the production of iNOS which can, in turn increase nitric oxide.  This loop alone constitutes a potential vicious cycle and there are a number of other loops, diagrammed in the figure that can collectively make up a much larger vicious cycle.  The challenge, according to this view, in these illnesses is to lower this whole pattern of elevations to get back into a normal range.  You will note that the cycle not only includes the compounds nitric oxide, superoxide and peroxynitrite but a series of other elements, including the transcription factor NF-kappaB,  oxidative stress, inflammatory cytokines (in box, upper right), the three different forms of the enzymes that make nitric oxide (the nitric oxide synthases iNOS, nNOS and eNOS), and two neurological receptors the vanilloid (TRPV1) receptor and the NMDA receptor.”

The NO/ONOO- cycle provides a reasonable explanation for why it feels as if a bomb has gone off in the body of the floxie.  It also is an explanation as to why the adverse effects of drugs that damage mitochondria and cause oxidative stress are not transient.  There are feedback loops within the cells that perpetuate the damage.

Here is Dr. Pall’s table of signs of the NO/ONOO- cycle –

Explanations for Symptoms and Signs

Symptom/Sign Explanation based on elevated nitric oxide/peroxynitrite theory
energy metabolism /mitochondrial dysfunction Inactivation of several proteins in the mitochondrion by peroxynitrite; inhibition of some mitochondrial enzymes by nitric oxide and superoxide
oxidative stress Peroxynitrite, superoxide and other oxidants
PET scan changes Energy metabolism dysfunction leading to change transport of probe; changes in perfusion by nitric oxide, peroxynitrite and isoprostanes
SPECT scan changes Depletion of reduced glutathione by oxidative stress; perfusion changes as under PET scan changes
Low NK cell function Superoxide and other oxidants acting to lower NK cell function
Elevated cytokines NF-kappaB stimulating of the activity of inflammatory cytokine genes
Anxiety Excessive NMDA activity in the amygdala
Depression Elevated nitric oxide leading to depression; cytokines and NMDA increases acting in part or in whole via nitric oxide.
Rage Excessive NMDA activity in the periaqueductal gray region of the midbrain
Cognitive/learning and memory dysfunction Lowered energy metabolism in the brain, which is very susceptible to such changes; excessive NMDA activity and nitric oxide levels and their effects of learning and memory
Multiorgan pain All components of cycle have a role, acting in part through nitric oxide and cyclic GMP elevation
Fatigue Energy metabolism dysfunction
Sleep disturbance Sleep impacted by inflammatory cytokines, NF-kappaB activity and nitric oxide
Orthostatic intolerance Two mechanisms:  Nitric oxide-mediated vasodilation leading to blood pooling in the lower body; nitric oxide-mediated sympathetic nervous system dysfunction
Irritable bowel syndrome Sensitivity and other changes produced by excessive vanilloid and NMDA activity, increased nitric oxide
Intestinal permeabilization leading to food allergies Permeabilization produced by excessive nitric oxide, inflammatory cytokines, NF-kappaB activity and peroxynitrite; peroxynitrite acts in part by stimulating poly ADP-ribose polymerase activity

Sounds pretty familiar, doesn’t it?

STOPPING THE NO/ONOO- CYCLE

What can be done to stop the NO/ONOO- cycle?  How can one heal when cells are reinforcing the damage done to them over and over again?

Here are Dr. Pall’s recommendations – http://www.thetenthparadigm.org/therapy.htm

Additionally, a very smart and appreciated floxie noted in a comment on this site, that uric acid has been shown to decrease peroxynitrite.  Per the article, “Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis,” “Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger, as demonstrated by the capacity to bind peroxynitrite but not nitric oxide (NO).”  (There has been some debate about whether floxies want to increase or decrease nitric oxide.  I think that we want to increase NO because too much of it is converted into peroxynitrite.  Here’s an article on how NO helps with tendon healing – “The role of nitric oxide in tendon healing.”)  Uric acid.  The stuff that causes kidney stones and gout – it’s a powerful antioxidant that scavenges peroxynitrite.

The role that uric acid plays in getting rid of toxic peroxynitrite makes sense to me on a personal level because of a couple of things that have made me feel significantly better post-flox – brewer’s yeast and uridine supplements.  Both brewer’s yeast and uridine are high in purines, which are converted into uric acid in the body.  I always thought that the purines and uric acid were a necessary evil and that the good done by brewer’s yeast had to do with its high amino acid and/or B vitamin content.  Now I’m thinking that the necessary evil was actually the active ingredient.

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Here are a couple more articles about the role of uric acid in peroxynitrite neutralization (thanks again to the floxie friend who pointed them out):

There is a very real risk of kidney stones and gout when consuming too many purines that lead to excess uric acid.  Even though brewer’s yeast has helped me immensely, I feel quite conflicted about it.  I don’t want a kidney stone and gout would probably make my flox-induced peripheral neuropathy look like a cake-walk.  Now that I’m feeling well, I’m probably going to cut way down on my brewer’s yeast consumption.  I really don’t know which are worse – the diseases of too much uric acid (kidney stones and gout) or the diseases of too little uric acid (“patients with MS have significantly lower levels of serum uric acid than controls” and peroxynitrite is associated with lots of other nasty diseases – like cancer and Alzheimer’s).  This isn’t exactly a great predicament.

Another consideration is that fluoroquinolones deplete cellular magnesium and proper amounts of cellular magnesium are necessary for 300+ enzymatic reactions.  (Fluoroquinolones may inhibit and deplete enzymes through means other than depletion of cellular magnesium too.)  If one doesn’t have the enzymes to metabolize uric acid, well, too much isn’t a good thing.  Too much peroxynitrite is bad too though.

I wish that the answers were more clear.  I hope that this post at least gave you some information with which you can make an informed decision!

In researching this post, I stumbled upon this interesting web site – http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/R/ROS.html  It is noted on the site that uric acid is an antioxidant and that, “Perhaps the long life span of some reptiles and birds is attributable to their high levels of uric acid.”  Bird shit and reptile blood are full of the stuff.  If there is a cure for fluoroquinolone toxicity, it’ll probably come from bird turds or alligator blood.  Great.

 

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Fluoroquinolone Antibiotics Damage Mitochondria – FDA Does Little

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The Pharmacovigilance folks at the FDA know that fluoroquinolones are damaging mitochondria.  Yet, they look the other way.  Adding a more severe warning about peripheral neuropathy to the warning label isn’t helpful.  People should know that they are increasing their risk of every chronic disease associated with mitochondrial damage and oxidative stress when they take a fluoroquinolone.  That would actually be helpful.

Here is the post, on Hormones Matter – http://www.hormonesmatter.com/fluoroquinolone-antibiotics-damage-mitochondria-fda-adds-warning/

 

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