In 2013, the FDA updated the warning labels on all fluoroquinolones (Cipro, Levaquin, Avelox, Floxin and their generic equivalents) to note that permanent peripheral neuropathy is a potential effect of all fluoroquinolones. The FDA safety announcement noted that, “The U.S. Food and Drug Administration (FDA) has required the drug labels and Medication Guides for all fluoroquinolone antibacterial drugs be updated to better describe the serious side effect of peripheral neuropathy. This serious nerve damage potentially caused by fluoroquinolones may occur soon after these drugs are taken and may be permanent.”
Since that announcement, patients, patient advocates, researchers, and lawyers have been trying to figure out exactly how fluoroquinolones cause peripheral neuropathy. The FDA documents going over the link between peripheral neuropathy and fluoroquinolone use point toward mitochondrial damage as the mechanism through which fluoroquinolones cause peripheral neuropathy. There is certainly evidence that fluoroquinolones damage mitochondria, and that damaged mitochondria are responsible for peripheral neuropathy. Given the evidence available, it is most likely that fluoroquinolones cause peripheral neuropathy through damaging mitochondria.
However, in this post, I would like to explore another possibility.
Flouroquinolone Antibiotics and Charcot-Marie-Tooth Disease
Might fluoroquinolones trigger the expression of Charcot-Marie-Tooth (CMT), a neurological disorder that is a form of muscular dystrophy? According to MDA.org, “CMT is the most commonly inherited peripheral nerve disorder affecting about 1 in 2,500 people. CMT causes damage to the peripheral nerves, which carry signals from the brain and spinal cord to the muscles, and relay sensations, such as pain and touch, to the brain and spinal cord from the rest of the body.”
Charcot-Marie-Tooth has several genetic markers and is thought of as a purely hereditary disease. However, there is a fascinating case-study that was published in The Annals of Pharmacotherapy in October of 2011 entitled “Hereditary Neuropathy Unmasked by Levofloxacin,” that goes over the case of a 56-year-old, formerly healthy man with “no history of medical problems,” who developed difficulty walking, numbness, and burning pain and weakness especially in his legs after taking levofloxacin. The patient’s health problems persisted after he stopped taking the levofloxacin and he was subsequently diagnosed with Charcot-Marie-Tooth disease. The article notes that:
“Charcot-Marie-Tooth disease is a clinically and genetically heterogeneous group of hereditary peripheral neuropathies. Toxic or idiosyncratic reactions to drugs may uncover a preexisting asymptomatic polyneuropathy. Fluoroquinolones, including levofloxacin, have rarely been associated with sensory and motor polyneuropathy, perhaps because of the fact that physicians sometimes have difficulty in associating this adverse reaction with fluoroquinolone therapy.”
Is it possible that this case-study isn’t unique and that the permanent peripheral neuropathies brought on by fluoroquinolones are a result of the triggering of Charcot-Marie-Tooth disease? Certainly, more research would need to be done for an answer to be found. The thought of fluoroquinolone antibiotics, drugs that are prescribed to millions of people every year, unmasking of Charcot-Marie-Tooth, a disease with no cure, is horrifying to say the least.
How could Fluoroquinolones Trigger a Genetic Disease?
One might wonder how fluoroquinolones could trigger the expression of hereditary diseases. The possibility that fluoroquinolones trigger epigenetic changes is noted in the post, “What is Fluoroquinolone Toxicity?” It is noted that:
Fluoroquinolones are topoisomerase interrupters. The mechanism for Cipro/ciprofloxacin, and all other fluoroquinolone antibiotics 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.”
Topoisomerases are enzymes that are necessary for DNA and RNA transcription. Topoisomerase interrupting drugs have been found to profoundly affect gene expression. It may be possible that fluoroquinolones trigger the expression of dormant genes. So, for example, those who have a predisposition toward an autoimmune disease may bring on the autoimmune disease with the fluoroquinolone. Anecdotally, it seems as if any existing weakness a person has is exacerbated by fluoroquinolones.
It is hypothesized in “Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology,” that all adverse reactions to fluoroquinolones are due to epigenetic mechanisms:
“The quinolones are a family of broad-spectrum antibiotics. They inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription. Eukaryotic cells do not contain DNA gyrase or topoisomerase IV, so it has been assumed that quinolones and fluoroquinolones have no effect on human cells, but they have been shown to inhibit eukaryotic DNA polymerase alpha and beta, and terminal deoxynucleotidyl transferase, affect cell cycle progression and function of lymphocytes in vitro, and cause other genotoxic effects. These agents have been associated with a diverse array of side-effects including hypoglycemia, hyperglycemia, dysglycemia, QTc prolongation, torsades des pointes, seizures, phototoxicity, tendon rupture, and pseudomembranous colitis. Cases of persistent neuropathy resulting in paresthesias, hypoaesthesias, dysesthesias, and weakness are quite common. Even more common are ruptures of the shoulder, hand, Achilles, or other tendons that require surgical repair or result in prolonged disability. Interestingly, extensive changes in gene expression were found in articular cartilage of rats receiving the quinolone antibacterial agent ofloxacin, suggesting a potential epigenetic mechanism for the arthropathy caused by these agents. It has also been documented that the incidence of hepatic and dysrhythmic cardiovascular events following use of fluoroquinolones is increased compared to controls, suggesting the possibility of persistent gene expression changes in the liver and heart.”
It is possible that fluoroquinolones are profoundly changing gene expression, and that the adverse effects of fluoroquinolones are a result of altered gene expression. Fluoroquinolones are, after all, topoisomerase interrupters.
Are Fluoroquinolones Expressing Other Genetic Diseases?
It has been suggested that fluoroquinolones trigger other diseases that are considered to be hereditary. Ehlers-Danlos Syndrome (EDS) is one that is mentioned often. Fluoroquinolones cause collagen synthesis problems, and Ehlers-Danlos Syndrome is “caused by a defect in the structure, production, or processing of collagen or proteins that interact with collagen.” Might some aspects of fluoroquinolone toxicity be Ehlers-Danlos Syndrome triggered by fluoroquinolones? Again, research needs to be done before asserting this as truth, but it is a possibility that should be explored.
It has also been suggested that fluoroquinolones trigger latent endocrine and thyroid disorders. In Fluoroquinolone Antibiotics and Thyroid Problems: Is there a Connection?, it is noted that, “I would suspect that anyone with any underlying genetic predisposition, or possibly harboring a subclinical, latent, or silent endocrinopathy might be ‘pushed over the edge’ into full blown clinical pathology. This is actually what I think may have happened with me, even though I had no overt indications of any kind of thyroid or endocrine disorder prior to taking the Cipro.” The connections between endocrine and thyroid disorders and fluoroquinolones are thoroughly explored in the site www.fluoroquinolonethyroid.com.
Are Dormant Genes Destiny?
Some might say that these diseases are a result of faulty genes, not fluoroquinolones. I strongly disagree with that assertion. Other than the infection that fluoroquinolones were prescribed to treat, most people who take fluoroquinolones are healthy. If they have dormant genetic diseases, those diseases are not being expressed. They have no symptoms of underlying diseases until they take a fluoroquinolone. Fluoroquinolones are making healthy people sick. If it is through the changing of gene expression, that doesn’t make it any better.
Again, the notion that fluoroquinolones trigger expression of Charcot-Marie-Tooth disease, Ehlers-Danlos Syndrome, and other genetic diseases is a hypothesis, not an assertion of fact. However, it is a hypothesis that should be explored. Thus far, there has been no good explanation as to why fluoroquinolone toxicity symptoms vary so significantly from one person to the next. Perhaps the explanation is that each person’s genes are different, and different genetic weaknesses are exposed by fluoroquinolones in each person.
As I explore the multiple mechanisms for fluoroquinolone toxicity, I keep coming back to their mechanism of action stated on the warning labels – fluoroquinolones are topoisomerase interrupters. They intentionally disrupt the process of bacterial DNA and RNA replication. We do not know enough about that process to foresee its unintended consequences, and, unfortunately, I think it’s entirely possible that fluoroquinolones are triggering the expression of many “genetic” diseases that would have stayed dormant if it weren’t for the fluoroquinolones. More research is certainly necessary, and I hope that there are some scientists who are willing to examine this hypothesis.
Information about Fluoroquinolone Toxicity
Information about the author, and adverse reactions to fluoroquinolone antibiotics (Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin and Floxin/ofloxacin) can be found on Lisa Bloomquist’s site,www.floxiehope.com.
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This article was published originally on Hormones Matter on March 7, 2016.