A Delicate Balance: Fluoroquinolones Disrupt Cellular Homeostasis

This post was inspired by, “My Father’s Body, at Rest and in Motion: His systems were failing. The challenge was to understand what had sustained them for so long.” by Siddhartha Mukherjee, published in the January 8, 2018 issue of The New Yorker. (When not noted otherwise, all quotes are from “My Father’s Body, at Rest and in Motion.”) It’s a poignant personal account of Dr. Mukherjee’s father’s decline and death. It is also about the beautiful and delicate balance that is life. I cannot do the article justice in taking excerpts from it, and I suggest that you read it yourself. It is only related to fluoroquinolone toxicity peripherally (if at all), but I think there are lessons to be learned about fluoroquinolone toxicity within it. There are certainly lessons about life, and death, within it, and I recommend it to anyone who likes thoughtful, New-Yorker-esque articles.

I never thought about cellular homeostasis before I got floxed. Who, other than biochemists and med students, thinks about cellular homeostasis?

“There’s a glassy transparency to things around us that work, made visible only when the glass is cracked and fissured. Look, it’s nothing. To dwell inside a well-functioning machine is to be largely unaware of its functioning. That’s its gift, and we accept it thoughtlessly, ungratefully, unknowingly.”

Homeostasis, the ability to maintain internal consistency, is crucial for life. Indeed, “Homeostasis, the capacity to maintain a functional equilibrium, would turn out to be one of the cardinal principles of all organisms; it’s often described as one of the defining principles of life.” The dance within our cells that maintains homeostasis, that keeps us functioning properly, that keeps each feedback and feed-forward loop operating optimally, is necessary for health, and for maintaining life.

Fluoroquinolones disrupt cellular mineral levels, the balance of antioxidants and ROS within cells, hormonal balance, gut biome balance, and more. They cause mitochondrial apoptosis, and nervous system dysfunction. Fluoroquinolones disrupt homeostasis—the delicate balance and intricate dance of keeping minerals, hormones, vitamins, etc. in-balance within our cells. Fluoroquinolones disrupt crucial functions, and in doing so, throw a wrench in health, and in life.

What happens when homeostasis is disrupted by fluoroquinolones?

The answer seems to depend on multiple factors. How many physiological processes were disrupted? To what extent? Where? What feedback and feed-forward loops were triggered? What is the downstream damage? What are the genetic (and other) predispositions of the individual who has been hurt? What is the ROS/MMP burden on the body/cell at the time that a person takes ciprofloxacin or levofloxacin? What are the hormone levels at the time that a person takes the pill(s)? What are the compensating factors that make a person stronger or more resilient? What makes someone vulnerable? Who? What? How?

In theory, we can know the answers to these questions. In practice though, we can’t, and a certain amount of luck, or lack thereof, enters the equation. We cannot know the answers to those questions before we take any pharmaceutical, and thus, we are playing Russian Roulette with our bodies when we take drugs like fluoroquinolones that disrupt multiple systems, and cause disrupted cellular homeostasis.

“Indeed, once self-regulation fails, complex systems of all kinds can be claimed by a version of this process, sometimes called a failure cascade. A storm-battered tree takes down a transmission line; the increased load causes another network component to fail, further increasing the load, turning a local outage into a regional blackout. The failure of one division in one bank can trigger a global cataclysm. That’s a failure cascade.”

Perhaps the difference between a person who takes multiple fluoroquinolone prescriptions without notable effect and a person who experiences severe toxicity and even death, is whether or not the fluoroquinolones throw a person into a “failure cascade.” Homeostasis can be disturbed a bit with no notable effect (our healing and stability mechanisms kick in), but if it is disturbed enough to throw a person into a “failure cascade” everything goes wrong in his or her body, and it feels as if a bomb has exploded.

“Yet maintenance defies measurement; it’s the glass pane that’s visible only when it cracks. In the several months of my father’s decline, hospitalization, and death, we recorded the values of hundreds of things in his body: potassium, temperature, breathing rate, creatinine, bicarbonate, chloride, the oxygen saturation of his blood, the output of his urine. What we didn’t measure—couldn’t measure—was how hard his body was working to bestill these values, how much “unnatural vigilance” was required to keep things steady, and how deeply his physiology must have collapsed when the numbers finally dipped into abnormalcy. We had, in short, no real measure of homeostatic resilience, of physiological reserve.”

In “My Father’s Body, at Rest and in Motion” Dr. Mukherjee is writing about his elderly father, whose body is failing because of old-age and a bad fall. As difficult as it is for the elderly people (and their loved ones) who enter a “failure cascade” due to old-age and/or trauma, it is expected that old-age brings bodily failures, and that some of those failures will lead to other failures. We expect that time will disrupt homeostasis and that our cellular functions will eventually fail. But we don’t expect that a drug—a popular antibiotic no less—will trigger a “failure cascade.” They do though. Ciprofloxacin, levofloxacin, moxifloxacin, and other fluoroquinolones trigger multi-symptom, chronic, disabling illness—often in young people.

How do people who have been hurt by fluoroquinolones get back to a healthy state of cellular homeostasis? How do you stop the feedback loops that are leading to the “failure cascade?” I don’t know the answer for any individual, and nothing on this site should be interpreted as medical advice (I’m not a doctor), but some basic advice, that seems to have helped other people, can be found in the post, I’m Floxed, Now What? 

It struck me as I read “My Father’s Body, at Rest and in Motion” just how little we (collectively–including doctors and scientists) know about health, or even life (not how to live life, but the actual process of life, and our cellular processes that are at the center of life). Health, healing, and even life, are things that are easy to take for granted, and to fail to study or even notice, until they go away or are threatened. I barely thought about my health, much less my cellular homeostasis, until it was threatened by ciprofloxacin. After I got “floxed” I had a reason to notice how delicate and precarious my health was. Health and its basis of homeostasis are both robust and delicate. Our feedback and feed-forward loops work as they should–until they don’t. Without homeostasis, without the processes that compose life working the way they should, life ceases. Fluoroquinolones disrupt homeostasis, and cause many physiological systems to go hay-wire. The damage that fluoroquinolones do can be severe–particularly if a “failure cascade” is triggered. With every fluoroquinolone pill taken, damage is done, and the risk of a “failure cascade” occurs. Nothing is worth risking a “failure cascade” if that cascade results in death, and very few “floxies” would say that treatment of their infection was worth the pain and disability caused by fluoroquinolones. We may not fully understand the delicate balance of life, or the processes occurring in our cells, but they are important none-the-less, and throwing a wrench in them with fluoroquinolones is both damaging and foolish. 

 

 

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