Cellular Stress, Chronic Stress, and Fluoroquinolone Toxicity


stress-and-zen

My Healing Journey

Acupuncture helped me immensely in my journey through fluoroquinolone toxicity, and I even credit my acupuncturist with saving my life when I felt like a bomb was going off in my body. Several people have asked me what my acupuncturist did that helped me through fluoroquinolone toxicity. The honest answer is—I’m not sure. I don’t know enough about acupuncture or to tell anyone else how they might be able to replicate his methods or my healing. I do know, however, that I was spiraling when I first saw him. I was anxious, scared, and on the verge of panic because something was wrong with my body, and I had no idea what was going on or how to fix it. My acupuncturist was able to stop my cycle of anxiety, fear, and panic. He was able to calm me down. It helped—immensely—and it saved me from getting worse physically and psychologically.

A lot of the things that helped me to heal from my adverse-reaction to Cipro/ciprofloxacin were things that diminished my anxiety, quelled my fears, and calmed me down. I took a Mindfulness Based Stress Reduction class (through my health insurer—Kaiser Permanente) within weeks of getting floxed, and it helped a lot (I always felt better the day after the classes). I learned to meditate and I started some spiritual practices, and those were helpful as well. I removed stress and fear inducing things from my life (mainly, I got off the internet), and I found that I felt better when I removed those influences from my life.

I’m not saying that fluoroquinolone toxicity reactions are because of stress or anxiety, or that they’re “all in your head.” I am, however, saying that reducing stress helped me to recover, and that things that increased my stress levels made me feel worse. I also think that we shouldn’t have knee-jerk reactions against hypotheses about fluoroquinolone toxicity that look at how we react to stress—after all, stress affects everything (hormones, mental function, cardiovascular system, digestion, etc.). Additionally, there have recently been some interesting studies and hypotheses about how people respond to stress on a cellular metabolic level that are likely applicable to floxies.

Are Some People Genetically Predisposed Toward Shutting Down in Times of Stress?

On Dr. Sharon Meglathery’s web site, http://www.rccxandillness.com/, she hypothesizes that people who have a variety of multi-symptom, chronic illnesses (including ME/CFS, fibromyalgia, POTS, EDS, autoimmune diseases, psychiatric diseases, etc.) have a common set of gene mutations that make them unable to cope with stress on a cellular/chemical level. She notes that:

Let me illustrate how a clinically “healthy” carrier for a non-functioning CYP21A2 mutation (or a person with 2 mutated copies of partially functioning genes) could possibly develop chronic illness: Cortisol is a hormone needed for a normal stress response. Cortisol is made from 17hydroxyprogesterone by the enzyme called 21hydroxylase. 21hydroxylase is coded for by the CYP21A2 gene in the RCCX module. If a carrier for a CYP21A2 mutation which makes no functioning 21hydroxylase or a homozygote for partially functioning 21hydroxylase has chronic stress and needs to make lots of cortisol all of the time, it is possible that there may not be enough 21hydroxylase available to make the amount of cortisol the body needs. In this case, cortisol levels would be abnormally low for the amount of stress, 17hydroxyprogesterone would be abnormally high causing symptoms and some of the 17hydroxyprogesterone would be used by an enzyme coded for by CYP17 to make an abnormally high amount of androgens (male sex hormones) also causing symptoms. As I will show later, the symptoms caused by these hormonal abnormalities are shockingly familiar to those with chronic illness. Further, high cortisol releasing hormone (CRH), released when cortisol is too low can turn on devastating inflammatory cascades, including mast cell activation. (High CRH has recently been found to be associated with FM).”

Could the people who get “floxed” have CYP21A2 mutations that make them unable to cope with stress on a cellular level? Might the multi-symptom, chronic illness and disability that many floxies suffer from start with improper cortisol synthesis? It certainly sounds like a reasonable hypothesis to me.

Of course, the hypothesis that Dr. Meglathery is putting forth needs to be studied in order to be verified, and then further studies would need to be done to see if people suffering from fluoroquinolone toxicity have these genetic mutations, in order to verify that hypothesis. We are in the very early stages of figuring out what is going on in the bodies of everyone suffering from multi-symptom, chronic, illnesses—especially those caused by pharmaceuticals.

The Stress and Chronic Illness Cycle

Dr. Meglathery also explains how chronic stress could lead to the following ailments in people who are genetically predisposed to being unable to produce sufficient levels of cortisol:

At this point, if you are aware, you usually see some mild MCAS symptoms (allergy symptoms: hives, migraines, food intolerances, asthma, diarrhea, irritability, brain fog, increased distractibility and escalating sensory issues). CRH, the hormone released by the hypothalamus telling the body (via the pituitary) to make cortisol when cortisol is inappropriately low, is released in a pulsatile fashion. CRH is the most potent activator of mast cells in the body and found to be high in FM (Published by Dr. Theoharides, 1/16). It also decreases stomach acid, possibly contributing to dysbiosis and malabsorption; it stimulates the sympathetic nervous system causing the release of even more adrenaline and nor-adrenaline (norepinephrine) and it directly turns on the immune system. CRH release may be the master switch which propels a person with CYP21A2 mutations into irreversible chronic illness by effecting downstream changes which place an insurmountable and persistent stress load on the body. The demand for 21hydroxylase can now never be sated. I believe that people with CYP21A2 mutations who are exposed to Borrelia burgdorferi, the pathogen in Lyme Disease (which directly activates mast cells) and other strong infectious stressors, like EBV, jump straight to immune system activation, flipping the switch by bypassing CRH initially, but CRH rises later in response to the chronic stress of infection, locking them into chronic illness. Low blood volume/orthostatic challenges worsen (POTS), pain syndromes develop (via low cortisol, increased subluxations/injuries, inflammatory mediators affecting nerves, high 17hydroxyprogesterone), raised intracranial pressure/acquired chiari malformation can occur (via progesterone, low magnesium, brain inflammation from MCAS, etc.) and MCAS is present consistently.

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With the immune system dysregulated, dysbiosis becomes fully established with gut inflammation and malabsorption. The body becomes colonized with new pathogens (through the porous gut and other pathways) and SIBO can occur. Pathogens already present start to cause problems (fungus-athlete’s foot, herpes virus-cold sores, low virulence bacteria and viruses like mycoplasma, etc), the ability to fight serious infection drops and in many, the ability to fight the viruses which cause colds increases. The body is now under tremendous physical stress and the person is under tremendous negative emotional stress, both of which increase the cortisol deficit and sustain the growing list of medical issues. If brain inflammation is part of the picture (likely as part of MCAS), we get psychosis and severe mood disorders plus or minus the physical issues. This is a downward spiral which few escape.”

Many of the symptoms that Dr. Meglathery mentions in the above paragraphs are too familiar to people who are floxed. Mast cell activation (MCAS), and the symptoms that come along with it—hives, migraines, food intolerances, asthma, diarrhea, irritability, brain fog, increased distractibility and escalating sensory issues—are common among those who are floxed. Low stomach acid, dysbiosis and malabsorption are also common among those who are floxed. Many people with fluoroquinolone toxicity also suffer from symptoms of POTS/dysautonomia. Small intestinal bacterial overgrowth (SIBO) has occurred in those suffering from fluoroquinolone toxicity as well. Symptoms of brain inflammation, sometimes including psychosis and other severe mood disorders, can also occur in those with fluoroquinolone toxicity.

As you can see from Dr. Meglathery’s connections above, stress, especially chronic stress, can start a cycle of chronic illness in those who are genetically predisposed, and the chronic illness cycle includes many of the symptoms of fluoroquinolone toxicity.

Cellular Stress and Chronic Illness

The tendency for chronic illness to be self-perpetuating on a cellular level is also demonstrated in Dr. Robert K. Naviaux’s acclaimed 2016 study, “Metabolic Features of Chronic Fatigue Syndrome,” which finds that, in ME/CFS patients, mitochondria respond to stressors by decreasing oxygen consumption and the transfer of cellular energy production—ATP—from inside the cell (where it belongs), to outside of cells (“Finding ATP outside a cell is a sign that something major has gone wrong.”). People with ME/CFS get “stuck” in a state of “hypometabolic response to environmental stress similar to dauer” – a cellular state that is similar to hibernation. This hypometabolic/dauer state is triggered by mitochondrial stressors (mitochondrial stressors can include emotional and psychological stress, as well as things like viruses, toxins—including many pharmaceuticals, malnutrition, etc.). It is noted in “The Core Problem in Chronic Fatigue Syndrome Identified? Naviaux’s Metabolomics Study Breaks Fresh Ground” that:

Naviaux believes the mitochondria are able to sense every kind of danger – from pathogens to pH changes to toxic elements from pesticides, heavy metals, etc. to inflammation. They sense trouble in the form of an infection when they detect a drop in voltage caused by the diversion of electrons (NADH / NADPH) to make viral components or respond to a broad variety of toxins.

In the cell danger response (CDR) the mitochondria respond instantaneously to that loss by decreasing their oxygen consumption – thus thwarting pathogens from using the building blocks of the cell to replicate. Because the oxygen is no longer being used, it builds up in the cells causing a oxidatively charged environment which interrupts viral synthesis. The CDR also stiffens the membrane of the cell to stop pathogens from exiting it, warns other cells of the danger, and emits ATP in order to warn other cells to get their defenses up.”

Fluoroquinolones can cause mitochondrial damage, and may trigger the CDR, by depleting mitochondrial DNA. Fluoroquinolones have been shown to “cause mitochondrial dysfunction and ROS overproduction in mammalian cells.” For many people, the cycle of stress, chronic illness, hypometabolism, and dauer, starts with an assault on mitochondria from fluoroquinolone antibiotics.

Concluding Thoughts on Stress and Fluoroquinolone Toxicity

Again, I want to emphasize that these connections are hypotheses, not proven facts. However, as the fields of metabolomics and genetics progress, I suspect that we will find answers to fluoroquinolone toxicity, and all other multi-symptom, chronic illnesses.

You may be wondering, how does one get out of the stress/chronic illness cycle? As anyone who has researched or experienced a chronic illness knows, that question is much easier asked than answered. The fluoroquinolone toxicity recovery stories on this site give some valuable suggestions for those dealing with fluoroquinolone toxicity, as does the post “I’m Floxed, Now What?” Before getting too overwhelmed with advice though, a first-step in the right direction may be to reduce stress. We all have stress in our lives—but if there are things that you can do to avoid it (staying away from people and information that give you anxiety, and also avoiding mitochondrial toxins), or that help you to cope with it (meditation, mindfulness, etc.), those things may be helpful in starting your fluoroquinolone toxicity (or other chronic illness) recovery journey. It is difficult to reverse the cellular cycles of chronic illness, and reducing stress is not a quick-fix or easy answer, it is more like a starting point.

I know that it sounds simplistic and dismissive to tell you to “reduce stress,” but hopefully the information above demonstrates that stress is related to every bodily function, and it is intimately connected to chronic illness. Neither chronic illness nor stress, nor their connections, are trivial or to be dismissed in any way. If Dr. Meglathery is right, and there are some people who are genetically predisposed toward an inability to handle stress on a cellular level, avoiding stress (including toxins, viruses, etc.) may be key for avoiding chronic illness for those people. I suspect that everyone who is “floxed” falls into the category of “those people” who are more succeptible to harm from stressors than others. It isn’t easy to avoid stress (or stressors like toxins and viruses), but doing so may be necessary for your health, and it also may be a key to your healing. Most stress-reduction exercises and tools are inexpensive and easy to access, so they’re almost certainly worth a try.

 

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2 thoughts on “Cellular Stress, Chronic Stress, and Fluoroquinolone Toxicity

  1. tammyrenzi January 9, 2017 at 8:07 am Reply

    Lisa, as always, you provide such great information and food for (scientific) thought. Reducing my stressed helped my healing in a BIG way – from staying away from stressful people to taking an MBSR class. I’m doing very well now but stress still can flare up my anxiety. By using meditation, gentle yoga, and mindfulness, I am learning how to heal myself. It’s not to say other “things” might work, but I am relying on fewer supplements and more natural ways of healing.

  2. Jodi Sarda February 22, 2017 at 9:28 am Reply

    I couldn’t agree more, based on my experience. Acupuncture was a very important part of my recovery, as well. I noticed after a while a very direct link between my symptoms and stress – my body simply couldn’t function. I had a very deadline driven job and used to thrive on the adrenaline of that. In fact, I prided myself on my ability to stay calm under pressure. But even so, the slight changes in stress hormones that come with being under a hard deadline would wipe me out instead of feeling energized. My naturopath confirmed that I have low cortisol levels. I have also been diagnosed with ME/CFS. I felt it was consistent with mitochondria damage and oxidative stress. It literally feels like all the energy is just drained from every cell. My best medicine has been to be vigilant about my mental health and happiness, hormone replacement therapy, and finding the sweet spot between staying active and getting enough rest. Four years out from 3 floxings in 6 months (2 Cipro, 1 Levaquin) and still every day is a challenge. I am happy to say it mostly doesn’t show to others. I am fortunate that I don’t have to work anymore. Trying to maintain my pre-flox life just about did me in.

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