Normal Blood Tests Do Not Always Mean Normal Health -Why Millions of Patients May Be Told “Everything Is Normal” While Their Cells Tell a Very Different Story

“Your blood tests are normal.” Every day, millions of patients hear these reassuring words before leaving their physician’s office. In most cases they are accurate, and modern laboratory medicine deserves enormous credit for transforming healthcare. 

Routine blood testing has dramatically improved our ability to diagnose infections, anemia, diabetes, kidney disease, liver disorders, endocrine abnormalities, electrolyte disturbances, and countless other medical conditions. Few advances in modern medicine have contributed more to early diagnosis and improved patient care. Yet a fundamental question deserves greater attention.

Does a normal blood test always mean that the body is healthy? For many patients, the answer appears to be far more complicated.

Across numerous chronic illnesses, physicians encounter individuals whose routine laboratory values remain largely within reference ranges while their quality of life continues to decline. They report profound fatigue, exercise intolerance, muscle weakness, tendon pain, connective tissue problems, unexplained weight loss, hair loss, brittle nails, cognitive dysfunction, hormonal disturbances, neuropathy, poor wound healing, gastrointestinal symptoms, and increasing sensitivity to physical or emotional stress. Their symptoms are real, often progressive, and sometimes disabling. Yet standard laboratory investigations frequently fail to explain the severity of their condition.[1–5]

This apparent contradiction has become one of the greatest challenges in modern medicine. The problem is not that routine laboratory testing is inaccurate. The problem is that it answers a different biological question.

Most conventional laboratory tests evaluate the composition of circulating blood and identify evidence of organ dysfunction. They reveal whether the liver is releasing abnormal enzymes, whether the kidneys are filtering waste appropriately, whether blood glucose is elevated, whether infection is present, or whether significant electrolyte abnormalities have developed. These tests are indispensable, but they were never designed to determine how efficiently billions of individual cells are producing energy, repairing damage, synthesizing proteins, responding to oxidative stress, or adapting to chronic metabolic challenges.[6–9]

To understand this distinction, we must begin with one of the most remarkable principles in physiology: homeostasis.

Every second of every day, the human body works relentlessly to maintain a stable internal environment. Blood glucose, calcium, sodium, potassium, oxygen saturation, body temperature, blood pressure, and acid-base balance are regulated within remarkably narrow physiological limits because survival depends upon their stability.[10–13]

Homeostasis is often mistaken for evidence of perfect health. In reality, it is evidence of extraordinary adaptation. The body does not maintain normal blood chemistry because nothing is wrong. It maintains normal blood chemistry because allowing those values to drift outside critical limits would threaten immediate survival. To accomplish this, human physiology continuously redistributes available resources, prioritizing the organs that cannot tolerate interruption. The brain, heart, lungs, kidneys, and other vital systems receive preferential support because their failure would rapidly become life-threatening. Other tissues, although important for long-term health and quality of life, gradually become secondary priorities whenever energy production, nutrient availability, or metabolic efficiency decline.[14–18]

This biological strategy has allowed humans to survive famine, severe illness, trauma, infection, and prolonged physiological stress throughout evolution. It also explains why symptoms often appear long before laboratory abnormalities.

Hair follicles provide an excellent example. They are among the most rapidly dividing tissues in the human body and require continuous ATP production, amino acids, iron, zinc, thyroid hormone signaling, and numerous growth factors to sustain normal growth. During prolonged physiological stress, the body redirects resources away from hair production, causing follicles to enter the resting phase prematurely. Weeks later, diffuse hair shedding develops—a condition recognized clinically as telogen effluvium.[19–22]

The same principle applies to fingernails. Healthy nails require continuous protein synthesis, sulfur-containing amino acids, zinc, iron, adequate circulation, and sufficient cellular energy. Chronic metabolic stress commonly produces brittle nails, longitudinal ridging, thinning, and slower growth. These changes are rarely considered together with fatigue, muscle loss, or hormonal alterations, yet they often represent different manifestations of the same adaptive physiology.[23,24]

Muscle tissue tells a similar story. Most people think of skeletal muscle primarily as the organ responsible for movement. From a metabolic perspective, however, skeletal muscle also represents one of the body’s largest reservoirs of amino acids. During prolonged physiological stress, inflammation, malnutrition, or impaired energy production, muscle proteins may be broken down to supply amino acids required for immune function, gluconeogenesis, enzyme synthesis, tissue repair, and maintenance of vital organs.[25–28]

Patients notice the consequences long before physicians identify objective abnormalities.

➤They become weaker.

➤Recovery after physical activity takes longer.

➤Exercise that once felt routine becomes exhausting.

➤Muscle mass gradually declines despite adequate motivation and, in many cases, adequate caloric intake.

The bloodstream may remain remarkably stable because the body is preserving blood chemistry at the expense of structural tissue. Bone follows the same biological logic. Far from being an inert framework, bone serves as a dynamic reservoir of calcium, phosphorus, magnesium, and numerous signaling molecules. Continuous remodeling depends upon healthy osteoblasts, osteoclasts, hormones, amino acids, micronutrients, and sufficient mitochondrial energy production. If physiological demands exceed available resources, the body maintains circulating calcium by drawing upon skeletal reserves while remodeling efficiency gradually declines.[29–32]

Connective tissue presents another important example.

Collagen is the most abundant protein in the human body and provides structural integrity to tendons, ligaments, fascia, skin, blood vessels, and many internal organs. Its synthesis requires adequate ATP production, vitamin C, glycine, proline, lysine, iron, copper, and numerous enzyme systems. When these requirements are not fully met, tissue repair slows, tendons recover less efficiently, skin becomes thinner, and healing after injury may be significantly prolonged.[33–36]

Although these observations appear to involve different organs, they share a common biological denominator

– the mitochondrion.

For decades, mitochondria were described simply as the “powerhouses of the cell.” Modern cell biology has revealed a far more sophisticated picture. Mitochondria regulate oxidative phosphorylation, ATP production, fatty acid oxidation, intermediary metabolism, calcium homeostasis, reactive oxygen species signaling, apoptosis, innate immunity, steroidogenesis, and communication with the nucleus through complex signaling pathways that influence gene expression and cellular adaptation.[37–42]

Every organ depends upon these functions. Every tissue depends upon ATP. Every repair process depends upon mitochondrial metabolism. Consequently, when mitochondrial function becomes less efficient, the effects rarely remain confined to a single organ system. Muscles, nerves, connective tissue, endocrine organs, gastrointestinal tissues, and the immune system may all be affected simultaneously because they rely upon the same fundamental cellular machinery.

This concept may explain why patients suffering from very different diseases often describe remarkably similar symptoms despite entirely different diagnoses. The initiating cause may vary, but the biological response frequently converges upon common pathways involving altered energy metabolism, oxidative stress, endocrine adaptation, inflammation, and redistribution of metabolic resources.[43–47]

Perhaps the greatest misconception in modern medicine is the belief that disease begins when laboratory values become abnormal.

➦Biology tells a different story.

➦Disease often begins with adaptation.

Long before an organ fails, its cells may already be consuming more energy, activating stress-response pathways, slowing protein synthesis, conserving nutrients, and postponing repair in order to preserve immediate survival. By the time routine laboratory values finally become abnormal, those compensatory mechanisms may have been operating for months- or even years. Understanding this distinction does not diminish the value of conventional laboratory medicine.

It expands it.

Routine blood tests remain one of the greatest diagnostic tools ever developed. However, they represent the beginning of the investigation rather than its conclusion. The future of medicine will likely depend upon integrating traditional laboratory testing with a deeper understanding of cellular physiology, mitochondrial biology, metabolomics, endocrine adaptation, and systems biology. Only then can we begin to understand why so many patients continue to suffer despite hearing one reassuring sentence:

“Your blood tests are normal.”

If the body is capable of maintaining apparently normal blood chemistry while tissues gradually sacrifice their own reserves, an obvious question follows. How does this happen, and why does it often remain invisible to routine laboratory testing? 

The answer lies in one of the most elegant survival strategies in human biology.

The bloodstream is one of the body’s most tightly protected environments. Every organ depends upon its stability. As a result, the body will invest enormous physiological effort to maintain normal concentrations of glucose, calcium, electrolytes, oxygen, and countless other molecules circulating through the vascular system. When dietary intake, cellular metabolism, or energy production become compromised, the body rarely allows these values to change immediately. Instead, it begins drawing upon internal reserves.

 ♦️ Muscle supplies amino acids

 ♦️ Bone supplies minerals

 ♦️ Adipose tissue supplies energy

 ♦️ The liver mobilizes glycogen and regulates glucose production

 ♦️ Hormonal pathways shift toward conservation rather than growth

For the patient, these adaptations are experienced as symptoms. For the laboratory, they often remain invisible because blood chemistry has been successfully preserved.[48–52]

This distinction becomes particularly important when considering nutritional status. Modern medicine has traditionally focused on identifying overt nutritional deficiencies - conditions such as severe vitamin C deficiency, profound iron deficiency anemia, or advanced protein-energy malnutrition. Yet between optimal nutrition and severe deficiency lies a much larger biological spectrum. Cells may receive enough nutrients to survive but not enough to function optimally. Mitochondria may continue producing ATP but at reduced efficiency. Antioxidant systems may remain operational while gradually losing reserve capacity. Tissue repair may continue, but more slowly than before. These changes may substantially influence quality of life long before they produce abnormalities in routine laboratory panels.[53–56]

One of the clearest examples involves amino acid metabolism. Amino acids are often viewed simply as the building blocks of proteins, but their physiological roles extend far beyond structural support. They participate in collagen synthesis, neurotransmitter production, immune regulation, glutathione synthesis, methylation reactions, nitric oxide production, hormone synthesis, and mitochondrial metabolism. During prolonged physiological stress, available amino acids may increasingly be diverted toward essential survival functions rather than tissue maintenance and regeneration.[57–60]

The consequences are often visible throughout the body.

Muscle mass declines because structural proteins are continuously recycled to support critical metabolic needs.

Connective tissue repairs more slowly because fibroblasts cannot maintain normal collagen production.

 ♦️ Hair follicles prematurely leave the active growth phase.

 ♦️ Nails become brittle.

 ♦️ Skin loses elasticity.

 ♦️ Recovery after physical activity becomes increasingly prolonged.

These observations are not isolated events. They represent different expressions of the same biological strategy: preserve life first, postpone optimization until resources become available again.

The endocrine system undergoes similar adaptation. Hormones do not function independently from cellular metabolism; they respond to it. During prolonged physiological stress, growth hormone secretion may increase while insulin-like growth factor-1 (IGF-1) activity declines because adequate protein intake, liver function, and cellular energy are required for effective anabolic signaling. Thyroid hormone metabolism may shift toward reduced triiodothyronine (T3) production to lower energy expenditure. Leptin decreases as adipose reserves diminish, reducing reproductive signaling and modifying appetite regulation. Cortisol patterns may change as the body attempts to maintain glucose availability during chronic stress. Collectively, these responses reduce energy consumption while preserving the function of vital organs.[61–65]

Importantly, these hormonal adaptations should not automatically be interpreted as primary endocrine disease. In many circumstances they represent appropriate physiological responses to altered metabolic conditions. The challenge for clinicians is determining when adaptive physiology has become maladaptive and when persistent compensation begins contributing to chronic illness.

Mitochondria remain central to this discussion because virtually every adaptive response ultimately depends upon cellular energy. Oxidative phosphorylation supplies ATP required for protein synthesis, membrane transport, tissue remodeling, immune responses, hormone production, and cellular repair. Mitochondria also regulate reactive oxygen species, calcium signaling, apoptosis, innate immunity, and communication between the nucleus and cytoplasm.

Disturbance of these functions may therefore produce multisystem manifestations rather than isolated organ-specific disease.[66–70]

Increasing evidence suggests that chronic oxidative stress and impaired redox homeostasis may further amplify these metabolic disturbances. Reactive oxygen species are not inherently harmful; they serve essential signaling functions under physiological conditions. Problems arise when production exceeds antioxidant capacity or when antioxidant systems become depleted. 

Excessive oxidative stress may contribute to mitochondrial dysfunction, altered protein folding, lipid peroxidation, DNA damage, and impaired cellular signaling. At the same time, reduced glutathione availability and altered redox balance may further compromise the cell’s ability to recover from ongoing metabolic stress.[71–74]

These concepts have led to growing interest in functional metabolic assessment. Unlike routine laboratory testing, metabolomic approaches attempt to evaluate biochemical pathways rather than isolated circulating analytes. 

Organic acid profiles may provide indirect information about intermediary metabolism and the Krebs cycle. Amino acid profiles may identify altered utilization patterns. Acylcarnitine analysis may reveal disturbances in fatty acid oxidation. Oxidative stress markers may provide insight into redox balance. 

No single test can diagnose a complex chronic illness, and these methods should never replace careful clinical evaluation. Nevertheless, they may identify biochemical patterns that complement conventional laboratory findings and generate hypotheses for further investigation.[75–79]

Tests such as NutrEval represent one example of this broader functional approach. They are not disease-specific, nor do they provide definitive diagnoses. Their value lies in evaluating multiple metabolic pathways simultaneously, potentially revealing abnormalities in nutrient utilization, oxidative stress, amino acid metabolism, mitochondrial cofactor requirements, fatty acid metabolism, and selected organic acid pathways. Interpretation requires clinical context, scientific judgment, and awareness of each test’s limitations. Used appropriately, however, these assessments may provide information unavailable through routine laboratory testing alone.[80–82]

These principles may have particular relevance for patients with chronic multisystem illnesses, including inherited mitochondrial disorders, prolonged malnutrition, critical illness, chronic inflammatory diseases, and Fluoroquinolone-Associated Disability. Although each condition has distinct underlying causes, many ultimately converge upon common biological pathways involving altered mitochondrial function, oxidative stress, impaired tissue repair, endocrine adaptation, and redistribution of metabolic resources. Recognizing these shared mechanisms does not imply that the diseases are identical. Rather, it highlights the possibility that understanding fundamental cellular physiology may improve our understanding of seemingly unrelated clinical conditions.[83–87]

Medicine has achieved extraordinary success by identifying disease once organ dysfunction becomes measurable. The next frontier may be recognizing cellular dysfunction before irreversible structural damage develops. Doing so will require continued advances in metabolomics, mitochondrial biology, systems physiology, nutritional science, and biomarker discovery. More importantly, it will require curiosity—the willingness to investigate persistent symptoms even when conventional laboratory testing appears reassuring.

Normal blood tests remain one of the greatest accomplishments of modern medicine, and they will continue to save countless lives. Yet they should never become the final word when patients continue to deteriorate despite apparently reassuring results. Biology is more complex than any single laboratory panel can capture. The absence of abnormal blood chemistry does not necessarily indicate the absence of cellular dysfunction. As our understanding of human metabolism continues to evolve, one principle becomes increasingly clear: maintaining life and maintaining optimal health are not always the same biological process.

If this article encourages physicians to look beyond isolated laboratory values, researchers to continue exploring cellular metabolism, and patients to seek evidence-based evaluation rather than abandoning hope, then it will have served its purpose.  Some concepts discussed herein represent established physiological principles, while others remain active areas of scientific investigation. 

 🟢  Acknowledgments - Editorial assistance, language refinement, structural organization, and literature research were provided with the assistance of AI. Final scientific interpretation, opinions, and conclusions are solely those of the author, Jerzy Tyzskowski, Founder.

🟢Disclaimer 

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When we look at FQAD after fluoroquinolones such as ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin or norfloxacin, it is easy to focus on single symptoms: anxiety, insomnia, tremors, derealization, palpitations, tendon pain, brain fog. In reality, this is a multi-system syndrome in which several major axes of damage overlap. It is becoming increasingly clear that four pillars sit in the center: damage to GABA receptors, degradation of collagen and the extracellular matrix, mitochondrial dysfunction and DNA modification with disturbed gene regulation. It is not “just Cipro”, but a whole class of drugs – from ciprofloxacin and levofloxacin to moxifloxacin, norfloxacin, ofloxacin and other FQ antibiotics – that can trigger the same pattern of injury in susceptible individuals.
 

Fluoroquinolones are powerful antibacterial chemotherapeutics, but their impact on the human body does not end with killing bacteria. Recent work has shown that they can exert mitochondrial dysfunction, increase oxidative stress, damage collagen and connective tissue, disturb CNS conduction and act as genotoxic agents in mammalian cells [1–8,26–37]. For some patients the effect is transient; for others – those with FQAD – it becomes chronic and progressive.
 

 🧿 The first pillar is GABA receptor injury. GABA is the main inhibitory neurotransmitter in the brain. In healthy physiology it functions as an internal hand-brake, calming excessive neuronal firing, helping you fall asleep, lowering anxiety and stabilizing blood pressure, heart rate and muscle tone. Benzodiazepines artificially boost this system by binding to GABA(A) receptors; with long-term use the brain adapts, and abrupt discontinuation leads to a severe withdrawal state with panic attacks, insomnia, seizures and autonomic chaos [9–14]. Fluoroquinolones are not benzodiazepines, but some of them compete at GABA binding sites and enhance glutamatergic excitation, lowering the seizure threshold and producing CNS over-stimulation [1–8]. When you add mitochondrial dysfunction in neurons, chronic inflammation and oxidative stress, you have a recipe for sustained loss of GABAergic inhibition even in patients who never took a benzodiazepine [5–7,26–29].
 

This is why many FQAD patients present with what looks like long-term benzo use followed by too rapid a taper: persistent insomnia, racing thoughts, anxiety and depression, panic attacks, derealization, depersonalization, light and sound sensitivity, paraesthesias, tremors, “electric” sensations, tachycardia, blood pressure swings, shortness of breath, orthostatic symptoms and the feeling that the nervous system has “no skin” [9–14,19–21,25]. The symptom clusters described in detail in our Adverse Effects Evaluation Form fit perfectly with the picture of chronic GABA deficit and closely resemble what the literature describes as protracted benzodiazepine withdrawal [9–11,14,25]. The key difference is that in FQAD, the root cause is not misuse of a sedative, but toxic injury to the inhibition system itself.
 

 🧿 The second pillar is collagen and connective tissue. Early warnings focused on tendinopathy and tendon rupture, especially of the Achilles tendon, but it has become clear that the problem extends to ligaments, cartilage, fascia and even vessel walls. In vitro work on human tendon cells shows that fluoroquinolones disrupt the extracellular matrix, alter metalloproteinases, signaling proteins and caspase-3, leading to collagen degradation and tenocyte apoptosis [30]. Animal studies confirm reduced collagen fibril diameter, increased spacing between fibers and loss of integrins and other structural proteins [30,32–34]. Large cohort and pharmacovigilance studies demonstrate an increased risk of severe tendinopathy and tendon rupture, and an association with aortic aneurysm and dissection, suggesting deeper disturbances in collagen and elastic-fiber metabolism [31–34,37]. Clinically this becomes tendon and joint pain, cracking and popping, a sense that the body is “coming apart,” ligamentous instability, spinal problems and greater injury risk – all against the background of an already hyperexcitable, poorly inhibited nervous system.
 

 🧿 The third pillar is mitochondria – the cellular power plants. Because of their bacterial ancestry, mitochondria are natural targets for antibiotics. In vitro studies on human retinal MIO-M1 cells show that ciprofloxacin and tetracycline reduce mitochondrial membrane potential, disrupt metabolism and activate inflammatory and apoptotic pathways [26]. Other work documents that fluoroquinolones impair the respiratory chain, decrease ATP production, increase reactive oxygen species and damage mitochondrial proteins and DNA [27,28]. The latest chemical-proteomics study by Reinhardt and colleagues mapped multiple mitochondrial protein off-targets of ciprofloxacin and levofloxacin, including components of complexes I and IV, which may explain disturbed cellular respiration and chronic neurological, muscular and fatigue symptoms in patients [29]. A patient with FQAD and injured mitochondria has very limited exercise tolerance, crashes after minimal physical or chemical stress, is temperature-sensitive, shows glucose dysregulation, severe fatigue and poor tolerance of many drugs and supplements that further burden the mitochondria.
 

 🧿 The fourth pillar is DNA and gene regulation. Fluoroquinolone action in bacteria is based on poisoning DNA gyrase and topoisomerase IV, causing double-strand breaks and cell death. Increasing evidence suggests that related mechanisms affect mammalian cells and that fluoroquinolones can behave as topoisomerase II poisons in human cells [17,27,35,36]. Spectroscopic studies show that fluoroquinolones bind to human DNA, intercalate and trigger oxidative damage including 8-oxoG lesions and strand breaks [35]. Other studies document clastogenicity, micronuclei formation, chromosomal aberrations and an integrated picture of nuclear and mitochondrial oxidative stress [27,36,37]. There is growing discussion about stable drug–DNA complexes that may persist over time and potentially affect fertility and offspring health, though this area requires further independent research.
 

When you combine these four pillars – GABA disruption, collagen degradation, mitochondrial disregulation and genotoxicity – you get a coherent clinical picture of FQAD. The nervous system becomes chronically hyperexcitable and the patient shows symptoms indistinguishable from severe benzodiazepine withdrawal, despite never having taken benzos. The musculoskeletal system loses stability as tendons and ligaments weaken and collagen repairs poorly. Mitochondria cannot keep up with energy demands, so every exertion feels like a marathon and every stressor like a hammer blow. At the same time, DNA and repair systems are under pressure, which may lead to genetic instability and unusual reactions to chemical stimuli, drugs and infections.
 

From a diagnostic point of view, this means that an FQAD patient is not “a collection of random complaints,” but the victim of a single, coherent injury syndrome. The neurologist sees seizures, paraesthesias and derealization. The orthopaedic surgeon sees tendon pain and ruptures. The cardiologist sees POTS and arrhythmias. The gastroenterologist sees IBS and food intolerance. The psychiatrist sees anxiety and insomnia. Only when someone asks about fluoroquinolone exposure and looks at the four main axes – GABA, collagen, mitochondria, DNA – does it become obvious that this is one "condition".
 

In clinical practice the goal is not to promise miracles, but to be honest and careful. FQAD patients need to avoid drugs that further block GABA or overload mitochondria, change psychoactive medications, if at all, only in micro-steps, support mitochondria, protect collagen, work on autonomic regulation and receive psychological support that does not deny the biology but helps them survive it. 

 ➦ The key is to move away from “this is just anxiety” towards understanding that FQAD is a complex damage syndrome in which low GABA and a “withdrawal without benzos” picture are only the visible tip of a very deep iceberg.

Disclaimer
This article is for informational and educational purposes only. It is not medical advice and does not provide a treatment protocol. Any decisions about medications (including benzodiazepines, anti-seizure drugs, antidepressants, sleep medication and “mitochondrial” supplements) must be made together with a qualified physician who knows your medical history. Abruptly stopping GABA-acting drugs can be dangerous and should never be done without medical supervision.
 

REFERENCES
[1] Kawakami J. et al. Inhibitory effect of new quinolones on GABA(A) receptor–channel complex in rat dorsal root ganglion neurons. Eur J Pharmacol.
[2] Green M.A., Halliwell R.F. Selective antagonism of the GABA(A) receptor by ciprofloxacin and biphenylacetic acid in the rat isolated vagus nerve. Br J Pharmacol.
[3] Halliwell R.F. et al. Effects of quinolones and NSAIDs upon GABA-evoked currents in the rat central nervous system. J Antimicrob Chemother.
[4] Schmuck G. et al. Determination of the excitatory potencies of fluoroquinolones in an in vitro guinea-pig CNS model. Antimicrob Agents Chemother.
[5] Wanleenuwat P. et al. Antibiotic-induced epileptic seizures: mechanisms of action and clinical considerations. Seizure.
[6] Bhattacharya P., Mukherjee S., Mandal S.M. Fluoroquinolone antibiotics show genotoxic effect through DNA-binding and oxidative damage. Spectrochim Acta A Mol Biomol Spectrosc.
[7] Rusu A. et al. Overview of side-effects of antibacterial fluoroquinolones: neurotoxicity, tendon damage and beyond.
[8] Freeman M.Z. Fluoroquinolones-Associated Disability: It Is Not All in Your Head. Biomedicines.
[9] Fluyau D. et al. Challenges of the pharmacological management of benzodiazepine dependence and withdrawal. Neuropsychiatr Dis Treat.
[10] Noyes R. Jr. Benzodiazepine withdrawal: a review of the evidence. Addiction.
[11] Finlayson A.J.R. et al. Experiences with benzodiazepine use, tapering, and discontinuation: An internet survey. Ther Adv Psychopharmacol.
[12] Vinkers C.H., Olivier B. Mechanisms underlying tolerance after long-term benzodiazepine use. Adv Pharmacol Sci.
[13] Donepudi M. Benzodiazepine Withdrawal Syndrome: Presentations and Emergency Department Management. emDocs.
[14] Huff C. et al. Enduring neurological sequelae of benzodiazepine use. Lancet Psychiatry.
[15] Barragán A. et al. GABAergic signalling in the immune system. Acta Physiol.
[16] Jin Z. et al. GABA is an effective immunomodulatory molecule. Amino Acids.
[17] Bhat R. et al. Inhibitory role for GABA in autoimmune inflammation. Proc Natl Acad Sci USA.
[18] Bhandage A.K. et al. GABAergic signalling by cells of the immune system. Cell Mol Life Sci.
[19] Sánchez-Manso J.C. et al. Autonomic Dysfunction. StatPearls Publishing.
[20] Cleveland Clinic. Dysautonomia: What It Is, Symptoms, Types & Treatment.
[21] Liu L. et al. Visceral and somatic hypersensitivity, autonomic cardiovascular dysfunction and low-grade inflammation in a subset of IBS patients. J Zhejiang Univ Sci B.https://img1.wsimg.com/.../Adverse%20Effects%20Evaluation...
[22] Mayer E.A. The Gut–Brain Axis. Annu Rev Med.
[23] Shaikh S.D. et al. Irritable Bowel Syndrome and the Gut Microbiome. J Clin Med.
[24] Konturek P.C. et al. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol.
[25] Miller B., Fluoroquinolone Toxicity Study Foundation. Fluoroquinolone Toxicity and Potential Mitochondrial Impairment – Medical Evaluation Preparation Form.
[26] Salimiaghdam N. et al. Effects of fluoroquinolones and tetracyclines on mitochondria of human retinal MIO-M1 cells. Exp Eye Res.
[27] Fief C.A. et al. Impact of antimicrobial fluoroquinolones on human DNA, mitochondrial function and oxidative stress. ACS Omega.
[28] Jiang T. et al. Mitochondrial dysfunction is underlying fluoroquinolone toxicity: an integrated mitochondrial toxicity assessment. Mol Cell Toxicol.
[29] Reinhardt T. et al. Chemical Proteomics Reveals Human Off-Targets of Fluoroquinolone-Induced Mitochondrial Toxicity. Angew Chem Int Ed.
[30] Sendzik J. et al. Fluoroquinolones cause changes in extracellular matrix, signalling proteins, metalloproteinases and caspase-3 in cultured human tendon cells. Toxicology.
[31] Daneman N., Lu H., Redelmeier D.A. Fluoroquinolones and collagen-associated severe adverse events: a longitudinal cohort study. BMJ Open.
[32] Lewis T. et al. Fluoroquinolones and tendinopathy: a guide for athletes and sports clinicians. Clin J Sport Med.
[33] Huruba M. et al. A VigiBase descriptive study of fluoroquinolone-induced serious tendon disorders. Sci Rep.
[34] Romanowska M.J. et al. Fluoroquinolone-Induced Achilles Tendon Damage. Int J Mol Sci.
[35] Bhattacharya P. et al. Fluoroquinolone antibiotics show genotoxic effect through DNA-binding and oxidative damage. Spectrochim Acta A Mol Biomol Spectrosc.

[36] Riesbeck K. et al. Ciprofloxacin and the mammalian DNA damage response (immunomodulatory and genotoxic stress data). Antimicrob Agents Chemother. 

[37] Rusu A., Iordache F., Gurban C. et al. Overview of Side-Effects of Antibacterial Fluoroquinolones: New Issues of Concern. Medicines / Pharmaceutics.

In a groundbreaking study published in Angewandte Chemie International Edition in February 2025, researchers revealed alarming new insights into the hidden dangers of fluoroquinolone (FQ) antibiotics  - a widely prescribed drug class that includes ciprofloxacin and levofloxacin.  Using cutting-edge chemical proteomics, the study titled Chemical Proteomics Reveals Human Off‐Targets of Fluoroquinolone Induced Mitochondrial Toxicity has mapped for the first time how these drugs directly disrupt human mitochondrial function, shedding light on a mystery that has plagued countless patients suffering from Fluoroquinolone-Associated Disability (FQAD).

The Mechanism: How Fluoroquinolones Attack Our Cells
Researchers found that fluoroquinolones  🡇

1. Disrupt the Electron Transport Chain (ETC):  FQs inhibit key mitochondrial complexes —>> Complex I and Complex IV. This causes cellular energy production to collapse and triggers overwhelming oxidative stress inside cells.
2.  Directly Bind Critical Mitochondrial Proteins:  Using photo-affinity profiling, they discovered FQs binding to
>AIFM1 (Apoptosis-Inducing Factor 1), crucial for mitochondrial protein import and electron transport chain assembly.
>IDH2 (Isocitrate Dehydrogenase 2), responsible for maintaining antioxidant balance inside mitochondria. Their disruption leads to mitochondrial destabilization, oxidative injury, and impaired survival of affected cells.
3.  Inhibit NUDT1 Enzyme: FQs also block NUDT1, an enzyme responsible for cleaning up oxidatively damaged nucleotides. Inhibiting NUDT1 allows damaged DNA to accumulate, promoting mutagenesis and chronic cellular stress.

Additional Discovery: Fluoroquinolone Accumulation Over Time
The study highlights that mitochondrial toxicity does not occur immediately after fluoroquinolone exposure.  Instead, mitochondrial dysfunction develops over a longer time with prolonged drug treatment and potential accumulation within cells.  Specifically, the researchers wrote: “FQs do not exhibit acute cell toxicity and primarily a different mode of action must be responsible for the observed mitochondrial toxicity, which rather develops over a longer time of drug treatment and potentially accumulation."

This delayed toxicity model may explain why many FQAD patients:

 🔸  Feel relatively normal initially but progressively worsen,
🔸 Experience persistent symptoms long after stopping the antibiotic,

 🔸 Show signs of long-term mitochondrial dysfunction, despite no ongoing antibiotic exposure.

Global Impact: Why This Matters
These discoveries could finally explain why so many patients develop severe fatigue, neuropathies, musculoskeletal damage, and cognitive impairments after taking fluoroquinolones  - symptoms that have often been ignored or misdiagnosed.

The study provides a molecular fingerprint of the destruction:

➤ Cellular energy collapse  

➤  Oxidative stress buildup  

➤  DNA instability, and opens new pathways to finally diagnose and treat FQAD sufferers, a medical community long waiting for answers.

Can this finding lead to a treatment for FQAD?
Absolutely, and it offers real hope.  Now that specific molecular targets (like AIFM1, IDH2, and NUDT1) have been identified, researchers can begin:
• Designing therapies to protect or repair damaged mitochondria,
• Developing specialized antioxidants or redox-restoring treatments,
• Exploring gene therapies or small molecules that can reactivate damaged pathways.
Moreover, targeted therapies might stop or slow disease progression in patients suffering from FQAD today.

Fluoroquinolone Resistance in Bacteria: A Growing Public Health Concern

Beyond human mitochondrial toxicity, fluoroquinolones are increasingly linked to the rise of antibiotic-resistant bacteria. Bacteria can develop resistance to fluoroquinolones through several mechanisms: 

🟡 Mutations in Target Enzymes: Changes in DNA gyrase and topoisomerase IV reduce drug binding, diminishing efficacy.

 
🟡 Efflux Pumps: Overexpression of efflux pumps expels the antibiotic from bacterial cells, lowering intracellular concentrations.

 🟡 Plasmid-Mediated Resistance: Genes such as qnr can be transferred between bacteria via plasmids, spreading resistance traits rapidly.

 
Notably, resistance can develop swiftly, sometimes even during a single course of treatment. The widespread use of fluoroquinolones in both human medicine and agriculture has exacerbated this issue, leading to the proliferation of multidrug-resistant bacterial strains. This growing resistance not only compromises the effectiveness of fluoroquinolones but also poses a significant challenge to public health, as infections become harder to treat and control.

Could fluoroquinolone damage cause mutations passed to future generations?
This is a potential major concern.  By damaging mitochondrial DNA and interfering with DNA repair pathways, fluoroquinolone exposure might: 

➤  Cause mutations not just in somatic (body) cells but also in germ cells (sperm and eggs),
 ➤ Lead to transmission of mitochondrial dysfunction or genetic defects to offspring,
➤ Increase risks of inherited diseases in future generations.

Additionally, fluoroquinolones are well known to induce bacterial hypermutation, speeding up antibiotic resistance.This dual threat - genetic damage in humans and rising superbugs in the environment - poses a serious long-term public health risk.

Conclusion: A Wake-Up Call to the World
This study is not just an academic breakthrough, it’s a global health warning.  It exposes the hidden costs of widespread fluoroquinolone use and demands immediate action:

 ✴️ Tighter antibiotic prescribing guidelines,
✴️ Long-term patient monitoring,
✴️ New therapies to protect and regenerate mitochondrial health.  

And for the millions already suffering from FQAD, this breakthrough offers the first real hope that help may finally be on the horizon.
 

Disclaimer

_________________________________

Reference:  

Chemical Proteomics Reveals Human Off-Targets of Fluoroquinolone Induced Mitochondrial Toxicity.
https://doi.org/10.1002/anie.202421424 

Downloadable version here: 

https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.202421424?fbclid=IwY2xjawKTlr1leHRuA2FlbQIxMABicmlkETFSU0ZFZmV3aEV5T2NnNVFoAR7WeFWXtx_q3qiD1FfirPps7zMAEMGEa0H5UfuHpkRPFCFvJfzJSutYiNa6oA_aem_aOCtxb0iCTipP3I30Sb6yg 

It's totally understandable that people with FQAD (Fluoroquinolone Associated Disability) are hesitant about taking more medications, especially when it comes to anesthesia. Research has shown that fluoroquinolone antibiotics can interfere with mitochondrial function, which is very concerning since mitochondria are the powerhouse of your cells and play a huge role in overall systemic health.

Most anesthesia guidelines for mitochondrial safety are specified for primary mitochondrial disease (PMD) - a genetic condition, though they might be helpful for those dealing with FQAD.  The three types of anesthesia are general, local and regional, and due to the amount of information, the following information is geared just toward major surgeries requiring general anesthesia.

What to Know:

For individuals with mitochondrial issues, anesthesia isn’t always straightforward, and here’s why:

 ➡️  Heightened drug sensitivity may prolong sedation or muscle weakness because the body struggles to metabolize anesthetic drugs efficiently. 

 ➡️  Anesthesia can push an already struggling energy system into overdrive, sometimes leading to the inability to clear lactic acid properly, which can be made worse by supporting medication used during surgery. 

 ➡️  Certain muscle relaxants sometimes used, such as succinylcholine, may cause extended paralysis in patients with compromised mitochondrial function, making post-surgical recovery more challenging. 

 ➡️   Some anesthetics and perioperative factors can increase oxidative stress and neuroinflammation, which may contribute to temporary cognitive or neurological symptoms in susceptible people. In FQAD, direct evidence is limited, but it may be reasonable to take  precautions to reduce physiologic stress during anesthesia and recovery. 

When it comes to mitochondrial issues, some anesthesia agents are generally considered more favorable than others, though opinions vary within the scientific and medical community. The choice of anesthesia depends on several factors, including the patient's specific condition, the type and length of surgery, and which drugs will be used to induce and maintain anesthesia. Total intravenous anesthesia (TIVA) is often preferred over inhaled anesthetics. 

Propofol, while commonly used in surgeries, should be approached with caution due to its multiple effects on mitochondrial function - it's recommended for induction rather than continuous infusion because of this. Patients with mitochondrial dysfunction are likely at higher risk to develop propofol infusion syndrome. 

Ketamine is another intravenous option, often combined with dexmedetomidine, a drug which provides sedation with minimal respiratory depression and has a more favorable profile for those with mitochondrial dysfunction. This combination allows for lower doses of ketamine, thus reducing potential risks. Anesthesiologists may also tailor their approach by mixing different agents to balance effectiveness and safety. 

 ⚠️ Avoiding Issues:

To mitigate possible issues, there’s some things you can do before surgery such as: 

- Select a reputable University or hospital where you can choose your anesthesiologist as opposed to those that are subcontracted and show just before surgery;

- It is vital you have a conversation with the anesthesiologist well in advance of the surgery date; 

- Schedule your surgery for the first morning slot to minimize fasting time and reduce stress on your body and energy levels for a better outcome. 

Conclusion:

Unfortunately, direct human data is lacking when it comes to anesthesia and mitochondrial response and remains variable to interpretation and debate.  It is important to remember that the absence of published reports of adverse effects with an agent does not mean that the agent is safe, it more likely reflects a possible publication bias. To protect your health, always research in advance and ask detailed questions about all medications, IVs being used, as well as potential side effects based on your medical history. Finally, ensure you have proper notation in your medical file about possible mitochondrial damage due to fluoroquinolones in case you must have emergency surgery at some point. 

See this as video: https://www.youtube.com/watch?v=2O-8mu8pgB8&t=27s

Disclaimer

_________________________________

Note: 

Anesthesia types - General, Regional, Local

Common inhaled anesthetics - Sevoflurane, Isoflurane, Desflurane 

Common intravenous (IV) anesthetics – Propofol, Ketamine, Etomidate

References:  

Fluoroquinolone-induced serious, persistent, multisymptom adverse effects

https://pmc.ncbi.nlm.nih.gov/articles/PMC4600819/

Propofol Is Mitochondrion-Toxic and May Unmask a Mitochondrial Disorder

https://pubmed.ncbi.nlm.nih.gov/27488955/

Mitochondrial Disease and Anesthesia

https://med.stanford.edu/content/dam/sm/pedsanesthesia/documents/mitochondrial-disease.pdf

Propofol Infusion Syndrome in Adults: A Clinical Review.

https://pmc.ncbi.nlm.nih.gov/articles/PMC9671386/

Anesthetic Considerations in Patients with Mitochondrial Defects

https://pmc.ncbi.nlm.nih.gov/articles/PMC3711963/

General anesthetics cause mitochondrial dysfunction and reduction of intracellular ATP levels

https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0190213

Anesthetic hypersensitivity in a case-controlled series of patients with mitochondrial disease

https://pmc.ncbi.nlm.nih.gov/articles/PMC8280249/

Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society

https://www.nature.com/articles/gim2017107?mibextid=Zxz2cZ

Contrast dyes, like those with gadolinium or iodine, help improve MRI and CT scans, but they might pose issues for people experiencing adverse effects from fluoroquinolones (FQ’s). These antibiotics have been linked to mitochondrial issues, which can cause oxidative stress and sometimes impaired kidney function, the organ responsible for excretion of substances.  The following are just two of many contrast agents.

Gadolinium-based contrast agents (GBCAs):

Recent studies show Gadolinium can possibly accumulate not only in the kidneys but also in other organs, even in people with normal kidney function, more typically after repeated exposures. Health issues can also increase with higher contrast concentrations and with particular brands of contrast agents. The amount of contrast used in an MRI depends on the specific imaging needs and the area being examined, so this is useful to find out in advance.  There are two types of gadolinium-based contrast agents based on their chemical structures - linear and macrocyclic, with the linear contrast agent resulting in more retention within the body for a longer duration [see brands in Table 1 FDA reference].  In review of the research, it appears that any consequences of residual GBCAs (deemed to be variable) have not been greatly investigated.

Iodine Based Contrast:

This contrast is used for X-rays and CT scanning, methods cautioned in Part 1 of this series.  Considered relatively low harm, though still with a chance of severe adverse effects in some, patients with pre-existing cardiovascular, respiratory issues or damage to their blood brain barrier should be aware. Unfortunately, lack of contemporary studies and ongoing research aiming to clarify the true risks, to include those of kidney and thyroid issues, remain unclear. Reactions can be dependent on contrast volume as well as the route of administration.

Non-Contrast Imaging Alternatives:

✳️ MRI without contrast & Ultrasound

✳️ CT Scans without Contrast (see Part 1 in this series for warnings) 

 ✳️ Functional MRI (fMRI): This specialized type of MRI detects changes in blood flow and brain activity

 ✳️ Non-Contrast MRA: This is an advanced technique to image blood vessels

Alternative Contrast Agents:

• Vegetable-based dyes are sometimes used in gastrointestinal and eye imaging 

• Microbubble Ultrasound Contrast

• Iron-based MRI Contrast Agents: use iron oxide nanoparticles 

Note: An overload of iron ions can  trigger Fenton reaction resulting in possible oxidative damage and cellular stress but reportedly not at the imaging level if slow infusion and post-dose vitals/observation are monitored; research is ongoing and should be discussed with your doctor prior.

If Contrast is Necessary: If an MRI with gadolinium is necessary, you may consider discussing with a functional medicine doctor or nephrologist: 

 🡆 A preliminary kidney function test and kidney monitoring 

 🡆 Exploring macrocyclic type contrast agents and their potential side effect differences

 🡆 Precautions to be taken before and after imaging 

As with any drug or medical procedure, arm yourself with knowledge by reading the references under “Reviews” which will provide more overall detail.

See this as video: https://www.youtube.com/watch?v=xgzS0uJwpzU&t=61s

Disclaimer

_________________________________

References:

See Contrast Brands’ Chart:

https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-gadolinium-based-contrast-agents-gbcas-are-retained-body

Reviews:

Toxicity Mechanisms of Gadolinium and Gadolinium-Based Contrast Agents—A Review

https://pmc.ncbi.nlm.nih.gov/articles/PMC11012457/

Pathophysiology of Contrast-Induced Neurotoxicity: A Narrative Review of Possible Mechanisms

https://karger.com/ene/article/87/1/26/879615/Pathophysiology-of-Contrast-Induced-Neurotoxicity

Mitochondrial dysfunction is underlying fluoroquinolone toxicity: an integrated mitochondrial toxicity assessment

https://link.springer.com/article/10.1007/s13273-022-00263-9

Contrast-induced nephropathy and oxidative stress: mechanistic insights for better interventional approaches

https://translational-medicine.biomedcentral.com/.../s129...

Gadolinium-free contrast agents for magnetic resonance imaging of the central nervous system https://pubmed.ncbi.nlm.nih.gov/29431424/

Iron oxide nanoparticles induce ferroptosis under mild oxidative stress in vitro

https://www.nature.com/articles/s41598-024-82917-3?utm_source=chatgpt.com

Side Effects of Radiographic Contrast Media: Pathogenesis, Risk Factors, and Prevention

https://onlinelibrary.wiley.com/doi/10.1155/2014/741018

Microbubble contrast agents: a new era in ultrasound

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1120332/

Non-contrast MRA provides safe diagnostic alternative for patients with kidney disease

https://medicalxpress.com/.../2016-09-non-contrast-mra...

Medical imaging -  CAT (CT) scans, MRIs, and X-rays, play a crucial role in modern diagnostics. But for individuals suffering from Fluoroquinolone-Associated Disability (FQAD), particularly those with mitochondrial dysfunction, these seemingly routine procedures may pose hidden risks. It’s time to shed light on how medical imaging can exacerbate symptoms in people already grappling with fluoroquinolone-induced toxicity.

Understanding the Risks - 

Fluoroquinolone antibiotics, such as ciprofloxacin (Cipro) and levofloxacin, are known to cause mitochondrial damage, compromising the cell’s energy production and making them more vulnerable to external stressors. When an individual with FQAD undergoes medical imaging, especially those involving ionizing radiation, their already fragile mitochondria can suffer further harm.

Ionizing Radiation and Mitochondrial Vulnerability - 

 💠 1. Generation of Reactive Oxygen Species (ROS):

Ionizing radiation from CT scans, X-rays, and nuclear medicine imaging (PET and SPECT) generate ROS—unstable molecules that cause oxidative stress. In healthy cells, mitochondria can often handle this stress, but in FQAD patients, the already-damaged mitochondria are overwhelmed, leading to increased cell damage and dysfunction (Smith et al., 2017).

 💠 2. Mitochondrial DNA (mtDNA) Damage:

Unlike nuclear DNA, mtDNA lacks protective histone proteins and efficient repair mechanisms, making it particularly vulnerable to radiation-induced damage. Studies have shown that mtDNA mutations accumulate more readily in cells exposed to ionizing radiation (Wallace, 2013), which may further impair energy production and trigger apoptosis - programmed cell death.

 💠 3. Cumulative Effects of Radiation:

The damage isn’t just immediate - it builds over time. For example, a simple CT scan of the sinuses exposes the body to about 0.371 millisieverts (mSv) of radiation, nearly four times more than a standard X-ray (Radiological Society of North America, 2020). Multiple scans over time can cumulatively exacerbate oxidative stress and mitochondrial dysfunction.

 Implications for FQAD Patients❗ 

For those with FQAD and related conditions like MCAS, the effects of medical imaging can manifest as worsening fatigue, neuropathy, muscle weakness, and even cardiac complications. Given the delicate state of their mitochondria, even low doses of radiation can tip the balance, leading to a cascade of symptoms that may take weeks or months to resolve.

What Can Patients Do?

While medical imaging is often essential, there are steps FQAD patients can take to reduce risk:

1. Minimize Unnecessary Scans:

Always discuss with healthcare providers whether imaging is absolutely necessary and explore alternative diagnostic methods or low-dosage CT.

2. Opt for Non-Ionizing Imaging:

MRI (magnetic energy and radio waves)  and ultrasound (sound waves) do not use ionizing radiation and are generally safer for those with mitochondrial vulnerabilities (World Health Organization, 2018).

3. Space Out Imaging Procedures:

Allow time between scans to enable the body to recover from any oxidative stress induced by radiation.

4. Use Antioxidant Support:

While more research is needed, some studies suggest that antioxidant supplementation may help mitigate radiation-induced oxidative damage (Ghosh et al., 2014).

5. Refer to the dosage comparison charts for specific body areas in below reference list  ⬇️ 

or ask your doctor.    

Conclusion:

Tissues with high energy demands, such as the brain, heart, liver and muscles, can be more vulnerable to mitochondrial damage from radiation, which can potentially worsen symptoms like fatigue, neuropathy, or cardiac dysfunction. Imaging outcomes may vary between individuals depending on factors such as:

 ✅  what body part is being imaged (duration/dosage of treatment varies with body area)

 ✅  your size, age, weight, and the sensitivity of the tissue being targeted

 ✅  type of machine used

&

 ✅  possibly the extent of FQ toxicity, stage of FQ toxicity, prior health conditions

See this as vdeo: https://www.youtube.com/watch?v=pIQa7GKVpKk&t=7s

See Disclaimer

________________________________

References:

Radiation Dosage Charts - Multiple Areas of the Body:

FW Radiology

https://fwradiology.com/radiation-dose/

NeuroLogica

https://www.neurologica.com/blog/ct-scan-radiation-dose

• Ghosh, S., Das, N., & Chattopadhyay, D. (2014). Radiation-induced oxidative stress: A review. Journal of Clinical Biochemistry and Nutrition, 55(1), 1–7.

• Radiological Society of North America. (2020). Radiation dose in X-ray and CT exams. Retrieved from RSNA.org

• Smith, R. A., Murphy, M. P., & Dragunow, M. (2017). Mitochondrial dysfunction and reactive oxygen species in aging and disease. Free Radical Biology and Medicine, 112, 9–17.

• Wallace, D. C. (2013). Mitochondrial DNA mutations in disease and aging. Environmental and Molecular Mutagenesis, 54(7), 533–545.

• World Health Organization. (2018). Ionizing radiation, health effects and protective measures. Retrieved from WHO.int

· McLaughlin, P. D., Chawke, L., Twomey, M., Murphy, K. P., O'Neill, S. B., McWilliams, S. R., et al. (2018). Body composition determinants of radiation dose during abdominopelvic CT. Insights into Imaging, 9(1), 9–16. 

· Effective dose (radiation). (n.d.). In Wikipedia. Retrieved from https://en.wikipedia.org/wiki/Effective_dose_(radiation)

Fluoroquinolone antibiotics are often overlooked in discussions about surgeries and their associated possible risks. However, patients experiencing serious adverse long-term effects from these antibiotics should be informed and encouraged to discuss concerns with their doctors or dentists beforehand. 

In surgeries, fluoroquinolones can be present in or associated with the following:

Antibiotic-Impregnated Sutures: Some surgical sutures may be coated with fluoroquinolones to prevent infection at the surgical site.

Topical Antibiotic Solutions: These are used during surgery to irrigate wounds or surgical sites and can sometimes contain fluoroquinolones.

Antibiotic-Impregnated Sponges or Meshes: Used in surgical wounds or implant sites to reduce infection risk, these may be impregnated with fluoroquinolones.

Implants and Prosthetics: Metal implants, screws, or prosthetics may be coated with antibiotics, including fluoroquinolones, to prevent post-surgical infections.

Post-Surgical Wound Dressings: Some dressings used after surgery are treated with antibiotics like fluoroquinolones to help prevent infections.

Be prepared and speak up!   
Before surgery, ask and maybe get in writing, exactly what’s going in, on, or around your body.  We can't always rely what is specified on our allergy list, medical bracelet or medical chart.  If there’s a safer alternative to fluoroquinolones, make sure you know it.  

PLEASE NOTE: Fluoroquinolones may also be given as a prophylactic during surgery in IV form

See Disclaimer

________________________________

References:

In Vitro Antibacterial Efficacy of Sutures Coated With Aloe vera and Ciprofloxacin: A Comparative Evaluation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555338/...

​Temperature-sensitive liposomal ciprofloxacin for the treatment of biofilm on infected metal implants using alternating magnetic fields. https://europepmc.org/article/PMC/6034688...

Ciprofloxacin-Collagen-Based Materials with Potential Oral Surgical Applications

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563124/...

The FDA has specifically provided warnings that these medications cause peripheral neuropathy.  Multiple systemic adverse effects may stem from nervous system dysfunction, and the following is just a simplified outline that aims to provide some insight into what you might be experiencing:

Peripheral Nervous System (PNS)

The PNS consists of all the nerves outside the brain and spinal cord. It has two main components: the somatic nervous system and the autonomic nervous system.

1. Somatic Nervous System:

 💠 Voluntary Control:  Controls voluntary movements by innervating skeletal muscles. For example, moving your arms or legs.

 💠 Sensory Input: Transmits sensory information from the body to the central nervous system (CNS), such as touch, pain, temperature, and proprioception (sense of body position).

2.  Autonomic Nervous System (ANS): 

The ANS controls involuntary body functions and is further divided into three branches: the sympathetic, parasympathetic, and enteric nervous systems:

 a. Sympathetic Nervous System:

"Fight or Flight" Response: Prepares the body for stressful or emergency situations. This includes increasing heart rate, dilating pupils, dilating airways, and inhibiting digestion.

Energy Mobilization: Mobilizes energy stores to provide quick energy.

b. Parasympathetic Nervous System:

"Rest and Digest" Response: Promotes relaxation and recovery. It slows the heart rate, constricts pupils, stimulates digestion, and conserves energy.

Homeostasis: Maintains regular bodily functions and conserves energy.

c. Enteric Nervous System:

Gastrointestinal Control: Regulates the functions of the gastrointestinal tract, including peristalsis (movement of food), secretion of digestive enzymes, and blood flow to the gut.

Autonomous Functioning: Often referred to as the "second brain," it can operate independently of the CNS but also communicates with it.

Functions Controlled by PNS and ANS

 💠 PNS:

• Voluntary movements (walking, typing, etc.)
• Sensory perception (touch, temperature, pain)
• Reflexes (knee-jerk reaction)

 💠 ANS:

• Heart rate and blood pressure regulation
• Respiratory rate and airway constriction/dilation
• Digestion 
• Gastrointestinal motility
• Pupillary response and eye accommodation
• Sweating and thermo-regulation
• Urination and sexual function

The PNS and ANS work together to ensure that the body can respond to both voluntary actions and involuntary needs, maintaining overall balance and homeostasis.

 Fluoroquinolones have been shown in studies to cause mitochondrial dysfunction, impacting the energy production essential for cellular function.  Given the high energy demands of neurons within the ANS, mitochondrial dysfunction can have several effects detailed below:

 🡆  Cardiovascular Issues: Mitochondrial dysfunction can possibly impair the autonomic regulation of heart rate and blood pressure, potentially leading to conditions like orthostatic hypotension (a drop in blood pressure upon standing) and arrhythmias.

 🡆  Gastrointestinal Problems: The ANS controls various functions of the digestive system, including motility, secretion, and blood flow. Mitochondrial dysfunction can lead to gastrointestinal issues such as gastroparesis (delayed stomach emptying) and constipation.

 🡆 Respiratory Difficulties: The autonomic regulation of breathing can be affected, potentially causing issues like sleep apnea or other respiratory irregularities.

 🡆 Thermoregulation: The ANS helps maintain body temperature. Mitochondrial dysfunction can impair this regulation, leading to problems with maintaining an appropriate body temperature.

 🡆 Sweating Abnormalities: Mitochondrial dysfunction can possibly affect sweat gland function, leading to excessive sweating (hyperhidrosis) or reduced sweating (anhidrosis), which can impact thermoregulation and skin health.

Overall, the proper functioning of the nervous system is crucial for maintaining homeostasis in the body, and mitochondrial dysfunction can significantly disrupt these vital processes. 

 ✅  For more information about nerve damage in those affected by fluoroquinolones, please view Part 2 of our series with Dr. Stefan Pieper, who treats “floxed” patients in his practice in Germany: https://www.youtube.com/watch?v=slxWylnNzQ8

 ⚫  List of drugs in the fluoroquinolone class

 ⚫ 2013 FDA Warnings: Due to concerns about nerve damage, the U.S. Food and Drug Administration (FDA) issued a Black Box warning about fluoroquinolones and the risk of peripheral neuropathy. 

See Disclaimer

_________________________________

References: 

Autonomic Nervous System

https://my.clevelandclinic.org/health/body/23273-autonomic-nervous-system

Peripheral Neuropathy Associated with Fluoroquinolones

https://www.academia.edu/11210092/Peripheral_neuropathy_associated_with_fluoroquinolones

Fluoroquinolone-induced serious, persistent, multisymptom adverse effects

https://escholarship.org/uc/item/44d5r44g

Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2

https://pdfs.semanticscholar.org/6d82/ae7622517a5731eab55ff3fa63ad73085078.pdf

The exact mechanism by which fluoroquinolone antibiotics can cause inner ear damage is not fully understood and has only been analyzed in animal research, but there are several mechanisms that could possibly result in such issues:

➡️Disruption of Mitochondrial Function: Fluoroquinolones have been shown to interfere with mitochondrial function in cells. Mitochondria are the energy-producing structures within cells, and their dysfunction can lead to cell death. The delicate hair cells of the inner ear, responsible for transmitting sound signals to the brain, are particularly vulnerable to mitochondrial damage.

➡️Formation of Reactive Oxygen Species (ROS): Fluoroquinolones can increase the production of reactive oxygen species (ROS) within cells. ROS are highly reactive molecules that can cause oxidative stress, inflammation and damage cellular structures, including those in the inner ear (choclea). 

➡️Inhibition of Ion Channels: Fluoroquinolones may interfere with ion channels in the cochlea, disrupting the normal flow of ions required for proper hearing function.

➡️Tendon and Connective Tissue Effects: These antibiotics are known for their potential to damage connective tissues, including tendons. Similar effects might extend to the delicate structures in the ear, such as the ossicles(small bones in the middle ear) and tympanic membrane (eardrum).

➡️Neuropathy:  Fluoroquinolones can cause peripheral neuropathy, which involves damage to nerves. If the auditory nerve (cranial nerve VIII) or vestibular nerve is affected, it can lead to symptoms like: Hearing changes or loss, Dizziness, Balance problems

➡️Tinnitus:

Tinnitus is a frequently discussed concern within the FQ-affected community. You can explore more about others' experiences and insights in the support group linked below. Per the Mayo Clinic, here are some other conditions that can cause tinnitus:

• Meniere's disease. Tinnitus can be an early indicator of Meniere's disease, an  inner ear disorder that may be caused by abnormal inner ear fluid pressure.
• Eustachian tube dysfunction. In this condition, the tube in your ear connecting the middle ear to your upper throat remains expanded all the time, which can make your ear feel full.
• Earbone changes. Stiffening of the bones in your middle ear      (otosclerosis) may affect your hearing and cause tinnitus. This condition, caused by abnormal bone growth, tends to run in families.
• Muscle spasms in the inner ear. Muscles in the inner ear can tense up (spasm), which can result in tinnitus, hearing loss and a feeling of fullness in the ear. This sometimes happens for no explainable reason, but can also be caused by neurologic diseases, including multiple sclerosis.
• Temporomandibular joint (TMJ) disorders. Problems with the TMJ, the joint on each side of your head in front of your ears, where your lower jawbone meets your skull, can cause tinnitus.
• Blood vessel disorders. Conditions that affect your blood vessels — such as atherosclerosis, high blood pressure, or kinked or malformed blood vessels  — can cause blood to move through your veins and arteries with more force.  These blood flow changes can cause tinnitus or make tinnitus more      noticeable.
• Other  chronic conditions. Conditions including diabetes, thyroid problems, migraines, anemia, and autoimmune disorders such as rheumatoid arthritis and lupus have all been associated with tinnitus.

Please see the excellent Mayo Clinic article link below for much more detail on tinnitus and what to try to mitigate the issue. Not everyone who takes fluoroquinolone antibiotics will experience inner ear issues or damage, and the severity and duration of the ototoxic effects seems to vary among individuals. 

Good to know: NSAIDs, such as aspirin, ibuprofen, and naproxen, can alter blood flow to the cochlea (part of the inner ear critical for hearing). Reduced blood flow may temporarily affect auditory nerve function, leading to tinnitus.

See Disclaimer

_________________________________

References:

Tinnitus (Mayo Clinic)  Nov. 30, 2022 

https://www.mayoclinic.org/diseases-conditions/tinnitus/diagnosis-treatment/drc-20350162

Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: a reasoned and updated guide

https://www.europeanreview.org/wp/wp-content/uploads/956.pdf

Ophthalmotoxicity and ototoxicity of the new quinolone antibacterial agent levofloxacin in Long Evans rats.

https://europepmc.org/article/med/1622440

Ototoxicity of Topical Moxifloxacin in a Chinchilla Animal Model

https://onlinelibrary.wiley.com/.../MLG.0b013e318148b275

Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2. 

https://academic.oup.com/nar/article/46/18/9625/5088042

Types of Medication That Can Cause Tinnitus 

https://www.healthline.com/health/medications-that-cause-tinnitus?utm_source=chatgpt.com

It’s that time of year when some will travel by plane to another destination for the holidays.  Those that had their lives greatly impacted by the adverse effects of this antibiotic class may experience issues that could make them more susceptible to low oxygen levels and physical side effects not to be ignored, particularly during flying. 

FQAD encompasses a range of long-term side effects from fluoroquinolone antibiotics, including damage to mitochondria, which play a crucial role in energy production and oxygen utilization in cells.

Why FQAD Could Affect Oxygen Levels:

1. Mitochondrial Dysfunction:

 🔸 Mitochondria are essential for cellular respiration, the process that generates energy from oxygen. In individuals with FQAD, mitochondrial damage can impair this process, making cells less efficient at using oxygen.
🔸 This may cause a heightened sensitivity to low-oxygen environments, such as during flights, where cabin pressure reduces oxygen availability.

2. Nervous System Effects:

 🔸 Fluoroquinolone toxicity can cause autonomic nervous system dysfunction (dysautonomia), leading to poor regulation of breathing, circulation, and oxygen delivery to tissues.
🔸 Symptoms like shortness of breath, palpitations, or poor oxygenation may become more noticeable during flight.

3. Cardiac and Pulmonary Issues:

 🔸 Some people with FQAD report heart-related symptoms (e.g., arrhythmias) and respiratory issues, which can further compromise oxygen delivery.
🔸 Reduced physical activity due to chronic pain or tendon damage can weaken the respiratory muscles over time, exacerbating oxygenation problems.

4. Inflammatory or Vascular Effects:

 🔸 FQAD is often associated with systemic inflammation and sometimes possible vascular damage, potentially reducing blood flow and oxygen delivery to tissues.

5. Altitude Sensitivity:

 🔸 At cruising altitude, the air pressure inside an aircraft cabin is equivalent to 6,000-8,000 feet above sea level, where oxygen levels are lower. Individuals with compromised oxygen utilization or mitochondrial function may feel the effects more acutely.

Symptoms of Low Oxygen in FQAD Individuals During Flying:

➤ Shortness of breath or difficulty breathing
➤ Fatigue and weakness
➤ Dizziness or lightheadedness
➤ Increased heart rate (tachycardia)
➤ Cognitive difficulties ("brain fog")
➤ Tingling or numbness in extremities

Precautions for FQAD Individuals When Flying  ⬇️

Consult a Doctor: Discuss any experienced air travel problematic symptoms. They might recommend supplemental oxygen during a flight or other options.

Use Supplemental Oxygen: Some airlines allow passengers to bring FAA-approved portable oxygen concentrators or may provide oxygen upon request (@$300?).

Hydration and Movement: Stay hydrated and move around during the flight to promote circulation and oxygenation.

Compression Socks: If circulation is compromised, these can reduce the risk of blood clots and improve blood flow.

Avoid Stressors: Minimize additional stress on the body by avoiding alcohol, caffeine, or other dehydrating substances.

Monitor Symptoms: Carry a pulse oximeter to monitor oxygen saturation levels during the flight, if possible.

If symptoms of low oxygen (e.g., confusion, severe shortness of breath, or chest pain) occur during or after flying, seek immediate medical attention. A personalized approach is needed in treating FQAD patients, with consideration to patient’s unique symptoms, medical history, severity level, and metabolic requirements.

See Disclaimer

_________________________________

References:

   Fluoroquinolones-Associated Disability: It Is Not All in Your Head
https://www.mdpi.com/2673-4087/2/3/17?utm_source=chatgpt.com
   Fluoroquinolone-related neuropsychiatric and mitochondrial toxicity: a collaborative investigation by scientists and members of a social network https://www.mdpi.com/2673-4087/2/3/17
     Medical Advice for Commercial Air Travel https://www.aafp.org/pubs/afp/issues/2021/1000/p403.html...
   

   Evaluation of patients for supplemental oxygen during air travel
https://www.uptodate.com/.../evaluation-of-patients-for...
   Mitochondrial dysfunction is underlying fluoroquinolone toxicity: an update on mechanisms and implications https://link.springer.com/.../10.1007/s13273-022-00263-9...
    How Airplane Travel Affects Your Body https://health.clevelandclinic.org/dehydration-exhaustion...
    Air Travel - Air Travel - Merck Manual Professional Edition
https://www.merckmanuals.com/.../medical.../air-travel...