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Fluoroquinolone toxicity

What are fluoroquinolones (FQs)?

Fluoroquinolones are broad-spectrum antibiotics commonly used for urinary tract infections, gastroenteritis, and pneumonia. Ciprofloxacin, levofloxacin, moxifloxacin, delafloxacins, ofloxacin, and gemifloxacin are examples of fluoroquinolones.


Black box warning

The FDA has added and enhanced the black box warning to fluoroquinolones a couple of times since 2008. Details of the black box warning include:

  • Increased risk of tendinitis, tendon rupture, aortic aneurysm, and dissection.

  • Risk of worsening symptoms for those with myasthenia gravis.

  • Potential irreversible peripheral neuropathy (nerve damage).

  • Potential permanent side effects involving tendons, muscles, joints, nerves, and the central nervous system.


How fluoroquinolones cause severe side effects

Fluoroquinolone toxicity refers to severe side effects from taking FQs, which is also commonly referred to as being “floxed” or having “FQ toxicity.” Fluoroquinolone toxicity is not very common but it can result in a wide range of severe and potentially permanent symptoms. The underlying mechanisms and symptoms include:


Toxicity to musculoskeletal tissues, degradation of collagen, and damage to the cartilage

  • This can cause symptoms like joint pain, joint stiffness, tendonitis, and tendon rupture.

Damage to the nerve cells (neuropathy)

  • Which can result in numbness, tingling, burning, pain, tremors, changes in sensation (e.g. touch, temperature) in the arms and legs, and dizziness.

Downgrade of GABA-A receptors and cause neurotoxicity

  • GABA is responsible for calming and inhibitory effects on our central nervous system. What FQs do is that they bind to GABA receptors but instead of exerting an inhibitory effect, they do the opposite. So they not only compete and prevent the binding of GABA and other molecules like benzodiazepines (medication used to treat anxiety and insomnia) to GABA receptors, but they also induce stimulant effects on the central nervous system. This can result in a series of neuropsychiatric symptoms like anxiety, agitation, insomnia, and seizures.

  • Other possible symptoms include depression, nightmares, paranoia, confusion, hallucinations, suicidal thoughts, convulsions, and psychosis.

Increased oxidative stress and damaged mitochondria

  • FQs can generate oxidative stress which can cause damage to the mitochondria function and result in reduced energy production. Mitochondria are the “power plants” residing in every single cell in our body, they are responsible for the generation of energy in the form of ATP.

  • When there’s mitochondrial dysfunction, symptoms like fatigue, brain fog, and weakness can happen. Also, it can impede the repair of tissues resulting in long-term musculoskeletal and neurological sequelae.

  • FQs, especially ciprofloxacin, and levofloxacin, have been observed to cause a reduction in plasma antioxidants and increased oxidative stress.

Cardiotoxicity

  • FQs can disrupt the heart's normal rhythm and lead to a life-threatening arrhythmia called torsades de pointes.

  • Other symptoms caused by toxicity to the heart include chest pain and palpitations.

Hepatotoxicity and nephrotoxicity

  • FQs can cause damage to the liver and the kidneys, resulting in side effects like increased liver enzymes, jaundices, hepatitis, liver failure, blood in urine, and renal failure.

Blood sugar dysregulation

  • Depending on the fluoroquinolone class, FQs can lead to high or low blood sugar.

  • FQs have been shown to lead to insulin resistance and increase the risk of developing type 2 diabetes mellitus.

Chelate metals like magnesium, calcium, copper, zinc, iron, and manganese

  • FQs are capable of binding to these metals and removing them from the cells.

  • While magnesium, copper, and zinc are necessary cofactors for enzymes taking part in major metabolic pathways, deficiencies of these minerals in cells and tissues can impact multiple systems and functions of the body.

  • For example, the depletion of zinc can impair DNA repair mechanisms and further enhance DNA damage. Depletion of magnesium is associated with FQ-induced arthropathy.

Change in gene expression

  • Gene expressions decide how enzymes work in our body, and enzymes are responsible for biochemical and metabolic pathways running in our body. These pathways support the normal function of our cells, tissues, and organs.

  • Changes in gene expression can contribute to many of the above mechanisms of how FQ causes damage to our body, which include increased inflammation, less fibrocartilage, and poorly organized collagen.


Long-lasting effects of fluoroquinolones

Symptoms from FQ toxicity often last for years because FQs can remain in the cells for a long time. Symptoms can be debilitating for some people as it greatly affects their quality of life. Repairing the damage of FQ can also take a long time because repairing damaged mitochondria, tendons and cartilages can be a slow process. Also, people who have been floxed can feel overwhelmed easily, so modifications in diet and lifestyle, and implementation of protocols might need to be carried out slowly. Additional mental and emotional support is often needed to help them continue with the healing journey.


Ways to support the body to heal from FQ toxicity

Mitochondria repair and antioxidant support

  • Antioxidant support is crucial because FQs can result in long-term elevation of oxidative stress. Our mitochondria are also especially susceptible to oxidative damage. Glutathione, CoQ10, carnitine, vitamin A, vitamin C, and vitamin E are powerful antioxidants and crucial nutrients needed for mitochondria function.

  • Another way of repairing the mitochondria is to reduce oxidative stress. Toxins (heavy metals, environmental hormones, pesticides, herbicides, mycotoxins) and infections (bacterial, viral, fungal, parasitic) can lead to increased oxidative stress and worsen symptoms resulting from FQ toxicity. So it's important to work on reducing the toxin and infection load in the body.

  • Curcumin from turmeric also plays a crucial role because it's capable of helping the mitochondria detox and eliminate toxins.


Tendon and cartilage repair

  • Vitamin C, vitamin K, and amino acids are needed for the repair and regeneration of connective tissues.


Neuropsychiatric support

  • Address neuroinflammation

    • Inflammation of the central nervous system (including the brain) can potentiate neurological and psychological symptoms. It's therefore vital to eliminate and address common triggers of neuroinflammation like chronic infections, leaky gut, estrogen dominance, and excessive consumption of high glutamate and high histamine foods.

  • Support neurotransmitter balance

    • Since the function of GABA receptors has been affected by FQs, it's important to make sure other excitatory neurotransmitters like norepinephrine, epinephrine, dopamine, histamine, and glutamate are not in excess, and there’s a sufficient amount of inhibitory neurotransmitters.

    • Optimal B vitamin, magnesium, vitamin C, zinc, copper, and iron status is also key to keeping these neurotransmitters in balance.


Nutritional support

  • Address nutrient deficiency, especially deficiency of magnesium, zinc, copper, and iron, since these are the targeted metals to be chelated by FQs.

  • Replenishing these minerals and the nutrients mentioned above will also help restore cell and metabolic functions.


Additional support & holistic approach

Besides repairing the mitochondria, tendons, and cartilage; underlying health conditions and dysfunctions will often need to be addressed in order for the mitochondria to resume their normal function and for the body to heal.


Optimize endocrine function

  • Support the adrenal and thyroid glands

    • Optimal adrenal and thyroid function is always crucial in healing any chronic health conditions because when they aren’t functioning properly, the body cannot heal.

    • Our thyroid hormones also directly affect mitochondria function. As we can see how important it is to repair and optimize mitochondria function after FQ toxicity, it is equally important to help support thyroid function.

  • Balance out male and female hormones

    • Imbalanced sex hormones can worsen neuroinflammation and impede the body’s healing mechanism.


Optimize digestive function

  • Ensure proper digestive and absorption of nutrients to ensure optimal nutritional status.

  • Address underlying digestive issues like dysbiosis and leaky gut.

    • These digestive dysfunctions can increase the overall inflammation and oxidative stress, affect the proper absorption of nutrients, and potentially affect our brain health through the gut-brain axis.

  • Also, antibiotics tend to disrupt the gut microbiome so it’s necessary to help restore the flora.


Remove toxins

  • Toxins can affect mitochondria and endocrine function, and it’s often a major trigger for neuroinflammation.

  • Remove exposure to heavy metals, environmental hormones, pesticides, herbicides, mycotoxins, and biotoxins.

  • Support the emunctories (organs of detoxification and elimination of toxins – liver, kidney, bowel, skin, lungs) to help facilitate the detoxification and elimination of toxins


Address underlying infections and biofilms

  • Infections, especially chronic infections, are a major source of inflammation and oxidative stress. Infections often affect our endocrine and mitochondria function, and are capable of disrupting our gut microbiome, causing leaky gut and leaky brain. All these can potentially contribute to the side effects of FQ toxicity.

  • Also, resistance to FQ drugs is on the rise and some people might not have their infections completely cleared after taking FQ. So it’s important to reassess the infections and see if there are any obstacles to clearing up the infections, like biofilms.

  • Biofilms are like walls built up by bacteria and other pathogens to help protect them from the attack of the immune system and antibiotics or antifungals. When there are pathogenic biofilms present inside our body, it’s hard to clear the infections completely and effectively. People with pathogenic biofilms often present with chronic and/or recurrent infections (e.g. sinusitis, bronchitis, gastroenteritis, intestinal bacterial/fungal overgrowth, vaginitis, UTIs). This can be another source of inflammation and oxidative stress and it can be a major obstacle for people to heal from FQ toxicity too.


A healthy, well-balanced diet

  • A whole foods, anti-inflammatory and organic diet can be helpful in optimizing antioxidant status, ensuring adequate intake of B vitamins, magnesium, and amino acids, decreasing inflammation, and minimizing toxin exposures.


Mental emotional support

  • Ensuring there’s a network of support.

  • Flower essence, aromatherapy, homeopathy, diaphragmatic breathing, and meditation, can all be helpful in supporting the person holistically.


The process of healing the body from FQ toxicity can be complex and require a thorough assessment of your body function and factors like toxins, infections, diet, lifestyle, etc. If you suspect yourself of being "floxed," it's important that you seek assessment and care from a professional health provider before taking supplements and making any diet and lifestyle changes.






References

  1. Baggio, Diva, and Michelle R Ananda-Rajah. “Fluoroquinolone antibiotics and adverse events.” Australian prescriber vol. 44,5 (2021): 161-164. doi:10.18773/austprescr.2021.035

  2. Michalak, Krzysztof, et al. "Treatment of the fluoroquinolone-associated disability: the pathobiochemical implications." Oxidative Medicine and Cellular Longevity 2017 (2017).

  3. Freeman, Maya Z., et al. "Fluoroquinolones-Associated Disability: It Is Not All in Your Head." NeuroSci 2.3 (2021): 235-253.



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