Let's talk About Supplementation #9
Peripheral neuropathy remains one of the most perplexing and debilitating manifestations of fluoroquinolone-associated disability (FQAD), yet its underlying mechanisms are still poorly understood. While the link between fluoroquinolone antibiotics and nerve damage is increasingly recognized, the variability in clinical presentation—ranging from burning pain and numbness to profound fatigue and cognitive disruption—has long puzzled both patients and clinicians. Why do some individuals develop severe, persistent neuropathy after a single course of antibiotics, while others recover with minimal intervention?
Recent evidence suggests the answer may lie not in a single pathway, but in a systemic disruption of enzyme networks across multiple organs. Fluoroquinolones are not merely DNA gyrase inhibitors; emerging data reveal their ability to modulate hundreds of enzymatic processes, including those critical to neurotransmitter balance and cholinergic signaling. In animal models, ciprofloxacin has been shown to differentially alter acetylcholinesterase (AChE) activity in the liver, blood, and brain—effects that are time- and tissue-dependent. These findings point to a complex, multiorgan interference with enzyme regulation rather than isolated neurotoxicity.
In the central nervous system, studies on fluoroquinolones report opposing changes in neurotransmitter levels across brain regions: reduced GABA and serotonin in the frontal cortex, elevated excitatory amino acids, and divergent AChE activity in the hippocampus. Such regional imbalances challenge simplistic models of neuropathic pain and suggest a dynamic, context-dependent dysregulation of neural circuits.
This growing body of evidence shifts the conversation from whether fluoroquinolones cause neuropathy to how—and why responses vary so dramatically. Understanding these mechanisms is not just an academic pursuit; it’s a crucial step toward developing targeted, individualized approaches to support recovery.
Peripheral neuropathy in FQAD encompasses a constellation of symptoms—burning pain, tingling, muscle weakness, sensory loss, and cognitive fog—suggesting a deep dysfunction in neural maintenance and signaling. Among the most consistent biological clues emerging from this clinical landscape is a downregulation of nerve growth factor (NGF) expression. As I wrote recently, it is possible that there is a fundamental disruption in the trophic support system that sustains peripheral neurons, particularly those reliant on cholinergic signaling—nicotinic and muscarinic acetylcholine receptors (AChRs)—which are increasingly implicated in both sensory and motor nerve integrity.
What makes this observation especially intriguing is that NGF isn’t just a passive bystander in nerve health. It’s an active architect: it promotes neurite outgrowth, supports the survival of cholinergic neurons in the basal forebrain and peripheral ganglia, modulates synaptic plasticity, and regulates inflammatory cascades within the nervous system. When its expression falters—or when downstream signaling pathways are disrupted—a cascade of functional decline can follow. This has led me to explore whether restoring NGF activity could be beneficial for acquired peripheral neuropathies where trophic support is compromised.
I have already discussed a natural and free therapeutic option in my article on the effects of sunlight, pointing out how UV rays could modulate NGF expression. However, I am fully aware that not everyone tolerates sunlight in the same way. Unfortunately, there are genetic differences, particularly those related to the type of melanin we secrete (eumelanin versus pheomelanin), which do not place us on equal footing and do not grant us the same recovery chances through sunlight exposure. There is therefore a clear need to express NGF differently than through UV radiation for individuals living in the northern hemisphere and possessing a phenotype that renders them vulnerable to sunlight.
After nicotine, whose properties are double-edged, I will therefore discuss today a fungus, in fact the second in a list of supplements that one of my contacts shared with me, which, according to him, significantly improved his symptoms. Not only were his symptoms reduced during the intake of these two fungi (see my article on the first one here), but when he stopped taking them, the symptoms gradually returned. I know that n=1 is not sufficient from a statistical standpoint to establish a correlation, and that this remains anecdotal at this stage (an appropriate term when an observed effect is not statistically significant), however, upon doing some research, I wanted to find out what scientific studies said about this mushroom. And here is what I managed to gather as evidence: