Fluoroquinolone Toxicity and Acetylcholine (ACh) Damage

acetylcholine-pictures

I suspect that fluoroquinolone antibiotics deplete, inhibit, or otherwise affect acetylcholine (ACh). ACh is a neurotransmitter that has the following functions:

  1. It is a neuromodulator of the central nervous system, the autonomic nervous system, and the peripheral nervous system.
    1. In the autonomic nervous system, ACh has key roles in both the sympathetic and parasympathetic nervous systems, and affects motility through the digestive tract, sweating, tear production, balance, heart-rate, breathing, etc.
    2. In the central nervous system, ACh plays a role in regulating arousal, attention, sleep, and motivation.
    3.  In the peripheral nervous system, ACh controls muscle activation (both skeletal muscles and smooth muscles–the muscles that involuntarily contract and release).
  2. It affects vascular tone.
  3. A lack of ACh is linked to Alzheimer’s Disease, Parkinson’s Disease, autism, schizophrenia, bipolar disorder, and other chronic CNS illnesses.
  4. It suppresses inflammation.
  5. It affects the release of hormones.

Fluoroquinolones damage connective tissues (tendons, ligaments, cartilage, fascia, etc.) throughout the body, as well as the nervous systems (central, peripheral, and autonomic). After getting “floxed” people often suffer from autonomic nervous system dysfunction (including dysautonomia, loss of digestive motility, problems sweating, balancing, etc.), central nervous system dysfunction (including psychosis, insomnia, changes in personality, etc.), and peripheral nervous system dysfunction (including peripheral neuropathy). Fluoroquinolone toxicity often resembles autoimmune diseases in its symptoms, and, like many people with autoimmune diseases, inflammation is often rampant in those who are floxed. Many “floxies” have reported hormonal problems, including thyroid hormone abnormalities, as well as undesirable levels of estrogen, progesterone, and testosterone.

There is significant match-up between the list of documented effects of ACh (summaries of ACH effects can be found HERE and HERE) and the documented effects of fluoroquinolones (the warning labels go over most of the symptoms of fluoroquinolone toxicity, but the personal stories on this site, as well as the stories on www.fqwallofpain.com, facebook, and other places on the internet better exemplify the actual effects of these drugs).

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In addition to the obvious links and overlaps noted above, the links between fluoroquinolones/fluoroquinolone toxicity and ACh damage are more thoroughly explored in the post, “Acetylcholine (ACh) – Related Damage” on www.fluoroquinolonethyroid.com. In it, JMR describes the connections between fluoroquinolones (and fluoroquinolone toxicity) and acetylcholine:

“Still, there were many reasons I felt that many of my problems could be ACh related, and here are some of them.  As I’ve already stated, I felt that many of my symptoms and acute flox reaction could be described as “cholinergic/anti-cholinergic” in nature, and/or MG (myasthenia gravis) related.   Drug label warnings specifically state the Fluoroquinolones have neuromuscular blocking activity, so pharma is giving us a big clue here.  ACh modulates a host of physiological processes in the central and peripheral nervous systems.  Centrally, ACh regulates motor function, sensory perception, cognitive processing, arousal, sleep/wake cycles, and nociception, while in the periphery it controls heart rate, gastrointestinal tract motility, and smooth muscle activity.   Non-neuronal ACh and AChE are distributed throughout the body, making ACh transmission and metabolism important for all cells in the body, not simply neurogenic cells.  Additionally, Non-neuronal ACh and AChE are found in tendons, and increased expression of both occurs in pathological tendinosis, and is thought to contribute to tendon pathology. (Forsgren/Danielson lab studying role of non-neuronal ACh in chronic tendinosis and tendon pathology  – search “non-neuronal ACh Tendons”).  In relationship to the thyroid, cholinergic interaction with the thyoid gland is extensive, and common epitopes may exist relating thyroid autoimmunity and ACh/muscarinic receptor autoimmunity.  ACh appears to be necessary for iodine organification (so this might be one underlying mechanism of action to explore for Hashi’s).  MuSK form of MG (myasthenia gravis) may be a separate condition from MG and there is a known association between “MuSK MG” and Graves disease.  Magnesium prevents or controls convulsions by blocking neuromuscular transmission and decreasing the release of acetylcholine at the nicotinic ACh motor nerve terminals (the analgesic properties of Mg are due to NMDA receptor blocking action). In (my) Year 5 post, as my symptoms progressed, it became apparent that Magnesium was actually exacerbating my muscle weakness, presumably by blocking neuromuscular transmission, and magnesium is something that is known to exacerbate MG symptoms (so for any flox victims for whom magnesium makes your symptoms worse, especially muscle weakness, this is something to consider).   ACh is an underlying common denominator anytime we eat; distention in the stomach or innervation by the vagus nerve activates the Enteric Nervous System, in turn leading to the release of ACh.  Once present, ACh activates G cells (produces gastrin) and parietal cells necessary for digestion.   From an FQ-Induced collagen/connective tissue damage point of view, appropriate collagen formation is also very necessary for AChE function and ACh transmission, and lack of it can result in Myasthenia Gravis like symptoms, as these COL Q studies confirm: 1, 2, 3, 4,  (and suppression of collagen prolylhydroxylation as in this FQ study here can affect COL Q; also scroll to “collagenous domains as substrates”, AChE, in this “Prolyl 4-hydroxylase” paper here).    Because of the necessary symbiotic relationship of mitochondria with their host cells (as I described here), anything that affects the host cell will often affect mitochondria as well, and this most certainly will include ACh-related problems.   However, never to be left out of an opportunity for direct damage, it turns out mitochondria also express a number of nicotinic acetylcholine receptors too (1,2).  I won’t be surprised if muscarinic receptors will also be found in mitochondria some day as well.”

I highly recommend reading the entire post to understand the arguments as to why and how fluoroquinolones may be connected to ACh disorders.

Can fluoroquinolones trigger anti-ACh antibodies? Can fluoroquinolones trigger a form of myasthenia gravis? How are autoimmune diseases connected to ACh depletion? We know that inflammation is a feature of autoimmune diseases, and that ACh modulates inflammation. We also know that lack of vagal nerve tone is related to both inflammation and autoimmune diseases, and that ACh is produced by a healthy and toned vagal nerve. We know that many of the symptoms of fluoroquinolone toxicity resemble symptoms of various autoimmune diseases, including rheumatoid arthritis, Sjogren’s Syndrome, Lupus, M.S., etc. How are autoimmune diseases, vagal nerve tone, ACh production and/or depletion, and fluoroquinolones related?

I’m not sure of the answers to those questions (I’m not sure that anyone knows the correct answers to them), but I do think that both vagal nerve tone and ACh production and/or depletion is related to fluoroquinolone toxicity (more on that assertion can be found in this post – https://floxiehope.com/2015/06/13/hacking-fluoroquinolone-toxicity-via-the-nervous-system/).

How can floxies increase their ACh? One way to increase ACh is to eat foods that are rich in choline, a precursor to acetylcholine. Choline-rich foods include:

  • Eggs
  • Chicken
  • Fish
  • Liver
  • Nuts

Some herbs and supplements that can increase ACh are listed HERE and HERE. Interestingly, caffeine, which many floxies respond negatively to, is on the list of things that increase ACh, and the supplements noted that decrease ACh have reportedly helped some floxies. As with everything, caution is warranted, and it’s best to consult with a trusted medical professional before starting any supplement protocol.

Exercises and practices that stimulate the vagus nerve can also stimulate the production and movement of ACh. Some things that stimulate the vagus nerve include:

  • Meditation
  • Breathing deeply and slowly
  • Singing
  • Playing a wind instrument
  • Submerging your face in cold water
  • Gargling
  • Chanting “OM”
  • Laughter
  • Exercise
  • Massage
  • Acupuncture
  • Chiropractic adjustments
  • Positive social interactions

More information about the benefits of stimulating the vagus nerve can be found HERE and HERE.

Many of the vagal nerve stimulating exercises and practices listed above helped me in my recovery from fluoroquinolone toxicity. Meditation and mindfulness were key elements to my recovery. Acupuncture, massage, breathing exercises, and support from loved ones (positive social interaction), were key as well. Even though none of these exercises are “quick fixes” or “big guns,” they are healing practices, and the ACh and vagus nerve connection may be how they help to repair the body and mind.

I hope that some research is done into the connections between fluoroquinolones/fluoroquinolone toxicity and ACh. It’s reasonable to think that there are connections–they just need to be proven.

Until then…. meditate, breathe, laugh, and eat liver. They really do help.

 

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18 thoughts on “Fluoroquinolone Toxicity and Acetylcholine (ACh) Damage

  1. tammyrenzi November 15, 2016 at 8:00 am Reply

    Lisa, thank you for always providing us with research-based information!

    I eat a plant-based diet (not because I was floxed in 2006…just because I chose to eat this way starting in 2013), so finding choline from plant sources is important to me. Here is a great list of plant foods containing choline for anyone who is interested. It contains many foods such as quinoa, soy milk, peanut butter, pinto beans, almonds,walnuts, broccoli – foods that have many other health benefits as well.
    http://extension.oregonstate.edu/coos/sites/default/files/FFE/documents/choline-rd.pdf

    Meditation, gentle yoga, and mindfulness have been an important way I have found to reducing relapses and to leading an overall happy life!

    • Lisa November 15, 2016 at 8:08 am Reply

      Thank you, Tammy! I also heard that prunes are high in ACh. 🙂

  2. Tracy Whiteside November 15, 2016 at 8:13 am Reply

    Gee, Thanks to Margaret Hamburg, Obama, and, Hillarys greed, we all get to suffer, all day, every day, we need to be writing letters to the FBI, and, Obamas , broken Dept of Justice, so, Obama can pardon this monstrous demon, Hillary Clinton, and, the nazi, mass murderer, Margaret Hamburg, and, her Eugenics program , Levaquin. They need to all.be in prison, along with the mass murderers, Bill Weldon , and, Alex Gorsky,

    • Harold May 27, 2017 at 9:27 pm Reply

      And while we’re at it, let’s not forget to add in the Bush administration for pushing Cipro on so many servicemen/women and other government workers thanks to the anthrax scare. Or better yet, stop being a partisan wingnut and take some of the suggestions on this site for those who have suffered. Take a deep breath. Don’t read material you know upsets you (or watch upsetting material). Focus on things you enjoy instead of things that make you miserable.

  3. Ron Hanson, MD November 15, 2016 at 9:03 am Reply

    Thank you for such an informative and well-informed post, Lisa.

    I agree with you nearly completely across the board. Here is a copy of what I give other providers (most of whom know very little about floxing–as most floxies are well aware):

    Background
    Fluoroquinolone antibiotics were originally developed and chemotherapeutic drugs, but concerns about effectiveness and side effects sidelined their use for decades. They re-emerged as “powerful antibiotics” to be used with broad spectrum effectiveness. Concerns have developed for many years about their detrimental effects, first centering on Achilles tendon tears-for which the class was given a black box warning by the FDA. Over time, the severity and breadth of injuries has become more concerning, now centering more on neurologic dysfunction than soft tissue injuries. The FDA’s warnings have followed suit, with a recommendation that the class is not used as first line agents anymore.

    Basic care
    As with every other type of condition evaluated and treated at OrthoCure Clinic, patients are encouraged to work with us on diet, nutrition, supplements, minerals, medications, medical conditions, and hormones to ensure that an optimal physiologic environment is available as a part of healing. The rare talents of highly specialized functional medicine physicians are directed toward genetic analysis (23&me), methylation genetics pathway optimization and hormone analysis. This care is highly individualized and requires not only a basic understanding of each of the areas described above, but also how to coordinate each part to optimize the body’s ability to regenerate and heal. A large portion of Dr. Hanson’s career in the last 10 years has been dedicated to learning and integrating these very mechanisms. This coordination is extremely important for this group of patients.

    Alignment, Stability, Motion
    Maintaining appropriate posture, position and motion should be a mainstay of any orthopedic and neurologic condition. Dr. Hanson believes that these foundations or principles are part of what provides the underlying information needed to create an approach that leads to healing the patient. Dr. Hanson works with a limited number of physical therapists and chiropractors in a very collaborative manner to ensure patients have the best opportunity to achieve relief and independence.

    Interventional care
    Fluoroquinolone injuries are some of the most complex group of conditions to treat. From severe tendon/ligament degradation that are treated with advanced cell concentrates to debilitating neurologic injuries that mimic (and are treated similarly) to complex regional pain syndrome, a comprehensive approach from the beginning is necessary. Patience and appropriate expectations needs to be encouraged. Very specific injections into nerves with platelet and cell concentrates has been the most successful intervention for this group of patients. Dr Hanson has injected thousands of nerves over the last decade, the precision and experience required to perform these procedures exceeds all other regenerative techniques. The vast majority of floxies improve >50% with treatment and continued care.

    That’s long-winded, but seeing the success that comes from a coordinated multi-modal approach, I hope other clinics start doing as much as possible–so I throw my template out there for them.

    Building a new website focused only on treating FQ injuries, it will be up in the next month or so: healingfloxies.com

    Be Well

    Ron Hanson, MD
    Founder & CMO OrthoCure Clinic

  4. Brooke November 15, 2016 at 11:38 am Reply

    Thank you for writing this, Lisa. I most definitely suffered with acetylcholine issues, specifically all of the liver detoxification phase 2 pathways, which acetylcholine is just one of them as you know. I knew I had these issues when I reacted horribly to amitriptyline (a non-cholinergic) and anything affecting acetylcholine during floxing. In fact, I reacted to all the choline-rich foods on your list. My central nervous system went bonkers. I think our entire liver is damaged from fluoroquinolones. I am much better now finally 4 years out!

    • Lisa November 15, 2016 at 3:57 pm Reply

      I am so glad that you are improving! I have learned so much from you, and you are greatly appreciated, Brooke! Have you read http://www.fluoroquinolonethyroid.com? I wonder if comparing your experience to hers would be helpful/interesting.

      Regards,
      Lisa

  5. Jaci November 15, 2016 at 3:59 pm Reply

    This could be the explanation of why caffeine helps calm me.

  6. Gary November 17, 2016 at 2:57 am Reply

    Alpha-GPC and choline will increase it. But some people can’t tolerate excessive amounts of either, and choline has numerous papers on pubmed and it seems safe (and has high bioavailability)

  7. […] Dr. Ron Hanson’s letter to fellow healthcare providers – https://floxiehope.com/2016/11/15/fluoroquinolone-toxicity-and-acetylcholine-ach-damage/comment-page… […]

  8. Donna December 3, 2016 at 4:58 pm Reply

    Is there a certain brand or type of this supplement that anyone can recommend?

  9. Donna December 4, 2016 at 10:13 pm Reply

    Thank you Lisa!

  10. Lisa December 22, 2016 at 4:05 pm Reply

    The Yoda-esque sentence structure throughout this is a bit odd, but it has interesting information none the less, http://medlicker.com/871-how-to-increase-acetylcholine

  11. Andrea October 4, 2017 at 7:49 pm Reply

    This article is so intersting to me. Here’s my experience : before I was floxed, I tried citicoline for a mild neuralgia on my arm, due to my weightlifting training. It was a wonderfoul supplement to me. Not only it cured the pain on my arm, It made me feel more calm and motivated. It also affected my sexual life and libido in a positive way ( something described by a few studies). And it was not a placebo effect : I knew almost nothing about citicoline when I took it, at that time. But after being floxed, I’ve tried it again, and sadly, it was now a disaster. Since being floxed I’m suffering from overactive bladder-like symptoms, and citicoline, like all cholinergics, can sometimes cause an increase in urination frequency, something that didn’t happened to me the first time I used it, anyway. But now, everytime I try it, it’s pure hell! I sometimes have to go to the bathroom up to 15 times a day. It makes my bladder symptoms WAY worse. So, I think, and it’s just my opnion, that FQ has defently caused ACh damage and has probably damaged my autonomic nervous system too.

  12. dezorz October 10, 2017 at 6:28 am Reply

    hello. i am trying to find out more information about Muscarinic antagonist. Can floxies use them? Ihave been 3 ytears since floxed, getting much better, still some slight issues,, sometimes small relapeses. It seems I have overreactiung bladder and I have been prescribed trospium which is anticholinergic agent. can i take it. recently i have a relapse, stronger then anything yet. i have been prescribed 2 months ago alfuzosin, which is Alpha-1 blocker. no CNS side effects mentioned though, i wonder, mayh this stronger relapse be because of it? sghoudl i continue use it? anyboby knows, has expenrience? cannot find much information about it.

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