Metronidazole: The New Mitochondrial Nightmare

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Metronidazole toxicity

When “Rare” Happens to You

On June 13, 2015, I lost the ability to walk and speak. These symptoms came on suddenly, and were accompanied by hand tremors, shortness of breath, weakness, difficulty concentrating, and dizziness. My mother drove me to the ER, but despite my deteriorating condition, I was confident the problem had a simple solution.

I’d been taking the antibiotic, metronidazole (Flagyl), for c diff (a gut infection). When my symptoms abruptly manifested, I looked the drug up online and, sure enough, all of my symptoms were listed as side effects of the medication. So my mother and I thought this would be easy, that the trip to the ER was a mere “technicality” for me to be put on an alternative antibiotic.

When it comes to having an adverse drug reaction, I would learn the hard way that things are never easy. What followed were six weeks where I could not care for myself. While a few symptoms diminished after discontinuing the medication, others randomly popped up to take the stage, this jumble of problems that didn’t seem to connect to one another:

  • Difficulty swallowing
  • Frequent urination
  • Constipation
  • Asthma-like respiratory issues
  • Complete loss of appetite (twenty pound weight loss)
  • Inability to stand up straight
  • Difficulty walking
  • Shortness of breath when talking
  • Chest pressure
  • Heart palpitations
  • Face flushing
  • Dry mouth
  • Cough
  • Headache
  • Pressure at the back of the head
  • Neck pain and stiffness
  • Constant adrenaline rushes
  • Anxiety
  • Depression
  • Crying spells
  • Insomnia
  • Extreme fatigue

I was the medical version of a Picasso painting. Nonetheless, there was one connection between these symptoms; they’re listed as side effects of metronidazole.

The Google Patient

During those first two months, I went from the patient who sees her doctor once or twice a year, to the compulsive consumer, calling several times a week, setting up appointments, and being put through the ringer of medical exams.

In total, I saw eight general practitioners, including my primary care physician, and almost every specialist known to medicine: a cardiologist, an immunologist, a pulmonologist, an ENT doctor, a psychiatrist, and a psychologist. There were tests, from multiple CT scans to X-rays, EKGs, an upper GI, an echocardiogram, a heart monitor, a laryngoscopy, several lung function tests, and about 30 vials of blood taken.

I insisted the cause of my symptoms was the metronidazole, but no one listened. After two months and no answers, my primary care physician handed down the diagnosis of depression and an anxiety disorder. That was the moment I lost faith in the medical community.

So I did the thing that doctors hate—I Googled. A lot. Medical literature is a language all its own—a new version of Pig Latin, MD edition—and I didn’t know what to search for, what the magical keywords were to unlock the “prize.”

Eventually, I ran across another group of people suffering from an adverse drug reaction—the floxies.  This group of patients had suffered an adverse reaction to another type of antibiotics called fluoroquinolones and, as I read their stories, I was horrified how their experiences mirrored my own, including their doctors usually dismissing their claims about the drugs. There were numerous blogs, YouTube videos, local media coverage, books and medical literature about their condition.  Fluoroquinolone antibiotics can directly damage mitochondrial DNA (the energy source of our cells), and people who suffer from this can become permanently disabled or even die. The effects are systemic, with certain regions of the body like the tendons, the heart, and the brain especially affected.

They called it “getting floxed,” and said they suffered from “fluoroquinolone toxicity.”  Reading this phrase, I plugged the words “metronidazole toxicity” into Google.  The answer I’d been searching for flashed on the screen.  What I had, it had a name:

Metronidazole-induced Central Nervous System Toxicity

If you lose the ability to walk and speak while taking metronidazole, there’s a 93% chance lesions have formed on the back of your brain, specifically the cerebellum, followed closely by the brain stem and then the basal ganglia. The effects cause motor control issues, seizures and an “altered mental state.”

From Patient to Blogger

Upon finding numerous pieces of medical literature to back up my claim about metronidazole toxicity, I presented the information to my primary care physician. When I tried to set up another appointment a short time later, she banned me from her clinic. It took a meeting with her supervisor and the clinic’s Risk Management to receive the proper diagnoses on my records—cerebellar dysfunction and altered mental state.

My ban from the clinic was never retracted.

At this point, it became clear that, not only did the medical community not have a way to treat an adverse drug reaction like metronidazole toxicity, they refused to even acknowledge it existed.

Nonetheless, the diagnoses didn’t fully explain my symptoms. There were others, like heart palpitations (including irregular blood pressure), constipation, dry mouth, loss of appetite, difficulty swallowing, and breathing issues that just didn’t match with cerebellar dysfunction.

Over nine months, my condition had greatly improved. I was able to work and enjoy social activities again, but some lingering symptoms would still randomly “flare up,” either due to over-exerting myself, an illness, allergies, or for no reason at all. I used to be an avid biker and that was no longer possible.  There were times, when a flare up would be too great, that I’d end up back in bed.

I decided to take the medical literature on metronidazole and create an online blog for others who might need answers. In addition, I started a support group on Facebook for metronidazole victims; when it began, there were three of us.  A year and a half later, there’s over a hundred, and counting.

Each of us have different issues, but almost all of them fall into four categories:

  • Cerebellar dysfunction (dysfunction of the cerebellum)
  • Autonomic dysfunction (dysfunction of the brain stem)
  • Altered Mental State (neuropsychiatric issues)
  • Polyneuropathy (damage to the nerves throughout the body)

Despite metronidazole’s ability to damage the brain stem, there’s little medical literature connecting metronidazole to autonomic dysfunction. The autonomic nervous system controls all the “automatic” operations of the body, like heart rate, breathing and digestion. As I listened to various stories from other patients that matched my own about uncontrollable heart palpitations, irregular blood pressure, dry mouth (dysfunction of the salivary glands), digestive issues, asthma-like respiratory issues, irregular sleep patterns, swallowing issues and the like…it became clear that this was the final puzzle piece to the metronidazole mystery.

Some patients have recovered as well as I have or better; others are disabled and housebound.  Almost everyone has flare up’s, months or years after taking the drug. Some people have full relapses and worsening symptoms long after they took metronidazole.

So the question keeps being asked—why? Why are these symptoms still here so far out from taking this drug?

Metronidazole and Thiamine

It was November of 2017 that I had the biggest flare up in two years. I had begun a second job on the weekends to get some extra cash for the holidays. My symptoms had remained steady for well over a year at that point, with only mild flare up’s. By the second weekend of work, my condition worsened, with symptoms that I thought were long-gone returning in full force. Heart palpitations, weakness in my legs, difficulty breathing, dizziness, brain fog, chest pressure, and even the anxiety came roaring back. On top of these, two new symptoms developed—pain in my hands and feet, and ringing in my ears. I had to quit the seasonable job, and, with the exception of going to my full-time work, I stayed mostly in bed for weeks.

At this time, I happened upon Dr. Lonsdale and Dr. Marrs’ new medical textbook, “Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition.”  The title caught my eye because I vaguely recalled, through my metronidazole research, the word “thiamine” had popped up multiple times. So I bought the book.

Everything I had experienced was listed within its pages. Thiamine (aka vitamin B1) is essential for oxidative metabolism. It is the gatekeeper of our mitochondria and, without it, the cells cannot properly convert food into fuel. In addition to this, without thiamine, oxygen cannot be properly utilized, causing our cells to—for lack of a better word—suffocate.

This suffocation (called “pseudohypoxia”) leads to our autonomic nervous system to activate its “fight-or-flight” response, which causes extreme anxiety, insomnia, emotional instability, a heightened sensitivity to stimuli, and an overall lowering of our stress threshold. In addition to these symptoms, there is a paradoxical one; the body is not designed to run on its fight-or-flight response for days or weeks on end. This over-use of the body’s energy reserves results in extreme fatigue.

Thiamine is found all over the body, but there are places where its use is concentrated, the brain being the most crucial, followed by the heart and our nerves. When there’s a deficiency, dysfunction typically hits the back of the brain the hardest—specifically the cerebellum and brain stem. Lack of thiamine causes:

  • Cerebellar Dysfunction
  • Autonomic Dysfunction
  • Altered Mental State
  • Polyneuropathy

After reading Dr. Lonsdale and Dr. Marrs’ textbook, I went back to all the medical literature I had pulled about metronidazole toxicity (and then some). It turns out, metronidazole and thiamine are antagonists; the drug inhibits thiamine from being absorbed into the body, which can plummet the victim into deficiency. The chemical structure of metronidazole is similar to that of the third ring within thiamine’s chemical structure; when the body mistakes metronidazole as this third ring, it turns thiamine into “thiaminase”—an inhibitor of thiamine.  This is called “thiaminase poisoning,” and it plummets the body into deficiency.

The symptoms of thiamine deficiency and metronidazole toxicity are identical.

Theoretically, the reason patients cannot recover from metronidazole toxicity adequately is because they never restore their thiamine after discontinuing the drug. The deficiency is too great to recover from by simply eating thiamine-rich foods; it requires high-dose supplementation over months to resolve the underlying problem. Therefore, victims of this toxicity are, at best, skating on the edge of this deficiency, and when a stressor enters our lives—illness, work, exercise—we exhaust the limited thiamine we have.  We plunge back into deficiency and the neurological symptoms manifest once again.

To conventional medicine, thiamine deficiency is considered a relic of the past—something that belongs in history books like scurvy—and rarely happens in the industrialized world. But there is one modern-day condition that is still being recognized by the medical community—Wernicke’s encephalopathy. This is an alcohol-induced thiamine deficiency that causes lesions to form on the back of the brain, specifically the cerebellum and brain stem.

In medical literature, metronidazole toxicity and Wernicke’s encephalopathy are constantly being compared because their symptoms and presentation of brain lesions are almost exactly the same.

Metronidazole and the Floxies

It all comes down to the mitochondria. For two years, I’ve read various stories and spoken directly with dozens of victims of metronidazole toxicity. Many times, they have commented about their symptoms being similar to that of the floxies, with several of them even stating that they’ve been “floxed.”  I’ve corrected them, explaining that metronidazole is in a different class of antibiotics and, while it causes damage to the brain, there’s no significant medical literature proving that it causes mitochondrial damage.

Nonetheless, as I’ve read numerous accounts from the fluoroquinolone community, I couldn’t help but note the similarities in our neurological symptoms.  Metronidazole victims don’t have the ruptured tendons…but the polyneuropathy and central nervous system effects (including psychiatric effects) are indistinguishable.

One website I focused on during my metronidazole toxicity research was askapatient.com. It houses one of the largest collections of customer reviews on the internet for medications, and metronidazole/Flagyl is the most reviewed drug on the site.  It also has the 5th highest number of 1-star reviews (Cipro and Levaquin are 1st and 2nd).

I compared metronidazole and its central nervous system side effects to that of those two popular fluoroquinolone medications from reviews between 2000 and 2015, totaling the number of reviews complaining about CNS symptoms:

Reviews Metronidazole Cipro Levaquin
Total # of Reviews 3312 1828 2032
Total # 1-star Reviews 1246 1352 1432
Dizziness 733 200 246
Fatigue 471 206 144
Anxiety 556 281 229
Panic Attack 180 95 65
Depression 641 185 152
Confusion 155 53 69
Disorientation 96 20 19
Paranoia 76 26 38
Headaches/Migraines 837 263 209
Suicidal Ideation 33 47 36
Numbness 157 121 119
Burning Sensation 51 151 133
Tingling Sensation 225 130 120

If metronidazole toxicity is caused by thiamine deficiency, then this deficiency is causing mitochondrial dysfunction and possible damage. And since thiamine concentrations are highest in the brain—specifically ,the cerebellum and brain stem, which is also the highest in mitochondria—this means that metronidazole is ultimately causing the same CNS issues as the fluoroquinolones.

Essentially, people with metronidazole toxicity are getting brain-floxed.

Can Something Be Done for Victims of Metronidazole? What I Have Learned

Unlike those who suffer from fluoroquinolone toxicity, those with metronidazole toxicity might have one advantage—our mitochondria haven’t been damaged directly by the antibiotic. Because it is a thiamine deficiency that is, in theory, the true culprit in this crime, it might be possible for victims of metronidazole toxicity to have a relatively clean-cut treatment plan.

Dr. Lonsdale and Dr. Marrs explain in detail about thiamine deficiency in their textbook, including the condition’s history, its symptoms and how they’ve implemented this information into action for various patients with documented case studies. If you believe you’re suffering from thiamine deficiency, reading this text would be the first big step in your treatment plan.

Depending on your level of deficiency, you will need to decide what works best for you. To sum up, there are several versions of thiamine to pick from; thiamine mononitrate and thiamine HCL are readily available at pharmacies and health food stores. Because they are water-soluble versions of thiamine, it is difficult to overdose on them; however, if you have severe or chronic thiamine deficiency, their benefits might be limited due to their short time span in the body and their inability to penetrate the cell without a protein transporter (making the absorption a little more complex).

Other versions may only be available for purchase online, but they cut out that “middle man.”  Allithiamine is naturally derived from garlic and is a fat-soluble version of thiamine. Because it is fat-soluble, the body stores it longer and it works better on the central nervous system and nerves.  Benfotiamine is another fat-soluble version, synthetically made, and works well on nerves but not the brain.  Lipothiamine has similar effects as Allithiamine, but is synthetically made.

You must supplement magnesium with thiamine. These two nutrients go hand-in-hand; thiamine supplementation will not work without magnesium. One option is Natural Calm Magnesium Powder that dissolves in water; you can control your dose of magnesium easily. If you notice loose stools, cut back. It’s available at several health food stores like The Vitamin Shoppe and online.

As the book details, patients who are severely and/or chronically deficient might need to “megadose” on thiamine before they notice improvements. If you feel you need to megadose, it would be a good idea to be monitored by a physician. Integrative physicians are more likely to support nutritional therapy than conventional doctors. Because this is new medical knowledge, you will probably have a lot of “trial and error” before finding the right type of thiamine and dosage that helps your condition and it could take months before treatment starts to work if you have a severe or chronic case. Do not begin by megadosing, however—start small and work your way up.

Thiamine has limited side effects, but they can happen, as can allergic reactions at high doses. If you are severely deficient in thiamine, there’s a good chance you’re deficient in other nutrients and taking thiamine might make those deficiencies more apparent. You could also have a “paradoxical” effect at first, as your cells have adapted to not having adequate thiamine (this is actually a good sign, as it confirms your body is no longer well-adapted to thiamine due to deficiency).  The paradoxical effect is temporary, but if you feel uncomfortable, scale back to a smaller dose and then work up from there.

One issue that could arise with high doses of thiamine over time is an imbalance of the other B-vitamins. However, this works both ways. If you are deficient in thiamine, then taking high doses of other B-vitamins right now could further imbalance your thiamine. After speaking with patients suffering from metronidazole toxicity, one misdirection is to take high doses of vitamin B12 (some even get injections).  This seems to result in worsening of the toxicity symptoms. Eventually, you’ll want to supplement other B-vitamins to keep everything in balance, especially if you wish to megadose on thiamine for a longer duration.

Unfortunately, there is no clinical trial for me to point when it comes to metronidazole toxicity and thiamine. It is taking medical literature from one side of the spectrum and connecting it to the other side.

I started taking thiamine mononitrate about two weeks after my major flare up began, 100 mg’s.  It did nothing, so I doubled it to 200mg. After two days, I started to feel better. I switched to thiamine HCL, 300mg, after another week and, again, noticed improvement. After reaching 600mg, I switched to Allithiamine at 50mg. I had a slight “paradoxical reaction” the first day, with anxiety and shortness of breath that dissipated quickly. Now, I’m at 200mg of Allithiamine, and my flare up has gone from debilitating to mild.

I still have a long way to go, but for the first time in two and a half years, it finally feels like my health is curving in the right direction.  There is a light at the end of this very long tunnel. Just like me, if you feel you suffer from metronidazole toxicity, then there might be something you can do about it.  There might be hope in treating your symptoms. Please be advised, however, I am not a physician and this post does not constitute medical advice. It is simply what I have learned over the course of my illness. To treat your illness, you will need to educate yourself, learn everything you can, and work with a physician.

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Image credit: Pablo Picasso, Weeping Woman under creative commons license.

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18 Comments

  1. Thank you for this❤
    I was floxed 4 times and given Flagyl with it. I’ve had 80% of the black box side effects. I was always able to work, sometimes in pain, but my mental state was fine, so I went on. One year ago I was having a diverticulitis attack, the doctor insisted Flagyl with Bactrim since I can’t take Cipro. I begged her to find something else, but she said there wasn’t anything that would work. All HELL broke loose, this was my 6th time and last time taking Flagyl. I had the normal side effects of severe headache, vomiting and no appetite, but what was horrible this time is I had extreme anxiety, heart palpatations, depression and suicidal thoughts, my flowing symptoms came back with a vengence, but after a year, I still get anxiety, which before this I never had, only with meds I’ve had anxiety, but after stopping it would go away. Now, after a year, I still have bouts of anxiety weekly, extreme fatigue, constant dizzy feeling, my muscle weakness is getting worse, all over body pain, probably from being floxed, but something scary happened Dec. 30th, I don’t go out much because of my condition, but I had passes to a concert and I went, I was on my feet for hours at a time, I was wearing a slight wedge heal, which makes you use your muscles in you legs more, but the end of the night, going back to my room, I had to be helped back because my legs stopped working, they were lilke noodles, it was the weirdest felling, it was from the middle of my thighs down to my feet. When I went to use the bathroom I tried to wall and fell flat on my face, I had to crawl. I do have two torn meniscus in both knees, but this was my whole legs not working. The next night while lying in bed, I bet my legs up to slip them under the cover and got an excruciating pain in the tendons behind your knees, I stood up to stretch them out, the pain started to go away but they were weird weak noodles again, my legs weren’t working right again. I had to hold on to anything to make my way to the bathroom. For about a week, my legs were very weak, but I could walk, and had much pain in both knees, which I think may be the torn miniscus, and falling on them again when my legs gave out. Has this happened to anyone else? I feel if I exert my muscles at all, they become weak instead of strong. I want to strengthen my body, but I can’t, this is so frustrating. I don’t remember what it feels like to feel good, I pray for that day. I’m on my way to join your Facebook page. Thank you so much. B-1 and garlic for me, I can’t wait to see if this helps my brain. Oh, and I did have an MRI on my brain, and they said no lesions, I hope this is correct, and I can hopefully heal from the Flagyl, but the Fluoroquinolones are another battle. Just typing this is making my eyes weird and blurry.

    1. Sorry for everything you’ve gone through, Cindy. I know a lot of people who have had issues with both metronidazole and fluoroquinolones (often prescribed together). I can’t account for the pain in your legs, as that sounds like a floxie-issue, but metronidazole affects the brain first and foremost, and it sounds like your difficulty walking is what I’ve gotten when I have a bad metro-flare up. The lesions from metronidazole toxicity disappear soon after taking the drug, but there’s a poor correlation between those lesions disappearing and resolution of symptoms. I’d definitely suggest, as one patient to another, of taking high doses of vitamin B1 and also get yourself some magnesium (don’t forget the magnesium, this won’t work without it!). It’ll take time–don’t expect to take it one day and be better the next–I’ve been doing this since November, and I feel so much better, but it’s a slow process. Good luck!

      1. Thanks Erin, I take my magnesium everyday, I just started B-1 yesterday. Did you have dizziness and an out of it feeling? This last Flagyl really did me in. I’ll update when I start to feel better.

        1. Oh, yes–the “detached” feeling lingered for a long time but it got better. The dizziness didn’t hit me as hard as others I know with metronidazole toxicity, but to put this into perspective, metronidazole has the highest complaints about dizziness on askapatient.com than any other drug. So you’re definitely not alone.

  2. I had a reaction to flagyl and cipro, I believe and it lasted for 8 years. It was a cascade of problems. A downward spiral of hell. Nad therapy helped me. Nad is a molecule being investigated as the principal component of aging itself. Please check out some helpful info:

    A site to get nadtherapy: http://Www.nadtreatmentcenter.com

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    The upcoming conference on Nad:

    Nadsummit2018.com

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  3. Erin
    Thanks you for sharing your journey and for never giving up and pushing until you founds answers. We clearly have so much to learn about medications and my hope is that people like you who bravely go “From Patient to Blogger” (and I would add “and leader”) will continue to lead the way. And that more and more doctors will read blogs like this and learn that they have much to learn too.

    I’m familiar with the adverse effects of fluoroquinolones, having first learned about them on this wonderful Hormones Matters site when I read an article by Lisa Bloomquist. I learned even more when I interviewed her so I could share this important info with my community of anxious women.

    I was not aware of these issues with Metronidazole and appreciate all your work and the thiamine work of Chandler Marrs and Derrick Lonsdale. And will be sharing this article widely.

    I’d love to hear if you came across similar issues with other classes of antibiotics such as cephalosporins (like Keflex)?

    1. Hi, Trudy. I don’t know about Keflex; my medical knowledge doesn’t go far beyond metronidazole and fluoroquinolones. I can say that I haven’t heard anything about Keflex, but that doesn’t mean there’s nothing there.

      Thank you for the nice comments. I think it’s time there was more awareness about the dangers of metronidazole and all adverse drug reactions; if doctors implemented appropriate care, it’s estimated that we could cut down ADRs by half. Just looking at people who die from ADRs annually in the US (roughly 100,000, although that number is very outdated), that means we might be able to save 50,000 patients.

      Lisa is wonderful; I adore her. She’s extremely kind, down-to-earth, and very knowledgeable. She’s taken her suffering and turned it into something positive.

      I’ve spoken to Dr. Marrs and she has been such a great support. I highly recommend her and Dr. Lonsdale’s textbook for anyone who believes they could be suffering from thiamine deficiency. It’s very well-detailed and offers a variety of case studies and how those patients were treated with thiamine and magnesium.

      Again, thank you for the comment. It’s very appreciated. –Erin

  4. I have been suffering for over 2 n half years from this toxicity and would love to talk to others and the author if possible is that possible?

  5. I am 11 years FLUOROQUINOLONE toxicity, connecting 2014. I recently quit taking b complex a few months ago as I learned B6 can aggrevate PolyN and I simply was sick of supplements. Im drained. My heart and soul. I too lost MD faith. I have severe autonomic and poly neuropathy from FQ’s. For 2 months, I have become very weak to walk, so weak my mouth muscles are affected, my mouth hangs open. I immediately started back b complex and cq10. It’s helping. My doctor thinks the weakness is severe polyN and of course, autonomic. I also took flagy given for digestive issues from fq’s by gastro. Double dip.
    Thanks for listening. I’m lost and weak.

    1. For fluoroquinolones, I’d suggest looking at Lisa Bloomquist’s lovely website, https://floxiehope.com/. There is so much medical literature and patient stories, including things they did to recover.

      It could be metronidazole toxicity only or fluoroquinolone toxicity only…it might be both. It’s hard to tell, as both can cause the issues you’re describing. I’ve heard the B6, at high doses for long periods of time, can cause neuropathy. Is there any way to take other B-vitamins and avoid that single one? I’m not a doctor, but if you’re concerned about that one vitamin, maybe it’s something to consider.

      Also, if you believe you’re suffering from thiamine deficiency, then that alone can imbalance other nutrients (as the example of B12 in the article). It gets complicated.

      Good luck! I hope you feel better.

  6. For those readers that desire more reading on thiamin and its part in disease go to Amazon books and type in Derrick Lonsdale and Chandler Marrs

    1. Hi Dr. Lonsdale,

      What test to measure thiamine levels do you recommend is the most accurate? On the Mayo Clinic website, it suggests measuring thiamine in whole blood is now the best test. I recently had this test taken and my thiamine was well within range. Is the Erythrocyte Transketolase test (only available in London) still the most accurate?

      Thank you for your wonderful research!

  7. Excellent article. Thank you for sharing your story. Your story will help many others. I wish you good health.

    I attribute my lifelong health issues to a chronic thiamine deficiency. I now avoid all antibiotic therapy as much as possible. I will never take fluoroquinolones, thanks to articles like yours.

    1. Thank you! Yes, this experience has certainly made me wary of all drugs, especially antibiotics. No fluoroquinolones for me, either–they should only be given for life-threatening situations where other antibiotics have failed.

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