metronidazole wernickes

Metronidazole Toxicity, Thiamine Deficiency, and Wernicke’s Encephalopathy

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Dr. Marrs and I recently had a book published with the title of “Thiamine Deficiency Disease, Dysautonomia and High Calorie Malnutrition”. I was therefore extremely interested to read one of the book reviews published on Amazon books by a patient who had suffered from what has become recognized as metronidazole toxicity encephalopathy (brain disease). Subsequently, she shared her full story with us. It is published here.

A Comparison of Flagyl Induced Encephalopathy and Wernicke’s Encephalopathy

This drug, sold as Flagyl, is prescribed to treat infections caused by anaerobic bacteria and protozoa. Uncommonly, it causes central nervous system toxicity that has the same damage configuration in the brain as Wernicke encephalopathy (WE). WE is the condition that occurs in the brain in people with severe thiamine deficiency. A manuscript in the medical literature was entitled “Metronidazole-Induced and Wernicke Encephalopathy: Two Different Entities Sharing the Same Metabolic Pathway?”  There seems to be little or no effort to explain it as a cause and effect relationship rather than seeing the two situations existing with different causes.

Debilitating Symptoms Post Flagyl

The reviewer states that she has, for two years, suffered with what she describes as debilitating symptoms due to a reaction from Flagyl. She states how these symptoms mysteriously wax and wane. On some days she barely notices them, but of extreme importance, she adds that a mild illness or physical exertion will cause the symptoms to reappear, forcing her back to bed for a variable number of days. When she was taking the drug, she lost his ability to walk and speak, but experienced a dozen other symptoms that persisted. These include difficulty in swallowing and breathing, constipation, severe anxiety, insomnia, depression, heart palpitations, chest pressure and several other unspecified problems. She mentions that she has a borderline enlarged heart.

I must point out here that these additional symptoms are surprisingly common in patients attending physicians in America, often classified as psychosomatic. It is the anxiety, insomnia and depression that guides physicians to thinking that the entire list of “inexplicable” symptoms is psychosomatic. Even the use of the word borderline for heart enlargement indicates that the physician could not identify the total symptomology. If thiamine deficiency had been considered as a diagnosis, the “borderline enlargement” would have fit because it is a cardinal sign of this deficiency.

The patient had evidently done some research on her own and had discovered that metronidazole is a thiamine antagonist. She also reported that in the medical literature metronidazole toxicity is constantly being compared with WE. When she came across our book, she had evidently experienced a flare up of symptoms and began to take supplements of thiamine and magnesium. She stated that the flare up calmed down much more rapidly than usual, enabling her to return to work and function in social activities.

She discovered that doctors do not believe in adverse drug reactions and will not treat the condition since they will not acknowledge that it exists. As a result, she has started a support group for people who suffer from this toxicity. Starting with three affected individuals, there are now over 100, all of whom have the same symptoms. Interestingly, they even warn new members how their doctors will react, preparing them for the reality of being dismissed by the medical community.

Thiamine Deficiency and Psychosomatic Disease

As mentioned in our book repeatedly, the multiple symptoms described by this reviewer are common in the offices of American physicians. “Real” diseases, according to the present medical model, are supported “by laboratory confirmation”. Because vitamin deficiency is generally considered to be nonexistent in America, it is only a physician, open to the possibility, who will entertain the laboratory studies required. The cause of many abnormal current laboratory studies performed on behalf of a sick patient is often obscure. None are capable of identifying vitamin deficiency. When positive as a result of the biochemical changes induced in the body by the deficiency, they are ascribed to other conditions that are acceptable to the present medical model. Hence, the diagnosis of psychosomatic disease often rescues the physician from a failure to recognize his own ignorance. It has always seemed to me that blaming the patient for imaginary symptoms without thinking of the brain as an electrochemical machine represents a glaring deficiency in diagnostic perspective. Unfortunately, nutrition has for long been a neglected area of medical teaching and there are extraordinarily few physicians in practice who recognize its vital importance. What is even more important is the recognition that many drugs are capable of precipitating something as bizarre as thiamine deficiency.

Stress and Illness

I mentioned above that it was extraordinarily important for the reviewer to recognize that flare ups of symptoms occur following a mild illness or physical activity. To explain this, I turn to the teachings of Hans Selye, one of the early researchers in the effect of stress as a causative agent in precipitating disease. Stress must be defined as any environmental factor that imposes a necessity for an animal to adapt (resist). Just like a car that climbs a hill, energy requirement must increase to meet the demand. Mental stress is often more energy requiring than physical stress, explaining the breakdown of health that may follow divorce proceedings. Selye had recognized in animal studies that virtually any form of physical or mental stress imposed the requirement of some form of energy in the ability of the animal to adapt. This was pure genius because energy metabolism was largely unknown in Selye’s time. Modern biochemistry has unraveled a lot of its complexities and thiamine stands out as an absolute necessity in the production of energy. Adapting means that the animal being physically stressed in many different ways would be capable of maintaining a state of health. Failure to meet the increased energy demand was marked by many observed performance and biochemical changes commensurate with those seen in sick humans. One of Selye’s students had reproduced in thiamine deficient animals exactly the same manifestations as those caused by physical stressors.

Diseases of Adaptation or Maladaptation?

The conclusion must be obvious. Any form of mental or physical stress induces a complex reaction in the organism that requires a large amount of energy to run the necessary adaptive machinery. In fact, Selye had concluded that illnesses in human beings were what he described as “the diseases of adaptation”. Since it is a failure to furnish the necessary energy, I suggest a refinement by calling them “the diseases of maladaptation”.

A healthy diet is designed to meet the calorie and non calorie nutrients that fully enable the body to synthesize energy. If this capability fails to meet the demand, even under extreme environmental conditions that permit life to continue, disease follows. The weakness may be genetic or nutritional in character or the stress overwhelming. For everyday life, all three factors are in play continuously.

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Metronidazole: The New Mitochondrial Nightmare

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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.