As a metronidazole toxicity survivor and the moderator of the Metronidazole Toxicity Support Group on Facebook, I am amazed by how much medical literature has been published regarding metronidazole and its serious adverse effects. Just Google “metronidazole toxicity” and you will be bombarded with over half a century of case studies, systematic reviews, and theories related to this drug and its dangerous impact on patients’ brains, nerves, and overall health.
Since 84% of patients with this toxicity are not believed by their doctors, this bounty of knowledge has been the guiding light for victims of this condition. Unfortunately, for all the facts medical literature gets right about this toxicity, there are many “facts” it gets wrong. And this misinformation can lead to confusion and contradictions for physicians, with devastating results on patients.
Here we will go over the most common things medical literature gets wrong about the adverse effects of metronidazole.
Medical Misconceptions About Metronidazole
Metronidazole Toxicity Is Rare
This is what medical literature says and what doctors fall back on any time a patient presents with symptoms while taking metronidazole. While some doctors acknowledge that metronidazole toxicity can happen, they seem skeptical when it happens to their patients.
One of the issues is that “rare” is a subjective term. What is rare? When discussing a rare situation with the general population, the numbers can be as extreme as “1 in 10,000” to “1 in a million.” There is about a one in a million chance of dying in a plane crash and there is about a one in fifteen thousand chance of being struck by lightning. While both are considered rare, there is a huge difference between them. Since these numbers are ambiguous, it is fair to say that when most patients think of “rare,” it is under the presumption that one must be very unlucky to be included in this small number of people.
I seriously doubt most patients consider 1 in 400 to be rare, however. At its most optimistic projection, that is the chance of having metronidazole toxicity. According to Oxford University, in a study published in 2021, approximately 1 in every 400 patients (.25%) who are administered metronidazole will suffer from cerebellar dysfunction, encephalopathy (brain dysfunction) and/or neuropathy so severe, they end up hospitalized within 10 weeks of taking the drug. In the article, it is noted that this number is believed to be ‘an underestimation,’ and it only reports on people who were hospitalized due to one of these three conditions.
To put this into perspective of how much of an underestimation this number is, in our support group with over 4,000 members (as of July 2024), only 12% of them were ever hospitalized when experiencing their toxicity. And even the ones who were hospitalized with symptoms that correlate with cerebellar dysfunction, encephalopathy, and/or neuropathy, many were either misdiagnosed or not diagnosed at all. That is, the doctors failed to recognize that the symptoms were related to these serious conditions.
Anecdotally, I lost the ability to walk and speak in front of my doctors, and was told I was just being anxious. It took 9 months and nonstop persistence on my part before I was diagnosed with cerebellar dysfunction. So even with that diagnosis, I would never have been reported in this study due to the length of time it took to be diagnosed.
We have had members of our support group with MRI-confirmed white matter lesions who were told by their physicians that the lesions were not related to the drug. This is despite the fact that white matter lesions are clear indicators of this toxicity according to the FDA label.
Imagine how many people are missed within these numbers, but even noting that discrepancy, does any patient out there view 1 in 400 being a “rare” phenomenon?
It should also be noted that across the internet, metronidazole is one of the most reviewed and poorly rated antibiotics. It is the most reviewed drug on askapatient.com, and when all versions of it are counted, it also has the highest number of 1-star reviews on the site.
But sure…rare.
Seizures Are a Common Metronidazole Toxicity Adverse Effect
False. Seizures are reported to be one of the most recognized symptoms of metronidazole toxicity, because no doctor can deny there is something wrong when a patient has a convulsive seizure. In reality, however, seizures actually only account for 15% of metronidazole toxicity cases in medical literature.
The issue comes into play when this symptom is commonly discussed in articles, websites, and even medical journals, and treated as if seizures are a telltale sign of this toxicity—perhaps even a tool that can be used for diagnosis. Just Google “metronidazole toxicity” and seizures come up immediately as one of the most common adverse effects, but few people with this toxicity actually experience them. In our support group, seizures are one of the rarest symptoms discussed, and the number of members who suffer from convulsive seizures is far less than 15% of the group as a whole. This again displays a dangerous inconsistency in the cases being documented by medical professionals versus patients’ personal accounts.
Ultimately, having seizures is a sign of an over-stimulated central nervous system. This is potentially related to an accumulation of glutamate and lowering of GABA in the brain due to metronidazole’s negative impact on a vital nutrient called thiamine (vitamin B1). What else does this state cause? It can also be one of the many contributing factors of triggering an altered mental state, which is far more common than having seizures, but unfortunately, medical literature is incorrect on this information as well.
Altered Mental State Only Happens in a Small Percentage of Sufferers
Wrong. “Altered mental state” happens to almost everyone with metronidazole toxicity, but it fails to be recognized in over 80% of cases. Why is this? First, let’s go through all the reasons someone with metronidazole toxicity could have an altered mental state beyond what has already been stated. Metronidazole has a unique ability to destroy thiamine in the body. Thiamine is needed for mitochondria to function and create ATP, the energy our bodies live on. When the mitochondria become dysfunctional without enough thiamine, this causes:
- Sympathetic nervous system dominance. Metronidazole can cause dysfunction and/or damage to the brain stem, as noted by decades of medical literature. The autonomic nervous system contains two tracts of nerves, the sympathetic (fight or flight) and the parasympathetic (rest and digest). When the brain stem is compromised, the parasympathetic nervous system cannot function properly, leading to a dominance of the sympathetic nervous system. This leads to heightened, and often, mismanaged fight or flight responses.
- Hypoxia and pseudohypoxia. Metronidazole toxicity can trigger hypoxia, which is where oxygen cannot enter the cells and pseudohypoxia, where oxygen enters the cells but cannot be properly utilized by the dysfunctional mitochondria. Lack of oxygen activates a panic response in the body, which leads to high anxiety, heart palpitations, air hunger, and insomnia. One of the more common symptoms of metronidazole toxicity is the jolt-awake insomnia where you start to drift to sleep, then jolt awake. This is because the heart is trying to compensate for the lack of oxygen. When we sleep and the heart relaxes, it can’t beat fast enough to compensate, so the body “jolts” us awake.
- Low dopamine. This happens with thiamine deficiency disease, and dopamine, like GABA, helps calm the brain and provides an overall contented feeling.
- Vasomotor dysfunction. This is an unnatural dilation or contraction of blood vessels, and the symptoms associated with this are an increased sensitivity to stimuli, high blood pressure, heart palpitations, nausea, vomiting, and “substernal oppression” which feels like a pressure, tightness and/or pain in the chest. This can also cause a feeling of flushing similar to hot flashes.
All of these issues related to metronidazole and its negative impact on thiamine results in an altered mental state in 99% of patients with this toxicity. And yet, this is rarely discussed in medical literature and doctors fail to recognize it the vast majority of the time. Again, why?
If you sift through metronidazole toxicity case studies, you find a common and disturbing trend. First, almost all the patients who are documented—over 65% of them—do not have any altered mental state. This is because those patients presented with strictly physical symptoms: difficulty speaking, difficulty walking, nystagmus, seizures, and brain lesions on an MRI. This is why cerebellar dysfunction is mentioned far more in medical literature than brain stem dysfunction, despite both regions being shown to have lesions in equal measure (see systematic review, “Metronidazole-Induced Central Nervous System Toxicity: A Systematic Review” and “MR Imaging of Metronidazole-Induced Encephalopathy: Lesion Distribution and Diffusion-Weighted Imaging Findings.”
But what about the people with an altered mental state? Unfortunately, for patients in this state, their symptoms are ambiguous and can be excused away as something else; generally, with the common refrain: “you’re depressed and having panic attacks.”
Sensitivity to light and sound, shortness of breath, air hunger, breath-holding, loss of appetite and weight loss, insomnia, crying spells, racing heart, high blood pressure; all of these symptoms are common with metronidazole toxicity and represent neurological manifestations of the drug’s damage, but they are, more often than not, relegated to psychiatric illness. This is despite the fact that many of these symptoms are listed under the “ADVERSE REACTIONS” section of the FDA Label for metronidazole. Most neurological conditions (Huntington’s, Parkinson’s, Lewy Body Dementia, Alzheimer’s, Chronic Traumatic Encephalopathy, etc.) all express neuropsychiatric symptoms, with those usually presenting first before physical symptoms manifest.
What is worse, even if you do also present with physical symptoms, such as unsteady gait, difficulty speaking, difficulty swallowing, hand tremors, etc., those will be concluded as symptoms brought on by the anxiety, all the while anxiety is just another symptom in itself.
In other words, your altered mental state will hinder your ability to get a diagnosis for your physical symptoms.
“Altered mental state” is one of the first true warning signs that metronidazole is causing dysfunction in the brain. In almost all cases, however, if a patient presents with it, the doctor never documents the case, it never gets published, and it is never recognized in medical literature as a key component of metronidazole toxicity.
Metronidazole Causes Brain Stem Damage, but Magically, Shows No Symptoms of Brain Stem Dysfunction
Here is another strange conundrum. There is roughly 60 years of medical literature discussing metronidazole’s negative impact on the brain, with white matter lesions noted to affect two key areas: the cerebellum and the brain stem. The lesions can also be found on the basal ganglia and corpus callosum, but in most patients with the lesions, if they have them anywhere, they are on the cerebellum and the brain stem.
And yet, while medical literature is flooded with symptoms of cerebellar dysfunction, including seizures, dysarthria (difficulty speaking), ataxia (typically difficulty walking), and other fine motor control issues, there isn’t a peep about the dysfunction of the brain stem—namely, dysautonomia.
What is dysautonomia? It’s a dysfunction of the autonomic nervous system, which is mostly controlled by the hypothalamus and the brain stem, and is responsible for all the involuntary processes that the body handles with little to no regard to our conscious control. Things like heart beat, blood pressure, breathing, immunity, digestion, temperature regulation, sleeping cycle, etc., are all part of the autonomic nervous system. If someone has dysautonomia, it can trigger a whirlwind of random and sometimes difficult-to-connect symptoms. With metronidazole toxicity, these symptoms include everything from abnormally low blood pressure to high blood pressure, along with heart palpitations, POTS (fainting when standing), skin flushing, IBS-like symptoms, saliva production, excessive sweating or lack of sweat, asthma-like respiratory issues, electrolyte imbalances, Cerebral Salt Wasting Syndrome, and of course, the altered mental state we’ve already discussed. And that’s the short list.
So how do you have a drug that clearly shows it can damage the brain stem just as much as it damages the cerebellum, but people with symptoms of brain stem dysfunction are rarely recognized?
Again, it comes back to a piggyback effect in medical literature. Because metronidazole has been on the market for so long, it is assumed that the FDA, the pharmaceutical companies and doctors know everything they need to about the drug. “Surely, if someone had lesions on their brain stem and that was a problem, dysautonomia would have been rampantly discussed decades ago,” they think. Since it hasn’t been, then obviously the drug doesn’t cause those symptoms. This means that when a doctor has a patient with clear symptoms of dysautonomia, they don’t connect the dots to the drug and nothing is ever documented.
Most Patients With Metronidazole Toxicity Have Lesions on the Brain
Unknown. Here is why: most patients suffering from metronidazole toxicity never get an MRI while they are taking the drug. In “Metronidazole-induced Central Nervous System Toxicity: A Systematic Review,” when a physician did recognize a patient potentially had this toxicity, the patient underwent an MRI while they were still being administered the medication. In those cases, 93% of them had white matter lesions on their brains in the areas previously discussed.
Wow. That sounds like a concrete test for metronidazole toxicity, then. Except for a few flaws in this conclusion:
- Most patients who suffer from metronidazole toxicity don’t have an MRI while they are taking the drug. When 84% of cases go unrecognized by physicians, by the time a physician might decide to perform an MRI, the lesions are gone. In the systematic review, 83% of patients had a resolution of lesions within three months, with some having a resolution within just a few days of stopping metronidazole. This leads into the next problem.
- There is a poor correlation between the resolution of lesions and the resolution of symptoms. This means that the lesions have little to nothing to do with the symptoms of metronidazole toxicity. While the lesions help to identify where the dysfunction is happening in the brain, there are no clear cut symptoms associated with their presence. The presentation of lesions is simply one more effect among the several other effects triggered by this toxicity.
So what happens if a patient who has symptoms of metronidazole toxicity, like cerebellar dysfunction and/or dysautonomia, and doesn’t have the lesions? Firstly, physicians fail to take into account whether or not a patient suffering from metronidazole toxicity is still on the medication; if they have discontinued the drug, the chance of lesions being present on the brain is almost nonexistent after a few months. Secondly, because doctors put so much weight on seeing lesions as the key component of metronidazole toxicity, when a patient does not have the lesions, their doctor almost always fails to diagnose the patient with this toxicity.
Then the patient’s case is never documented. It is never published as a case study (or reported to the FDA), and it will never end up being part of a systematic review. Although the medical literature states that 93% of patients with metronidazole toxicity have lesions, in truth, we don’t know how many have them or not because the cases without lesions are never acknowledged. Again, this is a feedback loop of misinformation in medical literature.
Neurotoxicity Only Happens With Long-Term Use of Metronidazole
This couldn’t be further from the truth. Metronidazole toxicity happens within the first week of metronidazole use in 91% of patients. Yes, 91%. The most common days for the toxicity to occur are on Day 2 and Day 5 of taking metronidazole. This can include all the central nervous system effects like altered mental state, cerebellar dysfunction, and dysautonomia. The idea that a serious adverse event only happens with prolonged use of metronidazole has been debunked twice now in medical literature.
First, the Oxford University study that was recently referenced, reported hospitalized patients with cerebellar dysfunction, encephalopathy, and neuropathy within 10 weeks of taking metronidazole. Not 10 weeks of taking the drug, but rather within 10 weeks of taking it. That means someone could have taken the drug for 2 weeks and ended up admitted to the hospital a month later, and diagnosed with the conditions listed.
Next, the systematic review, “Metronidazole-induced Central Nervous System Toxicity: A Systematic Review” debunked this concept back in 2011. As stated, “it [metronidazole toxicity] does not seem to be a dose or duration-related phenomenon.”
In fact, the case study they used as an example of this toxicity was an elderly woman who took metronidazole and within just 2 days, experienced difficulty speaking, and within two weeks, she could no longer walk or stand.
This is also true of metronidazole-induced neuropathy. There are several case studies of patients with acute-onset neuropathy in medical literature, but beyond that, there is no difference in our support group of 4,000 members when it comes to experiencing central nervous system adverse effects versus neuropathic effects.
Once again, however, many pieces of medical literature, even recent ones, still revert to this old-school view of metronidazole toxicity. They will note that the toxicity can only happen with prolonged use, despite other pieces of medical literature debunking that fact years before.
Unfortunately, when you say something untrue over and over, it starts to turn into “truth” and this is what has happened here.
Physicians are still out of the loop when it comes to how quickly metronidazole toxicity develops. Again it turns into a vicious cycle, where only patients with prolonged use of the drug have the potential to be recognized as having this toxicity, and they are typically the only ones where their cases are documented and published. So when doctors see the medical literature and it states metronidazole toxicity only happens with prolonged use, they believe their patients can’t possibly have the toxicity after only being on the drug for a few days. Their patients’ cases are never recognized and published, so again, people with this toxicity suffer in silence.
Conclusions
Medical literature for metronidazole toxicity has done some amazing things for patients afflicted with this condition. The hard work of many researchers who compile information and dig deep into the drug’s chemistry and how it affects the body, are the reasons patients have managed to get a leg up in this fight to regain their health. Like all things, though, there is room for improvement.
One of the biggest is to never assume a patient can’t be harmed by a drug with a history of toxicity that spans over six decades.
If you wish to learn more about metronidazole toxicity:
- Blog: www.moxxed.com
- YouTube Channel
- If you believe you or a loved one has metronidazole toxicity, we have a support group for people with this condition.
We Need Your Help
More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.
Great article, Erin! You have helped thousands of people suffering from metronidazole toxicity.