As interest grows in repurposing benzimidazole antiparasitic drugs for cancer, this article examines their microtubule-disrupting mechanisms, questions surrounding reported clinical outcomes, and potential risks associated with mebendazole and fenbendazole use in oncology.
Mebendazole and fenbendazole are formally known as benzimidazole anti-helminthics. These -azole drugs are, unfortunately, often lumped in with the very different drug ivermectin. They are often even compounded together in a combination tablet.
To confuse these two kinds of products is a huge mistake, because ivermectin is helpful for cancer patients and COVID patients. But the -azole drugs are hurting some and killing others. Ever since the latest fad of applying anti-helminthic drugs to cancer, I have warned patients against the latter drugs.
Microtubules are Essential for Life
Microtubules are the scaffolding of our cells, maintaining cells’ shape and polarity and intracellular transport.[1] Microtubules drive the movement of cilia and are therefore essential for airflow in the respiratory tract and to move food in the GI tract. In the brain, microtubules support axons, and maintain the shape and function of synapses.[2] Microtubules are needed for cognition and memory.[3] They are also essential for DNA separation in cellular reproduction.
Why Benzimidazole Drugs are Used Against Parasitic Diseases
Microtubules are made of the protein tubulin. The benzimidazole drugs are designed to disrupt and de-stabilize tubulin. The hazard of taking the benzimidazole drugs is the damage done to microtubules generally, and tubulin specifically, by fenbendazole and mebendazole.[4,5]
The benzimidazoles are used against parasites, to treat parasitic diseases in humans and animals, because these drugs have 25 to 400 times the affinity for parasite tubulin than for human tubulin – in either normal cells or cancer cells. But cancer cells reproduce more quickly, more often using tubulin as mechanical ropes to pull chromosomes apart in cellular reproduction, which happens far more frequently in cancer cells than in normal cells. Hence the use of these drugs in conventional oncology.
Just like the chemotherapy drugs taxanes and the vinca alkaloids, the benzimidazole drugs destabilize and disrupt microtubules. The thinking behind the use of those drugs for cancer patients is that cancer cells reproduce faster than normal cells, and therefore, these drugs would have a selective toxicity against cancer cells.
Full Disclosure Problems Arise in Three Major Ways:
- Cancer patients are not being informed that these benzimidazole drugs are being given to them with the same toxicity goals of a chemotherapy regimen. The trade-offs of potential adverse effects versus potential benefits have not been revealed.
- Reports of success are being oversold.
- The taxanes and vinca alkaloid chemo drugs have some of the most notorious rebound effects among widely used chemotherapy drugs, and no one has yet shown proof that the benzimidazoles – having the same mechanism – are free of that risk. This type of conventional chemotherapy is notorious for rebound pro-cancerous effects. These commonly used chemotherapy drugs reduce cancer short-term but strengthen and enlarge it long-term.
But first let’s address a common sales hook of the fenbendazole/mebendazole sellers: a parasite-cancer connection.
“The argument that ivermectin is effective against cancer, and therefore so is any anti-parasitic, does not follow.”
Is Cancer Really Parasites?
A recurring fad over the decades is the allegation that cancer is really an undetected parasite. This is a popular notion likely because it externalizes the conditions that led to the cancer, as in ‘the worm got me,’ and this idea may be more palatable to some than realizing that decades of handling pesticides or other toxins perhaps could have been the cause of the cancer and maybe could have been avoided. So, parasite-blaming may be a more comfortable idea to hold than a forensic audit of one’s lifetime carcinogen exposure. But epidemiology does not support a parasitic cause of cancer in the regions where the latter is most prevalent.
Cancer affects far more people than parasites do in the U.S. Only 5,124 cases of helminthic parasites were reported in the United States in a 23-year period, in steady decline during that time. In that same period, 43,100,000 new cancer cases were reported.
Therefore, new cancer diagnoses outnumbered new parasitic helminth diagnoses by over 8,400 times from 1998 through 2020.[6]
Geographically, parasites favor equatorial regions, and cancer favors temperate zones.
Helminths and protozoa are the two main classes of parasites. From Brazil through the equatorial Africa and then north to China, helminthic disease incidence follows a band that mostly covers equatorial countries.[7] Protozoan parasite disease prevalence even more closely follows the equator around the earth.[8]
On the other hand, cancer incidence generally is more common away from the equator.[9] Colorectal cancer incidence specifically is most common away from the equator.[10]
So, cancer and parasites affect largely different populations.
If Cancer is Not a Parasitic Disease, Why Does Ivermectin Work Against Both?
One of most powerful known roles of ivermectin is as a zinc ionophore. And zinc has enormously helpful effects against both infectious pathogens and against cancer. The likely mechanism for ivermectin carrying zinc into a cell is that two ivermectin molecules encircle positive cations including zinc, surrounded by negatively charged oxygen molecules. [11]
Ivermectin’s action against parasites is to allow too much chlorine to enter the parasite, which results in paralysis and death of the parasite. This is also one of its effects on cancer cells, which leads to death of cancer cells, although it is observed to not have that effect on normal human cells.[12]
The argument that ivermectin is effective against cancer, and therefore so is any anti-parasitic, does not follow.
Full Disclosure About Benzimidazole Use is Needed, but is Not Being Provided, and Success is Touted, but Falls Apart on Examination
A company that has gained attention for selling mebendazole has claimed more success for its product than is revealed in the fine print. In the self-survey, 33% reported no evidence of disease (NED), although the survey required no endpoint imaging to confirm the self-reported NED or other results.[13] Also, healthcare providers chose among their own patients to be included. For this lack of clinical validation, the study received a letter of concern from the publishing journal and assignment to ethical audit, including “objective medical documentation supporting the reported anatomical regressions.”[14]
The study authors also reported that over 6 months of cancer patients’ self-reported initial and endpoint outcomes, 16% of the company’s customers self-reported tumor regression, and cancer spread or progressed in an equal portion of participants. 197 patients started the survey, but only 122 completed follow-ups. There is no information about the missing 75 patients, or whether they are alive. 63% of all patients began the study with stable, non-growing cancer, and most had previously had conventional cancer treatments and/or nutritional supplements and/or dietary changes.
Have Cancer Patients Been Informed that the Benzimidazoles Act as Mild Chemotherapy?
Just like stronger chemotherapy, the benzimidazoles disrupt microtubules, but gently enough (in the online pop-culture dosing protocol of 250 and 222 mg per day respectively) for the typical patient to not feel ill effects over a typical course of these drugs’ use. However, “chemo brain” is a common result of the microtubule disrupting chemotherapy drugs.
Chemo brain is a notorious condition of neurotoxicity caused by chemotherapy drugs, including those that damage or disrupt microtubules. Chemo brain victims commonly suffer from impaired memory, impaired cognition and encephalopathy. Like the taxanes, mebendazole crosses the blood brain barrier and has this exact same mechanism of action of risk to the brain (binding to mitochondrial β-tubulin) that causes “chemo brain” in cancer patients who have had taxane drugs.[15,16]
Chemotherapy Resistance is Even More Dangerous Than Antibiotic Resistance
Taxanes and vinca alkaloids are the most common types of microtubule-disrupting chemotherapy drugs in common use. The microtubule disrupting type of chemotherapy is notorious for rebound pro-cancerous effects. These commonly used chemotherapy drugs reduce cancer short-term, but they strengthen and enlarge it long-term.[17]
An even bigger problem than the ones discussed above is that cancer cells – not normal cells – mutate beyond the particular obstacle of β-tubulin protein binding. Cancer cells mutate to alter the drug-binding site (among other actions) in order to get around this problem, which has the result of younger cancer cells surviving the chemotherapy tool that previously worked against the parent cancer cells.
It has long been known that too little dosing of an antibiotic has the undesired effect of causing stronger, resistant bacteria that are now harder to treat and harder to eliminate. This leads to intractable bacterial infections such as MRSA (methicillin-resistant Staphylococcus aureus) and C. diff (Clostridioides difficile). Similarly, the use of benzimidazoles is especially unwise, because cancer is heterogenous and quickly mutating.
Therefore, cancer is capable of inactivating single-purpose molecules such as chemotherapy and the -azole drugs. This is because cancer mutates past the effects of those drugs fairly easily, resulting in cancer recurrence in an average of 15 months.[18]
So, in essence, while normal cells are weakened by these drugs’ β-tubulin protein binding mechanism, cancer cells mutate in such a way as to make themselves resistant to the drugs’ effects. This process has the result of leaving normal cells weaker and leaving cancer cells stronger.
Having a little bit of a mild chemotherapy is one of the worst strategies against cancer from what I have seen over the years. I continue to recommend avoidance of the benzimidazole drugs in cancer treatment.
