Fenbendazole is a stem cell killer and not harmless

[Callithrix]

Some two years ago, I wrote a warning about Fenbendazole because feeding it for 4 days to my homing pigeons had killed half of them. Since then, I did analyze the problem thoroughly to deal with the insurance company of the veterinarian who prescribed the drug without knowing its mode of action. Here is why one should be very careful in using it, as it can be harmful also to humans and mammals, even though these tolerate higher dosages than birds.

Fenbendazole is a cytostatic drug with a chemical structure resembling the well-known Docetaxel. But oncologists do have good reasons not to give anticancer chemotherapy drugs orally but infuse patients in well-timed intervals. As already pointed out in earlier comment in this forum, Fenben is a tubulin blocker. Tubulin is an important protein found in many cells. It builds up the transport ways within metabolically active cells, and is essential for aligning the chromosomes during cell division. So what happens if one consumes Fenben (even by using the recommended dosages suggested by Joe Tippens)?

It won’t affect much the upper part of the digestive tract and the stomach but its first target will be the billions of cells lining the small intestine and taking up the various nutrients. These cells (technically known as enterocytes) depend on tubulin-constructed beltways to transport the nutrients to the tissue beneath from where they enter blood (to the liver) and lymph vessels. These cells also transport some amount of orally ingested Fenben (maximally 20-30%) that is delivered to the liver and other body systems but then Fenben shuts down their transfer machinery and (fortunately) limits further uptake. Thus, the first effect is that nutrient uptake is restricted and that many enterocytes die and are shed into the smaller intestine. No big deal for most of us with some overweight: loosing a pound or two is not so bad after all, and occasional diarrhea may occur (what happens to other cells in the body facing Fenben will be explained later). But first the lost enterocytes must be replaced and here begin the problems.

The cells lining the small intestine are normally replaced totally within 3-4 days. New cells are generated in small pits at the bottom of the cell lining, known a Lieberkuhn’s crypts, each one harbouring 12-16 stem cells. These divide constantly in a 24h-rhythm pushing up new cells in order to replace the shed enterocytes. The stem cells react very badly to ingesting Fenben since the drug, like any other chemotherapy drug, blocks cell division; in this case by preventing the aligning of chromosomes along the so-called spindles made by tubulin. If this happens, stem cells invoke a very old safety self-destruction program called apoptosis and die. But the crypt stem cells do not work in synchrony and some of these cells will be in a cell division stage during which they do not build up these spindles, being thus temporarily unaffected by Fenben. But about half of them (say 8) will be inactivated by a first day of Fenben. The next day of consumption, the Fenben will kill again half of the four remaining cells, and after days 3 or 4 most of these stem cells will be gone and the small intestine will be dangerously damaged, indicated by numerous side effects such as vomiting and cramps. Fenben users (for treating themselves or pets) have probably noticed the stringent warnings of the manufacturers to stop medication after 3 days and pausing for prolonged periods, of course not indicating the reasons. They know exactly what is going on and must make sure that people permit for their pets recovery time for stem cells and enterocytes. But what can be read in the instructions is always how the drug kills the worms and nothing about the risks for consumers…

One can also ask what happens when Fenben gets into the body system. As said before, there will be a first wave making it, and their preferred targets will be cells having an active metabolism (for those having had courses in histology, these are the cells with bright cell nuclei found in liver, kidney and the brain). The first array of such cells is located in the liver, and so Fenben will inactivate a bunch of them and may cause some transient problems in liver function, see also Yamaguchi et al. 2021 below. But this organ will recuperate because its stem cells work at a slower pace. The much more dangerous effects take place when Fenben, after some days of intake, enters through the destroyed cell lining of the small intestine. Then it will attack seriously the second stem cell population working always at full speed, namely the cells producing white and red blood cells, the so-called hematopoietic system in bone marrow, spleen and lymph nodes. Thus Fenben in the body system is clearly immunotoxic. The loss of immuno-competent stem cells is doubly dangerous because many bacteria and viruses are entering the body that otherwise would be confined to the intestine. Immunotoxicity is in fact the main factor that kills birds after prolonged feeding of Fenben as they continue to die for 2-3 weeks by many bagatelle infections, comparable to HIV-infected people.

But why are birds more sensitive to Fenben intoxication? The reasons are not well known. For one, the body temperature is much higher than in mammals. Secondly, the bird species apparently affected most by Fenben are those feeding the offspring from a mixture of food and shed cells in their crops, a feature facilitating toxic Fenben uptake in throat or crop. Since homing pigeons and parrots can be expensive (up to 1.7 Mio Euro for a top racing pigeon), the manufacturers have issued warnings of treating those birds with Fenben, yet without explaining why.

Finally, one might wonder why there have been not more reports about dangerous side effects in humans. The chief reason is that Fenben is not approved for use in humans, and so there are no clinical studies. There is also no reason to study in-depth damages of the stem cells and cells lining the small intestine. For those interested in the matter, even normal chemotherapy by infusion damages seriously the intestinal stem cells (Keefe et al. 2000, below). A second reason is that repeated application of Fenben during restricted time windows considered as “safe” is likely to cause drug resistance. This means that intestinal cells do no longer absorb it or they use protective mechanisms to kick it out of the cell after entry. In this case, the drug fulfills the claims of the manufacturers that it only harms worms but will no longer enter the body systems to kill cancer cells. But we PCa patients have certainly other problems than intestinal worms and should preferably rely on clinically proven treatments.

Lastly, advocates of Fenben point to the fact that the suggested safe dewormer drug kills cancer cells in culture. But it would be difficult to find any tubulin blocking substance that is not killing cancer cells in culture – so what? In conclusion, everyone is free to swallow drugs known to kill intestinal and stem cells of the immune system. But the consumer should know what the drug is really doing in the body and public information about this is woefully missing, chiefly due to withheld information by the producer. Moreover, positive effects, if any, by killing prostate cancer cells (which divide rather slowly) will be uncontrollable and marred by hidden immunotoxic effects. Interestingly, the claims of Joe Tippens could apply to any other substance taken against cancer: about 5-10% of all types of treated tumors can show long-lasting remissions regardless of the treatment (Coventry and Ashton 2012, see below). But this is another topic yet probably more interesting for many of us than the discussion around Fenben.

Coventry B, Ashdown. Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation. Cancer Manag Res. 2012;4:137-149. doi.org/10.2147/CMAR.S31887

Keefe DM, Brealey J, Goland GJ, Cummins AG (2000) Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans. Gut 47:632-637. doi.org/10.1136/gut.47.5.632

Yamaguchi T, Shimizu J, Oya Y, Horio Y, Hida T (2021) Drug-induced liver injury in a patient with non-small cell lung cancer after the self-administration of fenbendazole based on social media information. Case Reports in Oncology 14:886-891. doi.org/10.1159/000516276

[Tall_Allen]

I continue to be amazed that cancer patients, who already have body systems debilitated by cancer, put such toxic drugs in their bodies. They usually point to mouse studies, somehow imagining that what works in mice must work in humans. Thanks for all your research.

[Hidden in reply to Tall_Allen]

If you are going to put toxic drugs into your body, it should at least kill the cancer too.

[Hailwood in reply to Tall_Allen]

Absolutely baffling

[CAMPSOUPS]

Appreciate your in depth explanation. Hope it doesn't fall on deaf ears.

You can with just about anything kill organisms in a petri dish but that doesn't mean they work within the complexities of the human body. (I.E. injecting bleach, rubbing alcohol, WD40 etc.)

Any of the above would kill step throat bacteria on a petri dish. Common sense should arrive when considering it takes antibiotics well researched to kill the bacteria and not the patient.

[33Ford]

Interesting for sure! Thanks for the post.

[TFBUNDY]

Wow an excellent and well researched post. Thanks

[clayfin]

Thanks for the article. I would be interested to know if you have done similar, in-depth research on the effects on the lungs from the dust created when cleaning pigeon lofts? My brothers and I spent our youth cleaning my fathers racing lofts weekly - I do not have lung issues but my brother does.

[Callithrix in reply to clayfin]

Dear Clayton, unfortunately, my experience in this field is limited and so I refrain from commenting. However, I am aware that many elderly pigeon fanciers were forced to give up their hobby because of lung problems. Hope that the condition of your brother is not too serious.

[Blackpatch]

I’ve not heard of any doctors prescribing Fenben (for people!) but theCare Oncology people do include Mebendazole in their repertoire, and claim that it targets cancer stem cells.

CO are reputable people as near as I can determine, and certainly their London staff are impressively credentialed.

Mebendazole is approved for prolonged use (years of continuous dosing), and it was on this basis that I took it every other month, alternating with Doxycycline, for two and a half years.

I actually stopped taking it because I began to experience episodes of severe tongue swelling which were pretty frightening - the swelling was a classic allergic reaction, and ceased as soon as I stopped taking the drug.

I know there are others here who have some interest in the CO protocol - but the only element of it that I have stuck with is the Atorvastatin - I kept up the 2 x 1000mg per day of Metformin for a few more months after dropping the Mebendazole and Doxycycline pair, until I started experiencing regular vomiting and nausea - which stopped as soon as I quit the Metformin

I dare say others may have different outcomes - there are plenty of people on Metformin for life - but I thought I would just report how CO’s protocol has played out for me.

I’m undetectable 3 years after eSRT and 12 months of ADT - but as with any of these “experiment of one” things, I have no way of knowing if the CO drugs have contributed to this.

Stuart

[Retiredstate in reply to Blackpatch]

Good morning bp, I was on CO protocol for about a year and had some initial success (psa down from 52 to 29) however it popped back to 50's a few months later and then escalated to 137. Being on ADT now for 7 months and having reduced the psa to 3, I would think mebendazole would be preferred initially over docetaxal if I become resistant to the androgen therapy. I still take metformin hoping for some pathway blockage and blood sugar control. Do you have an opinion on that?

[Callithrix in reply to Blackpatch]

Thanks Blackpatch, see my answer to johnscats

[GeorgeGlass in reply to Blackpatch]

good, thorough reply Stuart. thx

[MateoBeach]

Sorry about the loss of your clearly treasured pigeons. And thank you for this very precise and clear explanation of its actions. Will read the Coventry and Ashton article next. Paul

[dhccpa]

Thanks for your post. I've been on fenben for 19 months. I haven't seen any warning signs, but I'm going to double down on blood test scrutiny as I go forward.

Have you communicated directly with Joe Tippens about these concerns?

[Back2future in reply to dhccpa]

After being on fenben for 19 months what where psa results? Did you add other supllements like Joe Tippens?

[dhccpa in reply to Back2future]

Just saw your response. My PSA hit a low of 0.5 in April. I'm having new scans this month. I've been on Lupron since 11/2018, fenben since 2/2020.

[CAMPSOUPS in reply to dhccpa]

Are you still taking Zytiga ? Sorry to ask but your 2 posts on your "page" left me confused.

[dhccpa in reply to CAMPSOUPS]

I've never taken Zytiga, only Lupron (and Xgeva for bones). What's confusing?

And yes, I take other supplements as well.

[CAMPSOUPS in reply to dhccpa]

Hope no harm. Confused wasn't the best wording sorry.

I recalled your "dhccpa" from the past and wanted to kick my memory so I looked at your "home/bio page" and your first post mentioned taking Zytiga. That's why I wondered if you still are.

Here I copied and pasted the first paragraph from your first post that mentions Zytiga:

SOC standard info on starting Xgeva without bone issues.

dhccpa profile image

dhccpa•

6 months ago•20 Replies

In Jan. 2020, after I had been on Zytiga since 11/2018, my MO started me on Xgeva even though 1. I had never had a bone density scan and 2. Had no diagnosis of osteoporosis or other indicators of bone issues. In Sept. 2020 I had my first ever bone density scan and it was normal.

[dhccpa in reply to CAMPSOUPS]

No problem. And apparently my own mistake. That earlier post is incorrect, as I've never taken Zytiga. Instead, I started Lupron 11/2018. Must have had Zytiga on my mind from reading someone else's thread.

I've been on Lupron since 11/2018, Xgeva since 1/2020, fenbendazole since 2/2020. Numerous other things rotated in and out along the way.

[FRTHBST]

Thanks for the great write up on fenbendazole. I wonder whether people are drawn to alternative treatments to cancer because those recommended by SOC, though well researched, are often quite toxic as well. Doctors don't always offer in depth explanation that would help patients in deciding what treatment to take and why. You mention that fenbendazole has an action similar to docetaxel, that is, it's a serious drug with deep biological effects that extend beyond action on just the cancer cells. Docetaxel doesn't work for every patient and though there is a statistical knowledge base for recommending it in some cases and not others, we just aren't there yet in understanding the underlying biology of the cancer process. For example, the most effective treatments rely on inhibiting one of the nuclear receptors, AR. There are 48 others, a number of which seem to be implicated in the downstream epigenetic changes wrought by cancer. And androgen receptor inhibition comes with serious side effects. It's difficult to have a grounded rational conversation, much less make life and death decisions, with the limited knowledge available. Yet this is what we have to do everyday. We do the best we can and informative posts like yours can help in balancing risks in an environment where knowledge is on the one hand so voluminous that it's hard for any one person to absorb, but also so limited with respect to definitive outcomes.

[Callithrix in reply to FRTHBST]

Thanks for your well balanced response. I may come up (in due time) with ADT side effects on brain structures.

[johnscats]

Read with interest your evaluation of fenben the human type is mebenzenol which from what I can see has the same action as fenben this is human version is used by the care oncology group along with other drugs would like to hear your opinion on the human version if you have time

[Callithrix in reply to johnscats]

Thanks for your question. Following a somewhat lengthy response which might be of interest to others.

As you indicated, Mebendazole is one of the dewormers allowed for use in humans, and there are several clinical trials assessing its usefulness as anti-cancer agent (Guerini et al. 2019, see below). I have some doubts about the claim that mebendazole targets cancer stem cells as this would be a quantum leap for oncology. I also do not oppose that it is taken under medical control, but self-administrating people must consider the risks when using them. Yet most people feel that the dewormers are genuinely safe drugs developed specifically to kill worms and must, therefore, be harmless. Historically, however, this is not the case.

Like fenbendazole, mebendazole belongs to a class of substances known as benzimidazoles. The most popular ones are fenbendazole, albendazole, flubenole (used for animals) and mebendazole (used chiefly as anthelmintic in humans). They have a reputation as very safe drugs, for a specific reason, however. Originally, the pharma company Hoechst (now integrated in Merck, Sharp and Dohme, MSD) was looking for a drug that would kill worms but should be harmless for the host. They hit pay dirt after they succeeded synthesizing fenbendazole) belonging to the taxane family of cytostatics (cell division blockers used for chemotherapy) that dissolved poorly and showed the desired limited uptake in the small intestine. Other companies followed. These drugs were very convenient to get rid of tapeworms that absorb nutrients through their skin: after a high one-day dose they would die quickly and being excreted through the feces with the non-absorbed rest of the drug.

Veterinarians were happy because one could feed a high one-time amount of the stuff and the tapeworm was gone. The matter became a bit complicated with round worms (nematodes) because these have a solid skin structure protecting them against harmful substances in the intestines. Their heads penetrate the cell linings of the small intestine and they suck pre-digested cell tissue from beneath the cells lining the intestine. In other words, the poorly dissolving benzimidazoles had to be absorbed before the worms could sucking them up, and so the drug needed to be fed repeatedly in rather high concentrations. Since the developers apparently knew well the dangerous impact of cytostatic drugs for the renewal of intestinal cells, it became a marketing problem since most people would not be inclined to make an oral chemotherapy to deworm their pets.

The solution was two-fold: for pets (and most human indications), the intake was strictly limited to 3 days as this allows rapid rebuilding of the intestinal cells, and a next treatment required a safe interval of many days. For the consumer, the companies adopted a strict narrative that never made clear that the drug could also affect the treated animal. Sometimes they simply stated that the drug interferes with the glucose uptake of the worm (a typical effect of a tubulin blocker), sometimes it was said that it interfered with the synthesis of microtubules in the parasite damaging nutrient uptake and cell division. As the law requires listing side effects, they had to mention gastrointestinal problems such as diarrhea and pain, of course without telling why. But if one is plagued by worms, such temporary symptoms might occur anyhow, so there were not much questions.

As most people adhered to the user instructions, the drug sold well in the animal market (except for many bird species as explained before) and grew a reputation as being safe and harmless. Only specialists would recognize the telltale signs of a cytostatic drug (stop after 3 days, typical intestinal side effects, pause between applications). For those interested or not believing, just check the web for explanations of chemotherapy and look for taxanes. Interestingly, the unsubstantiated belief spread into the medical and pharmaceutical sciences as well, and thus the cytostatic properties of the benzimidazoles were noisily re-discovered as many people did believe that it was developed as a magical bullet against parasites and were surprised to see anti-cancer effects in cell cultures and occasionally in mice. The companies selling veterinarian anthelmintics were unhappy with this publicity because it might direct customer attention to the cytostatic effects. Interestingly, Wikipedia purged any notions how the fenbendazole worked (including the warning that it might kill birds), one is left wondering why.

Nonetheless, I would make clear that the benzimidazoles are still useful as dewormers for pets (though I discarded my Panacur paste for the kittens as soon as I had learned more). But I think that patients should not take orally classic cytostatic drugs with unpredictable and highly variable pharmacokinetics and unknown resistance properties until the outcome of the clinical trials is known.

My judgment is based on the fact that the literature barely mentions the unavoidable side effects of an orally ingested cytostatic drug on the stem cells replacing the lining of the small intestine. Having taught anatomy and histology of the intestinal system for decades, this omission appeared surprising to me – are medical and pharmaceutical students so forgetful? Damage to the intestinal stem cells was only reported for birds but to my knowledge never investigated in mammals. (If anyone of you has a paper showing histological pictures in mammals or humans having congested benzimidazoles, I would appreciate to know the source).

The problem is that the side effects are discrete as long as intake is restricted to 3 days. But in this time, even very low concentrations of the drug in those crypts can efficiently kill the stem cells and produces small holes (technically known as aponecrosis or cryptal lesions). These punctuations, in unpredictable numbers and locations, are rarely causing dramatic effects but serve as entry points for non-absorbed drugs, germs of various nature and other undesirable stuff. The immune system responds to the germs but is partially paralyzed at the same time by the circulating cytostatics suppressing the stem cells. The effects are unpredictable. For example, fenbendazole or mebendazole may interfere with T-cell production when the immune system just launches an attack by killer cells, consequently the infections spreads. Conversely, if the system is impaired in producing regulatory T-cells inhibiting the killer cells, a cytokine storm (remember Covid) or hyperallergic reactions may occur.

In sum, people may continue taking mebendazole under medical control. My guess is that intestinal cells may become resistant when the drug is taken regularly (which renders it truly harmless yet also ineffective) , but at least one should know some of the hidden risks. But simply ask your MOs or recommending agencies whether they believe that an orally applied cytostatic drug is sparing the intestinal stem cells. Perhaps they will then remember the Lieberkuhn crypts….

Guerini AE et al (2019) Mebendazole as a candidate for drug repurposing in oncology: An extensive review of current literature. Cancers (Basel) 11. doi: 10.3390/cancers11091284.

I did check their section on toxicity (the claim was that safety estimates are based 39 clinical studies with 6276 participants), but the official Italian Public Health website did not show any reference to these studies, presumably because the information had been provided by the manufacturer. The authors provide a good yet rather overoptimistic review, but seem to be unaware of the histology of the small intestine. Yet they also list some dangerous side-effects as cited below:

“Moreover, this compound causes DNA damage and in vivo studies revealed its genotoxic and teratogenic effect, leading to skeletal abnormalities and malformations in rats and mice [25] and to malformation of the retinal layers in a zebrafish model [74]; for these reasons, MBZ is contraindicated during pregnancy”.

In case you cannot get the paper, send me a private message

[johnscats in reply to Callithrix]

Thanks that was really interesting I was considering it but now will be definitely waiting on clinical trials on it thanks again for your research

[j-o-h-n]

Wow! Am I glad you took up my challenge two years ago. Your post above regarding Fenbendazole and it's harm to humans (and pigeons) is a winner. You are an asset to this group (but not every two years). All I can say now, is that I appreciate squab every now and then with a glass of grappa....

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 09/01/2021 10:02 PM DST

[Callithrix in reply to j-o-h-n]

Thanks j-o-h-n, I always appreciate your humor and had to take a Grappa after plowing through the Italian website...

[Retiredstate]

Would not mebendazole be a better initial recommendation over Docetaxel?

[Callithrix in reply to Retiredstate]

see my long answer to Johnstats...

[Callithrix]

I have no problems with that as long as people are informed and understand what they are taking. It is conceivable that different tubulin blockers may be more effective when delivered in a combo but I leave such questions to oncologists.

[Retiredstate in reply to Callithrix]

Since I am still sensitive to Lupron and Erleada I think I will wait and see the results of the Veru 111 trial and see if combining it with Mebendazole can work without the doxetaxel side effects.

[Retiredstate]

I think you should send this information to Care Oncology...I think they would appreciate it and respond

[Callithrix in reply to Retiredstate]

Thanks, I'll try it

[nayan123xyz]

If your analisys is true then howJoe Tippens still not feeling any severe side effect till 2024 taking fenben for almost 8 years?

[Callithrix in reply to nayan123xyz]

The most likely explanation is that repeatedly swallowed fenbendazole (FBZ) is not entering the circulation system. In this case it cannot cause side-effects such as suppression of the immune system (myelosuppression) by killing stem cells or causing hair loss and retarded growth of nails. The molecular structure of fenbendazole is similar to other chemo drugs known as taxanes, such as docetaxel (one of the standard cancer treatments). The latter is applied by intravenous application weekly or 3-weekly to control myelosuppression and other systemic side-effects. Infusion is the preferred way of delivering because taxanes, including FBZ, dissolve poorly in the intestinal tract and have a so-called low bioavailability resulting in reduced and uncontrollable uptake by the cells resorbing nutrients. A study investigating oral application of docetaxel reported poor uptake and severe gastrointestinal toxicity (doi: 10.2147/CPAA.S292746).

The second reason why Joe Tippens does not suffer from severe side-effects after many years of FBZ consumption is likely drug resistance, one of the main problems in prolonged chemotherapy but also in treatment of parasites. In this case, the drug is either not resorbed any longer, or is inactivated upon entering body cells. Thus, one should know his blood levels of FBZ. If they are zero, the FBZ enters and leaves the body without causing harm but also without killing cancer cells.