Yes, in the European countries Mebendazole can be found on the supermarket shelves.
Mebendazole is an anthelmintic drug that has been used since the early 1970s to treat a range of parasitical worm infections, including threadworm, tapeworms, roundworms, and other nematode and trematode infections in humans and domestic animals (Ref.). The drug is among those on the World Health Organization’s list (WHO) (Ref.).
Mebendazole became and remained one of my preferred drugs since I learned about it at the beginning of 2014. This was mainly due to the multiple strong points that are defining Mebendazole. Those strong points are:
- it has high potential for serious effectiveness against cancer supported by both
- it has nearly no side effects, and due to this reason
- it is an over the counter drug in most of the countries, which means there is no need for a doctor prescription
- and on top of all, it is a very cheap drug
- available virtually anywhere and everywhere.
The first website where I came across Mebendazole discussion was, I think, this one: http://www.abovetopsecret.com/forum/thread822776/pg1 I was happy to see in 2014, just a few months latter after I studied Mebendazole intensively and became convinced about its anti cancer relevance, a paper has come out from one of my favorite Anti Cancer Foundation, i.e. Anticancer Fund, consolidating a good amount of research and proposing Mebendazole as a re-purposed drug against cancer. Here is that nice paper published in 2014: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096024/ By that time, we were already using it.
Before and after the publication of the above paper by Anticancer Fund, there were multiple relevant scientific papers published around Mebendazole and multiple discussions, triggering me to start writing about Mebendazole. Interestingly and amazingly, in 2016, a drug company has decided to charge 200x higher price for Mebendazole (thanks to Helga, a reader of this website I learned about this) (Ref.). Fortunately, it seems that in the US there is still available a powder form that is cheap. Alternatively, it can anyway be ordered online as discussed below in the “Source” section. This was another point when I wanted to write about Mebendazole. Today, finally, I succeeded to write this post, triggered again by another publication coming from US Oncology center and School of Medicine, suggesting the re-purposing of Mebendazole as a replacement for Vincristine chemotherapy for the treatment of Brain tumors (Ref.).
Credit photo: https://valelab.ucsf.edu/research/microtubules/
While many of the constant readers of this website already know Mebendazole, I hope the article will help the awareness of new readers.
Indeed, Mebendazole, alone or combined with chemo, has been shown to be effective against multiple forms of cancer cells, such as:
- adrenal cancer (Ref.1, Ref.2)
- colon cancer (Ref.1, Ref.2)
- brain cancer, medulloblastoma, glioblastoma (Ref.1, Ref.2, Ref.3, Ref.4)
- melanoma (Ref.1, Ref.2, Ref.3)
- head and neck squamous cell carcinoma (HNSCC) (Ref.)
- cholangiocarcinoma or bile duct cancer (Ref.)
- gastric cancer (Ref.)
- breast cancer (Ref.)
- lung cancer (Ref.1, Ref.2)
- ovarian (Ref.)
- leukemia (Ref.)
- pancreatic cancer (Ref.)
A study, showed a high level of activity against leukaemia, colon cancer, CNS and melanoma cell lines, with lesser activity in breast, ovarian, renal and NSCLC lines (Ref.).
Based on all the research available, I would expected the highest chance of effectiveness of Mebendazole, against
- adrenal cancer,
- colon and colo-rectal cancer,
- brain cancer,
- melanoma and
- pancreatic cancer and
- lung cancer
However, given the low cost, limited to now side effects, its availability and potential, I would still try it for the other cancer types (next to other treatments), specifically for the aggressive cancer types. Based on the above results, the other potentially responsive tumor types seem to be those of
- bile duct,
Note: other anthelmintic drugs have also been shown to present strong anti cancer effects, but their main anti cancer mechanisms may be different. Of the anthelmintic category, Albendazole is one of my other favorites due to its unique anti cancer mechanism (to be discussed elsewhere) but that comes with some liver toxicity. Albendazole has been indicated to be effective against, e.g. ovarian cancer (Ref.). Here is a study suggesting that of the existing repurposed drugs, antiparazite medication is one of the most effective group of drugs against cancer, after typical anti neoplastic drugs (Ref.).
The ever growing evidence that anti parasitic medication is effective against cancers may also trigger medical doctors and researchers look at cancer from other perspectives, e.g. cancer as a parasitic disease, a perspective which so far has been only discussed outside the mainstream medicine. Here is an example that consolidated such a perspective http://jeffreydachmd.com/2016/05/cancer-as-a-parasitic-disease/ I think, successful researchers have to always keep their mind open, ready to consider new perspectives proposed by others and even better connect the available “dots” to generate new perspectives.
As we will discuss further, the only drawback with Mebendazole is that due to its absorption which can be different in different patients, the results may vary from patient to patient.
According to recent research, Mebendazole may inhibit Multi Drug Resistence (MDR) transporters (Ref.). These are the transporters used by cancer cells to push out chemotherapies in order to survive during chemo treatments. Therefore, using Mebendazole during chemo treatments may lead to increase effectiveness of the conventional therapies.
Case Reports in Humans:
Besides all the studies in the lab indicating the effectiveness of Mebendazole against various cancer types, below are two published scientific case reports that are clear and coming from trust-able sources. In both cases, Mebendazole has been applied after the patients were not responding anymore to conventional therapies. The medical doctors have decided to use Mebendazole following scientific results from various research groups suggesting Mebendazole may be effective for those cancer types. This indeed, was the case. The results were extremely promising:
A 48-year-old man with adrenocortical carcinoma had disease progression with systemic therapies including mitotane, 5-fluorouracil, streptozotocin, bevacizumab, and external beam radiation therapy. Treatment with all chemotherapeutic drugs was ceased, and he was prescribed mebendazole, 100 mg twice daily, as a single agent. His metastases initially regressed and subsequently remained stable. While receiving mebendazole as a sole treatment for 19 months, his disease remained stable. He did not experience any clinically significant adverse effects, and his quality of life was satisfactory. His disease subsequently progressed after 24 months of mebendazole monotherapy.
My comments: as discussed in the article, the patient received only 200mg Mebendazole each day. That to me is the lowest daily dose and according to multiple sources the dose could be further increased with no issues. In addition, Mebendazole is known to be poorly absorbed in the body and there are ways to increase its absorption. All these will be further discussed in the “Dose and Application” section below, but the point is that while the medical doctors authors of this article have my highest regards, in the future higher dose can be used to try increase Mebendazole effectiveness.
Drug repositioning from bench to bedside: tumour remission by the antihelmintic drug mebendazole in refractory metastatic colon cancer. https://www.ncbi.nlm.nih.gov/pubmed/24160353
Here is a PDF version available.
A patient with refractory metastatic colon cancer was treated with MBZ at the standard anthelmintic dose of 100 mg twice daily. The patient experienced no subjective adverse effects at all from the drug and computerized tomography evaluation after six weeks of therapy showed near complete remission of the metastases in the lungs and lymph nodes and a good partial remission in the liver. At this stage, the liver enzymes AST and ALT were found elevated up to five and seven times above upper limit of normal and mebendazole was temporarily stopped and then reintroduced at half dose. Liver enzymes slowly decreased and the patient still reported no adverse effects from mebendazole. The disease was stable at a new CT, confirming the response observed earlier.
My comments: Since Mebendazole is not associated with hepatic dysfunction (Ref.) and since the daily dose used here is on the very low side, I suspect the elevation of AST and ALT was due to the tumor lysis.
The primary anti cancer mechanism is related to the depolymerization of tubulin in human tumor cells caused by Mebendazole, inhibiting mitotic spindle formation, and therefore inducing mitotic arrest and apoptosis. This is a mechanism similar to that one I already described in details in the post on Griseofulvin: http://www.cancertreatmentsresearch.com/decide/ so I will not discuss again, here, the details of the mechanism.
Indeed, Mebendazole has been shown to cause mitotic arrest in parasitic cells as early as 197o’s (e.g. Ref.). As a reference for the reader, at some level, Mebendazole acts similar to microtubule dynamic inhibiting chemotheraphies such as microtubule-stabilizing (e.g., paclitaxel, docetaxel) or microtubule-destabilizing (e.g., vinblastine, vincristine, nocodazole, colchicine) agents (Ref.)
Mebendazole has been found to work against tumors via other mechanisms as well:
- angiogenesis inhibition (Ref.) MBZ may inhibit the action of VEGFR-2 by binding to it (Ref.)
- inactivates Bcl-2 and activates caspases to promote apoptosis in cancer cells, and the release of cytochrome c, which has also been shown to trigger apoptosis in malignant cells (Ref.). Here is how Bcl-2 fits into the picture (Ref.).
- hedgehog inhibitor (Hh) (Ref.) Here is how hedgehog fits into the picture (Ref.). The hedgehog (Hh) signaling pathway is activated in many types of cancer and therefore presents an attractive target for new anticancer agents. Hedgehog ligands or markers of downstream pathway activity have been detected in melanomas, lung cancers, ovarian cancers, adrenocortical cancers and colorectal cancers (Ref.), which are all responsive to Mebendazole, as discussed above. Interestingly, among other Hedgehog inhibitors that have previously identified are also drugs that interact with microtubules, including vinblastine, vincristine, and paclitaxel (Ref.). Itraconazole, that I previously discussed in a different post is also a hedgehog inhibitor: http://www.cancertreatmentsresearch.com/itraconazole/ So there may be a connection between hedgehog inhibition and microtubule dynamics inhibition.
- based on the fact that ultra low dose microtubule inhibiting chemotherapy is known to activate the immune system, (http://www.cancertreatmentsresearch.com/ultra-low-dose-taxol/) it has been proposed that Mebendazole could do the same (Ref.)
Interestingly, Mebendazole is not toxic against normal cells. Researchers speculated a defect in at least one mitotic checkpoint function in tumor cells leading to their higher sensitivity to Mebendazole (Ref.).
In general, the drug is well tolerated but some people may present adverse effects and may have to discontinue. Here is the product description https://www.janssen.com/canada/sites/www_janssen_com_canada/files/product/pdf/ver11192014cpm.pdf
At high dose, it has been found to possibly induce bone marrow suppression in patients chronic liver disease (Ref.) That reverted to normal after the drug was stopped. There are rare reports of reversible alopecia, urticaria, rash, gastro-intestinal upset, leukopenia, and neutropenia in some patients treated with high-dose MBZ (Ref.)
MBZ is contraindicated during pregnancy, due to its potential anti-angiogenesis properties.
In the event of accidental overdose, abdominal cramps, nausea, vomiting and diarrhea may occur (Ref.).
Dose and Administration:
One of the challenge with Mebendazole administrations is its low bioavailability which leads to only 20% absorption. The mebendazole plasma concentration-time profiles differed considerably between patients receiving 10 mg/kg Mebendazole; elimination half-lives ranged from 2.8-9.0 h, time to peak plasma concentration after dosing ranged from 1.5-7.25 h and peak plasma concentrations ranged from 17.5 to 500 ng/ml. (Ref.) Such doses are indeed in the plasma level reported to achieve anti cancer effects in the lab. Hoewever, as it can be seen the distribution of plasma level is wide so not everyone will reach high plasma level of Mebendazole.
Therefore, to address the challenge related to reaching a high level of mebendazole plasma level, which on one hand is due to the bad absorption and on the other hand due to a strong first pass metabolism in the liver, the following actions can be taken:
- administer with a fatty meal (Ref.)
- long term administration (Ref.)
- increased dose may increase the absorption (Ref.)
- given with Cimetidine (another of my preferred anti cancer drugs) (Ref.) will reduce its metabolism in the liver. Cimetidine can be found as an over the counter drug on eBay but should be used with care when combined with chemo as it will increase the plasma level of some of the chemos.
The low bioavailability is also probably why its side effects are very limited. Mebendazole is rapidly metabolized to less toxic metabolites by the liver, and this could be another reason for its low toxicity (Ref.). Increasing the plasma level with the strategy mentioned above, may also bring some side effects, so have an eye on that.
According to the literature, some people may absorb better Mebendazole compared to other, that may also lead to different effectiveness of Mebendazole in different people.
In the two successful case reports referenced above, the patients have used the minimum dose typically used against worms, i.e. 100mg 2x/day.
This, to my opinion is on the low side of the dose but could be the starting dose. A high dose, but still feasible, according to a World Health Organisation reference (Ref.) cited by the Anticancer Fund (Ref.), could be up to of 40–50 mg/kg/day for at least 3–6 months. This seems to be the long-term treatment of cystic echinococcosis. Another reference in terms of max dose still feasible is that used for alveolar echinococcosis, where 40–50 mg/kg/day is used with treatment for at least two years, and possibly longer for patients with inoperable disease (Ref.).
Based on the above, a person of 50kg could use up to 2.5g Mebendazole for months to years. Actually, this website pointed out a discussion on Inspire website where a caregiver said a brain cancer patient accessing a clinical trial at John Hopkins Hospital was “taking 2500mg in the morning, 3000 mg in the afternoon & evening.” (Ref.) That is really a huge dose.
Indeed, there was a clinical trial at John Hopkins Hospital, involving Mebendazole for Brain cancer gave it at 3x500mg/day with meals, on a 28 day cycle (Ref.). I haven’t found yet the results reported.
Following the above discussions, I would take the daily dose split into two, during or just after breakfast and dinner, if possible together with Cimetidine 400mg 2x/day. I would always start with a low dose Mebendazole and go up step by step to the target dose. If the target dose is very high, I would split that in 3x/day. Also, please note that in the clinical trail they did not used Cimetidine. And since Cimetidine may very much increase the plasma level of Mebendazole (some say by 50%), in case we use that I would make sure the target dose is lower than what was used at John Hopkins Hospital.
Janssen Pharma product descriptions states the following regarding the dose: “In controlled safety studies, humans have received from 100 to 1200 mg of mebendazole daily for up to 14 days with no reported side effects.” (Ref.)
The brand name is Vermox, Benda, etc. sold as a solution or tablet. I prefer the tablet version. Those tablets come in 100mg or 500mg version. I prefer the 500mg version and cut them in pieces if lower dose is required.
Mebendazole is available at many pharmacies in many countries, online and over the counter. Here is an example of a version that is available over the counter at a super market in the Netherlands: https://www.kruidvat.nl/kruidvat-anti-worm-mebendazol-100mg-tabletten/p/1023933 . In this case 6x100mg tablets costs 3 euro.
Another option is to buy from eBay or from sites like this one: http://smartproduct4u.com/?ref=285 many of which are coming from Thailand.
Finally, if there is no other option or would like to go the low cost version, we can buy it from China, via Alibaba, at a cost of about 200 euro/kg if I remember correctly. But that is powder version. Btw, just think about this: 200 euro for 1000g in China vs. about 800.000 euro for 1000g in USA, after the price increase initiated by a US drug company last year. Imagine the gross profit on this one. How can, we, the society accept something like this???
Other clinics recommending Mebendazole:
Care Oncology Clinic in London, UK: http://careoncologyclinic.com/ They usually seem to give to their patients a combination of drugs including Sratin + Metformin + Doxycycline + Mebendazole. Here is an article explaining in details the price, activity and vision of this clinic http://www.telegraph.co.uk/wellbeing/health-advice/crowdfunding-cure-cancer/
Mebendazole monotherapy and long-term disease control in metastatic adrenocortical carcinoma https://www.ncbi.nlm.nih.gov/pubmed/21454232
Repurposing Drugs in Oncology (ReDO)—mebendazole as an anti-cancer agent https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096024/
Mebendazole, a well-known anti-helminthic drug in wide clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical studies across a number of different cancer types. Significantly, there are also two case reports of anti-cancer activity in humans. The data are summarised and discussed in relation to suggested mechanisms of action. Based on the evidence presented, it is proposed that mebendazole would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of mebendazole as an anti-cancer therapeutic is warranted. A number of possible combinations with other drugs are discussed in the Appendix.
Repositioning of the anthelmintic drug mebendazole for the treatment for colon cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825534/
Sixty-eight compounds were defined as hits with activity in both of these cell lines (<40 % cell survival compared with control) at 10 μM drug concentration. Analysis of chemical similarity of the hit compounds revealed several distinct clusters, among them the antiparasitic benzimidazole group. Two of these compounds, mebendazole (MBZ) and albendazole (ABZ) are registered for human use. Data from the NCI 60 cell line panel revealed only modest correlation between MBZ and ABZ, indicating differences in mechanism of action. This was further supported when gene expression signatures were compared in the CMAP database; ABZ ranked very low when MBZ was used as the query signature. Furthermore, MBZ, but not ABZ, was found to significantly interact with several protein kinases including BCR–ABL and BRAF. Analysis of the diagnosis-specific activity of MBZ showed activity in 80 % of the colon cancer cell lines in the NCI 60 panel. Three additional colon cancer cell lines and three cell models with non-malignant phenotypes were subsequently tested, confirming selective colon cancer activity of MBZ. MBZ seemingly has repositioning potential for colorectal cancer therapy.
Repurposing the antihelmintic mebendazole as a hedgehog inhibitor https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297232/
The hedgehog (Hh) signaling pathway is activated in many types of cancer and therefore presents an attractive target for new anticancer agents. Here we show that mebendazole (MBZ), a benzamidazole with a long history of safe use against nematode infestations and hydatid disease, potently inhibited Hh signaling and slowed the growth of Hh-driven human medulloblastoma cells at clinically attainable concentrations. As an antiparasitic, MBZ avidly binds nematode tubulin and causes inhibition of intestinal microtubule synthesis. In human cells, MBZ suppressed the formation of the primary cilium, a microtubule-based organelle that functions as a signaling hub for Hh pathway activation. The inhibition of Hh signaling by MBZ was unaffected by mutants in the gene that encodes the Hh pathway signaling protein SMO, which are selectively propagated in cell clones that survive treatment with the Hh inhibitor vismodegib. Combination of vismodegib and MBZ resulted in additive Hh signaling inhibition. Because MBZ can be safely administered to adults and children at high doses over extended time periods, we propose that MBZ could be rapidly repurposed and clinically tested as a prospective therapeutic agent for many tumors that are dependent on Hh signaling.
Combination of Manumycin A and Mebendazole in Human Breast Cancer Cell Lines, a PhD thesis from 2010 https://uh-ir.tdl.org/uh-ir/bitstream/handle/10657/166/HADDADIN-.pdf?sequence=2
An article on Mebendazole, on a nice website of a breast cancer patient: https://magiccocktailquest.wordpress.com/2015/06/08/mebendazole/
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