Ivermectin and infertility - it is the combination with a Pgp inhibitor that creates risk, [Take two]
More detail on how Ivermectin might be risky to fertility - and gene integrity of sperm.
A commenter didn’t like the lack of supporting research in my last post, about the infertility claim for Ivermectin - you needed to watch the video or read the Substack by Tim Truth for the full story as these articles are paywalled, but I learned more. The risk of Ivermectin seems to be most specific to use along with quercetin or EGCG/green tea/pom peel in significant amounts. The FLCCC protocol does use both Ivermectin and quercetin and does mention to not take them simultaneously - stagger them over a few hours. That seems a little haphazard to me but … I don’t know.
Fertility changes have been observed with use of Ivermectin in human and animal research
Evidence from animal-based research suggests it is the combined risk of Ivermectin with Pgp inhibitors which may cause more negative effects on sperm. Ivermectin is described as a substrate for Pgp - it is a large enough molecule that it will not pass through to the brain to cause damage unless it has the transport help from the Permeability-glycoprotein. Only mild changes were seen in male fertility when only Ivermectin was given. When it was given with verapamil, a Pgp inhibitor, the negative impacts on sperm production were much more significant - causing: “increased frequency of meiotic structural chromosomal aberrations and increased X–Y chromosomal dissociation,” which suggests the mature sperm would then have genetic errors introduced during the sex cell division/meiosis. Dosing was once weekly for eight weeks. (El-Nahas, El-Ashmawy, 2008)
“Administration of permeability-glycoprotein (Pgp) inhibitors can modify the pharmacological properties or induce toxic effects of Pgp substrates.” (El-Nahas, El-Ashmawy, 2008)
Ivermectin is a Pgp substrate and verapamil is a Pgp inhibitor. The combination given to lab animals once weekly for eight weeks led to changes in how genes were divided during meiosis - sex cell division leaves have of the genes - only one copy of each. Errors in the gene division can cause spontaneous abortion (miscarriages) of a fetus or a fetus with mental or physical differences.
“The chromosome abnormalities associated with infertility are of two types. Karyotype alterations affecting cells of both somatic and germ cell lines and mitotic abnormalities. Both types can produce infertility either by spermatogenesis arrest or formation of chromosomally unbalanced gametes leading to spontaneous abortion and/or offspring with mental deficiency and malformations (Navarro et al., 1987). It is also reported that these abnormal gametes are produced as a result of altered intra-testicular environment that affect negatively the mechanisms controlling chromosome segregation during cell division (De Palma et al., 2005). Many authors recorded the undesirable effects of ivermectin on fertility (Tanyildizi and Bozkurt, 2002, Schroder et al., 1986).” (El-Nahas, El-Ashmawy, 2008)
“These findings indicate that ivermectin increases hyaluronidase activity of serum and semen in sheep, but it decreases sperm motility and concentrations. In conclusion, the use of ivermectin is not suitable during ramming season and in rams used for breeding due to the deleterious effects on fertility.” (Tanyildizi and Bozkurt, 2002) n=18 sheep *This study used only the Ivermectin, not a Pgp inhibitor too.
Another study with El-Ashmawy on the team also found that the combination of Ivermectin with verapamil led to much worse effects during pregnancy. Ivermectin is safe because the Pgp recognizes it as a substance to keep out - but it will be let in when used in combination with a Pgp inhibitor like verapamil in these examples, but like quercetin or ellagic acid potentially in a CoV protocol.
“Pgp (the product of mdr1a gene) was demonstrated in biologically important protective barriers, blood–brain barrier, blood testis barrier, maternal fetal barrier and intestinal barrier (Croop et al., 1989, Schurr et al., 1989, Schinkel et al., 1994). One major physiological role of drug-transporting Pgps is the protection of an organism against potentially toxic compounds that can be encountered in the environment by limiting the passage of drugs and compounds into the fetus (Smit et al., 1999). Placental Pgp can be partially or completely blocked by administration of Pgp inhibitors resulting in greatly increased transplacental passage to the embryo. Furthermore, placental Pgp tends to increase during pregnancy (Croop et al., 1989). Effectively, progesterone is a potent inhibitor of Pgp activity and its level increase with pregnancy age. Thus Pgp activity is probably strongly down modulated in mature placentas.” (El-Ashmawy, et al., 2011)
Treatment with Ivermectin caused a slight reduction in size of the testis, epididymis and accessory sex glands while the combined treatment with verapamil led to a greater reduction in size.
“The weights of testis, epididymis and accessory sex glands were slightly decreased (P 0.05) in ivermectin-treated group versus control, while the decrease in weights of these organs was more in rats treated with ivermectin plus verapamil.” (El-Nahas, El-Ashmawy, 2008)
More about Pgp, bullet points & Canine Caution: added by me:
“The low ivermectin toxicity has been attributed to its restricted access to some organs and brain tissues, especially for being a substrate of Pgp (Schinkel et al., 1994). Pgp is a member of ATP-binding cassette superfamily of transmembrane transporters and mediates the membrane transport of many hydrophobic compounds, including hormones, sterols, lipids, phospholipids, cytokines, and anticancer drugs (Bellamy, 1996). Pgp is located in many tissues and in the capillary endothelial cells of the testis and blood–brain barrier (Cordon-Cardo et al., 1990), where it functions as an efflux transporter of xenobiotics (Chen et al., 2004, Lin, 2003).
Interactions with substances that inhibit Pgp are of great interest, as they can potentially enhance the absorption of important medicines that are generally poorly absorbed, such as chemotherapeutic medicines.
Alternately, Pgp inhibition may theoretically increase the incidence of side effects or toxicity of some medicines, producing unwanted effects.
Many compounds are known to modulate the Pgp by reducing the efflux activity of the pump, e.g. verapamil, cyclosporine A, erythromycin and their analogs (Ford and Hait, 1990).
Therefore, the modulation of Pgp function by Pgp inhibitors, such as verapamil, can be an important factor in modifying the pharmacological actions of certain drugs.
Canine Caution: In spite of the approval for use of ivermectin in all dogs. It can, however, cause neurotoxicity at very low doses to genetically sensitive canine breeds collies. Increased ivermectin levels in the brains of sensitive collies appear to be due to ineffective brain-to-blood efflux caused by Pgp transporter (Dowling, 2006). (El-Nahas, El-Ashmawy, 2008)
And more about Pgp
“Pgp substrates are usually organic molecules ranging in size from 200 Da to almost 1900 Da. Most of them are uncharged or weekly basic in nature, but some acidic compounds can also be transported (Schinkel and Jonker, 2003). Drugs and xenobiotics that bear significant structural similarity to the physiological substrates have the potential to be recognized by the transporters expressed in the placenta (Ganapathy et al., 2000). Fetal tolerance to a certain level of maternal exposure to poor Pgp substrates will be lower than for equivalent amounts of drugs that are good Pgp substrates (Smit et al., 1999). Ivermectin (Pgp substrates), an acaricide and anthelmentic drug of the family avermectins, produced by Streptomyces avermitilis cultures, is a well tolerated drug and except for some genetically-modified animals (collie dog), no side effects in mammals at pharmacological doses were detected (Fisher and Mrozik, 1992, Mealey et al., 2001). The low ivermectin toxicity has been attributed to its restricted access to some organs and brain tissues, especially for being a substrate of Pgp (Schinkel et al., 1994).” (El-Ashmawy, et al., 2011)
It appears that the risk from Ivermectin would be fairly low unless taken along with a Pgp inhibitor - and that might happen following some of the current popular CoV protocols.
FLCCC responds to this concern with the caution to stagger the timing of ingesting Ivermectin (taken once a day) and quercetin (taken twice a day) over the course of the day - as if taking them hours apart is adequate to protect against Ivermectin passing through membrane barriers. I don’t really know if taking them hours apart is long enough to protect sperm development or a developing fetus or a person’s brain. (covid19criticalcare.com/protocol/i-care-early-covid-treatment/)
. . . The sheep veterinarian would recommend not taking that during ramming season. (Tanyildizi and Bozkurt, 2002) This isn’t just how well a sperm wiggles (motility) and if it can go forward instead of spinning in circles, this is also about the genes that it would be creating a new human from - are those genes damaged? Aberrant?
“Quercetin (or a mixed flavonoid supplement): 250-500 mg twice a day.
Due to a possible interaction between quercetin and ivermectin, these drugs should not be taken simultaneously (i.e., should be staggered at different times of day.) As supplemental quercetin has poor solubility and low oral absorption, lecithin-based and nanoparticle formulations are preferred.” (covid19criticalcare.com/protocol/i-care-early-covid-treatment/)
The post I had linked to on this topic was inflammatory in tone - sensationalized, however, there does seem to be reasonable concern here. The chimeric spike can affect miscarriage rate and fertility in many ways too.
I have certainly learned that I would recommend against using Ivermectin along with pomegranate peel - use one or the other, not both “simultaneously” - which to me would seem to be during the same day. The half-life of pomegranate peel’s effectiveness seems to be half a day, not just a few hours.
Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.
Reference List
(El-Ashmawy, et al., 2011) Ibrahim M. El-Ashmawy, Abeer F. El-Nahas, Aida E. Bayad, Teratogenic and cytogenetic effects of ivermectin and its interaction with P-glycoprotein inhibitor, Research in Veterinary Science, 2011, 90(1);116-123, ISSN 0034-5288, https://doi.org/10.1016/j.rvsc.2010.05.020. https://www.sciencedirect.com/science/article/pii/S003452881000189X
(El-Nahas, El-Ashmawy, 2008) El-Nahas AF, El-Ashmawy IM. Effect of ivermectin on male fertility and its interaction with P-glycoprotein inhibitor (verapamil) in rats. Environ Toxicol Pharmacol. 2008 Sep;26(2):206-11. doi: 10.1016/j.etap.2008.03.011. Epub 2008 Mar 29. PMID: 21783912. https://pubmed.ncbi.nlm.nih.gov/21783912/. *per the AI - but the article is paywalled and I didn’t see this in the abstract: The study also found that intraperitoneally injected ivermectin can induce the formation of aberrant bone marrow cells, and cause cytogenic side effects including chromatin fragmentation and apoptotic cell death. (El-Nahas, El-Ashmawy, 2008)
This study is not pertinent to the question of human fertility as it is about causing infertility in the mosquito that bites a man treated with Ivermectin - like a bug spray that isn’t about preventing mosquito bites but instead is about passing along an insecticide - like turning a human into an ant-trap baited with poison:
(Mekuriaw, et al., 2019) Mekuriaw W, Balkew M, Messenger LA, Yewhalaw D, Woyessa A, Massebo F. The effect of ivermectin® on fertility, fecundity and mortality of Anopheles arabiensis fed on treated men in Ethiopia. Malar J. 2019 Nov 8;18(1):357. doi: 10.1186/s12936-019-2988-3. PMID: 31703736; PMCID: PMC6842263. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842263/ .
A single oral dose of ivermectin given to humans can induce mortality and reduce survivorship of Anopheles arabiensis for 7 days after treatment. Additionally, a delayed effect on fecundity of An. arabiensis was observed when the mosquitoes took blood meals from treated individuals on day 7 and 10 after ivermectin administration. (Mekuriaw, et al., 2019)
I didn’t look at the debunking articles.
There is no question in my mind that chronic Ivermectin use... everyday for weeks and weeks, will stop sperm production. It is reversible, but it is real....
Having said that, there is no medical reason to be taking it everyday, day after day for weeks and weeks for any condition.
If this is of genuine concern, I wonder why the pharma cartel didn't use it against it in their war against ivermectin instead of silly things like "horse dewormer," etc.