Paternal Valproate Treatment and Risk of Childhood Neurodevelopmental Disorders: Precautionary Regulatory Measures Are Insufficiently Substantiated
... Abstract. On January 12, 2024 the safety committee of the European Medicines Agency (EMA) recommended precautionary measures over a potential risk of neurodevelopmental disorders in children born to men treated with valproate.
... In the United Kingdom, the Medicines and Healthcare products Regulatory Agency (MHRA) issued a far more stringent precaution, warning against prescribing valproate to anyone under 55 years of age.
Compare the warnings for the known teratogenic retinoic acid (Accutane.)
Must use two effective forms of contraception, etc. The difference is that Accutane generally only needs to be taken for a year or so. Valproate flavours are usually lifelong prescriptions, so have a much better profit potential.
In Canada most of our seizure patients were assessed and initiated on treatment by specialist neurologists so I don't remember initiating prescriptions. Similarly the bipolars were seen and started by psychiatrists and followed by GP's, but other than the rather dismissive warnings (Don't stop this, you may get worse, assess the risk of cessation, etc.) I don't recall a serious flag for pregnant or fertile women in four decades of practice.
Dear DoorlessCarp, how do butyrate / propionate compare to valproate on the positives (epilepsy) and negatives (teratogenicity etc.)? Do we have a typical Pharma issue that the natural variant is relatively safer but does not pay off in exclusivity to finance the studies?
I did a quick search, and someone has actually researched this. Pharma will not wish you to try something you can make yourself very cheaply. I make a batch every other week.
***
Benefits of multi-day supplementation with probiotic kefir in Rasmussen encephalitis: the first case report
... During the kefir supplementation, the patient presented only short-term absence seizures, quickly returning to activities. Additionally, he presented cognitive and language improvement, being more responsive to commands.
There is also this info on inducing synthesis of trans-9-elaidic acid in your article. As a trans fatty acid that potentially may disrupt anti-inflammatory PGE3 synthesis from omega-3 fatty acids. Quite some of the rest would follow.
Butyrate has a different mode of action, which is not teratogenic.
It's ironic that valproate also works against you by contributing to dysbiosis.
In theory, kefir intake should be associated with less seizures, and this area is being considered for a future review.
***
MicrobiotaâGutâBrain Axis and Epilepsy: A Review on Mechanisms and Potential Therapeutics
... Butyrate also ameliorates mitochondrial dysfunction and protects brain tissue from oxidative stress and neuronal apoptosis through the Keap/Nrf2/HO-1 pathway, thereby increasing seizure threshold and reducing seizure intensity (129). Propionate treatment may alleviate seizure intensity and prolong the incubation period of seizures by reducing mitochondrial damage, hippocampal apoptosis, and neurological deficits (128). These studies show that SCFAs are reduced in epilepsy models and their protective effect on epilepsy through different mechanisms.
There is never a lesson to be learned in the drug industry because profit comes before patient safety. The drug regulators are weak, greedy and lazy and are successfully managed by the pharmaceutical industry so we see the same type of mistakes repeated. I used to think the drug regulators were independent and there as a safety barrier to protect the population but they are enablers for the drug industry to achieve their ends with little punishment. I am suspicious of every medication now which I think should be the default position for all of us.
You dug deep, amazing work! Have you ever looked into the creators of the drug Prozac (used for psych reasons) ? The family that created it have the last name Solvay. This will blow your mind if you donât already know, but Iâm hoping you dig like you dug on the valproate sodium. Look into Solvay Chemical company as creating Prozac, also look up all of there fluoride mines, then look up a castle in Belgium that they own called mothers of darkness castle. Also look up the solvay conferenceâs, they changed science as we know it, you will find a young Einstein sitting at the first conference. Please if you have the time can you see what you can find in this rabbit hole? For some reason I think you will get further than I did.
Itâs dark, this particular family is very connected to the Belgium white march in the 90s, and also the UN. This kind of person/family has absolutely no business creating anything that is ingested by the masses who were/are falsely diagnosed with what ever name needed to get the desired outcome!!!!! I wonât say anymore other than this one is a game changer!!
DoorlessCarp, your in-depth research beats out even the best peer-reviewed papers I've seen.
I will confess in the modern era I do not have the capacity to absorb all of it in one sitting.
I think there's an analogy to be drawn between drugs that have caused harms for decades, and the refusals to examine vaccines for same/similar harms. Peer review is absolutely crooked, and society seems to be bent on an immoral track these days.
I never got payments to recommend sod valproate, lol. Where are those pharmacists?
Weâd keep asking for blood levels if patients were on it coming to hospital. As for pregnant women, youâd be told the risk from seizures was worse than from the drug, you overzealous pharmacists whoâs keeping my patients from getting treated.
yeah, not many choices I agree. Especially before Keppra and Lamictal were available (I remember those days). Phenytoin was likely a bit safer, carbamezepine etc. The real risk is using valproic acid in females who have bipolar disease.
Paternal Valproate Treatment and Risk of Childhood Neurodevelopmental Disorders: Precautionary Regulatory Measures Are Insufficiently Substantiated
... Abstract. On January 12, 2024 the safety committee of the European Medicines Agency (EMA) recommended precautionary measures over a potential risk of neurodevelopmental disorders in children born to men treated with valproate.
... In the United Kingdom, the Medicines and Healthcare products Regulatory Agency (MHRA) issued a far more stringent precaution, warning against prescribing valproate to anyone under 55 years of age.
https://pubmed.ncbi.nlm.nih.gov/39189597/
Generational effects of valproate. A 53% chance of your offspring being affected if you were valproate exposed.
Transgenerational adverse effects of valproate? A patient report from 90 affected families
Marine Martin et al. Birth Defects Res. 2022.
https://pubmed.ncbi.nlm.nih.gov/34866359/
Compare the warnings for the known teratogenic retinoic acid (Accutane.)
Must use two effective forms of contraception, etc. The difference is that Accutane generally only needs to be taken for a year or so. Valproate flavours are usually lifelong prescriptions, so have a much better profit potential.
In Canada most of our seizure patients were assessed and initiated on treatment by specialist neurologists so I don't remember initiating prescriptions. Similarly the bipolars were seen and started by psychiatrists and followed by GP's, but other than the rather dismissive warnings (Don't stop this, you may get worse, assess the risk of cessation, etc.) I don't recall a serious flag for pregnant or fertile women in four decades of practice.
Thank you for your insights. The more that comes out, the worse it looks.
Dear DoorlessCarp, how do butyrate / propionate compare to valproate on the positives (epilepsy) and negatives (teratogenicity etc.)? Do we have a typical Pharma issue that the natural variant is relatively safer but does not pay off in exclusivity to finance the studies?
I did a quick search, and someone has actually researched this. Pharma will not wish you to try something you can make yourself very cheaply. I make a batch every other week.
***
Benefits of multi-day supplementation with probiotic kefir in Rasmussen encephalitis: the first case report
... During the kefir supplementation, the patient presented only short-term absence seizures, quickly returning to activities. Additionally, he presented cognitive and language improvement, being more responsive to commands.
https://www.tandfonline.com/doi/pdf/10.1080/1028415X.2021.1970299
There is also this info on inducing synthesis of trans-9-elaidic acid in your article. As a trans fatty acid that potentially may disrupt anti-inflammatory PGE3 synthesis from omega-3 fatty acids. Quite some of the rest would follow.
Butyrate has a different mode of action, which is not teratogenic.
It's ironic that valproate also works against you by contributing to dysbiosis.
In theory, kefir intake should be associated with less seizures, and this area is being considered for a future review.
***
MicrobiotaâGutâBrain Axis and Epilepsy: A Review on Mechanisms and Potential Therapeutics
... Butyrate also ameliorates mitochondrial dysfunction and protects brain tissue from oxidative stress and neuronal apoptosis through the Keap/Nrf2/HO-1 pathway, thereby increasing seizure threshold and reducing seizure intensity (129). Propionate treatment may alleviate seizure intensity and prolong the incubation period of seizures by reducing mitochondrial damage, hippocampal apoptosis, and neurological deficits (128). These studies show that SCFAs are reduced in epilepsy models and their protective effect on epilepsy through different mechanisms.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.742449/full
https://www.nature.com/articles/s41380-024-02732-0
Valproic acid-induced teratogenicity is driven by senescence and prevented by Rapamycin in human spinal cord and animal models
Just saw the nature article 10 mins ago and then saw your post.
Thanks. So we have MTOR signalling:
... The VPA-mediated mTOR signaling pathway may enhance reprogramming efficiency and neuronal differentiation.
https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2019.00867/full
All I can say is âwow!!â
The same old con game over and over. . . Killing and maiming living creatures
There is never a lesson to be learned in the drug industry because profit comes before patient safety. The drug regulators are weak, greedy and lazy and are successfully managed by the pharmaceutical industry so we see the same type of mistakes repeated. I used to think the drug regulators were independent and there as a safety barrier to protect the population but they are enablers for the drug industry to achieve their ends with little punishment. I am suspicious of every medication now which I think should be the default position for all of us.
You dug deep, amazing work! Have you ever looked into the creators of the drug Prozac (used for psych reasons) ? The family that created it have the last name Solvay. This will blow your mind if you donât already know, but Iâm hoping you dig like you dug on the valproate sodium. Look into Solvay Chemical company as creating Prozac, also look up all of there fluoride mines, then look up a castle in Belgium that they own called mothers of darkness castle. Also look up the solvay conferenceâs, they changed science as we know it, you will find a young Einstein sitting at the first conference. Please if you have the time can you see what you can find in this rabbit hole? For some reason I think you will get further than I did.
Prozac. An SSRI that doesn't work. Is hard to withdraw from and can lead to worse depression, suicidal and homicidal tendencies.
Thanks, no I hadn't looked into it's history but I can add it to the list đ
Itâs dark, this particular family is very connected to the Belgium white march in the 90s, and also the UN. This kind of person/family has absolutely no business creating anything that is ingested by the masses who were/are falsely diagnosed with what ever name needed to get the desired outcome!!!!! I wonât say anymore other than this one is a game changer!!
DoorlessCarp, your in-depth research beats out even the best peer-reviewed papers I've seen.
I will confess in the modern era I do not have the capacity to absorb all of it in one sitting.
I think there's an analogy to be drawn between drugs that have caused harms for decades, and the refusals to examine vaccines for same/similar harms. Peer review is absolutely crooked, and society seems to be bent on an immoral track these days.
Thanks UD. I think it's like holding the tigers' tail with some of these cash cow legacy drugs. They cannot let go for fear of being eaten alive.
I never got payments to recommend sod valproate, lol. Where are those pharmacists?
Weâd keep asking for blood levels if patients were on it coming to hospital. As for pregnant women, youâd be told the risk from seizures was worse than from the drug, you overzealous pharmacists whoâs keeping my patients from getting treated.
Yes. I hated using valproate, because of the necessity to monitor serum levels and blood chemistries, and because of the side-effects.
TBH though, there was a time when there were not that many options. Phenobarbital, which drops IQ points mg by mg? Dilantin (not ideal)?
However, I've used it rarely in recent years. There are generally less toxic options.
Edited to add: I never used in children. Adults can listen to a risk:benefit discussion and make their own choices.
yeah, not many choices I agree. Especially before Keppra and Lamictal were available (I remember those days). Phenytoin was likely a bit safer, carbamezepine etc. The real risk is using valproic acid in females who have bipolar disease.
Cost and medicaid coverage had a lot to do with the continuance of widespread use.
Very true.
Amazing work. Thank you. The video was excellent - we must continue to call out lying pieces of shit. Peace.