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Rosmarinic acid improves hypertension and skeletal muscle glucose transport in angiotensin II-treated rats
"Rosmarinic acid administration can attenuate ANG II-induced cardiometabolic abnormalities in rats. Acute RA treatment lowered blood pressure and fasting plasma glucose levels. Extracellular signal-regulated kinase (ERK) activity may be involved in increasing skeletal muscle glucose transport activity. Chronic RA treatment can prevent high blood pressure and hyperglycemia in hypertensive rats. Therefore, RA may be an alternative strategy for increasing skeletal muscle glucose transport and protecting against ANG II-induced hypertension and hyperglycemia."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615279/
/Ling
"Rosmarinic acid administration can attenuate ANG II-induced cardiometabolic abnormalities in rats. Acute RA treatment lowered blood pressure and fasting plasma glucose levels. Extracellular signal-regulated kinase (ERK) activity may be involved in increasing skeletal muscle glucose transport activity. Chronic RA treatment can prevent high blood pressure and hyperglycemia in hypertensive rats. Therefore, RA may be an alternative strategy for increasing skeletal muscle glucose transport and protecting against ANG II-induced hypertension and hyperglycemia."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615279/
/Ling
Maia, I am told that Bumetanide is available in Austria, but you will need a prescription from a doctor (it can be a Polish doctor).
Our reader Agnieszka is a doctor in Gdansk. It is highly preferable to have a doctor helping you.
In Spain Bumetanide is called Fordiuran and if you ask nicely the pharmacy will sell it to you without a prescription.
It looks like many people buy online from Mexican pharmacies, where it is called Miccil.
Our reader Agnieszka is a doctor in Gdansk. It is highly preferable to have a doctor helping you.
In Spain Bumetanide is called Fordiuran and if you ask nicely the pharmacy will sell it to you without a prescription.
It looks like many people buy online from Mexican pharmacies, where it is called Miccil.
Hello,I'm new here. Thanks for the blog (it is brilliant!) I have a son (4 years old) with "aggressive" ASD. I just discovered the topic of bumetanid.Could you tell me how you deal with shopping? Where you buy IT? We live in Poland. It is not available here. I have already checked Germany and the Czech Republic but it is extremely hard (pharmacists- no one knows..)
Hi Ling, I am not sure; all I can say is that this ion channel looks relevant. A channel blocker would be simple to implement.
In TS it is a channel blocker that is helpful.
In TS it is a channel blocker that is helpful.
Peter, are you sure it is a channel opener I need?
I get the impression that TS mutations keep that channel open too long. Just saw this recent article on TS and SATB2, maybe I'm reading it wrong because I'm tired:
Aberrant calcium channel splicing drives defects in cortical differentiation in Timothy Syndrome
https://elifesciences.org/articles/51037
"Here we show that introducing TS-Cav1.2 calcium channels into mouse NPCs in utero reduces the fraction of SATB2-expressing cells
[..]
Our calcium imaging data, consistent with previous studies, confirms that the TS-Cav1.2 channels we introduced in utero result in sustained calcium elevations as compared to channels that do not express the TS mutation
[..]
our findings collectively reinforce the idea that elevated calcium is likely behind the changes we see in the relative abundance of CTIP2- and SATB2-expressing populations"
/Ling
I get the impression that TS mutations keep that channel open too long. Just saw this recent article on TS and SATB2, maybe I'm reading it wrong because I'm tired:
Aberrant calcium channel splicing drives defects in cortical differentiation in Timothy Syndrome
https://elifesciences.org/articles/51037
"Here we show that introducing TS-Cav1.2 calcium channels into mouse NPCs in utero reduces the fraction of SATB2-expressing cells
[..]
Our calcium imaging data, consistent with previous studies, confirms that the TS-Cav1.2 channels we introduced in utero result in sustained calcium elevations as compared to channels that do not express the TS mutation
[..]
our findings collectively reinforce the idea that elevated calcium is likely behind the changes we see in the relative abundance of CTIP2- and SATB2-expressing populations"
/Ling
Apologies Ling. I didn't realize that it was you who recommended the Fisetin! I will pair back on recommendations and do one thing at a time. Will see how things are in a few weeks. I am hoping at some stage this yer to trial Oxytocin Nasal Spray for sociability but that will not be for a while. Thank you also, Peter, for information on Potassium BHB. Sharon
Did someone already post this one? Mannitol is a sweetener.
Mannitol decreases neocortical epileptiform activity during early brain development via cotransport of chloride and water.
https://www.ncbi.nlm.nih.gov/pubmed/30711483
"We conclude that an increase in extracellular osmolarity by mannitol mediates the efflux of [Cl-]i and water through CCCs, which results in a decrease in epileptiform activity and enhances benzodiazepine actions in the developing neocortex in vitro"
/Ling
Mannitol decreases neocortical epileptiform activity during early brain development via cotransport of chloride and water.
https://www.ncbi.nlm.nih.gov/pubmed/30711483
"We conclude that an increase in extracellular osmolarity by mannitol mediates the efflux of [Cl-]i and water through CCCs, which results in a decrease in epileptiform activity and enhances benzodiazepine actions in the developing neocortex in vitro"
/Ling
Sharon, potassium BHB can be bought as a powder:
https://www.iherb.com/pr/Julian-Bakery-InstaKetones-Potassium-91-lbs-414-g/77539?rec=iherb-pdp-featured
or as a liquid (ketoForce). In the US both are easy to buy, but they are not cheap. Outside the US, KetoForce is hard to buy.
If someone has a genuine mitochondrial disorder or has a problem with glucose transport to the brain (as in Alzheimer's), then a trial of BHB is a good idea. Many BHB products are based on sodium or calcium. Potassium seems a better choice since many people with autism have calcium ion channel dysfunctions. Giving calcium to a child with autism can worsen their autism.
ALA is very similar to NAC and may produce the same result. ALA is as safe as NAC.
https://www.iherb.com/pr/Julian-Bakery-InstaKetones-Potassium-91-lbs-414-g/77539?rec=iherb-pdp-featured
or as a liquid (ketoForce). In the US both are easy to buy, but they are not cheap. Outside the US, KetoForce is hard to buy.
If someone has a genuine mitochondrial disorder or has a problem with glucose transport to the brain (as in Alzheimer's), then a trial of BHB is a good idea. Many BHB products are based on sodium or calcium. Potassium seems a better choice since many people with autism have calcium ion channel dysfunctions. Giving calcium to a child with autism can worsen their autism.
ALA is very similar to NAC and may produce the same result. ALA is as safe as NAC.
It's me recommending Fisetin, while Peter proposes NAC. They have somewhat different actions.
I asked one of the Fisetin researchers for dosing, and she suggested a daily dosage = weight in kg * 2-4 mg.
We use 50 mg for a 19 kg 4 year old with good results, but even at 25 mg we saw a change (this was on top of other interventions).
It sounds like you are doing a lot of changes at the same time; Guanfacine, Bumetanide and antioxidants. In my personal experience it's always better to try one thing at a time, with some time between. You get more confident with results this way, and don't mix them up with each other. I have regretted every time I did 2 changes at once.
/Ling
I asked one of the Fisetin researchers for dosing, and she suggested a daily dosage = weight in kg * 2-4 mg.
We use 50 mg for a 19 kg 4 year old with good results, but even at 25 mg we saw a change (this was on top of other interventions).
It sounds like you are doing a lot of changes at the same time; Guanfacine, Bumetanide and antioxidants. In my personal experience it's always better to try one thing at a time, with some time between. You get more confident with results this way, and don't mix them up with each other. I have regretted every time I did 2 changes at once.
/Ling
I just learned a bit on 'antioxidative stress' (not oxidative stress), and that high doses of antioxidants can have pro-aging and DNA damaging effects. There is also a bit more to learn on 'reductive stress', because it can drive oxidative stress.
Given that autism often shows up as opposite dysfunction, maybe we need to read up on this too?
"Recently, the term “antioxidative stress” has been introduced to describe the disruption of normal cell/tissue functions caused by an overabundance of AOs [antioxidants] in an organism. However, the number of experimental studies on this topic is quite limited. Among them, studies on the impact of dietary AOs show that antioxidative stress disturbs metabolic cues, regulating immune response of an organism and therefore promotes progression of various human diseases such as asthma, allergy, and obesity. Besides, it has been established that chronic antioxidative stress resulted from the constant overexpression of AO enzymes, as well as supplementation with some pharmacological AOs, such as N-acetyl-L-cysteine (NAC), induces the metabolic imbalance referred to as a “reductive stress”. The latter is defined as an abnormal increase in the level of reducing equivalents in the forms of NADH, NADPH, and GSH in the cell. Reductive stress has been shown to disturb cellular respiration metabolism and results in an increased mitochondrial oxidation and cytotoxicity. Furthermore, evidence has been provided that reductive stress precedes the development of some pathologies which are usually associated with elevated levels of ROS (cardiomyopathy, chronic hyperglycemia, neurodegeneration)"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361906/
Looks like reductive stress is happening before oxidative stress in Alzheimer's.
/Ling
Given that autism often shows up as opposite dysfunction, maybe we need to read up on this too?
"Recently, the term “antioxidative stress” has been introduced to describe the disruption of normal cell/tissue functions caused by an overabundance of AOs [antioxidants] in an organism. However, the number of experimental studies on this topic is quite limited. Among them, studies on the impact of dietary AOs show that antioxidative stress disturbs metabolic cues, regulating immune response of an organism and therefore promotes progression of various human diseases such as asthma, allergy, and obesity. Besides, it has been established that chronic antioxidative stress resulted from the constant overexpression of AO enzymes, as well as supplementation with some pharmacological AOs, such as N-acetyl-L-cysteine (NAC), induces the metabolic imbalance referred to as a “reductive stress”. The latter is defined as an abnormal increase in the level of reducing equivalents in the forms of NADH, NADPH, and GSH in the cell. Reductive stress has been shown to disturb cellular respiration metabolism and results in an increased mitochondrial oxidation and cytotoxicity. Furthermore, evidence has been provided that reductive stress precedes the development of some pathologies which are usually associated with elevated levels of ROS (cardiomyopathy, chronic hyperglycemia, neurodegeneration)"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361906/
Looks like reductive stress is happening before oxidative stress in Alzheimer's.
/Ling
Here is yet another, recent, article on the subject. It describes the effects of carnosic acid (found in rosemary and salvia) on both NRF2 and ATF4 and shows that simultaneous activation of these induces Nerve Growth Factor.
Concomitant Nrf2- and ATF4-activation by Carnosic Acid Cooperatively Induces Expression of Cytoprotective Genes.
https://www.ncbi.nlm.nih.gov/pubmed/30959808
It also briefly mentions other active substances here such as ISRIB, fisetin and royal jelly.
I'm pretty sure someone in the community previously posted about a synergistic blend of carnosic acid+something+something, but I can't find it.
/Ling
Concomitant Nrf2- and ATF4-activation by Carnosic Acid Cooperatively Induces Expression of Cytoprotective Genes.
https://www.ncbi.nlm.nih.gov/pubmed/30959808
It also briefly mentions other active substances here such as ISRIB, fisetin and royal jelly.
I'm pretty sure someone in the community previously posted about a synergistic blend of carnosic acid+something+something, but I can't find it.
/Ling
Talking about interventions for ER stress, I'm doing redrawal trials of a bunch of interventions, one at a time. Bacopa is the current one, and this is more or less ruining our holidays now.
Two weeks in (or rather off) and we're experiencing:
-Restless sleep, waking up every second night and moving around a lot while asleep
-Irritability every day, a lot of it
-Aggressive actions like hitting, pushing and hair pulling
-Fever (lasting one day, no other symptoms but fatigue, not even a runny nose, nobody else in the family is sick, nobody to catch viruses from...)
-Handflapping is back (it went away last time I upped the dose, so this confirms the relationship).
-Facial rash from skin contact with certain known foods but now it doesn't go away within an hour as usual but stays for days and requires attendance.
The effects from (adding) Bacopa slowly builds up over 3 months or so which makes them hard to spot. I didn't expect to see such a drastic worsening when removing it.
Fisetin is very similar and seems to stack with Bacopa at my current dose, but it has a much faster effect. Starting it you notice effect within 3 days, and removing it takes 2 days. When using both Fisetin and Bacopa I can't see any effect from sulphoraphane at all, though it also acts in this realm.
I'm not sure the family can live another week like this, but I need to remove the effect Bacopa has on serotonin/MAO to be able to test C8/keto again without hitting the 'happy mania' state.
/Ling
Two weeks in (or rather off) and we're experiencing:
-Restless sleep, waking up every second night and moving around a lot while asleep
-Irritability every day, a lot of it
-Aggressive actions like hitting, pushing and hair pulling
-Fever (lasting one day, no other symptoms but fatigue, not even a runny nose, nobody else in the family is sick, nobody to catch viruses from...)
-Handflapping is back (it went away last time I upped the dose, so this confirms the relationship).
-Facial rash from skin contact with certain known foods but now it doesn't go away within an hour as usual but stays for days and requires attendance.
The effects from (adding) Bacopa slowly builds up over 3 months or so which makes them hard to spot. I didn't expect to see such a drastic worsening when removing it.
Fisetin is very similar and seems to stack with Bacopa at my current dose, but it has a much faster effect. Starting it you notice effect within 3 days, and removing it takes 2 days. When using both Fisetin and Bacopa I can't see any effect from sulphoraphane at all, though it also acts in this realm.
I'm not sure the family can live another week like this, but I need to remove the effect Bacopa has on serotonin/MAO to be able to test C8/keto again without hitting the 'happy mania' state.
/Ling
You are right Tyler, but this is a mind game that doesn't lead anywhere. Any penny that is spent on autism research could save even more kids in countries where food and basic healthcare is rare. There is always a hole where the need is bigger. But I agree, money could be spent much wiser.
/Ling
/Ling
Hello Peter. Happy 2020 to you. Thank you for your replies to my previous posts. The DNA Testing we did via TACGA (the Australian Centre for Genomic Analysis) was the Intellxx DNA Test. I think that I need to go back to college to interpret it! We were given some help and recommendations via skype from TACGA. Thank you for the recommendation for Fisetin. I had been reading up on it prior to your recommendation so have ordered it on iherb. The capsules are 100 mg - can you recommend a dosage for my 12 year old son please? I looked up the Potassium BHB on iherb and it seems to be a drink for athletes. is this correct or would you mind giving me a link to it? We trialled 2500 mg of NAC on our son today (2 tablets in the morning, 2 at lunchtime and one in the evening. He was extremely echolalic and while not openly aggressive, he wasn't in great form either. Should we keep trying it or try ALA instead? Is Alpha Linoic Acid ok to take as a supplement? He has never taken ALA. He did take DMSA as a chelator over many weekends, following our biomedical consultant's recommendations two years ago. From memory I think it was ten weekends of DMSA every eight hours and then we had a break of a few weeks. We didn't see any great gains for our pretty much non-responder!! Thanks again for your time and thoughts Peter. sharon
Once again, thank you very much Peter.
With all this valuable information presented and shared by Peter and enriched with the experience of those who comment on each blog, the following years will be full of hope and improvement for our children.
For all of you, a Happy New Year and our thanks for everything you have taught us.
Claudia
With all this valuable information presented and shared by Peter and enriched with the experience of those who comment on each blog, the following years will be full of hope and improvement for our children.
For all of you, a Happy New Year and our thanks for everything you have taught us.
Claudia
Sharon, I do not know which genetic testing you have done; Whole Exome Sequencing (WES) gives useful information in about 35% of cases. This does require some proactive interpretation of the results. Hopefully you were given a written report.
Mitochondrial disease can be diagnosed (albeit subjectively) from a blood sample, as used by Dr Kelly. A muscle biopsy is a common mainstream test, but some autism doctors will say that it can just be a brain-specific dysfunction. If your son has poor exercise endurance that might be linked to a mito-problem; if he runs marathons, I doubt he has faulty mitochondria.
Anecdotally, people with late regressive autism do not respond to Bumetanide, but may respond to the ketone BHB. That would make sense if they have a problem using glucose from their blood as a fuel for their brain. You can buy potassium BHB online from iHerb. BHB is an alternative brain fuel, that bypasses some steps in the mitochondria, that glucose requires.
Your autism doctor could measure whether your son has oxidative stress (GSH/GSSG ratio), or you can just make a trial of antioxidants. NAC and ALA essentially do the same thing. There are sustained release versions of both. For NAC, 2,400mg split into 3 or 4 doses a day is typical.
If you get a positive test suggesting a mitochondrial disorder, you can try Dr Kelley’s suggested therapy.
Mitochondrial disease can be diagnosed (albeit subjectively) from a blood sample, as used by Dr Kelly. A muscle biopsy is a common mainstream test, but some autism doctors will say that it can just be a brain-specific dysfunction. If your son has poor exercise endurance that might be linked to a mito-problem; if he runs marathons, I doubt he has faulty mitochondria.
Anecdotally, people with late regressive autism do not respond to Bumetanide, but may respond to the ketone BHB. That would make sense if they have a problem using glucose from their blood as a fuel for their brain. You can buy potassium BHB online from iHerb. BHB is an alternative brain fuel, that bypasses some steps in the mitochondria, that glucose requires.
Your autism doctor could measure whether your son has oxidative stress (GSH/GSSG ratio), or you can just make a trial of antioxidants. NAC and ALA essentially do the same thing. There are sustained release versions of both. For NAC, 2,400mg split into 3 or 4 doses a day is typical.
If you get a positive test suggesting a mitochondrial disorder, you can try Dr Kelley’s suggested therapy.
Claudia, the only reported side effects from the several hundred children in France who are taking bumetanide relate to low potassium and dehydration.
Bumetanide has long been used in tiny babies and there are studies on its effects.
In the use of bumetanide in tiny babies at risk of jaundice an issue has been raised regarding bilirubin.
Bumetanide is a potent displacer of bilirubin and cause unconjugated hyperbilirubinemia in neonatal babies.
https://www.ncbi.nlm.nih.gov/pubmed/3304769
There is a small reaction between bumetanide and albumin.
Albumin Binding of Bumetanide
https://www.karger.com/Article/Abstract/457099
"Pharmacologic concentrations of bumetanide would not significantly affect bilirubin-albumin binding and should not increase the risk of bilirubin encephalopathy in newborn infants."
If you have concerns, you should contact the French researchers, who are actually very helpful.
Bumetanide has long been used in tiny babies and there are studies on its effects.
In the use of bumetanide in tiny babies at risk of jaundice an issue has been raised regarding bilirubin.
Bumetanide is a potent displacer of bilirubin and cause unconjugated hyperbilirubinemia in neonatal babies.
https://www.ncbi.nlm.nih.gov/pubmed/3304769
There is a small reaction between bumetanide and albumin.
Albumin Binding of Bumetanide
https://www.karger.com/Article/Abstract/457099
"Pharmacologic concentrations of bumetanide would not significantly affect bilirubin-albumin binding and should not increase the risk of bilirubin encephalopathy in newborn infants."
If you have concerns, you should contact the French researchers, who are actually very helpful.
Tyler, I think the problem is more organisation than funding. Autism research is like an orchestra with no conductor and no music, it looks very amateur. It is so amateur that it seems to pay up to do your own translational research, which really should not be the case.
Sharon, if you are dealing with aggression, irritability and OCD chances are good for antioxidants to work well for your son. However, most are weak and you do need to reach a certain level before you see any results. NAC is probably the strongest one, note the high dosing that is used for autism. ALA, Broccoli sprout works for some but personally I've seen more result from fisetin in combination with others
Good luck, if you find what works for your son life will get easier.
/Ling
Good luck, if you find what works for your son life will get easier.
/Ling
Great post Peter. BTW, have you taken a look at NIH spending priorities lately?
https://report.nih.gov/categorical_spending.aspx
I was curious after reading about how little success has been made in Alzheimer's research due to the intransigence in funding any research that is not centered around beta-amyloid and that the NIH spends two billion dollars a year on Alzheimer's research overall. Around 5 million Americans are estimated to have Alzheimer's disease at any given time, almost all of whom are in the final stages of their life while with autism using a conservative estimate of 1% you have roughly 10 million affected.
Nevertheless around 2 billion is estimated to be spent next year on Alzheimers's disease while only 250 million will be spent on autism. So you have twice the people with autism as with Alzheimer's disease, yet only one eighth the research resources devoted to investigation.
In fact, I would not be surprised if the medical research is skewed in a similar manner in your country as well, as well as just about every other country in the G-8 which can afford to employ public research dollars for medical research.
250 million dollars a year is basically the cost of two F-35 fighter planes to put into comparison or another way of looking at autism research spending is 25 dollars per individual with autism spent on hard research which is really quite pathetic in an extreme way. Even worse than that, if you look at the amount of money spent every year on useless and toxic political advertising and compare it to the paltry amount spent on autism research by the federal government, it disheartens the soul to imagine all of those people writing checks to political campaigns that could instead be written to help fund research to address a serious disability in the lives of so many people, many of whom lack the agency to advocate for themselves.
https://report.nih.gov/categorical_spending.aspx
I was curious after reading about how little success has been made in Alzheimer's research due to the intransigence in funding any research that is not centered around beta-amyloid and that the NIH spends two billion dollars a year on Alzheimer's research overall. Around 5 million Americans are estimated to have Alzheimer's disease at any given time, almost all of whom are in the final stages of their life while with autism using a conservative estimate of 1% you have roughly 10 million affected.
Nevertheless around 2 billion is estimated to be spent next year on Alzheimers's disease while only 250 million will be spent on autism. So you have twice the people with autism as with Alzheimer's disease, yet only one eighth the research resources devoted to investigation.
In fact, I would not be surprised if the medical research is skewed in a similar manner in your country as well, as well as just about every other country in the G-8 which can afford to employ public research dollars for medical research.
250 million dollars a year is basically the cost of two F-35 fighter planes to put into comparison or another way of looking at autism research spending is 25 dollars per individual with autism spent on hard research which is really quite pathetic in an extreme way. Even worse than that, if you look at the amount of money spent every year on useless and toxic political advertising and compare it to the paltry amount spent on autism research by the federal government, it disheartens the soul to imagine all of those people writing checks to political campaigns that could instead be written to help fund research to address a serious disability in the lives of so many people, many of whom lack the agency to advocate for themselves.
I don't think that neomycin is a solution.
https://www.bmj.com/content/bmj/4/5677/181.full.pdf?fbclid=IwAR3YHWZ9diq7tzbzCXXAFOlr9hme08fH64qitgmzXI58MzBggMhoHjL6G9M
https://www.bmj.com/content/bmj/4/5677/181.full.pdf?fbclid=IwAR3YHWZ9diq7tzbzCXXAFOlr9hme08fH64qitgmzXI58MzBggMhoHjL6G9M
Dear Peter,
Before starting Bumetanide with our son, we did a CMP to have a baseline. His potassium levels were close to the high range, so we decided not to supplement it and give extra bananas, avocado and increase water consumption. The only altered result in this test was total bilirubin that went slightly above the maximum range. This did not prevent us from starting Bumetanide because in the past our son has cyclically presented this alteration and since it has not been a highly significant record, the doctors who have treated him have told us that they are not worrisome because he has no other traits or symptoms of disease or liver risk.
After trying Bumetanide for two weeks, we did another CMP and to our surprise, the calcium, protein (total), albumin, and bilirubin (total) were all above their maximum ranges. We did not give anything new or increase the supplements that he is taking for mitochondrial dysfunction. The only possible thing could be that the increment in water consumption caused the calcium level to rise due to the Reverse Osmosis water filter that adds minerals ( magnesium and calcium) to improve the flavor and overall quality.
We have not reached the full dose to know if our son is a responder. So far, we have not had anything surprising that suggests a clear positive response but we have not either seen a negative sign that forces us to stop Bumetanide.
Is it possible that Bumetanide can move calcium, alter albumin and protein levels? Have you seen or known of any other cases similar to our son’s results in Bumetanide?
Thank you in advance for your help and comments,
Claudia
Before starting Bumetanide with our son, we did a CMP to have a baseline. His potassium levels were close to the high range, so we decided not to supplement it and give extra bananas, avocado and increase water consumption. The only altered result in this test was total bilirubin that went slightly above the maximum range. This did not prevent us from starting Bumetanide because in the past our son has cyclically presented this alteration and since it has not been a highly significant record, the doctors who have treated him have told us that they are not worrisome because he has no other traits or symptoms of disease or liver risk.
After trying Bumetanide for two weeks, we did another CMP and to our surprise, the calcium, protein (total), albumin, and bilirubin (total) were all above their maximum ranges. We did not give anything new or increase the supplements that he is taking for mitochondrial dysfunction. The only possible thing could be that the increment in water consumption caused the calcium level to rise due to the Reverse Osmosis water filter that adds minerals ( magnesium and calcium) to improve the flavor and overall quality.
We have not reached the full dose to know if our son is a responder. So far, we have not had anything surprising that suggests a clear positive response but we have not either seen a negative sign that forces us to stop Bumetanide.
Is it possible that Bumetanide can move calcium, alter albumin and protein levels? Have you seen or known of any other cases similar to our son’s results in Bumetanide?
Thank you in advance for your help and comments,
Claudia
Hi Peter. I only discovered your blog two days ago so am doing plenty of reading. I am a little confused as to if my 12 year old son has classic or regressive autism. He was 3 and a half years old when it was pointed out to me that he was doing the opposite to what he was asked in pre-school. After I started to investigate, things got rapidly worse. While his language didn't disapear, it stagnated a lot. Now, his (and our) challenges are anger outbursts, constantly repeating the same questions and he is OCD about the answers he wants. He finds it very difficult to listen and take instruction. I had genetic testing done for him with Dr. Elizabeth Way in Australia. She has suggested a lot of supplements but among them is the Broccoli Sprout, NAC and Ubiquinol. His psychiatrist recently prescribed Guanfacine (1 mg) for him at night which he started one week ago. We trialled the Bumetamide during the summer with no visible positive effect. I took it out two days ago and restarted it. I am thinking though that maybe he as regressive autism and these won't help him. Can I try ALA or do I have to do this at weekends every three hours (as per Andy Cutlar protocol). I would really appreciate any advise that you can give because my son seems to be a non-responder to most supplements we try. The one supplement that did work for him was Melatonin but we took him off it when his sleep improved. Kind regards. Sharon
Making low doses is possible by crushing a pill and then using cheap micro scales to split into 1/4 or 1/6 which you then put in a gelatin capsule. To make micro doses like 1/20 th of a pill then the glass bottle with water and a measuring syringe seems to work well.
A 50mg tablet in 125ml of water gives 0.4 mg per ml. You do need to mix it well.
Microscales are very cheap and available on Amazon, as are the gelatin capsules.
A 50mg tablet in 125ml of water gives 0.4 mg per ml. You do need to mix it well.
Microscales are very cheap and available on Amazon, as are the gelatin capsules.
Peter, I was recently looking through my old supplement bottles and such and found a bottle of 50mg Zolfot. I am interested in trying the low dose SSRI protocol that is sometimes discussed here. Since 50mg is a bit too much to split for this purpose it seems like making a solution would be the best option. I have a marked 125 mL glass Pyrex bottle that could do the job. I'm assuming preparing such a solution would be similar to preparing the Clonazolam solution in that a milk frother would be needed. Btw would you happen to know how much one mL would be from the 50 mg Zoloft and 125 mL capacity bottle also? Any other insight or advice would be welcomed of course. If any notable effects happen I plan to report back.
I am the recent LSD anon btw, I tried the nicotine patches but I don't believe they were very effective. The whole 7mg patch made me sick after a few hours and cut pieces didn't seem to produce much of an effect. I shared a cigar with a friend recently and a sort of anxiolytic effect did indeed occur; easier to speak as well. Nicotine of course is a very tricky drug to work the way you would like it in my experience, too much and the anxiolytic effect seems to start to dissipate. I'm also planning to trial a Keto diet somewhat soon for ideally around 2 months. I may even trial a low dose of Abilify at some point as well, which evidently is what Aspie has found great success with on his Reddit account. He says it helps him a great deal with anxiety and sensory filtering.
-H
I am the recent LSD anon btw, I tried the nicotine patches but I don't believe they were very effective. The whole 7mg patch made me sick after a few hours and cut pieces didn't seem to produce much of an effect. I shared a cigar with a friend recently and a sort of anxiolytic effect did indeed occur; easier to speak as well. Nicotine of course is a very tricky drug to work the way you would like it in my experience, too much and the anxiolytic effect seems to start to dissipate. I'm also planning to trial a Keto diet somewhat soon for ideally around 2 months. I may even trial a low dose of Abilify at some point as well, which evidently is what Aspie has found great success with on his Reddit account. He says it helps him a great deal with anxiety and sensory filtering.
-H
Also, thanks for the Dietary Considerations article (Sanctuary 2018), which mentions putrefactive metabolites due to incomplete protein digestion. Measuring stool pH is an easy way to find out whether your gut bacteria are producing too much ammonia, which easily goes into the bloodstream and crosses the blood-brain barrier, raising histamine levels in the brain, thereby causing behaviour problems or fatigue, among others. A possible cure is rifaximin.
Leen
Leen
If anyone is interested in trying an elimination diet, I suggest the golden standard: the Royal Prince Alfred Hospital elimination diet, or Failsafe Diet. Not easy but worth it.
Thanks for the article!
Leen
Thanks for the article!
Leen
Hi Peter,
As usual excellent post. But what I got most from it is the fact that Monty has no digestive issues. The reason being digestive issues have been proposed as a possible reason for some individual’s non responsiveness to Bumetanide, this is definitely plausible with my daughter, as she had zero side effects (or positive effects) when we trialed it. She’s been constantly constipated for as long as I can remember.
As usual excellent post. But what I got most from it is the fact that Monty has no digestive issues. The reason being digestive issues have been proposed as a possible reason for some individual’s non responsiveness to Bumetanide, this is definitely plausible with my daughter, as she had zero side effects (or positive effects) when we trialed it. She’s been constantly constipated for as long as I can remember.
Mighty long post, yes - but easy to read for anyone.
I wonder where in all this the topic of bile acids belong?
Great reading, thank you!
/Ling
I wonder where in all this the topic of bile acids belong?
Great reading, thank you!
/Ling
Thanks Petra,treating anxiety is not easy,will see how will he do with it. Merry Christmas to you and everyone!
Valentina
Valentina
My warmest well-wishes to all of you in the community, I hope you get the best of the season!
Peter-sensei, thank you for yet another amazing year with your blogposts. You have changed my way of thinking.
2019 was the year when I embraced your favourite quote 'anything is possible'. Set some things in motion, curious of where it will lead. :)
I'm looking forward with a very positive feeling for 2020, expecting great news like you AJ but also planning strategies to create some myself.
/Ling
Peter-sensei, thank you for yet another amazing year with your blogposts. You have changed my way of thinking.
2019 was the year when I embraced your favourite quote 'anything is possible'. Set some things in motion, curious of where it will lead. :)
I'm looking forward with a very positive feeling for 2020, expecting great news like you AJ but also planning strategies to create some myself.
/Ling
Merry Christmas Peter and all the readers of your blog.
My Russian Afobazole costs 425.00p, which is about 7 euros.
When I ordered from UK I paid 50 euros for two packets shipping included. Both options not expensive.
I have some reasons to suspect Afobazole is a cox2 inhibitor but I am not sure if this is due to sigma 1 or 2 receptor activation.
Cox2 inhibitors have been found to be effective in suppressing inflammatory neurodegenerative pathways in mental illness.
Petra
My Russian Afobazole costs 425.00p, which is about 7 euros.
When I ordered from UK I paid 50 euros for two packets shipping included. Both options not expensive.
I have some reasons to suspect Afobazole is a cox2 inhibitor but I am not sure if this is due to sigma 1 or 2 receptor activation.
Cox2 inhibitors have been found to be effective in suppressing inflammatory neurodegenerative pathways in mental illness.
Petra
Hi Peter, Friends, and community,
I just wanted to wish everyone and your families a very Merry Christmas!!!
Here's to having 2020 will bring each of us some great news.
AJ
I just wanted to wish everyone and your families a very Merry Christmas!!!
Here's to having 2020 will bring each of us some great news.
AJ
Hi Valentina, nice hearing from you. Valentina, Afobazole is like taking a mild painkiller and hope your son responds with no side effects.
The fact that is being trialled for autism shows that it may be useful.
Merry Christmas Valentina.
Petra
The fact that is being trialled for autism shows that it may be useful.
Merry Christmas Valentina.
Petra
Thank you Peter for the response, I heard some people saying they stopped the therapy and kids not regressing, just curious to know.
And every kid is different and I just heard people saying that(Not sure if I can believe 100%), and very grateful you accepted the fact. Thank you again and appreciate your efforts on your son.
And every kid is different and I just heard people saying that(Not sure if I can believe 100%), and very grateful you accepted the fact. Thank you again and appreciate your efforts on your son.
Petra, thanks for all the information. I have already received my Afobazole from Russia, it came very quickly.
Happy Christmas
Happy Christmas
Special Mom, NAC is one element of my son's Polypill.
https://epiphanyasd.blogspot.com/2019/11/polypill-v6-for-severe-autism-and-now.html
The combined effect has been that he has gone from being unable to learn anything at school, to being able to keep up with his neurotypical classmates at school for the last 6 years. In maths, science, art and music he is well above average. In English he is below average.
We of course continue to use his therapy since we want him to move forward at school and pass his exams.
He does regress if the therapy is stopped, but I hope not back to a 9 year old with severe autism. I do not intend to find out.
https://epiphanyasd.blogspot.com/2019/11/polypill-v6-for-severe-autism-and-now.html
The combined effect has been that he has gone from being unable to learn anything at school, to being able to keep up with his neurotypical classmates at school for the last 6 years. In maths, science, art and music he is well above average. In English he is below average.
We of course continue to use his therapy since we want him to move forward at school and pass his exams.
He does regress if the therapy is stopped, but I hope not back to a 9 year old with severe autism. I do not intend to find out.
Dear Peter,
Thank you very much for your response and for the additional information you gave me to continute helping our son. Your blog has been a very valuable source of knowledge for us.
Best wishes for you and your family,
Claudia
Thank you very much for your response and for the additional information you gave me to continute helping our son. Your blog has been a very valuable source of knowledge for us.
Best wishes for you and your family,
Claudia
Hi Peter,
After 6 years did you stop the medication? And are the improvements in ASD behaviors are still continued?
After 6 years did you stop the medication? And are the improvements in ASD behaviors are still continued?
Thank you Peter for your response and advice.
I hope you have a happy holiday with your family, Esteban
I hope you have a happy holiday with your family, Esteban
Hi Petra, hope you are well, I will make a trial of Afobazole in my son, he is in some place, between Aspergers and HFA, he has problemas with dopamine and anxiety and will start High School in almost 3 months. Do you think that afobazole could be useful for HIM? Don't know if your son is still taking it.
Valentina
Valentina
Hi Peter, hope you are well.
When I decided to use afobazole for my adult son my objective was to improve his executive functios. Anxiety for Aspergers is a complicated thing and lots of it comes through miscommunication and realisation of their disability to function properly, so I doubt there is a single pill to fix this short of anxiety.
Afobazole at 20mg dose was not anxiolytic in a gabaergic inhibitory manner, nor mood stabilizer. It is not sedative and doesn't help with sleeping disorders. It's really mild and I agree it should be used as a part of a polypill. It can help with concentration and learning somehow like a stimulant. It can also be useful in movement coordination. That mechanism affecting dopamine may bring arousal that's why you don't want to up the dose too much.
ER stress might as well affect my son according to pharmacogenetic tests. His serotonin short allele shows that he cannot bind serotonin effectively and drd2 Taq A1/A2 polymorphism shows low density being at risk of several serious mental and neurological illnesess and diabetes.
I used Propranolol in the past but didn't seem to work, probably because he doesn't have performance anxiety.
5ht2a looks normal, genotype 5ht2ar 102tt, but if you can find specific details about this please let me know, however you can never know the mechanism you get the help from.
My son looks much better when he gets more than 100% dietary vitamin A and beta carotene daily possibly through an increase in drd2 density which normalises dopamine binding.
If I missed something about afobazole you needed to know please ask again. I still have some packets of afobazole in case you don't have an easy access.
My best wishes
Petra
When I decided to use afobazole for my adult son my objective was to improve his executive functios. Anxiety for Aspergers is a complicated thing and lots of it comes through miscommunication and realisation of their disability to function properly, so I doubt there is a single pill to fix this short of anxiety.
Afobazole at 20mg dose was not anxiolytic in a gabaergic inhibitory manner, nor mood stabilizer. It is not sedative and doesn't help with sleeping disorders. It's really mild and I agree it should be used as a part of a polypill. It can help with concentration and learning somehow like a stimulant. It can also be useful in movement coordination. That mechanism affecting dopamine may bring arousal that's why you don't want to up the dose too much.
ER stress might as well affect my son according to pharmacogenetic tests. His serotonin short allele shows that he cannot bind serotonin effectively and drd2 Taq A1/A2 polymorphism shows low density being at risk of several serious mental and neurological illnesess and diabetes.
I used Propranolol in the past but didn't seem to work, probably because he doesn't have performance anxiety.
5ht2a looks normal, genotype 5ht2ar 102tt, but if you can find specific details about this please let me know, however you can never know the mechanism you get the help from.
My son looks much better when he gets more than 100% dietary vitamin A and beta carotene daily possibly through an increase in drd2 density which normalises dopamine binding.
If I missed something about afobazole you needed to know please ask again. I still have some packets of afobazole in case you don't have an easy access.
My best wishes
Petra
waz1, I think you should ask people with Asperger's for advice. You can join reddit and pose your question, or just read existing threads.
https://www.reddit.com/r/aspergers/
There is a very active community on Reddit, who are treating their issues with mood, anxiety, social, emotional and cognitive issues.
https://www.reddit.com/r/aspergers/
There is a very active community on Reddit, who are treating their issues with mood, anxiety, social, emotional and cognitive issues.
Claudia, that paper is interesting and I note they have already patented the idea. I am not aware of anyone trialing it for AMD.
I like the idea of making more mitochondria, which I think will happen with a PPARγ agonists and/or activation of PGC-1α
Glitazone drugs widely used for type 2 diabetes and trialed in autism are PPARγ agonists.
I also think the Russian drug Mildronate may help in complex 1 deficiency. Mildronate is used to increase exercise endurance.
Here is a paper explaining PPARγ and PGC-1α in mitochondria.
PPARγ and PGC-1α as Therapeutic Targets in Parkinson’s
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326663/
I like the idea of making more mitochondria, which I think will happen with a PPARγ agonists and/or activation of PGC-1α
Glitazone drugs widely used for type 2 diabetes and trialed in autism are PPARγ agonists.
I also think the Russian drug Mildronate may help in complex 1 deficiency. Mildronate is used to increase exercise endurance.
Here is a paper explaining PPARγ and PGC-1α in mitochondria.
PPARγ and PGC-1α as Therapeutic Targets in Parkinson’s
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326663/
Is there something that I can do relatively to my speech problems? Before I would speak subconsciously but now everytime when I speak I'm of aware of what I'm saying and going to say ( consciously ) there's something that I can take to bring it back to what was it before? I've been taking NAC but nothing or almost nothing changed. I've another problem which is the mood I don't seem to have a mood.. even though i've emotions. I don't have a mood because I'm never sad or happy unless something triggers it ( emotion ).
Dear Peter,
Thank you very much for sharing your findings and for giving us hope for a better future.
Our case was initially diagnosed as severe autism but after many years and much research, we are clear that it is AMD due to Mitochondrial Complex I deficiency. Our son has improved thanks to mito cocktail, various therapies and diet interventions.
We have been testing Bumetanide for a week but we are doing it very slowly (we started with 0.5 mg a day and we have just moved to 1.0 mg to reach 2 mg in the morning and 1.0 mg in the afternoon - 73 kg/ 18 years).
We know that we should avoid certain drugs that inhibit Complex I and that is why, to our dismay, we cannot try Atorvastatin.
Have you known of any case where Sulfarlem (OP2113) has been used in AMD? https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0216385&type=printable
Thank you for your comments,
Claudia
Thank you very much for sharing your findings and for giving us hope for a better future.
Our case was initially diagnosed as severe autism but after many years and much research, we are clear that it is AMD due to Mitochondrial Complex I deficiency. Our son has improved thanks to mito cocktail, various therapies and diet interventions.
We have been testing Bumetanide for a week but we are doing it very slowly (we started with 0.5 mg a day and we have just moved to 1.0 mg to reach 2 mg in the morning and 1.0 mg in the afternoon - 73 kg/ 18 years).
We know that we should avoid certain drugs that inhibit Complex I and that is why, to our dismay, we cannot try Atorvastatin.
Have you known of any case where Sulfarlem (OP2113) has been used in AMD? https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0216385&type=printable
Thank you for your comments,
Claudia
Esteban, it is the K+ you want and it can be attached many things.
One issue is stomach upsets. It seems that potassium supplements should be taken with a full glass of water. You can buy any commercial potassium supplement. You could buy cheap potassium bicarbonate powder and get the mild anti-inflammatory effect of the bicarbonate as a bonus.
There is potassium chloride, potassium citrate. If you want ketones, there is potassium beta hydroxybutyrate powder.
One issue is stomach upsets. It seems that potassium supplements should be taken with a full glass of water. You can buy any commercial potassium supplement. You could buy cheap potassium bicarbonate powder and get the mild anti-inflammatory effect of the bicarbonate as a bonus.
There is potassium chloride, potassium citrate. If you want ketones, there is potassium beta hydroxybutyrate powder.
Hi Peter,
When I was investigating about Hypokalemic Sensory Overstimulation for my young brother, I read that oral administration of potassium gluconate was recommended. Is this the only molecule of potassium that works or is there another form of potassium?
Thanks, Esteban
When I was investigating about Hypokalemic Sensory Overstimulation for my young brother, I read that oral administration of potassium gluconate was recommended. Is this the only molecule of potassium that works or is there another form of potassium?
Thanks, Esteban
Hi Petra, nice to hear from you again.
I would love to know more about how your son responded to Afobazole.
What dose are you using?
Was the objective to reduce anxiety? How does he describe the effect, both on anxiety and cognition?
I think Afobazole is only moderately effective at treating anxiety, that is why it is OTC in Russia. I think you need to target serotonin receptors (with SSRIs) or GABA receptors (with Benzodiazepines) to have a big effect on anxiety, but these drugs are not suitable for most people, due to side effects/addiction. Beta blockers like Propranolol are effective for some people's anxiety.
Some SSRIs are also sigma-1R agonists, it is not clear how much of their effect comes from which mode of action.
I see Afobazole as potentially improving a core defect (ER stress leading to protein mis-folding) that your son may not have, seeing that he is high IQ. But the anxiety effect may be very helpful. It is clear that many Aspies seem to benefit from 5HT2A agonists, to improve mood. This may be different to classic autism.
I would love to know more about how your son responded to Afobazole.
What dose are you using?
Was the objective to reduce anxiety? How does he describe the effect, both on anxiety and cognition?
I think Afobazole is only moderately effective at treating anxiety, that is why it is OTC in Russia. I think you need to target serotonin receptors (with SSRIs) or GABA receptors (with Benzodiazepines) to have a big effect on anxiety, but these drugs are not suitable for most people, due to side effects/addiction. Beta blockers like Propranolol are effective for some people's anxiety.
Some SSRIs are also sigma-1R agonists, it is not clear how much of their effect comes from which mode of action.
I see Afobazole as potentially improving a core defect (ER stress leading to protein mis-folding) that your son may not have, seeing that he is high IQ. But the anxiety effect may be very helpful. It is clear that many Aspies seem to benefit from 5HT2A agonists, to improve mood. This may be different to classic autism.
I am using Fumaderm Initial, from Germany, it contains 30mg of DMF. From 1 tablet I make 6 doses of 5mg DMF which are placed in enteric capsules. DMF is a stomach irritant and must be taken with an enteric coating.
You can also Skilarence or Tecfidera, which are also effectively just DMF.
You will need a prescription to get Fumaderm, Skilarence or Tecfidera. They are expensive in Europe and ultra expensive in the US.
You can even buy DMF as a chemical, which is cheap.
You can also Skilarence or Tecfidera, which are also effectively just DMF.
You will need a prescription to get Fumaderm, Skilarence or Tecfidera. They are expensive in Europe and ultra expensive in the US.
You can even buy DMF as a chemical, which is cheap.