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PolyPill for Autism

The objective was to identify the most effective drugs to treat Classic early-onset autism, having biomarkers of elevated serotonin, cholesterol, thyroid FT3/4 and growth factor IGF-1.  Except for the Potassium Bromide, these drugs are all generic, widely available and cheap.  The total cost per day is about EUR 1.3 ($1.6).

The dosage is based on a 13 year old child weighing 50kg / 110lbs. He has been using a very similar version for more than four years.

The Clonazepam dose is tiny.

Potassium bromide has the same effect as bumetanide, so whatever you see from bumetanide, you should see more of.  The human drug form is called Dibro-Be Mono, but is available only in Germany and Austria. 

According to the European Medicines Agency (EMA), most countries have an arrangement whereby patients can apply for access to drugs for off-label use, usually based on experimental evidence or clinical trials.  If you use these drugs, it would be helpful to collect data on the effect that can later be used by the EMA to evaluate the Autism Polypill.  You can send me the data.

Since most doctors continue to regard autism as untreatable, you will have to be proactive, if you want a drug to treat your child.


Updated 31 March 2019



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In case you have to deal with periods of the year where no intervention works, this may be due to allergies.

In the case I deal with, all the above therapies appear to gradually "stop working" from mid-May to October.  Very surprisingly, this is due to the affect of a pollen allergy, that outwardly looks quite mild; but the affect on behavior is dramatic.

The remedy is to use mast cell stabilizers to treat the allergy, but the most effective step is to increase the Verapamil dose to 1mg/kg 2 or 3 times a day.  Verapamil is calcium channel blocker (Cav1.2 channel) but also a very effective inhibitor of mast cell degranulation.  The combined therapy appears to be 100% effective; summertime behaviour is now just like the rest of the year. It has to be seen to be believed, almost too good to be true.

As mast cell stabilizers I am using Quercetin, Azelastine and Palmitoylethanolamide (PEA).  It may be that Verapamil is potent enough, that nothing else is needed.  Claritin, Xyzal, Ceterizine etc, all help, but not for long.  Without Verapamil things improve 50% for a short time; with Verapamil things return to 100% "normal" for the entire day.

Not all broccoli sprout powders are equal.  They must have high levels of active Myrosinase and low levels of Epithiospecifier proteins (ESP).  If not, when eaten they will not produce Sulforaphane, the most likely active ingredient .  According to lab testing, most broccoli powders produce little/no sulforaphane.  Check in my posts.  



198 comments:

  1. Have you thought about Baclofen as a possible piece of you polypill? Arbaclofen was under trial for autism, and despite falling through has helped many people. Personally Baclofen is the only thing that has made a great difference in my mood/sociability/irritability. In fact, it has helped every aspect of my condition. Gaba-B agonists seem to open the door of Autism into the Neurotypical world, helping me socialize and simply giving me a better quality of life. I'm sure you've been asked this before, and your research is second to none in my opinion.

    Also this polypill, is it something you plan on creating as an all in one treatment that will be available to all of us? Either way I appreciate the time and research you put into this blog.

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    1. It is interesting to hear that Baclofen works so well. What dosage do you take?

      I did write about Baclofen, R/S – Baclofen, Arbaclofen, and the best of all, Arbaclofen Placarbil. Baclofen also stimulates Growth Hormone production, which I thought might be very relevant.

      http://epiphanyasd.blogspot.com/2014/02/human-growth-factors-autism-and.html
      http://epiphanyasd.blogspot.com/2013/11/autism-clinical-trials-arbaclofen.html

      I did trial Baclofen and it did have a positive effect, but on nothing like the scale as Clonazepam. Baclofen does have some side effects and I want to use drugs that have the least chance of interacting with each other. Clonazepam and Baclofen both affect GABA, so I chose Clonazepam to replace Baclofen.

      My PolyPill is the current version of what I think is the best combination of drugs to treat my son’s type of autism. I have discussed it with the European version of the FDA and given them a presentation of the rationale for it. The next stage would be to trial it on other people, who have the same type of autism. This then starts to get quite complicated, time consuming and expensive. These are all generic drugs, so there is no financial pay back. I develop my PolyPill with a few hours a week of work, to get a drug approved costs tens of millions of dollars in the US. Anyone who wants to, can mix up the PolyPill at home, just like I do.
      Also, I keep changing the formulation, as I learn new things. So for the time being I am focused on the easy part, which is the drug discovery part. If Bill Gates has $20 million spare, he is welcome to come and talk to me.

      Mainstream medicine is not equipped to deal with autism and such a complex condition is unlikely to be considered as treatable for decades to come.

      Delete
  2. I'm working on adding Potassium (just read your post on it) but what type of potassium; gluconate, cloride, or citrate? I'm using magnesium citrate already - 75mg twice a day. Is one potassium better than the other?

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  3. I think potassium supplements are a good as a diagnostic tool, because you can see if your child's behavior is improved by a "spike" in potassium levels. In a typical person there is no effect. The problem is you cannot keep increasing potassium levels. It appears to be the effect of the increase, rather than a steady high level of potassium.

    Amongst those whose behavior is affected by potassium, consensus seems to be to maintain "high normal" blood potassium levels and avoid sodium (salt). In the body sodium tends to "oppose" potassium; so if you cannot increase potassium (very high potassium is bad for you) you can at least avoid excess sodium. Most people eat far too much sodium and too little potassium.

    You should measure potassium in the blood.

    If it is already high, it would not be good to give supplements.

    In the US, supplements of potassium are very weak. The RDA is 3,500 mg and the supplements are limited to 100mg. The reason is that very high levels can kill you.

    I am using a 500mg tablet, taken half in the morning and half in the evening. But we are using Bumetanide, which is known to lower potassium levels and I do monitor blood levels of potassium.

    I do not think it matters what kind of potassium you use. Some also have magnesium.

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  4. Hello.I gave Bumetanide last year.I started on September ,after 2-3 weeks we saw big improvement in comunication and social skills,it was wonderful but after 1,5 months of treatment the effect desapaered...it was Christmas and we stopped
    I gave 1mg on the morning,I don know if I made something wrong...
    We never had low potassium so web never gave K supplemet
    Isabel

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    1. I can only speak from my experience. After 6 months I had added NAC and Atorvastatin to the Bumetanide therapy, things improved greatly. Then in June everything, particularly NAC, seemed to stop working.

      Eventually I discovered that the problem is my son's very mild pollen allergy. This causes a reaction which completely masks the beneficial effect of the drugs. By going to mountains with different pollen in the air, the drugs started to work again. That is why there are`many posts all about mast cells and allergies on this blog. By adding Verapamil, Azelastine and Quercetin, 80% of the allergy effect goes away. Without these drugs, bumetanide would only work for 8 months of the year.

      Once you begin to treat autism you will discover other issues that were there all the time, but you never noticed. My son's allergy is quite mild.

      You may have other issues like a food allergy that cause the same problem.

      Even treating the allergy, I had to increase the bumetanide to 1 mg twice a day to get cognitive function back to the improved level. I can check this just by asking simple mental math questions. In May he could answer a question, but the same question in July was too hard. The 2mg dose fixed this.

      Start the bumetanide again and, if it stops working, look for allergies.

      Delete
  5. I am very interested that you have tried baclofen. I am a practicing paediatrician in the UK & have been trialing baclofen specifically for anxiety in autism, & have had very good results, presumably based on its GABA-B agonist activity.I have about 8 children who are benefiting enormously, more relaxed, fewer tantrums, better sleep - parents are very impressed.

    However, I am using it off label of course. We use a lot of drugs off label for children because often the clinical trials are too difficult & expensive to make it worth while for the drug companies to get the licence, plus their profits will be relatively small compared to the adult poulation. However, it is expected that off label use is supported by at least a couple of respectable trials &/or a general consensus among colleagues, & I have only been able to find the arbaclofen trial which is very limited & was terminated early.

    So - I am out on a limb. I think it has enormous potential for the children at the more able end of the spectrum who are very prone to anxiety, especially the girls for some reason.

    Someone anonymous above has tried it & found it helpful, I would like to know how he got it, was it prescribed, if so by who? I am looking for other prescribers to support me, or some evidence in the form of research, otherwise I can't go any further with this

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    1. Tomorrow I will post about the Russian GABAb drug that is widely used there for autism and ADHD. You may then use the Russian research to support your ideas regarding Baclofen. Arbaclofen failed because start ups do not know how to plan clinical trials. In some children it was very effective.

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  6. Hi Peter,
    I am a parent of a 21 yr old. We have tried so many things...Your model of looking at autism treatment is exactly what I wish the myriad of doctors we have seen would use.
    Seth was diagnosed at 3, after beginning to gain skills (language, social skills) then lost them. He began ABA shortly thereafter and regained so much. At around 5, he developed brain fog, intensive stimming, and severe inability to focus and retain previous skills.
    At around 19, he added rages and mood swings to the mix. OCD began to creep in. He was diagnosed with lyme and the presence of viruses. His current doctor goes after whatever seems to be the order of the day and I keep thinking we should look backwards to that baffling regression at around age 5.
    Your thoughts as to what our detective work should consist of at this point?

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    1. Seth does fit the pattern of what I called "double tap" autism, where the initial autism later gets worse in a second step. In some people this is a mast cell (allergy) problem, in some it is mitochondrial dysfunction, in some it seems to relate to variants of PANDAS. To figure out what it might be look for what makes things worse or better. Look for external triggers, even simple things like diet, the time of year, stress etc. You could see if simple things like ibuprofen have an effect. If it is immune related, then it might well result in good days and bad days. If it is mitochondrial disease, this can be tested with standard lab tests. Things like stimming should respond to NAC. Also look back to see how he responded when he ever had antibiotics, or ever steroids.

      Delete
  7. This is fascinating. Antibiotics have not done much to improve things observably. Parasite treatments seem to calm down his "buzzing" body (it's painful to watch how wired he can be at times). The muscle tensing and jaw tensing--a weird form of seemingly uncontrollable stimming, seem to go down with the herbal parasite pulsing. Grapefruit seed extract has helped off and on.
    We have some sort of genetic testing from Yasko but if we need something further to better understand treatment, I am all for ti. My late husband's nephew was diagnosed at one point and my husband himself felt like he was on the spectrum. He took his life 5 years ago.
    What kind of genetic testing does one do?
    Thanks.

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    1. In most cases genetic testing does not seem to be that helpful, which is a pity. There is no easy way to figure out what to do, so it is a case of trial and error, but you can look for what other symptoms exists and what external factors affect the autism. I think that supplements will only take you so far, drugs that target specific dysfunctions are needed, but you may struggle to access them.

      Delete
  8. Hi Peter,

    I just found your website while investigating mast cell disorders, and it is amazingly informative. I am a 30 year old woman with Aspergers. I have had symptoms my entire life, but only became aware I was on the spectrum in my late 20s. As a result, I have always had strange physical anomalies and drug reactions, which were overlooked in my youth.

    Three years ago, I suffered a bout of Lyme disease, and either inflammation, encephalitis, or the drugs I took caused a traumatic brain injury. About half a year later, I contracted HSV1, and it damaged my immune system. I now have a natural killer cell deficiency, myriad allergies and intolerances, and potential mast cell issues, in addition to chronic viral and bacterial activation.

    I also noticed that I have developed more "classic" spectrum behaviors such as stimming, sensory overload, seizures, a loss of self and social awareness, as well as empathy, and a tendency to be less spontaneous/more self absorbed. I am not sure if these are the result of the brain injury.

    I read about your "double tap" theory, and wonder if it could apply to me, even at 30. Are immune defects common in autism? I cannot suppress viruses in my body at all now, and seem to have become intolerance/allergic to many substances. Do you have any advice as to where I could seek to address this? (Being on the spectrum and trying to persuade doctors of anything is a daunting task.)

    Also, thank you again for sharing all this information and being so proactive with your son. As a person on the spectrum, it really means something to see such a caring parent.

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    1. Depending on where you live, you may find a helpful allergist/immunologist. Otherwise you may have to self treat. Many things are available OTC. I would try NAC, common H1 antihistamines, statin, pregnenolone etc. Most of these things work very fast, if you are responder, so it does not need a lot of time or money. By finding what helps you can narrow down what the problem is.

      I am sure a double-tap can happen at any age, it just would not be called autism. TBI is very interesting as is post traumatic stress disorder, these are just conditions where homeostasis got disturbed. There are many overlaps with some autism.

      Delete
  9. Hi Peter,

    Here is a long overdue feedback on Verapamil and Bumetanide.

    Verapamil: Started May 2014

    Epilepsy: Seizures went from two a week to one after 45 days. A few months later we had one more such gap of 48 days between seizures. The rest of the time, she went back to once every 28 - 30 days, which had been her pattern prior to a secondary hit caused probably by severe allergies.
    Most fevers would also result in a large tonic clonic and from 2010 onwards she had been having recurrent sore throat and fevers, several times a year. She has not fallen sick once since Verapamil and therefore, no febrile seizures. (I also read that in TBI, the brain gets a good 2 to 4 degrees hotter than the rest of the body, so while the thermometer may be showing 100, the brain might already be at 104. In future, I have decided to cut the fever as soon as it begins.)

    Health: Obviously, immunity improved, in fact I took out the zinc that she had been supplementing with for years and that was supposed to help so much. For a while there I thought taking it out had somehow improved her immunity until I realized it was the verapamil. Interestingly though, verapamil does nothing directly for her seasonal allergies.
    Very good for anxiety, can stop an anxiety episode cold. If dosed properly, without missing doses and at the right gap, keeps it away.

    Autism: Flare ups, rages, sib, all of these stop within 20 minutes to half an hour. But allergies can cause a meltdown within 2 hours of dosing and we would have to come in with something else.

    ReplyDelete
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    1. Thanks. I also fiind it odd that verapamil treats the autism flare up caused by allergy, but not the allergy itself.
      In the allergy season I cut the verapamil pills in half and use more frequent, but smaller doses. It works well.

      Delete
    2. We moved from 80mg twice a day to 60mg thrice a day. Is it worth dividing this even further?

      I wish I had learnt this earlier as I get the verapamil compounded in capsules and could have easily had it done in a sustained release form.

      I have the prescription for 60mg four times a day, because this is the maximum dosage in the study by Mayo clinic for seizures. Btw, that study completed this year and was successful though the full results have not been published yet.

      Delete
    3. Verapamil has a short half-life, that means to maintain a high enough dose in the body you either need an overly high dose or a more frequent low dose to stay within the therapeutic range. I was using 40mg three times a day, but three or four hours after the first dose the effect is lost. So I use a pill cutter and start the day with what ends up as the bigger half and then three hours later at snack time at school, my son gets the smaller half. This has resulted in better performance at school. I also keep in my pocket some half pills and also NAC. The other day we went to an opera that finished at 10.30pm, so in the interval I gave a half pill of verapamil, to ensure all went well. It did. Verapamil is well tolerated, but one reader, Maja, did encounter side effects. This drug is really helpful for my son and so I would not want to encounter side effects, so I am keen to use the lowest total daily dose.

      Delete
  10. Bumetanide: Started May 2015

    This has been a big one for us.

    Epilepsy: Since starting bumetanide, most of the seizures have been the mildest we have seen, with easy and immediate return to normalcy. We have had only two tonic clonic seizures and both were at times when we had not dosed the bumetanide yet that day. coincidence? We are at only 1mg once a day. In the past, an hour past a seizure, she would be irritated, mildly distressed with a lot of jaw pressing and stimming intensely for hours. Since bumetanide, we have had the post seizure irritability only once, and for a short time, and it was after the tonic clonic where we had not dosed yet. I think it also raises the seizure threshold as I see many instances such as after exercise, allergies, etc where she might have otherwise had a seizure. These days, I am giving it before going to the gym.

    Social: much more demonstrative and affectionate with her dad. She had a great time with my brother when he visited, interacted with him quite a bit, and did not want him to leave. We had no clue that she liked him so much, we thought she did not care. Since the visit, she has also been willing to talk to him a little bit on the phone. Has also been talking to my parents on the phone, laughing and excited with them.

    Cognitive: Briefly, about my daughter, she has regressive autism, dyspraxia with a lot of motor coordination deficits and visual agnosia. She speaks hundreds of single words, and some phrases, but never been able to expressively use verbs. So, a lot of communication takes place with single words and songs. She is very bright, though cannnot be tested, does calculations as to time, date etc in her head and will then use words such as 'four saturdays' etc. Not a savant skill, actually calculates. Until bumetanide, ABA has not been possible.
    She is now using verbs, making phrases. Is even occasionally using adverbs. Able to answer a lot of 'what is he/she doing?' questions. Need to work systematically on this. Looking at ABA programs now, because she is able to point much more reliably. Her eye hand coordination is much improved, especially with pointing. Her finger does not tremble as much and she is able to be search out with her eyes first and then follow through with her finger, and all of this pretty fast.
    Writing has always been a huge challenge because of the vision issues, but suddenly now, she has taken a big leap forward. She remembers the form of the alphabet and is able to move to mid points, diagonal lines, etc. She is also writing the alphabet as dictation, without visual cues.
    Reading: In the past, I relied more on her very good memory to acquire reading skills, now we are much more systematic, and she is on her way to mastering the phonemes, and is able to blend them and read out loud.
    Classes have now become so interesting and fun these days. There have been so many more things that are changing day to day.

    Peter, just cannot thank you enough for all that you do, it is invaluable.

    ReplyDelete
  11. Hi Peter,
    Was wondering if you have added any other medicines to the poly pill, like coco flavanoids
    My kid is currently on Bumex and Clonozepam (minute dose), and is doing better.
    Looking at brocolli sprouts next.
    Have you heard of MNRI (mastugova) and ANAT baniel methods of sensory integration and neural path development, my OT is starting to use some of these, but to get trained is expensive for MNRI.
    BK

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    1. Hi BK, no I have not added anything yet to the polypill.

      In the end my therapy will be very specific to one person with autism.

      There are therapies for the core of autism and others that help the secondary problems that vary widely from person to person.

      In terms of improving cognitive function, which is what Bumex and Clonazepam are doing, the statin has a real impact in my son. It has an effect from the first dose.

      I have not heard of MNRI/ANAT. There are numerous therapies.

      Delete
    2. Hi BK,

      We did the Anat Baniel program at her main center here in California. It was week long and included sessions with her and Dr. Neil Sharp. It was good during and for about a week after the program. But the changes would not hold. The program was crazy expensive, I think we paid several thousand dollars. The mistake I made was that I had assumed that the program would help my daughter develop a good body schema and that we would build from there on. This was not the case, and I learnt later that many of the glowing testimonials come from people who work with them for months at several times a week. To work with them on an ongoing basis would have cost me about $6000 per month. In my opinion, it is a far better program than those offered by OTs, but useful only if it can be done consistently several times a week, probably for months or more.

      I think your son is very young yet, but do keep literacy in mind, I see it sidelined in a lot of specialist programs. It can take him to a much better functional place developmentally. Here is a link to a wonderful article written by a nonverbal autistic boy:
      http://journal4hari.blogspot.com/2012/05/a-hypenated-american-in-nth-dimension.html

      Delete
  12. Hi RG,
    Thanks for your reply, do you mean the ability to understand and write when you say literacy, I think that would be definitely very important, for us, he is 3 years 5 months, speech is his biggest issue, Bumex has helped a lot where he is playing and smiling with us.
    Yeah I feel like I am getting ripped off too several times on this journey (DAN doctors), but our OT who we feel is good mentioned about MNRI, what I am trying to do is watch and learn and try it at home. So I will keep trying that. MNRI was very expensive too.
    Thanks
    BK

    ReplyDelete
  13. Hi BK,

    Sorry for the late reply. By literacy I mean reading and writing with comprehension, and also math. Starting with reading and writing words, to simple books, to academics. As much as speech is an important and wonderful thing to have, I believe that literacy is even more important, as with it, one can have communication. Many interventions can be tried for speech, but one can never be sure if it will come and to what extent. Whereas, the chances for reading and writing and comprehension are very high. It can engage and challenge the mind, and lead to a quality of life that is intrinsically rich. It is one of the key requirements for a person to live independently.

    My daughter is an older kid, and what I have seen is that, every autism intervention, including doing nothing, has about one percent of kids who 'recover'. This blog is the only one that is completely rational and systematic. By translating so much research into practice, Peter is bridging the chasm and offering something completely unique. He gives us all a chance to succeed.

    ReplyDelete
  14. Hello Olga
    Thanks, we do add coQ10. I think all people on statins should take this supplement. One symptom of coQ10 depletion is muscle pain. Many adults on statins complain about these pains, but atorvastatin seems to be the best tolerated statin. I give 100mg a day of coQ10.

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  15. Dear Peter,
    For a non verbal child who is doing well with NAC what pharmaceutical drug would you suggest might be useful for speech from your polypill,to trial first secondly another that might not be in your polypill.as Monty has speech I know this might be tricky .Thanking you

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    1. The drug that has plenty of evidence to support its use in raising cognitive function is bumetanide. I think all non-verbal kids should give it a one month trial. 1 mg twice a day is the dose the researchers are using.

      Some kids with autism seem to "get stuck", in that they cannot complete a desired action as if something is inhibiting them. This was the case with my son. I can imagine this effect also stopping a kid from speaking. This issue was solved using Atorvastatin. This therapy was not based on anything in the autism literature, but it works for us and stopping the drug the old habit returns.

      Speech is such a big issue I would start with bumetanide for a month, continue if you notice positive changes and then add atorvastatin for a week. If atorvastatin has an effect it will evident in a couple of days.

      Bumetanide takes longer because it gradually lowers the level of chloride within neurons and can take 2 weeks in some and longer in others.

      So these two drugs affect cognitive function and improving this should move your child towards speech. You can combine this with behavioural strategies like PECS or just lots of 1 to 1, face to face interactions.

      Some people may not have speech for other reasons like rare metabolic dysfunctions. Bumetanide is treating a very common dysfunction, so I would start there.

      Delete
    2. This is very useful This is very useful would it be acceptable to say your poly pill can be all mixed together to give with no interactions.Would any supplements need to be used at the same time .Thanking you

      Delete
    3. In our case there were no interactions. It is best to try each one step by step, rather than start all at once, since not everyone will be a responder to everything. Everything can be mixed togrther. There are many types of autism and so not all people will be responders.

      Delete
    4. Peter I read in one of your write ups on potassium and magnesium is needed to ensure potassium is of benefit.My son the DAN says has magnesium deficiency but there are reactions to the magnesium supplement when given other people seem to have success with magnesium as calming etc I see agitation
      So can not give.
      I would like to introduce potassium 200 mg a day for a 7 year old before introducing Bumetanide .what should one do the doctor was Not interested in having my son tested for levels of potassium again is it a must to give magnesium with potassium and if he reacts to potassium what next

      Delete
    5. If you give bumetanide you are likely to lower potassium levels, but the autism researchers found that many did not need potassium supplementation, since the drop was small. A significant minority did lose more potassium and these people really do need extra potassium. There is far more potassium in one banana than in a potassium supplement. I doubt you will find potassium gives a negative reaction, if it does then use bananas.

      There is a difference between dietary potassium and supplements. It seems that in some people with autism the sharp/fast increase in potassium from the supplement has extra benefit. But you can replace the potassium lost by diuresis by eating bananas.

      So you could always give bumetanide and two bananas a day, until you have found a way to test potassium.

      Delete
  16. I am the mother of a 20-year-old male on the spectrum. He suffers grestly from eosinophilic esophagitis, reflux, allergies, and keratoconus (a thinning of the cornea believed to be connected to allergies. He clears his throat and is congested constantly and also has trouble swallowing. He has been on multiple medications and has seen the best specialists but nothing helps. I am interested in Verapamil and whether that would help. Do you have any other suggestions?

    Thank you!

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    1. Verapamil may help greatly, you would know in just a couple of days.

      You could try the Biogaia probiotic, which in my son greatly reduces his allergies, it works from the first dose.

      In addition to the standard drugs to lower stomach acidity (PPIs and H2 drugs) you can also use larger doses of melatonin (like 5mg) this is shown to help GI problems and melatonin is produced in the GI tract, so you are just adding more of what is already supposed to be there.

      There are mast cell stabilizers like cromolyn sodium and ketotifen, but you likely have tried these.

      You could contact Agnieszka, who wrote the guest post on Verapamil. She is very helpful. Her email address is in her post.

      http://epiphanyasd.blogspot.com/2016/03/verapamil-use-in-autism-request-for.html

      She knows a lot about this subject and she is a doctor and she is collecting case studies on people like this.

      Delete
    2. Peter I have stopped everything at the moment since 7 nonverbal year old child is on antibiotics for hpylori.apart from nalcrom and loratadine which helps itching from the treatment
      I know that there is a positive response to bumetandine she is more attentive and as you say foggy .I read a comment recently whereby a mother said her child displayed a few negative reactions .Coming to think of it ours also developed a sensitivity to sounds and some flicking of fingers near the eyes now that we have taken of the bumetandine this has subsided .I cant say its the antibiotics that helped this but will be certain when I reintroduce
      The bumetandine a 1mg tablet crushed works better than the liquid version.2 mg a day brings about a bad reaction.after the treatment for hpylori I am undecided on trialling either statin or diamox .
      verapamil was not successful which is a big shame as I found a reasonable source in the uk.I cannot find a source for Clonazepam which ideally I would have liked to have trialled.Peter does it matter which I trial first and for diamox what dosage would be suggested.
      Thank you

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  17. Hello Peter, Christine.

    So now we have at least three reports of some kind of minor negative reaction to bumetanide. It seems more a result of increased sensory issues which probably manifest as anxiety on Christine's son because of his age and in the younger one as sensory overload. The causes could be multiple.

    Cognitive impacts remain to be assessed.

    But we can conclude that bumetanide might not be entirely benign.

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    1. Kritika, some readers of this blog find increasing potassium solves sensory issues, so it is logical that a drug known to lower potassium worsens sensory issues. The solution, in those cases where bumetanide enhances cognition, would be to supplement potassium. You might also say that increased sensory sensitivity is a symptom of too low potassium level.

      Delete
  18. Peter,

    It's not as simple as that though I thought the same thing. My son had potassium levels at the extreme higher end before starting bumetanide. I also supplemented with potassium..to no avail.
    I suspect it's some other mechanism..imbalance in overall electrolyte balance, not just potassium, comes to my mind. It could also be slight physical discomfort.

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    Replies
    1. Kritika, potassium channel dysfunction exists in autism and other conditions. We have one reader with Anderson Tawil Syndrome, and she also has autism in her family. She tries to maintain a very high level of potassium. My son' s potassium level was very high naturally, but responded very well to small does of potassium. Clearly you do not want dangerously high levels of potassium. We know that channelopathies are part of autism but will remain undiagnosed. Bumetanide will disturb electrolytes and so for some people this may affect some present channelopathy.

      Some people trialing bumetanide get the side effect of low blood pressure because they did not replace lost fluids.

      So we should be cautious about all drug/supplement intervention. Side effects may occur and not all people can tolerate things long term. This is why it is important only to use drugs that give a big net gain and not use 20+ supplements a day.

      Delete
    2. My daughter had normal potassium levels a month after bumetanide. I tried 200mg of potassium because of sensory issues but it seemed to cause mild irritation. I gave it with magnesium and it took care of the irritation but did nothing for the sensory issues. I stopped it thinking it was of no use for us. Later, reading Agnieszka's comment, I dosed 400mg with magnesium and it has eliminated her hyperacusis, as well as improving many other sensory issues, such as haircuts, readily trying new foods with unusual tastes and textures, etc.

      Delete
  19. Agree with you Peter..completely. And right now giving him just bumetanide plus lots of water and yogurt, prunes and orange. Keeping a close watch and will not go on doing this hoping for some miracle unless I see something really significant.

    Would love to try Picorrhiza sps..it's a standard auyrvedic drug. I would not really put my hopes up high on herbs because Ayurveda may help mild lifestyle diseases and there it may help a little with IBS and other issues. In a latest research the most potent nootropic has been identified as our humble Brahmi. But how much it translates into real substantial improvements in patients with neurological disorders remains as big a question as ever.

    Will surely try kutki, though, as the suggestion comes from you.

    ReplyDelete
  20. I agree with Peter and just wanted to add that in the Bumetanide French trial they checked potassium levels before the treatment and then after 7, 30 days and 3 months as far as I remember - I wrote it from memory, but for sure there were several measurements. Children had their potassium supplement adjusted to the results. One left the trial because hypokalemia could not be corrected.

    I checked potassium level in the same way when started Bumetanide. My son might be exceptional but he needs 4-5 x 470 mg (12 mEq) potassium daily to get his K+ blood level wnl. I consulted this apparently high dose of K+ supplement with pediatric nephrologist and Prof. Ben-Ari as well and got reassured to continue with no safety issues provided he has no kidney disease.

    But it was after I introduced diet and lifestyle modifications when my son got clearly better also in terms of sensory sensitivity - all despite his blood level had been already corrected before. These included: dietary potassium, potassium supplement without carbs to avoid insulin spike lowering K+ blood level after meal and activating dysfunctional potassium channels, low sodium table salt - check previous Tyler’s comment on this, very helpful as well as recommendations for people suffering from hypokalemic periodic paralysis. As complicated as it may sound, it is all easy and comfortable in practice. M. went with all these potassium supplements on a summer camp with no issues for example. I think it’s worth a try.

    ReplyDelete
  21. Peter, Angeiszka,

    When my son started displaying sensory sensitivities on being put on bumetanide, I have him 100 mg potassium as potassium citrate which I upped to 250 mg once a day and then when sensory issues remained unabated, to 100 mg morning and 250 mg evening one fateful day. The next day my son had such a horrible gastrointestinal episode..holding his chest and stomach in pain, screaming, unable to stand straight. It was after i gave him cyclopam that he felt better. And now I have stopped potassium and the sensitivities have subsided although they do rear up sometimes as peripheral vision. So in all likelihood, it's unrelated to potassium and if it is, that will be another cause of worry after my son's experience with potassium. The potassium citrate had a small amount of mg as well. But that episode has really left me shaken as at one point I thought my son is slipping away.

    I do not like the idea of playing with electrolytes too much as I have experienced first hand how drinking excessive water leading to depletion of sodium and probably other electrolytes as well left my aunt with a serious neurological impairment and she never recovered completely.


    ReplyDelete
  22. Angeiszka,

    Could you elaborate on lifestyle and dietary modifications to keep K levels high..low carb meals to avoid insulin spike? And I can't find Tyler s comment on low sodium diet.

    I feel Na levels also have to be kept in mind at least for some individuals. Too low a Na concentration might create problems of its own for some. I do not have a medical background but have done lot of hospital sit ins for relatives.
    .and this is what I always heard the doctors discussing.

    Please give your opinion..

    ReplyDelete
  23. Hello Kritika,

    I am sorry to hear about your son's pain episode. I feel for you, especially having recently been to the ER with my son due to unexplained, severe abdominal pain (resolved already). The good thing is that using drugs discussed in Peter's blog the risk of serious adverse effects is really small if you follow basic safety rules. Well, it is not the first thought you have on your mind when your child is in pain though, at least in my case.

    You are right, it is not all that obvious. What I wanted to say was that in doubt checking potassium (along with other electrolytes) blood level could be helpful. At least some of the concerns can be exluded or addressed when you know the result. If you don't check, you can only guess. Perhaps it's easy for me to say that, as I am lucky to have a child who does not mind blood drawing.

    Did you use liquid potassium or tablets?

    ReplyDelete
  24. Kritika, I did not saw your previous comment before.

    Yes, it's best to have all electrolytes balanced.

    To keep dietary potassium high I found a list of potassium content per 100 mg in foods, unfortunately it's in Polish, and I have it now printed in my kitchen. I don't count details, just choose products that really have high potassium content and my kids like them. This way I found that in our case kiwi is better than banana.

    Also there is a paper by the doctor who suffers hypokalemic periodic paralysis himself:
    http://www.translational-medicine.com/content/6/1/18

    I found it very useful although obviously neither my son nor yours has hypoKPP. According to this paper, high carbohydrate meal induced insulin spike lowers your blood potassium level and "triggers inappropriate activity of mutated voltage-gated ion channels” (in those persons who have such dysfunctional channels of course). The paper says that significant carbohydrate load in banan makes it less useful to raise K+ blood level than potassium supplement. He also advises K+ prophylaxis before carbohydrate meal or exercise, so I give potassium to meals 3-4 times a day. Btw I use effervescent supplement and this way I am sure my son is hydrated well.

    I do not follow any special low sodium diet, but use low sodium/high potassium table salt and this is also one way to keep potassium high, easy to apply. Where I live you can buy such salt in most groceries.

    All in all it’s not really disturbing and the “side effect” is that it is quite healthy diet in general. Your son may not need it on the other hand. My son turned out prone to hypokalemia, so it was necessary to let him use Bumetanide at all. Before I tried these potassium targeting interventions I did not imagine it could be so helpful and easy.

    ReplyDelete
  25. Angeiszka,

    I used the liquid potassium but mixed it in half a mug of water and added some mango juice to subdue the potassiums horrible taste.

    Yes, I am using low Na table salt but mostly will use either rock salt or Himalayan salt for my son's meals as it is considered to have other minerals as well and not as highly processed as the standard table salt.

    I am doing the oranges and kiwis already. But will try to work a way out of possible lowering of K following a high carb meals. One thing good about Indian meals is that it's quite balanced..legumes, veggies, carbs, ghee and spices. But there is always scope for improvement.

    Could you, when you get the time, relate how your bumetanide experience went..in case you can recall the initial response when you started it..and how it unfolded. I have already read your and RG s comments mentioned in the blog.

    Thanks for being a sympathetic ear and your suggestions

    Wishes



    ReplyDelete
    Replies
    1. Do you think that it is potassium supplement that your son reacted to with pain? Was it the only time you gave him potassium?

      Re your question: initial response to Bumetanide in my son might not be typical, as he was still on a very low dose of Valproate tapered down when I started Bumetanide. I saw the distinct mood change the same day and this was probably related to Valproate+Bumetanide combination. Peter discussed low dose antiepileptic drugs effects here before.

      You can have a look at our notes from early days on Bumetanide in this table, previously a food diary recommended by allergologist that somehow evolved into treatment diary:

      https://docs.google.com/spreadsheets/d/1FxzsS_QSAS_X1YNSH-InoxTQt4WqNnFQpAZd-iXE4wk/edit#gid=0

      One can be surprised by the hype about 8 yo greeting a parent coming back from work or counting to two, but it’s the answer for “just what is autism?” question at my house. So writing about Bumetanide response in my son, I describe what happened in a child profoundly affected by “autism”, deemed to be able to have only 1:1 classes at his previous autism center and not progressing.

      My husband was not aware for what I gave Bumetanide, but it was him who wrote “seems like it’s possible to teach M. something” - after 3 weeks on this treatment. This is the best summary how Bumetanide helped our son as several months/years before he had lost the ability to learn any new skills. In short it was Bumetanide which allowed him to attend mainstream preschool class (with aide and IEP) and improved his communication to the point he could tell us about headache, previously misdiagnosed as mood disorder by psychiatrist. My son went hypokalemic (3.1) after one month of Bumetanide use, then I started K+ supplements.

      Bumetanide did not help for migraines in my son and during headache episodes, at times lasting a week or more, his sensory sensitivity increased. That’s when increasing potassium helped. Otherwise some sensory issues (pressing against objects, vocal stimming) disappeared completely on bumetanide, which I did not expect.

      I was lucky to talk to Dr Lemonnier once (thank you Treating Autism!) and I learned that he has been treating some children with Bumetanide for 8 years now. He told me that Bumetanide long term use seems more beneficial than can be expected from the results of their published trial as this treatment enables proper neuronal maturation. So in my opinion, if Bumetanide helps (it does not for everyone), then it’s worth to continue even if there are things to overcome such as potassium issues.

      Delete
    2. Hi Angeiszka,

      Sorry I missed your comment and just saw it while going through other communications on Peter's polypill.

      Angeiszka, I am pretty sure that if not entirely responsible, potassium did aggravate a stomach issue. I had started with NAC and100 mg potassium after observing visual stimming in my son on starting bumetanide. On finding no respite, I upped the potassium to 250 mg and noticed a mild discomfort. To rule out the role of nac here I stopped it and continued with just potassium. Finally, no improvement in his sensory behaviour led me to niece that I need to further increase the potassium. This decision was based on experiences shared by readers and also Peter with regards to potassiums ability to rectify sensory overload. But when I increased potassium to 300 mg, given in two devided doses, the next day my son reacted with severe pain.

      In fact after I stopped the potassium that the peripheral vision became less frequent although it's still very prominent. So if my son's potassium levels go down when on bumetanide and I see continued cognitive enhancements with it, I will have to largely manage it through diet and probably giving supplemental potassium in smaller doses.

      Getting blood works done is not very easy, not as much because of my son getting upset but due to requirement of a doctor's recommendation..I feel so irresponsible trialling drugs on my son without supervision of a doctor. Will surely get the electrolytes assessed once my son completed 30 days.

      Angeiszka, I will go through your detailed observation ..I am so grateful to you for sharing your notes on bumetanide effects on your son with me. It must be so difficult to take out the time to respond to queries and you have two kids and a career. I really appreciate your very balanced suggestions.

      One disturbing observation about my son for the past few days is that he is weirdly running up to all the electrical sockets one by one and staring at the holes. This kind of visual behaviour I have not seen in him ever before. I convinced it's due to bumetanide.. whether it's temporary needs to be seen. I am following Christine advise to me about sometimes letting the child's body adjust to changes and attain a new equilibrium and then decide what is worth continuing.

      Thanks again for your time and concern





      Delete
  26. I am of Indian origin. I find it hard to digest many traditional Indian foods like legumes and beans and eat them only occasionally. I think you mentioned that you and your son are vegetarians because of your experience with your father's negative reaction to meat. Have you ever tried giving your son meat? My daughter was vegetarian until about seven, at which point I switched her and it was the best dietary decision I made. Her health improved quite a bit including anemia, a tendency to eat ice constantly, and most importantly, rolling around screaming in pain.

    It will be easier to have a more balanced, easily digestible diet if you could bring yourself to give him some meat.

    ReplyDelete
  27. RG,
    My mom has eaten fish and mutton all through her life and has been anaemic and I have grown up loving non veg food and am anaemic. In fact, my ma's haemoglobin levels went up in the past few years as she became really regular with fruits. And this was after non veg meals became quite a rarity because of my father's experience.

    I am a vegetarian by choice and had turned into one long before my father's episode. I am passionate about things that walk and swim and fly and cannot munch on them. I spent the last night thinking about your cousin and thought that is where I too was headed. I have been a painfully shy and a non fitting individual and was rescued only because of my deep passion for animals which my parents thankfully never discouraged. I would routinely bring in all kinds of sick creatures home and the whole family accommodated. Most of you who are whole people cannot understand what how deeply tormenting it is to be coered into fitting in. It just takes away your self worth and leaves you wretched and wrecked. I claimed my strong identity and emotional stability after first having to prove my intellectual credentials. But I was neurotypical. Most high functioning autistics cannot do that. As a society we have to accept individual diversities and rather than making people conform aim to make them self respecting, functional and stable. And I may be biased here, but I strongly feel, if we could somehow get our autistic kids, at least the cognitively more advanced into care taking roles, say animals, it might provide some kind of anchor and meaningfulness into their emotional lives.

    And RG, if I need the feel to add mutton to my son's diet i will do so. Not at all rigid there.

    As usual, thanks for your wisdom.

    ReplyDelete
  28. Peter, Just wondering if you have had to make any adjustments or deletions in your polypill list since your son hit puberty? I am assuming based on some of your posts he would be well in to adolescence now - is he about 14 yrs old?

    ReplyDelete
    Replies
    1. Tanya, he is 13 and a half. Puberty has not so far had any effect on his autism. The polypill did not change.

      This is the time many people with autism develop epilepsy and I had expected some worsening of autism. Our only issues are pollen allergy and milk teeth. The last milk tooth is about to fall out, finally.

      Delete
  29. thanks Peter. epilepsy aside - I guess what I really mean is social-emotional issues popping up at this time. This might be too personal of a question - and don't mean to pry. Anyone here with teenagers would love to hear from you. Just curious of other experiences during this unique time of development and certain medicines to avoid etc.

    ReplyDelete
    Replies
    1. I think it is people with Asperger's that may struggle as a teenager, particularly in co-educational schools.

      We have had no issues. NT teenagers, like Monty's big brother, worry about what brand their T shirt is and whether they are cool. In our kind of autism we do not need to worry about that.

      Some people with more severe autism who have not had some behavioral therapy as a young child can exhibit what is seen as inappropriate sexual behavior. Taking clothes off, touching other people, touching themselves etc. This is resolvable with a good ABA consultant. No magic pills.

      The big thing to avoid is epilepsy. I think the kinds of treatments we use have reduced the chance of epilepsy, but it would be impossible to prove. My advice would be to treat your channelopathies way before puberty.

      Delete
  30. oh the "autisms" - so many different flavors.. I disagree based on our experience - my son just turned 17 and his situational anxiety has increased a bit and seemingly depressive moments. He does not have aspergers has never exhibited the behavior you mention (in fact i know a mom with a higher functioning kid who had some of those troubles at school). tExperience has taught us, if I want more angst and autistice meltdown, then add a behavior therapist to the mix. Some kids learn and respind better in more natural settings and approaches. Wasn't asking for magic pill but wondering about benzodiazepams and the adolescent brain in terms of addiction susceptibility - but you've answered my question anyway - we missed the boat on treating channelopathy before puberty...... Thanks so much for your time Peter. Greatly appreciate your blog.

    ReplyDelete
    Replies
    1. Tanya, benzodiazepines at the regular doses seem to cause endless problems and leave you worse off than when you started.

      You might find something no-addictive. Propranolol is used by some people with autism and is also used by actors for stage fright. It may also have other benefits in some people with autism, the trial below was in young adults:-

      Propranolol May Improve Social Skills in Youth With Autism
      http://psychnews.psychiatryonline.org/doi/full/10.1176/appi.pn.2016.PP2b2

      Delete
  31. Hello Peter,
    Daniel Here, We are wanting to trial Bumetanide on our 3 year old son with autism. he weighs about 32lbs What would you suggest we start with dosage wise? I think the trial used 1 mg twice a day? should we start lower and work up to that? Also is there anything he should not take while trialing this? I don't think i can get a doc to prescribe a Potassium lvl check, should i just feed him bannas, Orange juice etc? Or Should I just use a potassium supplement. I am in the US so I had to order Bumetanide from Mexico under the name Miccil. This is the same thing correct?

    ReplyDelete
    Replies
    1. Hi Daniel,

      Not Peter, but Miccil is the same. It was the first one we tried when we started verapamil and it was very effective.

      Delete
    2. Daniel, the researchers give the same dose regardless of weight, that is 1mg twice a day. Miccil is the Mexican brand name of Bumetanide.

      I would add dietary potassium as you plan. In our case I added 250mg of potassium twice a day, this itself has benefits in addition to what the bumetanide achieves.

      RG (from the above comment) uses a higher dosage of potassium which makes the sensory issues go away.

      In the US potassium supplements are limited to 100mg. Where I live I buy a 500mg effervescent tablet and split it in two.

      Ideally you would measure potassium in his blood and maintain it at high normal.

      You normally need to wait a few weeks to know if your son is a responder. In our case it was two weeks. The level of chloride in his neurons slowly reduces to a more "normal" level and this takes time.

      Bumetanide is well tolerated but often drugs interact with each other. So if you add another drug you should check for known interactions. Bumetanide is an old drug and so well known. We have used it for nearly 4 years with no problems.

      Delete
  32. We started Bumetanide at 0.5mg 2x/day for our 7yo son (22kg). How long do I have to wait to see if it is doing anything? So far, nothing, but he has been taking it for only 2 days.

    ReplyDelete
    Replies
    1. Vladimir, it is highly variable. It could be a week or a month. In our case it was about 10 days.

      Make sure your son is drinking lots of water, most people do this automatically, to compensate for fluid lost due to diuresis.

      Add extra potassium in diet (eg banana, kiwi etc) and/or add potassium supplement. Bumetanide will likely cause a loss of potassium.

      Delete
  33. Hi,

    Our son started taking Bumetanide .5mg twice a day about a week and a half ago. His biggest gains seem to be social - playing more with siblings and me, doing things to get a reaction. He also seems to have a much easier time with schoolwork....it seems less challenging to him. He is speaking more, and in more complicated sentences...but not as much as I hoped for. I'm happy he is on this medication and I thank you for shedding light on it. My question- if he is showing improvement on .5mg, should we consider upping to 1 mg twice a day at some point to maximize the effect?

    ReplyDelete
    Replies
    1. 10 days is still quite early to judge the effect, you may find the effect grows in the coming days.

      The bigger the dose, the bigger the effect up to a point when the effect may plateau (this is what happens in diuresis). As you raise the dose you will get more diuresis and so lose more potassium and fluids. The side effects of bumetanide are caused by not replacing the potassium and the fluids. Loss of fluids causes dehydration and drop in blood pressure.

      Depending on how big your son is, you might consider a higher dose based on the findings from the clinical trials. My son is now 50 kg / 110 lbs and I have moved up to 2mg in the morning and 1 mg in the evening. He started 4.5 years ago on 1 mg once a day.

      You need to do things gradually and to find out if your son easily goes hypokalemic (low potassium). My son does not, but some people have this problem and they are the ones which will experience side effects, if the parents do not add back enough potassium. You need to measure the level of potassium in his blood and maintain it at the higher end of normal.

      Delete
    2. Austin, I think after a month the biological effect will have peaked and your son will have got used to the new way his brain functions. That is the time to judge the effect. Then you can decide if you want to try a higher dose.

      Delete
  34. Peter
    Do you have any advice on how to create tiny doses of capsules, pills etc? Since my daughter is still very small I need to divide most medicines that are aimed at adults or older children.
    /Ling

    ReplyDelete
    Replies
    1. Ling, on Amazon you can buy micro scales very cheaply. You can then crush a pill and weigh a precise amount very easily. You can even prepare a mixture of different things and store in a gelatine pill, then on the day you need the mixture open the pill and add to food/drink.

      Delete
  35. Hi Peter,

    I have gotten my hands on clonazepam, what daily dosage would you recommend for an adult with a weight of 95kg?

    ReplyDelete
    Replies
    1. I think the low dose effect would need about 0.05 mg perhaps slightly more. It takes 3 days to reach a stable level. So you could try 0.05mg for three days and see if it takes effect, if no effect try 0.06 mg for three days. If you get a negative effect, the dose is too high. If there is no effect then this therapy is not for you. There is a narrow range where GABA is made more inhibitory in some people, which gives beneficial effects.

      Delete
    2. Ah ok right, i will be trialing it soon.
      I have gotten great success with sulforaphane so far, very drastic results tbh, but i have ran out atm, new supply incoming though.

      Been trying ginkgo, arachidonic acid and pas (phospha acid/serine complex).
      Great results with lowering stress levels with phospho lipids tbh, how come you never mention them, they are needed for the prostaglandins.
      Also theres a study out there (asd/aspergers) whichactually shows aspergers have elevated epa and dha! and lower arachidonic acid levels.
      Also both the dha:ara and epa:ara ratio is much higher in aspergers than in healthy individuals. I found this striking and shocking... for years we have been bombed with the so called fact that people with asd arw low in epa an dha, while this study shows the oposite is true!!!!! P<0.05 or smaller btw.
      I found this striking as i always found fishoil to be emotionally dulling even more so than my baseline.
      Been on arachidonic acid 350mg a day for 3 weeks now and i seem to actually just walk outta the house and wanting to be around others.
      Im honestly shocked arachidonic acid gets never mentioned on any website!
      The fever effect is mediated by pge2, arachidonic acid is only one step away from it.
      Also inositol seems to make me more social, there needs to be looked more into the prostaglandin/5ht2a system imo.
      I know for myself i have a very underactive 5ht2a system i have tested this a few times in the past where i took magic mushrooms together with friends, they were tripping their asses if while i would feel just emotionally mormal for a few hours.
      After all the 5ht2a receptor is basically the perception system, including social and emotional recognition.
      Along with the water sensing system and acid-base systems which fuel social cooperation as a survival mechanism.

      Delete
    3. Peter,

      I have started 0.05mg clonazepam per day as you recommended.
      However further looking I have also seen you have recommended 2x 0.05mg a day for an individual weighing 70kg (I weigh 95kg). Is this because I should fradually increase my dose if no effect within a couple of days?

      Thanks

      Delete
    4. Based on feedback, most children respond to about 0.025mg, which is less than I expected. I think you should start at 0.05mg and after 3 days increase slightly if there was no response. The effective dose does vary between people, even factoring in their weight.

      Delete
  36. One final question Peter,

    I know this is my first day on clonazepam, but is the somewhat mild sedative effect I am experiencing partvof the therapeutical effect or will this gradually fade after 3 days?

    ReplyDelete
    Replies
    1. Ok thanks,

      Im not liking the effects of clonazepam at all so far, it seems to induce boredom and irritability in me, guess it is not for me.

      I have looked up on wikipedia and aggression and irritability are quite frequent side effects, peak plasma is reached in about 4hours, I started feeling worse 1hour after intake.

      Hope other people with aspergers respond better to this than me.

      Delete
    2. Are you sure you have the right dosage? If you have a 0.5mg tablet, you need one tenth of it, or if you have a 2mg tablet you need just 1/40th of it. It is easy to get it wrong by a factor of ten.

      Delete
  37. Yes I crushed the 0.5mg pill with the back of a spoon to fine powder and empty the powder in a small glass jar.
    Then I measured 100ml water to the jar and very firmly shaked it for a while and took 10ml with a syringe.
    Guess it might help others but not me.

    On a side note im now back again on na-r-ala and 3x2 capsules broccomax a day and feeling so much better again.

    I have ordered galantamine and it should be arriving within a week, I will be trying it.

    Also im still taking arachidonic acid and phosphatidylserine.
    I find that they help to keep me calm, open and receptive for social interaction.

    ReplyDelete
  38. Hi Peter,
    Thanks so much for your fascinating blog, I stumbled upon it when researching NAC as a supplement for my aspie son -(which has been very successful) and I have enjoyed the wealth of information presented so clearly and intelligently.
    I am looking at gradually trying out various supplements you recommend, but I would like to try and ramp up my symptom tracking. I was wondering how you go about this in terms of what do you measure? Do you scale things etc, and keeping it to a manageable level! Any tips?
    Best wishes,
    Teresa

    ReplyDelete
    Replies
    1. Teresa, I am glad that NAC works so well.

      The most important thing is try one thing at a time and not to draw conclusions too quickly. Many people find certain things work well for a couple of weeks and then either appear to stop working, or make things worse. You will see many wonderful reports on the internet of what happens on day one or two, what matters is what keeps working after 6 months or 6 years.

      Some methodical people keep a diary that records variables relevant to their child's specific issues, which naturally vary widely.

      When you stop taking a supplement/drug you should expect a return to the previous base line. Restarting should then give the same improvement, if the drug is effective.

      Some drugs do stop working when things like allergy get worse and so you could record general health issues in the diary.

      Some people with Asperger's respond to bumetanide, which surprises me. Many seem to benefit from Baclofen. I would try these two.

      For almost all therapies you will find people who respond negatively, and that even includes NAC.

      If NAC works well, then try the sustain release NAC, which may work even better.

      Delete
    2. Maybe it's not such a big surprise that bumetanide works for others than those affected with classic autism. We have seen that some readers of this blog have the adverse benzo response without being autistic. We also know some factors that can alter the GABA I/E balance (hypothyroidism, brain injury, allergy) a long time after birth. Also, I guess that GABAA is more prominent in some areas of the brain, with differences from person to person.
      The result should be that depending on when in life the I/E balance goes off, how much it goes off and where in the brain it goes off we get different results like autism, schizofrenia, brain fog or Alzheimer's.
      Often not as the only cause of course.

      /Ling

      Delete
  39. Hi Peter,

    After my bad experience with clonazepam I am now back on sulforaphane and it has again shown me its sustained effectiveness to reduce social and daily stressors aswell as boosting my energy levels.

    My galantamibe has arrived 2 days ago and ive used 4mg in the mornings so far.
    It gives a nice calming effect to me but i feel it takes the reward for achieving things away a bit for me allthough its not very bad.
    Would also like to add galantamine seems to indeed enhance my sleep quality as science claims it to do.

    Would you recommend lowering to half a capsule (2mg) or doubling to 8mg to bring hopefully some rewarding sensation back?

    Also next on my list is buteamide, can you recommend any cheap european source.

    ReplyDelete
  40. I started searching for natural blockers of NKCC1, and found that quercetin, forskolin, and possibly all NGF and BDNF activators actually increase Cl- through NKCC1 activation, an action opposite to Bumetanide. If Bumetanide inhibits NKCC1 and neurite outgrowth, what are the long-term effects of Bumetanide on development? Do excitatory GABA receptors even exist. From https://en.wikipedia.org/wiki/GABA_receptor :
    There have been numerous reports of excitatory GABAA receptors. According to the excitatory GABA theory, this phenomenon is due to increased intracellular concentration of Cl¯ ions either during development of the nervous system or in certain cell populations... However, the excitatory GABA theory has been questioned as potentially being an artefact of experimental conditions, with most data acquired in in-vitro brain slice experiments susceptible to un-physiological milieu such as deficient energy metabolism and neuronal damage. The controversy arose when a number of studies have shown that GABA in neonatal brain slices becomes inhibitory if glucose in perfusate is supplemented with ketone bodies, pyruvate, or lactate,[15][16] or that the excitatory GABA was an artefact of neuronal damage.[17] Subsequent studies from originators and proponents of the excitatory GABA theory have questioned these results,[18][19][20] but the truth remained elusive until the real effects of GABA could be reliably elucidated in intact living brain. Since then, using technology such as in-vivo electrophysiology/imaging and optogenetics, two in-vivo studies have reported the effect of GABA on neonatal brain, and both have shown that GABA is indeed overall inhibitory, with its activation in the developing rodent brain not resulting in network activation,[21] and instead leading to a decrease of activity.[22][23]

    ReplyDelete
    Replies
    1. Vladimir, one doctor at UCLA thinks that bumetanide is unwise in very young children, he suggests those people take Ponstan and then switch to bumetanide when they are a little older. This is only an issue for people who get diagnosed at 18 months. In many countries it is 3, 4 or 5 years old, before the word autism is mentioned.

      Delete
  41. Our son has classic autism. We gave him 600 mg NAC 4 times/day and the improvement in his speech is amazing. We ordered broccoli sprout supplement from Jarrow and looking forward to receiving it. One of the issues still remaining though is hand-flapping, which hasn’t improved and is also combined with screams of pleasure and morphasms. Any suggestions for those? Sorry for my English. Α young couple from Greece. Our son is 8 years old.

    ReplyDelete
    Replies
    1. Thomas, it is hard to say what will help for a specific behavior. In some people NAC would stop the hand-flapping, which is stereotypy, but not in your case.

      If he has classic autism I would next try bumetanide, if you live in the north of Greece you can drive to Serbia and buy it very cheaply in any pharmacy. It is not available in Greece.

      Delete
    2. Hi Peter

      Other than bumetanide are there any other drugs in your list not suitable for 2y.o with autism?
      I have read that sulphurophane supplements are ineffective and hence have been giving my son one teaspoon of broccoli sprouts twice daily? What is your view on this? And is there a particular supplement that you recommend that is as effective?
      Final question what are your views on methyl b12 supplements? Some publications suggest it is effective for autism

      Delete
  42. Hi Peter !
    My son now aged 15 is diagnosed with PDD-NOS at the age of 3.5 years at NIMHANS, Bengaluru, India. Apart from Behaviour Therapy, we were advised to give clonidine 0.05 mg twice a day. As we are living in a rural place, we don’t have access to Behaviour Therapy and we are giving therapies what we learnt at NIMHANS. His cytogenetics report revealed NO Chromosomal Abnormalities. His urine test for abnormal metabolites is negative. His brain CT scan is normal. At that time he has extreme hyperactivity and strong obsession to wards GOD’s photos and completely non-verbal.
    At Hyderabad, at the age of 5, we have consulted an Allopathic Doctor, who specialized in developmental disabilities. He diagnosed my son is having Mild MR with behavior problems. There at Hyderabad, he went to Speech therapy and Behaviour therapy with great difficulty. At the end of 6 month therapy One word he could able to utter.
    We met another Doctor at Hyderabad, who is treating autism cases. She advised us to use Omega-3, Calcium supplement ,Lactobasillus Tabs,B6 and GCFC diet. We have followed her advice and we have given meds for a year. We have observed reduction in hyperactivity and improvement in cognitive ability, but the obsession towards GODs photos continues. For various reasons we had to be away from Hyderabad for 3 years and could not get the much needed therapies.
    Based on a research finding that the Minocycline is helpful in the reduction of Autism symptoms, stopping the above Meds, we have started Minocycline and continued it for 4 months. No improvement except black circles around eyes is observed. Thereafter we have discarded Minocycline and continued the earlier medication as it is safe. We have used the memantine for about 2-3 months, but it is of no use.
    At Hyderabad, my son (completed 9 in 2013) is admitted in a special school. The psychologist assessment during admission is Moderate Intellectual Disability with Autism. An Ayurvedic Doctor friend of mine advised me to contact a Doctor in Kerala, who is specialized in treatment of developmental disabilities. His diagnosis is Classic Autism and my son requires both Behavior Therapies and Medication. He prescribed some detoxifiers apart from Ashwagandha and dhara therapies. We have consultations with the Doctor every year as the herbal Medicines could able to reduce hyperactivity and rocking movements. We have continued the meds till Nov 2017. All these year he has been going to a special school. Doctor advised me to test my kid’s blood for serum ammonia, serum lactate and serum pyruvate, accordingly we did it in 2014.
    The results for Ammonia ( Method : GLDH)
    Observed Value: 143.3 Units: ug/dl Biological reference Interval : 17-90
    Result for lactate (Method:Spectrophotometry )
    Observed value: 74.4 Units: mg/dl Biological reference interval : 4.5 – 19.8 mg/dl
    Serum pyruvate test is not available at Hyderabad and as such we could not get it done.
    As no behavior disturbances are seen, now our concern is speech (as he is non-verbal) and basic academic skills.After stopping the above meds we have used leucovorin calcium-15 mg twice a day (Brand Name : Recovorin) for about a month and benfotiamine + biotin for one month and forsultiamine for a month. For all these no specific improvement is seen.
    I have been following your blog since Oct 2017. After stopping the Above Medications, from Mid-December, I have started Bumetanide to my kid ( 2mg in the Morning and 1 mg in the evening).I have added Potassium and Magnesium Citrate 2.5ml twice a day ( 5ml = 1100 mg K and 375 mg of Magnesium).
    After one month I have added NAC 1200 mg twice in a day. The result I could see is reduction in fear, drive and vocalization (sounds but not words). The effect is observed till March 2nd week. Now that sounds disappeared and the undesirable outcome is hyperactivity/rocking.
    Now I am confused. I request you to guide me with regard to Medication.
    Sorry for my lengthy post

    ReplyDelete
    Replies
    1. I do think that you will need a combination of some kind of 1:1 intervention (be it ABA, or something else) and the appropriate drug therapy.

      Finding the appropriate drug therapy is not easy and even with all the tests you could run, it often still comes down to some trial and error.

      Looking for clues in any medical comorbidities can be helpful to put your son in a sub-group of autism. GI problems, allergies and physical features etc.

      I would make a long lest if all the interventions you have tried and note which gave some tangible benefit for at least a month.

      If your son responds to bumetanide for a couple of months, he is a responder. Something may subsequently occur that blocks this effect, but you know that chloride levels are very likely elevated.

      The same is true with NAC, if he responds well within a day or two, you can be pretty sure that oxidative stress is an issue. You can have oxidative stress and not tolerate NAC.

      The elevated level of lactate is something that you should follow up with a specialist. This might be caused by a metabolic disorder and quite likely a mitochondrial dysfunction. You may have to travel to a big city children's hospital, but I am sure you can get this evaluated in India.

      If it is a case of mitochondrial disease, there might well be physical symptoms such as lack of exercise endurance.

      Delete
    2. Hi peter
      Earlier we have given leucovorin calcium tabs, but the dosage low. I have read somewhere that leucovorin contains both D form and L form but the L form is active and is helpful. I wish to add L Methyl folate 7.5 mg/day inaddition to current medication (bumex 1mg twice,NAC 1200 MG twice and K + MG citrate). Your advise please ....

      Delete
    3. In Dr Frye's 2016 paper he gave 2mg/kg of leucoverin with a maximum dose of 50mg. He has done a lot of work in this area and so I would assume leucoverin is the best drug for people who are positive for folate receptor-α autoantibodies (FRAA).

      So I think if you want to follow Dr Frye you either send a sample for FRAA testing or use his 2mg/kg dosage.

      He apparently gives his FRAA negative patients the same therapy.

      Delete
  43. Hi Anonymous,

    I am mother to a six year old autistic child and reside in Delhi. I have been trying to acquire bumetanide which as you know is not available in India. Would you be kind enough to share how you sourced it.

    I wish the best for your son and hope you are able to get help from Peter and his knowledgeable commentators.

    ReplyDelete
  44. Hello Peter,
    I have recently found your blog and am amazed at the amount of information you have complied over the years. I have a quick question. I am in the US and would like to start giving my son Zeke several of the items from the polypill. As you mention the Bumetanide is hard for us to get I think I found some via online mexican based internet sales but assuming it helps Zeke I would prefer for that not to be the main way i source it in the future. So I purchased potassium bromide via amazon. My question is it says for lab use, not drug use. I am no chemist by any means, just a dad looking to try something but want to do it in a safe manner. It is HIMedia GRM6363. Anyways if you could let me know if this is the right stuff.
    I also plan to give him NAC and Stabilized Suloforaphane per your polypill recipe.

    I plan on giving him these for the next 30-45 days to see what type of results I may see.
    I'll take notes and pass them on if you would like. I had seen on other posts this may be of use to you.
    Again, thank you.
    Zeke's Dad

    ReplyDelete
    Replies
    1. Hello Zeke's Dad, all feedback both positive and negative is helpful to other readers.

      I would try the Mexican bumetanide before potassium bromide. The Mexican bumetanide works just fine and if you make a trial, it will take 2-3 weeks to lower chloride levels and then you will see if Zeke is a responder. Potassium bromide takes much longer.

      It looks like most people in the US are buying Mexican bumetanide. Not ideal, but that is just the way it is.

      NAC and sulforaphane take effect within a day or two, if you are going to be a responder.

      Delete
  45. Hi Peter

    Thank you for this amazing blog. My son who is 2.10 years old might be one of the youngest on the polypill. It's only been 3 weeks since I started Bumetanide 1 mg once a day and my little boy has gone from few words to singing rhymes repeating words and more imitation. All the gains are cognitive and not social but still is a big leap forward for us. We saw no side effects and giving extra potassium supplement and lots of water didn't seem like a big deal at all. ( I known it can be a problem for some kids ) I still feel the need to tweak the dose maybe 0.5 mg twice a day or 1 mg in morning and 0.5 in evening to get more benefit but will go steady for now. He is also on Simvastatin and NAC. The statin does help a bit with more initiative like he rides a bike and goes on it independently but still has a few issues like wont eat food in front of him and pulls our hands to feed him. After I gave him NAC and bumetanide my husband noticed his increased awareness and speech. I do feel there could be some more improvements like his eye contact and complex speech but again I guess we have to be realistic too. Maybe he needs time to catch up on learning he never did...
    Next steps ..trying to get hold of Clonazepam (if I ever manage that ) have ordered Miyari from Japan , possibly stem cells and bit more research on C8 and BHB !! Funny my family thinks I have gone crazy and I need treatment not my kid !!
    Thank you once again
    Vicky

    ReplyDelete
    Replies
    1. Vicky, that is great news. Over time, the improvements will accumulate and hopefully the rest of your family will appreciate your work.

      Delete
  46. How fast does sulforaphane give effects? because we gave the first pill yesterday (Solaray Broccoli) and today my daughter is on a whole other level. Can it be possible, that is has such a fast visible effect? Also, regardless of the cost, do you think Avmacol is superior to the brand you use? If it works I want the best possible brand.

    ReplyDelete
    Replies
    1. Tatjana, when I first started using broccoli/sulforaphane there was a dramatic effect after about 30 minutes. I think the supplements may well have now improved. I am not sure Avmacol is the best, but they are using it in trials and it is being tested for content. So as long as the product they sell is identical to what they use in trials (which it might not be), it should be a good choice.

      If the Solaray product works, you might as well use that.

      The result does depend on myrosinase, which some people product a lot of in their gut.

      Delete
  47. We are thinking about adding nutritional mcg dosea of lithium to our therapy. I can see that lithium and bumetanide do not mix well because bumetanide is reducing the clearance. do you think this will also be a factor regarding the doses we have in mind? I would not think it because there are water sources in the world containing such quantities...would love to hear what you think.

    ReplyDelete
    Replies
    1. Tatjana, lithium is a very interesting drug for neurological disorders, it has been used for 60 years in bipolar without really knowing why it helps.

      Lithium affects GSK3 signalling and so Wnt signalling. Lithium activates the canonical Wnt pathway. This will then affect the expression of multiple genes.

      Some types of autism need more Wnt signalling, such as Pitt Hopkins. Some types of autism probably need less,

      People whose autism has features of bipolar, like some of our readers, might well benefit from lithium and I know that some do take it.

      Bumetanide increases the plasma level of lithium. This just means that if you take bumetanide you would need to lower your dose of lithium.

      I am not sure that tiny doses of lithium will have any effect.

      Delete
    2. Hi Tatjana, what dose do you have in mind for lithium orotate? I was thinking of using 1 or 2 mg lithium O with 1 mg bumetanide.
      Valentina

      Delete
    3. i wanted to start really low, like 0.3mg and work up to 1mg. I like to start low and then i go quite quickly up, but i always start basically as low as the dosage method will allow me. my daughter is a lovely looking child but she is onyl 20kg at age 6. its not a case of growth issues, she is on average for her age according to all charts but in real life i have yet to see a 6 year old with lower weight than her.

      Delete
  48. miniature doses apparently do have an effect and in our case she has repeatedly shown a lack of lithium in its sense as a mineral in tests. we go from big to small issues and now we are in the ‘solving several small issues’ phase. its about drops of lithium orotate, so even if the bumetanide were to double the blood concenctration, I do not really think it can matter much. this article points somewhat to what I have been reading up on. sadly unlike you, I read study upon study, form a conclusion and absolutely forget anything about the studies I have read and remain only with the conclusion. this mode of action makes a lot of sense for me, cleaning out memory storage, but its very stupid when I want to explain how I got there to someone else. https://www.google.com/amp/s/www.psychologytoday.com/us/blog/evolutionary-psychiatry/201201/could-you-have-lithium-deficiency%3famp

    ReplyDelete
    Replies
    1. Tatjana, it is impossible to remember everything. I regularly search my own blog to find things.

      There are other elements you do not want to be short of, selenium is another one; most people have plenty, but depending on where you live, you may lack it.

      Delete
    2. The broccoli product we use now says at the back: Broccoli seed extract (guaranteed 35mg sulforaphane glucosinolates and supplying myrosinase enzyme activity), 13 mg od myrosinase enzyme and 50mg of organic freeze dried broccoli sprouts. We currently give one a day. Any specific time of day and do you think the dosage is good? i will order the one you use once I use this up.

      Delete
    3. Some people find it makes the child go a bit hyperactive and so it is best to take in the morning. In trials the dosage is quite high, so you might want to check the effect of a higher dose. In some people, after long term use, they need to increase the dosage 2 or 3x their starting dose to maintain the effect.

      Delete
  49. Thank you for the valuable information - really appreciate your effort and expertise! Question about Bumetanide - are there any significant side effects to consider when withdrawing from the drug. I am currently cycling from the drug and am experience mild water retention, and I was curious to hear your thoughts. Thank you once again.

    ReplyDelete
    Replies
    1. You are experiencing a known side effect that affects some people when they stop taking a diuretic drug.

      Rebound sodium and water retention occurs when diuretic treatment is stopped
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1112648/

      We have stopped and restarted bumetanide many times in the last 6 years, with no issues. This is just to confirm it still has a beneficial effect.

      Bumetanide affects your electrolyte levels because it causes diuresis and so it is the kind of drug that you should not stop and start for no good reason. You body wants to maintain homeostasis and finds this hard if you keep changing how much urine you pass.

      Delete
    2. Got it, thank you for the information. It's interesting that in the study below, the oedema reached its peak during week 3 before starting to return to baseline:
      https://www.bmj.com/content/308/6927/511.full.print

      The feedback loop seems quite long. I'll be titrating down slowly next time if I choose to quit again.

      Thank you for the insight once again.

      Delete
  50. https://youtu.be/KbRdP4aIFig

    All,

    Found the above video of a presentation by Dr Rossignol very useful, highly recommend to watch this once.
    Dr R has classified/categorised supplements and medications currently available for Autism. It's ordered by the number of research papers published and gives a comprehensive guide to parent. Most of the supplements/medications tried by parents in this blog is covered in that list.

    Regards
    Deepak

    ReplyDelete
  51. My 23 yr old is classic, and I believe " double tap" severe autism. He is diagnosed with other comorbidities including epilepsy. His anxiety and aggression are off the scale and I would like to try Verapamil but he already takes propranolol and carbamazepine which I understand could be a dangerous combo. Interestingly, he has had no seizures in 6 months since weaning off fluoxetine ( seizures started after adding fluoxetine to risperidone). Does anyone here have experience of Verapamil with epilepsy?

    ReplyDelete
  52. I think for classic autism, you might want to look into bumetanide. There is an issue with verapamil combined with propranolol, but it comes down to the dosage used.

    Verapamil as an Adjuvant Treatment for Drug-Resistant Epilepsy
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161577/

    ReplyDelete
  53. Peter, my understanding is that quercetin stimulates the activity of NKCC1, as described in these articles:

    https://www.ncbi.nlm.nih.gov/m/pubmed/19251944/
    https://www.ncbi.nlm.nih.gov/m/pubmed/21865857/


    “These observations indicate that quercetin activates NKCC1 without any increase in the expression of NKCC1 protein. ...”



    ReplyDelete
  54. Did anyone try Colostrum ? It was suggested by my son’s functional medicine doctor for his allergies and eczema but researching it, I learned that the proline rich polypeptides it contains increase Il-6 and TNF-aplha among other things.
    But it should also contain oxytocin and this review from a certified buyer on amazon is very interesting, particularly the part related to its diuretic effects:

    ‘This product has made my skin feel good and improved my eczema...the patches are more smooth and less red. And the best thing is those eczema patches itches less...in fact from nasty to hardly even noticeable. My skin as a whole and my back especially also itch less. I take no prescriptions and am always careful to try only one new nutrition product at a time, so I am a good test subject!

    Update: After taking these for about 2 months, our skin was nice and smooth, eczema seemed to be healing nicely, but the need to urinate became so frequent and urgent that I had to discontinue use. I may try collagen for my eczema, but for now I have moved on to using digestive enzymes instead. We know that digestive enzymes diminish as we age, so that was my reason for moving to those. And they have been working very well with no side effects yet (two months...using Opti-Zyme). Other people may have not problem taking colostrum, but for myself (57) and my mom (82), it just isn't bladder/kidney friendly.’




    Enhanced Absorption Liposomal Colostrum Powder - Proprietary Colostrum-LD Tech Provides up to 1500% More Bio-Availability Over Regular Colostrum - 50 Grams Travel/Trial by Sovereign Laboratories … https://www.amazon.com/dp/B01KWH9HFO/ref=cm_sw_r_cp_api_i_edtYCb8QRT2SN

    ReplyDelete
  55. carmel yamberger30 May 2019 at 14:33

    Hi, i'm new to this blog and i'm very interested in Bumetanide to my 4.5 yo ASD son. what is the best source of getting it un-prescribed. i know i can get on ebay the Mexican brand and that in Serbia it can be bought in any pharmacy. i'm form Israel. any other sources? is the Mexican brand is ok?

    ReplyDelete
    Replies
    1. Carmel, some people buy it in Spain without a prescription. It is a cheap generic drug, so I really doubt there are fake versions. Care has to be taken to monitor potassium levels and to replenish fluids lost due to diuresis. I will soon post again our Dr reader Agnieszka's guide to its safe use in children.

      Delete
    2. carmel yamberger3 June 2019 at 10:09

      i'm looking forward to read it

      Delete
  56. Peter,

    Just looking through your polly pill list. Again very useful. I will certainly add some others as we continue our treatment with bumetanide.

    Just thought I would add a suggestion for you to look into and consider adding. It is a peer reviewed potent Nrf2 called PB125 from pathwaysbio.com only available in the US but I get it into the UK via reship.com

    It is essentially for reducing oxidative stress to that of the level of a healthy 20 yr old. Its $50 for 60 caps and 1/2 cap daily for child so pretty cheap. Not only that but it regulates gene expression in I believe 4000 to 5000 genes and detoxes homocysteine which is a big deal for autism. It also uses warfarin A as a natural mtor inhibitor which was chosen it mirrored the effects of metformin and rapamycin. It has a few other additional benefits but if you facebook add the inventor Dr Joe Mccord he can answer any questions you may have on it.

    Here is one of the lastest peer reviews on pb125 https://www.mdpi.com/2076-3921/8/5/119/htm

    I only share this with you because I gather from what I have read on bumetanide it is effective in 40 percent ASD population but it has the potential to be effective in upwards of 70 percent if they have their inflammation under control and PB125 would certain to a great deal in that area and can cross the BBB also.

    This is just my opinion and what I am using on my son but if you feel it might be of interest to you then it may be something to look into.

    Thanks

    Clare

    ReplyDelete
    Replies
    1. Clare, if you do get a TSC diagnosis, you can look up animal models of TSC1 or TSC2 and then look for "rescue models" where they reversed the condition.

      This does initially look very complicated, but it is mot really.

      You can then focus on your son's precise condition and save a lot of time and money.

      https://gene.sfari.org/database/animal-models/genetic-animal-models/TSC1/Mus%20musculus#rescue-models-tab

      Delete
  57. Thats really interesting Peter, thanks for sharing. I looked it up seems 5 of the rescue treatments are rapamycin. In the TSC groups rapamycin is prescribed to many not sure they have recovered from TSC with it but may be helpful for the autism part and cognition. I need to do alot more reading on it and side effects. Definitely interesting really hoping for so good results from bumetanide. He is coping fine so far on 1ml x 2 per day. When you see a response is it likely to be for a short period of a few hrs after the medication and then wear off again until the next dose??

    Had a few episodes of better eye contact and wanting to be play togethet but only slightly and comes and goes... is this normal or is this coincidence as wouldnt make any difference after a few days. Once he has been on bumetanide for some time if responding am I likely to get better eye contact throughout the day or just for a time after medication given? Not sure which way it works?


    We are still awaiting result back from the nhs genetics department but will be looking into options based on the info you gather, appreciate that.

    Clare

    ReplyDelete
    Replies
    1. Clare, it normally takes 2 weeks or more for bumetanide to lower chloride levels enough to see a beneficial effect. The effect is maintained all day long from then onwards, if you keeping taking bumetanide.

      Delete
  58. That is great to know thank you Peter. I have been looking to Afinitor/rapamycin/everolimus studies show it works very quickly and improves autism greatly in TSC in some cases non verbal to verbal sentences in a few weeks. You can even buy it cheapier on indiamart which is where I got my Leucovorin. Tsc group report a mix of side effects from non to mouth ulcers mainly but some have had more severe. I plan to wait for an offical diagnosis but if prescribed looks very promising massive drop in cars and atec scores in autism in studies it could be a definate rescue drug from what I have read. I checked the amount of warfarin A in pb125 with dr Mcoord here is what he said....
    "The withaferin contribution to PB125 is relatively small, I think, but how its ability to inhibit mTOR compares quantitatively to that of rapamycin may not be known. The ashwagandha extract we use contains 3% withaferin A, whereas the root powder used in Protandim contained about 0.3%, and I doubt that they even assay it since I left. I need to read some more about rapamycin and autism." He also sent me an interesting study on how withaferin A mimics rapamycin but said there are only 4 paoers identifying this.

    Just incase you are interested.

    Anyway I just enjoy looking into all this as options its interesting it isnt used in classic autism but may be die to mechanism or side effects maybe you already know?

    Thanks
    Clare

    ReplyDelete
    Replies
    1. Rapamycin might will help some types of autism, but it is very expensive.

      Delete
  59. Peter,

    The cost of rapamycin is ridiculous but cheaper at indiamart.

    Look at the paper Dr McCord sent me on withaferin A as a mimic to rapamycin I cant add it so google :-

    Towards natural mimetics of metformin and rapamycin

    Also google Dr Joe McCord very impressive biochemist

    I am working on a way to use Withaferin A in replacement of Rapamycin. Its easier to share with you what I sent to Dr Mccord. Not sure if he will reply but hope so will let you know if I find a way.

    "So I read the study you sent me which is, just wow ��

    Have you looked at the studies on rapamycin in TSC autism its pretty incredible and shows massive reduction in CARS and ATEC scores, non verbal to short sentences in little over a month, etc I feel like I need to try it. I can wait for diagnosis and see if I can get on prescription but then there is side effects which from that study look likely. Not many reported in tsc group bar mouth ulcers some had to stop using but from that study you would not want to take the risk.

    Keep coming across other papers on withaferin A use like this in cancer https://www.ncbi.nlm.nih.gov/m/pubmed/24498382/

    I can in fact find little reason against taking it. Considering the positive effects of rapamycin on autism and tsc. Once I get an idea that I think is good im like a dog with a bone. Cost of buying rapamycin is ridiculously high btw but cheaper from indiamart.

    Found i can buy the compound of withania somnifera and make my own caps.... Am I crazy stupid to attempt to do this ? You used 23mg for 3% bio available withaferin A ? So would 766.6 mg = 100% bio available withaferin A this is where I am a complete novice but according to this even if you give high doses it would be safe as within the 2000mg/kg given in this mouse study on saftey assessment
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910650/

    So what if tried 766.6mg x 17 kg and round down to 13,000mg get it compounded and split the dose ... does that sound ridiculous and totally the wrong amount

    I can buy the actual root from indiamart not sure how i would give it to him though

    https://m.indiamart.com/bengaluru/withania-somnifera-extract.html

    I could buy some ashwagandha caps already on the market but not sure how good the product is or that its even the same thing really

    https://www.bocsci.com/withaferin-a-cas-5119-48-2-item-120734.html?gclid=CjwKCAjw6vvoBRBtEiwAZq-T1btCq18s9bWl6p0iG56pkosGRZ0kSWTd2rEykDL7VoEy8QZf0MfNWRoCY1oQAvD_BwE

    Thanks Clare

    ReplyDelete
  60. I did chickenpox in pregnancy and from what I read here it affected and it can cause TSA: https: //www.ncbi.nlm.nih.gov/pmc/articles/PMC4108569/ Has IGG CMV increased from 4.99u / ml he has 9.8u / ml and always comes up with high CRP instead of 0-10 mg / l he comes out 64mg / l.He is 5 years old and doesn't speak in sentences.

    ReplyDelete
    Replies
    1. Denisa, Maternal Immune Activation (MIA) is a well studied cause of autism in the research. You will never know for sure to what extent MIA was the cause of your child’s autism. Many people with severe autism have an over-activated immune system and so an elevated CRP is not unexpected. The problem is that the immune system is extremely complex and there is no one-size-fits all remedy.

      Numerous anti-inflammatory therapies are reported to help in individual cases, many have been reviewed in this blog.
      The list includes antibiotics that are immuno-modulatory (beta lactams, azithromycin etc), all types of NSAIDS (even ibuprofen), Montelukast, statins, some specific probiotics (Biogaia Gastrus), PEA, Ibudilast, some parasites (eg TSO), some people say GcMAF.

      You can read about the MIA model of autism and see what drugs the mouse version responds to. Subacute inflammation in the brain not only affects neural development, but also acutely influences ongoing postnatal behaviour.

      Reducing inflammation will help current autism symptoms, but much more can be done to correct the faulty neural development, which likely includes ion channel/transporter dysfunctions among many other issues.

      Delete
  61. Thanks!What analysis do you recommend besides this data by a doctor?HLG, blood glucose, sideremia, tgo, tgp, urea creatinine, cholesterol ldl hdl, homocysteine, ac.methylmelonic; vitamin d3 oh, vitamin B12, total E, ionogram, coproculture, urine summary

    ReplyDelete
    Replies
    1. Denisa, I do not think that any analysis exists that can tell you what will work. In theory you could measure the many cytokines and see which were elevated/reduced, but nobody has really correlated this to specific therapies. It is a case of trial and error using what you have available to you. Start with things that are cheap and safe (eg Montelukast).

      Delete
  62. Thank you for your informative blog. Do you have an opinion on the use of B12 for autism widely recommended by biomedical Drs.

    ReplyDelete
    Replies
    1. B12 does seem to benefit some people with autism, but certainly not all and some people have a negative reaction.

      Delete
  63. Thank you for fighting the good fight. I have worked in the US medical field (in management) for 30 years, so I'm not surprised that physicians take a pretty passive approach toward autism. They do better with diagnostic certainty and with treatments where the effects and side-effects are well-known. Obviously not there yet with autism.

    Like yours, my interest in this is personal. While it is easy for me to get over my skis in the bio-chemistry of all of this, it looks to me like if you reduce the neuro-inflammation, oxidation and excito-toxicity, a lot of ground might be gained. My research has led me to honokiol, from magnolia bark (used widely in Asia for other purposes). It (readily enough) crosses the BBB following oral ingestion, inhibits TNF-alpha, IL-1, IL-6, IL-12, IL-17, MMP9, NF-kB, IDO (thereby quinolinic acid), and microglial inflammation, while acting as a PPAR-y agonist, boosting Nrf, and GSH. Among other things that might help. It makes so much sense to me to try it for ASD, but I have seen nothing in the literature. I'm curious about your take.

    The other thing that strikes me is that ASD seems to come in at least two major varieties - under-processing and over-processing. To me, a failure to clarify that difference renders statistical analysis of treatments almost worthless. It would be like testing treatments on a mixed group of cardiac patients, some with bradycardia and some with tachycardia; it wouldn't work. Likewise, I would expect the effective treatment of a child who ignores stimuli to differ from one who is hypersensitive to it. I'd be curious as to your thoughts.

    ReplyDelete
    Replies
    1. Both Magnolia and Honkiol have been mentioned in earlier posts and in the comments.

      To find those references you just enter the following into Google.

      Honkiol "site:epiphanyasd.blogspot.com"

      Many natural substances do have very interesting properties that are relevant to treating many types of autism.

      The drawback is that these products are sold as supplements, with quality control far below pharmaceutical standards, meaning you really do not know what is in those capsules. Is one batch of product even vaguely similar to the next? I think using Korean or Chinese traditional medicine requires one of their long-established traditional pharmacies, rather than a cost-cutting Western supplement company.

      I see substances like Honkiol as the basis on which to produce a standardized drug, but you cannot patent a naturally occurring substance. You can take a naturally occurring substance, make a tiny change to it and then patent the new molecule. Without a patent nobody will invest in high quality clinical trials.

      Clinical trials using a mixture of subjects with entirely different types and severity of autism is indeed pretty pointless and many millions of dollars have been wasted so far.

      Products like Honkiol are interesting because you do not need a doctor to help you acquire them, but I think the really potent therapies are prescription drugs.

      Delete
  64. Thank you for your response. I'm curious about your take on potassium bromide versus bumetanide. If I interpret your chart correctly, you believe that the effect of bumetanide fades over time, but that of potassium bromide continues. Concerns about risk of chronic administration? Does you son take both? Interaction effect?

    Another general observation. I'm relatively new to this, but it looks to me that the real opportunity is in combating neuro-inflammation and its sequelae in the early post-natal period, followed by some opportunity up to 2 as the brain develops and 2-5 as pruning is accomplished. Most of the research tests subjects much older. It seems to me that what might work at 6-12 months or 2-5 years may have a very different effect on an older child or adult.

    I had read that Dr. Sahin is doing clinical trials of rapamycin in 1-2 year olds. I'm very curious about whether that trial will replicate the success of early treatment in murine models.

    ReplyDelete
    Replies
    1. Bumetanide continues to work after 7 years of use (I guess that counts as chronic use). Potassium bromide's use is limited by the fact that it causes "bromo acne". I now use Bumetanide and Azosemide. Azosemide does what Bumetanide does but with less urgent diuresis as the side effect.

      Version 6 of my PolyPill is in this video:-

      https://youtu.be/T8-ukM2uuQ4

      In some single gene autisms there clearly is a treatment window, after which it is too late to use certain clever drugs.

      Bumetanide will benefit adults with autism who have elevated intra-cellular chloride.

      Delete
    2. i read that bumetadine can benefit autistic people who have bad reactions to benzodiazepines...my daughter was suffering from severe insomnia and after my doctor's advice I gave her Valium at evening,,,,she did not sleep at all, all night long awake...I was told "it can happen in children" can it be a sign of elevated intra cellular chloride ?

      Delete
    3. Yes, a benzodiazepine drug working in "reverse" is a sign that GABA is not working as inhibitory/calming, as it should. Sometimes valium triggers extreme aggression and then people call the police for help and go to hospital. Unfortunately, there is no information system to tell doctors that if Valium works "in reverse" in an autistic person, you have very likely identified a bumetanide-responder. When you have a fault in your car, the mechanic goes online and looks up what the database has to say about it.

      So, as you say, your daughter likely has high intra-cellular chloride and should definitely make a 1-2 month trial of bumetanide.

      Read this post:-

      https://epiphanyasd.blogspot.com/2019/06/the-safe-use-of-bumetanide-in-children.html

      Delete
  65. 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

    ReplyDelete
    Replies
    1. 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/

      Delete
    2. 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

      Delete
  66. 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 ).

    ReplyDelete
    Replies
    1. 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.

      Delete
  67. 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

    ReplyDelete
    Replies
    1. 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.

      Delete
    2. 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

      Delete
    3. Hi Peter,

      Sadly, we believe that our son is a non responder to Bumetanide.

      He has been for more than a week in 1.0 mg of Bumetanide.

      At first, we started to see a few amount of stereotypes that were controllable. As time went on, these stereotypes started to increase in amount and severity. Now they have become uncontrollable and the worst thing is the reappearance of others that had been controlled.

      Additionally, we have noticed a very light sleep pattern while on Bumetanide. He has had for the first time episodes of screaming and/or laughter at dawn.

      We had already decided to wait until full dose to see if Bumetanide was an option to our son. However, after those episodes, we can not feel confident in increasing the dose. We believe that in mitochondrial dysfunction like our case, other scenarios may alter the good effects of Bumetanide.

      We have made the decision to stop but we do not know if we can do it overnight or we have to gradually lower the dose. Could you please tell me how to do it?

      Thanks in advance,

      Claudia.

      Delete
    4. Claudia, you can stop bumetanide without the need to gradually lower the dose.

      Most people take at least two weeks to show a benefit from bumetanide.

      Delete
    5. Thank you very much Peter.

      We started Bumetanide on December 15 at a dose of 0.5 mg because in the past our son has had unexpected reactions to medications that have caused us to end up in the emergency room. Three days later, we went up to 1.0 mg and we were so far monitoring tolerance and studying possible changes. We have been testing Bumetanide for more than two weeks and although we know that it is not the full dose for his weight, in these last days he has been very erratic in his behavior and as we have seen a gradual worsening we were afraid to increase it. Despite this, we will continue researching, looking for more options and above all we will continue learning from everything that is shared in this blog.

      Best Regards, Claudia

      Delete
  68. Hi, I would like to know if there's some site where I can get bumetanide without prescription? I want to know how do u guys get bumetanide? All of u ask for a doctor's precription? I don't even know the Portuguese name of bumetanide..

    ReplyDelete
    Replies
    1. If you live in Portugal, go across the border to Spain and ask for Fordiuran in the pharmacy. In Spain you do not need a prescription, if you ask nicely. It will be Fordiuran 1mg which is Bumetanide 1mg.

      Delete
    2. I don't live in Portugal's main territory. I live in a island.. I would like to get bumetanide on internet.. it's my only option.

      Delete
    3. Many people buy on the internet/eBay as Miccil from Mexico.

      Delete
    4. There's some site that u recomend? On ebay it doesnt ship to Portugal as I've seen.

      Delete
  69. Hi Peter and readers

    Wanted to ask few question

    Is clonzepam same as diazepam ?

    How long does it take to see the effect of atorovastatin?



    Is there any reputable website to buy bumetanide?


    You might have all the answers in the web but to honest it's difficult for to go through all the sites since I am aspie my self


    Thank you very much ,

    ReplyDelete
    Replies
    1. Riza, Clonazepam is similar to Diazepam, but only Clonazepam has the very specific effect at low doses on a subtype of GABAa receptors, that is beneficial to some people with autism.

      Atorvastatin has a beneficial effect on the autism of some people, and this effect is apparent after a couple of days.

      I have never bought bumetanide online, but I know many people buy it online under the brand name Miccil from Mexico.

      Delete
  70. Thanks Peter

    For now I tried propranolol 10mg and it made his asd symptoms worst

    So do you believe low dose of propranolol might work for him

    Oh will he get better later on 10mg

    Or do I need to give verapamil

    Thanks

    For now I am looking for speech ( he is totally nonverbal)

    ReplyDelete
    Replies
    1. Riza, some non-verbal people with autism have low IQ and some have normal IQ. In people who are non-verbal with low IQ, I would start by trying to raise IQ. Bumetanide is the best thing to try to raise IQ (also Azosemide and low dose Clonazepam).

      In some people with autism Piracetam, a nootropic has a good effect. Short term use may trigger some change.

      You really need to consult someone face to face, to define what kind of autism you are dealing with. If you are an Aspie, your son probably does not have a single gene autism.

      Delete
  71. Hello Peter. I have been reading your blog for a month and have finally convinced myself to try bumetanide. We have already tried the Nemechek protocol which has done nothing to alleviate the core symptoms of my baby's issues. I even went as far as taking rifaximin. Some good signs but not enough to continue so hard
    My question is i want to try bumetanide but are there other pills that would work when bumetanide does not? Thank you for all your work

    ReplyDelete
    Replies
    1. Taiye, there are hundreds of substances that can improve autism. The problem is determining which ones are helpful in your unique case. This is not an easy process.

      Bumetanide is a good drug to try early on because a substantial percentage of people are responders. In the case of severe autism great strides forward are then possible.

      Delete
  72. Hi Peter
    We giving clonzepam 0.025 mg to son
    First 3 days we saw some improvements
    Like more affection, imaginative play , few new words , calm

    And all the sudden he had a fewer now he back to square one

    Do you have any idea about it please ?

    ReplyDelete
    Replies
    1. Clonazepam has a long half-life, which means if you take it once a day, it takes 3 days to reach a steady level in your blood.

      In my son I give the same dose every day. If I stop for a few days, when I restart, it takes 3 days to show a beneficial effect.

      The effective dosage range is very narrow.

      If your dose is too high, it will work briefly and then after 1 or 2 further doses, the level in his blood will be above the effective range. You need to start again, after a pause of a few days, at a lower dose.

      It takes time to find the dose that is effective long term.

      Delete
  73. Thanks Peter, what a great resource you've/you provide/d and what great strides you've made with your son's symptoms.

    I was wondering what your perspective was on the research for effective options for patients with ADD issues that represent significant executive function challenges and resist medications. The trouble is in planning/visualizing things based as rules/concepts instead of disorganized collections of details. ADLs are fine, but higher level functioning--ability to maintain directed social relationships/set goals--is sporadic and inconsistent. Occur with significant mood and anxiety issues.

    Did 23and me gene testing and found NRG1 mutation--interestingly linked to impaired top down attention--but doesn't suggest what might be helpful. Also mutations in ANK3/CACNA1C. Tried many medications and other interventions without success.

    ALCAR/Capryllic Acid/Magnesium and Gaba are probably things that help significantly. Caffeine helps for mental stamina, but doesn't help with planning/careless errors.

    Thoughts on what type of symptoms this correlates with in the literature? And on what kinds of biomarkers to target to address this collection of symptoms?

    ReplyDelete
    Replies
    1. Mutations in CACNA1C are associated with ADHD, bipolar, schizophrenia, autism etc

      CACNA1C: Association With Psychiatric Disorders, Behavior, and Neurogenesis
      https://academic.oup.com/schizophreniabulletin/article/44/5/958/5048933

      This gene encodes the Cav1.2 calcium channel.

      The Cav1.2 channel can be blocked with a cheap drug, like Verapamil, normally used to lower blood pressure.

      ANK3 is associated with autism, aggressive behavior and even bruxism (teeth grinding).

      https://www.genecards.org/cgi-bin/carddisp.pl?gene=ANK3

      "Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption""

      That would suggest you should check your electrolytes. If Magnesium is low, it is easy to supplement it.

      NRG1 is another schizophrenia gene that is also an autism gene. You probably would want to turn off NRG1, which is possible using an anti-NRG1 antibody. This gene encodes Neuregulin 1 which is a very important protein.

      I think you could further research these 3 genes and also look at schizophrenia translational resaerch (ie drugs for schizophrenia). Try chewing a piece of nicotine gum.

      Delete
  74. Hello Peter

    I have my 8 yold asd son 1mg Bumetanide

    But so frequency of urination very high

    Shall I try a lower dose or will the side effects subside ?


    TIA

    ReplyDelete
    Replies
    1. Riza, Bumetanide usually causes diuresis for the first 90-120 minutes. I give it around 6.30 AM and my son leaves home for school nearby at 8AM. It is no longer troubling. Your son will adapt, the dosage is fine.

      You just have to adapt your schedule, so your son has fast access to a toilet. Tell the school he may need to leave the class to visit the toilet.

      Tips for safe use of bu,etanide are here:

      https://epiphanyasd.blogspot.com/2019/06/the-safe-use-of-bumetanide-in-children.html

      Delete
  75. Hello Peter
    We are on 1mg bum. For last 5days
    No wow yet
    But very less stimming

    So wanted to ask you stackdonapzil with bum.

    Or there any other drugs or sup.


    Thanks

    ReplyDelete
    Replies
    1. Riza, keep going with Bumetanide for a month, then judge the result. After that you decide if the results are worthwhile or not. Bumetanide alone is not going to fully resolve anyone's autism, it is just one part of what needs to be a polytherapy (multiple drugs).

      Delete
  76. hi. i was diagnosed with aspergers in kindergarten struggled but completed high school, had jobs and have some aptitudes, and some defects in communication (a typical scenario, mild "idiot savant"). ive been severely effected by drug use which resulted in anxiety and emotional lability, one thing i noticed is amphetamines help a lot and ive read adhd symptoms, emotional lability, and autism have overlapping symptoms and co-occur.. im fascinated by these approaches on this blog to helping with this area of defecits. who here has a strong opinion: amphetamines vs poly pill approach or combining the two for better effect? also anyone here considered paychedelic drugs, 5ht2a agonists (which have worked well for me, temporatily) or is it better to go at this from a poly pill suppliment approach to address the causes and more cellular level issues? also gone off and on with escitalopram (ssri) which is good for mood but i dont like how it reduces focus so no longer taking it. its crazy trying to decide what is the best knowing that many things have potential, but im on a tight budget. i am 24

    ReplyDelete
    Replies
    1. I am surprised how many Aspies say they get a benefit from the therapies I am writing about here for severe autism.

      Many Aspies do use psychedelic drugs and an increasing number use micro-dosing. Apparently in Silicon Valley the techie Aspies are doing this (micro-dosing). Redddit is place on the internet to get advice from fellow Aspies.

      The biggest problems in severe autism are impaired cognition and lack of speech. The biological issues do overlap with Asperger's (and ADHD, schizophrenia, biploar) but you might be best taking advice from fellow Aspies.

      Delete
  77. Hi Peter
    I got a general question pls reply

    Atorovastatin Vs donapzil

    Which would you choose?

    ReplyDelete
    Replies
    1. Riza, I never dried Donepezil. The similar drug Galantamine looks much better than Donepezil.

      Atorvastatin is completely different, all I can say is that it works great for us. It may help your case, or it may do absolutely nothing.

      Delete
    2. Thanks Peter
      About galantamine
      We could get Rivastigmine

      And we tried it and within hours he became calm more like sedated

      Do you think Rivastigmine could help him in the long run

      Delete
    3. Riza, I would not want my son to be sedated, but this is the effect of some anti-psychotics widely used to treat autism in the US.

      Galantamine, Rivastigmine and Donepezil are closely related, but different. You might want to try all 3 and then decide what to do.

      If more acetylcholine is indeed helpful, you might try Piracetam or Alpha-GPC.

      Delete
  78. Hi Peter, what is the main way to distinguish between regressive and classic autism? You mention biomarkers of elevated serotonin, cholesterol, thyroid FT3/4 and growth factor IGF-1 here, but are there any biomarkers you typically find specific to regressive autism? I have Aspergers, however I can't work out whether I had this from birth.. apparently I started banging my head against the ground repeatedly after receiving the MMR vaccine according to my parents and appeared to never be the same afterwards. I only received a diagnosis after age ten, shortly after having an amalgam dental filling. My anxiety progressively got worse and worse and I was referred to a psychiatrist for evaluation. I believe this was a late regression, with one regression after MMR and another after the exposure to the Mercury from the dental filling, but I could be wrong. I do feel as if mitochondrial dysfunction could be the culprit, but what are the specific laboratory tests best suited to identify this, as I believe some of the tests do not detect a milder problem? Do people with classic autism typically not have a mitochondrial dysfunction? I do believe I have high levels of inflammation from oxidative stress, which appear to improve when taking NAC and other antioxidants. Why is it the classic autism therapies may be ineffective?

    ReplyDelete
    Replies
    1. Adam, people with regressive autism lost important skills that they had previously mastered; usually it occurs in children three and under, but it does happen even in five-year olds.

      Dr Kelley from Johns Hopkins claims that nearly all the children they see with regressive autism have mitochondrial disorders.

      Some research suggests that mitochondrial disorders are also common in non-regressive autism.

      The standard test requires a muscle biopsy. Parents want to avoid this so clinicians look at various chemicals in blood samples and now there is a buccal swab test, that takes a swab from inside your cheek.

      https://religendx.com/mitochondrial/

      The question is how accurate the swab test is. They claim 80%, but it would be nice to know what independent experts think.

      There are hundreds of different causes of autism and so there will be very many therapies that help a sub-group, but do nothing for the majority.

      Delete
    2. Peter,you need to update your information on regressive autism.It is not all mitochondrial.I suspect most of it is immune related.The research has proven autoimmunity,and systemic inflammation,is much more common in autism,than mitochondrial disease or dysfunction.Mitochondria are not the only cause of regressive autism.Genetic,or inborn/inherited autoimmune disease is another.Most cases of autism may be immune related.Especially regressive autism.

      There are multiple conditions that can result in autoimmune disease,presenting as autism.There are outright autoimmune diseases,like childhood onset lupus,that can present as regressive autism.This is usually inherited,although there are environmental,and epigenetic triggers.These usually happen before birth,not through vaccines.Family histories are key here.There are primary immune deficiencies,that can present as autoimmune disease.Again,not unknown with autism.There are de novo mutations of cancer genes,not uncommon with autism,that can also present as autoimmune disease in children.I believe this was the case with me.To say nothing of PANDAS,PANS,and related disorders,or mast cell disease.This is complicated stuff,and autism symptoms can only be one presenting symptom of any number of conditions,especially when regression is involved.In cases of regressive autism,an extensive medical,and genetic workup should be done,to determine the underlying cause.

      Delete
    3. As far as Adam's case is concerned,I once met a woman on Facebook,who was diagnosed with autism in her 40s.She claimed she had regressed after a severe illness,and was eventually diagnosed with mast cell disease.This woman denied any history of prior regressions,which struck me as odd.This is the opposite of my case.According to my mother,I had a very early regression,before the age of one year,following pneumococcal meningitis.If you search the literature,early regression like this is rare,but not unknown.

      Delete
    4. I think Roger has a point here, that regressive autism looks very related to the whole immune/neuroinflammation field. The non-verbal participants of the suramin trial were reported to have regressed at an early age (I think at 2). QBiomed also mentions regressions on their site as one symptom. Maybe mitochondrial dysfunction is just a secondary hit, caused by the immune response/inflammation that shuts down several functions of the brain cells?

      /Ling

      Delete
    5. This is a complex subject.

      Dr Kelley, a world expert on mitochondrial disease, and someone who worked at the top hospital in the US for treating pediatric developmental disabilities, tells us that in almost all cases he found mitochondrial disease in people meeting his definition of regressive autism.

      I think it is foolish to doubt him.

      What he defines as regressive autism is likely very much narrower than what some readers of this blog are considering.

      I invented the term “double tap” autism to describe people who have been diagnosed with autism and then a second event occurs to make autism much worse. This is not regressive autism, but it is autism getting much worse.

      Autism is often a progressive disease in early childhood. So someone born with autism, may slowing appear more and more autistic from 2-5 years old. This is not regressive autism.

      The term regressive is so vague and liable to misinterpretation it is going out of use with researchers. To be of use it has to be very clearly defined. I recall Dr Chez does this in his book.

      Delete
    6. Hi I think in terms of the mito issues it can be chicken and egg with some of the other immune related problems.

      I always had the link that immune disregulation causes inflammation which causes oxidative stress which impairs mitochondria and reduces the methylation cycle. Maybe a simplistic view but it was key in my son's improvements.

      So of course if Kelley looks at mito issues he will always see them as they are downstream of the root cause.

      These could also be in cyclical dependencies so it's not as linear as I've listed it.

      For my son we did biomed to address methylation plus some of the other deficiencies (folinic for frat mild positive antibodies etc.)...ATEC went from 65 down to 45 with these...then mito cocktail and strong antioxidants such as ALA to come down some more points...

      But when we discovered gut infections, Lyme antibodies (along with other co-infections and an asymptomatic mother with same fingerprint of the same) and walked backwards to address immune system through two years of continuous antibiotics and used high dose ivig in parallel it's when significant improvements were seen. ATEC went from 40 down to 10 and those are hard earned point drops.

      Trying to wrap it up now there's lost development and some damage for sure so we're trying to 'applicate' around this since medically it's hard to find new things to treat. All gut, organic acids, etc. tests are now in range and unremarkable.

      Delete
  79. Thanks, I'll look into this. Why is it that the standard therapies might not work? I've tried Riluzole (50mg twice daily) but it only seemed to result in a slight reduction in anxiety.. I've heard Riluzole has been shown to be effective in raising the prefrontal levels of glutamate in Autistic patients but not in controls (https://www.ncbi.nlm.nih.gov/pubmed/28534874).. could this be due to the GABA shift to inhibitory not being observed in Autism? Would this "lack" of shift to inhibitory still be observed in regressive autism?

    ReplyDelete
    Replies
    1. Sorry I actually meant it's been shown to lower glutamate.

      Delete
  80. Hi Roger, what tests can I get, genetic or otherwise to rule out immune dysfunction and other systemic diseases? How can I get my doctor to order these tests? I just feel completely paralysed from the financial aspects of investigating these problems and feel my GP will just laugh me out of the door.

    ReplyDelete
    Replies
    1. Adam, sometimes it is better to skip the tests and try the treatments instead. There are so many ways and reasons why the immune response or mitochondria or E/I balance can go wrong. Sometimes there are no tests, or each test will only cover a narrow spectrum of causes. Maybe better spend the money on a few interventions that you find plausible to work, and draw conclusions from that.

      /Ling

      Delete
    2. Thanks Ling, I think you're right. I'll concentrate on the mitochondria treatments and reducing inflammation through antioxidants/ pregnenolone and keto for the time being and then focus on the tests as the money becomes available.

      Delete
  81. Hi Peter
    Wanted ask about the urine affect on Bum.

    We started .5 mg on our 8y old and within 4 hours he had 10 urine passes

    Will the side effect subside in the long run?

    TIA.




    ReplyDelete
    Replies
    1. Riza, I think people take some time to adjust. Most people seem to get used to it. It varies from person to person.

      Delete
  82. Hi Peter
    It's look like .5mg bumm. 2 times a day may be working better in my sons case

    Less stimming , eating more food
    So far that's it
    Hope to see more gains

    Just wanted to ask you do happend to know anything to help with attention for asd kiddos ?

    Thanks

    ReplyDelete
  83. Hi, I've seen that here a lot of people takes bumetanide, how does they get it prescribed? I'm asking this because in my country they are prescribed for people who has high blood pressure..

    ReplyDelete
    Replies
    1. Autism is now a well documented off-label use of bumetanide.

      In some countries you will find a doctor willing to prescribe it. (e.g. USA, France)

      In some countries you do not need a prescription (Mexico, Spain etc).

      Delete
  84. Where can I buy potassium bromide? I'm from Portugal btw.

    ReplyDelete
    Replies
    1. The drug form is used to treat Dravet Syndrome and other pediatric epilepsy, mainly in countries near Germany. It became much more expensive I am informed.

      Delete
  85. Hi, I've tried NAC ( took 1200mg per day ) but didnt notice nothing.. is it normal? My diagnosis is Asperger and OCD but didn't notice an improvement while taking NAC.. might it be because I was taking low dosage?

    ReplyDelete
    Replies
    1. waz1, Asperger + OCD is just an observational diagnosis, is does not tell you about the underlying biology.

      In some people it looks like oxidative stress causes their OCD or stereotypy; in those people NAC at high doses will help.

      You could try a higher dosage to check if you are a responder. If not, your OCD is caused by something else.

      Delete
    2. Yeah I'll try NAC again. I take fluvoxamine 50MG at night and a part of my OCD is gone. I don't know what's the fluvoxamine target but it works..

      Delete
  86. Hi Peter,hope you are well
    Thanks you so for sharing your journey,I have been inspired to start Butenamide for 3 boys who are completely non verbal
    1mg twice a day for 7 year old and 1mg once a day for 4 year old.i have seen significant improvement in calmness,attention,better sleep,stimming and piano finger for 7 year old is fading away
    I really want to try it longer but am running out of supply,am wondering if there is someone you can link me with that we can source it through..


    ReplyDelete
    Replies
    1. There is no magic source. Ideally you ask your doctor for a prescription. It is effectively OTC in Spain and some other countries. It all depends where you live.

      Delete
    2. When I try to buy Fordiuran in internet it asks for a prescription.. there's a way to get it instead of going to spain?

      Delete
    3. Unfortunately there's no Fordiuran in Spain since November 2019. It is not manufactured anymore and it's not possible to order it. I have write to Leo pharma and to Tora laboratories and seems they have some authorisation problems. There is no substitute also..

      Delete
  87. Hi Peter

    We tried bumetadine around 20 days on and off

    The day I give him Bumetadine He laughs a lot

    But of I don't give he stims a lot

    Then I came across this article

    "Abstract
    The effects of furosemide and bumetanide on immunologically stimulated rat peritoneal and human lung mast cells were compared. Furosemide and bumetanide had different modulatory actions on the rat peritoneal mast cell. Furosemide inhibited anti-IgE-induced histamine release. Preincubation of the cells with the drug, prior to anti-IgE stimulation, significantly reduced furosemide's inhibitory effect. In contrast, bumetanide potentiated anti-IgE-induced histamine secretion from the rat peritoneal mast cell. Both diuretics were modest inhibitors of anti-IgE-mediated histamine release from human lung mast cells. For furosemide, inhibition decreased with preincubation, while preincubation increased bumetanide's inhibitory action."

    As per article is my son have histamine reaction for the bumetadine

    If so how can treat it please



    ReplyDelete
    Replies
    1. Riza, if you want to lower chloride with bumetanide, it needs to be taken every day. If not, you will just get other effects of the drug.

      The impact of each day's pill is tiny and so you need it every day, otherwise the chloride level just rises back.

      If inhaled, furosemide can reduce some asthma symptoms.

      Make a trial of bumetanide every day for a month and then decide if you have an overall benefit.

      If you have an overall benefit then consider how to deal with any side effects like laughing.

      Bumetanide does affect mood and indeed some research shows it effective in one type of depression. I would not assume the laughter is linked to histamine.

      Delete

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