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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.  



288 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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  2. 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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  3. 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.

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  4. 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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  5. 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.

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  6. 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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    Replies
    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.

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  7. 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.

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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.

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    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.

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    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.

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  8. 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.

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  9. 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,

      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

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  10. 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.

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  11. 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.

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  12. 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.


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  13. 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..

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  14. 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?

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  15. 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.

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  16. 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



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    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.

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    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





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  17. 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.

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  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. 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
  38. 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
  39. 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
  40. 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
  41. 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
  42. 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
  43. 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
  44. 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
  45. 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
  46. 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
  47. 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
  48. 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
  49. 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
  50. 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. 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
    3. 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
    4. 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
  51. 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
  52. 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
  53. 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
  54. 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
  55. 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
  56. 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
  57. 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
  58. Hi Peter
    I gave my son spirolectone 50mg
    His memory skills and drawing skilld improved very much on
    But his stimmng got worse

    Do you have any idea about it please ?

    ReplyDelete
    Replies
    1. Riza, it is great that you saw positive changes.

      You could try a lower dose, say 25mg and see if you keep the benefits and reduce the stimmimg.

      The other point is that some negative effects can be short term and may just fade away as the brain adjusts to its new normal.

      For example, increasing cognitive function in ID/MR seems to often increase anxiety. When you think about this, it is a perfectly normal reaction. Over time as the person learns how to deal with their new mental function, you would expect anxiety to reduce.

      Delete
  59. Hello - I am very new here and have some very elementary questions, forgive me. Is Clonazapam Sodium Bromide? My son is almost 13 and I want to try this poly pill but I’m afraid because he has epilepsy and is already taking maintenance meds twice daily (Depakote). Is that safe to be on and add in the Clonazapam too? He’s also on Guanfacine and Prozac. Still ok to start the poly pill with those being taken? We’re weening off .5 of Risperdone also. Please advise and give you opinion. Thanks a bunch.

    ReplyDelete
    Replies
    1. Michele, Clonazepam is not Sodium Bromide.

      Your son is taking 4 drugs already and you do have to be careful how they interact.

      Guanfacine is an ADHD drug that is sometimes used to reduce disruptive behavior in autism, but it lowers blood pressure. Prozac is for anxiety. Risperdone is for irritability/aggression associated with autism. Depakote/Valproate controls seizures but may also improve some features of autism.

      The choice of therapy depends on the type of autism the child has and what their problems are.

      Bumetanide is the best choice to start with for many people, because it significantly benefits 30+% of people, it is very well researched and it is very safe.

      Low dose Clonazepam does help some people, but the effect is less than Bumetanide and while it is very safe, it has not been studied in human autism, so your doctor is unlikely to help you.

      I would ask your doctor for Bumetanide, called Bumex in the US.

      Delete
  60. Peter, is it possible to see the effect of bumetanide in the first dose? I just tried it with my 2 and half year son this afternoon 0.5mg and his eye contact is so much different. And less stimming as well. He urinates a lot so we keep giving him water and feed him potato pumpkin and banana. I know this is not in my head because he literally more awares with his environment. Is this too good too be true? I am so happy right now. Thank you for sharing this valuable info! /christine

    ReplyDelete
    Replies
    1. Christine, it is unusual to respond immediately to the first dose of bumetanide, but you are not the only person to experience this. Another reader told me that stimming disappears almost straight away with Bumetanide and returns if he stops giving it.

      I would not be concerned about the reaction being so fast and so rather unusual. There are many possible reasons for this.

      I am happy that you are happy.

      Delete
  61. Hi Peter,

    I am sure this has been mentioned on the blog already, but I am having difficulties locating it.
    Could you please tell me how and when is Atorvastatin dosed? Additionally, do you give Atorvastatin and Clonazepam constantly or do you pulse them in some manner, for example one month on, one off?

    Thank you in advance for your time and efforts!

    Regards,
    Todor

    ReplyDelete
    Replies
    1. Todor, I am using Atorvastatin 10 mg every day. I also use the micro-dose of Clonazepam every day.

      Delete
    2. Thanks Peter.
      Are the 10mg dosed for a 50KG child, or does the amount given follow some other dosing scheme? For example, am I to give around 5mg per day for a 20KG child?

      Delete
    3. Todor, I started with 10 mg 7 years ago and have not increased the dose. In a 20 KG child it would be prudent to give 5 mg. In some countries there are 5 mg tablets, otherwise you will have to cut the pill in half. The effect in my son is very fast and so you may only need to make a short trial to see if this therapy is beneficial in your child.

      Delete
  62. Peter, my son is 25-mo and diagnosed ASD on ADOS-2 in Oct 2020. I started to throw myself into the myriad of journals and with my A-Level Biology my understanding has been stretched. I was drowned. Then I found your page while I was searching intensively around GABA switch. You are a godsend.

    Since the diagnosis, we have kicked off traditional therapies and his eye-contact has improved a lot. Despite of this, his receptive language is still poor. He is also non-verbal, but he can sign melodies of songs like Jingle Bell all day. He still cannot tell who is dad, mom, or etc, though he did not resist to play with us with simple interaction sometimes. He throws off tantrum by screaming every now and then. He stims by tactile touch on his finger tips, i.e. touching anything uneven gratifies him. So far he is the classic infantile autism with clear onset back in 18-mo or earlier (now we became aware). He has mild eczema when he is 1-yo but this has not come back anymore (so far) despite a change of seasons.

    May I ask if you would suggest Bumetanide, or anything that may target more specifically to his speech and cognition? We have already put him on Omega 3, probiotics (Biogaia's LR), colostrum, multi-vitamins, MTHF, COQ10, and Vit-D3. No changes so far.

    ReplyDelete
    Replies
    1. I would start with NAC and see it if has a benefit - this needs only a few days. Then make a 4 week trial of bumetanide. Then make a trial of Calcium Folinate (Leucovorin). Then try sulforaphane.

      You have a good chance that you will get cognitive and speech benefits from this.

      Delete
    2. I forgot that I did also give him folinic acid (last 3 weeks) and yet to see any improvements. For one, his screaming (when needs are not met) have only escalated. I will seek NAC and bumetanide first. Thanks Peter.

      Delete
  63. May I ask if I should stop any of the current supplements, e.g. omega-3 (1,000mg) too?

    ReplyDelete
    Replies
    1. The Folinic acid that seems to help with speech is 1mg/kg, which is much larger than typical supplements.

      As regards your other supplements, use what you find is beneficial. There are hundreds of supplements people take, some are beneficial, but many probably are not. You have to decide.

      Delete
    2. That's true. I used one from iHerb and it is only 400mcg per drop. My son is about 14kg now. Will see how to adjust it accordingly. Found that particular research.

      Delete
  64. There is a new trail result of bumetanide reported:
    https://www.spectrumnews.org/news/bumetanide-may-benefit-only-a-subset-of-autistic-children/

    Seems not all symptoms are related to GABA switch/ratio. And there must be some sub-types come with a different ASD pathogenesis? Could that be related to structural issue of receptors? Or lack of / too much of certain kind of synaptic chemicals? What is your educated guess Peter?

    ReplyDelete
  65. I got this Thorne NAC from iHerb with 500mg per capsule. What should be the dosage for a 14kg 26-mo?

    I also got the broccoli seed extract with enzyme. 35mg sulphoraphane per capsule. Not sure if I should start with dipping one capsule powder into his milk first? Likely I will have to split the capsule into 2-3 meals to mitigate the special flavor otherwise he would invest.

    The bumetanide is ordered and on it way.

    Trying to put him on 100mg arachidonic acid plus 1000mg DHA/EPA since last week. Also have started with NCIMB 30242 and Biogaia Protectis.

    ReplyDelete
    Replies
    1. The effect of NAC only last 3-4 hours, so try giving it 3-4 times a day. The NAC supplements do not contain what they say on the label, because NAC is not stable. In older children, the trials at Stanford used 2,700 mg of expensive NAC a day. I would suggest you try 200ish mg 3-4 times a day to start with.

      Do not try all the new supplements at once, or else you will not know which are beneficial. Go slowly, step by step.

      In some countries they sell NAC as a powder for young children. Fuimucil is one well known brand.

      Some of these products taste bad, but many children will take them. I think this may also avoid later problems with fussy eating, that are very common in autism.

      Delete
  66. Is there a therapeutic difference between say a single dose of 1 mg of Bumetanide vs 2 doses of 0.5mg (apart from practical considerations)?

    ReplyDelete
    Replies
    1. SD, in my son there does seem to be a difference. A larger single dose is more effective. Bumetanide very poorly crosses the blood brain barrier and so this makes sense. Some people's blood brain barriers are more permeable than others, so the amount of bumetanide that actually gets inside the brain will vary from person to person.

      Delete
    2. Thank you Peter! Did you see zero impact with the starting 0.5 bid or a small one that improved after moving to 1mg?

      Delete
    3. SD, I started at 1mg once a day when my son was 9 years old. After 2 weeks there was a clear positive effect. Later I tried splitting the dose to see if I could increase the effect, but the effect was reduced. 0.5 mg bid was no good.

      I am told that in the US the MAPS doctors do not see much benefit from Bumatanide, but they seem to be prescribing very low doses, like 0.5mg once a day in teenagers. US teenagers with autism are very likely to be very large and will need larger doses.

      My son with 60 kg / 130 lbs now takes 2mg once a day.

      Delete
    4. Thanks Peter! I have tried 1mg once a day on my 53lb son and I don't see a clear positive yet at the end of two weeks. I plan to continue as-is for 2-3 more weeks and re-assess. I might try Acetazolamide next.

      What is your recommendation for the not early responders? increase dose to 2mg and try for 4 weeks? Do the full 3 months like in the trial?

      Delete
    5. SD, I would continue for at least a month, to be sure. If your son has any inflammatory conditions, this will blunt the potential effect of bumetanide. You could try a higher dose for a couple of weeks, to see if that makes a difference.

      Delete
    6. Update: We tried 1mg Bumetanide once a day for almost 5 weeks. At the end, my son seemed to go into some sort of flare (may be unrelated) that I had to pull this. He was having high irritability, non-compliance, OCD, shouting etc behaviors that have still not returned to baseline. He also had a loose tooth at that time, though behaviors continued even after it fell. I am dosing Ibuprofen on demand and waiting for things to normalize back, as he is getting slowly better.
      At this point, I am not sure if it is worth trying Bumetanide again. Also the blood test done on week 5 of trial had K level of 4.2 (ref range: 3.5-5.5), so I assume that wasn't an issue.

      How do you prioritize treatment trials when you have far too many hypotheses?

      Delete
    7. SD, losing milk teeth and gaining permanent teeth raises inflammatory cytokines like IL-6. This causes a lot of problems for some people with autism and it is not about pain.

      Without a stable baseline, it is very hard to determine if new therapies have any benefit, particularly with drugs like bumetanide that take weeks to show effect. Fortunately many drugs have a near immediate effect and so you tell by starting and stopping a few times whether a perceived benefit is genuine.

      In my son's case, losing milk teeth and getting permanent teeth seemed to take forever. Ibuprofen was my therapy of choice.

      Some people in some countries use a single dose of Valium/Diazepam to see if the person is a likely Bumetanide responder. In a person who is a bumetanide responder (GABA acting as excitatory rather than inhibitory) a drug that increases the effect of GABA (like Valium/Diazepam) will produce the opposite effect to the expected one. Instead of a calming effect, there will be agitation/aggression. In a large person this is a risky thing to do, because you may not be able to control their aggression.

      Delete
  67. https://www.nature.com/articles/s41398-019-0587-2

    BDNF lower in ASD cases aged 9 or below.
    BDNF is also about E/I balance and a whole lot other functions.
    Wonder ASD treatment is very age-dependent.

    Seems bumetanide fits those age 9 or above to reverse the overflow of BDNF and thus over-exhibitory effect. But for those younger should we focus on modulating proper growth of neurons? E.g. making sure BDNF level is “normal“?

    ReplyDelete
    Replies
    1. I would start with Bumetanide ASAP. Very likely the same advice is valid for folate deficiency, if you are in the 75% with this problem.

      All the growth factors are disturbed in autism, but not always in the same way and at the same time – both hypo and hyper are possible. Things do change very much with age, so too much much growth, can then be followed by a period of reduced growth. My son went from the 90% percentile to the 20% percentile. This is all to be expected, from the research.

      Atorvastatin increases VEGF, and BDNF - which should be helpful. It also increases the expression of the tumor suppressor and autism gene PTEN. Increasing NGF is also interesting. Atorvastatin increases striatal and hippocampal levels of NGF in rats - but in humans?

      Delete
  68. Peter I really want to know your views on Chez's book and his ideas.

    I do understand there are subtypes of autism, but the fact that you did not get an EEG or MRI for Monty as Dr. Chez says where would it put you ?

    Because you did not do an EEG how would you know that monty was having subclinical seizures, what if his jumping was related to abnormal activity in the brain ?

    What would you have done if he had an abnormal EEG ? would you have treated him with valproic acid like chez says ?

    What would I do if my son has an abnormal EEG, trial bumentanide or valproic acid ? Trial a statin or agree with the doctor to treat with prednisone ?

    Its evident from the studies that inflammation has a role to play, where does that leave us from a mainstream doctor like chez and his findings ? which path to take ? side effects might have a key role to play in the choice here I suppose.

    ReplyDelete
    Replies
    1. I do have a copy of Dr Chez’s book. It was published in 2009 and I expect it was written around 2007; a lot has changed in autism knowledge since then. Dr Chez has moved on to stem cell research.

      Some of his patients are readers of this blog, they like him and he is supportive of new ideas. He is not your typical mainstream doctor.

      If you have access to testing of any kind, it does make sense to use it. Interpretation of the results is very important and you also need to know the limitations.

      Dr Kelley from Johns Hopkins clearly has very different ideas to those of Dr Chez when it comes to regressive autism. There is no right and wrong, I am sure both have patients who responded to their therapies.

      I am happy with the effect of 8 years of my own therapies. Clearly these are not therapies that Dr Chez or Dr Kelley would have given. I am lucky because I only have one autism case to master.

      There is no easy way to find effective therapies for your child.

      I have used both prednisone and valproic acid. I used low dose valproic acid, which has a more subtle effect but avoids potential side effects. Prednisone is a key part of my "autism toolkit" and I have it on hand, if I need it, to treat acute onset verbal or motor tics.

      Delete
  69. Peter,
    For clonazepam I clearly see gains
    Even at .1mg/10mcg my son is very aggressive
    Should I push through or lower the dose

    Your thoughts please

    ReplyDelete
    Replies
    1. For someone with 50 Kg the effective dose, for those who respond, is about 0.03 mg once a day. This 30 micro grams. 1 mg = 1000 mcg.

      Your dose looks too high. Above the beneficial therapeutic zone, there are negative effects like aggression.

      Delete
  70. Hi Peter .
    What Do you think about sulforaphane and myrosinase toxicity..

    https://www.kevinstock.io/health/health-dangers-of-cruciferous-vegetables/

    ReplyDelete
    Replies
    1. Ky, this article is written by a dentist who writes about diet and even bitcoins.

      As I write in my blog, sulforaphane could well be harmful in someone who has cancer. Cancer cells are fast growing and so vulnerable to oxidative stress, for these people antioxidants would be counter productive.

      Cruciferous vegetables, if you can actually get your child to eat them, are pretty universally regarded as very healthy, except by a dentist called Kevin Stock.

      Delete
  71. Dear Peter, I have just seen that you are now have switched the second dose of bumetanide to azosemide. I am wondering what the dosage is. And also, given the lesser side effects, if you have considered switching to azosemide completely?

    ReplyDelete
    Replies
    1. Liz, I do see Azosemide as a potential alternative to Bumetanide. The problem is that Azosemide is not as easy to obtain and is likely to be much more expensive, depending on where you live.

      If Bumetanide does the job, there is no reason to change.

      If you do have the opportunity to obtain Azosemide 60mg, you might want to compare its effect to Bumetanide 1mg.

      In my son's case we only use Bumetanide once a day and give a big dose. The idea is to get as much as possible across the blood brain barrier and so have the maximum effect on blocking NKCC1. The 2mg dose of bumetanide does cause a lot of diuresis and doing this twice a day would be very disruptive.

      Azosemide is also a diuretic, but does not have the acute effect that Bumetanide dose. If it was established that Azosemide was equally effective as Bumetanide, ie not just by Peter, then indeed people might switch entirely to Azosemide.

      The problem is where to get Azosemide cheaply. In many parts of the world Bumetanide is very cheap. Azosemide is available in Japan and in parts of Asia.

      Delete
  72. In my case, I'm nervous about managing potassium levels. My son also hates getting blood draws, so minimizing the need for those would be helpful.

    ReplyDelete
  73. Hi Peter,

    first of all thank you for this blog, very new to it and have been glued since discovering it. Its answered so many questions and allows me to know that I am not alone. So Thank You.

    I have watched your recent video regarding different drug therapies, very informative. I have a 2year&5month son, who has not been diagnosed but has been showing signs of autism.

    He has many words and even sentences now, not all fully clear. I want sentences, Can count 1-20, backwards too, can recite all his ABC, some imaginative play, smiles, laughs, cheeky. Looks when I point to something, Will point to varying objects and people when I say lets play pointing game, i.e point to the sky. Hello, Bye and very loving.
    My concerns are some hand flapping when he gets excited when we give him a little bit of his tv, a funny sound when he does a task such as paint, or play with his cars, "eeehhhh" sound. And he doesnt always turn when you call his name and eye contact and engagement not always great, along with not being very engaging with his grandparents and other family members and kids. Sometimes just not there, not present, so awareness not great. Not toilet trained as doesn't understand

    We have had his urine tested, which came back as high Oxidative stress and high Glutamate. It was pretty hard to get a urine sample and I have read that a urine sample for this test is not always accurate. We have since put him on a no gluten no dairy diet. Not sure if we're seeing great results, but there are some gains.

    We have introduced NAC, Sunflower Lecithin, Theanine, Valerian&Passiflora drops, Symbioflor Escherichia coli Drops, Omega 3, and Simple Spectrum multivitamin powder to his plant based milk once a day.

    My questions are, what testing would you recommend to get accurate results?

    As we dont have an official diagnosis would you recommend we get this first before undertaking any drug therapy?

    I have also read though your varying replies that for mild signs, Bumetanide will not work? Is it still worth trying?

    We are UK based and I read that there is not major testing or help.

    Look forward to your reply

    Thanks
    Sam

    ReplyDelete
    Replies
    1. Sam, nowadays an autism diagnosis does not mean much. If you really want an autism diagnosis, someone will give it to you.

      The "not present" behavior is something that suggests Bumetanide is well worth a try. The sooner a responder starts, the more profound the effect will be.

      It is quite common for very young children to become more autistic as they get older, so it is better to take action now. There is no real downside.

      Testing is often of very limited value.

      If you want to trial Bumetanide you will have to do it yourself. You will most likely get no help from your GP.

      Delete
  74. Hi Peter,

    thanks for coming back to me.

    There was a mention of a drug targeting Glutamate in your video. Would that be something to start with knowing Glutamate is potentially high?

    Or simply start on Bumetanide? How would we intro Potassium, would we need to test for that first to work out what his levels are and give him the subsequent amount accordingly?

    thanks

    Sam

    ReplyDelete
    Replies
    1. Sam, best to start with Bumetanide.

      High levels of glutamate in the brain can be harmful, but having elevated glutamate in your blood does not mean it is elevated in your brain.

      There is a guide to safely use Bumetanide here:-

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

      Most people seem to need to take about 200 mg of potassium with their 1 mg of of potassium, plus add a banana a day to diet. Testing potassium in blood is wise and then adjust potassium intake accordingly.

      Delete
  75. Peter,

    Few months ago
    I tried bumetenide and azrosimide in different times nothing happened

    This time I tried azro with low dose Clonazepam and he got hard on and started rubbing and touching his private part more often
    So had to stop it.

    Few weeks later I tried bumetenide with LD Clonazepam
    And I think it worked from the first day for good
    He started using bathroom on his own


    Now I have access to only xurinK which
    .5mg+S.release 573mg potrasium

    Is safe to give 2 pills of xurinK at once for 9yold

    Your thoughts about azro+Clonazepam with above mentioned problem

    Thanks and sorry for my bad English.

    ReplyDelete
    Replies
    1. Riza, Xurin-K contains 0.5mg Bumetanide plus 573 mg of delayed release potassium chloride.

      Taking two pills contains more potassium than necessary from a supplement, but it is delayed release, so it equates to the potassium in one and a half bananas. The recommended daily intake of potassium in a 9 year old is about 4,000 mg, the safety issue is about taking it slowly. Your potassium is delayed release, which is good.

      You have to find what works in your specific case. Sometimes thing happen by coincidence, so you have to make more trials to be sure what drug(s) are genuinely helping.

      Delete
  76. This comment has been removed by a blog administrator.

    ReplyDelete
  77. Hi, I wanted to reach out to see if in your thoroughness you've learned anything about autism mechanisms/treatments that may be similar for add mood rejection sensitivity/coupled with poor emotional processing. I'm fortunate to not have autism, as far as I'm aware, but have my own set of difficult issues. I get flooded, and get frustrated when things are difficult, and often miss the rules/pieces to complete work tasks, and then get intense feelings of rejection/fear/and sometimes thoughts (no plans) of suicidality. I can't leverage enough to get myself to a better mood state, and this interferes with job and life stability. I've tried medications (DBT, ACBT) for 12+ years, along with therapy and lifestyle, and just can't budge. Trials included lots of med classes and supplements. I am off in my planning and assessments, and my mood is okay until I realize how off I am, which in itself is frustrating to feel delusionally happy. I'm at a loss of what to do. Had 23andme raw analysis done through selfdecode. Have ANK3 mutation, and am on lamictal/pristiq, but that doesn't seem to be helping enough. Also have bdnf, SCL6a4 and nothing seems to help with those. I had explored the polypill, and appreciated the thoroughness, but not sure if there's any reason to think there's applicability, and have not had noticeable effects from NAC/sulfurophane. Would appreciate any perspective, feeling like I've unturned every stone.

    ReplyDelete
    Replies
    1. I think SL6A4 is very likely to be relevant. It is very well researched and there is a nice summary in Wikipedia, with details of the common mutations.

      https://en.wikipedia.org/wiki/Serotonin_transporter

      The SL6A4 gene produces the serotonin transporter (SERT). This transporter is the target of many antidepressant drugs of the SSRI and tricyclic antidepressant classes. This means that numerous cheap drugs exist that might be beneficial.

      BDNF is also very important. In most, but not all, genetic mutations the result is reduced expression of the gene. BDNF has been referred to as “brain fertilizer”. There are many ways to increase expression of BDNF, the simplest and safest is to increase your level of regular exercise. Atorvastatin is one drug that increases BDNF.

      Delete
  78. Hi Peter,

    I have been reading through all of your research and am excited to have found this valuable resource! My son is 10 months old and has missed many of his communication milestones. He has been formally evaluated by several developmental specialists who have found he scored very low in social emotional skills and communication, meaning he has a higher chance of autism, although it is too early to say if he will go on to have autism. However, recent research really is showing that those who miss early communication milestones have a significant chance of later being diagnosed with autism. Obviously I am concerned and want to do as much as possible especially now when his brain is still developing. He is working with community resources and I am using some of the ABA therapies. I also plan on correcting his microbiom through Sun Genomics and will be adding fish oil to his daily multivitamin. However, I am very hesitant to try any drug therapies or herbal supplements given his young age and developing brain. However, at the same time I realize changes made now could have a huge impact further along. My question is, what would you do if this was your son? Again, thank you for all of your research and responses!

    ReplyDelete
    Replies
    1. I presume you live in the US, because in most of the world nobody would be considering autism in a 10 month old. The CDC tells parents to act early and contact their pediatrician if early milestones are missed. The protocol in the US is to start early 1:1 intervention and then hope for the best.

      In reality most autism diagnosed in the US is level 0, it is trivial autism that does not need treatment. If your child has severe autism, it most definitely will need treatment and while behavioral intervention may well help, it will not substantially reverse it.

      In theory, if you knew what pharmacological interventions were effective in your specific case, the earlier you started them the greater the benefit would be. It would not be easy to judge the effectiveness of an intervention in someone so young.

      One proposed intervention, Ponstan (Mefenamic Acid), is suggested to be used very young, to avoid the development of severe autism. This idea is just in the research. Ponstan is expensive in the US, but in most of the world it is a cheap drug given to toddlers to lower temperature during fever.

      https://epiphanyasd.blogspot.com/search/label/Ponstan

      If your child has any unusual physical features you should ask for whole exome sequencing (WES).

      Delete
  79. About 3 years ago I asked the same questions on several forums about my then 11 month old son.
    My son was diagnosticated with Benign external hydrocephalus at the age of 7 months old. Although he was very sociable (plenty of interactions and smiles), there were some things that worried me: he lost his babbling at around 7 months and instead developed gutural vocalisations (tourette like); when frustrated, he was repeatedly hitting his head with his palms; he had weak muscle tone; he had awful tantrums sometimes going on indefinitely until he got what he wanted. Occasionally he would ignore everything surrounding him. He was born by c-section about a week earlier than the due date due to the fact that he was in unstable position (he had a little more liquid in the womb and he had lax joints - he still has). He had bad eczema and several severe food allergies (for which we got an epipen later on).
    I did a lot of research (including this forum) and I believe so far, the upregulation of NKCC1 and/or calcium channels theory explains best the connection between being born early and/or via c-section, head trauma and autism and even why some parents report regression after some vaccines (via inflammation) or why gut problems are more prevalent in children with autism. NKCC is not expressed only in the brain, but also in the gut and other places in the body.
     
    I researched OTC supplements that downregulate NKCC1 and upregulate KCC2. I tried a bunch but ended up with a few that after being given continuously for 1-2 months, I knew I was on the right path. The changes were subtle at first (more calm, less tantrums, he had more energy). It was a lot of continuous work. I was 1:1 with him all the time for 2 years. 

    ReplyDelete
    Replies
    1. It is good that you received an accurate medical diagnosis at such a young age. As the name suggests Benign External Hydrocephalus is caused by too much fluid surrounding the brain, this often causes the skull to expand and produce a big head (macrocephaly). As a big head is common symptom of autism and intellectual disability, you are lucky that was not the diagnosis.

      The condition is benign, because it usually rectifies itself, without any intervention, but manifests as a developmental delay, which would undoubtedly be very worrying until matters improved.

      “A transient delay of psychomotor development is commonly seen during childhood. A long-term outcome is scarcely reported, and the results are varying. Although most children with external hydrocephalus seem to do well both initially and in the long term, a substantial number of patients show temporary or permanent psychomotor delay.”

      Delete
    2. My son's head circumference was in the 99% percentile and his fontanelle was not closed so we were able to do an ultrasound instead of an MRI that revealed extra axial liquid, but no internal hydrocephalus (I don't recommend an MRI at that age because infants need to be sedated during the procedure).

      Delete
  80. This is what worked for us:1. Mommy's bliss organic multivitamin (unfortunately I cannot find the organic version anymore). It had I believe the right ingredients: all the antioxidants (A, C, E) and a good portion of daily value from B1,B2, B3, B5, B6. I tried multiple multivitamins and the ones that contained B12 made the tourette part worse. 
    The closed to that multivitamin is this: 
    https://wellements.com/products/organic-multivitamin-drops?currency=USD&variant=19613994483800&utm_medium=cpc&utm_source=google&utm_campaign=Google%20Shopping&gclid=Cj0KCQiA7oyNBhDiARIsADtGRZatZEvCfboCxj8JKayFcruNODVY0R8Lmi7ZtpCtJyU5ct6DDVzbTVUaAjkjEALw_wcB
    2. Zinc (only gave him 1ml/day)https://www.amazon.com/Infantum-Infant-artificial-flavor-Liquid/dp/B016CCVJQS/ref=asc_df_B016CCVJQS/?tag=hyprod-20&linkCode=df0&hvadid=312169186997&hvpos=&hvnetw=g&hvrand=257395081651581968&hvpone=&hvptwo=&hvqmt=&hvdev=c&hvdvcmdl=&hvlocint=&hvlocphy=9010794&hvtargid=pla-593464284434&psc=1
      3. Magnesium (only gave him 1/2 gummy)https://www.amazon.com/Natural-Vitality-Anti-Stress-Magnesium-Supplement/dp/B076414SYD/ref=sr_1_4?keywords=magnesium%2Bgummies%2Bcalm&qid=1638121326&s=hpc&sr=1-4&th=1

    ReplyDelete
  81. 4. Daily probiotic taken fresh from health stores (the ones ordered online were not potent): https://www.vitacost.com/flora-toddlers-probiotic?CSRC=PPCADW-GGL_SEM_NB+PURE_US_PRO_DSA_Vitamins+%26+Supplements_NA-&network=g&keywordname=&device=c&adid=39700047316658794&matchtype=b&gclick=Cj0KCQiA7oyNBhDiARIsADtGRZYYYmhcyYQQyWhni5lwG-eVjBQPmom6YkD1236ZM5k-sgaliN38Qu8aAr-OEALw_wcB&ds_agid=58700005320605356&targetid=&s_kwcid=AL!9700!10!%7bAdId%7d!%7bOrderItemId%7d&gclid=Cj0KCQiA7oyNBhDiARIsADtGRZYYYmhcyYQQyWhni5lwG-eVjBQPmom6YkD1236ZM5k-sgaliN38Qu8aAr-OEALw_wcB&gclsrc=aw.ds

    5. Fish oil with more DHA than EPA:https://www.amazon.com/Nordic-Naturals-Arctic-Orange-Omega-3/dp/B002WTCM3K/ref=sr_1_1_sspa?gclid=Cj0KCQiA7oyNBhDiARIsADtGRZZOtqBQRpSmuqf-ZkMgcV6KPoq5rEaH196RiRqPTcr0Ur8PKGRADC8aAlXGEALw_wcB&hvadid=241571657488&hvdev=c&hvlocphy=9010794&hvnetw=g&hvqmt=e&hvrand=17592593405059995058&hvtargid=kwd-6033020943&hydadcr=15286_10335082&keywords=cod%2Bliver%2Boil%2Bnordic%2Bnaturals&qid=1638121596&sr=8-1-spons&smid=AD4JTYB7A7HOQ&spLa=ZW5jcnlwdGVkUXVhbGlmaWVyPUEzRk43OEFQMFlLTVM3JmVuY3J5cHRlZElkPUEwNTk5Nzg3OExWTFNDSzVCTktCJmVuY3J5cHRlZEFkSWQ9QTAzNDE1ODUzNUxLWTRWN0VBMlMmd2lkZ2V0TmFtZT1zcF9hdGYmYWN0aW9uPWNsaWNrUmVkaXJlY3QmZG9Ob3RMb2dDbGljaz10cnVl&th=1

    6. Occasional Alpha Lipoic Acid in small doses (3mg every 3 hours for 3 days, then break for a week)This improved a lot but also lowered his immune system (he was getting colds easier when on ALA). I used to avoid visits or exposure to lots of people while on ALA. 
    7. Occasionally, Selenium 
    8. Diet: no calcium sources (like dairies), gluten free, reduced carbs (almost keto diet) until he was age 2. Broccoli sprouts. It really was not hard because he did not know otherwise. Vitamins, he did not like them at first but I eventually found ways to give them.
    When I was discontinuing treatment for more than 4 days, I saw small regression, including regression in the way he walked (he would bump into things, fall more often, more tantrums). I tried different combinations of supplements on different days and kept journal to track progress. B6 and the multivitamins were helping with speech and cognition. Mg and Zinc with calming and even sleep. Selenium, less OCD and more affectionate. 
    He is now a very smart 4 year old with an amazing memory and logic. He is a little more shy than other toddlers, but it's really a joy to be around him.  


    ReplyDelete
  82. You can also add a little more B6 to the above list:

    https://www.amazon.com/Renzos-Bright-Dissolvable-Vitamins-Oh-Oh-Oh/dp/B06XY2TGXW

    and maybe either DMG or betaine anhydrous (also known as trimethylglycine or TMG). We tried TMG but I stopped because it made my son's eczema much worse.

    ReplyDelete
  83. Hi Peter,

    My son has 5 years, he is ASD, verbal, he reacts to commands, I would say that he has mild autism. He is hiperactive, does not play with toys, has no need to be with other children. He always put things (usually toys) in his mouth and bites them (even toys made of wood), he likes pressure on his forhead, so he bangs his head in the floor or wall, or in my forhead (when he bangs his head this is not too hard). Also he is always hungry, and he can always eat sweets, bread, salami, some fruits....but his craving for these kind of foods (especially sweats) is like addiction... He is always negative, even when he wakes up, when I tell him to go to pee, he is angry saying: no, so I have to order him in treatening tone i order for him to do what I say. He is not aggresive. We started 1mg yurinex a week ago, I don't see any gains, we will continue at least for 3 weeks.

    What is your opinion in regards to his behavior noted above (byting things, craving for sweats, bread, banging head), what would you recommend we try if there are no gains with yurinex?

    Thanks in advance.

    ReplyDelete
    Replies
    1. You do need to give Yurinex/Bumetanide a full 4 weeks to be sure whether it provides a benefit or not. You should see a change in mood and play skills, plus improved cognition.

      If he already has high cognition, I doubt he will respond to Bumetanide. A significant number of people with mild autism and some with severe autism seem to benefit from Baclofen/Lioresal, which is easy to try.

      Putting non-food objects in your mouth is usually called pica. Some children just chew on the object, while others swallow the objects. Pica can be dangerous.

      Pica can be associated with nutritional deficiency (for example, iron or zinc). It can be caused by supplements (eg vitamin B12 injections).

      Pica can be caused by very many other things (sensory stimulation, teething/toothache, anxiety etc). It can just be stereotypy/stimming or OCD.

      You could try the antioxidant NAC, which often reduces stereotypy and OCD.

      You have to make sure liking pressure on his forward does not develop into real head banging, which is a feature of autism. Does he always exhibit this behavior? Or just sometimes? Maybe he has some mild pain? What happens if he takes some Brufen?

      Some children with autism avoid eating, while others over eat. It is best to gradually stop buying unhealthy foods, so he cannot eat them.

      Delete
    2. Hi Peter,

      Thank you for your answers. I will try bumetanide at least 4 weeks.

      In regards to banging head, my son usually does this when he is stimulated (when he is running from one place to another in the apartmant). We rarely give him brufen, only when he has a fever (when his temperature is higher than 38.5 degrees). What is strange, when he has a fever (not too high, up to 38 degrees) he acts more like NT child as he is calmer and not so stimulated.

      I didn't know about Baclofen. What is the recommended dose for a 5 year old (30 kg)?

      Delete
    3. The fever effect is well known in autism and the improvement can be profound. Nobody has yet fully explained it.

      A typical dose of baclofen used in autism for young children would be 5mg once a day, in larger chidren 10mg. Much larger doses are used for other conditions. It is worth trying, there is likely to either be no effect or a good effect.

      Delete
  84. Hi Peter, this has been very insightful read, big thank you. i red through the article as well as all of your responses to questions above. i was trying to figure out if there are any ways to predict bumetanide response before trialing it. i could only note 3 points:

    1) agitation/aggression with use a single dose of Valium/Diazepam
    2) bad reactions to benzodiazepines
    3) Quercetin? There was a mention of it, but was not clear if that can be relevant tester

    My question is : anything to delete or add to the list? and what would be top choice?

    thanks a lot Peter, for address all these questions. much appreciate it.

    ReplyDelete
    Replies
    1. Timur, in a bumetanide responder GABAa receptors give the opposite signal than the brain expects. So anything that activates these receptors will cause agitation rather than calming.

      Benzodiazepine drugs like valium, picamillon, whivh is OTC outside the US, could all be used to test for a negative response. It all depends what you have access to, where you live.

      Quercetin will not help you.






      Delete
  85. Hello Peter
    I've been checking your blog for a while now and it's absolutely eye-opening. Thank you for all the effort to share your experience.

    I am from Egypt. Research on autism treatment is not very common here. I must say I'm not from a scientific or medical background but I am a parent who has two eyes and a brain and I want the best for my child. So I'm reading your words and a lot of what you say rings a bell.

    Mo is currently 4,5 years old. Weighs 17-18 kg. He had laryngomalicia as a baby. Born in C section. Not breastfed. Had eating difficulties since birth. He could not breastfeed. He spat up, gagged, and choked a lot when bottle feeding, and when trying to introduce solid foods. He walked a little later than his older sisters. He was 16 months old when he started walking. But he teethed pretty fast at 6 months. And of course his language was delayed (no autism diagnosis so far). He had all of 3-5 functional words until the age of 3 and he used to call his sisters names but he stopped. The rest was humming unclear song lyrics and occasional words from cartoons he liked. He had a couple quirks/stims/repetitive behaviors. He sometimes walked on his heels (not toes) while flapping his hands when excited. We called it the penguin march. He would occasionally spin things. He didn't play with other kids. Rarely interacted with us. Rarely responded to his name. Poor eye contact. TV was his main pastime. Sensitive to certain textures. He never chewed on chewing Toys as a baby. Hardly put anything in his mouth. Didn't want to touch food or eat with his hand or utensils. He was mostly spoon-fed by his mother. We realized later he had weak fine motor skills.

    He'd been on Vitamin D drops (on and off) since he was a baby. His diet was mostly soft food. baby cereal, yogurt, banana, tea biscuits. Milk. Occasionally soft bread. So mostly wheat and dairy. Meats, rice and veg had to be softened in food processor. And he was constipated most of the time.

    Age 2 he had his first major seasonal allergy attack. he would hardly sleep at night. and woke up 2 hours later congested, screaming, throwing himself and squirming on the floor. stomach pain. blocked sinusitis.

    His pediatrician said it was indigestion and prescribed digestive enzymes. Also glycerin suppositories which didn't work and made things worse.
    A colostrum supplement sachets supposedly for a better immunity made his constipation worse AND WORSE.
    Zyrtec seemed to help and made him calmer but we gave it on our own. Doctors did not prescribe it. And as he grew up it seemed to lose its effect.

    Mostafa

    ReplyDelete
  86. Age 3 the allergies recurred around late February and we started to have a clue what was going on. We lived in a village with orange fields and once the orange blossoms popped, you could smell the pollen in the air.

    Later we moved to Cairo. the city. and allergies seemed to get milder symptoms, but they still exist.

    We also suspected he had issues with certain foods. Dairy, wheat, and legumes in particular. We decided to put him on a GFCF diet and his bowel movement and stomach issues in general got better. We also have been giving him half a cup of camel milk which seemed to help somehow with the GFCF diet. He started to be more verbal and interactive. Not much but better than before. When we changed the diet he suffered a mild rash on his thighs but eventually it resolved.

    Later We tested him for food sensitivities (ELISA) and he tested positive for everything we suspected and MANY MORE. About 50 food items tested positive. He's currently on an elimination diet and it seemed to help his cognition and focus a bit. But sometimes he still gets constipation and a sour mood and we are at a loss! We're now suspecting D drops and possibly Omega 3 but not sure. We recetly stopped both and his bowel movement is back to normal...

    Age 3.5 (January 2021) he started old fashioned speech and skill building therapy (we will start ABA next week) and he improved quickly even though it was on and off (due to a couple of sinus infections and/or allergies). He's now better at expression and forms longer 4-5 word sentences . A bit more articulate. Better eye contact. Responds to his name most of the time. A bit more interactive. But sometimes we feel something is blocking his progress. And he started getting more "stimmy" after he started those sessions. It might be because the therapists keep commenting and we started to notice them more. Or stress of the high demand they put in him. or them telling him off or blocking his stimming. Not sure. But right now. Even after we limited screen time and reduced sessions, he kept scripting cartoons (now his words are much clearer) and flapping more than usual. He never gritted his teeth until he began taking those sessions. Some other strange behaviors came but went and we never know the cause.

    He's got the "Fever Effect" once as well. It was clear he was more present and interactive. He'd gotten antibiotics and ibuprofen then. Plus he had severe diarrhea which I now think the flushing of minerals helped decrease the chloride in his body???? Electrolyte poweder seemed to make him more "awakened"... Then months later we all got COVID-19... he only ran a mild fever and the progress started to fade. It is all just confusing. Skills coming and going.

    He keeps getting those times of being bright and present and times of being lazy and lost. Sometimes he does imaginary and interactive playing, utilizing phrases from tv into real life and sometimes he becomes more "aloof?" And reluctant to interact. He keeps getting those ups and downs throughout his progress and we can't determine the definite cause.

    Sorry I'm ranting a lot but I just need to help my son. So I've been reading you and I am fascinated by all the possibilities that could help him.

    We're now trying NAC 600 (split into two 300 mg doses) and it seems to work! He's been only a few days but I already noticed he's more interactive and in a better mood (the flapping is still there though), even though he's got another allergy attack (quick trip to town during a dusty weather) his allergy medication seems to help (chloropheniramine maleate + phenylephrine) but we're not sure of the right dose for his age/weight.

    I would really appreciate any kind of help regarding dosing and/or other "safe" treatments to try. Thanks again for the amazing blog...

    Mostafa

    ReplyDelete
    Replies
    1. Mostafa, it sounds like immunity issues are very central to your son. A lot points to the gut having a central role in how our bodies learn what to react against. So working on gut health and improving mucosa and microbiome, and learning more on Th1/Th2, Tregs and microglia is recommended.

      Long-term you want to decrease "stress hits" (immune, allergy, gut issues, social...) when possible, strengthen barriers (gut/blood and blood/brain) and work on putting microglia to rest (takes years).

      If allergies affect cognitive abilities - go for the old style medications that penetrate the blood-brain barrier (they will have sleepiness as a side effect).

      You still have a short window to affect immunity issues, the sooner the better.

      /Ling

      Delete
  87. Mostafa, there is a relatively short list of therapies that do benefit a significant sub-group of autism.

    I know that bumetanide is available in Egypt. I would suggest you make a trial for 1 month, say 0.5mg twice a day.

    If generic calcium folinate is available, it is worth a try. This is called Leucovorin in the research. Apparently about 70% of people with autism have antibodies that block folate from entering the brain – these people should benefit from calcium folinate.

    Memantine and Baclofen are both inexpensive and do seem to work for some people.

    I suggest you read up about these therapies and the clinical trials before deciding what to do.

    You could also try increasing the NAC dosage or its frequency and see if it gives a greater benefit.

    ReplyDelete
  88. Hi Peter,
    First of all thank you so much providing this great blog to us. I have been following for some time and have benefited from it so much. Thank you again.

    I would like to have your opinion on a recent research done with clemastine :https://www.biorxiv.org/content/10.1101/2021.12.14.472570v1

    It is stated that clemastine may cause impairment of "developmental" myelination. I have been giving my 5yo son 0.67 mg of tavegil daily for 4 months but after seeing this research i am a bit worried now. Do you think could a 5 yo get impacted by this "develomental" myelination impairment risk?

    Thanks in advance,
    Oktay

    ReplyDelete
    Replies
    1. Oktay, it is not unusual in the research to find contradictory findings. We also have to accept that mouse models are not always going to behave exactly like human brains.

      Clemastine is an approved drug to treat hay fever in children.

      Clemastine is given at very high doses to treat multiple sclerosis. I would not consider this a safe long term strategy in children with autism. In part because it will lower levels of acetylcholine in the brain, which may reduce cognition.

      I decided to trial clemastine for autism using a dose much lower than the approved hay fever dose. It did indeed seem to trigger cognitive changes, in particular developing of his opinions, rather than just doing what he was told. If I had seen no effect I would not have continued.

      In your paper the mice were treated with 50mg/kg/day, i.p.

      I am not an expert in converting mouse doses to the human equivalent. But it may well be that this is a jumbo dose compared to your 0.67 mg/day.

      If you are worried then you should stop giving Clemastine.

      Delete
    2. Thank you Peter for your time and reply.In addition to Clemastine, I'm giving him 1g D-BHB+10 ml C8, and probiotics to address dysbiosis in his gut (zonulin > 544). I see great improvements after starting these therapies and i don't really like to break this combination. I can't thank you enough!

      Oktay

      Delete
  89. Hi Peter,

    I stumbled upon this blog a week ago while looking up Suramin and have been reading up as much as I can since then. It has been eye-opening to say the least and I am convinced that I need to try medical interventions for my son. As a starting point, I would like to choose a doctor in the US who can help us with appropriate tests and prescriptions. I will lay out my son's case history to see if that helps.

    My son Vik (age 4yrs 7mo) was born two years after we emigrated to the US from India. He had a vaginal forceps delivery - no complications during pregnancy. His birth weight was low (~10th percentile) but had a relatively big head (90th percentile). He has been going to daycare since he was 10 months old. During his first year of day care, he had frequent ear infections and he had a surgery at 2 yrs age to put ear tubes in and he has not been majorly sick since then.

    He met his motor milestones on time and by the age of 2 he was reasonably social and had a few words but was not making two word sentences. By age 2.5, he was able to request for what he wanted ('I want __", "lets go to __") and he knew his colors and shapes. He started to be fascinated by alphabets and I remember him spelling the word 'vegetable' which was a bit of a surprise.

    Then covid hit and he stayed home for an entire year during which time he mostly played with his few toys and watched alphabet/numbers videos. During this time we started to notice that he was getting increasingly anxious to be with people, to the point of totally avoiding everyone else except family members. This was also the time when he slowly started to withdraw into himself more. When we restarted daycare at age 3.5, we were told that he is not very communicative and prefers to play by himself. It was at that time that I noticed how much more the other kids were speaking and the difference was stark. I am not sure if this is a regression - he did not lose any language he previously had, he just plateaud badly and fell behind.

    By age 4, the anxiety started to subside, but his language was not improving and what he had was mostly echolalia. That was when he was referred for any autism screening and he was diagnosed ASD at age 4y4mo. His CARS score was 33 and his GCA (IQ-proxy) based on DAS-II scale was 76 (verbal- 75, non-verbal-72, spatial-95). We have started speech, OT and ABA in the last 3 months. Speech-wise, I would say he has made a lot of progress in the last 6 months, but some issues like lack of attention, impulse control, anger etc. have worsened over this period. We have had no issues with his sleep and barring the last few months, no issues with eating either (he has become much more picky of late). He has a vocal tic that he recently developed that sounds like he is stressing the syllable 'K' while clearing his throat (making 'king' sound like 'kkkhhhing') - but I am not sure if that means anything. 

    We have started a trial of NAC (500mg twice in a day), but we have not seen any significant effect (positive or negative) so far (3 days). I have ordered Bioagia Gastrus and will start it tomorrow. Our primary goal for now is to improve his attention and not 'tune out' frequently.
    Apologies for the long post. I just wanted to present as much info as I can.

    I have a couple of questions:
    1) Is there a specific doctor who might be willing to help us with testing and prescriptions (we were thinking of Dr. Anjum Usman, Chicago)
    2) Is there a sub-type of autism that is evident from the details?

    I sincerely appreciate Peter's and the rest of the community's efforts to help kids on the spectrum. I will do my bit and add my observations on the trials.

    With gratitude,
    Anvesh

    ReplyDelete
    Replies
    1. Anvesh, treating autism remains highly controversial and your doctor appears to have had some issues with the medical regulator. It is always an issue when the doctor is selling you their own supplements, compounded pharmaceuticals and hyperbaric oxygen equipment.

      The very pronounced size of your son’s head relative to his body at birth may well be relevant. I would suggest you carry out whole exome sequencing (WES) to see there is a known genetic cause of his autism. Lots of people in the US use a company called Gene Dx, who seem to give you a discount if you need one.

      There are many partially effective therapies that benefit sub-groups within autism. The large head would suggest the hyper-active pro-growth signaling type of autism (which is most autism).

      You can spend a vast amount of money on tests, but the validity of the great majority is questioned by mainstream doctors.

      If there is no clear genetic cause, you are left with trial and error using the many drugs and supplements that have shown benefit in the many clinical trials that have been published.
      Many autism doctors have their own pet therapies and so you may need to see more than one doctor to access all of the possibly beneficial therapies.

      Delete
    2. Peter,

      Thanks for your quick response.

      I will get in touch with Genedx to get his WES. I will also try to see if I can get in touch with more than one doctor (I was thinking Dr.Frye/Dr.Rossignol) to see I can get different perspective, though I read elsewhere on your blog that the waitlist may be too long and it might be pretty expensive.

      I would like to add a couple of things I missed in my previous comment about my son's symptoms. Despite his head size, he always looked much younger than his age. He is 4.5 years old now, but looks like 3.5 years old - though I am not sure what this means medically (should I check for growth hormone?). He is now more or less proportional w.r.t weight, height and head size.

      The other thing that I wanted to bring up is that he compulsively tunes out mid-sentence even when he is interested in the conversation/activity. He is either vocally stimming or you can 'see' it in his eyes that he is reading a page from a book or a scene from an episode. In some rare occasions, he even talks about what he is seeing. Agreed that his happens more when he is doing an activity he does not like, but I can also see that it is not entirely in his control to focus on the task at hand. This probably is common across the spectrum, but I am posting this to see if someone had success with any drug/therapy in improving joint attention.

      I am in the process of procuring bumetanide from India to start a trial next month. Will post the results after that.

      Thanks again,
      Anvesh

      Delete
    3. (Commenting here to keep all the updates on one post)

      Hi Peter,

      My son Vik used to be a very good eater until about 4 years of age. He used to eat a variety of fruits and veggies and had regular bowel movements. In the last 6-8 months though his food intake (volume and variety both) slowly decreased to less than half of what he used to eat. It was also roughly at this same time that his irritability and oppositional behaviors emerged. Our Paediatrician said that he might have developed food fads or sensory issues towards some food textures etc. There were no complaints of tummy ache and he still ate a lot of fruits and had bowel movements twice a day, so we did not suspect constipation. Our DAN doctor suggested it might be good to get an abdomen X-ray anyway. We went ahead and got it, expecting to see nothing but the report said that there was a large amount of stool in his colon. We were told to give enema and start a bowel cleansing procedure as soon as possible.

      Peter, I wonder how long he had been having the constipation and how can he have stools of good texture but still have severe constipation? Can't help but think that at least some of his behaviors must have been the effect of constipation.

      I hope this is a useful lesson to other parents.

      Anvesh

      Delete
  90. Hi Peter,
    Thanks for the blog and all you do for this effort. I was a regular reader/contributor, my son did not make much progress between 2 & 5 when we did ABA etc., we want to try again as he turned 9 and seems to be paying more attention.
    Recently you talked about a probiotic on the blog, can you tell us the name again, dont think it is biogaia, wanted to start off with that.
    Thanks
    BK

    ReplyDelete
    Replies
    1. Welcome back BK.

      Most recently I have mentioned Lactobacillus plantarum 299v, which was suggested as a possible autism therapy many years ago. It is widely available and used by people with GI problems.

      In my son it has a mood enhancing effect, very similar to what sulforaphane/broccoli powder used to provide, but the effect lasts all day.

      https://www.cancer.gov/publications/dictionaries/cancer-drug/def/lactobacillus-plantarum-strain-299v

      Lactobacillus plantarum strain 299v

      A nutritional supplement containing a strain of the probiotic bacterium Lactobacillus plantarum 299v (Lp 299v) with potential antimicrobial, immune-boosting, and anti-inflammatory activities. Upon oral ingestion, L. plantarum strain 299v adheres to the intestinal mucosa, modulates the composition of the normal microflora, helps maintain adequate colonization of the gastrointestinal (GI) tract and improves digestion and metabolism. Upon colonization of the GI tract, the probiotic may form a protective barrier, thereby preventing attachment of pathogens, protecting against infections and boosting the immune system. In addition, Lp 299v stimulates the secretion of protective mucin and produces lactic acid and hydrogen peroxide as well as other substances, thereby creating an acidic environment which prevents growth of pathogens.

      Delete
    2. Hi Peter,

      i have started to use L299 a month ago after reading your post and all 3 expensive urine test showing high kyruneric acid, i helped with her sleep. i give it before bed (1 caps 10b CFU as night snack sprinkled on cereal (along with 50B CFU pure encapsulation probiotic mix).

      She usually gets "drunken happy" after night snack, not sure why :). i used to add L-theanine too, but i am also a bit thoughtful l-theanine impact on gaba which may give excitatory effect, so ordered picamilon to test her potential bumetanide responder

      Main issues with my daughther is: poor speech, social and most importantly sometimes crying with no reason and irritability (any thoughts what kind of subset of autism this is? mood and anxiety disorder maybe). i am starting P128 probiotic and will see what it does. i also use Rg3 nasal spray (ginseng) possibly can help with irritation.

      If P128 will work, i will keep L299, P128 and maybe later test Biogaia L reuteri.

      i will also switch to Avmacol (was using broccomax), as you rightly mentioned better to use ones that used in clinical trials.

      She also had high lipid peroxides and low glycine in urine, so started NAC (pure encaps) which had good effect, but slown down after reading another post around B12 depletion.

      As ever, very grateful for your thoughts. i am learning a lot from your blog, thank you.

      Delete
  91. Thank you for the information.

    With the recent action against NAC and NAC Sustain being off the market, do you still see ALA Sustain being the best replacement or regular NAC (minus the B vitamin pairing)? Which would you prefer for Monty?

    Any thoughts on ALA Sustain dosage equivalents in replacing NAC Sustain?

    Much appreciated.

    ReplyDelete
    Replies
    1. Kan, I assume in the US eventually there will be no NAC available.

      I still use NAC Sustain. When my supply runs out, I will go back to using the NAC in gelatin capsules that I originally used. If I could not access NAC, I would use ALA.

      Nobody seems to quote an equivalence between NAC and ALA. Most supplements are both 600mg, except ALA Sustain which is 300mg for some reason.

      The reality is that NAC sold in capsules has substantially degraded (hence the smell) so 2 jars may contain very different levels of antioxidant. It will vary by brand and by batch.

      The effects of ALA and NAC are not exactly the same and neither are the possible side effects.

      My father-in-law has been taking oral ALA and intravenous ALA for 20 years, with only good (anti-neuropathy) effects. I tried ALA on myself and got a side effect, so it all varies person to person.

      If there was no NAC, I would probably start with 600mg of ALA 3 times a day and then see the effects.

      Delete
    2. Makes sense - we'll be testing more NAC against the ALA Sustain.

      Thank you for the information.

      Delete
    3. Hi Peter,

      Considering NAC and ALA are not gut dysbiosis friendly, is there any alternative to these which is ok when child has dysbiosis (yeast overgrowth)?

      P.S. i was using Pure Encapsulation brand for NAC which is good brand, then just for one batch i switched to Biocare NAC which was smelling horrible (egg smell), so i am back to Pure Encapsulation. also tempted to order Fluimicil or Pharmanac for the next round.

      regards
      Teymur

      Delete
  92. Hi Peter,
    Is there an alternative to Bumetanide if the child is allergic to sulfa drugs?

    ReplyDelete
    Replies
    1. The alternative to Bumetanide might be Azosemide, but all the trials use Bumetanide. Unfortunately, Azosemide is in the same class of drugs as Bumetanide and also contains sulphonamide.

      But, it looks like being allergic to say an antibiotic containing sulfa, does not means you are allergic to all drugs with sulfa. So it is not really a true sulfa allergy.

      Read this:

      https://www.webmd.com/allergies/sulfa-allergies

      Sulfa drugs, also called sulfonamides, include antibiotics as well as other types of drugs. Allergies happen most often with antibiotics. About 3 percent of people have some type of reaction to them.

      Some sulfa drugs may be OK

      Even if you’re allergic to antibiotics that have sulfa, you might be able to take some other types of sulfa drugs without a reaction. Ones that may be safe to take include:

      • Glyburide (Glynase, Diabeta), a drug for diabetes
      • Celecoxib (Celebrex), a nonsteroidal anti-inflammatory drug (NSAID)
      • Sumatriptan (Imitrex, Sumavel Dosepro, Zecuity), a migraine drug
      • Water pills, or diuretics, including furosemide (Lasix) and hydrochlorothiazide (Microzide)

      Bumetanide is a water pill, very similar to furosemide.

      You might want to carefully check if bumetanide is indeed well tolerated in your case.

      Delete
  93. Thanks Peter. Bumetanide wasn't tolerated. But we'll give a try to Diamox. It's not a diuretic, so it is easier too. My son doesn't tolerate Celecoxib, but he can take Sulfur-supplements such as Nac at rather high doses.

    Additionally he is allergic to penicillin and there is a cross/reaction -people who are allergic to penicillin have more chances to be allergic to sulfa drugs, and should be careful.

    ReplyDelete
  94. Hi Peter

    Thanks for this blog and for helping families with Autism.

    My son is 3 years and four months old, vocal but non verbal, doesn't follow instructions for most of the time, flaps his hands and grinds his teeth, doesn't wave or point, also he rarely responds to his name. We live in the UK ( Manchester). He hasn't been diagnosed yet however the paediatrician mentioned that he might have autism. We are still awaiting for the diagnosis referral. My son has had some low level of iron and he was eating from the floor. When he had his iron medication he stopped the habit of eating from the floor. After reading your insightful blog about the different types of medications that you have given to your son. we really want to go through this route.


    To be honest, we don't know where to start and we are little worried about giving medication to him at this age. It would be greatly appreciated if you can advice on what medications/supplements should we start giving our 3 year old son and what are the appropriate dosages.


    Many thanks.

    ReplyDelete
    Replies
    1. I just wrote this reply to Mat, also in the UK.

      "Mat, other UK readers of this blog are using Bumetanide and other therapies via Dr Antonucci in Italy. I have never spoken to him myself, but I am pretty sure he will be able to help your daughter - he also has a daughter with autism.

      Just google "dr antonucci autism"

      I would not bother trying to convince UK doctors; their employer, their regulator and NICE are very strongly anti treating autism.

      Best to knock on an open door. The consultations are online, so it is very simple. You do not need to speak Italian!"

      Since you will struggle to obtain any prescription drugs in the UK, I think you might as well just go straight to Dr Antonucci.

      Delete
    2. Thank you very much for your reply. Much appreciated.

      Delete
  95. Hi Peter
    Wanted to share.
    LDN @2.5 mg works well for my 10y old asd son's pans/pandas symtopms
    Same as giving pentoxfilne.




    ReplyDelete
  96. Hi Peter,

    Thanks for publishing this great resource. I'm a young adult just diagnosed with high functioning autism / Aspergers.

    I'm starting to research treatments for my Aspergers, but I'm overwhelmed. Do you have any advice for how to search through the insane amount of medical literature for things that might help? How did you approach this when you were first starting out with your son?

    And do you think any of your polypill might help my Aspergers as well?

    Thank you again for this great resource you have provided

    ReplyDelete
    Replies
    1. There is a lot of research, but there it a lot of trial and error involved to find effective therapy.

      I was lucky that my very first trial (bumetanide) was highly beneficial and showed that my son’s autism was treatable.

      For Aspies, a good place to start is any medical comorbidities. For example many Apies have IBS/IBD or ulcerative colitis at the extreme.

      Many Aspies seem to benefit from antioxidants like NAC. Some benefit from Agmatine, some from Baclofen. All the broadly anti-inflammatory therapies (statins, pentoxifylline, pioglitazone, low dose naltrexone etc) are potentially beneficial.

      There are groups on Reddit and elsewhere where Aspies discuss their therapies.

      Delete

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