Do you tell it as it really is? Or sugar-coat it, to make it more appealing?
It looks like in the English-speaking world we are more and more being driven by emotional political correctness, rather than calling things out as they actually are. Now this does not really matter if you are talking about relatively trivial subjects, which is what we deal with most of the time, but is a problem when dealing with a serious subject. When it comes to autism, giving the cold truth is quite upsetting to many people.
Bryna Siegel, a Californian Psychologist working with autism for a few decades has been promoting her new book, The Politics of Autism, in various articles.
She tells a lot of home truths that many parents and professionals do not want to hear and people often react very emotionally and quite aggressively. I have found myself on more than one occasion giving her support.
She has several key points to make. Autism is indeed over-diagnosed and as long there is a financial incentive for this, prevalence will increase.
She is very critical of the results of inclusive education, based on what young people are actually able to achieve when they leave school. The idea of inclusion sounds great, but what actually matters is the end result, in terms of independent living skills and job prospects. She wonders if people with more severe autism are being taught the right skills, rather than just a dumbed-down version of the standard curriculum.
At times, even I think she is perhaps a bit too brutal, but I think I will buy her new book. Monty’s assistants are also keen to read it, so maybe I will also donate a copy to be shared.
I know one little boy with severe autism, who is entirely non-verbal, and has no sign language or facilitated communication device. I do not think he can read or write. At primary/junior school he now has to learn a foreign language.
Autism Misinformation
A good example of autism misinformation occurred recently following on from a popular UK daytime TV show, and was highlighted in the Questioning Answers blog.
The host was interviewing a mother about her son with autism and he asked the very reasonable question “has your child always been autistic?” This prompted an outcry from the public and a supposedly knowledgeable organisation called the National Autistic Society (NAS), the UK’s dominant autism organisation. The host was blasted for not knowing that apparently “autism is always present from birth” and “it is not something you can grow out of” and of course it is un-treatable.
Given this child was described by his own mother as having regressed at 18 months and lost his speech, he might well not have been born autistic. The research has shown that many things can trigger “autism” during childhood and we know that about 10% of kids diagnosed with autism do indeed later go on to lose their diagnosis, so they do pretty much grow out of their autism. But why let the scientific facts get in the way of the simple storyline?
I always found the idea of raising autism awareness to be odd; it very often is just promoting misinformation, or putting one random person forward to explain the condition to others. This just confuses other people.
It is much better to just raise public awareness of disability in general, both physical and mental and to tackle bullying at school. Kids should be aware that a small percentage of their peers have severe problems and a much larger percentage have less disadvantaging problems, that can often be mitigated with extra help and understanding during all those years spent at school.
People need to know that just as autism is a spectrum from severe to mild, so are many other conditions like ADHD or dyslexia. Some people just need a little extra help, but some others have profound problems. Sometime soon 10% of all kids will have a medical diagnosis, but only a small fraction will be disabled by it.
You can have dyslexia and still make it through medical school, but don’t dream about it if your kid has Down Syndrome.
“Dr” Wakefield
I do think Andrew Wakefield was very unfortunate to have studied medicine in the UK and not the US; had he done so I rather doubt he would have ever lost his medical license and he would never have become so well known. He has a right to his opinions and there are some far more cranky physicians merrily practising today in the US.
Wakefield seems to making himself a new life with Elle Macpherson. This clearly upsets the UK tabloid media, who still portray him as the devil - how can the devil end up with a super model? I wish them well.
Wakefield likes to refer to autism as brain damage, which is rather brutal like Dr Siegel; but he is right in case of DSM3-type autism.
Nowadays people get upset if autism is called a disease, or a mental illness and even some researchers want to sugar-coat it and call it a condition as opposed to a disorder (Autistic Spectrum Condition).
Giving a nice name to something disabling does not make it go away. It just makes some people without that disability feel better.
Having mentioned Wakefield, I suppose we have to touch on vaccinations.
It would also be great if it was possible to be entirely honest about what we know about vaccines and autism. It is well established that mitochondrial disease can be triggered by vaccinations and it can manifest as regressive autism. This does not mean that all regressive autism is caused by vaccines. This does not mean that people should not be vaccinated; it just means that there is a small risk of something bad happening. Left unvaccinated there is a much larger risk of something else bad happening. Public health believes lay people are too dumb to understand this, I disagree; you just need to be 100% honest and explain it. It is fashionable to be selectively truthful, or let pass a little white lie. I think being 100% honest, brutally honest, is what is needed when dealing with such an important subject.
Details do Matter
Whether it is an unusual medical condition like autism, or any scientific investigation, all the details in their entirety are extremely important if you want any chance of solving the problem.
I just had a medical procedure to correct a problem that I first raised 40 years ago. I had an operation 40 years ago for a Meckel’s diverticulum, but it was the wrong operation and for the wrong diverticulum. Last week I had the right operation and, what could/should have been identified and treated in childhood, got treated decades later. When I read the summary of the completed treatment, it is a very well written concise explanation, with all the diagnostic inputs.
Now when I compare this to autism, which is far more complex, I can see mainstream medicine in not yet prepared to try and treat it.
Where do you go to get a precise summary of your child’s unique variant of autism / brain damage, all in 100 words? Perhaps this will also take another 40 years?
A first small step would be make sure what we do actually know about autism is more widely shared and that at least Autism organisations, with public funding, should be required to have a detailed understanding of what they are supposed to be advocating for. There are excellent organisations to represent other medical conditions, for example diabetes or even Rett syndrome, but not for autism.
Whilst waiting for my operation I had a visit from a curious Nephrologist who dropped by to take my photo (an ultrasound image) to show her friends. Being a liver specialist, she did naturally take a peek at that as well and asked if I knew I had some fat in my liver. Off she went, leaving me to figure out where this fat had come from.
I am pretty sure it comes from another misdiagnosis I had recently. I had a sudden reduction in hearing in one ear and not being able to resolve it myself, I went to an ear nose and throat clinic. The diagnosis was a simple case of wax in the ear. Unfortunately this was the wrong diagnosis; by the time I had returned from a trip abroad, quite some time had passed. The second doctor I consulted very quickly diagnosed an inner ear problem (Endolymphatic hydrops) that apparently is quite common but is often left untreated, leading to life-long problems. It leads to a degree of permanent hearing loss, tinnitus and potentially vertigo. A virus, infection or even a physical shock can cause a build-up in pressure in the fluid in the inner ear. If you begin treatment within a week, you have a good chance to avoid permanent hearing loss. My treatment started after almost one month, which was far too late, so I had ten days of injected steroids, starting at a very high dose.
I am pretty sure it comes from another misdiagnosis I had recently. I had a sudden reduction in hearing in one ear and not being able to resolve it myself, I went to an ear nose and throat clinic. The diagnosis was a simple case of wax in the ear. Unfortunately this was the wrong diagnosis; by the time I had returned from a trip abroad, quite some time had passed. The second doctor I consulted very quickly diagnosed an inner ear problem (Endolymphatic hydrops) that apparently is quite common but is often left untreated, leading to life-long problems. It leads to a degree of permanent hearing loss, tinnitus and potentially vertigo. A virus, infection or even a physical shock can cause a build-up in pressure in the fluid in the inner ear. If you begin treatment within a week, you have a good chance to avoid permanent hearing loss. My treatment started after almost one month, which was far too late, so I had ten days of injected steroids, starting at a very high dose.
High doses of steroids can have many side effects, one of which is causing fat to get deposited in your liver. It seems the fat spotted by the curious nephrologist should gradually disappear. I hope so.
Not wanting to be left deaf in one ear and noting the doctor did not seem entirely hopeful, I did quickly engage myself and read up on the science and the medicine. I regularly do this for my son, but did not think I really should have to do so for my own ear problem. Ménière's disease is an incurable condition, of unknown cause(s), that has major similarities to what was affecting me. I found a study, with supporting MRI images of the inner ear, showing that the amount of fluid in the ear can be reduced by taking the diuretic acetazolamide/Diamox, at least in some people. I did take note of a Cochrane review saying there is no evidence that diuretics have any benefit, but I did check the MRI images for myself. There is plenty in the blog about Diamox and autism. In Ménière's disease, Diamox responders lose the benefit when they stop taking the diuretic and this is reflected in their MRIs. Since my condition was hopefully not yet chronic, I thought the immune suppressing actions of the steroid were indeed the long term fix, but at this late stage only pretty immediate rather than gradual loss of inner ear fluid would avoid permanent hearing loss.
Since I have Diamox from a few years ago sitting at the back of my autism pill shelf at home, I decided to add that to my therapy for a few days. Diamox is cheap, except in the US, and is usually very well tolerated. As a bumetanide family we have a good supply of potassium supplements and bananas, so no chance of hypokalaemia.
My hearing returned and I have no related symptoms (tinnitus, vertigo etc). I have no idea if Diamox helped, but I am certainly glad I took it.
Another side effect of high dose steroid plus acetazolamide/Diamox was a change to my eyesight, both near and distant vision. Both drugs can affect your eyesight, but I think it was the steroid, since I took Diamox once to avoid altitude sickness with no side effects. The vision side effects gradually fade away when you stop taking the drug.
All this was a timely reminder that drugs and supplements can have unexpected effects and it is best not to get carried away with how many you give your child. I did recently take Monty, aged 15 with ASD, to see a paediatric cardiologist for a lengthy ultrasound investigation and ECG because, rather bizarrely, his autism drugs are mainly repurposed heart drugs. Where we live it is simple to arrange such a check-up and there is open access to lab tests. I am fully aware that in countries with universal healthcare trying to access anything unusual may not be possible, unless your GP “gatekeeper” is supportive. One French parent told me that his doctor would not prescribe bumetanide for his son, but was willing to authorize the blood tests to monitor potassium, if he acquired the bumetanide somewhere else.
Conclusion
In a recent comment our reader David from Spain, who is trying to get his child into the large Stage 3 trial for Bumetanide, informed us that the current prediction is 2023 for commercialization of this autism therapy. That would be 11 years after my son began to benefit. That is how long it takes to repurpose an existing drug.
This really makes me think that it is not just a case of autism needing personalized medicine, but rather parent-inspired personalized medicine. This is much easier if the parent is a doctor.
As I know to my own cost, medicine currently can struggle with even slightly unusual conditions, so we should not expect wonders from strangers, even when they finally do have approved drugs to prescribe.
The key will remain parent-inspired personalized medicine. When you do finally get 0.5mg of bumetanide twice a day as an approved autism therapy, it will be up to parents to realize that 1mg once a day or 2mg once a day might actually be much more beneficial.
If you ever have sudden hearing loss in one ear, go to your doctor straight away and have him/her specifically rule out an inner ear problem. If you live in the UK, hopefully you will not be made to wait 2 weeks to get an initial appointment with your GP. If you don’t live in a country with universal healthcare or don’t have insurance, I suppose some people just go deaf.
Dear Peter, I could go on and on about what I think on this subject - and thank you for recommendint a book that deals with this, I will read it if I ever decide that I can cope with this subject which I mostly try not to think of (the politics, not the autism itself). But can you perhaps share a more personal info: What do you think are the reasons for autism having such a, historically, unique treatment? I am especially interested in why the numbers (which are official however people may regard them) are not raising more resources and interest and general...happening.
ReplyDeleteTatjana, by broadening the definition of autism, the word no longer really has much meaning. Dr Siegel even raises the question "what isn't autism?".
DeleteIt used to mean something pretty terrible, now it just means "a bit odd". Odd is not so bad and many people with this type of autism are happy the way they are. So no real need for extra resources.
If severe autism (AKA DSM3 autism) was exploding in prevalence, society would have a big problem and I would hope extra resources would be found.
The same is true with ADHD; diagnosis has exploded to 7-11% of all kids. But only a small number have really big problems, most do not; yet in the US they drug all 11%. The result of over diagnosis is many people think all ADHD is just caused by kids being badly brought up and is not a serious issue. The fact that ADHD is rarer in France and drug treatment is <1% does support this idea. I can tell you that in France parents are much stricter than in Anglo-saxon countries, though still very loving. It is tough love.
There is a well known book on ADHD over-diagnosis.
A Disease Called Childhood: Why ADHD Became an American Epidemic
I can see in my own elder son, if he is left to play on his smartphone, video games, PC etc, his personality/behavior changes and not in a good way.
Just as you can acquire autism in extreme cases (see the Bucharest Early Intervention Project), you most definitely can acquire mild ADHD, very easily.
This comment has been removed by the author.
ReplyDeleteThis comment has been removed by the author.
ReplyDeleteI can agree about ADHD, but hardly about autism...if children aged 3 have fine motor skills issues, barely speak, have bad eye contact, OCD tendencies and sensory problems, I think we can safely say that they have autism. The fact is that beyond this point I just sort od described, we can have a child who can’t cope with life at all, or one who is not so noticeably bad but in the end still isnt near normally developing. In your sons development, there was probably a time when you were thinking ‘Will my child ever be able to live on his own?’ and perhaps, I think so at least, a time when you stopped wondering about that and realized that he probably will. I think all parents who have that question in their heads can safely assume that their kid has autism and is not ‘misdiagnosed’. Also, having this thought means that the problem is a horrible one, a life changing one. Human society usually does give more attention to problems of this magnitude, and I do not know how to fully explain the current low level of attention. I know that is is a diagnosis that covers a lot - but so is diabetes. A diabetic can, as the result of his illness, have too much weight, not enough weight, too much or too little appetite, they can really like sweets or really not like them, be sporty or a couch potato, but since we know what diabetes IS, we feel comfortable calling the mildest and most severe cases the same, because they have the same organic cause. Why should all people have to suffer the same severity in order for something to be the same disease? if two women have breast cancer and one is healed quite swiftly with little therapy while the other one goes through several rounds of chemo, radiation and surgeries and still dies, did they have different diseases or different bodies?
ReplyDeleteTatjana, autism parents clearly do spend time thinking about what will be and what might have been. This is natural, but exaggerated because many feel powerless.
DeleteI am not a typical parent, I do not worry about how independent Monty will become, or what his future holds. I have done my homework and I know what the problems will be and what the reality is. My focus has always been to do something about it. I can then know that whatever the results will be, they are much better than would otherwise have been. That is much better than worrying, or complaining about what the State gives you, how long you wait for diagnosis, what the local school offers you etc. I do not expect anything from the State.
Having covered behavioural intervention, education and medicine my next project will be preparing him for some kind of job.
Oh Peter, we are of the same kind. i even got kicked out of a parent group on FB while I was pregnant because on a post about how people don’t stand up for pregnant women in public transport etc I wrote that they know the society they live in and its irresponsible of them to have a child if they don’t understand that they will not get any help from anyone. but they did not kick me out before telling me in many insulting ways that i would be the worst parent ever. They had no logical explanation for that nonsensical stance, and I was very amused. Just recently when once again faced, through the news, with the fact that society cares 0 for kids, be they sick or healthy, I thought back on them and wondered how they cope with the shock of reality. You know my country, and you know that the state health system is seductively free. We insured her privately the first week of her life and we have since not once used anything free the state has to offer - even when we had to visit a state hospital, we would pay. The reason being that I do not want the state to even know about my child, or to be interested in it. I just wanted to say that if people have reason to be worried or perhaps a better term for you is to be unsure whether their child will live independently, the autism is not misdiagnosed.
DeleteHi Peter,
ReplyDeleteHope all is well.
Peter, I wanted to reach out to you directly on something, and was wondering if I could do so at the same e-mail address we had connected on in April?
Thanks in advance!
AJ
AJ, sure you can
DeleteThanks Peter! I will send you a message later today.
DeleteHave a wonderful day Peter!
AJ
SpectrumNews has an interesting article discussing a new finding that may be relevant to diuretics and some other blood pressure drugs helping with autism symptoms:
ReplyDeleteArticle:
https://www.spectrumnews.org/news/young-children-autism-may-show-brain-fluid-buildup/
My son has a larger than average head but went to the emergency room recently for a false alarm that could of been easily addressed had he been verbal like 99% of the rest of the world. During the fun and expensive trip they took his blood pressure and it was completely normal (in the 120/80 range), but I sometimes wonder that at night some autistic kids such as my son will collect too many fluids from excess vasopressin or else vasopressin receptor supersensitivity and this causes many of them (such as my son) to wet the bed unless they are forced to go to the bathroom before bedtime.
It would be interesting if a simple study on those with autism would take different blood pressure readings throughout the day and compare them to the general population to see if there might be some sort of circadian disruption going on that may contribute to excess fluid buildup and cranial pressure at night time in particular. If so, perhaps a mild diuretic 3-4 hours before bedtime might be helpful, even though naturally the superchiasmatic nucleus releases vasopressin shortly before bedtime to stimulate thirst since dehydration is not good for the brain while sleeping, so you obviously would not want the diuretic to be too strong for this very reason.
Tyler, it would be interesting to know which diuretic affects which fluid. You have fluid in your eyes, fluid in your ears, spinal fluid and of course blood.
DeleteDoes taking bumetanide affect the volume of cerebrospinal fluid, which the studies show is elevated in autism?
I don't know the answer to that question though it is interesting that mean arterial pressure is related to cerebral perfusion pressure in that cerebral perfusion pressure decreases from a rise in intracranial pressure which prompts a response by the body to increase mean arterial pressure. This might be one an explanation for hypertension in autism, in addition to a hyperactive HPA Axis, and perhaps genetic factors inherited from the mother as hypertension in the mother during pregnancy is one of the leading environmental risk factors for autism.
DeleteLoop diuretics, including bumetanide, are the first line of defense for pharmacologically lowering persistently raised intracranial pressure:
https://www.ncbi.nlm.nih.gov/pubmed/2242656
Tyler, where did you find that vasopressin is highest before bedtime? Also vasopressin actually supresses thirst and holds water.
DeleteThis paper looked interesting since it mentions the vestibular system, PKA, bumetanide and glucocorticoids in the same text. It was however a bit too technical for me. It looks like bumetanide perhaps is working in the opposite direction from PDE inhibitors in this part of the body(??)
Deletehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622586/
/Ling
Aspie, I read a lot of neuroscience for a project I have been working on for about half a decade or more now and as part of that project I have to know as much as I can about every part of the brain in the broadest sense (there are over 2 million neuroscience papers in existence now so knowing everything in depth is impossible nor desirable for my purposes).
DeleteAnyways, one part of the brain is the superchiasmatic nucleus which regulates circadian rhythms and besides providing inhibition on a circuit in another part of the hypothalamus which if not inhibited will stimulate a convoluted pathway down to the spinal cord and back up to the pineal gland to produce melatonin. Another function of the superchiasmatic nucleus is to release vasopressin in the early evening hours to encourage the animal (such as a human) to drink more fluids so that at nighttime the brain does not become dehydrated. Access to water in the middle of the night is not always possible out in the wild, so being thirsty in the early evening is important so that the animal will not need water in the middle of the night (or in the case of nocturnal creatures in the middle of the day).
Also, vasopressin does not suppress thirst, rather it is known in the periphery as ADH or anti-diuretic hormone. ADH encourages the body to hold onto its water stores and also encourages the basal blood presure level to raise by stimulating thirst in the animal (more fluids equals higher blood pressure). So, if you get a sudden burst of vasopressin in the periphery, your brain will be telling you that you need more water, i.e. that you are thirsty and if water is available you will drink more water.
If vasopressin levels decrease too fast or at the wrong time (like before waking in the morning) and you are sleeping and don't wake up from the urge to urinate, well then nocturnal enuresis will be the result.
So many contradictionairy reports... studies... responses from people. Regarding the 2million papers, thats exactly the problem its time to tie the knots, rather than scientist having their mini-ego boosted by look I have done this paper blablabla. The amounts of data available is staggering, now if only.... just only.... different branched learned to communicate better to work towards solutions.
DeleteAlso this literally taken from the vasopressin wikipedia page:
"There may be a connection between arginine vasopressin and autism.[35]
Deficiency:
Decreased AVP release (neurogenic — i.e. due to alcohol intoxication or tumour) or decreased renal sensitivity to AVP (nephrogenic, i.e. by mutation of V2 receptor or AQP) leads to diabetes insipidus, a condition featuring hypernatremia (increased blood sodium concentration), polyuria (excess urine production), and --->> polydipsia (thirst)." <<---
One thing that dehydration/long term thirst does do is upregulate OXTR mRNA and AVP mRNA, through a histaminergic H1 mechanism.
Vasopressin is not the only peptide/hormone governing the thirst response. If the brain senses water levels are low for any reason, it will stimulate thirst whether that be because the water levels go below the floor level due to diabetes insipidus making the body unable to raise its basal water level via vasopressin signaling or else because the basal level of water in the body increases due to increased vasopressin receptor signaling in the kidneys.
DeleteTyler, can I ask you what dose of Niagen you use(d) for your son (mg/kg)?
ReplyDelete/Ling
The recommended adult dose which is 250mg per day (each capsule is 125mg). How much is an optimum dose is an open question with regards to addressing autism comorbities relating to mitochondrial issues and oxidative stress, especially since the human research done on NR is geared towards adults with pathological conditions that are more easily measurable (aging, diabetes, etc.). In normal people, NAD+ does not start going down until a person's mid 20's so supplementing NAD+ in the form of NR before then is likely not going to do much (this has not been proven though). However, in children or young adults with mitochondrial issues boosting NAD+ can be theoretically beneficial.
DeleteIn one trial of NR for obesity, they gave doses as high as 2000mg a day. There is also animal research showing boosting NAD+ in girls who inherit obesity from their mother can prevent adult-onset obesity with the idea being here that sluggish mitochondria are the culprit.
I expect NR to eventually be a lot cheaper once some of the patents involving its production run out, and there is an open question right now if supplemental Nicotanimide Mononucleotide (NMN) is a better way to raise NAD+ levels in the body.
Also, just to reiterate the original reason for supplementing NAD+ was to address any potential brain pellagra issues from BCAA therapy restricting kynurenine levels in the brain as L-Kynurenine is needed to produce quinolinic acid which is then combined with Vitamin B6 and other enzyme I can't remember to yield NAD+.
I found this recommendation on dosages of niacin for children:
DeleteThe Food and Nutrition Board established a tolerable upper intake level (UL) for niacin of 10 mg for ages 1-3 years, 15 mg for ages 4–8 years, 20 mg for ages 9–13 years, 30 mg for ages 14–18 years, and 35 mg for ages 19 years and up [97]. These levels, however, apply to the general population and do not apply to individuals receiving niacin under medical supervision.
https://ods.od.nih.gov/factsheets/PrimaryMitochondrialDisorders-HealthProfessional/
Not sure how to convert niacin dose to niagen dose though.
/Ling
Ling, my son takes 500mg of niacin sometimes 2 per day. Only high doses are therapeutic. If you take it with a good multivitamin no side effects up to 2 g.
DeleteValentina
Niacin is not the same thing as NR, as niacin will not increase the NAD+/NADH ratio as niacin ends up initially as plain NADH. There is an enzyme that recycles NADH to NAD+ which is what happens with niacin up to a certain amount, but that enzyme has a limit. Beyond that the body naturally produces NAD+ through the kynurenine pathway which has many steps which again are rate limited by other enzymes.
DeleteIf you want to raise NAD+ levels artificially, the best way I know of to do it in humans is NR supplementation. Maybe in the future gene therapy to boost the salvage pathway in older people might be a thing, but NR right now is your best option.
Also, as best I know you can't really poison yourself from too much NR. You can however go broke if you are not rich because 250mg at the moment is a little under a dollar a day. You can get a three month supply for around 100 dollars.
To be honest, I don't know what I want right now.
DeleteMy efforts this fall have been to raise ERK1/2 activation through as many pathways as possible:
-cAMP/PKA (using PDE4i, cinnamon)
-PKC (using buttermilk powder)
-5HT2a [via PKC pathway?] (using Fisetin, Bacopa)
-BDNF (using VegEPA, Fisetin and many of the above)
The missing parts here would be:
-ATP
-And/or more CamK via VGCCs.
I have definitely had my thoughts on interventions like Clemastine (on P2RX7 that sensitizes ATP response), ERbeta agonists (acting on CXCL1->P2RX7), a mitococtail (?), synergies of PDE3+PDE4 inhibition (Ibudilast) and, ahem, maybe Angiotensin II.
As anyone can guess, my head has been ripe to explode for a while.
And, then I fell into this "unfolded protein response" that I've never heard of before this week.
My daughters dysfunctional gene is, at least in roundworms, responsible of creating the proteins that work to remove unfolded proteins in the mitochondria. It's kinda downstreams of the whole electron transport chain, which I know is important in regressive autism. But I don't know if it would help with more ATP or even more NAD+.
I am currently looking at this picture, with the green DVE-1 gene at the bottom left partly missing, and obviously NAD+ has an arrow pointing close to it:
https://ars.els-cdn.com/content/image/1-s2.0-S2213231714000883-gr2.jpg
Anyone who made it this far in my overly long comment - What do you think? I do have two bottles of Niagen on the shelf.
/Ling
Ling you can try methylene blue if you cave not already looked into it. Methylene blue serves as an alternative electron transport acceptor for complex I, and then an electron donator for complex IV if my memory serves correctly. It is also thought to function as a mitochondrial antioxidant at lower doses while very large doses are thought to be pro-oxidant.
DeleteTyler, thank you so much for answering a question that I am not really able to define myself. I have not looked into methylene blue before, only read the name somewhere once or twice before. I'll look it up!
DeleteMy Satb2 journey, which more looks like a roundtrip in autism land, was not supposed to suddenly bring me to mitochondrial territory too. I'm still very new to the subject, but I wonder if there are ways to minimize mitochondrial stress, to make the load on the UPR system less heavy. Maybe the answer is just an improved ETC?
Anyway, thanks again Tyler and just let me know if there is any way I can help you with your kids or your project. :) I'm not as knowledgeable as you, but I am good at spotting things, and I read a lot.
/Ling
Tyler,
DeleteAs you might know Ive used niagen a fair bit in the past. Let me tell you first from my own experience that it literally feels like mental and physical recovery in a pill. Lets say if I did very strenous exercise in the evening and I would be extremely sore the next morning, if I took 500mg niagen within 30minutes it feels as if you are completely recovered. As you might know Ive used like literally 70-100 different supplements and medicines and nothing besides niagen has ever done this for me. I still find it hard to get a grip how powerfull it actually is at that, all that being said Ive been following the longecity threads on niagen for years and there are some concerns that giving exogenous NAD+ (which niagen basically is) might be like throwing fuel on the fire for cancer cells aswell. Now they all agreed on the fact that this obviously would not affect everyone, however increasing NAD+ system wide, the body will find a way to get rid of the excess NAD+ (and I dont mean in a good way).
Some benefits Ive noticed on niagen:
* ENERGY (very pronounced, not a jittery stim like feeling, but just a never ending supply of natural energy)
* my skin seemed to look better and smoother on it (it was way more pronounced than supplements such as ginkgo and ginseng haev done for me or amino acids)
* mood stabilizing (a bit too much however, it totally annihilates stress for me but it also throws my libido down the drain)
* anti-anxiety (see mood stabilizing)
* somewhat altered perception, hard to describe, but I definetely felt as if my view on daily life was somewhat different (nothing close to my psilocybin trial though).
* more positive attitude towards life and less negative (this one I liked the most)
the bad:
* hypothesized to possibly be bad for those with autism/asd considering we allready have mtDNA problems and theres a chance that niagen could aggrevate this
* possibly throwing fuel on the fire for cancer cells (in other words, what is just enough NAD+ for neuroprotection/healing stress without overdoing it)
Well a lot of the Niagen stuff on longevity involves people opining about risks without reading the actual studies in animals and now humans. As per cancer specifically, poor mitochondrial health will effect autophagy as well as the reliability of the immune system, both of which are critical to preventing cancer as I am sure you well know. I have no idea about the autism claim, so perhaps you could dig up the thread about it (not debating you on this just personally curious).
DeleteAlso, I take Niagen as well after testing it out to see if I had any adverse reactions before giving it to my son. After doing so, I continue to do so due to the scientific research backing it now regarding aging, as well as all the anecdotal reasons you listed above. It is really nice having muscle recovery times double or more faster than in my 20's or.even high school after a game of soccer, especially as I get older.
Tyler, niagen is incredibly new, therefor speculating that it is/might be save is based upon wishfull thinking.
DeleteFact is nobody knows, neither you nor me. Also the fact that it enhances recovery (something which I also noticed very drastically) does not equal that it will be save.
It 'feels healthy', but if its actually going to be save in the long run nobody really knows, animal studies look somewhat promising, but the whole mtDNA autism and niagen makes me skeptical.
Dear Peter and all,
ReplyDeleteI wish to know your opinions on this article:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106692
Thank you,
Luis
I can't explain the results of that study, but I don't find them very surprising either. As I've read numerous articles on long term memory and the excitatory part of "I/E balance" by now, it is striking how hard it seems to raise BOTH excitatory AND inhibitory mechanisms with a single intervention.
DeleteI think I saw a study on the MIA autism model where Bumetanide decreased (in this case normalized) NMDAr subunits NR2A and NR2B. This could definitely affect memory negatively (but other things positively).
What I find interesting is that there doesn't seem to be many negative reports on cognition after Bumetanide use. There were two persons here who said something about language regression for a while. Of course, small changes in memory might be hard to spot especially if cognition goes up.
Add to that, that in some autisms it seems as if GABA works in reverse, which most studies don't take account for. And then we have all the stuff with sustained vs transient stimulation that can have opposite effects.
I hope you get a better answer than mine.
/Ling
Ling, this is why I have been looking into sigma receptors, they seem to potentiate nmda signalling and at the same time prevent toxicity.
DeleteI'll give the donepezil that I have laying here in house a go most likely early on in the new year, but Im somewhat scared of cholinergics now tbh. Especially since they seem to aggrevate my gut problems and that I have find out that I have a washlist full of genes that pre-dispose me to crohns, colorectcal cancer and such.
Luis, I have wondered by some bumetanide responders seem to have a very different benefit to that experienced by my son. In my son the big effect is cognitive enhancement.
DeleteMy assumption is that the benefit my son experiences is due to lowering chloride rather than the effect of blocking NKCC1. In your paper bother furosemide and bumetanide had the same effect. They do both block NKCC1 but they do not both reduce chloride levels, because as I mentioned last time, furosemide also blocks chloride leaving neurons via KCC2.
Here is some new neuroscience research on mitochondria that is specific to neurons that I hope some autism researcher looks into as well:
ReplyDeletePress Release:
https://www.sciencedaily.com/releases/2018/11/181127110959.htm
Paper:
https://www.nature.com/articles/s41467-018-07416-2
The main takeaway from the paper was that the research team found that mitochondria localized to dendrites and axons are smaller and differently shaped under normal circumstances than other mitochondria in the neuron as well as every other cell in the body (presumably). Instead of simply providing energy to the cell, the smaller mitochondria also have a functional role in the uptake of calcium, in that when the researchers deleted a gene which regulates the size of mitochondria, the now larger mitochondria took in more calcium. This can be a problem as the more calcium the large mitochondria accepted, the less calcium that was available presynaptically at the synapse. Not enough presynaptic calcium being released at the synapse will have deleterious learning effects as long-term potentiation and long-term depression are both calcium dependent.
This begs the question as to another possibility (among many) of how calcium channel blockers like Verapamil could potentially help some types of autism where hypothetically you have a problem with larger than should be mitochondria localizing at the synapses taking in too much calcium, thereby depriving calcium stores for presynaptic release by the neuron.