tag:blogger.com,1999:blog-655962722302095847.post2900450672354674374..comments2024-03-27T20:20:54.505+01:00Comments on Epiphany: Mitochondrial Disease and AutsimPeter Lloyd-Thomashttp://www.blogger.com/profile/10173383229834614994noreply@blogger.comBlogger26125tag:blogger.com,1999:blog-655962722302095847.post-87309258213294559622023-04-25T19:44:44.675+02:002023-04-25T19:44:44.675+02:00You read my thoughts! I was planning to contact Ja...You read my thoughts! I was planning to contact Jacky Harris or Peter Barker at KK just before I finally got an appointment with children's mitochondrial diseases department at Necker a couple of days ago. I will certainly write to Dr. Naviaux- just was not sure he was seeing the cases outside of his research work.<br /><br />Also, I think, autism doctors can certainly help. As you mentioned in your book- most of the ASD patients have one or the other form of MD. My child was on comprehensive ASD protocol for the past two years- and it seems to work. It is just ASD doctors are shooting extremely wide, while with a specific MD the target should be narrowed down to get the best results. <br /><br />Warmly,<br />MarinaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-11209836083008247052023-04-25T10:44:24.153+02:002023-04-25T10:44:24.153+02:00COXPD-35 (combined oxidative phosphorylation defic...COXPD-35 (combined oxidative phosphorylation deficiency 35) is extremely rare) and I do not think autism doctors are likely to be able to help. There are some researchers who have published case studies, they would be the best people to contact and ask about therapies.<br /><br />Even though you are not in the US, you could try and contact whoever is now in charge of mitochondrial medicine at Johns Hopkins / Kennedy Krieger. They might be interested in such a rare condition.<br /><br />Also, Dr Robert Naviaux, best known for Suramin, is actually specialized in mitochondrial medicine. He does answer emails. He is at:<br /><br />https://profiles.ucsd.edu/robert.naviaux<br /><br />If you write to him, ask specifically about COXPD-35. I expect he gets hundreds of emails about autism. <br /><br />Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-14583173439391807342023-04-25T08:53:57.693+02:002023-04-25T08:53:57.693+02:00Hello Peter, here I am again!
I have just receive...Hello Peter, here I am again! <br />I have just received the Mitoswab results. Immediately dove into literature, but still struggle to connect the dots. My son's RC-I and RC-II are in the normal range (a bit towards the lower end), RC-IV is slightly lower (44% of the normal mean value), RC II+III is low (9% of the mean), and Citrate Synthase is very high. <br /><br />Citrate Synthase (CS) reflects the mitochondrial density in skeletal muscle. My son, 3,5 y.o., has low muscle ton, always had. He always struggled with the weight gain and muscle growth, despite a healthy meditarranean diet, proper resting time and supplementing with amino acids. I learned that CS activity can be increased by endurance training or high-intensity interval training, which should further indicate a high performance and maximal oxygen uptake, right? But why CS is so high in my LO, who struggles with energy production, easily fatigues/gets tired quickly? <br /><br />Earlier I wrote a post in your blog regarding our WES finding revealing a genetic mutation linked to COXPD-35, where mitochondria energy production is disrupted. This diagnosis is not yet confirmed, and I am trying to work on this ''puzzle'' while we are waiting for the consultation at Necker this summer. <br /><br />I am not sure if I am hooking on the right things- COXPD-35 and very high CS activity. But these parameters make some kind of sense to me, considering the major concerns (i.e., struggle with weight gain, struggle with muscle growth, speach delay, difficulties in communication etc.) While I share your phylosophy on ''Fear of doing a therapy vs regret of not doing the therapy'', my personal fear has always been future comorbidities. I bumped on this little article (https://www.proteinatlas.org/news/2016-09-23/citrate-synthase-and-mitochondrial-disease) <br />which mentions that the CS cycle is a key in tumor genesis as cancer cells require excess energy to maintain their rapid reproduction. Now I am asking myself a question: where do all amino acids and b-vitamins go in my chid's body? Why don't I see its supposedly anabolic effect on his muscles and increased energy level? Am I paranoic :)?<br /><br />Maybe some parents here had a similar experience? Do elevated NSE and S-100 have something to do with this (high CS activity), besides indicating a neuroinflamation? Would you remove/reduce/increase amino acids (Creatine, Arginine, A-L-Carnitine, Taurine)? I would greatly appreciate your insights. <br /><br />P.S. We are going to have an autism summit this week in Abu-Dhabi. I went through the list of speakers and many of them I've met and talked to in person, including the renowned international speakers. They all sound very knowledgeable presenting their slides, but, unfortunately, not very helpful when working on a real case, like my child. Two years later, days in Pubmed, dozens of tests- and I still find it challenging to navigate through the diagnostic on my own. Thank you for what you do, Peter!<br /><br />Marina<br /><br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-63115210129709213192023-03-05T16:44:19.823+01:002023-03-05T16:44:19.823+01:00Marina, you will struggle to find a clinician will...Marina, you will struggle to find a clinician willing to try personalized medicine in a 3 year old. But the earlier the intervention is started the great the potential benefit.<br /><br />Good luck.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-34868684590389075242023-03-05T10:20:40.528+01:002023-03-05T10:20:40.528+01:00Peter, I have recently contacted a researcher, who...Peter, I have recently contacted a researcher, who used to be an expert in mitochondrial diseases. He was kind enough to go through the report and refer us to his ex-student, now a professor at big hospital in France. Hopefully, he will be able to help us. <br /><br />I am with you on ''supplements will lack potency to have much effect''. However, it is, probably, what kept my child floating. With Fra and COXPD35 you may expect to see someone in really bad cognitive shape. While I have a background allowing me to manipulate the supplements, it is not enough for experimenting on a 3 year old with the pharmaceuticals without an expert beside me.<br /><br /><br />Ling, yes- according to the wes report and further re-analysis, our findings are directly related to COXPD35 and it IS pathogenic mutation. While the researcher I mentioned earlier immediately refered us to the department of paediatric mithochondrial diseases, we were not aware of the possibility of genetic issues with our child. We performed wes almost two years ago and discussed the results with two (local) geneticists who did not express any concerns. Interestingly, despite the clinical information (i.e., global developmental delay, ataxia, abnormal muscle tone etc.), the lab itself classified the mutation as ''pathogenic'' and ''nonsense'' at the same time. I cannot explain this until I see an expert working at larger facility in more (healthcare-wise) advanced country. <br /><br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-14958508733965294032023-03-04T22:20:46.026+01:002023-03-04T22:20:46.026+01:00Marina, there are no approved drugs to effectively...Marina, there are no approved drugs to effectively treat mitochondrial disease. The various mito cocktails are trying to avoid further deterioration. You really want better.<br /><br />Pioglitazone is not a pediatric drug, nonetheless it has been trialed in young children at what I would consider high doses of 30mg and 60mg. Those trials were not related to PGC1alpha. Take a look at the published trials. I would have thought 15mg would be a more conservative dose, <br /><br />You could contact one of the clinicians who ran the autism trial.<br /><br />I think activating PGC1alpha would need to be a long term therapy.<br /><br />It always seemed to me to be a logical trial to make for someone with mitochondrial disease. I think supplements will lack potency to have much effect<br /><br />Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-56276422737890628272023-03-04T22:11:56.023+01:002023-03-04T22:11:56.023+01:00Marina, a "nonsense" genetic mutation do...Marina, a "nonsense" genetic mutation doesn't mean it has no clinical meaning, it means your child most likely have only 50% of the corresponding protein produced. If the protein is very important this will cause pathology.<br />If the mutation on the other hand is considered "benign" it means it has been found in healthy individuals and doesn't cause disease.<br />There's also the alternative that the mutation is a "VUS" = variant of unknown significance. This means it is not known yet if it causes disease or not.<br />If you have the genetic report you will find some of these words on it.<br /><br />/LingAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-26855670512082828242023-03-04T19:21:12.405+01:002023-03-04T19:21:12.405+01:00Hi Peter,
We were actually suggested against the k...Hi Peter,<br />We were actually suggested against the keto diet (by the same neurologist). In addition, my little one has FRa- so no dairy. I also wonder if increased meat consumption plus Carnitine we are heavily supplementing with would not promote atherosclerosis in the future ( https://doi.org/10.3389/fcvm.2021.723886)- more tests to rule TMAO out (?) From Genova's Organic Acids test I can see a malabsorbtion of fats, probably indicating a fatty acids oxidation disorder (?) <br />So, quite a few questions to figure out before shifting my little one to a keto diet. <br /><br />I will have to look at Energy Needs, which has been already suggetsted. It is just most of its ingredients my child is already supplementing with. However, I am interested in Taurine (may help with fatty acids absobtion) and Arginine, which helps to improve energy storage in brain and CNS- both are in Energy Needs. If I understand it correctly, Arginine also activates PGC1a, as well as resveratrol and bezafibrate? I feel somewhat confident with trying Arginine and Resveratrol with a toddler, but not sure about pharmaceuticals. What would be the dosage for pioglitazone? Can it be taken together with our polypill? Is it usually taken as a course (what would be the duration?) or on a long-term?<br /><br />Thank you for your insights!<br />MarinaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-3865314613090285652023-03-04T13:13:30.454+01:002023-03-04T13:13:30.454+01:00Marina, you might as well try the OTC mitococktail...Marina, you might as well try the OTC mitococktail that is prescribed by the autism doctors. There is Spectrum Needs or you can use Dr Kelley therapy.<br /><br />If you like dietary therapy, you can try and shift towards ketogenic. The OXPHOS process is different to when glucose acts as the fuel input. As a result people with a deficiency in one of the enzyme complexes may benefit from ketone as the fuel input. <br /><br />To make more mitochondria you can activate PGC1alpha with the T2 diabetes drug pioglitazone.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-12807269519820059072023-03-04T11:02:09.628+01:002023-03-04T11:02:09.628+01:00Hi Peter, thank you for your response. Yes, all th...Hi Peter, thank you for your response. Yes, all the signs of COXPD, except seizures. I'm not sure about microcephaly- the child is rather slim, the head is not large, but we have a steady growth chart (Head Circ has always been in the 25 percentile). Regarding the physician you mentioned earlier- we saw him. The physical exam did not go beyond reflexes and a stethoscop, considering the efforts we made to make the consult happen- I expected more. Furthermore, the genetic findings were not addressed at all. We were asked to do a mitoswab, but I wonder how it could help us. I have the feeling that often physicians keep loading you with the new tests when they have nothing else to tell you or do not understand what's going on with the patient. In our case, besides genetic pahology, there are also high levels of NSE and S100, which were also disregarded.<br /><br />The list of tests for COXPD35 is long and, to be honest, I do not understand the purpose of all of them. The problem is, and you are right in this- we could keep doing the tests, which for me is like shooting in the dark. But without an experienced geneticist and, more importantly, neurocounceling (with a personalized intervention)- the tests findings are not going to improve the outcomes of my child. In the region we are now- it is tragic. ''Not too bad'', ''Come back in 1 year'', ''The genetic findings are nonsense in your case'', ''Most probably, he will be functional, let's see''- we have seen dozens of those neurologists, geneticists, physicians etc. So, now I am trying to reach out the big hospitals abroad. Also, I have the feeling that these ''touring'' physicians which you can see at every ''Autism'' conference are not the answer and, often, a waste of time and money. They build their ''boxes'' of intervention based on their previous practices and will not step out for every single child, but rather will try to fit him into this ''box''- which may not fit at all this particular child. <br /><br />Yes, I looked at the research in OXPHOS. There was an interesting paper back in 2009 (doi: 10.1016/j.bbadis.2008.10.015) and I'm trying to connect to someone in Necker. <br /><br />Marina<br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-73131187108002404852023-03-03T19:15:52.270+01:002023-03-03T19:15:52.270+01:00Some mutations in your gene TRIT1 will lead to com...Some mutations in your gene TRIT1 will lead to combined oxidative phosphorylation deficiency 35 (COXPD35), characterized by global developmental delay with intellectual disability, microcephaly, and early-onset myoclonic and other types of seizures. Affected individuals have variable deficiencies of mitochondrial respiratory enzyme complexes resulting from a defect in mitochondrial metabolism.<br /><br />The first thing is whether your child has a small head and other features of COXPD35?<br /><br />There are numerous possible tests for COXPD35 listed, just click on the link below.<br /><br />https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=54802[geneid]<br /><br />What you want is a practical clinician rather than a list of tests. <br /><br />If you are in the US you could contact Dr Frye <br /><br />https://www.autismprecisioncare.com/mitochondrial<br /><br />He has a long waiting list.<br /><br />You could also contact researchers/clinicians who have published papers on this subject.<br /><br />One way is to use Google Scholar and see who is writing about this subject.<br /><br />https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Combined+oxidative+phosphorylation+deficiency+35&btnG=Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-16269507599733556682023-03-02T18:15:52.328+01:002023-03-02T18:15:52.328+01:00Hello Peter,
This is an old post, but I have a few...Hello Peter,<br />This is an old post, but I have a few questions. Could you please help me figuring them out? <br />Does it make sense to do Mitoswab after completing WES? Doesn't WES look at the same ECT (I-IV)? Furthermore, if WES already presents a genetic finding of a TRIT1 gene mutation clearly correlated with OXPHOS deficiency 35, would Mitoswab be of any help? Maybe more broad test like WGS+MULTIOMICS (e.g. from Centogene) could be more informative? I'm not sure what to do with our OXPHOS deficiency-related gene; our physicians, geneticist and multiple neurologists certainly do not know what to do with this mutation and prefer to call it a "nonsense", even though it DOES make sense in terms of the clinical presentation of my child. <br />Thank you in advance for your insights! <br />Madina Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-69052294731217821722018-11-13T20:42:34.323+01:002018-11-13T20:42:34.323+01:00Peter I would like to know your view on the follow...Peter I would like to know your view on the following as a I got a 'weird hypothesis' on 2 things:<br /><br />1st - hand flapping/self stimming:<br />I believe this is mitochondria related and the self stimming they do is probably ppar alpha/pgc1a related, self stimming could be a subconsious mechanism to upregulate/activate these mechanisms. FYI I also had hand rubbing when exited at young age, also I always walked without socks on at home and also would have periods where I would put my socks on to heat my feet, then 20-30secs later Id take them off again, then 20-30 sec later on again.<br />Now Ive talked before about TRPC/TRPV/TRPM channels, TRPM8 activation for example (the 'menthol receptor') which is activated during cold exposure, upregulates BAT (brown adipose tissue) at the cost of WAT (white adipose tissue) and increases PPAR-alpha/PGC1a transscription thereby increasing mitochondrial efficiency.<br /><br />2nd - poor smearing:<br />I believe this is the body subconsiously trying to maintain microbial homeostasis, the reason for this 'subconscious/compulsive' behavior is imo either:<br />a. to ward of competing strains that the body could possibly be exposed to by for example skin contact (yes certain strains also live on the skin hence why obsessive showering is actually bad for skin health).<br />b. re-inforcing the strains that are currently present in the child (basically the kid doesnt want to lose the strains through defecation, thereby is trying to re-introduce them by smearing).<br />c. animals such as dogs often also roll in the poop outdoors, it clearly has functions.<br />d. microbiome depletion in animal models (ocd cleaning anyone? fear of bacteria anyone) was shown to increase the response to cocaine (their 'high' was better = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067576/)<br />And for those who are wondering I also had this myself (when I was on SSRI's as a kid, I cant remember which SSRI made me do it though its been so long ago).Aspie1983https://www.blogger.com/profile/14186355234793738967noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-69719516018122653092017-06-28T03:35:04.897+02:002017-06-28T03:35:04.897+02:00The discussion of EMF/EMR and electrosmog needs to...The discussion of EMF/EMR and electrosmog needs to be addressed globally. The die off of species is happening. Eukaryotic organisms are at risk of a decrease in cellular functioning and part of our being is dying on many levels if we do not clean up this technology at all levels and at all sites. The likelihood that the damage was happening and occurring all along throughout development is huge and spans many disease pathways, many metabolic, mitochondrial, functional biological pathways. <br /><br />https://www.youtube.com/watch?v=M7mtQFijZpgAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-75938745642941095102017-02-24T13:12:02.011+01:002017-02-24T13:12:02.011+01:00Tyler, there is a disease called "Neurodegene...Tyler, there is a disease called "Neurodegeneration with brain iron accumulation".<br /><br />https://en.wikipedia.org/wiki/Neurodegeneration_with_brain_iron_accumulation<br /><br /><br />Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features<br />https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078858/<br /><br />The studies in autism looked at the level of ferritin and iron in the blood. As is often the case, this tells you little about levels in the brain.<br /><br />We need reliable and accurate methods to measure numerous risk factors inside the brain. Using samples from brain banks may often not give genuine results, although in the case of iron concentration it should do. Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-74492709079778515172017-02-24T12:55:43.303+01:002017-02-24T12:55:43.303+01:00Tyler, Rosiglitazone/Pioglitazone are interesting ...Tyler, Rosiglitazone/Pioglitazone are interesting and there are trials in autism. They have come up a few times on this blog, but not in connection with Wnt.<br /><br />https://epiphanyasd.blogspot.com/search/label/rosiglitazonePeter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-29630011730606434482017-02-24T10:15:32.764+01:002017-02-24T10:15:32.764+01:00I just came across a new method of inhibiting Wnt5...I just came across a new method of inhibiting Wnt5A signaling in a paper on a melanoma treatment, a topic you recently covered (Wnt signaling that is).<br /><br />Press Release:<br /><br />https://www.sciencedaily.com/releases/2017/02/170223114744.htm<br /><br />Paper:<br /><br />http://clincancerres.aacrjournals.org/content/early/2017/02/23/1078-0432.CCR-17-0201<br /><br />The researchers achieved this with an anti-diabetes drug called rosiglitazone. Now they directly applied this drug to tumor cells, so it is a bit of a stretch to immediately say this could be a great potential repurposing of an existing commercial drug for autism in an identified major autism pathway that is thought to lead to a disrupted E/I balance in the brain.<br /><br />I know there are other methods of antagonizing Wnt signaling which I believe you thoroughly covered, but this might be another vector of interest to add to the list of possibilities.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-58398328066309709822017-02-24T08:00:40.973+01:002017-02-24T08:00:40.973+01:00Another topic you have covered in the past deals w...Another topic you have covered in the past deals with iron and some new research on cocaine use suggests that iron processing and absorption problems as a result of cocaine use can both cause a peripheral deficiency in iron in the blood that causes increased permeability of the blood brain barrier which allows more iron to enter the brain and accumulate:<br /><br />Press Release: <br /><br />https://www.sciencedaily.com/releases/2017/02/170221110733.htm<br /><br />Paper:<br /><br />http://www.nature.com/tp/journal/v7/n2/full/tp2016271a.html<br /><br />In one area of the brain in particlar called the "global pallidus" (part of the basal ganglia and involved in inhibition) there was a large accumulation of iron in cocaine addicts.<br /><br />Now what does this have to do with autism? Well absorption issues of key nutrients via gut and digestion problems, as well as increased permeability of the blood brain barrier, and general problems with inhibition, and in particular the basal ganglia are all hallmarks of autism. What this study shows is one way deficiency in iron for whatever reason can paradoxically cause an increased accumulation of iron in the brain leading to inhibitory processing problems.<br /><br />So in addressing basal ganglia related symptoms of dysfunctional inhibition (autism, OCD) perhaps checking iron levels in the blood might be a simple intervention to employ, if for any other reason than to rule out this process of iron accumulation causing additional inhibition problems over time.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-75616636210251732052017-02-24T07:41:39.157+01:002017-02-24T07:41:39.157+01:00Hi Tyler,
What do you make of combination supplem...Hi Tyler,<br /><br />What do you make of combination supplements for mitochondrial health...mito cell from neurobiologix made me curious. It has pqq and nadh as the main ingredients...pqq, 'a powerful chemical found in interstellar dust' and pepper captured my imagination. This one is a new formulation, formulated by dr. Stewart. There was another older 'mito cell' with the pqq, this one by dr. Sinatra where astaxanthin was included along with others. You cant find details about it but it is still available. <br /><br />The regular commonnly used ones like mitospectra are not really associated with many rave reviews either so just thought why not give the alien stuff a try..who knows my wish upon a star might come true.<br /><br />Please give your opinion. If it has no potential to harm, I am willing to try it.<br /><br />RegardsKritikanoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-11326722243535218832017-02-24T06:38:05.369+01:002017-02-24T06:38:05.369+01:00Another thought I had relevant to mitochondria and...Another thought I had relevant to mitochondria and autism relates to a new paper I read today which isn't too surprising in that it supports the maternal immune activation theory with yet another environmental insult (this time genital herpes), but what I thought here was that perhaps maternal inflammation is damaging the baby's mitochondria itself, thereby leading to not just problems in generating enough ATP to drive cellular growth processes while in the womb (leading to developmental abnormalities), but also once the child leaves the womb. Women could have perfectly fine mitochondria that they pass on to their offspring, but perhaps the mitochondria are being damaged during gestation. I have not read anything to suggest to the contrary so this is just an idea here and nothing more.<br /><br />https://www.sciencedaily.com/releases/2017/02/170222131515.htmTylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-25119853855771424382017-02-23T12:00:36.518+01:002017-02-23T12:00:36.518+01:00Tyler, I think you have made a very good point her...Tyler, I think you have made a very good point here.<br /> I have noticed swings after Bumetanide, behavioural changes before/after diuresis. I saw that my son has usually delayed diuresis and thought there is oxidative stress coming from kidneys. I somehow observed an interplay of opposing diuresis forces in his behaviour.Anonymoushttps://www.blogger.com/profile/16138974464162606874noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-28493093825128955962017-02-23T07:08:48.534+01:002017-02-23T07:08:48.534+01:00I just had a little idea that popped into my head ...I just had a little idea that popped into my head concerning a topic I believe you covered a while back on vasopressin (ADH).<br /><br />First off, even though oxytocin has much more research specific to autism than vasopressin (especially in humans), I was thinking about alternative or complementary reasons why bumetanide and other diuretics seem to have a positive effect on autism symptoms, and in particular cognitive symptoms. Vasopressin as you well know is secreted in response to dehydration and signals the body and in particular the kidneys to retain more water. The osmality of water in the blood is detected via several nuclei in the hypothalamus that control the release of vasopressin in the pituitary gland as a response to decreased osmality of water in the blood. What if this feedback loop is interrupted somehow (or some threshold is too low) such that vasopressin gets released into the body in insufficient amounts because the hypothalamus is not properly sampling the blood to see if water levels are low (to put it simply). This could be because of an excitatory/inhibitory imbalance in these nuclei themselves or else they could be dysfunctional for any other number of reasons such as being damaged by oxidative stress or not properly developing in the first place due to developmental insults in utero.<br /><br />So what if the hypothalamus thinks the body has excess fluid either because it actually does or because the receptors are dysfunctional. This would mean vasopressin would not be released by the pituitary gland unless there was a sudden change in blood volume via a diuretic like bumetanide which would cause enough of an abrupt change, that vasopressin would be released in response. Of course diuretics are constantly triggering this vasopressin release which keeps the receptor count in equilibrium. In the case where vasopressin release is infrequent (vasopressin itself has a very short half-life), the receptors will upregulate in number and then when the bladder is finally emptied, you have a situation where vasopressin is finally released by the pituitary gland, but the vasopressin receptors in the brain and throughout the body are in excess. This in effect means you have a wild swing back and forth in vasopressin signaling which could be help contribute to the anxiety and aggression associated with it. So in summary, chronic use of diuretics could be helping maintain a healthy equilibrium of vasopressin receptors and prevent these big swings in signaling.<br /><br />It would be interesting to see the exact timing of how anxiety/aggression problems pop up in people with autism in relation to voluntary or involuntary (enuresis) voiding of urine as I have never seen a study on the matter that looked at this hypothesis one way or another.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-59632785898187812272017-02-23T06:40:08.260+01:002017-02-23T06:40:08.260+01:00Also I might add that the quantity of mitochondria...Also I might add that the quantity of mitochondria is associated with mitochondrial problems as when the cell cannot keep up with ATP production, its response is to create more mitochondria via fission. The more divisions you have over time, the more chances for errors in replication until enough of the mitochondria don't work at all anymore to keep the cell alive. Also, diseased mitochondria are supposed to be cleaned out via autophagy to make room for better copies of healthy mitochondria, but problems with this process can lead to disease as well. Nevertheless, certain lifestyle factors can limit autophagy and increase these kinds of problems (constant anabolism for instance which is only really supposed to happen in the pre-adult years).<br /><br />Of course mitochondria can increase in number in response to stress (exercise) or in some cases if the cell changes its function (white adipose tissue turning into brown adipose tissue), so it is really hard to figure out one way or the other where the hiccup happens to be. On top of that the vast majority of genes the mitochondria use for its purposes have their RNA transcribed in the cell nucleus, not from the mitochondria itself so a lot of problems can happen there as well.<br /><br />So in terms of useful interventions, I think it is really hard for anyone to directly diagnose mitochondria disease unless you get lucky with some known genetic mutation (or unlucky rather) that lets you know what may be the actual problems, so in my opinion the best approach if you suspect mitochondrial problems is to just try as many known interventions and hope something sticks to the wall. <br /><br />Eventually, the science will catch up as there are legions of billionaires pouring money into anti-aging research in their collective hopes they will be able to live forever while publicly claiming they just want to humbly help "the rest of us", so until the science explains exactly how all of this stuff works, addressing mitochondrial problems is going to be a gray area and any intervention you do is along the lines of hoping you get lucky in fixing whatever might actually be wrong.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-17375492658393719312017-02-22T23:39:16.333+01:002017-02-22T23:39:16.333+01:00Timely post Peter. I just received a sample repor...Timely post Peter. I just received a sample report for my daughters buccal swab, we had done the blood screen for mito disease came back normal but i read a paper by Dr. Michael Goldenthal (director of Mitochondrial Disease Lab at St. Christoper's Children's Hospital) regarding checking respiratory chain complex activity and checking via buccal swab. He has done research on ASD and mitochondrial abnormalities. I contacted him and he sent me a text kit for 200US. The results showed: complex 1 in the above range (like Roger Kulp above), and complex I/IV activity very high (3x the control) which apparently is common in ASD but of unknown significance for now. I am playing phone tag with him right now to discuss the results so I will update. AAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-36457569707197285572017-02-22T18:55:51.359+01:002017-02-22T18:55:51.359+01:00Peter, melatonin is also a highly relevant antioxi...Peter, melatonin is also a highly relevant antioxidant and it can also modulate, by acting as an agonist, a7 nicotinic receptors.<br /><br />I have never stopped melatonin, it always works very well. I currently use 1mg spray and I think it's too little for the case.Anonymoushttps://www.blogger.com/profile/16138974464162606874noreply@blogger.com