Lake Geneva with its famous fountain (Jet d'eau)
As some regular readers are well aware, people with autism are often prescribed psychotropic/psychiatric drugs to make them more manageable; this is particularly true of those who live in residential care homes and for those living in America. When it comes to adults, as Tyler just pointed out in a comment, 1 in 6 adult American takes one or more psychotropic/psychiatric drugs.
These drugs do not treat the underlying dysfunctions in most autism, but do produce a more compliant/sedated individual. They often lead to weight gain and its associated medical problems; some of these drugs are addictive, some can cause irreversible side effects (e.g. tardive dyskinesia).
In England there is a campaign called STOMP to stop this overuse of these psychiatric drugs in people with autism, which can only be a good thing.
STEP
Hopefully one day there will be a campaign to treat the underlying biological dysfunctions within autism, which could be called STEP (Start Effective Personalized treatment); not all treatments need to be drugs.
STALICLA
One reader of this blog has recently established her own start-up company, Stalicla, in Switzerland with the aim of treating individual sub-types of autism. I assume that her STP1, comprising two repurposed drugs, targeting her Phenotype1 subgroup, said to represent 15% of the total idiopathic ASD patient population, is the one she gives her son.
Good luck Lynn - you are going to need it.
STOMP
Stopping over medication of people with a learning disability, autism or both (STOMP) is the campaign in England.
“Public Health England says that every day about 30,000 to 35,000 adults with a learning disability are taking psychotropic medicines, when they do not have the health conditions the medicines are for. Children and young people are also prescribed them.”
Here is a case study example of an over-medicated young man with autism.
While I fully support the STOMP campaign, I guess many STOMP supporters would think my PolyPill and Lyne’s STP1 are complete folly. Hopefully Lynn’s clinical trials will be successful, not to forget many people hope Dr Ben-Ari’s phase 3 bumetanide trial will be successful. Kritika and many others are waiting for results on CM-AT.
So it looks too early to launch my STEP campaign (Start Effective Personalized treatment for people with autism and/or ID and/or epilepsy, not forgetting Down syndrome, Pitt Hopkins, SATB2, Sotos, Turner, Fragile X and all the others).
Conclusion
This blog is all about using drugs more intelligently, not to sedate people with autism but rather to do the opposite, to improve their cognitive function so that they are more able to be self-supporting.
The inappropriate use of potent psychotropic/psychiatric drugs helps to give all drugs a bad name.
Fortunately Lynn chose her company name beginning with ST, which fits nicely with stepping and stomping; I get to squeeze two posts into one and use a nice photo of Lake Geneva and not a photo of someone’s foot.
I live in America and started seeing a MAPS doctor several years ago when my son was a toddler. At the time I kept his interventions under "wraps" due to fear of visits from you-know-who.
ReplyDeleteWhile it is true that many in America may be over medicated, it is also sad that many "mainstream" physicians will not read the research and Rx off label drugs for children with autism, that is, we may not see a shift to personalized medicine for a while.
Most parents who do do MAPS treatments or follow this blog probably don't talk about it. This prevents open sharing of information, that may be used as "data" that ends up being pursuasive enough to trigger clinical trials. But who wants to stick their neck out - as a layman or laywoman - and scream from the rooftop that personalized medicine is the way to go ? Especially if there may be some very nasty consequences attendant to such a bold and open admission ?
Hi Tyler - would you kindly be able to provide your insights on Amino Acids? I know you've done a ton of research and I'm about to run an Amino Acids test on my daughter.
ReplyDeleteKnowing you have a lot of knowledge in this area, I was wondering if you could identify the amino acids that would affect other amino acids when supplemented.
So basically, if I were to supplement with Amino Acid X, it would reduce the levels of Amino Acid(s) Y (and Z). I seem to recall that there was such an effect. Also, for those that you do identify are impacted, do you have any strategies (i.e. take AA X in the morning, and then take AA Y in the evening, etc.)
If / when I do identify deficiencies in my daughter's tests, I don't want to supplement with the AA that was low, only to knock down other important AAs, essentially nullifying any benefit.
Thanks very much in advance Tyler!
AJ
Well, I think the thing with amino acids is if you eat a well balanced diet and have no rare genetic enzyme issues, then you have little to worry about either way. The BCAA therapy I have suggested is for a functional purpose, i.e. a sort of hack to get around other problems going on in the brain, rather than because of some sort of BCAA deficiency. You can just drink a glass of milk and get plenty of BCAA's. Really, you just want to get a balanced amount of protein in your diet which is easy to do for everyone who is not a vegetarian.
DeleteI have also suggested Aspartic Acid, again for a functional reason, not because I believe people have a deficiency in Aspartic Acid, even though it could be the case.
High or low levels of amino acids can mean many different things and unless any testing is done over a period of time and at random times in the day, you are not going to get useful information because the amount of amino acids in the blood or excreted in urine vary with the sleep/wake cycle.
For free-form amino acids, most of the time it is recommended they be taken on an empty stomach with water. Of course, some of them taste absolutely terrible so if they are not ingested via capsule you need a product with some sort of sweetener.
As far as the absorbability of one amino acid versus another, you have to just read the scientific reviews or at the very least go to sites like examine.com which do a decent job of curating that information. The main issue tends to be whether various amino acids use the same transporters to make it past the intestinal epithelium. There are also issues with gut bacteria as some will metabolize certain amino acids differently than others and gut bacteria profiles differ from person to person. Generally, you don't want calcium to go with a lot of supplements or amino acids and if you are worried about conflicts you can just split up dosing by 30 minute increments which is about the time it takes for liquids to pass through the stomach and make it into the small intestine.
Another thing to consider is that unless you have a very leaky gut, your intestines can only absorb so much protein at once anyways. You see these bodybuilders and athletes brag about eating 10,000 calories a day as if they are burning that much from exercise alone. This is largely a myth in terms of the number of calories people burn from exercise, as well as what happens with all that food, and especially protein as what happens to the vast majority of it is that it never makes it to the liver and instead it is just pooped out as waste. The people who eat too much and keep getting fat do so more because they ingest foods and beverages that are high in sugar and saturated fat which are easily absorbed. They can also sometimes also have an excess amount of certain types of gut bacteria in the wrong parts of the intestines which cause an overfermentation of sugars, leading to short-chain fatty acids being dumped straight into the portal vein, rather than being used by the large intestine for cellular energy for the very busy cells which line it.
As far as brain neurotransmitters go, restricting certain amino acids from the diet is usually pointless because your body will just break down lean body mass to maintain homeostasis with respect to amino acid levels in the blood. Nevertheless, even though you probably already know this:
Phenylalanine -> Tyrosine -> L-Dopa -> Dopamine -> Norepinephrine
Tryptophan -> 5-HTP -> Serotonin -> Melatonin
Glutamine, Glutamate, GABA, and Aspartate are all recycled within the brain to some extent and are rate-limited by the enzymes which convert them from one of these amino acids to another.
Increasing the amount of one of these amino acids in the blood may temporarily cause an increase in the blood of these amino acids, but the synthesis of downstream functional molecules is rate-limited by enzymes such as AADC which is used for many conversions including converting L-DOPA to Dopamine and 5-HTP to Serotonin.
Hi Tyler,
DeleteThanks for your insights - I really appreciate it!
I am thinking of situations in which testing shows us that my daughter is unusually low in some AAs, not due to dietary reasons as she gets a good amount of protein in her diet.
Some AAs appear especially important for brain health, so if she's unusually low in those, then I would supplement her a bit on those ones and see if there is any impact.
To your point, there may be various reasons for why someone may be very low on specific AAs.
Thanks again Tyler!
AJ
Dear Peter,
ReplyDeleteYes, indeed, I am waiting for the Curemark results, and I am desperately waiting for Ben-aris final findings and waiting and waiting for vasoprresin agonist (as well as antagonist) trials for treatment of autism. Something, somebody...anything! You see, in the absence of formal support, it becomes difficult for most individuals to even access drugs for our independent trials, leave alone monitoring for dosage and side effects. Case in point is bumetanide...my earlier lot expired and I cant find a single decent online site now from where I can repurchase the dru g. Interestingly, ebay india, is offering miccil (limited stock), but at a steep price. A single tablet of 1mg miccil would cost me around INR 150. Not impossible but definitely inconvenient to run a trial. If I had prescription and a doctors guidance, it would be a different story altogether. For now, forget a doctor, I do not even have my bitter half's (not a typo) support for these adventures. And I think I represent a good percentage of mostly, mothers, who are braving it all with a song on our lips and a prayer in our heart.
Kritika, there are indeed many barriers. There are fathers who read this blog who are doctors and can access these drugs, but their other half does not agree to make trials without "firm evidence". So evidence in the form of approval by a drug regulator somewhere in the world really should change things.
DeleteThis is one reason to trial several things all at once, before your spouse thinks it is all a waste of money. This is what our Greek reader Thomas did, although maybe not for that reason. When you see a profound change you cannot deny autism is treatable. If you try things one by one, you may get lucky, or after a few failed trials just give up.
Biomarkers for each therapy would help.
My son was enrolled in the Curemark study. We had to take him out because it was making him really aggressive.
DeleteIt is almost inevitable that some people will respond badly to any autism drug, since autism is a condition of opposites.
DeleteIt would help if Curemark actually said what was in their CM-AT drug. It might be that just one ingredient gave your son the negative reaction. As I understand it, CM-AT is a cocktail of amino acids and digestive enzymes.
Thank you for the heads-up on the Muccil, Krithika. I also tried - most unsuccessfully - to source the Bumex last year during my trip to India and was offered Lasik, instead.
ReplyDeleteI understand your frustration but even with the research in a "first world country", I am unable to source Verapamil for my son as my son's mainstream doctors don't seem "convinced", and not everyone can afford a MAPS. So, I, too, am sitting here with a song on my lips and a prayer in my heart and ... dealing with severe diarrhea, after my first trial pf 900 mg of PharmaNAC today :(
GRT,
DeleteSo I am finally ordering some miccil from ebay...want to make the best of summer season when my trial will not be disrupted by frequent viral infections, hopefully.
All the best for yours....and on a cheerful note
A song on my lips, and the wind in my hair
With a spring in my step and in my heart, a prayer.
GRT, just wanted to chime in re: NAC. My son could not tolerate NAC in the past. It is known to be “hard on the gut” for some - perhaps because it is a substrate for hydrogen sulfide?
DeleteThere is a form of SIBO/IBS due to an overgrowth of hydrogen sulfide producing bacteria. I know that smaller amounts of endogenous hydrogen sulfide is a good thing, but too much is bad. Maybe the diarrhea from high dose NAC can give you clues to other things going on. You may have already known about this possibility but wanted to mention just in case - as well as I welcome thoughts from others on these gut topics. I know all too well how a big a deal the gut stuff is. Sigh.
Kritika, I’m curious if you have ever tried pepto bismal for the bismuth part of it to see if it helped your son’s bloating? There are apparently successful protocols combining bismuth with certain antibiotics used for h. Pylori and SIBO/IBS . My son has been in a gut flare recently - first one since last fall - he’s been requesting pepto and is doing better. Now I will look into taking it further.
DeleteHi Tanya
DeleteNever tried pepto bismol but just looked it up and it seemed to come with lot of warnings.....also does not seem suitable for under 12 year old. Is it?
I would also like to share that after getting inspired by information about bimuno which you had provided, I thought of trying a probiotic, Bioamicus complete, which I had ordered when the probiotic theme was trending on Peters blog. Since this probiotic mix had strains helping out with histamine issues and lots of bifidobacteria, which GOS is said to support the growth of, I thought it should be a safe bet. But just five drops of the stuff (10 billion bacteria) left me an d my son with a very unhappy tummy.
Will not a prebiotic have a similar effect on us if it encourages proliferation of bacteria, beneficial though they may be, if our gi system is not able to control or tolerate this change?
Regards
Yes that is what happens with SIBO and using prebiotics except b-GOS is proving to be effective in SIBO cases bc it doesn’t produce gas. It’s the gas that causes the problem .. not sure about pepto under 12. Maybe you could try to see if it helps you. As far as warnings, I think like with anything, if used properly and for a short time that’s the key. No more dangerous that other things mentioned here. Even if it’s just used briefly and can aide in diagnosing - not such a bad thing..
DeleteStill waiting on Bimuno - shipping here from UK. Will let you know.
Ok Tanya, will give pepto bismal a try and bimuno too. You are right in that every intervention is potentially dangerous if not used judiciously. And clearly antacids are the more benign ones....
DeleteThanks Tanya....your assessment is usually uncannily accurate and suggestions are always extremely helpful.
Oh Kritika I don’t want you to think I’m telling you what to do - it’s good that you are cautious and you know how to make the best decision for your kid. I just mention things here because when I try something for my son, especially when he asks for it, and I see a little positive - it makes me wonder if other see benefit too. Especially In terms of sibo/IBS related gut issues bc it is such a tricky thing- and you had mentioned before luck with an antibiotic - it reminded me of the information I had read about bismuth and antibiotic combo being effective. It’s the bismuth part of pepto that has antibacterial properties. Always interested in hearing from others and their experience.
DeleteTanya,
DeleteIts ok...I understand. Dont burden yourself morally. I will make it short lest Peter finds the exchange a little too... you know what.
Fordiuran (=Bumetanide) was very available in spanish Canary islands. Unfortunately Coslan (Ponstan/mefenamic acid) was out of stock there at the moment. Also, melatonin in dosages up to 1.95 was sold everywhere.
ReplyDeleteIn countries where Ponstan is OTC, the regular pharmacies will ship it internationally. For example New Zealand. They do not charge inflated prices like internet pharmacies selling prescription drugs.
DeleteSome very interesting developments on mitochondrial disease issues came out today. The first report details the challenges many people with mitochondrial disease have in getting a proper diagnosis:
ReplyDeletePress Release:
https://www.sciencedaily.com/releases/2018/03/180326161004.htm
Paper:
http://ng.neurology.org/content/4/2/e230
The second paper should be interesting to everyone on this blog as it tests the effectiveness of seven well known compounds in combating oxidative stress in three different mouse models of mitochondrial disease:
Press Release:
https://www.sciencedaily.com/releases/2018/03/180327093948.htm
Paper:
http://www.mgmjournal.com/article/S1096-7192(18)30041-6/fulltext
Unsurprisingly, NAC (N-Acetyl-Cysteine) came out on top, but surprisingly Vitamin E was also very effective and two compounds that I would normally put up there with NAC for mitochondrial health only had mild effects, namely Coenzyme Q10 (not terribly surprised), and MS010 (aka MitoQ) (rather surprising).
Anyways, the study is rather straightforward so you can read for yourself and draw your own conclusions.
Hello everyone,
ReplyDeleteI have been researching the aryl hydrocarbon receptor a bit after reading some of the following that posted below. I did a search on the blog and there have been no posts about this yet so Im hoping to get a discussion going. AHR is control of things such as CYP1A1 and CYP1B1, which determine how cigarette smoke affects the chance of getting lung cancer for example, I can only speak for myself but chemical sensitivities seem to occur in alot of people with autism. For example cigarette smoke tends to create gas in me within like 10secs after I smell the odor.
Also there seems to be a strong correlation between AHR, vitamin a and vitamin d.
AHR seems to have a very large influence in the testosterone/estrogen balance and I think could be one of the reasons for the male:female ratio of autism???
___________________
Dysregulation of Notch and ERα signaling in AhR−/− male mice
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081633/
Testosterone-Dependent Interaction between Androgen Receptor and Aryl Hydrocarbon Receptor Induces Liver Receptor Homolog 1 Expression in Rat Granulosa Cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719679/
___________________
Emotion recognition associated with polymorphism in
oxytocinergic pathway gene ARNT2 (November 2017)
https://academic.oup.com/scan/article/13/2/173/4669739
Ligands of the aryl hydrocarbon receptor produced by gut microbiota
edepot.wur.nl/418954
"Enzymes are needed for the conversion of tryptophan to kynurenine and other compounds. One of those enzymes, indoleamine 2,3-dioxygenase (IDO), is needed for the conversion of tryptophan to kynurenine. It was found that the presence of Lactobacillus reuteri increases the activity of this enzyme, which in turn increases the conversion of tryptophan to kynurenine [43, 44]. Lactobacilli (such as Lactobacillus reuteri) are the bacteria most involved in the production of tryptophan derivatives [45]. The Lactobacillus reuteri occurs naturally in humans, but not in all individuals [46]."
Seems everything with an indole group affects AHR (yes that includes I3C also found in brocolli).
Genetic variant rs17225178 in the ARNT2 gene is
associated with Asperger Syndrome (2015) - P=0.001
DOI 10.1186/s13229-015-0009-0
Associations between oxytocin-related genes and
autistic-like traits
http://dx.doi.org/10.1080/17470919.2014.897995
"Furthermore, nominal associations were found between ASD scores and SNPs in OXT, ARNT2 and CD38."
Now CD38 was allready discussed earlier by Peter, this is controlled by the retinoic acid receptor, and indeed vitamin A supplementation seems to help restore a fair bit of the social problems.
Vitamin A improves the symptoms of autism spectrum disorders and
decreases 5-hydroxytryptamine (5-HT): A pilot study (2018)
https://www.ncbi.nlm.nih.gov/pubmed/29122693
"The DSM-V criteria and CARS score were used for symptom description and symptom assessment of the patients, respectively, before and after vitamin A supplementation (VAS). Serum retinol and 5-HT levels, mRNA levels of RAR α, β, and γ and TpH 1 expression were detected in autistic children before and after VAS and in normal children. Serum retinol levels in children with ASD were significantly lower than in control children. Serum 5-HT levels in children with ASD were higher than in control children, which were correlated with symptom severity of children with autism."
Now the difference between TPH1 and TPH2 is very important, TPH1 = blood serotonin, TPH2 = brain serotonin.
Retinoic acid (=vitamin A) drives aryl hydrocarbon receptor expression and is instrumental to dioxin-induced toxicity during palate development.
https://www.ncbi.nlm.nih.gov/pubmed/21807577
Very interesting ideas Aspie. One thing you probably already know is that excess dietary tryptophan is predominantly metabolized to the kynurenine pathway as the TPH1 and TPH2 are enzymes which rate limit the synthesis of serotonin. One could postulate that if there is a lack of L Reuteri bacteria in the gut, you could have an excess of peripheral serotonin as a result, especially if cells are under stress as serotonin in the periphery is generally pro-inflammatory. Just an idea here.
DeleteAlso, I think Peter talked about vitamin A before if I am not mistaken. I know I posted research a year or so ago about a link between Vitamin D and DHA having some strong interplay with the ratio of TPH1 and TPH2 which was before you started posting here, but the papers I linked to were different than the ones you just posted
Cinnamon (sodium benzoate) also affects AHR
DeleteD-Amino Acid Oxidase Generates Agonists of the Aryl Hydrocarbon Receptor from D-Tryptophan
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923838/
"Previously, we showed that the endogenous enzyme, aspartate aminotransferase (AST), generates the AHR proagonist, indole-3-pyruvic acid (I3P), by deamination of its substrate L-tryptophan. We hypothesized that other enzymatic pathways capable of producing I3P may generate AHR agonists in vivo. We now demonstrate that the enzyme D-amino acid oxidase (DAAO) catalyzes the production of AHR agonists through the enzymatic conversion of D-tryptophan to I3P."
"Sodium benzoate inhibits DAAO-mediated AHR activity"
"Based on the observation that UV-B exposure causes an increase in CYP1A1 and CYP1B1 expression in human skin (57), high-potency AHR agonists derived from Trp have been suggested to occur endogenously (58)."
My ASAT and ALAT values are basically always elevated every single bloodtest (only NAC could take them down into normal range).
Which brings me to the next questions, is ASAT elevated in people with autism as an attempt to raise AHR or as a cause of increased glutamate/aspartic acid excitoxicity.
Tyler, how is your daughter (I believe?) her sensitivity to cigarette smoke and other toxins, for me personally I seem to have an extreme sensitivity to toxins (urge to puke when smelling certain cleaning chemicals while other people do not seem to flinch for example).
I would like to know this from other parents aswell.
Nothing special to report on ASAT / ALAT from here, Aspie.
Delete/Ling
Well my kids would never know because they have never been exposed to cigarette smoke, nor have they shown any sensitivity to any particular chemical.
DeleteOne reason you might have an exaggerated visceral response to various chemicals is a hyperactive insula which seems to be a hallmark in many autisms. In other words, the part of your brain that has you feel sensations of disgust is potentially giving you faulty feedback from your environment. This is hard for a lot of people to understand, but the sensation as well as the sense of emotion from disgust can be really just "all in your head".
Aspie, my son most definitely was sensitive to polycyclic aromatic hydrocarbons like cigarette smoke - especially diesel exhaust, which is one of the reasons I did not want him to try riding the school bus when he was little and was attending a wonderful elementary school. We did genetic profile testing on his liver enzyme pathways and this was confirmed. This was many years ago when he was first diagnosed. I think the report recommended using resveratrol. Coal tar is also in that group of PAH and my understanding certain B vitamins are derived from that. Explained his extreme sensitivity to things back then a lot. He is not so reactive now. Apparently a lot of people with mast cell issues have these chemical sensitivities. As do some with bipolar. I wonder if there is an HPA/stress component too? Do you live in a big city around a lot of car exhaust?
DeleteTyler, emotional disgust is definatly registered there, such as seeing someone you bump into and dont like.
DeleteHowever bumping into a smell when walking on the street then having to squeezing my nose and holding my breath so I dont actually have to vomit is a response to an actual chemical.
Tanya the response Im getting to cigarette smoke and chemical plant fumes is very real, I will actually get sick if exposed too long to them.
AHR is involved in cancer suspectability, thats why I3C and other substances that are agonists/antagonists are researched for forms of cancer (breast cancer included).
Now AHR is obviously necesarry for a proper emotional response as proven by my studies posted, there is also a very strong link between cancer and autism.
Autism and cancer share risk genes, pathways and drug targets
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769654/
Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0149041
"Phenotypically, children and adults with ASD exhibited a protective effect against cancer, with a frequency of 1.3% vs. 3.9% (p<0.001), but the protective effect decreased with age. The odds ratio of neoplasm for those with ASD relative to controls was 0.06 (95% CI: 0.02, 0.19; p<0.0001) in the 0 to 14 age group; 0.35 (95% CI: 0.14, 0.87; p = 0.024) in the 15 to 29 age group; 0.41 (95% CI: 0.15, 1.17; p = 0.095) in the 30 to 54 age group; and 0.49 (95% CI: 0.14, 1.74; p = 0.267) in those 55 and older."
This Common Cancer Drug Could Help Fight Autism's Social Challenges (shank3 mutation and helps recover nmda signalling) - 2018 - it is a hdac2 inhibitor (things such as butyrate are also hdac inhibitors)
https://www.sciencealert.com/anti-cancer-drug-romidepsin-rescues-social-traits-autism-spectrum-disorder-mice
Could it be that people with autism their bodies are working overtime to fight cancer, thereby some errors are occuring in the AHR pathway thus neglecting social functioning.
@Tanya
Yes I live in a city with around 1million people and I noticed on days when Im out of the city (not just in nature, but in less dense populated areas = less diesel exhaust) I tend to function better.
To me its getting so obviousy now (and im 99.99% sure my 23andme results will confirm my suspision):
AHR mutations can explain:
* the sex differences which are so pronounced in autism (think esr1/esr2 and aromatase genes)
* chemical sensitivites/dysfunction in the nrf2/phase ii detox pathways
* connection to the gut (metabolites of tryptophan and aspartic acid in the gut can act as potent AHR agonists, l.reuteri regulates this and this is most likely the reason it can raise oxytocin)
* AHR strongly interacts/regulates how fat soluble vitamins work, fat soluble vitamins attach to receptors and these can induce things such as the pregnane x receptor, hormone response element, androgen and estrogen receptor sensitivity, etc.
Aspie,yes indeed these reactions are real. I saw it in my son - one example being in car drop off line at school if we were parked behind the school bus his behavior deteriorated rapidly and then he would have that “migraine look” - also could have affected his gut as well. He also used to have a very strong reaction to fragrances like perfumes and artificial scents. hanks as always for sharing. I look forward to reading through the links you provided
DeleteAnd I’m sure his reactions are still there but we avoid a lot of triggers so not sure how strong they would be. We do live in the suburbs, but most of the extracurricular things he enjoys are all out in nature - never city ventures. We are almost finished building a home in the country and starting up a small farm as a “business” for him . I look forward to another level of healing this can bring him
DeleteAspie, the part of the insula called the anterior insula deals more with emotional or psychological issues of disgust. The posterior part is thought to be more attuned to direct visceral sensations. In other words, a normal person may be mildly sensitive to cigarette smoke, perhaps even due to habituation, but someone with a hyperactive brain response to those signals from the peripheral nervous system may never adapt and feel violently ill whenever exposed.
DeleteThere are ways to discriminate if the issue is a peripheral response like an extremember allergy or a central response due to hyperactive brain circuits.
Tyler,
DeleteCertain smells and even touching chemicals that dont make others sick can make me sick and make me puke I am telling you it is just more toxic to some people with autism (myself included) than the general population, this has nothing to do with the brain. I do not feel less or more emotional when exposed to them.
Aspie you are absolutely right. When my son was at his most reactive I met many moms with kids with similar reactions. There is even a clinic in Dallas TX for environmental detox and it was not started by a “quack” doctor, my understanding. Many years ago my son also reacted to his OT’s new building - with new carpeting and paint off gassing. Within 15 min of being in the building his eczema would flare and he would start to wheeze. I mentioned the HPA stress axis as maybe having some small piece because I know stress is a big trigger for mast cell. In fact it may have been the only mast cell trigger for my son because now that we have removed his biggest trigger (psych stressor from a horrible school) he no longer breaks out in hives.
DeleteAspie,
DeleteNot my son but lately I have become very sensitive to toxins....I totally understand what you are saying. Leave alone the offensive smells like diesel, mosquitoe repellant or paints, which give me a nauseous headache, I cant tolerate the chemicals in perfumes, soaps, shampoos. I can literally smell out the chemicals out of the cocktail which I am sure are toxic in one way or the other..thinking of moving to pure essences or herbals.
Kritika, same. We used to could not take my son down the laundry detergent aisle in the grocery store - he would start smacking his head. We are a non fake scent home. My oldest recently came home during his spring break wearing an antiperspirant with a strong fragrance -after a few hours my lips started to burn and throat tightened. Weirdly, my ASD son didn’t react. I just have to wonder if lithium is helping him with this too?? Lots to google, plus later tonight reading Aspie’s links
DeleteTanya,
DeleteI am living in one of the most polluted metros, Delhi and unfortunately, because of sons therapy requirements, have to stay on,but seriously, its taking a toll on me as our city gets more and more noxious. I am sure my sons Gi issues will be solved if we move out....and mine too.
Hi everyone,
DeleteVery interesting topic for me ... in my late teens to my mid-twenties, I thought I had developed asthma (as did my GP who gave me Flovent for many years) as I would wake up in the middle of the night having a hard time breathing, and would have some difficulty breathing from time to time. It would come and go.
Then, I realized what it was after many years of great discomfort - it wasn't Asthma per se, but asthma triggered by certain chemicals. The worst culprit was the smell given off by dryer sheets (Bounce) or clothes that had been dried with them in the recent past, but also nearly as bad was any chemical cleaner (e.g. Mr. Clean, OxyClean, etc.)
So I eliminated all the chemical cleaners (with natural, no smell cleaners), Natural no smell Tide (for laundry) and natural (no smell) dryer sheets and I never had any issues any more.
To this day, I avoid the cleaning aisle in supermarkets, hold my breath when walking in an area that has just been cleaned with chemicals when outside, and avoid being near anyone whose clothes have that "dryer-sheet" smell.
Given this thread, I wanted to post my personal experience, especially if anyone is having similar difficulty breathing at times and cant figure out why. I wish I knew that these things were the cause of my issues when they originally developed, it would have saved me years of great discomfort (especially when I had trouble breathing in the middle of the night).
AJ
AJ, oh yes those dryer sheets and fabric softeners are the worst, aren’t they? So fortunate for you that your daughter doesn’t have those reactions :)
DeleteHi Tanya, Oh yes, of all the chemicals that make my lungs seize up, dryer sheets are the worst.
DeleteI used to take a train to work every day, and if someone sat beside me who smelled like a dryer sheet, I would have to get up and go somewhere else.
I'm definitely glad that my daughter doesn't have my chemical sensitivities :)
AJ
Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615256/
Cutting edge: progesterone directly upregulates vitamin d receptor gene expression for efficient regulation of T cells by calcitriol.
https://www.ncbi.nlm.nih.gov/pubmed/25548222
"Increased expression of VDR by progesterone allows highly sensitive regulation of T cells by vit.D even when vit.D levels are suboptimal."
Cutting Edge: AhR Is a Molecular Target of Calcitriol in Human T Cells
http://www.jimmunol.org/content/early/2015/08/14/jimmunol.1500344
Vitamin D, Neurosteroids and Autism
http://www.biomed.cas.cz/physiolres/pdf/2017/66_S333.pdf
γ-Tocotrienol (form of vitamin E) upregulates aryl hydrocarbon receptor expression and enhances the anticancer effect of baicalein (ingredient in chinese skullcap).
https://www.ncbi.nlm.nih.gov/pubmed/27055589
The naturally occurring aliphatic isothiocyanates sulforaphane and erucin are weak agonists but potent non-competitive antagonists of the aryl hydrocarbon receptor.
https://www.ncbi.nlm.nih.gov/pubmed/22643862
The aryl hydrocarbon receptor interacts with nuclear factor erythroid 2-related factor 2 to mediate induction of NAD(P)H: quinoneoxidoreductase 1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597779/
Resveratrol potentiates vitamin D and nuclear receptor signaling.
https://www.ncbi.nlm.nih.gov/pubmed/25536521
"Thus, resveratrol may affect VDR and other nuclear receptors indirectly, likely via the ability of resveratrol to: (1) potentiate 1,25D binding to VDR; (2) activate RXR; and/or (3) stimulate SIRT1, an enzyme known to deacetylate nuclear receptors. The results of this study elucidate a possible pathway for crosstalk between two nutritionally derived lipids, vitamin D and resveratrol, both of which converge on VDR signaling."
Flavonoids as Aryl Hydrocarbon Receptor Agonists/Antagonists: Effects of Structure and Cell Context
https://www.jstor.org/stable/3435207?seq=1#page_scan_tab_contents
"Chemoprotective phytochemicals exhibit multiple activities and interact with several cellular receptors, including the aryl hydrocarbon (Ah) receptor (AhR). In this study we investigated the AhR agonist/antagonist activities of the following flavonoids: chrysin, phloretin, kaempferol, galangin, naringenin, genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and diosmin."
Discusses mixed agonistic/antagonistic properties of alot of flavonoids (bi-phasic response? more is not always better it seems?)
Quercetin, resveratrol, and curcumin are indirect activators of the aryl hydrocarbon receptor (AHR).
https://www.ncbi.nlm.nih.gov/pubmed/22867086
There is also a complex relationship between estrogen and vitamin D and we know males with autism have low estrogen/estradiol and down regulated ERbeta. Perhaps this why some people with autism who eat oily fish and go out in the sun, still have low vitamin D?
DeleteActually I have insane estrogen dominance (2d:4d ratio), my phones charger isnt working right, but I will upload a photo of my hand when I get it working so you can see it for yourself.
DeleteIn my bloodtests my testosterone levels have always been spot on though and my estradiol levels seem in the healthy range for my age aswell, my shbg however seems to be mildly elevated but my free testosterone levels are still quite good.
I suspect however that I have alot of ERalpha receptors (I got a mild gyno at puberty and this never gone away naturally).
On top of that I have a very large frame, very wide shoulders and somewhat wide hips and a wide face but quite rounded.
Now as you might know Peter it is actually estrogen that is a bone builder more than testosterone, this is why all the powerlifter guys with high dht are of short statue and have low estrogen.
Aspie1983, and your vitamin D is also spot on?
DeleteYeah my vitamin d3 levels skyrocketed about a year ago (I remember posting several bloodtests here even one where it was at around 300 on a scale of 30-130, apparantly according to science 50-70 is the goldilock zone).
DeleteVitamin d3 supplementation is very very noticable, i can put my stopwatch on it till it basically starts working, ~1hour after intake and the effect lasts about 6-10hours (when i dosed 10.000iu), this is in line with the other papers I have read that plasma 1,25OH2 d3 is elevated the first 7 hours roughly after intake.
Oddly, it feels like to me that the initial 'burst' of vitamin d3 elevation in the blood is what my body likes, I become a total normal human being basically for half a day, however this effect does not stay... despite my d3 levels gradually building in my blood (as confirmed by many bloodtests). I guess its down to Vitamin D receptors temporarily desenzitizing.
For example, I noticed if I skipped a few days and then did 10k iu of d3 again, the effect was once again very very pronounced. Im talking effortlessly socialization, my head literally feels more enriched.
Calcium and mag are also spot on in the middle (I do not supplement with calcium as the dutch diet is quite high in it and I eat a fair bit of goat cheese, magnesium I do supplement though, currently 400mg worth of citrate and a bit of magnesiumoil at night to help me sleep).
Vitamin K2 (as MK-7) I have had a very very very very scary experience with. Think it took literally only a few days of 50mcg (yes this is considered a very low dose) before the potential deadly side effects could set in.
Some threads are here:
http://forums.phoenixrising.me/index.php?threads/has-vitamin-k-2-mk-4-or-mk7-helped-you.15605/
http://www.longecity.org/forum/topic/40531-reaction-to-vitamin-k2-mk-7/
http://www.longecity.org/forum/topic/68130-weird-reaction-to-vitamin-k2/
I was using both ginkgo and the k2 mk-7 at the time and I guess that might have aggrevated my reaction to k2 by having dangerous interactions.
Basically it did have a quite pronounced effect on my mood on me, first few days I felt socially alot better, but then all a sudden after a few days of mk-7 supplementation I felt off, very very off so to speak, my blood pressure skyrocketed, insane anxiety and panic attacks, these effects came in waves and at that time I had absolutely no clue what it could be.
DeleteSo all of a sudden I felt this pulsating feeling at the back of my eye sockets on top of the insane hypertension like symptoms that I had all over my body, I was quite scared, the pulsating and eventually when I looked the mirror I saw that the bloodvessels in my eyes ruptured and there was patches of blood and veins filled with blood in my eyes. So I decided to stop the k2 supplementation that same day (once again I was only doing 50mcg of k2 mk-7 in the morning) aswell as the ginkgo, to my surprise the hypertension like symptoms continued the entire day!! and the pulsating feeling at the back of my eye sockets continued to come and go every few hours (every time it happened more blood vessel ruptured). It was increased ocular pressure im 101% sure of that. Once again it didnt end there!!! That same evening I felt so off, in my head this time, I sat and leaned my head slowly to the right and left and everytime I could feel the blood going from one side to the other, this was probably the most scary thing I have ever experienced and admittedly yes i was afraid of dieing. Now I told myself, the next day you wake up it will be all gone, so eventually with alot of trouble I managed to fall asleep. I slept horrible, maybe 3-4 hours, woke up and the raised blood pressure was still there!!, The blood gushing from one side of my brain to the other was less but it was still there. It took like 5 days or something for it to all go away and it took over 1.5 years for the veins in my right eye to become minimally visible (first few months there was small patches of blood 'stuck' in my right eye).
DeleteNow only recently I managed to find the root cause of the problem why K2 acted as both a coagulant and anti-coagulant in me (not many people know it can act as one).
https://courses.lumenlearning.com/boundless-ap/chapter/hemostasis/
"Both calcium and vitamin K are needed to synthesize Protein C, an anticoagulant that prevents excessive coagulation after the coagulation cascade occurs."
I suspect this explains what the 'waves' in blood pressure/bloodflow were.
On top of that vitamin k is involved in the uptake/regulation of 5-HT blood platelets (something which is allready clearly very off in nearly every form of autism).
Speculations on vitamin K, VKORC1 genotype and autism.
https://www.ncbi.nlm.nih.gov/pubmed/27959270
Sex-specific serum biomarker patterns in adults with Asperger's syndrome.
https://www.ncbi.nlm.nih.gov/pubmed/20877284
The below 3 are implicated in aspergers (ripped fromt he study and they are blood clotting factors). I hope I can raise awareness if anyone reads this with aspergers to get atleast 23andme tested before you even touch any mk-7/mk-4 supplement as it can be dangerous for you.
Thrombopoietin P=0.0022
Factor-VII P=0.0316
Tissue factor (also called platelet tissue factor) P=0.0001
On top of that K2 seems to be implicated in glutamate and calcium release from soft tissues, for example I have cracking knees, apparantly these are calcium deposits.
Once again people I do not wish that anyone else will have go through that what I had to with vitamin k2.
One more thing I would like to say is that as a kid I often had spontaneous nosebleeds which were nearly impossible to stop, I also had this sometime on higher doses of NAC, which is one of the reasons why I decided to quit NAC.
I think if your kid has autism and has regular nosebleeds that seem never ending, be very carefull with k2 mk-7 and mk-4 supplementation. Oddly enough, food that contains K2 such as some dutch cheeses do not give me any of these problems!!! Also in the other forum links that I have posted I have seen people say that they only get it from supplements not from actually eating k2 rich food.
Forgot to add, I have done the 23andme test and the results I will probably have in max of 2months.
ReplyDeleteAspie, how do you do with zinc?
ReplyDeleteZINC NUTRITIONAL STATUS MODULATES EXPRESSION OF AHR-RESPONSIVE P450 ENZYMES IN VASCULAR ENDOTHELIAL CELLS
Huiyun Shen, Xabier Arzuaga, [...], and Bernhard Hennig
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2346446/#!po=51.1905
“zinc is commonly found as a zinc finger motif in transcription factors (Klug and Schwabe 1995). Classical zinc fingers have also been shown to interact with RNA and DNA/RNA complexes (Shi and Berg 1995). The susceptibility of zinc fingers to zinc deprivation is not well understood. For example, certain zinc-finger transcription factors, such as Sp1, EGR-1, vitamin D3 receptor and retinoid X receptor have been found to be inhibited due to loss of zinc as a response to zinc replacement by nitric oxide “
I do dose zinc daily (30mg as picolinate), high zinc intake can be toxic.
DeleteThe zinc/copper ratio seems to be off in both asd/autism and aspergers.
Adding zinc to the autism group did seem to help shift the ratio, but in the aspergers group it didnt.
Aspergers is also associated with excess copper as far as im aware, which is probably another reason why alpha lipoic acid has such a good mood boosting effect in me (it chelates copper very effectively).
Increased Copper in Individuals with Autism Normalizes Post Zinc Therapy More Efficiently in Individuals with Concurrent GI Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738468/
Analysis of Copper and Zinc Plasma Concentration and the Efficacy of Zinc Therapy in Individuals with Asperger’s Syndrome, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and Autism
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235993/
"Autistic and PDD-NOS individuals had significantly elevated plasma levels of copper. None of the groups (autism, Asperger’s or PDD-NOS) had significantly lower plasma zinc concentrations. Post zinc and B-6 therapy, individuals with autism and PDD-NOS had significantly lower levels of copper, but individuals with Asperger’s did not have significantly lower copper. Individuals with autism, PDD-NOS and Asperger’s all had significantly higher zinc levels. Severity of symptoms decreased in autistic individuals following zinc and B-6 therapy with respect to awareness, receptive language, focus and attention, hyperactivity, tip toeing, eye contact, sound sensitivity, tactile sensitivity and seizures. None of the measured symptoms worsened after therapy. None of the symptoms in the Asperger’s patients improved after therapy."
Now I do feel more calm on zinc, but the effect is not as pronounced as the pro-social effect i get from vitamin d3.
Another new mouse study on prenatal infections and postnatal infections and how they affect various brain networks came out today:
ReplyDeletePress Release:
https://www.sciencedaily.com/releases/2018/03/180328083434.htm
Paper:
http://www.jneurosci.org/content/38/13/3358
In effect, the researchers induced the immune system in prenatal mice with a chemical that mimics a viral infections just before birth as well as inducing the immune system of mice pups postnatally using a chemical that mimics the effects of a bacterial infection. In addition to a control group of mice, there were three total groups comprising one group testing prenatal viral infections, one group testing postnatal bacterial infections, and a third group testing both prenatal viral infections and postnatal bacterial infections.
The group of mice which had the maternal immune system of their mothers stimulated prenatally as well as having their own immune system stimulated postnatally, ended up having the most changes to brain networks in adulthood which looked a lot like what you find with autism.
In particular, they found that GABAergic signaling was disrupted between the medial prefrontal cortex and the basolateral amygdala which is very important in the regulation of behavior. Adults who have lesions to the medial prefrontal cortex tend to have severe behavior problems with one of the most famous people to have a lesioned medial prefrontal cortex being Phinneus Gage who had a railroad spike driven into his skull from an accident and who had a severe change in disruptive behaviors for the rest of his life after the accident.
@Peter
ReplyDeleteAs promised 2 photos of my hand, which strongly indicate estrogen dominance:
https://ibb.co/cZRAkS
https://ibb.co/exTeen