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Tuesday, 14 February 2017

A Medical Case for Curcumin? Apparently Not



One medical researcher, who reads this blog, sent me a recent article about the vast amount of research that has been carried out on curcumin, which is widely used as a supplement.


Many apparently interesting natural substances suffer from low bioavailability and the arguments put forward in the paper do apply to many other supplements.  On the other hand, there are natural substances that do have useful medical properties in humans; it is just very hard to identify which ones, without making your own research. 


Inside the golden-yellow spice turmeric lurks a chemical deceiver: curcumin, a molecule that is widely touted as having medicinal activity, but which also gives false signals in drug screening tests. For years, chemists have urged caution about curcumin and other compounds that can mislead naive drug hunters.  Now, in an attempt to stem a continuing flow of muddled research, scientists have published the most comprehensive critical review yet of curcumin — concluding that there’s no evidence it has any specific therapeutic benefits, despite thousands of research papers and more than 120 clinical trials. The scientists hope that their report will prevent further wasted research and alert the unwary to the possibility that chemicals may often show up as ‘hits’ in drug screens, but be unlikely to yield a drug.

The full paper is here:-


Curcumin is a constituent (up to 5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (panassay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No doubleblinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

At first, curcumin appeared to offer great potential for the development of a therapeutic from a NP (turmeric) that is classified as a GRAS material. Unfortunately, no form of curcumin, or its closely related analogues, appears to possess the properties required for a good drug candidate (chemical stability, high water solubility, potent and selective target activity, high bioavailability, broad tissue distribution, stable metabolism, and low toxicity). The in vitro interference properties of curcumin do, however, offer many traps that can trick unprepared researchers into misinterpreting the results of their investigations.

With respect to curcumin/curcuminoids and in vivo studies and clinical trials, we believe there is rather “much ado about nothing”. Certainly, the low systemic exposure levels reported in clinical trials do not support its further investigation as a therapeutic. Circumventing the requirement for systemic circulation, curcumin might provide benefit by acting on gut microbiota. Thus far, there is limited evidence to support this hypothesis, which will also limit the utility of this delivery method. Delivery systems such as lipid vesicles, nanoparticles, and nanofibers might be able to boost the bioavailability of 1, but this could also conceivably narrow its therapeutic window and lead to off-target toxicity by aforementioned processes. Available evidence demonstrates curcumin will ultimately degrade upon release into physiologic media, no matter the delivery mechanism. Analogues of 1 might address some of the delivery challenges but would be new chemical entities and would have to proceed through expensive preclinical work to be approved for clinical trials. In our opinion, analogues of curcumin are based on a fairly weak foundation.



Conclusion

It would be wrong to conclude that natural substances and supplements are of no medicinal value. One reader of this blog with type 1 diabetes has used some of the tips in the blog to improve insulin sensitivity so far that the requirement for insulin to be injected has been reduced by 50%.  As medical readers will realise that is quite remarkable.  It was all done with antioxidants of one kind or another (alpha lipoic acid, broccoli powder and cocoa flavanols) and without side effects.
Numerous natural substances reduce cholesterol or lower blood pressure and it is very easy to measure the results and see if they really work for you; cinnamon, beetroot juice, tangeretin, the list goes on.  
One problem is that even individual compounds often have multiple medical effects and natural substances can contain 20-30 or more different compounds, so it is impossible to say with certainty why broccoli improves insulin sensitivity.
Naturally occurring compounds cannot be patented and so nobody has a financial interest to do rigorous and costly clinical trials to conclusively show beneficial effect.  Why would pharmaceutical companies want to reduce the demand for their insulin by 50%?  They are apparently not so keen on repurposing cheap existing drugs to treat autism, and neither are some researchers.






54 comments:

  1. Yah the details really matter when you are trying to make objective sense of an intervention. You also need to read the actual papers and not just the abstracts (as many people do because they don't know how to get access to pay-walled research papers or else they don't want to), because the methods can be very important. For one, if it is an animal study, how is a particular compound being tested administered? If it is injected directly in the site of interest and has positive results, you really can't say "this compound will help XYZ disease or disorder" because it is likely only preliminary research intended to see if the compound does anything good (or bad). The next steps would be to see if the compound can be administered orally or at least with a general injection, rather than a localized one (such as in the brain). This does not mean that XYZ compound can't have an effect on a human (good or bad) through oral administration, rather it is just not known at the time. Now of course all the hoops from animal research to humans are very expensive and take a lot of time and very often promising research ends because the researchers can't get grant money, the team gets split up by moving around from university to university, etc. And drug companies are not going to make risky bets for the good of human kind either.

    All of this of course is extremely frustrating to many parents with autism considering only 300 million dollars was spent from public and private sources for research last year for a condition that affects millions of people in the United States and also happens to be a fraction of what is spent on diseases that affect old people in their last years of life (where a huge chunk of health care spending goes in the United States).

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  2. The best us parents can do here is hope that we can piggyback ideas off of the research into better-funded diseases and disorders that have similarities with autism that makes sense in exploring and that means having an open-mind. With respect to curcumin, a lot of people don't realize that turmeric from which curcumin is derived from, has many other compounds with interesting biological properties such as tumerone:

    https://www.sciencedaily.com/releases/2017/01/170118145047.htm

    Many people around the world swear by turmeric's health properties so perhaps this is a situation like with broccoli sprout extract and myrosinase where useful digestion of a compound depends on the constituent parts of the original plant. I personally am on the fence on curcumin/turmeric (even if I thought there was a specific good reason to supplement it), but I also don't feel strongly enough about the scientific evidence against it to tell people they are really naive to use it themselves (at least for autism) because they might be right and I might be wrong even though neither they nor I understand why curcumin/turmeric is beneficial or not.

    Unfortunately, for us parents the suggested interventions you are told from the get go are early intervention therapy, more early intervention therapy, and more early intervention therapy. But when you actually read the studies that support some of the most popular ABA type therapies, they have some very big problems associated with them when the handful of critical researchers look at the results over the long-term and with the severity of the research subject. This I feel is an even bigger problem than the cottage industry of parents trialing supplements/drugs that both have literally zero scientific evidence behind them and scientific evidence that they are useless or even harmful. In fact, just this week a study came out suggesting a gluten free diet (which is usually high in rice products) pretty much doubles the mercury and lead exposure of people that adhere to it, due to how well rice extracts heavy metals out of the soil. I bet the GFCF discussion boards are having a field day in light of that evidence.

    And since everything is a gray area with respect to autism, this makes the criticism from other family members, friends even more disheartening when they only think in absolutes and will only respect the opinion of medical authority figures, even when the extent of knowledge concerning autism from those medical authority figures is limited to a few chapters in a book they read in medical school sometimes decades ago, is taken more seriously than a parent who has dutifully educated themselves to the best of their ability to help out their struggling child. On top of that, it can also be frustrating when parents of children with rare diseases who do the exact same thing we are doing are held out in the media as heroes, while parents of children with autism are portrayed as a band of Jenny McCarthy worshipping crazies.

    This is why a lot of parents of children with autism don't tend to talk too openly about these issues (including myself) because other people don't understand there are no good answers at the moment for a neurological disorder that is poorly funded relative to other disorders and where many of those funds are arguably not spent wisely. In the meantime, we need to support researchers who are serious and need funding (for those of us who can help directly) and we need to support each other as well and be mindful not to criticize any parent making a comment who just got a recent diagnosis from their child and has been told by pretty much everyone around them a bunch of erroneous information concerning autism and that if they just pound a square peg into a round hole enough times, that their child will turn out OK, because we have all been down that road and we all know there is much everyone in our situation just has to learn the hard way to best help our child.

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  3. On another note, some very positive research (Alzheimer's though) that I believe relates to autism and should give us some new ideas for interventions just came out that showed a novel method of LTP (long-term potentiation, i.e. synaptic strengthening involved in learning) involving kainate receptors (classically LTP is thought to involve just the NMDA receptor):

    Press Release:

    https://www.sciencedaily.com/releases/2017/02/170213131454.htm

    Paper:

    http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.4505.html

    Of course, NMDA receptors are expressed not just on excitatory pyramidal neurons, but also inhibitory interneurons making NMDA antagonism a tricky subject in disorders with a perturbed excitatory/inhibitory balance such as autism where LTP seems to be elevated most of the time.

    So perhaps drugs or other interventions that selectively target kainate receptors via either agonism or antagonism might be therapeutic possibilities for autism.

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  4. And here is another great piece of research related to drug addiction that has direct applicability to autism (in my opinion):

    Press Relese:

    https://www.sciencedaily.com/releases/2017/02/170213131201.htm

    Paper:

    http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.4505.html

    Why this research is relevant to autism is that the research suggests an alternative explanation to one of the many theories of why various nuclei of the amygdala seems to be hyperactive and dysfunctional. This research suggests that an excess release of corticotropin-releasing factor overwhelms the stress constraining effects of endocannabinoids, leading to chronic stress and the kind of awful anxiety and aggressive behaviors of some people with autism. I even think Peter discussed CRH a bit in a previous blog post (I could be mistaken). So according to these researchers, rather than trying to treat stress with cannabinoid type interventions, it might be better to antagonize CRH receptors (my reading of it all at least).

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  5. Tyler, I couldn't agree more. And speaking of the early intervention/ABA therapies, doled out and paid for even in my very conservative state, as if it is the only way - why isn't this therapy scrutinized more? is anyone considering the harm it can do ? Most of these providers have no understanding or unwillingness to learn sensory issues let alone how, say, histamines could affect behavior for example. In spite of a parent's best attempt at educating them. I think this needs to be taken more seriously - these early intervention recommendations needs to be more deliberate and everyone needs to consider emotional health and how much that affects underlying health issues. I think there are many kids who received the wrong therapies and experienced trauma from it and that makes there "autism/health" worse. Why is this not being talked about? Why do these people get a free pass?

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  6. Tyler,This is exactly why you need to find a doctor willing to perform as many tests as possible on your child,until you get a medical diagnosis beyond autism.There are often underlying metabolic,immunological,and genetic disorders that can be found and treated.But I have found too many parents are unwilling to put the time,effort,and expense to do this,they simply say my kid's autistic,and accept it at that.I guess it takes a special type of self-motivation to look for answers beyond autism.

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    1. Well in my personal case, our family has had our entire genome screened now (Simons SPARK) and the only doctor I know of in our area (word of mouth) that does anything in the realm of what DAN's do (which I am very skeptical of to begin with) pretty much believes a GFCF diet cures half of all autism cases even though several very robust studies have shown that a GFCF diet does nothing to address core autism symptoms. This is second hand information on the doctor, but I was told she won't take patients unless the parents agree to a strict elimination diet which includes GFCF (and these diets have for the most part been debunked in the last 5 years yet many doctors stick to them).

      Also, I still have to bug the SPARK people to see if they can give us a copy of our own DNA code back since it has been several months now since they got all of our samples and presumably processed them (or maybe they are still being processed). If anything "popped up" then they claim they are supposed to let us know, but I have not heard anything back from them. If I can't get that data from them (I don't see why not) then obviously spending a grand for a full sequencing would be what I would have to do next and then start hunting through the genetics myself for answers as you pretty much have to be rich in the United States to afford the advice of a geneticist, and the rest of my extended family does not really take autism seriously. If someone in the family got cancer everyone would be jumping through hoops, wearing ribbons, and helping out any way they can, but with our extended family and autism all you hear are crickets.

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    2. As far as the other stuff you talk about, I believe I now know what the biggest risk factors were with respect to autism in my child (exactly what process entails those risk factors to manifest into autism is still a big matter of scientific debate and ongoing research). That does not mean something syndromic (like in your autism misdiagnosis that turned out to be a specific genetic abnormality) is not going on in my child, but his problems were likely the result of environmental insults in the womb due to risk factors with strong evidence behind them now which I am not at liberty to discuss here openly. Unless, I can build a time machine the only thing I can do now besides just give up on my child is to do my best to address his specific deficits, unless someone else out there finds a way to do it first.

      On another note, there is a research group now that claims they can diagnose autism with 80% accuracy in infants with older siblings who already have an autism diagnosis:

      https://www.sciencedaily.com/releases/2017/02/170215130707.htm

      80% is an amazing statistic as many children are probably overdiagnosed these days when in the past when there was less awareness many children went underdiagnosed.

      In fact, with respect to the findings of this study, my son one of his risk factors was that he had a very large head (99th percentile) as a toddler and was doing fine until shortly before the age of 2 when things went downhill pretty fast. He did take a long time to walk though (14 months), so maybe my wife and I just had rose-colored glasses on the whole time, but he could do his ABC's shortly before his second birthday and then the all too familiar downhill slope of extreme hyperactivity, strange and dangerous behaviors, and of course losing all his speech for a while ensued. Nevertheless, we are now seeing some real progress after I have had the opportunity to wrap my head around these problems after having learned the hard way that the advice I had been given by so-called "professionals" was so bad that I should of been able to sue them if we were talking about a medical condition the rest of society actually cared about. Pretty much putting the rest of my life on hold to deal with these problems is not fun and I wish that you I could just go to a doctor who actually had answers, but I am afraid we are not quite there yet.

      Last but not least, I did trial high dose folinic acid after the latest Dr. Frye paper and it didn't really do anything after a couple of weeks. However, I still do regular dose folinic acid everyday, but for whatever reason I don't think my son has as much of the oxidative stress issues as he had earlier in his life as it is likely other oxidative stress/inflammation interventions such as NAC, Nicotanimide Riboside, and the B-12/Folinic/P5P/TMG stack not to mention Biogaia Gastrus I think has helped a lot on that front.

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    3. Hi Roger,

      Would you mind sharing the name of the genetic specialist that you are going to be seeing soon?

      Many thanks.

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    4. Tyler, I agree with most of your comments and your insights are very helpful.
      But I do have to disagree on GFCF.
      1st of all, no I do not believe my child is less autistic because of the diet, but he is healthier in a visible way (no diarrheas, no extended belly, no digestion issues) and for this reason I did get a prescription for milk and gluten free diet from our Pediatric Dr. so daycare was obliged to comply.

      On the behaviour side of things, the diet means he is not running around the house screaming and laughing hysterically, but running around now and then laughing when having fun and no screaming, as it is to be expected from a 5yo full of energy. His nickname by aids at school is Zen (no sarcasm). Now the only times his behaviour deteriorates into this kind of frenzy are when he is sick.

      I never believed the diet talk, but I have the results in front of me. I would be willing to participate on research to answer the why its relevant to us, believe me, but as you say, no one cares.

      I do agree it’s not the solution for everybody. Most research do not separate symptoms or phenotypes so it’s hard to know who responds and who doesn't and results end up mixed or not relevant, and I remember only one research done in a more serious way about the subject (I think it was even a clinical trial), but unfortunately they excluded from it kids with GI issues, which are in my opinion probably the most likely to benefit. Not surprising then that their result was not stellar.

      Regarding nutrition, removing gluten seems hard for European/occidental culture, but other cuisines do not rely so heavily on gluten sources (or milk). I just replace wheat (and other gluten grains) for corn, cassava, quinoa, beans, potatoes, rice, coconut… whatever works best and is available. To say it’s a restriction diet is technically correct but doesn’t make it justice, because variation is plenty available if one cares to look for it. In the end I believed my kids are better nourished then most of their peers. But the cost is some extra work for me.

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    5. Hi Jane,

      My son, now 5, before the age of two used to wake up three times a night for his milk. I had breast fed him till one but it was as if he was never satiated so had to supplement with formula, even early on. Later, it was just warming up milk at nights and bottle feeding, then shifting to glass. But suddenly around two and a half he stopped needing mlk so much and then just stopped and this was the beginning of his,sleeping through the night. I do not know if it was caesin that was,causing the problem or because of his autism, he woke up frequently and drinking milk created some kind of security blanket for him to fall asleep again. And as he matured, he did not need it anymore.

      I wanted to know from you if digestive enzymes with dpp lV are a good option to test whether a gfcf diet will work for ones kid. Some suggest that if followed rigourously enough, adding enzymes to every meal or even after licking envelopes, one could fake a gfcf diet. Conclusions from research are mixed. Enzymes seem easier to me than the diet at least for trialling purpose.

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    6. About the diagnostic, I would like to see something like this one, done early on. After all the conditions detected with the neonatal heel prick test for exemple are way less prevalent then ASD, but the testing is universal almost everywhere.

      High-throughput screen detects calcium signaling dysfunction in typical sporadic autism spectrum disorder.
      https://www.ncbi.nlm.nih.gov/pubmed/28145469

      They do have to replicate with larger population though, but it seems promising. I think signaling differences would be detectable before the changes detectable by the MRI scans.

      I prefer not to comment on tiny little babies getting ABA though... I do hope this is the authors being politically savvy to get published...

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    7. Kritika, I'm not sure about the enzymes. I do have them, but I use mostly when I know I won't be able to control his food intake as usual, like birthday parties or events at school.
      My impression is it does help to a level, but not 100%. As digestion starts at mastication, and I'm not sure how much of this is digestion problems and how much some kind of light/hidden allergy to certain foods I'm not sure how far enzymes can really help.
      Maybe enzyme + antihistamine would work as well as restriction??? (Just an idea… I really don’t know how best to replace a real trial…)
      We did 4 weeks diet, than 1 week challenge with gluten back (for milk as I am lactose intolerant it was not such a weird guess to assume he was too). It was a little hard in the beginning because I was not so used with substitutions and not everything I tried to offer he liked. The good thing is, when he lost it during the challenge week (so hard to witness after a month of steady improvements), no one questioned that the diet was good for him. I got the prescriptions to make it official and his day care was wholeheartedly into it.
      I would say it took about 1 week to see benefits… 3 total to get it steady. But deterioration in the challenge week was fast and by day 2 the evidence was clear to me, but we kept on 1 entire week, to make sure it was not just a bad couple of days and to follow dr. orders to the letter as blood samples would be collected.

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    8. Jane, well I don't see the GFCF controversies going away anytime soon, just as is the case with vaccines and autism. There have now been several large studies of GFCF diets with regards to autism and so far they show no significant effect. Of course, one possibility as it relates to autism being a complex neurological disorder is that GFCF diets help significantly with some people with autism and actually hurt others with autism so that when you look at these large studies, these details get lost in the noise. I would hope that the epidemiologists that usually do these studies would cover this topic, but I have not seen it personally so far so maybe this has been overlooked. A study this week on a gluten (not casein) free diet showed that on average people following this diet got almost double the mercury exposure of controls and significantly higher heavy metal exposure from some other metals due to the reliance on rice in a gluten free diet (of course a gluten free rice free diet would solve this problem).

      But if you employed a GFCF diet and it worked for your son, and it works consistently (and I assume you have had situations where your child got a hold of some gluten bread or ice cream) and then they had a nasty reaction to those foods) then in spite of the current scientific evidence against a GFCF diet, there could be something else going on that results in your child avoiding those foods even if it is not the gluten and casein causing the problem. Or there is something wrong or missing in the methods used in the current research on the GFCF diet. Also, I just wanted to be clear I am not trying to insult your intelligence here because you probably know way more about the GFCF diet than I do as you have used it successfully, but I just wanted to point out my reasoning here especially on a subject I have found to be about as inflammatory as discussing politics with anybody here in the United States regardless of your positions.

      I would also like to point out, I think the original reasoning for the GFCF diet are sound (dysfunction of the opioid and immune system which are very much interrelated), just I don't believe the rest of the GFCF hypothesis is sound in that gluten and casein and a leaky intestinal epithelium are the culprits here.

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    9. Tyler, I get your point.

      And I also know I have no hope of convincing anyone by pointing to some research, because there is so much conflicting information and opinions.

      But it is an instance where as parents we can give a try and see for ourselves. There is no harm in trying to figure out hidden food intolerances and allergies, and the so called gold standard for this is elimination of a certain food from the diet and then do a challenge, as lab tests quite frequently present false positive/negative results.

      Knowing a little bit more about nutrition and being mindful of what we feed our families is to be expected, and should even be commended as nowadays so many just don't care.

      About the contamination on rice flour. Thank you for bringing it to my attention, its something to keep in mind, even if the research was not very conclusive.
      I wonder why they are considering GF diet (and rice flour) as risks but do not mention high rice consumption in itself or where it was produced?

      But as I said, our diet is varied and do not rely heavily on rice (and now will even less).
      Rice flour is one of the cheapest though, so its very common in industrialized GF food, but I use very few of those because even if they are GF, they are also free of pretty much everything else aside from calories.

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    10. Jane, thanks for sharing your experience. I was looking for short cuts...seems there are none when it comes to treating autism. I had put my son on a rigourous gfcf diet for a period of ten days shortly following his diagnosis at 2.8 years. Those were the longest ten days of my life but I guess too short a period when it comes to drawing definite conclusions. I did not notice anything but it is recommended that one trials the diet for at least three months.

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    11. Yes I agree Jane. We can all opine about our own hypotheses concerning what should work and what doesn't, but sometimes it is a question of throwing stuff at a wall enough times and seeing what sticks for our children.

      If the GFCF diet works for your son, nobody should be telling you that it doesn't because some study suggested it is no better than placebo (which was not my intent). Until there is a proven model that first defines what autism actually is biologically and what genes or environmental insults actually cause autism with a roadmap for how to treat it, then your guess is obviously as good as mine. We are all here just looking for ideas on what might work and help our kids since there is still no consensus among doctors as to how to treat autism (and may never be) and we can't all wait around literally for decades until a silver bullet is found.

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    12. Tyler, Jane, Kritika,

      When my daughter was very young, she would walk on tiptoes and eat only white, mushy, completely bland food, mostly made up of milk and porridge with mashed vegetables. This was before her diagnosis. My sister in law read a handout at my nephew's preschool about the GFCF diet, misinterpreted it as eliminating only dairy and told me about it. I decided to try it and took away all dairy cold turkey. The very next day my daughter stopped walking on tiptoes and ate toast and jam for breakfast. Six months later, after her diagnosis, we tried the GFCF diet proper and saw nothing.

      It might be worth separating the GF and the CF into two separate diets.

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    13. RG,

      This is what i did. Removal of caesin should show quick improvements if a child has issues with it...in my case going cold turkey on dairy did not result in any further improvement over and above the resolved sleep issues after just greatly reducing the overall amounts he was cobsuming earlier, that too self inititated. That is why I suspected its not caesin that caused lack of sleep but lack of sleep caused a dependance on milk in my sons case. Who knows? I then tried removing gluten but it was tough and I could not carry out for long.

      I do feel that kids with serious digetive issues should give restrictive diets a try. Food allergies are different from the rationale behind gfcf diet, though.
      But if something works, whatever the mechanism at play, we should not dismiss it just because of lack of a better explanation why it works..rather count your stars. My night sky is too cloudy...

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    14. Well another thing to consider with dairy (which primarily means milk to most people), is that milk, especially skim milk, is good at spiking insulin in a lot of people because it has adequate amounts of sugar in the form of lactose, as well as protein (which also stimulates insulin). My son also sometimes goes crazy over tomato pasta sauce and I thought it must be the tomatoes at first, but later on I realized how most store bought tomato pasta sauce is super high in sugar usually. There is this super sweet pizza (must have tons of sugar in the dough and sauce) his grandma sometimes gets from a local pizzeria that seems to make him go nuts while the pizza I have made him from scratch has no such effect, even though it has plenty of unsweetened tomato sauce.

      The thing that bothers me sometimes about gluten this and casein that is that you can be straight gluten and you can more or less get straight casein (cottage cheese) to see if it is indeed the gluten or the casein or both that cause problems. If your kid does not show negative symptoms to either, then you know pretty much right then and there that any success from a GFCF diet must be attributed to something else that has been eliminated, or else added since you literally have to completely change your diet around and add new foods in order to strictly follow a GFCF diet and still get a good balance of vitamins and minerals.

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    15. Thank you all.
      I understand its sketchy and I wish I had better answers to provide. But all I can do is provide my own testimony. I believe it can be relevant to others as it was for us, so I had to mention it.

      For whatever its worth, I would like to add that my kid did had moderate to severe chronic GI issues after a severe gastroenteritis at 18 months of age. This improved a lot under the diet.

      I think its relevant to mention that as a natural consequence of the diet, we also reduced considerably our consumption of industrialized foods (as fillers and process adjuvants commonly contain gluten).

      For him, to ingest milk/milk products seems to cause less severe digestive problems for 2 days. Gluten causes behavioural, motor and GI problems that take about a week to wear off and are very disruptive. Both together are worse then any of them by itself (the drunk/high effect is very clear in this situation).

      I haven't tried a 1 week challenge for milk as I did for gluten as I see no point on going through this process now.

      IgE blood tests regarding gluten were "inconclusive".

      I'm not sure if what we see here is about the rationale on opioids and undigested proteins or something more on the lines of inflammatory/immune condition like IBS / Chron's or even if both are exactly unrelated.

      Just to be clear, despite the effect on motricity, GI, behaviour and overall health, we saw no changes regarding communication and language impairments with the diet specifically.

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    16. Jane, the whole hypothesis for the GFCF diet is that the idea was that due to intestinal permeability (from other factors) these proteins would get into the blood stream and act as opioid-like drugs once they got into the brain. The connection was that many of the symptoms of autism are similar to people who are long-term users and addicts to opioids (which I agree with). Also, some of the most commonly cited areas of the brain that seem disturbed in autism (amygdala, nucleus accumbens) are rich in opioid receptors.

      So in effect the idea is if you stop giving your kid food heroin (in the form of gluten and casein), then just like a drug addict abstaining from heroin or oxycodone, their symptoms will improve over time.

      So while I believe there is clear evidence the opioid system in the body and brain is disturbed significantly in most cases of autism, I think the problems are with endogenous opioid production (endogenous morphine, i.e. endorphins), not because of exogenous opioids in the form of gluten and casein.

      Just my opinion. Doesn't mean I am right or wrong, but that is just my understanding here.

      With regards to Chrohn's disease, there are plenty of people who have severe intestinal problems (including Chrohn's) but they don't have autism, as well as it seems like things start going wrong most of the time in the womb, long before the baby has had its first meal. This does not mean that all autisms develop this way, just that is what the current evidence (which is always subject to change) suggests which means there is a nexus of problems stemming from the baby's own development (genetics and epigenetics from mom and dad) and the uterine environment (inflammation, serotonin and SSRI's, drugs like valproate, etc.).

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  7. Tyler, yesterday I bought Niagen Hpn, 2 bottles, 120 caps, 125 mg at US60 both.
    Valentina

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    1. Yes that is what you want. The recommended dose for an adult is 2 a day, but if all you want to do is the minimum (since it is expensive), just do one capsule a day to keep NAD+ levels at a healthy amount in the brain when blocking tryptophan/L-kynurenine into the brain via BCAA's. More than 2 a day is probably a waste.

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    2. Tyler, gfcf didn´t work for my son,one start to eliminate rice, potatoes,sugar, milk, etc, etc,in a way that when you want to wake up, your soon is in a poor health state and you became paranoid. I used to think that all was yeast and food issues. Not anymore, wish would have gone this route earlier.
      Valentina

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    3. Well, I do know sugar (birthday cake and ice cream especially) will cause my son to go manic. The best guess I ever came up with for this is that lots of sugar dumped into the blood stream will cause insulin levels to spike. Insulin will also drive BCAA's from the blood and into the muscles which makes it less competitive for aromatic amino acids (tryptophan, tyrosine, phenylalanine) to make their way into the brain. This is one reason (of many) it is thought that sugar can be addictive because it causes the brain to be flooded with serotonin (via tryptophan) and dopamine (via tyrosine/phenylalanine) which seems to be associated with improved mood and pleasure. Also, L-Kynurenine enters the brain in increased amounts from insulin causing BCAA's to be dumped into the muscles which if the brain is in an inflammatory state (activated microglia), I believe can cause excess quinolinic acid to be produced which causes secondary issues of excitotoxicity of NMDA receptors.

      Of course protein (and in particular L-Leucine in BCAA's) as well as any carbs will cause a rise in insulin, but the muscles can only uptake so many BCAA's from the blood at once so that is why supplementing it directly in free form can help block L-Kynurenine and aromatic amino acids from getting past the blood brain barrier.

      So I may have not mentioned this, but in addition to BCAA's it is probably advisable not to have massive insulin spikes via high glycemic carbs, especially if you have not supplemented BCAA's a half hour to an hour before a meal that will spike insulin (this is why the timing of taking BCAA's pre-meal is important).

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    4. Ok Tyler, sugar is the only thing that I don´t negotiate, at home there is no sugar, only stevia. He almost never eats icecream and he doesn´t like cakes. He returned to drink milk after a year, i give it with bitter cocoa and stevia. Gymnema is excellent to destroy sugar between other excellent things. With respect to the risk that my son develops epilepsy, it is unlikely as he has been taking valproate since he was 3. Now he is almost 11. But, his subcortical epileptiform electrical acitivity is in the frontotemporal region,a very dangerous one, could be prone to degeneration.
      Valentina

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    5. Hi Valentina,

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

      "The fenamate NSAID, mefenamic acid (MFA) prevents convulsions and protects rats from seizure-induced forebrain damage"

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  8. Hello Peter,

    My son is,down with moderate high fever, a bad viral/bacterial with deep chesty cough, sore throat and nose full of stuff and I am elated. A round of consultation with the homeopath and he
    was presvribed a remedy which I found is given for oral sensory issues as well as issues with physical and mental lerhargy folowing various illness including streptococcal infections. Two days into the remedy, he was waking up with a smile like before, chewing and biting and oral senstvities just gone. He was also acutely aware and expressive but something else was cooking..an acute infection. So now its a round of amoxicilin for five days. I do not know whether it was coincidence or homeopathy just brought out a suppressed illness..antibodies slowly accumulating in my sons body creating toxicity. Whatever..my son is at at his cognitive best...clear, covering up his mischief on spotting me, acute auditory awareness.

    It would be really useful if therapists, doctors and teachers get a little more invol ed with the kids they care for and fine tune their antennae for distress signals which they sweep away as autistic behaviours. Behaviours are complex but do not materialise out of thin air...they have a basis in the human body and its unique biochemistry which shifts as uniquely under different stressors.

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  9. RG
    I am going to see Dimitry Niyazov in New Orleans.Here is an overview of his work.
    https://www.ochsner.org/doctors/dmitriy-niyazov

    Here he is speaking at AutismOne last year.
    https://www.youtube.com/watch?v=bjuV8efK46o

    What I was told was that Dr. Niyazov does not just see anybody with autism,adult or child.He is very restrictive of who he sees.I was told in order to see him,you have to have a proven genetic diagnosis in addition to autism.I have seen Rossignol and Frye,which is how I got a WES in the first place.

    Tyler,
    Does your son have folate receptor autoantibodies?I know high dose folinic acid is given to children with autism on a trial basis,without testing for the autoantibodies.I had very high autoantibodies,both blocking and binding.I also have Severe MTHFR Defciency,pernicious/megaloblastic anemia,and many other lifelong medical issues.I have a unique disease in the Ataxia-Telangiectasia/Nijmegen Breakage family of diseases.I have been on folinic acid since 2009,it took me about 3 1/2 years to reverse my autism,but I am still very sick and disabled.It was about six weeks into treatment,that I saw my first improvements.My autism was verbal,but otherwise low functioning.

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    1. Hi Roger,

      Thank you very much for the information. I thought Dr. Frye and Dr. Rossignol tested you specifically for the folate receptor antibodies? I wanted to see if my daughter could be tested per the Treatable ID people in Vancouver in a more comprehensive manner. Unfortunately, I have not heard back from them. Do you know of anybody else who might do a similar screening?

      Many thanks.

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    2. I was going to order the test that Peter linked to a few months back but have not gotten around to it. Probably worth a shot even though my gut suggests his problems are more along the lines of complications from mild macrocephaly and the sensory hypersensitivity issues associated with it (especially in the visual cortex). Do you have macrocephaly or do you know if folate receptor autoantibodies are associated with macrocephaly (I don't know, but was wondering if you had any idea yourself)?

      Also, one of the first interventions I employed and still employ (now more for just glutathione support) is methyl-B12, Folinic Acid, P5P (B6), and TMG (Betaine). I have not seen any overt behavior changes from this treatment, but this intervention was never for those purposes specifically. I have never employed super high doses of any of those vitamins except briefly for folinic acid when I determined it was safe. There was no noticeable improvement though this was a brief period of time as crushing the 800mcg caplets was very time consuming and expensive relative to the high dose caplet you get via prescription (25mg).

      Other than autism, my son is healthy as an ox, but he only speaks in 3-4 word sentences now so if something is bothering him, he can't really express it very well yet other than to cry or jump in his bed under the covers.

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    3. RG, last year, I contacted the Vancouver clinic via email and phone calls many times, and never a response. The clinic nurse's line only goes to voice mail. I plead my case to any living human who answered their phones to at least give me some response, to no avail. Incredibly frustrating. I have considered just studying their testing and seeing which ones might sound more like how my son presents and asking my pediatrican to order. Just not sure how useful this would be, if interpretation is a big part. Very frustrating for them to dangle this carrot via news stories etc., and not even respond to queries. So instead just focusing on what seems to be my son's biggest health issues which is mast cell/histamine/allergy. If you hear anything from them, please share.

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    4. Tanya, they do respond to doctors. So it might be worth asking your pediatrician to send an email for you. They offer whole genome sequencing "for research purposes", which should be the best test. I think they do not want to talk to regular parents.

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    5. Peter they they should put that on the answer machine we only deal with medical practioners !,,instead of ignoring the request from desparate parents sick of the way we parents are treated it shouldn't take Peter having to do all this .

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    6. Thanks Peter! My doctor is quite supportive, so his office would be willing to make the call.

      Tanya, do you think your doctor would do this as well? I'll definitely keep you posted on happenings.

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    7. Tyler, my daughter also used to be very strong, energetic and healthy when she was your son's age. Since you are of a proactive bent, I want to mention that we have added a variety of issues including epilepsy, GI difficulties, mast cell activation, hypothyroidism, adrenal issues etc. So I highly recommend that you do everything you can right now to ensure that the healthy status quo continues.

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    8. A lot of what you describe sounds like what happens in aging and mitochondrial issues are one of the leading candidates now for being what drives lots of other aging symptoms, even though the treatment for those symptoms often involves replacing hormones or expensive drugs that dampen down inflammation of one sort or another.

      The other thing these symptoms sound like is hypothalamus dysfunction which can be involved in all of those factors you listed which can be for many different reasons as well, including a tumor.

      I know that a large head and an autism diagnosis dramatically increases the risks of comorbid epilepsy. What can be done to prevent this from happening when puberty ensues (when most epilepsies begin) is a tough call, though everything I have read suggests the best thing you can do is to treat the child as if they already have epilepsy because once epilepsy starts, it generally increases in frequency and if bad enough sometimes the only options to keep your child alive involve brain surgery. Nobody wants that to happen of course. Not me, not you, but nobody.

      There are various supplements that can treat mitochondrial health, but one of the most important factors is to not have the body in an anabolic state 24/7 for a bunch of reasons I have probably stated over and over again here in the comments. This means no calories after early evening, and even exploring intermittent fasting as if your child has a PTEN mutation then mTOR will be hyperactive (mTOR drives anabolism). In fact, I sometimes suspect this might be part of my son's problem as I personally gain muscle ridiculously fast from athletic training even though I have no outward signs of high testosterone levels. If for whatever reason mTOR is upregulated in me, then it might be passed down to my son either is a direct PTEN mutation or just extra copies of genes that promote mTOR. I did 23andMe several years ago, but you won't get this kind of specific information from SNP's, so I am hoping maybe I will have some answers one way or another soon which should help because most of the interventions I have employed have been based on educated guesses as they relate to his symptoms and physical characteristics and the mountains of scientific papers I have read since his diagnosis. Usually, you can't attribute autism to just one gene or one risk factor so for me I know what a lot of the possibilities could be so at this point I am not looking for more possibilities, rather I am trying to rule out as many possibilities as possible to get a better idea of where to focus my efforts on helping him (at least when it comes to interventions involving something going in his body).

      Nonetheless, thank you for your recommendation.

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    9. Hi Tyler,

      My daughter has been on IF for about two years now. 16 to 18 hours. It helped stabilize her weight but other than that I have seen nothing. We only keep it on because she prefers to eat this way. In the last few months, she has also considerably reduced the amount of food she eats though her weight continues to be the same.

      Thank you for helping me see things in a new light. I have always chosen interventions aimed at treating epilepsy or to increase cognition and functionality.

      Since the addition of low dose clonazepam and Diamox, her mitochondrial dysfunction is much improved. Maybe I should be doing more. Do you have any recommendations for other areas/interventions I should be looking at?

      Many thanks.

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    10. Hi RG, Tanya - I have a contact for Vancouver if you want to try to get into the MSSNG study which is whole exome sequencing, I am not sure if they are still recruiting but we were able to get in in december and had our blood draw at children's, were told results could take up to a year. Also you can get the FRAT antibody test done your paediatrician can sign of on it. If you want more info email me at nieszka_m@hotmail.com, A

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    11. RG, the thing with mitochondrial disease of which could be the root cause of several types of neurodegenerative disease (there is obviously no clear consensus here) is you should not simply rank an intervention just by if it "makes things better", rather you have to also look at "has anything gotten worse". In Alzheimer's there are some drugs that can improve cognition a little bit, but really the goal once Alzheimer's is diagnosed is to slow the disease as much as possible. I know this is hard for us as parents because we are hopeful that the myriad of problems with autism can be reversed and maybe someday those types of therapies will exist in a predictable form, but the IF might at least be helping her. In the last week alone, a very important paper (in my opinion) came out that showed why caloric restriction improves health and the conclusion was that the lack of anabolic activity gives the ribosomes (protein factories in cells that transform RNA to DNA) a chance to rest and repair themselves. When the body is in an anabolic state all the time, these ribosomes get worn out and start producing dysfunctional proteins which in the case of Alzheimer's and Parkinson's disease are the most widely studied vectors of those diseases.

      I don't know what country you are from (I am American), but Americans literally on average have a feeding window of 19 hours a day which for my personal lifestyle seems hard to believe, but considering how many people live to eat rather than eat to live in this country, it is not too surprising. Human beings are not elephants who are designed to literally do nothing but eat tons of plants 20 hours out of the day, and yet we have the eating patterns of elephants nowadays and who knows how many health and disease problems now can be attributed to not just how much Americans eat, but how often they eat. Autism is now strongly linked to obesity and gestational diabetes and I suspect America's hedonistic obsession with equating food with happiness is a large part in the recent surge in autism rates over the last 30 years. And amazingly obesity rates are finally leveling off in this country and autism rates are as well. Of course correlation does not mean causation as well as the fact there are plenty of children with autism born to skinny kale obsessed mothers, but it is hard to argue that the American way of life these days resembles anything that is natural when compared to how human beings have lived for the last several hundred thousand years.

      All of that being said, as far as mitochondrial stuff I have my own opinions on that matter which I am sure a lot of people would disagree with. The top 3 supplements off the top of my head for mitochondrial support (which dare I say are controversial) would be:

      (1) Nicotanimide Riboside
      (2) Methylene Blue
      (3) C60 Oil

      The last two are a lot more controversial than the first. If you want to talk about general cellular health, keeping chromatin packed tightly to prevent jumping genes (transposons) from mutating things too much, as well as a whole host of other topics related to cellular health, I have my own opinions on those as well that you would probably not find too many doctors, if any, who would agree with me on most of them because there are not many human studies on stuff in this area as doing long-term human studies (or even studies on primates) are severely complicated by the long lifespan of human beings and the ethical guidelines in doing medical research on human beings who have no immediate medical conditions.

      Just wanted to be honest about all of that.

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    12. Tyler,

      I know I am putting forth a very loose query, but is there a protocol you think will benefit/prevent further damage in most idiopathic autisms. My son is healthy like yours, did not even have that early diarrhoea like ypurs, head size average and though heigt and weight in the nintieth percentile in his fourth year, his weight has just stabilized and he is now gaining height (I happen to be small but husband is tall, heavy boned). He is quite like your son, though probably better regulated behaviourally..and receptive. No stereotypy and even sensory issues have greatly improved. Hyperactivity is also a non issue now. Language and social skills...core autism traits are the ones I want to chip away bit by bit, if at all it is possible. Only yeaterday, he gestured to us to give him the loose currency lying on the fridge and verbalized 'buy'. So you see he is picking up certain things spontaneously but his autism makes it all disorganized, incoherent information. I feel the next two years will be really crucial and doing my best to help him acquire language...and the intent and will to use language. I am tired and also bored a little bit as I chased personal freedom throughout my life and things have come a full circle and probably life has a way of making you come face to face with that what you are trying to escape. So for me, freeing my son from as many restrictive issues as is possible, be it medical, psychological, emotional is the only redemption I hope for. This is what all parents do, those with different kids do it a little harder.

      What do you make if interventions like clonazepam...I think you had reservations? I do not want anything which can make things worse, short term or long term. Can medicines treat communication deficits? I have asked this many times before too but I ask you again...in absence of severe physically explicit issues, should I rather focus on Fern Sussman and Steven Gutstein and educational and experiential a activities. Time and energy is a precious commodity specially when you are doing most things singlehandedly. Please give your honest parent opinion.

      Before I end, I am sorry, but seseriously, where do you get these funny female images from...infertile alcohol guzzling worriers, irresponsible fat cows, skinny kale obsessed mothers.

      Regards

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    13. There are many different thoughts on language development and autism. The traditional view is that the brain just is not working properly at an early age and the window for language development passes and you have a non-verbal person for the rest of their life who won't be able to function normally in society. I think in the last ten years especially), the idea that the brain is not has hardwired as once believe is a new idea that has been getting more and more weight behind it over time.

      Based on gross size abnormalities in the brain, the caudate nucleus which is thought to be acutely involved in language and behavior is generally enlarged in autism. There is a recently discovered white matter pathway called the aslant tract which links the caudate nucleus to another very important part of the brain involved in planning behavior and planning language called the pre-supplementary motor behavior. This white matter tract is found to be weaker in autism, while white matter tracts in the primary motor cortex are denser and thicker which probably contributes to excessive neural noise that can cause motor output from walking to speech movements of the mouth to be uncoordinated.

      So as best I know there is nothing receptor special about the pre-supplementary motor area, but it is a very important part of the cortex, relative to its size. The caudate nucleus on the other hand has glutmatergic inputs (such as mglur5 receptors that Peter has talked about with his Pureh tea post), with dopaminergic and GABAergic projections to other areas of the basal ganglia system. So targeting the caudate nucleus (input or output) can be done a variety of ways, but selectively is difficult. The brute force method of dealing with these problems are drugs like risperidone which are broad spectrum dopaminergic antagonists. Personally, I think mglur5 receptor drugs (none of which are being developed for autism, but are being developed for other disorders) show much more promise in addressing the "behavior" and probably language impairments in autism.

      One of the other major networks in autism that is perturbed and impairs learning is the so-called mirror learning system. Fortunately, the primary areas of the MNS are on the lateral cortex (inferior parietal lobule, pars opercularis AKA Broca's area) which means they could be targeted with Transcranial Magnetic Stimulation (TMS) or Trancranial Direct Current Stimulation (tDCS). There are research groups I believe actively working in this area, but even though these kind of therapies don't involve drugs, rTMS is not very accessible and tDCS though accessible (you can buy kits for not much money) has a lot of question marks on long-term safety as well as efficacy in some areas.

      Then there is the technology I have been working on for the better part of the last 3 or so years (I have lost track exactly how long) pretty much nonstop which can target any part of the brain and concurrently with any number of other parts of the brain which among many other possibilities has been pursued primarily to address autism.

      There are many other opinions I have on possible "autism treatments" that are independent of the run of the mill supplements/therapies you see pushed by DAN's and 99% of the autism blogs (aside from this one which is excellent), but that would take a very long time to explain them all and the reasoning behind them.

      In short, there are no easy answers.

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  10. Hello Tyler,

    First of all, I want to share with you that a few days back I shot out a polite but firm letter to his school reminding them that they better learn to bear with a little anxious behavior as kids on the spectrum have issues, especially during seasonal changes and ill health. And when I went to pick him up from school, the air had changed. I came to know that the principal had visited the class and met my son and a young teacher, all saccharine, whom I do not know came out of her way to meet me and give me tips on teaching him and inviting me to take whatever help anytime. I thanked her, all saccharine myself. I told you, your experience emboldened me and this is what I got. It's another thing that he fell very sick after that day and could not attend school. So now I have a medical testimonial too in support of my hunch which I will duly send to his school once he is in a condition to reattend. Our government is really protective of rights of all kids to education and in a regular school setting. And this particular school belongs to a group of educational institutions which provide advance degrees in autism related research. What a sham and what a shame! I think if we as parents stop being apologetic about our out kids and treat them as having an deficit borne out of a bodily illness, it will help tremendously in shifting attitudes. But when it comes to disorders arising in the deep dark recesses of the human brain, it is much easier said than done. Keep sharing your courageous encounters...you might be inspiring someone.

    Secondly, I would really appreciate if you could advise me if I could try niagen on my son... Seems to be safe, imparting some of the benefits of calorie restriction, including oxidative stress, neuro protection and mitochondrial dysfunction if any. The only issue seems to be with mythylation status... I do not know about my son. If I start out, what should I watch out for in terms of negative.

    Finally, unlike you, I wish the world would just shut up and out and let me hear the crickets again.

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    1. OK here is the really short description of Niagen (Nicotanimide Riboside) as best I can tell you.

      First off it is simply another form of Vitamin B3. The other forms of Vitamin B3 that are commonly consumed as "vitamins" are niacin and niacinimide. You can do pretty much do any high dose of niacin but it will cause flushing (which makes it useful for seeing if there are histamine sensitivities) while niacinimide has been shown to cause liver damage in high doses (people take niacinimide instead of niacinimide when they don't want the flushing). There is also inositol hexanicotinate which is sold as "No-Flush" Niacin and is popular among some people because it does not have the downsides of niacinimide's toxicity at large doses.

      So why is Nicotanimide Riboside special? Well, other forms of vitamin B3 are metabolized down a particular pathway that leads to an increase of NADH which is the reduced form of NAD+. NADH on its own is usually sufficient in creating NAD+ via the NAD salvage pathway which recylcles NADH to NAD+ via an enzyme called NAMPT. The other way NAD+ is produced is via the kynurenine pathway from tryptophan and once the NAD+ is used and converted into NADH, it is then recyled again back to NAD+. However, your cells will only and can only produce so much NAMPT so as you age or if your mitochondria are dysfunctional for other reasons, the ability of your cells to keep the NAD+/NADH ratio at a healthy level becomes compromised. Nicotanimide Riboside is not really produced much in the human body (it is highest in breast milk from my understanding) and its degradation into an alternative B3 processing pathway into NMN and then into NAD+ is evolutionarily conserved for some reason not known (yeast for example share this same pathway). So what this means is you can directly create more NAD+ rather than just increasing NADH. This is important for another reason as for some reason overall cell health signaling is tied to not just the amount of NAD+ and NADH in the cell, but the ratio as well. And if NADH is fully depleted or else if NAD+ can't be recycled fast enough from the available NADH, the cell initiates suicide via apoptosis.

      Personally, I think everyone over age 40 would benefit a lot from NR (I take it myself) even though it is expensive because diabetes and other diseases including Alzheimer's and Parkinson's have strong scientific evidence now suggesting that mitochondrial dysfunction is either the root cause or a major cause of these diseases even though accumulation of amyloid-beta or alpha-synuclein end up being what kills the cells at a later stage of the disease.

      But for autism, it might benefit some people who have compromised mitochondria that lead to some of the synaptic dysfunctions for similar reasons to what seems to happen in Alzheimer's and Parkinson's. In this sense, NR won't cure anything but it may help mitigate the consequences of some hiccups in the mitochondrion.

      I don't believe methylation status has any effect with Niagen, though I have read some people who suggest hypothetically that supplementing methyl donors (B12, TMG, Folic Acid, SAM-E) would improve things, especially with PARP activators like resveratrol as lots of NAD+ is used in DNA repair. I would be very, very, very surprised if your son had a negative reaction to Niagen. The only really negative thing about it is its high price (a couple years ago it was 50 dollars for a 1 month supply and now it is more like 35 dollars for a 1 month supply).

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    2. Thanks Tyler. I do appreciate your simplifying things to make the information non taxing for my brain.

      Regards

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  11. Peter, I am quite sure that my son belongs to the subtype of ASD with GABA dysfunction.
    This paradoxical effect of benzodiazepines, which even the slightest above the lowest dose of Clonazepam can make him much worse, could be the proof. Made a mistake and gave it with tea for a couple of days and must have built up. We stopped the tea and things got much better. Maybe caffeine also interacts with it.

    I read in the wrong planet blog about Aspergers who are on benzos and say how helpful they are and they are only concerned about developing tolerance. He cannot identify with them.

    My son detests smoking and alcohol. He says that he would never feel pleasure out of them. He uses two or three cigarettes a day for strictly medical reasons. If this keeps working he stays with it, otherwise he quits.

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  12. Tyler, Peter and others,
    My family also did the Simons SPARK study. I was told that we wouldn't receive any results unless something significant showed up and that could take as little as several months or as long as years. I wish we were able to get some information sooner!
    Speaking of testing, I would like to get feedback from the group as to the most useful testing you suggest.
    My son is 12 years old. Also what are your thoughts on 24 hour or 48 hour EEG's to detect abnormal brain activity? I have heard that seizure activity is common during puberty.
    Thank you for your opinions!
    -Christine

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    1. I think regular testing and imaging are important for our kids. Its unfortunate that its not done as a matter of course, and there is hardly a useful database.

      If you can, a multi day EEG is very good. It will certainly detect epileptiform activity if it occurs in the time frame. My daughter has epilepsy, but on a recent, 5 day EEG, nothing showed up. What they call a clean EEG. I was told that her EEG was normal. When I specifically asked if the normal was the same as that of a neurotypical person, I was told that it wasn't. That it was normal per autism and other neurologically affected population. That there is a mild slowing. I couldn't get anything more out of the neurologist. I am hoping to get a better read out of Dr. Mike Smith in Chicago.

      My takeaway from this is that there are some common aberrations that most of us are not aware of. If we did, we could treat better. In my daughter's case for instance, they stopped all her meds while we were there, and on one of the days she had a 'brain freeze' in the middle of lessons. I have never seen anything like this before. So I wonder if an EEG with all the meds including Diamox and verapamil would have given a different reading.

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  13. My son had an ambulatory 24 hour EEG done when he was 3 and it turned up negative for petite mal seizure activity. In your case since your son is older, it would probably be best if you did an overnight EEG with him rather than the ambulatory version because EEG readings for petite mal seizure detection I believe are suspect to begin with, so if you are going to try and use EEG readings to detect ictal activity, you want to make sure professionals are around to make sure the readings are as of high a quality as possible. Even then, it is sometimes too late to diagnose seizure activity before outward seizure symptoms with EEG because the quality of the EEG signal can be so bad in some setups.

    And yes grand mal seizures most often start popping up in puberty if they were not already around throughout adolescence.

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  14. Hi Peter, I put two nicotine patches on my son's spinal cord in the morning, as lots of times he says something, not fully understood, about a spinal cord discomfort and probably pain coming from there.
    I read that spinal cord injuries can give numbness and loss of sensation in your hands, fingers, feet and toes. Some people use nicotine patches for pain and inflammation and the dose should be about 16-25mg nicotine for adults.
    Since my son loses self esteem by smoking, we went back to e-cigarette and uses it whenever he feels stressed.
    In the evening he started talking about balance problems and his feet always in socks don't have the chance to get proper stimuli. He took of his socks and had a foot bath.
    I think he received a good feeling out of it.
    I should also have to mention that in schizoprenia trials findings there was a considerable improvement in sensory gaiting with nicotine treatment, much like autistic sensory overloads, leading to meltdowns and aggressive behaviours involving SIB.
    Next thing in mind is choline supplements and/or nicotinamide.
    If I give 350mg choline, would it be better than 250 mg choline/ 250 mg inositol?

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    1. Petra, those 3 substances nicotinamide, choline and inositol are quite different.

      The paper below suggests that too much nicotinamide in modern diet may contributing to schizophrenia and autism.

      Excess nicotinamide increases plasma serotonin and histamine levels
      http://www.actaps.com.cn/qikan/manage/wenzhang/2013-1-05.pdf

      Nicotinamide riboside is a new supplement sold as a NAD+ precursor. It is expensive.

      Choline is used by many people. It can help, makes things worse or do nothing. It is cheap.

      Inositol helps some people's OCD. It is cheap.

      It is best to try things one at a time. There is no way to know for sure in advance whether these things will help.

      The e-cigarette sounds a better idea than a real cigarette. It will be interesting to see if the nicotine patch has the same effect. A slow release of nicotine may have a different effect to a quick release.

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    2. Ok. I'll try to fix choline/inositol levels through food for a start.
      I just need an explanation for slow/quick release of nicotine, does this have something to do with calcium influx?

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    3. Petra, the way the nicotinic receptors behave probably differs when exposed to a gradual release of nicotine from a patch versus 2 minutes smoking an e-cigarette. I recall they are very sensitive to small amounts of nicotine whereas they get "overloaded" by heavy smoking. So the delivery of the nicotine probably is important. Someone else commented that cigarettes worked and patches did not.

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