tag:blogger.com,1999:blog-655962722302095847.post3753282772721976638..comments2024-03-29T10:24:53.156+01:00Comments on Epiphany: Melatonin for Kids with Autism, and indeed their ParentsPeter Lloyd-Thomashttp://www.blogger.com/profile/10173383229834614994noreply@blogger.comBlogger22125tag:blogger.com,1999:blog-655962722302095847.post-73250268077483052102018-11-16T15:25:58.685+01:002018-11-16T15:25:58.685+01:00Aspie, from the viewpoint of me and my personal li...Aspie, from the viewpoint of me and my personal life as an undiagnosed mildly autistic person what you are saying resonates so much with me. I have always had trouble having several ‘levels’ of relationships - my sister, husband and good friends were all the same to me. It was a disastrous recipe, because it was impossible for my friends to keep up with what I was both expecting and offering. I was 28 when I realized this and started making changes, and it was a rational learning process. To me, trusting someone is still the most attractive characteristic there is. When I would be asked what drew me to my husband when we first met 15 years ago I always replied - I felt I could trust him immediately. The things you say here have deep personal meaning for me since they have colored my whole social life all my life. Its not a small thing, and I think there is a lot of merit to it. In my daughters case, she is a COMPLETELY different person in situations with different persons. A person she disliked could probably spend 5 days with her and not get a single look or verbal expression with her whereas with us at home she is really bubbly. Tatjanahttps://www.blogger.com/profile/00856934973958247860noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-33190095282192676932018-11-16T12:53:38.201+01:002018-11-16T12:53:38.201+01:00Valentina,
Something that I forgot to say but woul...Valentina,<br />Something that I forgot to say but would like to add and emphasize (I found this was striking and I have seen it in multiple animal studies and think it is of relevance):<br />In studies where they use valproate as a deficit of social interaction I think they are overlooking 1 major problem that is infact the balance in the social preference test, to be exactly: stranger vs familiar social interaction!<br /><br />All the compounds they test vs valproate in attempts to 'fix social dyfunction', note: they class social dysfunction as social adaptation/novelty preference.... HOWEVER in the context of 'family/friends' how would it make sense that a compound that shows social preference for a stranger rather than a familiar person be beneficial.<br />Once again I found this striking, as the whole idea of relationships is to choose the familiar (partner/family/friends) over a stranger. This is what valproate seems to do, keeps the balance at social preference for the familiar person/animal. Imo this is 'social bonding/social defending', would this is indicate that valproate would increase social defensive behavior? I think so, would it mean more trustworthy relationships? I think so.<br /><br />Its fascinating, its almost as if those with autism cannot flip the switch between social preference for familiar/stranger, they are either going 100% for the familiar (family/known friends) and dont step foot outside the door or they are going to be never satisfied and keep on 'searching' for another person (social novelty), once again highlighting the inability to adapt, it all points to immune dysfunction. And after reading up on it seems that thyroid hormones (TSH to be specifically) play a HUGE roll in this.<br /><br />Cant imagine nobody ever mentioned this before btw: <br />homeostatic drive theory - https://en.wikipedia.org/wiki/Drive_theory<br /><br />This would also explain the global wide problems in autism and why multiple meds (bloodpressure, antifungals, statins, diuretics and god knows what else) can have such a profound effect. Mito dysfunction is very common in autism/asd and this has a stronger relationship with endoplasmic reticulum stress (er stress), this is exactly what sigma receptors seem to control btw, global wide signalling.<br /><br />Autophagy as a survival response to sigma receptor ligand-induced endoplasmic reticulum stress<br />https://www.fasebj.org/doi/abs/10.1096/fasebj.24.1_supplement.485.11<br /><br />"Together, these data suggest that autophagy is a survival response to sigma antagonist-induced ER stress."<br /><br />Loss of Sigma-1 Receptor Chaperone Promotes Astrocytosis and Enhances the Nrf2 Antioxidant Defense<br />https://www.hindawi.com/journals/omcl/2017/4582135/<br /><br />"We found that Nrf2 (nuclear factor erythroid 2-related factor 2), which functions to overcome the stress condition, was enhanced in the Sig-1R KO systems especially when cells were under stressful conditions. Mutation or deficiency of Sig-1Rs has been observed in neurodegenerative models. Our study identifies the critical roles of Sig-1R in CNS homeostasis and supports the idea that functional complementation pathways are triggered in the Sig-1R KO pathology."<br /><br />"Here, we used Sig-1R KO mice to examine brain expression profiles of astrocytes and ubiquitinated proteins, which are both hallmarks of central nervous system (CNS) pathologies. Our results showed that Sig-1R KO induces increased glial fibrillary acidic protein (GFAP) expression in primary neuron-glia cultures and in the whole brain of fetus mice with concomitantly increased accumulations of ubiquitinated proteins."<br /><br />This suggest that NRF2 induction is due to LOSS of proper sigma-1 functioning, this is actually bad it seems.Aspie1983https://www.blogger.com/profile/14186355234793738967noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-19556860720935867442018-11-16T03:46:06.897+01:002018-11-16T03:46:06.897+01:00Hi Aspie, thanks for this info, leptin is proinfla...Hi Aspie, thanks for this info, leptin is proinflammatory and one way of lowering it is by increasing adiponectin with niacin.I also use blak cumin and cayenne pepper.It would be interesting to now if my son has high leptin.This would confirm so many things about his type of autism.<br />ValentinaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-81061307409066572772018-11-15T17:16:15.587+01:002018-11-15T17:16:15.587+01:00Valentina,
It seems that your son just like myself...Valentina,<br />It seems that your son just like myself respond drastically to modulating leptin/adiponect ratios and ghrelin modulation.<br />I dont really have the time atm to fully go into it, Ill leave that to yourself but Ill give you some examples:<br /><br />A new anti-obesity drug treatment: first clinical evidence that, antagonising glutamate-gated Ca2+ ion channels with memantine normalises binge-eating disorders. (in other words memantine protects hypothalmic leptin signalling)<br />https://www.ncbi.nlm.nih.gov/pubmed/15886075<br /><br />Extended-release niacin raises adiponectin and leptin.<br />https://www.ncbi.nlm.nih.gov/pubmed/16887123<br /><br />"METHODS AND RESULTS:<br />In a randomized, placebo-controlled, double-blind study 30 men with the metabolic syndrome were treated for 6 weeks with 1500 mg extended-release niacin (n=20) or a placebo (n=10). Adiponectin increased by 56% (p<0.001) and leptin by 26.8% (p<0.012). Resistin, TNF-alpha, IL-6, and high sensitive CRP remained unchanged. In spite of the increase in adiponectin there was no improvement in endothelial function. The HOMA index actually deteriorated by 42% (p<0.014).<br /><br />CONCLUSION:<br />Short-term treatment with extended-release niacin causes a pronounced increase in adiponectin but fails to improve atheroprotective functions attributed to adiponectin, such as insulin sensitivity, anti-inflammation and endothelial function."<br /><br />So an improvement it decreased lepting/adiponectin ratio, which is good in autism.<br /><br />Adiponectin receptor R1 is upregulated by valproic acid but not by topiramate in human hepatoma cell line, HepG2<br />https://www.sciencedirect.com/science/article/pii/S1059131108000654<br />Aspie1983https://www.blogger.com/profile/14186355234793738967noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-66017388409740647522018-11-14T16:28:10.146+01:002018-11-14T16:28:10.146+01:00Aspie, in my son there were so little intervention...Aspie, in my son there were so little interventions that had remarkable effects: valproate, bacilor a probiotic with l rhamnosus lcr35, BCAAS, niacin . Don´t know if you had medical conditions, my son has SIBO chronic constipation and mitochondrial dysfuction. I agree and think that all neurologists sohuld have the genetic data of each patient and work based on that. May be you will be able to find it in a futuristic office of a simple doctor.<br />ValentinaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-33876309975714187612018-11-13T18:02:23.577+01:002018-11-13T18:02:23.577+01:00Thanks for your reply Valentina and I agree 100%, ...Thanks for your reply Valentina and I agree 100%, during puberty it is absolutely not a good time to try administrate exogenous hormones, even if little amounts.<br />Regard donepezil/memantine, that is striking, considering my mood was absolutely through the roof on memantine and I was very much socially engaged by taking away daily stress.<br />Galantamine I respond very poor too, it gives me TOO much clarity and too much cognition and thereby shutting off completely my emotional pathways. Ive addressed this before, there seems to be an antagonistic effect between cognition and emotion, which makes sense from an evolutionairy perspective.<br /><br />So interesting too see how your son and I respond like 180degrees around to medications. This once again highlights the importance of subtypes of autism/asd.<br />As you have might have read before Im someone who strongly believe in genetic data (such as 23andme), after all our genes can reveal what the eye cannot.<br /><br />I hope in the future (with a strong emphasis on maintaining privacy) some sort of databases can be created, where if you upload your genetic data or by giving it to the doctor then he/she can run it through some machine which can determine what medications are good and which are not good. Unfortunetely I feel as if thats still years and years away :(.Aspie1983https://www.blogger.com/profile/14186355234793738967noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-44022780351679915282018-11-13T15:45:24.815+01:002018-11-13T15:45:24.815+01:00Aspie 1983,regarding progesterone, my son is enter...Aspie 1983,regarding progesterone, my son is entering puberty,I don´t think it is the right moment to do a trial. About donepezil, it made him less engaged, less eye contact and hyperactive. He also din´t do well on Namenda and cholinergic medications. But you can do your trial with a very low dose and see how it goes. Good luck!<br />ValentinaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-74946461214984892612018-11-12T13:56:25.812+01:002018-11-12T13:56:25.812+01:00I know what you mean by the difference between sev...I know what you mean by the difference between severe autism and mild. I personally think the problem is that right now its a behavioral scale. There is no other organic disease with this problem - we will call insulin resistance and diabetes type 2 two different things but we understand that essentially its all degrees of one thing, and they all have the same organic problems and belong to the same doctors and the same therapies. if you drop below a certain autism score on whatever scale is used you ‘loose the diagnosis’. but instead you get another diagnosis, and if you, say, worked dilligently with your kid and used various therapies and he ‘lost the diagnosis’ and now has the diagnosis of ‘mild speech delay and apraxia’, and tomorrow stem cell therapy is made standard of care for autism, the child would not get stem cells because its not standard of care for ‘mild speech delay and apraxia’. But this child has ‘autism’ as a disease. It just has been managed down on the scale. I personally am terrified of losing the diagnosis and will do all it takes to have it as long as we need it. So while I agree from a parental,’ worry related standpoint, that serious autism and mild are not the same at all, I believe that there are maybe 2-3 root ‘causes’ and that many types of autism. And that the severity is not necessarily related to the cause. Those are just my personal hunches from reading research and talking to lots of fellow parents. Tatjanahttps://www.blogger.com/profile/00856934973958247860noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-20545614980374909212018-11-12T12:31:09.719+01:002018-11-12T12:31:09.719+01:00Hi Valentina,
Thanks for your response and yep I h...Hi Valentina,<br />Thanks for your response and yep I have noticed this a lot that people in autism/asd sometimes need drugs that work in oposite direction. Also you are right about sigma receptors affecting analgesia, sigma1 agonists antagonize sedation by opioids, where as sigma1 antagonist potentiate painkilling effects.<br />I personally dont want go down the hormonal path, but progesterone is a sigma1 antagonist, maybe something to look into valentina. Im guessing donepezil made your son hyperactive/emotional?Aspie1983https://www.blogger.com/profile/14186355234793738967noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-9663940255277668972018-11-12T09:21:19.593+01:002018-11-12T09:21:19.593+01:00Tatjana, it will take many decades to have a compl...Tatjana, it will take many decades to have a complete knowledge of autism, we still only have a partial knowledge of how the brain works.<br /><br />There are hundreds of autism interventions used, but I think only a much smaller number ever have a significant impact. To find your 3 key interventions you certainly will need some trials, but if you combine it with either genetic data, or just comorbidities you can narrow it down to a manageable number.<br /><br />There is an ARI paper that rates the old DAN interventions.<br /><br />https://www.autism.com/treatment_ratings_asd<br /><br />The remaining problem is that what counts as "autism" varies so much. I think many of the new drugs in the pipeline are for mild autism and will have minimal impact on DSM3/severe autism. <br /><br />Some of the things that count as issues in modern autism, like inappropriate giggling or behaving "goofy" really seem totally trivial to me.<br />Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-52712156947923136442018-11-12T01:23:23.905+01:002018-11-12T01:23:23.905+01:00Hi Aspie, my son didn't do well on donepezil. ...Hi Aspie, my son didn't do well on donepezil. May be is because it is a sigma agonist, something that my son needs to stay away, due to his dopamine supersensitivity.He would need a sigma antagonist, I don't now what kind of analgesics are being investigated as sigma antagonists.<br />ValentinaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-86270721530178484642018-11-11T22:43:25.378+01:002018-11-11T22:43:25.378+01:00I have read this and understood about 60 percent o...I have read this and understood about 60 percent of it. But, I have a more systemic question to ask - there are constant reports of children getting better to the point of completely being cured with this or that therapy. I even know some children personally who have gotten so much better that an autism diagnosis is not at all anything you would associate with them. While there is hardly ever in my personal experience been a case where one thing just did the deed, almost always there is one thing, one ‘cure’ that solves the majority of the symptoms and then there is fine tuning to be done. Even in the case of Peters son, we see that a very small number of ‘cures’ did a great deal of good. And yet on this blog and in science there are SO MANY things people associate and research about in autism. I recall there being a failed project called autism360. The idea was to fill out a large profile of your kid and then add what worked for you, so that it might suggest other parents with similar profiles to try the same. It did not have the necessary popularity to make it work fully but with its numbers, it listed a number of things that worked most often and they were mb12 and GAPS diet. So, overall, while there is a lot of suspects in genetic make up for this or that problem in autism, the research AND symptoms seem to fall into a few distinct categories: 1. Gastro, 2. Immunity issues, 3. Metabolism/Detox issues, and tentatively I would add 4. Genetic (tentatively because those issues also always come back to the first three groups). The reason i write this whole thinking process down is because while I was reading what you just wrote down on sleeping issues, I was struck by the fact that Gcmaf resolved all (they were very mild) sleep issues my kid had and did the same for anyone I know who tried it. Gcmaf is anyways not a very well researched thing, and all I van hypothesize is that its effect on vitamin D is what makes it work for sleep issues. So my question was - isn’t in the end more likely that, were we to have complete knowledge of what autism actually is, it would provably be a question of slotting 1-3 keys into the requisite keyholes, and not hundreds of tiny fine tuning supplements and therapies? Tatjanahttps://www.blogger.com/profile/00856934973958247860noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-19855982991410161242018-11-11T15:58:27.889+01:002018-11-11T15:58:27.889+01:00Sleep problems in autism seems to be due to improp...Sleep problems in autism seems to be due to improper melatonin synthesis. Donepezil seems to increase REM sleep in kids with autism to a fair degree and also happens to be a potent sigma-1 agonist.<br /><br />Heritability of the melatonin synthesis variability in autism spectrum disorders.<br />https://www.ncbi.nlm.nih.gov/pubmed/29255243<br /><br />"Hyperserotonemia and low melatonin levels are among the most replicated endophenotypes reported in ASD, but their genetic causes remain largely unknown. Based on the biochemical profile of 717 individuals including 213 children with ASD, 128 unaffected siblings and 376 parents and other relatives, we estimated the heritability of whole-blood serotonin, platelet N-acetylserotonin (NAS) and plasma melatonin levels, as well as the two enzymes arylalkylamine N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT) activities measured in platelets. Overall, heritability was higher for NAS (0.72 ± 0.091) and ASMT (0.59 ± 0.097) compared with serotonin (0.31 ± 0.078), AANAT (0.34 ± 0.077) and melatonin (0.22 ± 0.071). Bivariate analyses showed high phenotypic and genetic correlations between traits of the second step of the metabolic pathway (NAS, ASMT and melatonin) indicating the contribution of shared genetic factors. A better knowledge of the heritability of the melatonin synthesis variability constitutes an important step to identify the factors that perturb this pathway in individuals with ASD."<br /><br />Sigma receptor modulation of noradrenergic-stimulated pineal melatonin biosynthesis in rats.<br />https://www.ncbi.nlm.nih.gov/pubmed/8667004 / http://sci-hub.se/10.1046/j.1471-4159.1996.67010287.x<br /><br />". This enhancement was prevented by pretreatment with rimcazole, a specific sigma-receptor antagonist. These findings suggest that, in rats, the activation of pineal sigma-receptor sites does not affect the biosynthetic activity of the pineal gland during daytime, whereas it potentiates the production of melatonin when the gland is noradrenergically stimulated either by isoproterenol administration or by the endogenously released norepinephrine at nighttime."<br /><br />So the sigma agonists only enhanced melatonin production during darkness and not during daytime, which is exactly what you want as increased daytime melatonin leads to fatigue/drowsiness. Pretty unique stuff tbh<br /><br />Melatonin in Children with Autism Spectrum Disorders: How Does the Evidence Fit Together?<br />https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478596/<br /><br />In reference to defects in melatonin degradation, there are numerous polymorphisms located either within the CYP1A2 gene, or in intronic regions, that are reported to influence subsequent enzymatic activity.[47–53] A potential relationship has also been implicated between presence of predicted slow-metabolizing alleles in CYP1A2 and susceptibility to ASD with comorbid sleep problem.[35, 36] Interestingly, all of the individuals included in the Braam et al., 2013 study (n=11) were diagnosed as slow melatonin metabolizers and it was observed for these children that the efficacy of supplemental melatonin exhibited disappearing effectiveness over the course of 4–8 weeks.<br /><br />This shows that melatonin supplementation indeed has tolerance!<br /><br />We also evaluated slow-metabolizing alleles in CYP1A2 and the relationship to expression of sleep onset insomnia in a small population of children with ASD and comorbid sleep onset insomnia (n=15).[40] While we were only able to evaluate a small sample of children, we observed increased frequencies for variants in the CYP1A2 gene related to decreased enzyme activity (p≤0.0007).<br /><br />So CYP1A2 slow metabolizers in autism have sleep problems (P<0.0007), thats very significant.<br />I looked up my CYP1A2 metabolism by putting my genetic data through codegen. CYP1A2 also regulates arylhydrocarbons and how the body detoxifies them (chemical sensitivities such as car exhaust and cigarette smoke).<br /><br />https://ibb.co/de51AA - shows im a slow cyp1a2 metabolizerAspie1983https://www.blogger.com/profile/14186355234793738967noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-70718143399941975712016-01-27T02:30:33.684+01:002016-01-27T02:30:33.684+01:00Hi nd,
My daughter has never been able to handle...Hi nd, <br /><br />My daughter has never been able to handle a complete multi B. I used to supplement them all individually. The troublesome ones were the b3 and the b6. I used to give just a smidgeon of the nicotinamide and had to give p5p with magnesium. I only wanted to try the p5p for seizures and gave the others just so they wouldn't be depleted. I also used a methylcobalamin spray. I don't do any of it now. Here, the big mood stabilizer has been sytrinol. <br /><br />B12 also appears to act differently on people. Nothing for my daughter. I have tried injectable, buccal, oral. For me, in the daytime, even energy, clears my head if depressed. Interestingly, at night, it calms me and helps me fall asleep. It has also brought back the vivid, interesting dreams, sometimes nightmares, that I have had for for as long as I can remember, but that had stopped a couple of years ago. RGhttps://www.blogger.com/profile/07458829468580940361noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-61190032860711690172016-01-26T13:10:12.838+01:002016-01-26T13:10:12.838+01:00Maybe some of the B vitamins are helpful and other...Maybe some of the B vitamins are helpful and others are not. They all have different functions (and possible side effects). When you ran out of them, what happened to sleep? Perhaps NAC close to bedtime is the problem?Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-19502991307510779992016-01-26T12:47:28.079+01:002016-01-26T12:47:28.079+01:00Thanks for responding. Actually, when I ran out of...Thanks for responding. Actually, when I ran out of B vitamins (my son and I both have homocysteine issues), his rages crept back up. I added the B vitamins back in and they dropped again somewhat. I added in second Homocysteine Supreme and mood stabilized even more.So I am fearful of removing them.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-26949909807693700852016-01-26T09:11:44.773+01:002016-01-26T09:11:44.773+01:00Nancy, a known side effect of supplementing vitami...Nancy, a known side effect of supplementing vitamin B12 in autism is hyperactivity (there was a clinical trial by the MIND Institute).<br />If it was me, I would stop giving B vitamins and see if sleep goes back to normal. I am giving NAC without any B vitamins. <br />B12 is interesting and there will be a new post on it because there has been a new study. Some people with autism have low B12 in their brain, but this would not show up in blood tests. It has long been known that a small percentage of people (circa 10%) do indeed benefit from extra B12, but 90% do not and some get side effects quoted as being hyperactivity and pica. Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-58892035865757312542016-01-26T01:43:37.740+01:002016-01-26T01:43:37.740+01:00I am wondering what might be best to help my son w...I am wondering what might be best to help my son who has been waking between 2 and 3 for the past couple months. I upped his B vitamins because he is taking 3600 mg of NAC daily. I don't know if the B vitamins are waking him up. I give the last dose late morning or early afternoon for this reason.<br />At this point, neither of us are sleeping again once he wakes up. Any advice would be great.<br />Thanks.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-85745004214506451352014-02-04T17:08:05.688+01:002014-02-04T17:08:05.688+01:00 Grapefruit juice is known to interact with many p... Grapefruit juice is known to interact with many prescription drugs like hormones.<br /><br />Do you have valide information if grapefuit interacts whith melatonine ? Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-67887282992698424842014-01-23T19:40:36.609+01:002014-01-23T19:40:36.609+01:00Bumetanide is worth a quick trial. You will see w...Bumetanide is worth a quick trial. You will see within a few days whether it works for Kirsten. The effect ranges from zero to profound. It seems more effective in early onset classic autism, than regressive types. The only way to know, is to try it. It seems a safe druf for long term use.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-53693551457677419132014-01-23T18:56:40.366+01:002014-01-23T18:56:40.366+01:00Melatonin worked for my daughter Kirsten and enabl...Melatonin worked for my daughter Kirsten and enabled her to get into school in the morning. Increased my quality of life!. Interesting that dose of 1mg and less just as effective as higher one as she was prescribed 3mg. On a break from it at the mo - but if needs to be taken again will try breaking up tablet to see what happens. Am also interested, like previous commenter, to know whether supplementing melatonin for relatively long periods causes pineal to further decrease it's own production and whether effects permanent. Re in an ideal world melatonin levels would actually be tested - I will try asking for this. Thank you again Peter Lloyd-Thomas. Your blog is one of the most worthwhile on the net at the mo. Ben-Ari did reply and advised me to speak to Kirsten's specialists about bumetanide. Will leave comment on your relevant article if get to give it a go.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-26736833174948515992014-01-23T02:58:55.331+01:002014-01-23T02:58:55.331+01:00Whether the pineal grand will further decrease Mel...Whether the pineal grand will further decrease Melatonin production after Melatonin being given to the children? _yiAnonymousnoreply@blogger.com