Precision Medicine for Autism and Psychosis-common Characteristics

0:08 Great so it's my honor to invite and welcome and introduce Dr. Deb Simkin who will be presenting today Dr. Simkin has been an integrative psychiatrist for a long time she's board certified Child, Adolescent, and Adult psychiatrist has been trained by The Institute of Functional Medicine as well as neurofeedback and she has been a Pioneer in psychiatry and integrative psychiatry for a long time she did her Child and Adolescent Psychiatry fellowship at Harvard's mlane and Mass General hospitals she's been active as chair and co-chair of various

1:02 committees at acap including the complimentary and Integrative Medicine committee and has co-edited and written a lot on many aspects of Integrative Medicine and child adolescent Psychiatry and we are just so so fortunate to learn from her and I just welcome you deb all yours so what I'm going to do is cover some things that apply to both autism and psychosis and then try to do catch up and tell you some things about it I'll probably get through the autism stuff first The psychosis I co-wrote psychosis and autism and PTSD I did PTSD myself but I'll share the the

1:53 table on psychosis because I think it's one of the best tables in the book but let me just go to the slideshow so if we if I'm going through this and I lose you you'll have a copy of this just ask me a question but we only have what 35 minutes and this probably would take it two hours if I did it really slowly but so I'm going to start here and basically wait why is it moving I don't know why it's not moving there's something wrong here oh there we go so there are three ways to approach autism there's neurophysiologically and metabolically neurophysiologically you're

2:41 talking about decreased pruning that occurs at synapses in the first year of Life excessive local connectivity and reduced long range connectivity there's increased excitatory and inhibitory ratios of neurotransmitters and inflammation and about 20 to 50% of autistic kids will get seizure the metabolic has to do a lot with mitochondria for instance I always get look at mold or candida or heavy metals because those can really interfere with the electron transport system and but it also the mitochondria is influenced by oxidized stress and you can look at the kreb cycle and

3:30 just for instance just get a succinate level and a fumerate level and if your succinate is high and your fumerate is low you got you already know something's interfering and you have to start exploring it that's one of the most common reasons for chronic fatigue syndrome by the way the mitochondria of course can be damaged by oxidative stress through many different areas medications heavy metals toxic chemicals pbcs pesticides gene mutations shortages of key vitamins and minerals and certain bacteria and viruses and here's your old med school electron transports you can see certain things in here need to be available I get Coq 10 levels here's nasin ribal flavor Vitamin K Vitamin C so if you have deficiencies in any of this you should be treating

4:19 it I'm going fast guys sorry but one of the most interesting things in psychosis and in autism and in fact in depression as well is the role of methylation cycles what I always tell people in the last seven years I haven't treated any child or adult for depression with an anti-depressant except one and only because he insisted if you look at the research domain criteria which is looking at environmental insults the age at which the insult occurs how it causes epigenetic effects how that affects inflammation and then you're going to look at you know the connectivity in the brain you're really getting to the source of why we have these disorders it's not that I

5:04 don't believe in DSM but I think we're in the Dark Ages when we continue to use it because we're not looking at why we are there and the whole reason for that was at the flexer report in in 1910 which closed all psychiatric hospitals check closed down naturopathy chiropractors I mean the AMA was calling for chiropractors to be jailed at one time so the research that was in medical schools and the only thing they would allow for medical schools to be accredited was to teach chronic disease and so that arena allowed that area to be researched we fell by the wayside and we're trying to catch up but I really don't use DSM I use really the research domain criteria from n imh

5:52 so when you look at folate and methylation cycles you have to really be aware of several things this is just one of them MTHFR obviously and you can have the MTHFR can either have AC CT TT alleles if you have MTHFR and you have two t alleles or a CT you're not going to convert inactive vitamin B9 which is folate to the active form now I'm going to show you why that's important in a few seconds but other defective genes and disbiosis can prevent the absorption there's actually a gene in the gut that prevents the absorption of folate so when you look at a metaanalysis of folate and

6:37 I was making this point last night at the meeting you know you can have a metaanalysis and may say well it's not that good but that's not a good metaanalysis because none of the studies really looked at what are this F MTHFR Gene do you have a folate antibody receptor so you can't get folate into the brain do you have for disabsorption due to either disbiosis or having that gene for it do you have and the list goes on and on which I'll go into so I think we have to be very careful when we look at metaanalysis people think oh metaanalysis it must be true but you got to know the material and you got to know what you're reading to know whether you should rely on it and that's what I think we have to catch up on and teach people the methylation cycle you have to

7:26 look at all the genes in there that's involved and the folate cycle to see if they're working well because if they don't you know you're not going to be able to produce SAM-e and I'll show you in a minute what that means SAM-e is not only responsible for producing neurotransmitter it's responsible for DNA methylation the formation of DNA and if all of that's not working very well early on you're going to have certain things happen that are going to affect the child for the rest of their lives so here is the methylation cycle and some of you probably seen this with me before but here is folate a folic acid or folate it's inactive in this form it has to be converted to L methyl folate which is 5 mthf and I'm showing you a little bit more detail

8:16 here usually when we show this we say okay here's dhf usually goes directly to thf and then comes over here and goes right here but there are many other steps in this particular sequence there's something called dhf and then it has to become thf then it has to become N5 n10 methyl and thf and then we finally get here what is needed here is B6 and once you have the active form of L methylfolate or folate that combines with homocysteine and methyl B12 right to come up here and produce methionine and then of course you get SAM-e and you get DNA methylation and the production of neurotransmitters on the other hand homocysteine sometimes may not be available

9:05 to the methylation cycle if you have oxidized stress because then it's going to be pulled here and this is irreversible when it occurs and so what happens is you're using it to produce more glutathion to get rid of a reactive species or free radicals so getting homoy levels are really a part of my workup you can get it on at Quest by doing a cardio IQ of lipids and it'll pull it up it'll also bring up hscrp but you have to add homosysteine to it so it tells me a lot of what is going on but if you have this is just all the enzymes involved there's a metanalysis whoops I'm sorry there was a metaanalysis of the association with mtfr and autism and you can see

9:53 that results of met analysis indicated that the MTHFR C>T may be a associated with increased risk of autism overall however the 1298 A going to C was reported to be significantly a risk for autism but only in Caucasians so we have some ethnicity here that you have to look at too so when you're looking at this is what I just explained so you can see here folic acid or folate coming in MTHFR is then going to produce five L methylfolate that combines with methyl B12 that combines with homocysteine comes up here and ends up producing your SAM-e but there's a

10:39 lot more to it so what then could happen that may not involve this these two the folate and methylation cycle directly but indirectly well if you're not absorbing B12 if you're not absorbing B9 you know or you have deficiencies obviously that's going to be a problem if you have disbiosis and you have leaky gut you may not be absorbing things the way you should there's genes again as I said one is called the foh1l and that is the one that prevents folate from being absorbed even in a healthy gut if you have the folate receptor antibody folate cannot enter the brain and so it's not going to get in and then of course if you have the mthfr gene for CT you're only converting

11:27 from the inactive form of folate to the active form about 35% of the time if you have TT you're only converting about 65% of the time and so you can tell whether everything's working if you look back here my homocysteine levels are high and I've got an mthfr gene I know it's going it's not being utilized and the thing you should know about schizophrenia is that high homosysteine levels and actually in everybody high homosysteine levels actually cause cognitive problems and make the the cognitive problems with schizophrenia worse but homocysteine levels in your labs may say 4 to 12 actually in functional medicine has to be four to eight so if it's above eight you still need

12:13 to be adding the B6 the B12 and L methyl folate you can get a combination of it really cheap $19 a month at forget the name of it dang it I'll have it'll come to me later but it's easy to do it that way and I monitor it so I'm going to go back to just showing this for a second I want you to be familiar with it here's your folic acid comes dhf becomes thf then becomes N5 n10 methylene thf now normally that would go to L methyl folate but I'm going to take this area because believe it or not there's a cycle to the left of this right that a lot of people don't even pay attention to and that's what I'm going to go into now it's another reason why you may not be

13:02 able to form or produce DNA it's another reason why you might have oxidized stress and it's also another reason why you may not be able to produce neurotransmitters so let me show you and whoops sorry okay so here's folate becomes dihydrofolic acid DHF that then becomes THF goes to N5 N10 methylin THF and then it gets your active form but you have to understand that sometimes it does not go directly to elmeth folate it's pulled out well what's pulled out so what you look at here and again this is the things we're talking about in red so you'll know and this is the original that was came out it's confusing so I'm going to simplify it so here is folate and here's DHF now

13:54 sometimes that DHF is turned into THF and then goes to 5 10 methylin however it doesn't go to L methylfolate instead it's pulled out here and it can go back and cycle back to DHF but if it's pulled out there is a interaction here that occurs and this is responsible for producing peridin like cytosine and thyine bases for DNA now if you have a defect and you can't do this then you're not going to be able to properly methylate DNA what about this way this one's really interesting to me this is THF now it can go back to 10 formyl THF and come back to THF again or it you can see sometimes it can go to 10 formaline and go directly to 5, 10 methylene but

14:44 that's not what's important what's important here is this one when you come here sometimes that 10 formyl THF is there two enzymes involved and what it's going to do it's going to form the purine bases so this is adenine and guanine if you don't have that working properly you can't methylate DNA but here's a big piece of the picture that's so important you also produce something called GTP so keep that in mind it's very important GTP is one of the major things that we have to look to when we're trying to find out if you're able to produce neurotransmitters or you're getting oxidized stress or you know if you're even being able to produce more did I say neurotransmitters

15:32 yet yeah maybe so but I'll show you specifically folate or decreased production of THF due to the DHFR enzyme being having a defect may affect DNA synthesis so what why isn't GTP so important well oxidized stress increases if GTP is not produced right so it's essential if you have some defects and a lot of kids who are autistic have defects in the DHFR enzyme you're going to get more oxidized stress because you can't produce GTP but there's a reason for this and this may look complicated but it's really not so let me explain it the GTP coming in here produces something called BH4 this

16:22 has been used in some studies with autistic kids not with schizophrenics yet but it is BH4 is a co-actor for enzymes over here producing serotonin dopamine and nitric oxide which gets rid of oxidized stress if you don't have BH4 you're going to produce more of the free radicals and because you can't produce nitric oxide you won't be able to produce serotonin and dopamine and what happens here is you have BH2 produced and that causes the formation of free radicals so you can see that if you have and you can see the enzyme here if you have you need that to convert DHF to

17:13 THS but you the DHFR cell also can take this B2 if it's around and convert it to BH4 if you don't have enough GTP so what a lot of the work that's been done in autism you'll see this at the end is using BH4 they have they haven't always been able to get the the enzymes identified so they just go in a different direction first and we also know that if you have a very low level of bh4 you're probably not going to produce much THF and produce L methylfolate whoops why because the DHF prefers

18:00 and will be have a greater Affinity to change BH2 to BH4 but then what happens on the other side of this is THF goes down right and BH fail and it's basically here you just got to realize that if you don't have enough BH4 and you don't if you have any defects here right and go on its way to L methyl folate you're in a lot of trouble and that has definitely been seen with autistic kids any questions about that I know I'm going fast okay so if BH2 levels are high then TH levels will be down and this is what at the point I was trying to make and the reason for that is DHFR has a higher affinity for B2 than DHF and why because it's trying to produce take that BH2 and produce

18:48 more BH4 and so this is important the lack of dihydrate DHFR dihydrofolate is one of the main deficits we see in autism and now you can see how it's influencing it my personal opinion is we should be measuring these things at birth and and because we could prevent maybe the severity of the disease but and if you find it even though you may not have autistic symptoms being shown at that time because they may not show up till later I wonder if you would see them as badly later on or you may not see them at all but that research hasn't has been done yet so this is again what I was just talking about so the other thing about oxidative stress is that with oxidative stress

19:40 if you have a lot of it your SAM levels go down for another reason (SAM-e) and the reason this happens I'll show you here is that if you have a lot of oxidized stress and you don't have a lot of homosysteine right because it's being pulled off whoops it's being pulled off then SAM-e will also be sacrificed and instead of going over here to methylate DNA it's going to be it's going to produce SAH that's going to produce more homocysteine to go in this direction to produce more glutothione in order to get rid of reactive oxygen species or free radicals so you can see if I want to really look at this and you can go to genova and you can actually do a work up and

20:27 look at every one of these enzymes you could look at all of the the pieces of the picture in here and I've had some kids get remarkably better when I've done that but it is expensive it's about $400 to do it because insurance companies don't pay for it and it is both a buckle swab as well as blood to do it so this is just showing you that how glutathione is used it's reduced by the way it requires selenium so I do include that in my initial labs not only for this but for thyroid function and then you are going to neutralize the free radicals and what's left is oxidized GSSH now if you want to run a GSH to GSSH ratio you can if this is really low and this is really high

21:18 you know you got a lot of oxidized stress and you definitely would want to use knack because what does knack do it increases glutathione right and maybe you won't be stealing in so much humble cysteine from the methylation cycle right so the problem again I just said this before that if you have MTHFR with CT that you only convert to the active form about 35% of the time TT about 65% of the time but there's two other things I need you to really pay attention to with TT and this was in a mood disorder chapter if you have TT kids who have chronic or history of chronic abuse use get much severe much more SE severe depressions and you should pay attention to that but also if

22:05 you have two t alleles and your homocysteine level goes up you're increased risk for cardiac disease so this is where a functional medicine comes in we're going to be looking at other systems here not just as it pertains to psychiatry so if you look at glutathione obvously an antioxidant but you will also have other things that can influence oxidative stress so that you have to require glutathione environmental toxins heavy metals cause neurotoxicity because of this you get a degeneration of the intestinal tract and it becomes more permeable and that's related to autoimmunity you get increase th2 and these are the T cells that produce more cytokines when the

22:57 gram negative bacteria disbiosis occurs in the gut and the membranes break down because when the membranes break down it produces LPS it causes the immune reaction T cells produce more cytokines because your vagus nerve will pick this up and go to the brain now thats a lecture I did yesterday for the PGY3s but I think I shocked them they were very quiet anyway so you also have to look at vitamin C and E why they're also antioxidants you have to look at every component because just giving the knack may not be enough if your C is down or your E is down A A E shoot which one am I thinking about A D E and is it C are the one no A D E I know are the ones that you have to watch

23:48 because they are fat soluble and if it gets too high it can become toxic but what thank you thank you Amelia okay gotta have a group here to help me here anyway so when you have decreased methylation you could see that decreased methylation can occur for many reasons right and you know that's going to cause damage to cells and by the way if you do a comp gene right comp if you have Val Val means that you're breaking down dopamine too fast met met means you have too much dopamine and Val Val is what most people have but that Val Val means that you're not methylating the DNA that's another

24:35 reason it's not happening and so you would know there's so many pieces of this picture I could give you my labs and show you what I do but there's so many pieces of the picture that you really have to slowly start looking at and to maybe prevent yourself from having to use a lot of psychiatric meds arsenic is a big problem really increases oxidative stress and I get heavy metals on everybody right we already talked about that so in autism also the immune system is involved we know there's a higher risk for allergies or keep sorry kids who have allergies or autoimmune or inflammation they're at higher risk for autism and mostly that happens because you're depleting the microbiome you know anything stress toxins antibiotics H2 blockers anti acids because it

25:28 changes the pH of the gut and kills off all the good bacteria Roundup big one glyphosate acts as an antibiotic kills off all the microbiome lack of sleep excess alcohol chronic sexual or physical abuse as a child I mean all of these things contribute to causing disbiosis and so there are components of this and this is where a lifestyle comes in right this is what we do a lot of in complimentary integrative medicine why am I asking you to sleep more why am I asking you to eat organic foods that don't have pesticides on it right because we can't change lifestyle and this is just my belief I think the American diet is why we get so sick so often even though we've got the best probably the best medical system around in the world so you know but changing people's minds

26:21 and convincing them that this is going to make a difference from them is what's hard and that's where motivational enhancement therapy comes in but I also take out slides and I show them to patients because I'm not the kind of doctor and I don't think anybody in here is like this that somebody comes to and we don't explain why we're doing what we're doing it empowers people so anytime any of this happens you're going to have more oxidative stress now the big one with brain HPA hypersensitivity that definitely is linked to autism and cytosis but that happens when the vagal nerve picks up you know the the cytokines that are being produced because of disbiosis and what happens is the bloodbrain barrier opens up and you cannot shut down the HBA axis why the cytokines

27:12 are blocking where cortisol would normally bind to cause negative feedback but there's also a gene called SK I'm gonna forget it SKAF5 but either way you can have chronic abuse as a child under age seven and the reason that most medications and treatments don't work in those kids is because you are having an epigenetic insult on the brain and you turn on this gene that reduces the number of corticoglucoid or the receptors where cortisol would bind so it can't shut down so there's so much that is so important in what we do and I think that if all of us you know could get

28:01 everybody to do what we do we'd probably prevent a lot of not just psychiatric disorders but a lot of chronic disease as well so this is what I was talking about disbiosis occurs because of LPS from the the gram negative walls when they break down that then crosses the bloodbrain barrier if you don't have good bacteria you don't have short chain fatty acids that maintain gut integrity nor serotonin that does the same that binds to a dendritic cell that signals the t-cell to produce all these cytokines and then as the LPS goes in you cause more of these cytokines to be produced but here's another thing that you may not know you also when all of this occurs is that it causes a turn on of tnf Kappa Beta tnf Kappa beta is going to cause genes other than

28:55 some of the psychiatric genes that we know to be turned on and the result is cancer the result is autoimmune diseases the result is diabetes the result is high blood pressure so this gut is tied into almost every chronic illness out there and so it's not just that we I don't think of myself as just saying you know mental illness I don't even call it mental illness I'll say you've got a brain disease just like if you have diabetes and I'm tired of people you know kind of classifying this as a separate thing that's where we've gotten in so much trouble and I know everybody sitting here agrees with me so I'm not going to spend much time on that now there was a study looking at methylation cycle and trans sulfuration that's when you're producing

29:42 the glutathione and children who are autistic and they found that methionine Sam-e was very low and you had higher levels of homoy and higher levels of SAH so what happens sam-e being pulled off and you had low levels of cystathione cysteine and total glutonione so you have to go back and look at this again who oops sorry so what's happening here is you're getting lower levels of this because it's being remember once homocysteine it goes in this direction it's irreversible and if you've used up all the homosysteine and the cystathione you can't produce glutathione if you can't produce glutathione because you've used up all your homocystine sam-e is going to move

30:28 in this direction you can't have DNA methylation or neurotransmitters and when all of this happens you also see low-levels methionine right so that is all associated with autistic kids and you can get measurements of that you have to use certain labs but I have to tell you that Quest does most of everything Quest you can order MTHFR on now I mean it's really easy and Quest has a whole like a genom mind but the entire Geno array now it's not paid for by every insurance company but they can do it so you know just as a basic reminder what I'm trying to say it's not just MTHFR it's not just having low folate or low B12 you have to look at what's going on to the left of this

31:16 which we talked about you have to look at where the Sam-e can be produced you have to look at if homocysteine levels are high I already know that not enough L methyl folates being produced I'm going to have worse cognition I'm going to have much higher risk for psychosis and that's why Knack has been found to be so effective in preventing early psychotic episodes and if you look at the chapter on that which I co-wrote with the Noid and Batina you can see that but again I will give you the the table on that when we finish today and I send you the slide this is another one where they took 800 milligrams of folinic acid and bentine remember we were talking about bentine for

32:03 three weeks and what happens here is that folinic acid can enter the brain if you have a folate receptor antibody but folate itself cannot enter the brain right so bentaine it provides a folate independent pathway for regenerating methionine so let me show you that so you can actually take if you have enough homocystine you can actually take this used bentaine and you can produce more methionine again if you do the folate methylation analysis with genova all of this is available with an explanation this is where folinic acid comes in right here at the 510 methylin THF so if you

32:52 have an antibody to the folate receptor and it can't pass through the bloodbrain barrier this can get in now for the people can afford to do that that's about $295 I found a lot of kids with it they have a folate receptor antibody to the bonding site or the binding site bonding is more effective if you have it you give them folinic acid and I had one kid we did this with who wasn't speaking very well a month later he was speaking really well and there is some direct correlation to that with research this is again just reminding you where it would come in so if you find that you have somebody who has a positive folate receptor antibody you want to use folinic acid and insurance companies will pay for this if you can prove that it's called lucorum

33:43 right otherwise it's very expensive now there was another study that showed if you looked at the GSH versus GSSH ratio there was a two-fold increase in GSH being a low and GSSH being high but when they used the folinic acid that reversed so you were now able to utilize homocysteine appropriately and not having to pull it off also you can see here sam-e levels increased the SAH levels went down the adenosine levels decreased that's using producing the glutathione so we can look at other ways to show that this works you may not have to do all of these but you know it's just for

34:32 you to know that there's research to back this up I think many of the studies are very small right now and they have to be larger but because of this I've seen some remarkable changes in kids I've had kids who I don't know if you guys know this but there is something called mega cisterna magna and it is one of the least they thought it was one of the least problems for having arctoid cysts but it turns out that there's a high level of psychosis in those kids and so what I've been doing with them is using the methylation and folate cycle and look at all these things to try to change it and two of them gotten remarkably well usually they're destined to have psychosis and cognitive problems the rest of their life you can also look at markers for oxidative stress and

35:24 so and I'm not going to go into this but you can also look into lactate and pyruvate levels in the Kreb cycle to see if maybe it's being disrupted because that means a lot of oxidized stresses also going on well Deb can I pause just for a moment just because we're getting close to the end of the hour and I see some questions because I think you probably brought up more questions than for people hearing this presentation so just because it kind of as a basic can you share a little bit about your background where you got training if people want to learn more about this especially since you're a Child and Adolescent psychiatrist where you suggest to kind of dive deeper in this functional medicine I mean I think everybody should get certified in complimentary

36:11 integrative medicine but you know I do think functional medicine is the way to go now are they going to really be able to help you as much as in psychiatry no but all of the information about the effects of the leaky gut and things like that can then be utilized in what we know in complimentary integrative medicine right and what you're doing with functional medicine is you're looking at antecedants you're looking for genetic predisposition or family history then you're looking for triggers did they have some chronic you know did they have some environmental insult and what age did it occur right was there other things that happen did they get really ill

36:57 have a kid who had cancer and had to have two bouts of chemotherapy by the time he came to me and you know those environmental insults really wreak havoc on him but you look at that you look at the triggers and then you look for things that sustain it so diabetes right lack of sleep all the chronic diseases sustain the inability for us to use medications and medications will never be as effective if you're not looking at that as well so I think I think getting certified in functional medicine and then taking what we know in complimentary integrative medicine is the best combination right can you a little bit about where you went to get training because there's several places for functional medicine to get trained I like the Institute of Functional Medicine because

37:45 it I I'll tell you it took me two years to do it because you got to review all your internal medicine again and you have modules you have to go through and they go in tremendous detail and being a you know person with a lot of learning disorders I did it slowly but you know and then you get certified and then you can take what you know in complimentary integrative medicine and really utilize it in the research domain criteria there are others out there I can only tell you about the one I took but I think that that introduced me into a little bit more depth I don't think if I hadn't had the integrative medicine certification I don't think I would have been able to apply it as well because quite honestly at The Institute of Functional Medicine I don't think they do a good job in terms of psychiatry they do a good job in terms of chronic

38:34 disease but that applies to psychiatry and where did you where do you suggest people I mean there's lots of places out there where did you where did you get training in Integrative Medicine or I did the original Integrative Medicine with ABIHM and really got upset with myself because I realized I couldn't get boarded in Integrative Medicine because I didn't know I was supposed to be grandfathered and I actually called Noshene and said now does this does this mean I have to take a fellowship she said no I don't think so but you know I think that really the best thing is what you guys have in Arizona I mean I think that is the perfect model the premier model for training in complimentary integrative medicine and I don't think there's any other better program out there

39:23 to be honest with you there's a lot of them but I don't think they would apply to psychiatry as much as the one in Arizona I mean that's my just as the last question because I know where are you over time but Claudia Dr. Chapa asked what book are you referring to you've been talking about a book and I know what book you're talking about we were all co-authors on it okay so it's called Complimentary Integrative Medicine and Child and Adolescent Psychiatric Disorders it's by El it's actually our second version of this we did the first ones in 2013 2014 this is much better because we graded the research in terms of metaanalysis and then which had to have two or more rcts with kids but we went up to age 25 and then you had had the second rating was two rcts or more and the

40:11 third was one RTC I think specifically people are looking for correct me if I'm wrong but you would look for the pediatric clinics of North America yes and elere but if you Google that it pops up I'm sorry thank you for reminding me but I do want to I want to say something real quick about folate if you find somebody with and you can look through the slides and see this if you find somebody with a folate receptor antibody and they're drinking milk you're not going to help the kid at all because the antibody still stays high even if you're taking folinic acid because the milk is what's causing the antibio to stay high it's been research you'll see it in the rest of these slides so just real quick I know we got to go let me just tell you what else is important here because this

41:03 is all the studies on it what are the things that are important well you know about folate folinic acid supplementation Omega-3s and this is what I was telling everybody about you can't just look at folate you have to see if there's MTHFR genes you have to look at you know MS which converts utilizes B12 and and homocysteine if you got a defect there you're going to have a problem and you also have MTRR which means if you can't remethylated B12 to be utilized that's the enzyme that does it then it's you're not going to be able to produce Sam-e so again all of that is and this is the one I was telling you about that prevents at the bottom folh1 that's the one that

41:48 prevents folate from being absorbed from the gut so you know this is research domain criteria what and you can see it here here is the MTR here's the one that takes the oxidized B12 and remethylates it that's MTRR you can look at every one of those enzymes and each all these substrates in the genova test what about melatonin why why is it working autism because most kids who have autism great number of them have a defect in this particular gene right here and so that's why you need to give them melatonin and that's why helps so much with irritability when you look at omega-3 fatty acids you really need to know and I think I'm preaching to the choir here you have to have

42:36 a 2:1 ratio of EPA to DHA that's been recommended by research internationally and it has to be at least 2,000 milligrams so again when you look at a metaanalysis and it says oh Omega-3s don't work look at what they used right vitamin D would it be possible for you to send us these slides so we can send them out oh absolutely because I think some people might have to run yeah go ahead but if you're able I just put the email address of our coordinator if anybody wants these slides just grab that email address and we'll have Deb send them to us because there's clearly a wealth of knowledge and it didn't do you justice to give you 35 minutes so we'll have to have you back but thank you but that's okay thank you very much I mean if you have any further questions my email

43:25 if you have a pen is deb62288@aol.com my son's birthday and don't laugh at AOL.com