 We're gonna get started now So our final speaker of the day is Dr. Tim Gerstmar Dr. Gerstmar is a naturopathic doctor with a practice in Richmond, Virginia Redmond Virgin Redmond Redmond Washington slightly different. Don't go and look for me on the East Coast. You won't find me there Thank you He specializes in hard-to-treat cases and numerous types of digestive issues Please welcome dr. Gerstmar Well, thank you all for showing up. I know it's the end of the day This talk hopefully will be a little bit of a relief for you in the paleo ancestral world We talk a lot about things that are your responsibility that you are responsible for doing and as you can see today We're going to largely talk about things that are your parents fault two nice examples of Parents who did the wrong thing. Maybe your kid does not want to pose next to the lion very much and then You'll see this dad with his nice little daughter smoking an absolutely massive joint there probably not Good decisions. Like I said, it is the end of the conference I know most of us probably feel like our heads are going to explode again I appreciate you coming in and I hope this talk maybe will change you a little from that to that by the end of our talk That's my goal. I have two little preambles before I begin The first is I've spoken at ahs a couple of times deal with a lot of digestive problems So I always mention bowel movements and feces and I just felt like I couldn't give a talk at ahs without bringing it up So For people watching the video for Steve and Jordan the toilet is just for you guys The others I've been very impressed by the quality of presentations like Jamie Scott's looked really beautiful Mine kind of looks like a second grader put it together, so I apologize for that But having said those two things, let's get into it We're talking about methylation today, and it's how one simple carbon Affects your your mood your brain your DNA and everything in between Again, this is me not Virginia Redmond Washington. That's Seattle If I've been told all the cool kids are on Facebook and Twitter, so if you want to follow me there That's where you'd find me and I just need to say that methylation is really cutting-edge stuff We've heard about it to my surprise a few times in this conference A lot of the data is brand new and just coming out and there's a lot We're trying to piece together and explore so while I feel like I have a decent handle on this information You know there are gonna be things in here that aren't included or that are wrong because simply this information is new stuff But let's see if I can lay it out for you. The question that I have is why don't people get better, right? They do the basic paleo stuff. They eat well. They get exercise. They sleep They manage their stress and they're still sick and then they come see me and we're turning over rocks looking for the reasons That people aren't getting better. That's what led me to get into methylation is a way to look for still sick patients About what is keeping them sick? So with the base of the pyramid? I know you guys all know this sleep diet Exercise and stress if you don't manage these things you're building your house the metaphorical house It is you on quicksand and you're not gonna stay healthy no matter how many pills you take no matter How many treatments you take like the you know the macrophage Destroying things that we saw earlier great, but at the end of the day you still got a sleep diet exercise and stress And as we know from Rob Wolf's website and the cool testimonials out there some people really sick people Do this stuff and magically get better and rainbows come out. They don't tend to come see me Excuse me. They don't tend to come see me though It's people who are still sick. So what do you do when you've done these things and you're still sick? Well for me the next level to address and and gratifyingly we've talked a lot about gut health at this conference is gut health Other issues with you know Environmental toxicity and as a side note I spoke on each of these at AHS 11 and 13 So check that out if you're interested, but what do you do when people are still sick? And that's what I'm gonna talk about today, which is methylation and the genetics around methylation So methylation that like that's great. I've heard that word, but I have no idea what it is And so that is a methyl group that only excites chem nerds though So for any chem nerds out there there you go But that is a methyl group and that is ultimately what we're talking about These are the methyl donors. So these are compounds things nutritional things that we take in that really like to give That little methyl group off to something else. So choline Which we've heard mentioned methionine which was mentioned which becomes Sammy we'll talk about that later folate methylcobalamin or B12 and serine and glycine that was mentioned in The broth talk from earlier. So these guys are our methyl donors and what do they actually do? So we've heard of we know what a methyl group is we know what? Compounds tend to give these methyl groups and what are they actually good for so to my great Surprise and and I thought it was awesome. We actually had a talk on epigenetics Because it's already in my presentation. I'm going to go over it again. So if you missed it the first time Let's go through it. So obviously we all have DNA is the the code that makes everything that is you you But the question is why is a skin cell different from a lung cell and a Bone cell and a nerve cell when they all have exactly the same DNA in them They should all therefore be exactly the same well epigenetics obviously turn Epigenetics turns DNA on or off Methylation is largely Responsible for turning off DNA another process called acetylation is largely Responsible for turning on DNA. So of course What makes a skin cell different from a brain cell is simply the epigenetic programming that that cell has received that says either essentially become a skin cell or become Become a brain cell, but as we know epigenetics goes beyond Just Programming cells what to become so a good analogy here is that your DNA is the dictionary or the encyclopedia of I got two of these things here Let's see is the dictionary or encyclopedia of you and acetylation are the little bookmarks that tell that essentially tell everything to read here and Methylation are the paper clips that keep certain pages closed and prevent access to those passages I don't know if anybody saw MacGyver. I'm kind of old now But so that's how we tend to think of epigenetics now Hopefully you guys saw this a few years back. This is in a this is in a goody mouse We have bred them to break them essentially so that they become diabetic and obese the cool thing however is that is also in a goody mouse and the story goes this the mother was Pregnant and they supplemented her diet with some of those methyl donors that we saw earlier and when she delivered She had these normal looking a goody mouse that weren't diabetic were not obese And had normal fur color and we found out that the methyl donors had epigenetically silenced the a goody genes and essentially made The these little guys as normal as you can call a little lab mouse Normal so that was exciting that we could that that these methyl donors could cause such a massive difference Between these two guys, but did that apply to humans? So this is a study that just came out showing accumulating evidence that low maternal b12 if you'll remember b12 is a methyl donor And protein intake are going to be associated with risk of neural tube defects something we'll touch on a later but essentially The problems with the brain and spinal cord low lean mass which speaks a little bit to the muscle talks and Jamie's talk from yesterday Why are our kids having low lean muscle mass? Well part of the answer clearly is environment in the diet that they're eating But unfortunately part of the answer may lie in the epigenetic changes that occurred in those kids While they were in utero Excess adiposity increased insulin resistance. So again, someone can say why in the world of my pre-diabetic or diabetic? I eat really well. I exercise I do everything that I'm supposed to be doing and still I have issues the bad news is it could be your mom's fault Okay impaired nerve development altered risk of cancer. So we see that these things really Probably have a major and significant impact On us another study came out recently showing that if your grandmother smoked You have greater risk of asthma. So your grandmother smoking while she was pregnant with your mom Your mom never smoked a day in her life. Your asthma might be your grandmother's fault So again more epigenetics. This is scary Methoxychlor is a DDT Replacement that was brought in in the 70s when they phased out DDT It was banned in 2004 because low and behold they found out it's also terrible but Michael Skinner at WSU found that by exposing pregnant rats to this methoxychlor At high normal ranges that they saw increases in kidney disease ovary Disease and obesity But the worst part is that it spanned three generations and got worse as it went along So just to make clear the great-grandmother rat was exposed to methoxychlor Neither the grandmother the mother or the children had any exposure whatsoever and yet the epigenetic Effects persisted down through the generations So my takeaway for this and this isn't the primary piece, but is that pre-conception care is really really important Now this isn't a popular message I find when I talk to women who come and see me because they'd rather be pregnant yesterday Then do three or six or even 12 months of pre-conception care around optimizing their nutrient status Detoxifying and trying to get some of these compounds out of their lives and out of their bodies But I think it's a critical piece that we need to be emphasizing and we see in Ancestral communities there was a real emphasis placed around maintaining the health of the mother Not to beat beat too much of a drum there. So we've talked about epigenetics That's one thing that methylation does another is it's simply involved in the creation of things So if you happen to like DNA you can thank the methyl donors for helping to make that possible for you Another piece is the neurotransmitters. So dopamine serotonin Melatonin the things that help you get to sleep help you get excited about things Help you not freak out. We need those methyl donors to create them Phosphatidylcholine is a primary fat and cell membranes. So if you like having cell membranes Then methylation is important Carnitine lets you burn fat without it. You're stuck being a carb burner Coq10 protects all your cell membranes and is important for the function of your heart and if you like doing high-intensity Exercise you like having creatine as well. So all of those compounds need methyl donors or they cannot be synthesized effectively Lastly to biotransform or detox also requires methyl donors So I dug up an interesting study about arsenic and this was a population in South America That's been chronically exposed to high levels of arsenic in their drinking water. So it's a naturally occurring They they got some bad luck when they decided to live there and what they found is that polymorphisms, which is the fancy way of saying mutations This a s3 mt is actually arsenic methyl transferase. You can see it has the word methyl and transfer right in it So it is a methyl dependent Detoxification enzyme involved in arsenic and the genes in one carb and metabolism, which is another way of saying methylation And they found that this population had more Beneficial mutations in these enzymes to deal with the arsenic that they've been exposed to for a few thousand years now So methylation important for detoxification as well. So the question becomes well, how do you screw this thing up? How do we mess up our methylation? So we talked about the methyl donors, but they don't work by themselves. You need cofactors like zinc and riboflavin magnesium cysteine B6 or pyridoxine and Methyl B12 kind of redundant there in order for them to function certain prescriptions like ant acids and methotrexate interfere with methyl donors oxidative stress Or high levels of inflammation are going to interfere. We talked about environmental toxicity And it is also possible to overload these systems So if you will go when you absolutely mega-dose in B12 or some of the other methyl donors You can actually shut down the pathways by simply having too much And then of course genetic mutations or as we like to say polymorphisms in these pathways We can divide these groups sort of into two ways to screw up your methyl donors functionally You can have these issues going on constitutionally you can have genetic mutations or polymorphisms That impair them and of course most of this at time we're stacking both on top of each other So let's talk about what methylation how the process actually works. Hopefully this will be simple and obvious for you So we begin with folic acid or folates So folates are found mainly in our green vegetables like collards Spinach asparagus turnip turnip greens broccoli cauliflower and also in liver And then we have made a synthetic folate called folic acid that's found supplementally and In most multivitamins and other folic acid supplements So I found this lovely this lovely chart here on gofolic.org saying hey It's no problem to get your folic acid because your captain crunch Of one bowl has 400 micrograms and hey if you're thinking of getting pregnant, you know just eat two bowls of it so That begs the question of course This is dr. Cordain here published an article relatively recently talking about flour fortification So in 1998 the USDA decided that they would fortify all flour With folic acid, so the issue is low folic at low folates. Excuse me. They are different low folates cause those Neurotube defects which the most common of which is spina bifida or Neural a genesis as well and those are absolutely terrible so most women when they realize they're pregnant they run out and they get a Prenatal multivitamin or a folic acid supplement because they've been told to do so But the problem is that that spinal cord and brain that early spinal cord and brain development Happens before most women know that they're actually pregnant So by the time they know and the time they go and take a supplement for it. It's already too late. So the Government decided that we would just take care of that because everyone eats grain pro, you know refined grain products anyways that will just add the folic acid to the grain products and Therefore we won't have that problem. Dr. Cordain here. You can please go check out the article does a nice job But the the bottom line is that with folic acid especially we have a lot of evidence Converging to suggest that that fortifying this food and you know significantly increasing many people's intake folic acid Has led to increases in breast prostate and colorectal cancer. So probably not the most awesome thing to do He and I are both gonna agree that folic acid not so awesome, but folates from food is Pretty great Okay, so we have folic acid again has to be converted by the body anyways into a more usable folate Then begins a long chemical process moving through these different forms as it's being transformed So folates themselves or folic acid are not actually usable by the human body for anything in particular that we know of at this time They have to be by there are raw material that needs to be biotransformed into something. That's actually useful for us And here we go at the bottom 5 mthf or 5 methyl Tetrahydrofolate is actually the useful form of folate that the body wants Now the last step in this process between 5 10 methylene tetrahydrofolate and 5 mthf is an enzyme called Mthfr which a lot of people call the mother for her gene So you probably will remember that now It uses riboflavin to cut to cause this final conversion and what we see here is that a Significant number of people have issues with their mthfr gene so There are two primary mutations that we look for in this Mthfr gene and they have the very memorable names of a1298c and 677t The a1298c is considered a more minor mutation the c677t is considered the more major mutation Now you have two sets of genes one came from your mother one came from your father This test here was one I ran on a on an autistic gentleman and as you can see here He's got a double c677t So his mother gave him one his father gave him another and as a side note I've yet to see an autistic individual without a mutation in the mthfr gene I'm not clearly not saying that's the only problem going on what I have seen it in in every Individual that I have seen so what does this do when we have these mutations and best is as we're able to tell This is what it does if you have one c677t you lose about 40 percent of the functionality of that gene To which are the autistic gentleman the last slide had you lose about 75 percent of the function of that gene a1298 again less serious a single mutation about 20 percent loss of function a double mutation about 40 percent loss of function and if you're a special flower and you have both Mutations it still only ends up being about a 40 percent loss of function What I can say though clinically what I have seen is the conventional community would consider a single a1298c to be Insignificant I have still seen it be be something that has affected people likely because we're black were stacking functional blocks on top of these Constitutional ones and I have never seen anyone with the double c677t who has not suffered significantly for having that mutation We do have a riddle though a question So these mutations are fairly prevalent in the in in the populations now They haven't been tremendously studied, but it is suggested that 30 to 40 percent of caucasians at least are going to have At least one of those mutations at least a single mutation going on and the question is why if if it affects Neurogenesis it should have some effect in terms of Rearing offspring and it should therefore be selected against and the answer why this persists that is I have no idea Maybe there's some beneficial aspect to having this mutation that hasn't been uncovered yet Or maybe it's not it doesn't affect child rearing enough to cause its own deletion Or it's possible and I'm going to mention there are some alternate pathways the body can take and maybe In an ancestral context with a higher nutrient density diet than what we have in the standard American diet It's not so significant for people, but it is an open question that we have why this mutation persists but This this piece of methylation is only unfortunately the tip of the iceberg it gets more complicated So let's see if we can make this a little more simple for you guys This is not the word same. It's actually Sam E. Which you may have heard about a supplement you can buy over the counter often used for insomnia and Mood issues so Sammy of course is a methyl donor It comes from methionine an amino acid in our diets I mean it likes to donate its methyl group and then when it does Sammy becomes homocysteine Which people may have heard about as well homocysteine kind of a toxic compound not really so nice We do want to get rid of it and what happens is the body then moves it along a pathway So we have two pathways known as the short cycle and the long cycle that serve to Recycle homocysteine and turn it back into Sammy again so that it can donate its methyl group and around and around we go The third pathway I just call a drain and it sort of moves homocysteine completely out of what's known as the methionine cycle So the short cycle and there's debate about how Significant the short cycle is in human beings in mice and rats This seems to be the primary way that they recycle their homocysteine back into Sammy But there's some suggestion in humans this only really occurs BHMT is only really expressed in the liver and kidneys and is a secondary pathway for humans But honestly, we don't know so this enzyme BHMT is responsible for taking homocysteine back up into methionine and Sammy with the use of choline or trimethylglycine and zinc then we have The second here the long cycle this lovely complex of enzymes MTR and MTRR And if you were paying attention on the arsenic slide, you can see the absolutely gigantic Proper name of these enzymes, but I'll spare you that so MTR and MTRR long cycle Considered to be the primary way that human beings recycle our homocysteine And require zinc and vitamin B12 in order to function Lastly the drain homocysteine involves an enzyme involves many enzymes but involves an enzyme known as CBS uses vitamin B6 or Pyridoxine and takes homocyste Homo cysteine to cysteine Which then can travel to either torene or glutathione and as you can hopefully know a glutathione really important endogenous antioxidant and involved in detoxification So just a tad bit important for us So three big pathways with different enzymes BHMT MTR MTRR and CBS So this is the methionine pathway But we can't forget earlier about the folate the folate pathway that gives us five MTHF So we're going to take this straight line We're going to bend it into a circle and we're going to smash it up next to the methionine cycle And what we see here is this folate becomes tetrahydrofolate through the wonderful action of MTHR becomes five MTHF five MTHF Then is a necessary co-factor of the MTR MTRR or the long cycle in order to recycle Homo cysteine back to methionine so an MTHR defect or mutation that results in less five MTHF is Going to impair the long cycles ability to clear homocysteine and maintain adequate levels of sami and Inadequate levels of sami are going to result in deficient methyl donor groups for a variety of processes that go on in the body Okay But I want to make it more complicated because that wasn't good enough. So five MTHF Also butts up against the tetrahydrobiopterine cycle, which is this BH4 right here Which is a necessary co-factor to take tyrosine and tryptophan into serotonin and dopamine So without adequate BH4 you can't make adequate levels of serotonin and dopamine and without adequate five MTHF You can't make adequate levels of BH4 So we start to see why methylation becomes important and I've spared you any more circles But it actually keeps going and gets bigger than this which is why the whole thing is so damn complicated So when we look at MTHFR, that's great But we've seen that other enzymes and other pathways are involved in methylation that go beyond simply MTHFR and This for example is a DNA methylation pathway profile Looking at a whole variety of these enzymes and this particular individual who had a great deal of anxiety Has no mutations whatsoever in his MTHFR But we can see mutations in the MTR in the MTRR in the BHMT in the CBS And in a whole host of other enzymes that we don't have time to talk about So it gets complicated You can also cheat a little bit if any of you have done 23 and me and let me just say I have no Affiliation with any of these companies But you if you've done 23 and me or something similar you can export the data out of 23 and me to another service Such as genetic genie And you can get a similar readout as we saw before. So again, here's MTHFR Here's MTR and MTRR BHMT CBS and a variety of others involved too So it's this is something that's accessible for people to look at if they choose to They can also take the 23 and me data and plug it into Prometheus if they're a glutton for punishment And then they can get the good news the bad news and this seems interesting, but we really don't know Then they can freak the hell out because they get Things that look like this increase risk of Alzheimer's disease two times risk of Alzheimer's disease And similar things So just a moment to say that genetics are pre our predisposition. They are playing the odds They're not destiny in most cases. So people who see they have increased risk of Alzheimer's or other issues Don't need to to conclude that they're doomed But if you're a little on the hypochondriac side, you may not want to plug your data into Prometheus. Just just FYI Alright, so what can we start to take away from all of this? We've seen some nifty biochemical pathways and some enzymes and some long names But what does this actually mean for us? First of all, I'd say, you know, again, don't panic about this stuff. It's complex It may feel overwhelming and you know, you may not even need to explore this so when do I look at methylation again when the case is tough and People are doing what they're supposed to and they're not responding like they should This is another avenue to look down And then with mental health issues It is an area that I explore Methylation defects as well because we've seen how crucial methylation is to the creation of neurotransmitters And when neurotransmitters are imbalanced Mood is also imbalanced So we'd argue the takeaway is the same as you hear almost everywhere else First of all, we should all be focusing on a nutrient-dense diet We know these pathways require the natural folates from things like greens and liver the other B vitamins as well beyond folates things like choline Zinc and other cofactors and you know to pad ourselves on the back We know that a paleo style diet tends to provide ample amounts of nutrients for people All right, then we do if you do think this is a concern for you I do recommend testing and smart supplementation So does everyone need to go out and buy the methylated forms of folate and B12 and start slamming them back? No, also, we know that high levels can inhibit it can cause inhibit Inhibitory feedback on these pathways and end up making people actually worse than they were to start with So Specifically what I'd recommend is if if this is a concern for you the easy way to start is by getting MTHFR tested so especially if they're mental health issues because again, we saw how MTHFR Plays into the creation of neurotransmitters The good news is that this test is commonly covered by health insurance, not always But often is covered by health insurance and the major labs run it So any doctor can technically order these they just may choose not to because it's meaningless to them The other good piece of news with all of these genetic tests is they're only ever done one time Because your genetics don't change over your lifetime If you have MTHFR defects you were born with them and you will die with them as well unless we get Nifty cool gene therapy or something So that's the great piece about the MTHFR as you saw earlier that test on MTHFR for the autistic gentleman I just ordered it as part of his regular lab work If you have an issue you can consider supplementing with five MTHF So again, this is not folic acid. This is not folinic acid to two forms of folates that are more commonly available So your average prenatal your average folic acid supplement is not five MTHF It really needs to be labeled five MTHF or L methyl folate If that's what you're looking for they tend to be available Most health food stores do not carry them, but the internet is a magic place that has almost everything So it's something that can be found And dosing is one of those areas that we really don't know at the moment So doses range from quite small 400 micrograms 200 micrograms all the way up to in some cases of depression and others 15 milligrams and we truly don't know what the ideal dose is or Necessarily what it is for anyone individual. I tend to start on the lower side of these high doses at 800 micrograms to 1 milligram because many products come in those dose ranges and assess what's going on For the individual and from there we may need to go up or down in dose a funny story I had a gentleman come in He had been a dower negative and depressive his whole life We tested MTHFR and found in his case a simple a1298c defect a single one affecting, you know, 20% of his is Follate conversion. He was up for trying some five MTHF. He came back and said the first week. He didn't notice any change But since then he's been happier which has been a little disconcerting for him He has been less moody which his wife is happy with and had less brain fog But he didn't really want to increase his dose because then he might be too happy and that would just be that would be bad So there are some side effects, especially around mental issues and it can worsenings It is possible to worsen anxiety depression cause mood swings Affects sleep and everything else It doesn't always happen. It doesn't even often happen, but it does happen And the good news is you stop taking the dose and the effects go away Usually quite quickly All right, you have the MTHFR and you have a therapy you can try if you have issues with MTHFR But as you've seen or I hope I've conveyed to you The MTHFR by itself is an incomplete look at methylation And if you feel like there's more going on or the MTHFR is Inconclusive for you then come becomes time to do more testing and again No affiliation, but the company doctor's data does you saw one example of their whole blood methylation? Typically you do need an alternative or integrative doc to order that test for you or you can do the 23andMe on your own It's fairly inexpensive. There are privacy concerns around it, which turns some people away That's for each person to decide and then you can Pilfer your own data and run it through genetic genie And if you're not too anxious run it through Prometheus as well and see what it tells you at that point Things really get complicated and having a good practitioner on your side becomes really important because Treatment really gets tremendously individualized from there depending on what's going on so We have our foundation and we should never stray away from sleep diet exercise and stress You've heard from other people at this talk about the importance of gut health I hope some of the talk on epigenetics has also convinced you that the issue of detoxification Is a real one and now we've just talked about methylation and genetics Which is not critical that every single person need to run out and do this But if you're still suffering health issues Despite having done your best in these other areas or you have money and time and really want to explore it Then it is something to look into Again, this is who I am. I hope I've convinced you that I'm more like this Or maybe like this, but either way I thank you all for coming. I know this is the last talk and I appreciate you being here I hope I've been able to give you some useful information and I think we have a couple of minutes for questions. Thank you Hi, first of all, that was awesome. Thank you so much. I have gone that down that rabbit hole I had 23 and me raw data into mth of our support, which I think goes to the same other website from ETH It's a very similar type of thing. Yeah, the thing that was missing was the context as to what to do Yeah And what I'm curious about is I know this you're sort of talking about it from perspective of treating people who have ailments What if you want to look at it from the perspective of optimizing sure and functioning better just in sort of everyday life? Personally my my big red sections were my IgG and IgE pathways. There's a lot of red there for some reason So I'm just wondering who other than maybe, you know, I'm hiring someone like yourself Are there resources out there and I'm not opposed to hiring you sure sure. No. No, but what can I where can I read more material? Yeah, it's I mean straight up. It's challenging, right? There are a few different websites You can see me that provides some information But you know the field is still pretty new honestly and we're all kind of struggling through Looking at the research papers and trying to piece it together and looking for some of the pioneers who've done some of the again for me clinically relevant Work because it's nice to to see pathways, but the question is exactly what you said what to do about it So maybe come see me afterwards and I can I can give you a couple of things. Thank you. Yeah Is there a downside to taking too much five mtf and THF yeah, well remember you can substrate inhibit these pathways So if you took if you take very high levels, you know very high levels of five mthf You can inhibit mthf our function And and possibly you know cause other pathways to shut down and how would how would that manifest through greater depression or? Well, if it's mental health. Yeah, I mean we see people, you know It sounds nice and straightforward, but we see people who you know What happens is we'll get them on the correct methylation regimen and they'll be doing better and better and then you know Doses will increase or whatnot and you'll see big crashes Or you'll see them flip back into depression or anxiety or cycling of mood or a variety of things So yeah, you definitely can you can take too much. Thank you. Yeah, thanks. Yeah, just an answer to that I still have the acne scars from homozygous six seven seven Pretty much everything is red on my 23 and me congratulations. Yes. Thank you. I have won that genetic prize but just kind of the opposite question because I Basically have also got on had to go down the rabbit hole. Yeah depression anxiety OCD anorexia done it all been there and You know, I've spent my weekends on PubMed trying to figure things out And so I'm just wondering clinically if you've seen kind of a Minimum effective dose of things to look at before it starts getting Overwhelming and too much. Yeah Well that 800 might for 5mth f at least that 800 micrograms to a milligram Seems to be a good starting dose for me like when we go down to 400 micrograms or 200 micrograms You just tend not to get a lot of clinical effect And so unless the person is extremely sensitive, which I do work with people who are then we tend to start In around that one milligram dose range now one thing just a little clinical pearl niacin or vitamin B3 Is sort of an antagonist and so if we get people in trouble with too much 5mth F we often will then dose them up with niacin and that burns through methyl donors very quickly And often we can you know bring them back basically Thank you. You're welcome. I Recently read a research support that said that high intensity exercise Increases your home assisting levels Yeah, which makes me wonder if maybe Home assisting from exercise is not a really a bad thing Well, that'd be I don't know I you know, I don't have the answer here But we saw it the very minimum creatine requires methyl donors for its creation, right? And so then the usage of methyl donors like sammy when it's being when they're it is being tapped to create things Like creatine or phosphatidylcholine for cell membranes Is would be used up and I don't have the answer for you But it's possible then you're seeing a transient elevation of homocysteine Because the exercise has put a greater demand on the system Normally we'd like to see that that you know that rise in homocysteine would be transient and that the three different Pathways would pick up the homocysteine and then you know recycle it or clear it out of the system We're all done. All right, if anybody has any questions, I'll stick around Please feel free to come ask me again. Thank you