Decoding MTHFR: What Every Healthcare Professional Needs to Know 7th Nov 2024

So for those people that are just joining, don't worry, we have literally just started. Oh, everyone's coming in, coming in hot right now. What are we on? We're right on time. Everyone that's popping in, we are just literally starting now. So if you haven't seen on the socials, you may have seen the email that came out. I have just come back from a huge event, the biggest event that I have been to and the reason I share this with you is because I believe this is the first time and I go to lots of conferences, do lots of international talks on nutrigenomics, on personalized health, preventative health, health. This is the first time that I have been somewhere where a country is actually embracing so precision health and wanting to turn their entire health care model into a preventative health care model. So what does that mean? They want to move from a reactive model where people are getting a diagnosis or getting sick to a prevention model which really includes genetics, AI and new technologies. So they want to do this by 2030 they've invested $13 billion and there is a big emphasis on genetics. So currently already in this country they are doing genetic testing on couples that want to get married to identify rare genetic diseases. So in Saudi they actually have a higher frequency of rare genetic diseases, but their plan is actually to do whole genome sequencing on the entire population or genetic testing on the entire population and is not just in the clinical genetic sense, which I'll explain, but also getting into nutrigenomics as well. So personalized diet, personalized health, so very, very exciting. I will just mention though, even though they're talking about the entire population, I get excited by it. I don't necessarily think that every single person should get genetic testing. I think this should be a choice. And you will hear this throughout the webinar. If someone wants to get tested, I believe they should get tested, but if they don't, they don't. So the healthcare landscape is transforming with the advent of medicine 3.0. We are moving towards a personalised data driven care which is referred to as precision health. And this brings in insights from genomics, epigenetics, lifestyle factors and it prioritises prevention, precision and optimising health outcomes. So we're going to be talking about MTHFR tonight and what I want you to understand is that although MTHFR is very important, it contains genetic variations that do have a significant impact on folate, homocysteine methylation, which, which potentially can affect diseases, well, health outcomes, fertility, cardiovascular disease, Alzheimer's, but it's just one gene amongst your entire genome. So we have about 3 billion bases. Bases are our nucleotides, A, T, C and G. These are the letters that make up your genome and within that we have about 20 to 25,000 genes. So MTHFR is just one. But what you need to know is that more than 99% of our DNA is identical. It doesn't matter what colour our skin is, our ethnicity, if we look completely different, more than 99%, it's predicted about 99.5% of all of our DNA is identical. However, we have these slight variations generally referred to as SNPs. SNPs are the most common variation. It's just one base pair change and we do have some heavy hitting genes and I include MTHFR in here, bdnf, apoe, tnf, alpha, et cetera. That can have a big functional effect and that's what we'll be talking about tonight, the functional effect that MTHFR can have and how this influences health, how to test for it. So tonight we'll be talking a lot about testing and then also what can we do from a therapeutic strategy perspective just before we get stuck into mthfr? I do want to differentiate the different types of genetic testing that are currently available in clinic. So we have medical genetics or clinical genetics. This has to be done by a medical doctor who has specialised, who's gone on to do advanced training in genetics. That doctor will then work with a genetic counsellor and this is when they are trying to identify genes that cause a disease. Very different to nutrigenomics where we're looking at things that influence nutrition systems and pathways. So this is about diagnosis. We've got pharmacogenomics which relates to the metabolism of drugs and pharmaceuticals, so personalized prescriptions and then we have where MTHFR fits this brand sort of nutrigenomics. Now don't be surprised in the coming years if this is all blended in one if the names change. But I'm just trying to help you understand that there are different types of genetic testing and depending on the type of practitioner you are, if you are someone that can provide nutrition advice, lifestyle advice and recommend supplements, you can be implementing nutrigenomics in clinic if you're not already. I do have a little comment there on the right, if you haven't seen it, you can get a recording. It's. I did a webinar with PLMI with Jeff Bland and he actually now calls it calls nutrigenomics lifestyle genetics and I do Think that will probably start to take over because nutrigenomics once upon a time was focused specifically on the interaction between genes and diet. So when I started 20 years ago in the nutritional genomics lab, we were looking at the influence of folate and mthfr, whereas now we're looking at genetics that influence chemicals and toxins. So you know, pollution, air pollution, you know, things like that. So it's sleep, exercise, so it's much more than just nutrition. So I've already mentioned what you'll be getting from today. I'll give you a lot of information that hopefully will help you decide if you think you should be testing for this, if you're not already. Clarity about the gene, different testing options, how to incorporate this into clinic. The communication part will come in your PDF and personalised health plans and there'll be more tables in relation to interpretation and more the therapeutic considerations around diet and supplements in the PDF as well. So I know that many of you here on the webinar tonight know me and, and a lot of you actually know how I practice already. But if you don't, I want to make it clear that although MTHFR is very important, it has a significant impact and I think we need to understand that, be able to communicate it to our patients. I don't test for it on its own and I never have. Even in the early days when I was doing this in a research sense in the public hospital, in the fertility clinics and the high risk pregnancy clinics, this was amongst a thrombophilia screen with Factor 5 and Prothrombin as well as other methylation related genes. So what I do now is more comprehensive testing. So I'm looking at and, and I'll show you exactly what I do, but I'm looking at tests that have lots of genes. Now when I said I'll show you what I'll do, I'm only going to show you the MTHFR part but I'll show you the different tests that are available. But the point is that I'm not doing a single gene. I'm looking at comprehensive DNA testing and I put this together in a method that I call the DNA connection method. It's easy to explain to the patients, it helps me have a system, we have the detect component. So with the genetics I'm often doing some other testing as well, whether that's some bloods, you know, hormone, stool, often the genetics, we not often. The reality is to make the most of DNA testing you do want to have some other complementary testing genes tell you about risk likelihood, you understand your lifebook, you understand, you know, your genetics. I feel like that's the foundation of everything. But we still need to have some other markers to understand that person's biochemistry or what's going on in that moment in time. So there's the testing component, the nourish is in relation to that action plan that I give them and then the align may be that we're coming back and repeating a test like they might have had a high homocysteine or, or they had high cortisol and we're going to redo a dutch or something with the stool. The genetics though, that stays the same. So once you've done DNA testing you don't need to do that again unless you are looking for a different gene or you want to utilise a different report, but the genetic results won't change. You can go back to those years and years down the track. So obviously I won't be going through all of that. We're going to do a deep dive into mthfr, but know that this is a very important gene part of nutrigenomics, which is part of what I do in the, this precision health approach. So when it comes to mthfr, I'm not sure if you, like me, have had a big resurgence in people wanting to know about it. So the term MTHFR I had a Google search is searched by Google on Google approximately 40 to 60,000 times per month. In addition to that it is looked at in relation to, if you look down the bottom, the mutation, health implications and treatment approaches. So we can see that there's a big interest from people wanting to understand it. Now I'm not sure if you've seen this software before, it's new to my world. When we did the Wednesday webinars, one of the lady reminded me what it was called. I think it's called Ask the Public. I did this a little while ago and I put into it you can put the country and what the sort of question is or what you want to know. So I put an MTHFR gene Australia and it came out with an average of 5,400 hits. But also you may not be able to see it if you're on a small screen. What it does is actually give you the most common questions that are being asked about mthfr. Now if you want to get all of them you have to pay, but in the free search you still get a lot of information. And when I looked up mthfr in the USA, it was at 40,500 searches on average per month. So these are the questions that popped up the main ones when I used this search tool. So some of them, we're not surprised. I'm sure you get asked this from your patients too. They want to know about MTHFR and folic acid, MTHR and folate, pregnancy, you know, mental health, iron. But there are some strange. Well, I think strange ones, and I shouldn't say strange, it just opened my eyes to the fact that I forget that people don't understand basic genetics. So if we just skip over to the second column here near the bottom, the second last question, can men have mthfr? When I saw this pop up, these are. These are the most common questions being asked in this search. I was thinking, how do people not know that men have mthfr? Or people are asking, is it real? You know, can you turn it off? And I thought to myself, I really need to think about the language I use because these are our patients. They are very confused and pulling things back a little. I do have a bit of an intro that I do. You might do something similar where I let people know they inherit their DNA from their parents and I go through things. But I have to admit sometimes it is a bit clear that people aren't understanding what I'm trying to communicate. For example, with vitamin D, particularly if you're using something like smart DNA with a red dot, people say, oh, vitamin D is bad. They just, they equate red with bad. And they'll say, but, oh, I've just had my vitamin D tested. How can I have the vitamin D? How can it, how can it be red? But my vitamin D levels are okay. So I then have to explain, okay, we're just looking at the genesis, not the level. So we do have to step it back and educate people. And when it comes to mthfr, yes, men have it. Every single person has it. And if we didn't have it, we would not be alive. It's essential for folate DNA synthesis. And the things that we'll talk about, well, we've just skipped ahead. So not only is there this sort of big interest, we now have people like Gary Brekker jumping onto Diary of a CEO and Joe Rogan and talking about methylation like he knows it all, has a supplement company in the background. It's a lot of money to do his test. It's not that many genes. And then he recommends methyl folate. And to my knowledge, it doesn't matter what the results are. I can't say that for a fact. But my patients who have, we'll just put you on mute there. My patient that has done his test before, he came to see me actually, Erica Wills is here. He's your patient as well. Not that we'll name him, but he's very interested in longevity space does a lot of testing he did that showed me it looked very similar to fit genes. Not that many genes, some of them with not a lot of evidence. But despite not having MTHFR677, in my opinion, not having a strong need for extra methylation supplements, he was still prescribed methyl folate. And I have to tell you a little side note, I didn't want to get distracted because we've got a lot to cover. When I did the Wednesday, the yesterday's webinar. So this is the second time doing it. The second I finished, my good friend Craig Harper sent me a message and I looked at it and it's a video from this guy. Like it's a five minute clip. I might share it with all of you if you're interested. The timing was unbelievable. It's a, it's a, it's a, it's a clip. And Craig just messaged me. Is this true? Basically it's Gary Brekker saying that people think they've got food allergies but actually if one day they can eat corn but the next day they blow up, they don't have a food allergy to sensitivity. Now I agree with that. I know that every one of you as a practitioner here understands that. But then he comes in and says what they're missing is methyl folate and 40% of people, 44% of people have this mutation and basically saying they need methyl folate and they'll fix that. And it's just like it's not that simple. Anyway, I'm going to send it all to you. But there's good and bad things about this. There is good things in the sense that he's bringing awareness to nutrition, to pathways. But we need to step in as practitioners and we need to clear this up, let people know it's not as simple as that. It's not just taking methyl folate. We want them to do, if they are going to do testing, you know, other testing as well and that, that comprehensive approach, whether you call it integrative medicine, functional medicine, neutropathy, precision health, it's not just one supplement. So yes, he's, yes, he's out there talking a lot about this. I wouldn't be surprised if you know, every One of you has heard it, and if you haven't, don't be surprised if some patients come to you soon. I now meet people on planes. The second I say I do genetics, it's, you know, people are like, do you know about methylation? Should I take methyl, folate? What about mthfr? Once upon a time, it was a unique group that were asking these questions. It was people that were generally sick, they had a chronic condition, they had fertility issues, they were seeking us out. Whereas now it's people that aren't even in that state. It's just general, the general population wanting to get well, wanting to optimise their health, which is an exciting time. But we as practitioners need to be providing accurate information, actionable information, and what I hope that every one of you, and I'm sure you are on board because you're here, is going to support this movement towards regenerative medication, medicine, preventative health, but sharing this information with truth and accuracy. And in case you don't know who I am, I think most of you do. I have been in this space for over 20 years, nearly 10 years as a scientist focusing on methylation testing, MTHFR, and 12 years as a practitioner. So all the information I'm giving you is based on evidence, based on science, but then also my clinical knowledge and opinions. So we need to reduce the confusion about mthfr. It's so important for fertility health. There's a boom in longevity. People are investing in genetic testing for their health. In addition, this is important for just reducing the burden of chronic disease, whether that's mood and mental health, cardiovascular or, you know, things like Alzheimer's and dementia. So right now, the medical model, our conventional medicine, so in Australia, we're a little bit different to Saudi. We are not pushing towards a preventative health model, a transformation by 2 by 2030 just yet. Hopefully, I think we will get there. But right now, the Genetic Advisory Committee for the Royal College of Pathologists suggests overall that we shouldn't test. But despite this, I do want to share with you what they've said in this document. They acknowledge that two variations do reduce the activity of the enzyme. There's a critical role for folate, and it's reasonable to postulate that MTHFR plays a role in the pathogenesis of many disorders. But despite acknowledging that the SNPs do reduce activity, it's likely to play a role. They then go on to say, if I can just show you this second point here that I'm circling, the clinical validity is not there because the evidence is conflicting. And what MTHFA doesn't do is consistently show an association with a specific disorder. Now, I think all of us understand that when we're looking at something like MTHFR because it influences folate, homocysteine, it can be modulated through our diet and our environment. We're not looking for a gene that causes disease. And I think that's where the biggest confusion is when we talk to the clinical geneticist here. Unlike some of the amazing clinical geneticists I met when I was away that are also doing nutrigenomics. One of the geneticists I met in the last trip who runs a clinical genetics clinic, is also looking at things like mthfr and methylation SNPs. And I was so excited to hear her say, as a clinical geneticist, a medical doctor doing genetics, that it's crazy not to be testing these methylation SNPs when we can do so much through diet and lifestyle to balance methylation, which can influence health. And that's really what we're looking for. We're looking for genes that influence pathways to optimise health or if someone is struggling to help them get back into balance and get well. So we're not looking to diagnose a disease. This is not clinical genetics. In addition, what is considered or why it's thought we don't need to test here in Australia is because in 2009 we've got mandatory fortification of folate and this states that people are less likely to be deficient in folate. But we'll talk more about that at the end. So where there are, I guess, considerations or what is advised for MTHFR testing here in Australia, and if you are international, excuse me, as I focus a lot on Australia, but I would say that most countries align with this, this sort of move towards preventative health that I've just seen in the Middle East. This is not adopted by most countries yet. So most, most countries will be similar to these and if not, please put in the chat. Let me know what the guidelines are for your country around testing for mthfr. But here in Australia, our guidelines state that MTHFR testing should be considered after stillbirth, after a baby is born with cleft palate or cleft lip, neural tube defects or congenital cardiac abnormalities, and really any congenital abnormalities, we know that folate does play a role in growth and development. In addition, the other time that we want to consider testing MTHFR is if maternal fasting homocysteine is high following fetal death associated with growth Restriction, preeclampsia and thrombosis. So when I was in the clinic, it was not this extreme. Testing MTHFR was part of the routine workup in our recurrent miscarriage clinic, but also in our high risk clinic. So if a woman had come in and had preeclampsia, had growth restriction. Growth restriction, and had a baby, so this is obviously post fetal death, we would test mthfr. So things have changed. The other indication for testing that you could get on Medicare that is considered in alignment with sort of more the conventional model is doing MTHFR testing if someone's had a stroke and they have elevated homocysteine. However, I really don't know any doctors. You might. I know there's lots of gps on here with us. Please let us know if, if you do this. But I know when my dad had a stroke, I asked for him to have his homocysteine tested and they weren't interested in doing that. So we do have some instances where MTHFR can be considered. It could be tested, you know, through the public system, through Medicare. But in general, again, they're looking more at diagnosis. The way that I see things, and I'm sure all of you here are as well, is we're not looking to do something after a baby has died or after someone has had a stroke. This preventative health model that we're going to is looking to identify risk factors, inform people of their risk, give them the information so that they can make lifestyle changes, they can make dietary changes to then reduce their risk. Now, I will make it clear that not everyone wants to make these changes. There might be someone out there who's smoking and drinking and they've got high homocysteine. And we don't need to test MTHFR because the reality is they want to keep smoking and drinking. But there are lots of people out there now, particularly as we have an aging population, that want to do something about their health. And we can now personalize this with DNA testing and then giving specific dietary or lifestyle advice and in some case supplements. So MTHFR is not a diagnostic tool, but there are two SNPs that we'll talk about that have a functional effect. They influence folate, homocysteine and methylation, which is a critical biological process in the body. And what we're doing when we test MTHFR is we are identifying pathways or nutrients that may require support in this space of preventative medicine. So what is MTHFR? Methylene tetrahydrofolate, reductase it's an enzyme that converts folate into 5 methyltetrahydrofolate. And many of you probably give this as a supplement. It's likely to be the most studied snp, but in time I imagine it won't be things like BDNF and apoe. There's a lot of money being invested in understanding these genes. So mthfr, really in the 90s there was a lot of research happening because there was a strong link with homocysteine and cardiovascular disease. And then when I started in the early 2000s amongst others around the world, we started doing a lot in the fertility space. And since then we've seen a lot of connections to or associations with mental health disorders as well. Now we know that these two SNPs, MTHFR677 and 1298 reduce enzyme activity and they impact the affinity, the binding of the CO factor, which is B2. People that have these SNPs are at risk for higher homocysteine. There is no doubt about that. The evidence for that is very strong. You can say that as a practitioner and you are fitting within the guidelines. We have strong convincing evidence. There's no doubt about IT, particularly the 677 TT or the compound heterozygote, that this links with high homocysteine, lower folate. And we have studies to show that these people are less responsive to folic acid supplementation. Now you might be thinking, well I don't want to give folic acid supplementation but the reality is majority of our research is with folic acid. We still don't have a lot with methyl folate to quote just yet. So with mthfr, the gene that has the biggest impact is or the SNP is the 677 SNP. If you're not sure what I mean by 677, when we have our genes, there's a start codon and a stop codon and we have all of these bases. And what we are saying is that at position 6, 7, 7, so along the gene at 677 some people will have a C that's considered the so called normal, the wild type associated with normal enzyme activity. Because the gene codes for a protein, in this case it acts as an enzyme. But some people at that Same position at 677 within the gene will have a T allele and this is called a single nucleotide polymorphism, a snp. Just one base pair change, one letter change. So here we can see the C allele. If someone has two Cs, a CC, they inherit a C from mum and from dad, they will go on to make a normal shaped protein. It binds to the CO factor Fad, that requires B2 riboflavin and it will convert folate push over to make 5 methyl metabolize homocysteine support methylation. However, if someone has a T allele, particularly if they have a tt, a CT as well, so maybe it could be a C from mum, a T from dad or two T's, what happens is the instructions are different. Then we get a different amino acid in that amino acid chain, that sort of amino acid peptide that is folded into a protein. The shape is different and it doesn't bind so well to that CO factor, therefore it influences the function of that enzyme. And this is what we mean when we say it's slower enzyme activity. It's not working so well. If you've come to my talks before, this table is not new. If you haven't seen it. I put this together quite a few years ago because a lot of practitioners would say to me, what about the combination of SNPs? What happens if, say, for example, if we look over here on the left, we've got our, the ccs, the ct, the TT that I was talking about, let's say someone. Now by the way, this is very, very rare, you wouldn't like likely see this, but let's just pretend. If we look at the third bottom row, a TT and an AA. If someone has a TT, which is the biggest impact with MTHFR677, that's about a 60 to 70% reduction. They've got an AA. Sorry, we do see that, the TT with the AA. I was meaning the bottom one, but the TT and the AA. The TT is the homozygote double variant for 677. AA is the so called normal, the wild type for 1298. So if someone has that, then that is a 60 to 70% reduction in enzyme activity. So meaning there's only 30 to 40%. So that's the TT that has the biggest impact on enzyme activity. But the other one, as a practitioner that you want to look out for with your patients that has a clinical effect is what we call compound heterozygote. And now you should have got your interpretation table, what I call that cheat sheet on that too you will see the compound heterozygote explaining what that is. So we've got one SNP at 677 and one at 1298 and that results in 50% enzyme activity. So it's only working at half pace. It's not converting as much of that folate around to make 5 methyl and to support homocysteine and methylation. So this is the pathway that I put together back in the early 2000s. Didn't get published till 2008. But I want you to focus just on the MTHFR. The reason I'm showing you the pathway is because, again, we're just putting this into context. It is not the only gene. There are other SNPs that influence methylation, homocysteine as well, but it's definitely the one that has the biggest impact, particularly the 677. But what MTHFR does is it specifically converts this form of folate that you can see just above it. You can see my mouse circling it.510 methylene into 5 methyl. So it does not convert folic acid. Folic acid comes in higher. It's the enzyme that converts folic acid is called dihydrofolate reductase. But it's 510 methylene and it is an active form. It's important because some people say too mthfr activates folate. Well, the reality is 510 methyl methylene is also important. This is a simplified version if you want to get super technical. There's lots of different types of folate. We call them functional folate derivatives. It's just that 5 methyl is very important. It's the predominant form in the blood, but it is what is needed to give a methyl group to homocysteine. SO5 methyltetrahydrofolate gives a methyl group to homocysteine. When that methyl group sticks to homocysteine, we've got methionine that then makes sam. If you can see that over here, now over on the left, S adenosyl methionine. That's your universal methyl donor for all the methylation reactions. And if you're used to seeing the pathway the other way, I put this one in as well. This is taken from one of the Pure Encapsulations webinars. Again, if you orientate yourself to the left when I'm looking at different pathways and you might find you probably do the same thing, but when I'm looking at pathways, because sometimes they're represented differently. Remember, we're just trying to simplify a very complex pathway. Sometimes people show it in different ways. But orientate yourself where the MTHFR is and what you should always see is the 510 methylene to the 5 methyl. I want to make a big point of saying that MTHFR SNPs are not necessarily bad. Yes, it links with higher homocysteine. We know high homocysteine is really an issue for pregnancy complications, miscarriage, cardiovascular disease, Alzheimer's, dementia. But the reality is, if this SNP was just bad, it wouldn't be so common and we wouldn't have evolved to have this SNP in the sense that the. The folate above it, 510 methylene. This actually supports what you can see over here on the right. So dump is representing uracil that's found in RNA dtmp. If you can see that there, that is thymine, one of the four bases of DNA. So this form of folate pushes over to make thymine, which supports DNA synthesis and repair. So this actually can help protect against DNA damage. We know that there are higher frequencies of MTHFR SNPs in certain latitudes where there's higher, like sun and UV damage. And there's some evidence to suggest that having this slower snip here actually protects against the UV DNA damage that we get. So it's not necessarily all bad. I mean, we don't need to go into nearly that much detail with our patients. But I'm just telling you that to put in context, because I get people coming to me, they've been told by a practitioner, they've got a diagnosis, they think it's a bad thing. They, you know, again, they're asking, how can I reverse it? This has caused my miscarriage, this means this, and they kind of go into panic mode, stress mode. So we need to put it in context of what it means in the pathway, that in some instances it may not necessarily be such a bad thing. But if they've got plenty of folate, B2, which is the CO factor, that's going to keep homocysteine in check, that's going to support methylation. So this is one of the research papers that we did looking at MTHFR in relation to foetal loss. So in this particular study we found that MTHFR did actually have a strong association with late fetal loss. So this is not recurrent miscarriage. So when I was talking about recurrent miscarriage, generally, we were looking at losses before 12 weeks, so this was a late loss. When we looked at the MTHFR of just the mother, we actually didn't see an association. In this study, we looked at the mums and the dads. And the reason we did that is because my previous study we Also didn't see an association with. So I was looking at light complications with MTHFR and preeclampsia. And that was a bit of a shock because the last author on this paper, Gus Decker, who came over from the Netherlands, he ended up being the head of maternal fetal medicine at the Lyle. Anyone who's in Adelaide, he's still over there working in this space. So he came over and he wanted to repeat research that he'd done in Europe and he had seen very strong associations with MTHFR and preeclampsia. So he came to Australia. That was part of the work I was doing in my PhD. We had funding from NIH and we did. We were not able to replicate the results. We didn't see this strong association with mthfr, homocysteine and preeclampsia that he'd seen in multiple cohorts in Europe. The difference was we were supplementing not just with folate too, but also B vitamins. So we were giving B complexes, prenatals and B complexes. So we think that the supplements were helping, which is what we do to support mthfr, and it was bringing that homocysteine down. So we weren't seeing that preeclampsia. But in this case, our second lot of studies, when I did my postdoctoral fellowship, we wanted to look at the genotypes of the mothers and the fathers. And when we counted the number of SNPs with the mothers and the fathers, we did actually see a strong association with mthfr. So the number of variant alleles in association with foetal loss. But I will say that these mothers that did have a late pregnancy loss also had high homocysteine. So if you're in Australia, you can do MTHFR testing through our major path labs, Sonic as well as others. If you are using the standard pathology labs, it's called an MTHFR screen, they give some information, instructions. Most of the time it's between 70 to $80. I say that now, in November 2024 it might change. When you are looking at the standard path labs, they do tend to show the results as 665. Just to confuse you, you probably know that if you're doing just MTHFR testing and also 1286, so the SNP is MTHFR677 and 1298. So the centre for Genetics Education states that this is outdated information. However, they've been reporting it like this since before I left the hospital and we were working very heavily in this space and we weren't changing our results, but the whole, the whole thing is just to let you know. And this is why you've got that interpretation sheet, what I call that cheat sheet, so that you can look at any result and you'll know what it means because this is a lot of the questions that I get from practitioners. Also if a patient has asked for their results from their doctor, they then get confused because it doesn't match what they're expecting. So with NutraPath they report the results as heterozygous or homozygous or wild type. Again, refer to your interpretation sheet for that to understand that further. And I do have that at the end to go through. So what does that mean? It means that they've got an AC or a CT one variant, one normal. I don't do single MTHFR testing, as I said, so I'm not using those standard path labs. But if you did want to do MTHFR testing, you can, as I said though you just likely are not going to get on Medicare. Don't request it on Medicare unless it is someone who's had a stroke, then with high homocysteine or as you saw post fetal death or fitting into those neural tube defects, congenital abnormalities. Otherwise the patient will have to pay. What I do is I mainly use DNA Life or Smart DNA. They're the testing companies that I mainly use and they do more comprehensive testing. So I'm looking at SNPs in methylation, inflammation, detox, etc, you know, HLA is looking at gluten sensitivity. So the DNA Life DNA core report is approximately $400. It can be slightly different from different labs. RN if you're here in Australia, Effects in New Zealand and DNA Life through Nordic Laboratories opposite offers it internationally. If you are international. We definitely had a few people on the last webinar. Nordic is really the most popular distributor in Europe, but they're also in the us. I use this for my international clients. So if you're seeing patients online like I do all over the world, you can definitely order through them all over the world, which is really good to know. So the difference with functional testing compared to some of the sort of standard laboratories is they do represent the results a little bit differently. I personally like the way these results are shared and also the patient feedback I get is that people understand this report more than the others and that is good for me because I want patients to understand their results. I don't want to be writing long complicated summaries or people coming back and being really confused so in this case, the MTHFR result is shown. It's a tt, so it's the double variant. They're saying the impact is high, so they use these dots and it's not red. So you're not getting that instant alarm, something's wrong. Because what happens with the red, green and orange? Feel free to put something in the chat. In your experience or if you, you don't find that, people get concerned. But I think that people get this, they just instantly think something's wrong. Like I use that vitamin D example. They're like, well, hang on, why is my vitamin D red? What's wrong? Why am I deficient in vitamin D when my blood levels are fine? So they're automatically thinking something's wrong. So this is really just saying we want to pay attention, support is elevated. We need to think about folate, B12, we need to think about supporting, you know, nutrition methylation. And it does give some advice. Over here on the right, this is one small section. If you don't use this testing company, if you're interested in doing, you know, more comprehensive testing and you don't grab a sample report from the company. The other one that I use is smart DNA. And when I say use, this is when I'm ordering. I get a lot of patients that have already done testing that comes come to me and you'll probably get the same. When you start telling people you do nutrigenomics or you can interpret mthfr. The way that they do this is they actually show MTHFR at multiple different points in the table. This is from the summary part. They are bringing the results together with the ctac and I do agree with this interpretation. They're suggesting that this, you know, is red. It requires support. We know that this results in about a 50% reduction enzyme activity. As I said, I don't love the red, but I can see why they've come up with that interpretation because that is the issue with some of the other testing companies. Their interpretation is not always correct. But the thing with smart DNA that sometimes confuses my patients, that if you're using this test, you just need to be aware of so that you can clear it up really quickly or let them know if they're reviewing it, why that's there so they don't come back later or they're not emailing you or getting confused. Is that the same result? MTHFR677 is shown further down in the report. It's still the CT but is green. Now, this confuses patients. They're like, well, how come up there it's red. Is this a different one? Does it mean that I don't metabolise B2? This is representing that B2, which is the CO factor I said before for the riboflavin, whether the person is likely to need more or less of that. I would say just from my clinical opinion, the research, you know, when there's a T allele, it is affecting the enzyme about 35%. I still think B2 is good. You want to give a B complex. I wouldn't necessarily put green if you're going to use the traffic light, I think maybe the yellow, but here they've got green and that definitely confuses people. And then further along in the report you do get a little bit more information. One thing that is good just before I move on from Smart DNA, though, is just moving away from mthfr, which I'll definitely come back to if you are doing testing and what I suggest is the comprehensive profiles, not MTHFR on its own. And you don't want to have apoe, which is linked with Alzheimer's and dementia. What you can do with smart DNA is there's a checkbox, so you can get all of the SNPs, but you can request that you don't get APOE. Now, I have to say that 99% of my patients do want APOE, but I attract a certain population, people that want to understand the genetics. But that is something to note because people need to know what results they're going to get. So FitGenes represents things a little bit differently. Again, they've got mthfr1 or mthfr2. The 1 refers to 677. The 2 is the 1298. I haven't ordered from them in a long time. One of the students in my mentoring or participants in my mentoring group shared this recently, so she told me it was 328. So in the past I've done a lot, I did a lot of fit jeans between maybe 2012, 2015. And one of the biggest questions I would get asked is, what's MTHFR1 or 2? So if you're looking at that sheet that I gave you, the interpretation sheet, that's why MTHFR 1 and 2 is there to show you that which one's 677 and which one's 1298? So now we're moving into direct to consumer. Now, this is one of many things that are available online in this particular test. So this is my results. I've Got results through Life DNA. So you can, people can just order a test or as a practitioner I've got a membership, I've got a membership to so many different DNA testing companies just as to see what they're offering. But here what they're suggesting is based on just genetics that I need to have or they're suggesting methyl folate at 1 milligram a day. And if you look at these up the top here where I've circled it, that the research strength meter that gray is all the way to the top, that I do have, you know, a higher need for this methyl folate, but these are my results and I actually don't. Methylation is a stronger point for me. I have other, I have other things. I got APOE with Alzheimer's, dementia, I got blood pressure SNPs but the methylation stuff is actually not my sort of so called genetic weakness or susceptibility. I do have the heterozygote, the SNP for 1298, but that has a minor impact and the 677 is normal. So what this testing company are doing is based on just one snp. They're suggesting I need to have this supplement which what I would consider high dose, 1 milligram of folate. So that's concerning. In addition, these are the results that also confuse patients and sometimes practitioners because they're giving you the opposite strand. So it's a C to a T but they're showing you a gg. So that's they're testing the opposite strand and then I've taken it out because it's too much information. Maybe I can do an extended recording or if you decide to come and jump into my academy, we'll go through all this stuff. They're also offering a different SNP that doesn't have evidence. So this can actually muck up the interpretation or what a patient might think if perhaps these two are green and this is red. Honestly I spent a good couple of hours just wondering where this came from. There's about four studies in the last 10 years. Took the slides out because I didn't want to go over time and now I'm going to tell you anyway. But about four studies in the last 10 years, three of those studies are from one cohort, one group they've just published, you know, different parts. So really it's only two studies. One was a specific condition in relation to pregnancy, another one with weight and then before that, way back in, you know, the early days when there was a big interest in mthfr a lot more funding. There were research studies then, but we don't even have a functional effect. We can't see that it's changing enzyme activity. So when you see things like this one, it's a red flag who's doing who, who is putting this information together. But secondly, for you as the practitioner, just to communicate this with your patient and let them know, hey, these are the only two that we want to pay attention to. These are the two with evidence. Ignore that. If they're looking at other SNPs if they've done 23andMe and they're coming to you with like five different SNPs that don't have evidence, you just need to tell them to ignore it. So this is my DNA, the Comprehensive Wellness Report. They also show the opposite strands, which can confuse people. As a practitioner, it is quite affordable. 235 I do think there's some limitations with the test though. But it is from a price point if you're wanting to start out and you want to have something a bit more affordable. The other thing is that patients can order it direct to consumer 3.95 so once you put yourself out there as a practitioner that is doing nutrigenomics, don't be surprised if they come to you with this report. So I get people coming to me that have done this and I'm glad they do. This is why I want you to be trained. Because I am not taking a lot of new patients at the moment. I have such a long wait list. But the reality is they're really confused. So if you haven't looked through this report, have a look through. It's got lots of great information, but there's almost suggestions they should be supplementing with lots of different things. Even the 1298, it says, consider holy basil, consider selenium, consider all these things. So, yeah, I really think it should be coming via a practitioner, not to direct to consumer. One thing I do like about that report though, is they are one of the only ones that suggests that MTHFR SNPs, the variants are slow, could potentially have a benefit. And that's in that DNA Protection and repair that I talked about at the start of the webinar. And then I couldn't help myself but add this in. When I was looking for testing companies, aside from the ones, the reports that I have, I wanted to share with you because a lot of practitioners say to me that introducing DNA testing is difficult because it costs them time. You know, you're not making money on this because you're spending time before and after, particularly when you're new to it. This I've taken off the branding and I'm not here to say anything bad, I'm just showing you for interest sake, this particular company, they are a supplement company is. So remember you get this for 235 as a practitioner or patients 395. This supplement company is charging $925 for the exact test. They do offer a 15 minute free consultation to help you with supplements and then they. I think it's like 160 if you want a longer consultation. But people are paying it. I'm not necessarily saying you should mark up your tests, I don't. They pay for the consult time with me but people are paying it and they're not getting the right information. That's what I want to communicate with you. People are jumping online but they're getting confused, they're not understanding what this means and often starting to take the wrong supplements. So this is Circle DNA. This is one of my patients in New Zealand. She got this on special for $600 reduced from $1,000. It didn't give any like allele results like the TTS, the A's, the C's. It gives all of these pictures I assume from this folic acid down the bottom saying normal. She does not have the MTHFR SNP's. But the most information you get from the report is here. I will say though, as part of that she got a consult, a phone telephone call from a clinical or a genetic counsellor. They said they were unfortunately there was a language barrier, she couldn't understand much of it. They sent through some information, it wasn't too bad but the main thing is she didn't know her results so she spent $600 and then came to me to help me interpret it and I had to say to her we're going to have to do another test. I can't use this. I can't tell you about your results. Looking at just these sort of scales here of normal or higher needs. The other one, if you're a dietitian or you're a nutritionist or you're very much focused on food as medicine, Nutrigenomics really targets food and I actually love their report. It's a great group behind them. If you look over here on the right, it's really clear for you as the practitioner and the patient, it's got the gene, the snp, the risk variant, the result. It says it's typical, it gives some advice, it gives Some information on food. I actually like it. I thought I would use Nutrigenomics for a little while because I get a lot of people coming to me wanting to know what should I eat? Here's my genetics, tell me about food. But the issue is they don't do the 1298. They're missing quite a few genes. On top of that, even though this looks quite good, there's some information. It says it's typical. Then when we get the variant, the double variant which is elevated, they don't actually change the information. What we want to do as practitioners is personalise health, personalise nutrition. So we don't want to have a test that says, okay, your typical is your recommendations, meet the RDA down the bottom and then you've got the tt, the strongest variant and we're saying, okay, still meet the RDA for folate. Now I know why Nutrigenomics is doing it. I know some of the people on the board, the advisors, a lot of them are actually scientists, some of the people I used to work with, so they're not practitioners. These are experts in nutrigenomics, they are very, very qualified in understanding genetics and nutrigenomics, but they're not practitioners. What we don't have yet is actually personalised guidelines. This will happen, I'm sure of it. Whether it's the next five years or so, our next lot of guidelines are about to come out. I don't think they're not. I know they don't have any personalization in them. It's more sustainability and cultural stuff that's coming through in the next lot. But in the future we will start to see some of this personalization, I can guarantee it. But at the moment I think Nutrigenomics are sticking to the guideline. But what I want to tell you is that if you see this, we are going to advise an extra serve of folate rich foods. We are going to talk to them if they need it, about supplementation and just know that I've added a lot more about this in your guide when it comes to advice around food and supplementation. The last one I want to tell you about is self decode. Give me a shout out in the chat if you know about self decode. They're doing some pretty exciting things. I was on the podcast which was quite interesting, which was after me making some comments about their methylation report. I just want to let you know, I don't think I'm going to tell you flat out, I might change my mind. But right now, November 2024. I don't think this is good for us as practitioners with patients. For me just to generate this one report on mthfr, I waited three hours and I had to leave it overnight. It has a wealth of information. If you're working with the biohacker people, if you've got people coming in and they're spending a lot of money with you and you've got hours and you can deep dive do that, okay. But unless it's the biohackers, unless you're wanting to spend days and days or you could do it for yourself, it's not the most user friendly for the patient interaction. So what's new with self decode is they have this decodey GP gtp. So on the weekend I was playing with it, getting ready for the webinar and I typed in MTHFR and this is what it told me. So it's looking at my results, it's scanned those and it's popped this up and it said RS1801133. So that is the MTHFR677 variant. Now I'm a CC and showing the opposite, the GG. Now that is normal but it says that's the risk variant and then I've got the heterozygote here. So I'm acknowledging that was on the 3rd of November. I'm sure that in the next months, maybe days, this will be updated. I think that if you're really interested in genetics, as I said, you know, the biohacker community, self decode does have a wealth of good information. However it's building, they do polygenic risk scores. The reality is I don't think the foundation behind the paleogenic risk scores are there yet. I know I need to get a move on, but I do want to say something about polygenic risk scores simply because one of the people in my mentoring group said why do we need to learn all this? Which is a great question. I loved it. But why do we need to learn all this if soon we're just going to have these polygenic risk scores? Like people will just put all of this information together and say hey, you need this much folate or hey, you're going to need, you know, selenium or whatever it may be. The reality is the genetics is a bit more complicated. The polygenic risk scores, to my knowledge at this point in time and I have advised and worked with some companies so I know how they're doing things, they're just counting the number of SNPs they're not weighting the evidence. So what we want to do with mthfr, if someone's got a TT that has a much stronger impact than say an MTR variant, you need to account for the difference in these, what I call heavy hitting SNPs, the Apoes the beating f the tumor necrosis Factor Alpha MTHFR. There are a lot of SNPs that yes, they have a functional effect but it's very small. So we can't just add them up together and expect that that's going to have an outcome. So we've just, we've got a little bit to learn before we can do that yet. If you're interested in self decode, these are the prices at the moment. I just pay for this one here and I do enjoy going in and playing around sometimes but it's, it's ours. So what we need is reliable research backed genetic information that is easy to interpret that we can go through in clinic with our patients. They understand what their genes mean, you know what to advise and they feel more empowered, they think, okay, I understand what my risks are, what I need to do. We want to check lab accreditations and I suggest if you are new to this or you want more information, definitely go and ask companies for sample reports what you would have got. I've just taken a screenshot. Obviously it's sort of branded. When I sent it to you, you have this interpretation table that I've put together and this table shows you the RS number. So up here we've got the 677, the alternate names, the description, it might be the alleles, the opposite strand, the classification, whether there's a variant and the positive negative. So you can use that, you can have that on your wall in your drawer. So if someone comes to you and particularly if they've done testing with a company that you're not aware of or it's shown a different way, you can quickly look and understand what the results are. Okay. So when it comes to doing this in clinic, I personally think that anyone that wants their DNA tested should be able to do it. I don't think we should be waiting, as I said, until someone's had a stroke and has high homocysteine. But what's important is that we're putting into context. We're not saying we're going to test MTHFR and it's the cause of your disease or putting fear in that person. We're helping them understand, hopefully genetics as a whole and then giving them the information for them to either get well if they're sick, you know, help them on that health journey, or ideally, as we move towards this medicine 3.0, set them up for preventative health. So these are a couple of testimonials. I initially planned to have some case studies, but in the essence of time, I couldn't. This is Kiralee. Some of you might know Tamara Nation. She sent her over to me. She'd had five miscarriages and five failed IVFs. So we went through DNA testing, tweaked a few things with her diet. She had the HLAS with the gluten, she had mthfr. We changed to a particular, particular prenatal with obviously the methylated folates and bees, and she fell pregnant actually, within a short amount of time. Now, it doesn't always happen that quickly, but this is the power of personalising things and giving people what they need. And then Sara, she's actually a relatively new patient. She came to work with me at the beginning of this year. If you came to Acnam, you would have seen her as a case study. She sees me more for healthy aging. She does have mthfr677tt as well. Homocysteine is something that we're working on. She's had high homocysteine, her father had Alzheimer's, but we've made massive progress with her. And again, not just with methylation, but just with diet. She's someone who tried everything and then by personalizing with genetics, we've had a lot of success. And she's actually doing my DNA connection program that I told you about. So stepping through that, which I'm doing now. So when it comes to introducing testing, we want to make sure that the facility is reputable, check on the quality control. For example, DNA Life does testing in triplicate, so they're doing their test, that genetic test, three times. You can be so confident that the results you're giving your patient are accurate when something is done in triplicate. So that's the gold standard. When I had a lab, everything was done in triplicate. That's just what we had to do. That does not mean that all these testing companies online, I can guarantee you most of them aren't, are doing things in triplicate. So that is the gold standard for delivering accurate genetic information when it comes to smart DNA. As I said, they're the two that I use. I'm not saying that you should use those, they're just the ones that I use. You do your own research and work out what's right for you. But with smart DNA, they use agrf, the Australian Genome Research Facility. I also know them very well. Towards the end of my research because things advanced so quickly, we didn't have the top equipment at the hospital and at the university, the medical school where I also had a lab, we started outsourcing to agrf. So CSIRO uses them, hospitals use them, they are the best and obviously have all the quality control and doing those things as well. When you're doing a test, you want to. You wanted to have both the 677 and the 1298, obviously with Nutrigenomics, the X test, which I think is very good for diet. Sadly it doesn't have the 1298. You can refer to the interpretation table. Always think, do we need some other testing alongside? Do we need to do a homocysteine? Are we worried about methylation at a really deeper level? You can obviously get a methylation profile with Sam and sar or do we need to go and look at a Dutch and hormones, depending on the case and obviously provide the recommendations. So just before we get onto the last section too, I wanted to just give you advice around homocysteine reference ranges because it's often the test we do alongside these methylation related SNPs, including MTHFR. So in Australia, our reference range generally goes to 15 micromol. So if someone's under 15, they potentially think everything's fine. But the reality is we know that 10 and under is actually associated with reduced risk of cardiovascular disease and that's what we want to be doing. So when we move into this precision health or this preventative approach, this integrative approach, we're actually trying to prevent these kind of chronic conditions. So ideally we want to get to these optimal ranges for Alzheimer's. Dale Bredesen has shown that to reverse cognitive decline, it can be helpful to get homocysteine down to 5 to 7. My work in relation to pregnancy outcomes, reducing fertility or pregnancy loss, preeclampsia growth restriction is between 6 to 9. At 12 weeks it does drop a little bit by 20 weeks, that's normal. And then Michael Fenwick, my supervisor, that does a lot in the world of DNA damage, suggests under 7.5. So this is what we want to be working in this optimal health, optimal ranges, helping people identify if they're at risk and then using biomarkers to track their health. So as I mentioned, MTHFR converts one form of folate to the to to 5 methyl. So if you are identifying these SNPs you definitely want to focus on folate. That's the thing you want to focus on first. So when it comes to food, we can get folate, a lot of folate from real food. The issue is not a lot of people are eating real food and if they do have these MTHFR SNPs, you may want to consider a slightly higher intake. But in reality a lot of people are not getting an adequate intake. So one of the questions on Wednesday is, do you give extra, do you give higher doses? In some cases you do, but we actually also just need to get to the fundamentals. Are they eating real food to start with? Because sometimes they're actually just not even meeting these recommended dietary guidelines. So if they've got good digestive health, which they may not, you might not need to overload them with folate rich foods. In your guide, I actually give more foods with levels of folate. And these are things that you can create, you can create some handouts for your patients and show them this is what 400 micrograms looks like, or if they're pregnant, you know, this is what 600 micrograms looks like with food. Obviously in pregnancy we're always going to supplement. But what I would suggest, particularly when we get to supplements, is depending on the patient, if you're not worried about sensitivities, 5 methyl is the form for supplementation that's directly going to help support MTHFR. The recommended dose of supplements is generally 400 to 500 micrograms. You may be considering more like, you know, 800 micrograms, even up to, in some cases, a milligram. But not everyone will need to you make that assessment. Have they got high homocysteine? Is this actually an issue for that patient? The other thing is the CO factors. Folate doesn't work on its own. So we need to be thinking about B12, B6, B2, those that came on Wednesday. I gave a list of suggested dosages, but now it's all in the handout, just to sort of get a wriggle on. And then a question that sometimes I'm asked, maybe not from an audience like this, but sometimes people say, well, you know, we've fortified our diet, you know, with, with folate, or we don't have folate deficiency in Australia anymore. But the reality is actually there's a lot of people that are low. They're not meeting the optimal ranges. They're homocysteine sitting at 13, 14, 15, 16, some in the 20s, their B12 is low. So we Know that certain populations, you know, including the elderly, those with digestive disorders, are likely to have lower levels and those under high and chronic stress. I mean, how many of your patients have digestive issues or under chronic stress? So although the diets of many people seem to be adequate in preventing clinical deficiency, so megablastic anaemia, they might not be actually getting that optimal health biomarker status. What we need to improve foetal development and pregnancy outcomes, what we need to reduce the likelihood of cognitive decline. And really, it comes down to the type of food we eat. You know, we're now eating a lot more processed food and we're not eating these whole foods. So I put this in here because I really want you, when you're communicating with your patients, to not make them think there's something wrong with their DNA. It's not that they've got bad genes. Our genes have adapted with our environment for us to be at the top of the food chain. You know, the species that have taken over the planet. Literally, what's changed is our environment. It's the chemicals and toxins, it's the diet, it's the lifestyle we lead. So actually, in some cases, just tidying up the diet, focusing on sleep a little bit, a bit of movement, can make massive changes. Now, that's not always the case. I acknowledge that some patients coming to you will be very complex. But again, this is where this testing is really helpful to know what's going on and some of these underlying drivers of what might be happening in their body. So the big question is, how much supplements do we give? How much folate, how much bees? We don't have evidence to say that in the guide, you'll get my clinical opinion. But despite not having those clear guidelines around personalised diet or supplements with mthfr, we do have enough studies, this is one example, to show that patients that have SNPs in MTHFR are more likely to need higher doses of folate or longer therapy with supplements because they don't bring down their homocysteine as quickly. Admittedly, this is folic acid. I know that most of you are not using 5 milligrams of folic acid, but the studies we have to date are mainly with folic acid. But we know that people require more or they're not getting the same effect. So if someone doesn't have an MTHF arsenic, and they've got high homocysteine for whatever other reason, you know, they're low often in folate and B12, that's the major Cause or it might be kidney issues or something else. But when we give these supplements, homocysteine in most cases will come down but it comes down at a slower rate with those with mthfr. So if you need to get homocysteine down quickly, you've got a fertility case, a cardiovascular case. You do want to be thinking about high doses. 5 milligrams. Just this is a whole other talk I need to get a wriggle on. But 5 milligrams of folic acid. The reality is I think we're a little bit outdated with that. We now know that's going to come through dihydrofolate reductase. It's going to saturate at 200 to 400 micrograms. You're going to get a hot a lot of, you know, serum folate and not getting into the tissues. If you've done my methylation webinars or the folate training, that's all other talks. I'm just letting you know that I don't prescribe 5 milligrams of folic acid. And I think we, we now know that collectively that we can do that a little better. Looking at cell culture studies comparing folic acid to 5 methyl tetrahydrofolate, we do see and this is not the only study, this is cell culture. We've got some others that are. I don't think we have as many in. I think we've even got one in humans. A couple of animal studies, not many. What's different about this one? And the reason I'm showing you this is it wasn't just looking at absorption. It actually then looked at levels of same. Most studies don't actually look at esodenosylmethionine because remember that's the big picture. It's the MTHFR influencing the homocysteine and then the same or the acetenyl methionine for all the methylation reactions. So despite 5 methyl tetrahydrofolate looking like it is absorbed better and there were different derivatives of folate, better metabolic activity, they didn't actually see a difference in SAM or homocysteine. I think the issue is we just need more studies. It's still cell culture, we need more work. But these are the studies that I guess are not getting us ahead. There's some improvement but not enough that we're seeing a big shift in moving away from folic acid. This is another review trying to look at the differences. The reality is there are limitations. Most of the studies are Looking at serum folate and that doesn't help us if we're comparing between 5 methyl and folic acid, because folic acid will raise that serum folate. Just to give you my opinion, as someone who's been in the space for 20 years, yes, we have lots of evidence for folic acid and yes, I gave for nearly 10 years and we had an 80% success rate in the recurrent miscarriage clinic. This is before mandatory folic acid fortification. I started in 2003, now that I work in this space and I understand and since then we have newer supplements, you know, 5 methyl tetrahydrofolate is more natural. If you've got a patient who is very sensitive or they've got fibromyalgia or they've got energy issues, every enzyme reaction requires, you know, ATP. If you can give something that's going to bypass mthfr, potentially be absorbed better and, you know, you need to support methylation. You've done the testing, you know, methylation is something that needs support. I would be jumping to methyl folate. I would not though be going to high. It's very rare, not never, but it's very rare that I would give high doses. I generally don't go over 1 milligram. And if you're staying under 1 milligram, you're also sitting within the guidelines, the upper limits for the guidelines, because post 1mg you can also start to mask B12 deficiency. However, I also don't advise giving folate on its own, folate with B12, B6, B2, et cetera. So when it comes to you doing testing in the clinic, each of you will have your own specialty focus on how this will support your patients. Ideally, I suggest doing comprehensive testing rather than MTHFR on its own. But if your patients come to you and they've already done MTHFR testing, hopefully you can watch this webinar again if you need to use the resources or you've taken enough notes that you are very confident explaining what those results mean. If you are testing yourself, choose a company that works for you, that obviously has accredited laboratories and remembering that this is one element, although a very significant gene impacting a very important pathway, it's just one element of that holistic approach. So when it comes to the genetics, and particularly in nutrigenomics, remember, it's not clinical genetics, we're not diagnosing a disease. But with genetics and nutrigenomic testing, it's the combination between the genes and the environment coming together to define the phenotype so often with phenotype, we're thinking about eye color. If you've done classical genetics and phenotype, it's, you know, it's your eye color, it's your height, but phenotype actually means what you're expressing. Are you expressing high homocysteine? So combination with your genes and your diet, we can change or in your environment, we can change our environment. Are you expressing type 2 diabetes? You might have all the genetic risk factors for type 2 diabetes, but that's only going to come about. You're only going to express that depending on the diet and lifestyle. So once we understand these genetic risks, we can then modify our diet, modify our lifestyle to change that phenotype to a phenotype of health. And that really brings us to that precision health model, that data driven model. So if this excites you as much as it does me, I know lots of you are already on the wait list, but I do have a wait list for an academy that will be going through a lot more than just MTHFR about implementing genetic testing. I'll be talking about epigenetics going through my biological age study. So the protocol around slowing the aging process. So if you're not on the wait list and you're interested if FJ is still here, is she here? Let me see, are you here? I don't know. Fj, if you're here, can you put, just in case someone here does want to know more about it or they're not on the list, put the link in. Otherwise it'll come as an email. The doors to that will be for those on the waitlist. You'll get early access will be next week and if you have questions about it, feel free to reach out to me now. I won't do questions now. We'll respect time. I know I've said a lot, but we'll get into all the MTHFR questions. Thank you, fj. Yes, if you can put that in the chat. So let me come out of here and stop share. There we are. Here I am in my hot little humid room. I should have left the aircon on. Don't know if anyone else is on the sunshine coast. It is hot. I'm gonna open my window. Excuse me, everyone. All right, so let's pop into the chat and you are depending on time. Welcome also to turn your camera off and have a chat. Or if I am unsure about a question, I will just refer back to you. Hello, Julianne, Very happy you're here as well. Lots of hellos Hellos. Okay. Melanie. I know. My goodness. Good question. Three by four. So I do think that 3x4, sorry, I've got to call it 3x4. I think that's what Yale said to me. I have done my test. I don't know if you want to hop on Melanie, if you're around, if you want to ask me a specific question, if you've. If you've got your test result. No, I haven't, I haven't done it. But the report appeals to me, the colors and things. But I haven't detailed as to what she's. What if there are any genes missing. It's stunning. The report is beautiful. So I had mine done and I thought, without a doubt, I'm going to use this. However, just in my opinion, it was a little bit overwhelming in the sense that. A bit like smart DNA, how it's got the mthfr, like it sort of repeats results multiple times. Yeah, the illustrations are phenomenal. Like it's just gorgeous. But the clinical, you know, actually going through that with a patient, which is always what I'm thinking. How can I deliver this to a patient? A little bit more difficult. I did meet with the team and they showed me all this stuff in the back end, which was great, but it was very complicated. I just need to spend more time. I guess it's like for all of you too that are introducing new tests, you know, with smart DNA, you know, fit genes I use for so long, it's easy to go through DNA life. I find really, really just easy interpret. But I think 3x4 could potentially be good. It does have a good reputation in the U.S. yale is. Has a fantastic reputation. Like I talked about nutrigenomics, having a really good team behind them, really good evidence. I think Yale is someone that we can trust. Everything is done to high quality. It's just how we use the report. And even though I've heard good things in the us there are some people now doing training here with people in the US and the feedback is too. It is actually quite complicated. So my advice is, if you haven't already, or you probably do, you've seen it, get a sample report and if you've got the funds, even do your own test. There are a couple of people here, if they're still here, shout out to Bram and Erica and maybe someone else who have got testing and wanted me to go through it. I haven't gone through their reports yet because I just need to understand mine. But keep updated with me. I will, I will go through it. And in future, I'll tell you. But my first. Yeah, my first impression was, this is amazing. I'm going to use it all the time. It's so beautiful. Yay. I was great. And then when I actually truly looked at it, I was like, this is complicated and difficult. How am I going to get this across to the patient? Yeah, good feedback. Because I find the. MY DNA one a little bit too complicated to the reporting. The. MY DNA one has very. A lot of limitations. A lot of the. The people in my practitioner mentoring have done it. They're very new to genetics. Often they don't want to be asking people to spend the higher amount, so they do it because it's cheaper. But in the end, it actually ends up being quite confusing. Even the opposite strand, which I can see. Steven, your next question. What is the opposite strand? So DNA has this beautiful double helix. And if you were to unwind that double helix, it's like a ladder. So you've got your alleles on one side, allele on the other. And a C will always bind to a G on that opposite strand of DNA and an A will always bind to a T. So when I say the opposite strand. Stephen. And when I go through. Sorry, I skipped a little bit over the interpretation table. I did go into it a bit more detail on the last one, but I was so over time on the Wednesday webinar. I was a bit considerate today, but that. Do you, Stephen, do you. Did you get the interpretation table that I called a cheat sheet that I won't be anymore? Calling a cheat sheet? Because it's not a cheat sheet. It's just a lot of information summarized. Sorry, it's Kim sue. Because I don't know why. It must be my husband's subscription. Sorry. Oh, that's okay. Sorry, I'm calling you the wrong name. I apologize. Thumbs up, like this. I'm so sorry. Yes, I did get the interpretation table. Yeah, I'm not. What you'll see on the allele side of that is the C's or the T's for 677. And then for 1298, you'll see A's and C's because that is how we report in the literature. And I will just tell you that even occasionally in the lab. So the reason why we test the opposite strand is sometimes when you're going through quality control, we add little things called primer. Just like making a cake. You're making a cake and you're amplifying your DNA and you're trying to, you know, get the snips. Sometimes it just works out that you get better results, more likely to get accurate results testing the other strand. But most of the time you'll get a C or a T. What we would do though, if I was publishing a paper or I was presenting at a conference, I never used a G or an A. I went to a conference in the US and just to toot my own little taunt, Mohawk, that that is actually an international award for the Society of Maternal Fetal Medicine. So, yeah, it was a long time ago, but it was a big deal back then. It's the biggest maternal fetal medicine conference in the world. So I was presenting my research and one of the SNPs, we did have opposite alleles, but I didn't get up there when I was doing the presentation and show the opposite alleles. I was showing, you know, I talk about the common ones. So I don't really know why these companies do it because I think it just adds an element of confusion. But yeah, it's the opposite strand. If you understand genetics, which hopefully now you understand it's the opposite. You just have to sort of have that moment in your brain where you convert it. It's the same thing. It's just the opposite strand of the DNA because our DNA has this sort of complementary strand. Does that now make sense? Great. If anyone else has a question about that, please let me know. It's probably one of the biggest questions that I get. Okay, moving on. Oh, this is actually you as well. I'll go back to you. I just skipped across to other people. So what about symptomatic patients with mthfr SNP but normal homocysteine. So can you tell me what you mean by symptomatic? Oh, you know, patients with chronic health issues long term and when they test, they've got, they've got the SNP, you know, 667. But the homocysteine is normal. So if the homo depends on what you think is normal, there's a potential the homocysteine is even low. Like six, did you say? Yeah, I don't think six is too low. Once you get under five, you're getting into issues because homocysteine is needed one to make methionine for Sami. So you could potentially be low in semi affecting methylation. But also homocysteine pulls down that transulfuration pathway for glutathione, those amino acids. So it's not always high. We tend to talk about high. And that will come out of My mouth a lot because particularly in the public hospital is always high. But now that I work in this space, often our most complicated patients will have low homocysteine. They're very deplete. And that's also a big impact on methylation. In those cases. We want to be careful giving our methyl folate in bees and pushing the methylation. We need to protect homocysteine. You can do that by giving NAC N acetyl cysteine because homocysteine pushes down to make cystathione cysteine. So you can kind of protect both pathways methylation. And though I did have one rare case, I actually discussed this on Wednesday. I don't often give same, but I had one patient where all of that stuff wasn't working and we couldn't get the homocysteine up and I actually went to same. I would say to you, if someone has symptomatic MTHFR itself doesn't necessarily cause symptoms unless it's affecting methylation because that level of same influencing breaking down of adrenaline or estrogen metabolism or, you know, energy production. So if the MTHFR is having an effect to go and cause symptoms, it needs to be. It needs to be changing the methylation status, which is then affecting all of these processes. So if someone's having lots of symptoms but their MTHFR is normal and their homocysteine is normal, that says to me it's something else. It's like, okay, well, it's actually probably not this. What else is going on? Have they got an infection, you know, have you done a stool analysis? Are they deficient in minerals, you know, zinc, magnesium, their co factors for hundreds of enzymes? So that then sort of helps you rule out one section. One thing I love about genetics is it helps you prioritize your treatment strategies. You can start to kind of go, all right, this is probably, we need to focus on inflammation here. Like, you know, maybe it's more so a chronic inflammatory thing or it's more so a something else thing because it's not always mthfr. You will get sick people. This is why I said MTHFR is not diagnostic. So it can be so helpful at helping you go. Methylation is where we're going to prioritize. Or actually this is not where we're going to prioritize. Maybe that's not actually your issue. Good question. Is that helpful to people? Yeah. Because even if someone has mta, this is why. This is why, I guess some of the conventional doctors here or the geneticists that I talk to. Because I've been slammed, you know, now that I've moved into this space. When I, when I presented as a scientist, I had respect from my community and I still get some respect. But one example was that I was presenting and I thought I was going to be able to make change. You know, we're just talking about preventative medicine making change like what we want to do. So this was a few years ago, but I was invited to an event with some people involved in government and hospitals and the health budgets blowing out and they can't afford the aging population. I was like, great, I'm here, they're ready to hear what I've got to say. I was not, they were not ready for what I had to say. So I can't, you might have heard me tell this story, Norman Swan, and I'm going to just say his name straight out. Norman Swan said to me, do you feel guilty when you test mthfr? And there is absolutely no evidence now, by the way, I'm pretty certain I didn't even mention MTHFR in my talk. So I don't know what he's seen about me. Maybe I did, maybe I showed some results, but I got up there and it was so much more than mthfr. I talked about understanding people's inherited susceptibilities, I talked about doing blood tests, basic stuff, lipids, you know, blood Sugars in your 30s, in your 40s, identify risk, help people understand what they can do to not get diabetes, not get whatever. No one was interested in what I had to say. At the end of two days of talks and workshops and roundtables, it came to that there was going to be a cutoff for certain surgeries after a certain age, some of them at the age of 70. So if certain things. And just like you could be, you could be 80 and still be really healthy. Actually we've got, and, well, I won't say your age, Dr. Rabinoff, maybe you can pop on. We have someone who's still working as a full time GP here who's over 80, he's my mentor, so I mean, that was a little while ago. We're definitely not there in the preventative space yet. But I want to let you know, when I went to Saudi, it blew my mind that they are all about this. Mind you, they've got a bit more money, all that oil money, we don't have that here. Okay, so, yeah, so with MTHFR just getting back to it, when you say it's symptomatic I understand what you're saying because the person is, is, is having issues, but it's probably not the mthfr. And this is where I think we start to have this divide because this is what. I guess if you actually go and read some of these clinical guidelines from the RACGP about MTHFR testing, there's actually a comment about a very well known clinic here in Australia that has MTHFR in its name. You know, it comments that this is not okay for naturopaths to be doing this. It causes a divide. They think we're doing things that are not evidence based. They think that we are doing that saying MTHFR is the cause of my disease. So hopefully, and if you need to watch it again or ask me a million questions, we can get really clear on the fact that it is super important. It can direct us on where we want to treat or, you know, support our patients, but it's not always the underlying factor. I'll get off my little high horse now. Sorry. I get very excited. Okay. And more questions. I love all your questions. It looks like actually we had so many questions on Wednesday. A bit less maybe because I ran through it faster Wednesday. I went so over time but we had so many questions and comments. How important is the role of B12? So important. If you give folate and someone's low in B12, it just gets stuck. Like the next step. When I say that 5 methyl donates a methyl group to homocysteine. It has to. It uses methyl B12, that is the CO factor for one of those enzymes. So if you do have a sensitive patient. Sounds like what you were talking about. Maybe. And you only want to give one supplement at a time. I would start with B12 before you start with folate and then think about your B6 and your B2. They all work together. But 100% B12 is super duper important and often B12 is the thing they might be low in, particularly if there's digestive issues. Right. It's quite hard to absorb. You need the pH. Right. We need intrinsic factor. It's huge. You know, if you've looked at B12 under the microscope, it's stunning, it's big, it's got a cobalt rod through the middle but it's very hard to absorb. It's our biggest like vitamin. So if there's any digestive issues, people are going to struggle with B12 absorption as well. There's a few steps. Okay. There's the waitlist of the academy. Thanks, fj. Lucy Hello, Lucy. Methyl intolerance and need for non methyl bees. Yes. Is there a way to identify these prior or is it just based on symptoms from methylated bees? Okay, so I'll do that bit first. That little line. Is that there? Yeah. So there's not really a way to accurately identify. However, even though I said I want to give methyl to support methylation directly, that's my first go to. If someone comes to me and they're highly sensitive, like they tell me they can't do perfume, they get headaches, they react to all these foods, they've reacted to supplements before. Even if they don't know if they're going to react to methyls, I just won't put them on a methylated supplement. I would definitely go with folinic acid and hydroxycobalamin. You're still going to be supporting the pathway and in some cases that can be, you know, that can be enough. Ideally you're going to get them well enough though that then they might be able to tolerate these, these methyl groups. So I would definitely be starting in those cases where you suspect it. I don't know how to. I think anyone who you think's got high chemicals and toxins too, like if you do do the GPL toxo, it's just change names or you think they've had heavy metal exposure, maybe they come to you, they've got high blood mercury. The thing with high blood mercury, arsenic is the. Actually we need methylation. That's sometimes where all the imbalances come to as well because you start kind of releasing things in the body. So methylation is one of the detox pathways for these heavy metals. So we do eventually want to try to get it in but I would start with the ones that's less likely to rock the system too much go with food, you know, hopefully as much food as they can kind of tolerate. Often they can't tolerate the sensitive people legumes and that's where a lot of the folate is. They can get really high doses in lentils and stuff like that. But yeah, just trying to get as much of the food in as possible and you will get a list in the, in the PDF and you can look that stuff up as well. But yeah, I don't have an exact way but anyone that's super sensitive, if they tell you they've got high toxins, if they tell you they've got really low blood pressure. Yeah then they can be issues as well. Did you want to ask anything else before I hop on to the next one more I can go to your next question but anything about. Okay, good, that was so MTHFR and the role of estrogen anywhere to look for this further? Yes, I love Dutch testing. So with Dutch you're going to get actually a little bit methylation dial. Now this does not reflect methylation overall we can't say that that is the methylation status or talk about epigenetics but when it comes to metabolizing those hydroxy metabolites we can get that. So I love Dutch testing. It's going to show you where the estrogen is pushing down and then if the methylation activity is high or low. So if you do see someone with MTHFR and comp comt being the enzyme involved in the methylation, the clearance of detox, you would, you know, I would then be thinking about a Dutch. I would be saying, well let's actually have a look if this is having an effect. Now sometimes you might not need to do a Dutch because they've got all these symptoms of high estrogen, reactive estrogens, whether that's endometriosis or whatever else and you can be pretty certain that they've got the reactive estrogens. But I always test. I understand that some people are not in a position to be asking people to spend all that money but I definitely would be testing and then doing a Dutch and then we know we can actually see those levels. Are you doing Dutch, Lucy? Oh, we can't hear you. Oh, there we go. That's all right, you can write more things. But I saw you nod, you are doing Dutch already. So if you're already doing Dutch, Mth, Char and Chris are in the body anywhere to look into this. So do you, are you asking then if you already do Dutch is there other genes to look for? I'll skip down, I can see that you're writing more. Oh, we got lots of questions actually, thanks. Oh, we've also got the winner of the FJ's own little thing for you. All right, I'll let you ask your put a little bit more in. And because there are other genes that are also linked with their metabolism too, I definitely look for NQO1 which affects the estrogen metabolites as well. So there's one more here over methylation I've done Bill Walsh's biobalance and found it brought up more questions than answers. Yes. So it was very difficult for me who had was a so called expert in methylation to move into this world of integrative practice and then learn about this over and under methylation, because we do talk about, at a scientific sense, hyper and hypo, hyper meaning, you know, high methylation. But I'm talking specifically about epigenetics here. A lot of my focus was to looking. I used to measure the methyl groups on the DNA, the mother's blood and the baby. So we have hyper and hypo looking at changes. Now with William Walsh, I think he has done some great work, but I too, couldn't comprehend it. And the reality is the over and under. Now, I'm not an expert. I know there's some other people sitting on this webinar that have done training. Feel free to pop in if you feel like you need to say something. But it's linking often to a lot of symptoms. A bit like what we heard from the lady's name, who's not Stephen. Sorry, you told me your name. You know, sometimes we're trying to match symptoms to something that are so varied that could affect other things. And back then, when I first started, too, they used to use histamine as a marker. And histamine can be influenced by so many things. Like, I just didn't think that was a good marker of meth. Histamine can be affected by, you know, exposures and all sorts of things and gut health, et cetera. So I do know that he's moved on to testing like Sam essendolmethione and sar, looking at the SAMSAR ratio. So I presented with him at a biobalance event and we had a conversation. He's doing things a little bit differently now, but whether that SAMSAR ratio is matching the kind of, you know, symptoms and the things he gave. But the reality is, I'll tell you as someone who. Who has spent so long in this methylation space, even when it comes to hyper and hypo in. In the sense of that, the genetics. And when we look at methylation, it's not consistent. It's not that you're an over or an under. When the body becomes out of balance, some things become more methylated and some things become less. We just start to get this. Think of methylation like a key regulator. It regulates turning on genes, it regulates your levels of neurotransmitters and adrenaline. It regulates your level of estrogen. So it's helping your body stay in what it thinks, if it's working properly, the optimal range, homeostasis. Methylation is so critical for regulation of so many pathways. Once you start having problems with methylation, it's not always consistent. It's just that regulation starts getting really mucked up. Some things are high, some things are low. So it's an imbalance. Think of it more like an imbalance. And when we talk even about hyper and hypomethylation with the genes, it's not consistent. We start seeing hyper methylation of some genes that shouldn't be methylated and then all of a sudden genes that are meant to be turned off and methylated are not hypo. So it's, it's just, it starts unraveling and we start getting these, these issues and that can be detrimental. It's linked with like psychosis a lot, with a lot of mental health issues, you know, cognitive decline, Alzheimer's, stuff like that as well. But yeah, so it's, it's not so much about it just going one way. The regulation system is no longer functioning properly and often it's more than just too just giving a bit of folate and bees. When you get to that level of dysregulation, like for example when I had Graves disease, you know, I was very, very sick. You need, you need that holistic approach. We're not just focusing on one thing. Like if you've got chronic inflammation, you've got free radicals and high oxidative stress, you've got methylation imbalance, you've got all of it. So that you just need to just stop, stop and get into a place that it's hard but like rest and digest. You just need to go into total. Everything's about healing. If you want to get out of something like that. You can't keep eating crap food and trying to work at a million miles an hour and scrolling your phone at night and doing whatever unhealthy habits because you're just going to stay really sick. You need to just be doing, you need to be giving your body everything to nourish it. Like the second part of my DNA connection method. Then nourish, then nourish. Give the body what it needs and then remove the stuff that is potentially triggering that. Okay, so can I ask about the difference between folate, folic acid and folinic? Which one to use? So I would use if you want to support methyl. This is a simple sort of thing. Obviously it can be a bit different. Think about, use your clinical knowledge of the patient. You know the patient better than me. But if it's for methylation, most of the time you'll use methyl, folate. I'm suggesting it, it's not in the guidelines yet. We don't have enough evidence But I'm suggesting on my, you know, 20 years experience. So it comes with a lot of clinical evidence with patients as well. I think the methyl folate most of the time, if there's some underlying issues, thyroid stuff, sensitivities, toxins, the folinic acid is really good and very rare. That I'd use folic acid. Again, I'd never say never, because sometimes you say never and then things happen. So I did have one patient who even reacted to folinic acid. She needed folate. You know, we knew that she needed folate and I did end up giving her folic acid. That's one in, you know, eight years or something. A bit like the case study we talked about just through the question time on Wednesday, because I kind of threw out, oh, I don't give same. And then I was like, well, actually, I've had one patient this year, fertility patient I gave Sami to. So I guess this is the sense of that personalized approach. We're always thinking about that patient. But generally it's. Generally it's the methyl. If you think there's going to be, you know, any sensitivities, then go with the folinic. Folinic's like a storage form of folate. It still needs to be methylated, still needs to turn into the methyl to work in the methylation pathway. And then it neat. And we have adenosole as well, but not in Australia. But adenosole is great for mitochondrial health. If you're not in Australia and you can access adenosole and you've got chronic fatigue patients or energy issues, definitely use adenosole or even a combination of adenosole and methyl. You've got the two active forms. Then the thing, if you've got lots of chemicals and toxins, folytic and particularly hydroxycobalamin. Hydroxycobalamin also helps neutralize some of the toxins and the inflammation as well. Hydroxycobalamin can be quite powerful. Thank you so much. MTHR results from Obs Gyne trying to use cheat sheet MTHFR heterozygous. Okay, so you are heterozygous 677 and 1298. So you've got about a 50% reduction in enzyme activity. This is for you, Sara. Common patient has one. Yes, that is correct. Associated with increased homocysteine. That's right. And risk for venous thrombosis. Oh, is this from your object? OBS and gyne. Okay. So at least they're okay. So it's not interesting saying it's risk for venous thrombosis. So we used to say that. We don't say that anymore. Interesting. You got that from your obs and gyne. So we used to do that with the obstetricians and gynecologists I work with. We did MTHFR as part of our thrombophilia screen. And if it came up, we would say it's part of, you know. Now, the guidelines I showed you from RACGP and the Royal Pathologist, they. They've kind of removed MTHFR from that. So it's interesting you got it. But it is, it's true in a sense. What you'd want to know is do you have factor five Leiden and do you have prothrombin? They're bigger risk factors for thrombosis, for blood clotting. Much bigger risk factors. Usually when we're doing a thrombophilia screen, when we used to, we did all of them together. So you might already have. If the. If the obstetrician's done this, they've probably done those as well. If you haven't been told that's really a good thing, it means you don't have them. The only way that this is going to cause thrombosis is if your homocysteine gets really high. So when homocysteine gets really high, it kind of metabolizes into this reactive metabolite that can cause a lot of damage inside the blood vessels called the endothelial cells. And when you get that high homocysteine, you get that endothelial cell damage that can start to increase risk of thrombosis and blood clots. So if your homocysteine is in check, you are not at increased risk of clotting. You don't need to tell me. We go through. But I imagine if you've done have. Usually this would be done, as I said, in a clinical setting, this is post something serious. If they've done it as preventative, that's wonderful. But in this day and age, as I said, this is not often done unless someone's had a serious. Something serious has happened. I hope that you're okay. Yeah. Fortunate that it was done. Preventative. Okay, good. Yeah, wonderful. Good obstetrician. Yes. Very hard to come by. Yeah. Okay, next question. Does equal combined reduce activity? Correct. Yes, it does by 50%. Additionally, does it reduce the ability to absorb folate fortified food? Mentioned. Does it reduce to convert food folate lead to toxic levels or is this a misconception? Yeah. So what it does, it doesn't affect directly the impact of folic acid, but it does the, like I kind of showed that five methyl, that one that kind of sits above it, you don't move as much to, sorry, the 510 methylene, you don't move, move as much to the 5 methyl. So you are at risk when you have these MTHFR SNPs of having less methyl folate. That is true. It doesn't mean that you don't necessarily absorb it because you could be pushing more towards that DNA synthesis, as I said, which is not always a bad thing. So it's not so much that you absorb it and I'm glad you said that because I had a practitioner just the week she couldn't make it, but the week before I did this message me and say one of her patients had seen someone else and was told with MTHFR she can't absorb folate, she needs to be on 3 milligrams forever. And I was like, that's not the case. It's actually not the absorption. It's just you're likely to be lower in one form. The methyl and you don't have to be on 3 milligrams is a lot. Now I hope that that person's also on B12 and B6 and B2 because that will start to affect methylation and then you can start to have other issues with the methylation cycle too. But you definitely don't need to jump into high dose. You know, I've been there, done that. We have enough knowledge now when it does come to absorption too, that even with 3mg you're probably not even going to absorb that much anyway. Like we have a limit to how much the body can absorb. So it sounds like your obstetrician is on top of it. You know, you might be one of those people that does fit into that category of wanting slightly, you know, needing, particularly from a fertility perspective, higher amounts of folate. I personally wouldn't go higher than a milligram, but if you want to be balancing that also with higher levels, you'll get it in your PDF guide with the B12, the B6, the B2, everything. In the rare instance, in the sad case that someone has neural tube defects or in certain conditions we might jump to 5 milligrams. But I. Yeah, most of the time you don't need to do that now unless it's a rare Circumstance. And then FJ. Thank you. Back at 7:52. If I click on this will it work. Did anyone else see this? So you. I don't know if you know that people that are here, the prize is you get to have a one on one with me. Woohoo. And. Oh, okay. It's going to open on my. Oh yeah. Okay, let me do. Do you want to see the wheel spin? Do I share the screen? Oh, where is it? I can't. Oh, is that the, Is that the person who won? Sara Wise. It's you. Can you see that? Okay, I can't open it. Anyway, so there you go. After all that you. Well, there you go. I can chat to your obstetrician anyway. That'll be in my, in my like happy place having a chat. So it sounds like they're obviously interested in this. That's the space I used to work in. Yeah. So just so if you, what we did is everyone that has come got put into a little name wheel and then we do the wheel and a random person gets chosen. And yeah, your name is there if you can see that Roi. So that's you. Okay, Bethany, your question. Why don't you use Sam very often? Same. So with same you're bypassing the whole methylation cycle. So you are, you know, I kind of say it's like you're coming in with these sort of, you know, heavy artillery. You just, you're just bypassing all of this. It can be really helpful if there are, you know, you say you've done a doctor's data methylation assay or you know, they're low in semi and you, you can't get things moving. That, that can happen. It's probably happened to me two or three times and I don't know why. You know, you, you use all of your knowledge. You think you know they're not protein deficient because that obviously influences methionine. You know they're not protein deficient. You know, you've done a stool analysis. It's not a digestive thing. You know, you go through everything and you think, well, why is the same low? I have had a couple of people where I say I'm going to have to give you same because you're low. And particularly in the case of fertility, you know, they're, they might not be able to maintain that pregnancy if they're so low with methylation and homocysteine. But I don't use it often because what I want to do is get that pathway working. I want to give it some folate and some B12 and the zinc that goes in with the MTR and I want, I want the body to be regulating itself. So when you give ethanazyl methionine, you're putting in a lot of a methyl donor and you're pushing methylation. In a sense, it can be good in certain circumstances where you can't get it up, or in the case of, say, mental health conditions, you know, if someone is benefiting from same and that is helping with their symptoms and their mood, and the alternate is a antipsychotic or an antidepressant, definitely have the same. That's with, you know, associated with a lot less side effects. But unless it's those kind of circumstances where I think it's really needed, we want to be able to understand the pathway, look at the SNPs, look at the homocysteine. You can do further methylation testing, get a really good insight to methylation, try to get that pathway working. So the body is regulating the amount of methyl groups that it needs. So that's the way that I practice, and I'm probably a little bit that way because we never gave same in the public hospital either. In the fertility clinics, we always use the B's because we did a lot of testing. We always use the B's to get everything happening. And as I said, you know, most often we had an 80% success rate in our recurrent miscarriage clinic. Our high risk patients, majority of those outcomes, despite having serious things before growth restriction, preterm birth, had good outcomes. I mean, it wasn't just me doing genetics. There was a team of people looking after them. But we didn't give same back then and we had good results most of the time. I think where same does fit in is a lot more of the mental health stuff. But again, if you've got the time, it's not an urgent situation I'd be starting with just trying to get the pathway working before you jump to same. Okay, Lucy, it looks like the methylation isn't working on the Dutch. Is it simply this. I've had a patient I sent to you tolerating hrt. Oh, you're working now. My microphone. Sorry, I'm not good at talking. I know who you are. Yes, hello. And I know who you're talking about. Yes. So I've had a couple of these people where, you know, I do certain things and they just do not respond how I expect them to. And I know there's a lot with the Compton everything, and I look at the methylation and try and help that on the Dutch, but I just feel like there's another missing piece that I don't know about that I'd love to look into. We just had a big chat about Sammy. If I am going from memory, and it was quite a while ago I saw her, but I think we gave her Sammy, didn't we? Didn't I. Did I prescribe that? Might have. Yeah, I'm sure I did. It's so funny. We just had this big conversation about Sammy. So Lucy is a gp. I've just realized who you are. Who's referred some people to me. Complicated patient. And we ended up doing further testing with her with methylation because we were trying to understand what was going on. She wasn't reacting to things, but actually. Oh, no. Was it the other way? Her methylation was high. I can't remember. Anyway, she was definitely a complicated one. My understanding, though, could be wrong, is that once we did the testing, we did a few things, she was feeling better. Is that right? Or if things changed again, she was feeling better. But we can't use. We haven't been able to do the hrt. So I'm sort of more interested in also now with that, trying to support patients that do want to take hrt, that aren't complex. Do you know Erica Wills? No, she's. Are you still here, Erica? You want to have a little wave? Are you still here? Yes, I think you are, Erica, who is who I refer to. She obviously does lots of testing as well for HRT and just throwing you under the bus there, Erica. Hopefully you're happy to conversation, but, you know, we. We're all here to help each other, but maybe at some point, or if you're part of Acnum, we're all. Yeah, you know, come and have a chat to us at the next Acnum event or. Erica's in Melbourne, but she's definitely my HRT specialist. I refer my women to her and she does Dutch and everything as well, so. I don't know, I'm just thinking she might have had a strange, complicated patient too and know something that I don't know. So, Erica, maybe I will, if you don't mind, because I've just totally put your name out there now. Anyway, pass on your details to Lucy if there's any. You might not. You might not have any information. If you don't, you can just put. I don't have any extra information. But if you do, you can have a conversation about it. But getting back to the genetics. Yes, the NQO one. So if the. If the. So there's. There's a few Pathways with estrogen, it's not just methylation. You got sulfation. The gut, though, I think her gut was okay. If there's high beta glucuronidase, that could be then influencing recirculation of the estrogen. And then she's really, you know, that's exacerbating the things. The other thing is, from a genetic aspect, aside from the other detox pathways that you want to look at that influence estrogen clearance, is that NQO1. But I'm pretty sure we did genetics on her and I would have looked for it. So it's the CYP1, B1, it's the COMPT. It's the NQO1, the MTHFR. They're the things I'm looking at in relation to estrogen metabolism. Thank you. Thanks. That's okay. All right. In your time in pregnancy clinics, did you see a lot of homozygote? 677 with ITP I? In general, we saw a lot of MTHFR SNPs with kind of everything. I guess we were looking at that, you know, that population. And the truth is they are quite frequent anyway, you know, just in. In the. As our Gary Brecker is telling everyone, 44% of the population has it. So, yes. Whether I think it's a link more so specifically with mthfr, I'm not sure specifically, but definitely did see it. Definitely. I would like to test for red cell folate. When I had a lab and we were in the hospital, we always use red cell folate. We said that serum really didn't always have. Unless you're looking for deficiency, serum doesn't have a lot of, you know, one thing we would always talk to our patients about is making sure they were fasting. Sometimes women need to have a little bit of something in the morning. But if someone has a fortified cereal in the morning that's fortified with folic acid and they have a blood test, their folic acid is so high in the blood, Red cell folate is giving you an indication of folate stores over time because it's, you know, what the body is sort of storing into that last 120 days, but it's very difficult to get. So if you can get that, Melanie, that's great. But most of the labs don't. Don't test anymore. And even towards the end of my time at the hospital, they were kind of phasing that out because it costs more money. We used to get red cell folate and B12 together. Like they Used to come together and then they just moved to serum folate because their interest is in deficiency, not really optimal health. And the serum folate, even though it's not a good marker of optimal levels, will actually tell you if it's really low. Same with B12. I don't think it's a great marker at all. But if someone's deficient, it will come out on the serum. B12 doesn't necessarily. If it's high, doesn't mean they got high levels because it might not be getting into the cells or the tissues, but the deficiency marker is there. Oh, that's it. There we go. If anyone else wants to pop on and say something, I know we've gone over time. I appreciate that you're all here. I hope that was really helpful. As I said, if you want to learn more, if you want to introduce this and, you know, come up with programs and packages around epigenetics, Nutrigenomics, check out the wait list, there'll be more information next week. Otherwise, I hope that if you are doing MTHFR testing, that was really helpful and going through some of those, which is really new to me, you know, usually I'm not comparing other testing companies. I hope that that was helpful because if you're not already telling people you do this, and once you do it, they will start coming to you with all sorts of different tests. So, yeah, definitely be prepared for that. Okay, I think that is it, everyone. So thank you so much for your time. Bram, you haven't said anything. Are you here? Are you off having a little bite to eat or something? Dr. Rabinoff is here, who I used to work with in the clinic. He usually has so many questions. Maybe he's just being kind and he's going to ask me later because he knows we talk all the time. Erica. Hello, Erica. Thank you for coming along. I hope that was helpful for you. If you've got any questions, you can always chat to me as well. I covered it all. Thank you, Erica. And what about Lucy reaching out to you. Thank you. No worries, Stephen, that was fine. Thank you. It's been amazing. Whoops. Can I. Can I take a screenshot of that? Bethany and I. I'll use that. Oh, thank you. So it's my first time running the workshop. Don't be. If you do have some constructive feedback. I know I tried to give too much. Believe me, if you saw the slides at the start, it was even more than that. Feel free to send me some notes where you like. This didn't make sense. I feel like some of the things I skipped over a tad quick, like people asking about the opposite strand. We spent more time on Wednesday, but I was mindful of your time because I went about an hour over on Wednesday. But yeah, my new favorite person. Oh, thank you. I can't lie. I love that. So good for my rockstar. Loving it. Oh my God. I'm gonna take all those. So yeah, I do hope to do more of these workshops so a couple little testimonials will be awesome. I know it's late. I know you're all so busy. I appreciate your time and hopefully this is going to help you with your patience and I'll talk to you all soon. Bye. Thank you. Back at 7:52. If I click on this, will it work? Did anyone else see this? So you. I don't know if you know that people that are here, the prize is you get to have a one on one with me. Woohoo. And oh, okay. It's going to open on my. Oh. Oh yeah. Okay, let me do it. Do you want to see the wheel spin?