Ep. 558 Your DNA Isn’t Your Destiny – The Most Actionable Way to Use Genetics for Weight Loss with Dr. Yael Joffe

Welcome to Everyday Wellness Podcast. I'm your host, nurse practitioner, Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives. today i had the honor of connecting with dr yale jaffe she is an expert in the field of nutrigenomics and has a phd in nutrigenomics in the university of cape town exploring the genetics of obesity she speaks at conferences around the world about translating the science of nutrigenomics into clinical practice and i had the honor of meeting her earlier this fall and absolutely wanted to bring her on the podcast to speak more about the role of lifestyle genetics. Today, we spoke about nutrigenomics and nutrition genetics, the impact of epigenetics and genetics, as well as SNPs, which she refers to as spelling changes in our DNA, and the impact of genetic testing in the industry as well as red flags, the importance of DNA health, a polygenic approach to weight loss resistance, the impact of perimenopause and menopause and what that looks like from a genetics and epigenetic perspective, the role of insulin signaling and glucose, Yale's specific work and her unique 36 metabolic pathways and polygenic approach and how she makes genetics and genetic information both accessible and actionable. This is a truly invaluable conversation, one you will likely want to listen to more than once. Well, I've been so looking forward to this conversation for listeners. You are a new friend. We just met a few weeks ago, but I was so grateful and appreciative that we were able to carve out time on our calendars and start this conversation because I was so interested, invested in you as a person. And then that kind of allowed me to learn more about your work and your gifts that you bring to this space, especially about genetics and helping my community understand what's more about themselves. Well, thanks, Cynthia. It was so lovely meeting you. I can't believe it took us so long to get to know each other. And I was very excited to be invited here today. So I'm looking forward to it. What is nutrigenomics? And why is it so important? How is it honoring our own innate bio-individuality? I love that. Just dive in. I could talk for like an hour. My listeners know. Okay. So what is nutrigenomics? Let's start with that question. I feel like there were five questions in that one question. So let me get started and then you'll just say, but what about that? Okay. So nutrigenomics pretty much is what it says, nutrigenomics, nutrition, genetics. And interestingly, there was a time in my life when I was a dietician and I was told about this beautiful field of nutrigenomics. And I said, surely there's no relationship between nutrition and genetics. Anyway, that was a long time ago, a good 25 years ago. And of course, now I've come to understand that there is a relationship in every single thing we do between not only our nutrition, which is the food we eat, but in everything, the food we eat, the toxins we're exposed to, the hormones inside or outside our body, the exercise we do, the stress, trauma. So even though we use this word nutrigenomics, I prefer using kind of a different concept of lifestyle genetics because it's everything and how it interacts with our genes so i always say flipping it the other way our genes determine who we are how we respond to the world around us our diet our lifestyle our exposures our stress the sunshine our connection and so that is the essence of this conversation is what is the relationship between all these things in our lives and the genes we inherited that make us who we are and also how those choices we make. This is the real quick version. How those choices we make in our life will change the way our genes behave. Well, and I think for so many people, they'll say, oh, I've inherited X, Y, and Z from my parents, not realizing that we do have quite a bit of control over whether or not these genes are actually expressed by our lifestyle choices. And so I love that, you know, you kind of are identifying up front that, you know, we have this genetics piece, yes, but how we respond to lifestyle plays an enormous role. And that's why we can't just be passive conduits to our health. That's why it's so important that we are conscientious about choices that we make or don't make, understanding that they have a large impact on how we age, how we perceive the world, how much energy we have, how connected we feel to one another. I always use the example that a lot of these events that I speak at, I get to see other speakers and experts who are, you know, really standouts in their field and they're thriving because they are truly embracing what they are sharing with their communities, you know, with other clinicians that we're speaking to. And so I love that we have some control. It's not like destiny is there. And we're conditioned that because we have this one genetic mutation, which I know you don't like that term, or spelling changes in the DNA, that because we have this one mutation or alteration, that's not our destiny, there's a lot that we can do. You know, something comes to mind is I for all your listeners is some, you know, we often make an assumption that when we talk about things like genetics or epigenetics, which is actually what we're talking about, that there's a broad-based understanding. So if you don't mind, I would love to just take a few minutes and just talk about my understanding of what is genetics and what is epigenetics, because your listeners are hearing these terms all the times, whether it's on media, Instagram, podcasts, and we're talking, you know, we're, you and I are jumping around because we know, but I'd love to just, if you don't mind, if you just go back to some basics and then from there we can have some fun in the conversation. So let's start with genetics. So in our body, we have our DNA. I think we all know this. And in every single cell, we have our DNA wrapped into what we call chromosomes, which wrap really, really very, very clever, brilliant engineering, all kind of tucked away and put into a cell. And when we open up these chromosomes, we can read our genes. Now we have about 20 to 23,000 genes in every single set of chromosomes and it's essentially these genes that determine who we are, how we respond to the world around us. When we open up these genes, it's just a code, just a code. Like English is a language and English has 26 letters and we take these letters and we put them together and we make words, words together make sentences and sentences can tell us the story. Genetics kind of works in the same way. So we take a bunch of letters. We've only got four in the language of genetics, A, C, T, and G. We put them together in three little words, makes it a bit more simple for us. And when we put all these words together, what do they make? They make the proteins in our body. So every single three-letter word is an amino acid. And of course, when we put amino acids together, they make proteins. And we know that whether we're talking about enzymes or hormones or brain messages or collagen or anything in our body, it's essentially coming from a protein, which means this code is the code for our proteins and how our body works. Now, 99.9% of the time, we're all identical in our code. Our code is the same, but at 0.1%, our code is different. And this is what you mentioned, Cynthia, about spelling changes. So it means that at 0.1%, we've got a couple of million spelling changes. that means that my spelling is a little bit different from your spelling and it's these spelling changes which are called many things we call them snips polymorphisms gene variants the word mutation gets used i don't like it because it's so negative i don't believe it should be like that they're just spelling changes so even though someone goes oh you've got that it's just a spelling change so what do these spelling changes do they give us information and in the world of genetics we read this information and it tells us something about you and if we know that something about you we can then curate the most personalized diet lifestyle supplement hormone plan for you okay that is genetics genetics 101 done now we're going to talk about a much harder concept which is epigenetics so epigenetics is like the new like kind of trendy term that everyone's using and most of us don't understand so i just want to explain it in a very simple way. Even though spelling changes determine who we are, it's what we inherited from mom and dad. Epigenetics is epi, means above genetics. It means it's got nothing to do with that spelling that I was talking about. It's about the behavior of genes, the expression of genes. So in essence, our genes switch on and off. When a gene switches on, it makes the protein. So if we have a gene that helps us break down caffeine in our body, if we drink caffeine, our body gets a message. We've got caffeine in this body. We need to break it down. It switches on the gene that makes the enzyme that breaks down coffee. And some of us are better or worse at breaking down the coffee. Why are we better at worse than breaking down coffee? Because of our spelling changes that we got from mom and dad. So if you can't drink a lot of coffee, you can blame mom and dad. So when we get these signals from our external world, we switch on genes and we switch off genes. Now, this is the beautiful world of epigenetics. Every single thing that we are exposed to, every second of every minute of every day, will switch on genes and switch off genes. And so the choices we make, you know, when I was a dietitian and new to the world of health, before I discovered genetics, I was told, you know, like everything in moderation never worked for me. But also that how we ate over a couple of months or a couple of years would determine our health. But if we think about it in epigenetics, every single time we make a decision, every time we eat something, every time we're exposed to something, every time we think about how we're breathing, every time we ingest toxins, we are switching on and switching of genes. And that means we have a lot of power. And that's when it comes to the power of genetics, because we can change that decision in the next minute, in the next minute. We don't have to wait a few months. Every single minute, we have an option to make a choice that changes gene expression. And that's why what you said was so right, which is, sure, we inherited some stuff and it gives us information about who we are. But every single second of the day, we get to decide how our genes are going to express. Sorry, that was a lot. But I think it sets a good playing field that we all know what you're talking about. Well, and I think listeners now understand why I specifically wanted you to come on the podcast, because you do such a beautiful job of making what is very complicated information, very accessible. And so when we're talking about genetics, epigenetics, these SNPs, or as you refer to them as spelling changes in our DNA. Let's talk about some examples of these, because I think these are the things that people have probably heard. They may not fully understand or appreciate it, but the common spelling changes. So I'm using new terminology, spelling changes that make us unique. And most importantly, as I shared with you before we started recording, I have one of the more common ones. And I think when people hear MTHFR, they automatically panic. And I'm like, wait, timeout, do not panic. And we'll explain why these more common, I think you refer to them as the top eight. Some of these more common things do not, they're not our destiny. There's so much that we can do that can support our health and our bodies and the trajectory of our natural lifetime and not be in panic mode, which is where I think 15 years ago, people were panicking if they had MTHFR. So this is a conversation about MTHFR. It's a conversation about the science, but it's also a conversation about the genetic testing industry. So when I started out in genetics in the early years, there were a number of companies that set themselves up as testing this gene called MTHFR, methylene tetrahydrofolate reductase. And I'll explain what it does, but I just want to tell you about the industry because they set up tests that literally you could just go test this one gene. And if you had the spelling change, trust me, they never used the terminology spelling change. It was mutation or defect. They would sell you a lot of supplements. And so a part of the genetic testing industry grew out of this MTH bar. Now, I have what I call my red flags in the industry. And so we'll start off with red flag number one. And red flag number one is if a genetic testing company is selling supplements, look deeper because we need to eat food first and foremost We need to figure out our lifestyle And then we going to choose what I call targeted supplementation where we very careful with which supplements because we don want to take 20 or 30 So if there a company who knows nothing about you your health goals your medical history your concerns, your blood tests, your gut and all they're doing is looking at some genes and then selling your supplement, it's a red flag for you. So I have spent a large part of my career trying to undo what happened because this gene is part of a process that happens in every single cell, every single nanosecond of every day of our lives called methylation. And methylation is one of the hardest, I don't know how you do it, Cynthia, I'll tell you how I do it, but it's such a hard thing to explain. Methylation is the hardest one, which is probably how everyone just said, okay, I'll buy the supplements. I don't want to try and understand this, but this is how I explain methylation. So we are brilliant when we think about heart health. We've been living our whole lives being taught about heart health, lung health, even skin health, hair health, eye health. We're great at this stuff. But what we're not very good at is the concept of DNA health. How healthy is our actual DNA? Because think about it, if your DNA is your code for everything that happens in your body, if your DNA isn't in its most healthy and wholesome state, then everything that I mentioned, heart, health, brain, eyes, skin is going to be impacted. And yet we never think about it. So this process of methylation, the job that it has is to keep our DNA healthy, to make new DNA that's very, very intact and healthy and wholesome. We don't want any potholes in our DNA. We want everything to be beautiful and intact. And when our DNA is damaged, which happens all the time because it's called life and living and breathing and metabolizing, we have enzymes that are really, really good at fixing our DNA to fill in those potholes so that our DNA remains super healthy. And down the road over a long trajectory of time, if our DNA doesn't stay healthy, one of the things that can happen is we are more susceptible to cancer. So we want to keep our DNA as healthy as we can. And so MTHFR is one of the genes, one of the enzymes that is involved in this process of keeping our DNA as healthy as it can be and in repairing any DNA that needs repairing. Now, there is a spelling change in MTHFR, which is very common. So I would say 25% of us have two copies. That means we got one of these spelling changes from our mom and one from our dad. And about 50% of us have at least one copy. So this is a super common thing. This is not rare. You're not like special. This is, we've all got it. I've got two copies, right? I think you said two copies, right? I have two, yep. You've got two. So what does it mean? It means that in this complicated process of methylation that does this really important job, one of the enzymes, just one amongst many, has a spelling change. And if we have the spelling change, we need to pay attention. What do we need to pay attention to? The food we eat. We want to make sure we have adequate amounts of vitamins like folate, vitamin B2, vitamin b6 vitamin b12 these are not special vitamins we know everyone's heard of the b vitamins the other thing is if you do take a supplement these new version of supplements that came out probably 10 years ago called methylated supplement methylated folate so you can get the clue here if it's methylated it's already making methylation easy then actually it bypasses mthfr and it doesn't matter if we have a spelling change so our whole industry was built on this drama around mthv but in actual fact it's just one spelling change it's part of a lot of spelling changes in methylation and there's so much we can do with it with good diet decrease our exposures to toxins because toxins can obviously damage our dna and some really good supplements that help us make sure that we're pairing in DNA. So that's the story of MTHFR. 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You'll learn why the same diet that worked in your thirties may not work now, how your gut influences hot flashes, mood, and weight, the truth about fiber, protein, and blood sugar in midlife, and the daily habits that help your body feel safe, stable, and resilient. Again, if you're tired of blaming yourself for changes that are actually biological, this book will help you understand what's really happening and what to do about it. You can pre-order the menopause gut wherever books are sold. And when you do, be sure to check out the special pre-order bonuses I put together for you. Again, you can go to www.cynthiatherlow.com. You'll click on the banner. It'll take you to multiple options for where you can order the menopause gut in presale. Well, I think, you know, if 75% of us have at least one copy, I think that is incredibly reassuring because 12 to 15 years ago, when multiple family members, and there's a lot of us that are in medicine, everyone was losing their mind. We were like, we have to work with a practitioner who knows what to do with MTHFR defects, because that's what we called it. And then realizing it was the domino effect, because it means I got a copy from each of my parents and my parents wanted nothing to do with the conversation, but talking to my siblings and cousins and all this brouhaha. So it's very reassuring to know this is something that we can work with. It just means there's probably a little more thought involved with dietary and lifestyle choices. When you're considering these spelling changes, what are some of the other more common spelling changes in our DNA that you see as a expert in this area? There's so many areas. I'll try to think of some areas. So one that I like to talk about is weight management. So I became a dietitian for many reasons. One was because my granddad from cancer, but also because I battled with my weight my whole life. I definitely had a bigger appetite than those around me. I loved eating and I would gain weight very easily and it would be quite hard. I used to exercise like crazy, but it would be hard. So I was very interested. I have two sisters incidentally who it was never an issue for like they were easily they just naturally so I had this like real question in my head of why was it harder for me and easier for them why do I gain weight so easily why am I so driven to eat food and so when I started studying genetics this was one of the questions I had because when I started looking at the scientific research it was pretty extraordinary that the influence of genetics was significant so we don't like giving one number like 75 but maybe like between 50 and 70 percent of us are impacted by our genetics in how we experience our weight journey now we all experience differently so for example this was like you know when you have one of those aha moments where you're like how did I not know this so this is one of them so genetics impacts our appetite how hungry we feel and full we feel so i always believed that we all are hungry in the same way so i said that you and i fasted for i know this is your area so let's just do a 14 hour fast right we fasted for 14 hours we get to the end of 14 hours and my experience of my appetite my hunger at that 14 hours is completely different from yours you'll be like ah that was nothing I'm going to carry on and I'd be like dying from hunger right then you and I go out for dinner because now we're starving I'm starving more than you and I order obviously not but let's just use an example cheeseburger and fries and I eat my cheeseburger and fries and I'm still hungry so I think oh I'm gonna order a salad as well you don't even get through half your cheeseburger because you're like that's enough I'm full now in the early days of the world of dieting and weight this was all about blame this was all about control self-control I don't have willpower I don't have self-control I'm greedy and this is the way the world I was brought up in and I'm sure many of you listening are probably nodding your heads and going, that was my world as well. I was brought up to believe I had no willpower, I had no self-control, and this was a failing of me. And so when I started, in fact, my PhD was in weight management because I was so interested, why was it so different? And that's just like one example. I call it the buffet gene. So there's this gene called FTO. And the reason I call it the buffet gene is because the scientific literature has shown that when you walk into a buffet now anyone who's traveled to Israel and been for breakfast in Israel will know the breakfast buffet is the best meal you can ever have in your it is extraordinary so I walk into the buffet and I see this beautiful delicious copious amounts of food so I fill up my plate and I go and eat it and then I'm like oh there's more so I go and I get more food and I eat it the buffet gene, this spelling change can actually change the way we respond around food. Our response called the locus of control, like how we control our response can be impacted by genetics. So that's just another example. That's fascinating. So is it the locus of control? Is it a visual stimuli that actually changes your perception? So I'm imagining being a visual person that depending on where you have these little changes in your DNA, it could make you perceive that you're hungrier more so than you actually are. And that's the visual response. So if you told me there was a buffet, but I didn't see it, it would have no impact. But if I smelt the food and saw the food and experienced that copious, beautiful, it's not just about the consciousness, it's just that sensory engagement with it, I would be inspired to eat because after the first two plates, I'm probably not hungry anymore, but it's very hard for me to control how I'm responding to the food. So it's just another example. Now, none of these spelling changes are that powerful by themselves. They do not determine your life, your weight journey, your relationships, but they do give us information about something about you and how you respond to the world around you. I think it's so fascinating because it's giving us information that can then kind of validate our own experiences because, you know, certainly our generation was kind of taught that as you appropriately stated it an issue with willpower You not strong enough You not exerting enough control You haven put your macros together in the right way And yet it so much more than that It my understanding that there are actually other types of genes like MC4R that actually control appetite. So I think about, I have teenage boys. Well, I have one teenage boy, one young adult and the amount of food that they can eat. I'm sure it's a byproduct of, you know, they're an incredible anabolic state. They're very fit. But I also think about friends, family members that have told me they feel like they have no control. Like it's not that they don't want to have control. I could imagine you could get a couple of these that would just make it much easier for you to struggle to maintain your weight, whatever your weight is that you're ideally kind of focused on because it's so relative and arbitrary. So you're talking about what I preach, which is a polygenic approach. And so I'm using examples like FTO and MTHFR, but actually I keep on saying there are a multitude of them. So what I've been teaching and doing for the last 10 years is grouping genes together. So if I think about appetite. It's never one SNP. It's not only FTO. It's MC4R and A2, and there's a whole bunch of them. And so what I built was kind of an algorithm, not in the AI sense, but in a set of criteria where you could evaluate all these SNPs together, bring them together and score them in a way to be able to say just how much are your genes impacting your experience of appetite and hunger. Now we can do this in many different places. I've built 36 of these. One of them is appetite. Another one is methylation. But we can talk about some others like hormone metabolism, right? Let's talk about hormones. Seems appropriate. So the way our body metabolizes hormones, both the hormones that our body is making internally and the hormones we're taking in from our environment, which I'm sure you all know about, will be to a degree influenced by these groups of spelling changes. So it's not just one spelling change, but there is a bunch of them that are responsible for metabolizing, not just estrogen, progesterone, testosterone, DHEA, all of these things that will influence why in one individual you take a certain hormone and you have a certain experience, and in another an exposure to another hormone creates a completely different experience so we also like we believe every single person should have a genetic test to know how their body is managing hormones because it gives the clinician information when they're prescribing when we talk about precision medicine we talk about you know and personalized medicine we use whatever we want But if I know how your body is responding, because hormones like caffeine, like lactose, like toxins get metabolized by the body and the genes, the spilling changes are going to impact how that happens. Well, just thinking about, you know, women telling me, you know, they're in perimenopause or menopause, they're starting hormone replacement therapy. And I would say 80% of women started, they feel great. maybe their weight stabilizes maybe they lose some weight and then there's definitely and this is relevant to our weight conversation there are women who say i got put on hrt and i gained a bunch of weight and so i'm sure it is not that they did anything wrong it's that their body's way of metabolizing and processing these hormones might be very different maybe this is someone in precision medicine who needs a lower dose to start. Maybe this is someone that needs to have a different type of hormone, maybe instead of mostly estradiol, maybe they need a weaker form of estrogen. So I'm just thinking from what you're sharing, like trying to connect the dots, because there's nothing more frustrating as a middle aged woman being told you need hormones, getting put on hormones, and then you gain weight. That is very frustrating. So genetics is not an absolute answer. You know, we're not diagnostic. We're not saying genetics is the only answer. You need to just think of it as, I know it's so cliche to say it, but it's a piece of the puzzle. It's a very big piece of our puzzle, right? And so I want to give you some more examples. Can we talk about mood, anxiety, depression? I mean, so there's two sides to it. The one is genetics and the one is epigenetics. So let's think about genetics. So we have these neurotransmitters, which are essentially brain messages, dopamine, serotonin, adrenaline, noradrenaline, but dopamine and serotonin are probably the two that you all know the most. And they really define to a large degree our experience of this world and whether it makes us feel better or makes us feel worse. And by worse, it could be anxiety. It could be depression. We also can talk about addiction, but that's another conversation. it's the same conversation where why are some so much more susceptible to an addictive personality and it can be drugs it can be alcohol but it can be carbs and sugar it can be exercise it can be shopping it can be shoes so it can be any of these things right it can be OCD behavior it's because our genes and their spelling changes are going to change the way we metabolize, convert, and break down these brain messages. So there is a situation where we are very, very good. We speed up the way the body breaks down dopamine and serotonin, which means we have low levels of dopamine and serotonin, which means we're more susceptible to depression, low energy, fatigue. But it can also work the other way and say, well, actually, the enzyme is not good at breaking down dopamine and serotonin. So actually, I stay in high levels. And high levels can be insomnia, restlessness, anxiety. So when we're thinking about what our experience of mood is, and we discussed many different versions of mood, we really want to know how our genes are impacting those neurotransmitters because the decisions we make about the intervention we get given the treatment plan the medication we may or may not going the supplements we're going to use the sleep hygiene that we plan we really want to know what is my body doing with these because i don't want to take anything whether it's natural or pharmaceutical that is going to increase my dopamine and serotonin if I'm not breaking down dopamine and serotonin so I always thought we want these insights we want this information because we're all so different now the epigenetic conversation which I loved when I started out in genetics I only believed in my naivety that nutrition exercise and maybe toxins change our gene expression switch on and switch off now I have this beautiful slide that shows how everything changes gene expression but I just want to mention it in relation to anxiety depression serotonin is connection community touch conviviality sharing a meal so whenever I go to conferences and I was recently at a conference where I met Cynthia I call it my hug fest because I have all these wonderful colleagues that I've known forever and I just go from hug to hug to hug every time I hug someone that I'm really happy to see, I am switching on genes that are switching on my dopamine and serotonin and making me feel fabulous. It's like plugging yourself into a serotonin wall plug and getting a supercharge. So when we had COVID and we were disconnected, we were lonely, we were alone, we were working from home, we suffered greatly in the mental health plan because we were not switching on these genes that give us more of these beautiful, pleasurable hormones and rather the opposite that we were suffering from the despair of it. So that's why when we think about who we are and the decisions we need to make, we always want to think about genetics and we want to think about epigenetics. Oh, that's so powerful. You know, it's interesting. I've spoken at multiple events this fall and the event that we met at in Scottsdale, which was a for M, there were so many amazing people that were speaking, people that attended people that I connected with. And you're right, when you have that synergy, not only when you're hugging someone, you're releasing oxytocin, which lowers cortisol, which makes you feel great. But that connection piece, I think is so often forgotten. And when we're having these more like technical conversations. And yet we are social beings. And I remind individuals that loneliness, if you look at it is as impactful on our health as smoking. And I think we don't talk about that enough. And I think about the impact of the pandemic. I think about older people, maybe that are retired, maybe they don't live close to loved ones. I mean, how important that connection piece is. So I'm so grateful that you brought that up because sometimes we get so caught up in like, how much did you sleep? Are you managing your stress? Did you exercise? What are you eating? And yet, when we're looking at Maslow's hierarchy of needs, that connection piece is equally as important as these other lifestyle measures. Absolutely. I mean, that was a big aha for me, like really big aha for me because I was so focused on nutrition for so many decades. I didn't think about all these other things. the weather changes our gene expression, right? So if you're a person who needs sun and you live in Seattle, I need to be really cognizant of the impact the weather's having on my emotional well-being, but actually on all my genes. And I need to put things in place to try and give myself that medicine. So everyone loves sunshine. Actually, my children don't have sunshine, but most people like sunshine. But for some of us, it's more important than others. and so we need to think about every single thing connection nutrition exercise exposure weather so the other thing that totally blew my mind is complementary medicine so when I was studying I was very science driven and I didn't get Reiki and I didn't get massage or touch healing and now I'm completely the other way I love everything but I suddenly had this understanding why is it so impactful acupuncture because it's driving gene expression energy drives gene expression when you have frequency work done any kind of frequency work done it's switching on and switching off genes to heal infrared sauna is healing so it suddenly was like this huge aha of like every single thing is changing this dance that our genes have, and we can control that. I think it's so fascinating. And I think sometimes when we're thinking about the hard sciences, we don't think about that connection piece. And so what an invaluable, an invaluable insight that you have found in your work. So I'm curious, when we're talking about women in perimenopause and menopause, because that's the bulk of the listeners, what are your thoughts when you, if you meet perhaps you meet someone or a colleague consults with you what is kind of your approach when you're looking at a woman you know 45 to 55 who's not sleeping well who's gaining weight which is arguably the biggest pain point women have at this stage of life and has inconsistent energy what are the things that you are thinking about in terms of through your genetics epigenetics lens as well as this kind of lifestyle perspective are there things that you start automatically thinking about as you're thinking algorithmically, because we'll talk to your kind of pathway of how you evaluate genes and genetic expression in a minute. But what is your kind of gestalt around those types of patients? Well, I have lived that. That's all my friends and family, my sisters. So I think there are many things I want to think about, because what was happening a while back is we were only thinking about hormones. And we have to think about hormones. And we have to think about the genetics of hormones. And we have to know our hormones we have to see what is happening we cannot guess and this is I think for me what I've seen the most of is not being heard and of course that's why your work is so important is because no one was listening to us when we were talking about the weekend or we were talking about not sleeping so I would say not sleeping for me was one of the most powerful in terms of like creating havoc in my life. So as I wasn't being hurt, when I start looking at it and saying, like, let's unpack this and understand what you bring to the table. There's a couple of things I want to think about. I want to think about hormones. I want to think about detoxification because a lot of the genes are similar to hormones, but a lot of them about how's my environment impacting me? How am I managing the things that are coming into my body through the world around me? that can have a significant impact. I want to think about things like inflammation and how my genes are changing inflammation because we know inflammation is like a base layer. But if we don get on top of that you know we not sleeping and we can resolve inflammation we never gonna to lose weight and we going to gain weight So when we think about weight we got to think about hormones We have to think about sleep which can be impacted by genes And we want to think about things like inflammation and detoxification. When I think about my emotional response to perimenopause, which is always significant, I want to think about my neurotransmitters And I want to think about my oxytocin, which is impacted by spelling changes, and dopamine, and serotonin, and adrenaline, and noregnen, and cortisol. I want to think about glucose. I know this is a lot, but I'm thinking about a lot. I want to think about glucose. Because if we don't manage our glucose from myostasis and keep it beautifully balanced, I don't use the word beautiful a lot, then it's really hard to balance all these other things. so those are the ones that just there was a lot that came to mind i want to think about histamine and my gut i always want to think about my gut because it's not going to get easier and better during menopause so if i haven't got it dialed in before it's going to be more difficult so i know it's a lot but in essence i guess what i'm saying is you know perimenopause menopause is a bump in the road and that means everything is going to impact that bump in the road and we mustn't only gets caught in this mthfr scenario where we're either focusing on one gene or we're focusing on one pathway like only focusing on hormones and the other one i'll throw in is cognitive so i've spoken about mood mood is different from cognitive mood is anxiety depression of those cognitive is brain fog cognitive is memory loss cognitive is firing on all cylinders in my mind and being able to work in the way that I always used to work. And there's a lot of genes that'll impact how cognitively I'm functioning. And I want to make sure, especially as I go into my menopausal years, that I'm keeping all of those enzymes, hormones, nutrients firing as big as possible. So it's, it's a lie. And there's certainly some messaging around social media. Well, meaning, I mean, I'm not being critical when I say this, that it's just the hormones. And I've had conversations with many of my integrative medicine colleagues, and they've said there's so much more to it than just replacing hormones. And you did a beautiful job really speaking to that. I think that, you know, one of the profound changes, I think for a lot of women, they navigate this perimenopause to transition is this loss of insulin sensitivity and shifts in glucose regulation. What does a polygenic approach demonstrate to us about how this insulin signaling and glucose is changing as we are aging? There's no other way to put it. You know, aging is inevitable, right? But you know, how we choose to age is something we do have control over. Yeah, I mean, glucose and insulin sensitivity or the homeostasis of this whole system is so important in everything. In fact, if you raised any health conversation I would have seen but it's really important now because we do lose sensitivity now there are things we can do especially on exercise and muscle mass that can try maintain or restore insulin sensitivity but again what is genetics it's about why am I responding differently some of us will lose sensitivity more than others some of us will have to really work hard on ensuring that we might wear a glucose monitor to check where we are because the olden days of just checking your glucose is archaic. It's an acute snapshot, but it really doesn't tell us what's happening in the body. So there's a group of genes that we look at that all impact how we metabolize glucose. That is relevant whether you're six years old or 16 or 60 years old the difference is when a bump in the road hits us any kind of change in how our body functions perimenopause and menopause we want to know how our glucose and insulin is managing that transition and for some of us it's going to be more difficult than others so this is true for anyone but when we go through this change and transition we're talking to a woman, I'm in my late fifties. I've got gray hair. You know, perimenopause was very hard for me until I found the right doctor. And I was lucky enough to come from the world of functional medicine and integrated medicine. And so I was heard and I got the hormones I needed and I got the care I needed and I got the nutrition advice I needed and I got a community to connect with. and once you can get through that it is amazing i just want to say that like for me it's been incredible and liberating and amazing so if you're not having that experience it's likely because you're not being heard because this isn't that's why i've been very careful the words that i use this isn't terrible at all and it can be empowering and powerful you've got to know who you are genetics is really helpful. And you've got to find someone to work with. You've got to read the right literature, as in behind Cynthia right there, and listen to the right people. And this can be a beautiful transition of your life, as opposed to feeling like this is something that was done to you. So I just wanted to say that in case I never got a chance to say it. No, I love the reframe. I think it's very important. And I never want the message to be perimenopause is doom and gloom and menopause you fall off a cliff because I think that certainly my mother's generation no one talked about menopause no one talked about perimenopause I certainly wasn't prepared and first couple years or perimenopause were a little rocky and then once I got the assignment it was like okay the word pause is important we have to reflect and change everything that we're doing and to your point working with a prescriber who's going to be able to support you in the capacity and the ways that you want and feeling seen and heard because validation is important. Whatever you're experiencing is real, right? And so I want to swing back to the messaging that we kind of started the conversation with that genetics and choice equals health. And so you have these metabolic pathways in your work. Let's kind of touch on this and make it relevant to this kind of perimenopause to menopause transition in terms of applicability, you know, working with testing and in conjunction with your healthcare provider. I mean, just that's important. Yeah. I think when a lot of these consumer led tests lead to more questions because there's information provided and then people are like, what do I do with this? Help us understand how these metabolic pathways are beneficial as we are navigating choices that we are making in middle age and beyond? Yeah. So I can only speak to my latest company, 3x4Genetics, and where I did things differently. And one, many things did differently. But for this conversation, the one is this polygenic approach that I didn't want to only look at one gene in detox, one gene hormones, one gene in inflammation. I wanted to look at the science, look at all the genes that were impacting methylation, impacting hormones, group them together, and be able to score them in a way that was really useful to you as a clinician, Cynthia, but also useful to everyone listening that it was really easy for me to understand, are my genes kind of, but, you know, playing a role here. So that's the first thing. The second thing is, I never want a clinician or a client or a patient to have to choose what genetic test to order. So what do I mean by this? There are some companies in the marketplace that will sell you a hormone genetic test and a brain genetic test and an exercise genetic test and a weight genetic test. And you get where I'm going. And you pay for each test or you can buy a bundle. Sometimes you can buy a bundle. And then your clinician has to download five or six PDFs and try to figure out what's important. So when I started 3x4, one of the most important things for me was there was only one test. And so in this one test are 36 of these, what I call pathways, but they're polygenic scores. So they're a polygenic score grouping of genes for a biochemical or metabolic pathway. and they start at the top of the hierarchy. So in our world of functional medicine, we always want to think what we call upstream, right? That what's happening at a cellular level, because if we don't fix what's happening at cellular level, we're not going to be very effective as we go down. So the way we built the report, based on the same idea, we start with those, what I call core cellular processes, inflammation, detoxification, methylation, which you're all experts in now, and oxidative stress. Then I move down to the next section. So each of those is a polygene score called the systems pathways. Now we're going to talk about glucose and insulin. We're going to talk about hormones. We're going to talk about collagen and joints. We're going to talk about bone health. All of these things are important. I should have mentioned them earlier for men and pauses a woman, right? We're going to talk about cognitive and mood. We're going to talk about histamine. So all important. Then we're going to jump down and then we're going to talk about our weight. How do we experience, I call it energy because I don't want to talk about dieting. How do we experience energy? How do we consume energy? How are we driven to consume energy? How do we experience when we put the energy in our body? How do we store the energy? How do we burn the energy? So that's six of those polygenic scores. Then we go to exercise. One of my favorite areas. What is my exercise potential? I know that I've been training my whole life. And even though I'm training so hard, same as everyone else, they're getting to the front of the pack and the podium and I'm still middle of the pack. I have exercised extremely hard because I love it my whole life and I'm always in the middle of the pack athlete whether it's running, swimming, cycling, doesn't matter. What is my potential? Because I want to know because I don't want to beat myself up that I'm never getting to that podium every time. Why do I always get an Achilles injury over and over again my whole life? Why am I more susceptible to getting this Achilles or collagen or any version of these injuries when everyone else is training the same as me and they're not because if I know remember if I know this information I can do something and lastly how do I recover from training so I'm someone who can't train seven days a week and in fact probably not six days a week I'm a five day a week trainer I need two days I need to recover I know people who can train six days a week and they just bounce back so knowing these things I just mentioned about myself, I can now curate exercise and training program that achieve my greatest potential. I recover as well as I can and I don't get injured. So that's six of those pathways in there. And then I think the last one would be nutrients. And of course, which is so important, how do I metabolize vitamin D? Why when I'm taking such a high vitamin D supplement, is my vitamin D level not going up in my blood work? How do I metabolize folate and B vitamins? Caffeine. Why when I drink decaf at noon, does it impact me in the afternoon? All right. So how am I metabolizing caffeine? And so all these things I mentioned, and I know it was a lot that I threw at you there, are in one genetic report. And they're all grouped. So you don't have to be an authority in genetics. You just, you're going to see which one of these is somewhere where you should be paying attention. And then of course we have like 7,000 clinicians in the country who are trained to interpret this. They're trained in the science. They're supported by mentors who can work with you to say, okay, what does this tell me about myself? And how do we now personalize my intervention based on this understanding? So that's a bit of a breakdown on 3x4. It's so exciting. I think it's so amazing. I feel so very fortunate that we were able to have this conversation today because you have an innate ability to take complicated information and make it really accessible. And that is exciting. And I love that you have this polygenic approach as opposed to calling out one spelling change. Yeah, I'm really having to work hard and not say mutation or defect. It's many years of using different terminology and helping people understand more about themselves from a very bio-individual perspective. If individuals are listening to this podcast and they're interested in connecting with you, learning more about your work, or actually doing the testing, please let them know how to connect with you. So 3x4genetics.com is the easiest way. And on our website, you will see a practitioner locator where you can just type in a postal code and it'll send you to the person closest to you who has been trained and mentored and educated to work with our test and all the information about the product. You'll also be able to download a sample report and be able to see what it actually looks like. Thank you so much for your time today. This has been truly invaluable. Thank you so much. 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