Is Genetic Testing Helpful or Harmful?
Welcome to the doctor Hedberg show for cutting edge, practical health information for the latest articles, videos and podcasts visit Dr Hedberg Dot Com. That's D R e.. D. R., G. DOT COM. The information in this show is intended for educational purposes, only always consult your healthcare professional before attempting anything recommended in this program and now here's Doctor Hedberg. Welcome everyone. Medicine Research on Dr, Hedberg and very excited today to have Dr. Tommy would on the show. We're going to be talking about genetics and genetic testing. and Dr would is a research assistant professor of Pediatrics and the University of Washington Division of neonatologist. Most of his academic work is focused on developing therapies for brain injury and newborn infants, but also includes adult neuro, degenerative and metabolic diseases as well as nutritional approaches to sports performance. Tommy received an undergraduate degree in biochemistry from the University of Cambridge before obtaining his medical degree from the University of Oxford After working as a doctor in central London Move Norway for his PhD and then to the University of Washington as Post Doc. So in addition to his academic training, he's coached athletes and dozens of sports weekend warriors to Olympia world champions. He's the outgoing president of the Physicians for ancestral. Health Society A director of the British Society of lifestyle medicine and sits on the scientific. Advisory, board of Hinson performance, which includes researching performance optimization strategies for Formula One drivers. Tommy's current research interests include the physiological and metabolic responses, the brain injury and their long-term effects on brain health as well as developing easily accessible methods with which the track human health performance and longevity. Doctor would welcome to the show. Thanks so much for having me. I'm excited to be here. Great. So. Before we got on. We were just talking about. A lot of the big issues in functional medicine include. Scientific and on validated testing and therapies and things like that. And, so that's why I was really looking forward to this. Because genetics is something that I've never really got on board with as far as testing and. Treating patients, so why don't we lay some bedrock for the listeners and if you could just? Let us know what is the current academic position by scientists on commercial genetic testing for snips and the interventions that. That some practitioners are using. That's a great question and. Having. Spent a lot of time sort of straddling both traditional allopathic medicine, traditional academic research, and then also functional medicine, particularly with athletes, but also with various clients with chronic health conditions. This real tension between the two in terms of what's what's done and the evidence that supports it, and I think that's that's where some of this genetics. Stuff comes into play and. When I started looking into this? You see very rapidly that. Academic geneticists who have been studying this these things for you know. To be two decades nowadays since the beginning of the human genome, project. The current state of the science would say that the rates consumer tests single nucleotide polymorphisms. Essentially useless in terms of their ability to either predict disease, risk or say response to a personalized. Nutritional supplements a regimen based on snips. Because most a the disease risk is is usually very small when you know if there is an increased risk associated with a snip and then. The vast majority. Ninety nine point, nine nine percent of suggested inventions based on snips just haven't been rigorously tested in any kind of clinical trial, so if you will get to ask academic geneticists about Darts, consumer tested actionable advice based on them. They would tell you. There's basically nothing that you can do with your twenty three and me for example. Right I. Do want to mention your paper for those interested. The title is using synthetic data sets to bridge the gap between the promise and reality, abasing health related decisions on common single nuclear tied polymorphisms. It's a great paper. It is freely available in all linked to that, so everyone can read it Let's just talk a little bit about. How these things are actually studied so when we're looking at disease, risk and genetics. What are the problems with the methodology in these studies from your point of view? So the main well, there's two two ways that you might look at. The heritage Bitsy of a certain. phenotype, so say a beast tea or an increase in BMI is perhaps one of the ones that was I looked at. And you can do twin and family studies, which tried sort of icy lately. Effective genetics, what is passed down from parents to two children the difficult to control for for the effects of a shared environment But sort of looking at population in general. You might do something genome. Wide Association study where you look at hopefully hundreds of thousands of people and then. Maybe millions of potential snips. And you look at which particular snips might be associated with a given phenotype, so say at increased risk of obesity all an elevated average BMI. And then from there, you sort of can can dig a bit further and tried to quantify. The effect. There is a problem with doing that because you're looking at more snips than you have people to study and FA statiscal reasons, this basically means you'll likely to to overestimate the effect size of a given snip. and. That's that's one aspect, but then when you tryin. Quantify the effect and then report it back, so you might want to tell somebody that is a given effect size of say. An F., T. O. snips or the fat and beastie associated protein. Is One snow in the that's probably the single snap is most associated with an increase in BMI or risk of. And they might say on average if you have one copy. You'll be am. I is point three higher. This is about two pounds in buddy. Wait for an average person, and then it's double that if you have two copies of Ezekiel have. Either one two zero copies of given snip. The the problem there is that. Those are based on singular averages. So you know you take the mean you add up all be a miser, everybody with a given genus hype. And you divide that by the the the number of people, and then you do the same for those with a snip, and then just on average, you might see a slight increase. The real problem comes from the there is so much variability which is lost when you try and describe the average increase. So the thing that I did in the paper was using. Basic Statistical Theory if somebody tells you the mean and standard, the standard deviation of sapien forgiven snippet. You can then reconstruct. A full set that had the follows a cousy and will normal distribution. which it should And then you can look at say how much does. The the full distribution of BMI is in those with a high a higher risk gene type overlap with those with a lower risk genotype and you can do that the any. Single Utah he could do it with a pledge in at risk goals as you know, multiple snips affect. The same a disease or disease risk. And what you start to see or what we saw. Is that. For most single snips that people are talking about in terms of disease risk, there is more than ninety percents overlap between the high risk in the low risk. Gina types so that means that if you have say two copies of the Higher Risk Seo snip. You still ninety percent of the people with that Gina type would have a BMI that is perfectly in keeping with a low risk. Gina type so then only ten percent of people might have a beer by that. That is associated with with an increased risk Ju Ju to type. And, so that's a very different way of talking about risk, so so if somebody just talks about the average effects, they might say oh. You'll going to be on average four pounds heavier. Whereas in reality, there are probably less than ten percent of people who will see any effects on their weight because of their genes aside. And when you look at the effect of the Gina type on BMI in total SEO. Gina type explains things about naught point, two percent of the very busy BMI it's. It's you know it's so tiny that is this basically inconsequential? I'd like to take a quick moment to make you aware of some important resources that are available to you. The first is to make you aware that I not only see patients in my practice. Nashville north, Carolina but I also have a virtual practice where I consult with patients worldwide through telehealth. So it doesn't matter where you live in the world, we consult through our telehealth software. The second resource is the resources page on my website where I list all of the supplements and products I use both personally and in my practice. This can be found at Dr Hedberg dot com forward slash resources. And the third resource for healthcare practitioners who want to learn functional medicine or improve their functional medicine skills. I offer online functional medicine courses at the Hedberg Institute. which is my online functional medicine education platform. You can see all the courses. I offer at HEDBERG INSTITUTE DOT COM and sign up to watch sample course video at no charge. That's Hedberg institute DOT COM and now back to the show. You that was so interesting about your paper. I mean some of these numbers. For some of the SNIPS that you mention. You know the overall. The actual impact on the individual was sometimes less than one percent, no point four percent. Point zero nine two point zero five percent I mean. That alone. Is Not factoring in all of the factors in an individual's life on top of that I mean we don't know if they were breastfed or fed formula, or if they had a lot of antibiotics, the first three years of life. We don't know they're necessarily. You know smoking exercise. Adverse childhood experiences I mean there's so many factors. That could come into play and these these numbers. Do you agree with that or do you think that there's been a good job of? Of Taking into account all of those confounding factors. So in the studies. You know as they do. The you know these Genome Wide Association Studies. And similarly with and Deleon randomize Asian Studies of the effective say a wide range of. LDL, cholesterol levels or homocysteine levels on. On disease risk. The, the baseline is assumption is if you look a large enough group of people than the effects of those exposures kind of disappear. So they don't account for them, because they assume that they have a large enough group size. It shouldn't be a problem and to some extent that is, that is true. And when you look. At the totality of the data that exists on. snips in their. Their effects on, any given, disease risk. In reality almost all of it is driven by the environments. And so those are all the things you mentioned and in particular when you're looking. At some of these snip so so again. ABC types diabetes. These. Are Diseases the a very common in industrialized societies. And if you look at, say apologetic risk, so you take all of the you take all of the snaps associated with obesity and the most recent paper I think one hundred and forty one total sniffs to create apologetic risk cool. But even those in the lowest risk genetic group, which is actually relatively read. That BMI was over twenty five so on average, even in the lowest risk genetic group. These people are overweight. And what I think re tells you is the if there isn't affected these snips, which is over what is very small, so in that paper? They said the one hundred forty one snaps. Predicted all was associated with thirteen percent in the variation NBA saying the eighty seven percent is directly driven by. Other factors in the environment. But these you can only say that this is the case even that thirteen percent and a population that is you know, baseline. Overweight or obese? And in the setting of modern westernized environment so once you take those facts away. If you'll know, you're working with a patient or yourself Removing some of these factors or changing your environment, you don't have the same genyk environment as the average industrialized population does. These snips become even less important. Interesting. Yes, that's why I wanted to have you on. Because your knowledge of statistics is exceptional, and and really understanding the so. So we talked a little bit about obesity, and it's just the psychology in this is really interesting, because people who. Some people just say yeah. You know I've got the fat gene There's not much I can do about it, but just the peers that that has very little impact on on the individual's ability to maintain. Normal BMI. and. When I was doing the graduate level. Courses in molecular genetics. Janet professor. He kind of explained these A. Way To explain it to to lay people is that? He snips. Genes are like an audio dial. You want to say a scale of one to ten, and they can be turned up to attend or turn down to a one based on all the factors in the individual's life. Sleep exercise stress nutrition, etc.. And I thought that was kind of interesting way of explaining it and. That's something that I. Think a lot of people don't understand. They think that if they have the snip. Then it's just one hundred percent. Active all the time and there's nothing they can do about it for the rest of their life. What do you think about that way of looking at? Yeah, I think this. Deterministic view of genetics. Really has all should have. died out as as we learned more and more about the genome apogee genome the sort of the interactions that occur there and. When you look at certain snaps will send genes based on maybe multiple snips. You might have a range of different functions. But. That tells you about the Funk, so so so say a snip. Or a gene encodes for a protein is an enzyme. And based on snips, the enzyme function my increase or decrease in absolutely it can be. Is probably you know it's unlikely that it's going to go all the way down to zero on the volume scale? But maybe it's going to be somewhere between. Three and ten thirty to seventy percent. with one hundred percents something like that. And so if you measure the activity of the enzyme and the test tube, you'll see that there's an effect that is less active enzyme. But when you think about what Jean does, and how it fits into sort of the systems within a body, so you you have the the activity of the enzyme itself, but then it does something right so it it has a substrate and product, and you know some things will be required to make the substrate and something's will end. The product will maybe do something as well. Well and those are going to feedback and tell the Saudi twenty make more or less of this protein, and they're gonna be all these other factors likes Acadian is going to is going to change transcription factors, which is gonNA change the level of of of the protein, and maybe maybe you're going to need some some cofactors awesome, some vitamins and nutrients for that system to function. So say I have. A combination of snips that reduces a the function of one of my enzymes fifty percent. Because of a combination of things, maybe I just make twice as much enzyme, and then I have essentially one hundred percent function. Or maybe all those other factors come into play, if I if I make sure that I maintain US Acadian with him and I have a good nutrients stasis by deceasing. Wide Range of nutrient dense foods. None of this matters anymore so. It's you see people. Talk about you know x percent function of a gene, but thus have you know even for that pathway? That gene has a very small part to play in terms of all the things you know, the the amount that gene is transcribed, the number proteins made all the different cofactors substrates things that are gonNA feed into that system and in reality you know maybe some balances found that means at this reading, no overall meaningful change in function of the system I think that's really what's happening. Most people have some slight changes in in function of genes and proteins, but the same overall balance is maintained as long as you know the necessary inputs there. Let's. Get. Into some specific snips. Let's let's cover the elephant in the room I which. MTA chaffar. this is this is definitely been the most frustrating for me as a practitioner talking to patients about MTA far because a lot of them will come in. Believing that it's a it's a serious part of their illness. It's. It's It's having a major impact and a cause of their disease and their symptoms. And everything they're that they're going through. And part of that is because of what they read online, and what people are talking about and forums and groups. And then you'll hear claims of well, you know. Nothing really worked for me until I just took a lot of methylated fully. And one of the things people need to understand is that there's any I mean studies show? There's anywhere from about forty to a ninety percent chance of placebo effect. If, you believe something is going to work for you. And so that's the first thing that comes into play. Then the other aspect is practitioners claiming that it's it's very important and every time I asked them well. What else did you do with the patient to the patient? Just come in. And you gave the methylated fully, and that was it. and that's never the case. It's always big changes to the Diet. Exercise other supplements so many different interventions going on, and so how can you single out an intervention like that as the cause of the patient getting better? So. What is your overall Take on on MTA far and what the research shows, and is it actually something that we should worry about or Or is it something we should just put aside? The MTA chief, obviously, if you've. Spent time in the functional medicine a Rena. It's you're right. It's that it's the elephant in the room and it's also a nice case study. Because like I intimated before there are two snips the most commonly talked about in the taste for gene. A once United C and C six seven seven T, and you can have you know one or two copies of either and they interact to create different levels of of gene function, so you can look at a fee type based on the percent function of the enzyme, which is reading, which is really nice sort of you. There's there's a rage. And so? It's worth I. saying that's more than eighty. Five percent of people have at least one of those snips results in less than one hundred percent Jean function right so the vast majority of people have as I've heard you know quite. You know smart. People say they have a an MTA. Gene that doesn't work properly, right? That's that's the language that immediately is brought forward. When you start talking about this which you know if if if that's the standard right, then then. Obviously, that's not true. You meant to begin with. So, you know I found this interesting for me because I have one copy of each knit, which means that I have more than fifty percent loss of the function of my gene. O of my notes MTA Chapelle protein if we look at it in test you. Like about it. So one of the ways that you can look MTA. Function In terms of a phenotype is home assistant level. And that's not perfect right? There are multiple escape pathways sixteen. It's not just affected by MTA Jaffar function. However, you know there are plenty of studies that look hat MTA. G Type and Tom Assisting so you can look at what effect you'll snip might have on or snips might have on your high Mississippi level and so. I did this in in a similar way. It's in the paper. People can go take a look at it. And what you see is first of all. The effect isn't linear, which is what most people assume when they're saying you know you have X. percent reduction in function, so you need X. percent more Co lead on with AFO night so that I see that's not true. And secondly, if you look across the range of the most common MTA, Chevelle snips and combinations. You'll MTA. Shofar genius hype. Basically. Explains About eight percent in the variability in home, assisting which is just a tiny amount considering like how how much people say. How important MTA shofar is a function of of this system. And in reality. All these you know so many things going to come into play and when you look at one specific outcome like homocysteine. Is Basically. Is Basically meaningless in terms of what your home assistant level is, and I find it really interesting because when I when I speak about. This so much pushback because they've you know. That's in empty. Asia is important. I remember being two to one to one is coach. She was saying that for them. You know knowing about M.. C. H. was reading it because it meant that they sort of. They found out that their home assistant level was elevated, and they did something. You know they I. Think they say you know. Improve that slightly maybe a bit more choline. and. Then things improved but I would. Ask? What does knowledge about the MTA gene assist with? If you just measured your phenotype right if you just measure sixteen level? What does knowing about MCA shofar do to improve your ability to act on that. And in reality there isn't any people have sort of attached this this level of importance So when you when you look and say Shofar and various outcomes. the the research is incredibly mixed Sometimes, it's postive, sometimes negative. If you if you really dig into the details, I'd say that most of the time it's. It doesn't really have any effect. But but you know it's hard to hear and that's. That's the one where I've gotten the most pushback. Despite the fact that. You know if you find the papers that you think say. MTA Shofar is associated with a given outcome. In my paper all the tools that you can use to prove me wrong and I'm very happy for you to do that. The there's nothing hidden there you all. You can use freely online available tools. You can dig into that yourself and I oversee Kant. No of it's shock on all the papers but you want people to to better understand how they can look at this themselves and I'm you know based on what I've seen I don't think MTA, pause really anything to worry about the most people as long as they have an adequate states, a decent diet and Minimize exposure to various environmental toxins, and over the next size, and all that kind of stuff of which I would, I would say that for anybody regardless of that of that genotypes. Exactly and I I. DO explain that the patients it's just not. This is just not really important and It, was it was it was my understanding about MTA far? Just looking at the whole biochemistry of it was if you had. If you're just if you get a have adequate, b twelve full eight, and and you know some adequate choline in your diet. And some and of course Riboflavin. that's I. Mean that's kind of it as far as the building blocks. To just make sure everything's working well in that pathway. Do you have anything to add to that? No I think that's that that that's it really and the Riboflavin is a great point because these these snips they basically affects the ability of the MCA. Enzyme to to bind to Eddie to which is which is made from Riboflavin, and there's some nice studies showing the, but typically with this those who are homeless I guess further six seven seventy Those guys have. About seventy five percent reduction in their enzyme function at a much greater variability. In the homocysteine levels compared to to everybody else, so that's why the effect isn't linear. But if you give those guys, just a tiny arrive and I think this study gives gave him one point six milligrams. Then that significantly reduces the homocysteine levels. So If. You a nutrient replete and again it's. Produce would require you to eat. You know occasionally a few eggs and some liver. Maybe. You know some some some meat fish That's GONNA. Do Most of the job. And I. Don't think you need to really worry about it beyond the. Agreed I. I did do a deep dive into the far. I think it was last year. I wasn't able to find any evidence that doing any kind of specific intervention really does anything as far as symptoms or reducing disease risk. In fact, the geneticists that I read their statements basically echoed that that. There's there's no evidence that. Treating, MTA chaffar really does anything. So. On that as well, yes. In line with that? I I. Put my my twenty-three inmates into an online choline calculator a which was supposed to tell me how much extra coating I should eat based on my My MTA Jaffar for and. And and one of the paper, and so the main paper that the recommendations based on. Over we'll have fifty percent loss in function so I should eat twice as much coding as you know as somebody. One hundred percent function was cut was kind of fish. Calculator said, but the the paper that was referenced was a paper where they gave extra choline to thirteen four late deficient. Mexican American men. So it's a tiny sample size. We know the s misty and race play a huge role in whether snips of penetration on not I'm and there was the confounded. The this group was already late efficient. And then they looked at methylation function. Our like total methylation and. Even despite giving them extra choline, there was actually no difference in methylation, but then this was the paper that was being used to recommend that twice as much coding so. Just so many parts of that make no sense whatsoever. And and like you say when you look. There s interventions None of them show a significant. Effect one way or the other and people with varying levels of anti-asia function. Yeah it's. It's difficult to navigate this this industry because. There's so many papers that you have to read to understand everything in fact, check everything and I understand why. Not every practitioner is doing that or has the time to do that I. Mean You almost need a research team to investigate every single thing that you're doing? And everybody does the best that they can. But it's interesting. You brought that up about the study was done on people with a fully deficiency, and you can let me know if you agree with this or not, but almost all of the papers that I read on micronutrients. You always get great results when the participants are deficient in that particular nutrient. But, not if there's sufficiency, so there's no, they're rarely any studies that I'm aware of where if the patient has sufficient levels of micronutrient that their body needs. Excess amounts. Don't necessarily. Give you exceptional outcomes. Would you agree with that? Or are there any cases where you you might disagree? Now I absolutely I think that's. There's obviously a baseline level that we require and I think for many nutrients Probably the majority of people eating a a westernized diets will be deficient or at least insufficient in those, and if you supplement with them, you will see. You will see benefits however Like you say I think particularly people listening to this podcast the patients. If you're recommending a nutrient, dense diet, and maybe do some. I would do some phenotype testing where you test for a level a given nutrient. Ideally in the blood, because we understand those much better than some of the other tests. And if somebody is deficient insufficient, you replace that you'll see benefit, but but beyond that. You. Know you almost never. See see benefit, and you know in some cases you may actually cause harm by by adding loads of some particular. Variant of a neutral to a system that that doesn't need it. Right. Right. Let's jump into the second of big snip. That's talked about. At least this is the one that I tend to common contact with the most with with patients and practitioners. Is Com t? In, this is the you know. The idea is that you're either a worrier or a warrior depending on your your CEO MT gene. Can you explain that and what the the actual impact is having? Co Mt. if there is any impact, yeah, absolutely this this this one again. When you look at this yourself, you can always find an interesting story that you want to want to better understand so so with the. Sierra Mt Gene There is a snip cools the change in amino acid. In Casco Low Michele transfers If you have two copies of the Methionine, snip then how foster supposedly a foster emt activity this means you a breakdown dopamine much faster so you have less dopamine in your prefrontal CORTEX. This makes you better. more more resilient to stress, but you have a low IQ and low executive function. So that's me. So if you're listening to me, talk about this stuff. Remember the I have a low IQ and poor executive function, so you probably know worth listening to anything. Conversely if you have two copies of the veiling version, then you have slow activity modes opening supposedly that means you have more likely to be anxious, but you have a higher. I Q and high executive function, and this is sort of. What is what is generally said about those those snips? And so what? What you might actually be interested in me, probably recap. How much does make is in your prefrontal Cortex? Care about cognitive function say so. If you look at the largest. looking at CNN t snips and their effects on various metrics of cognitive function. You know the big ones where you looking. At several hundred people basically say the VIZ, no difference. It doesn't make any difference. And so, if you really dig down you through the tests, I did find one study that looked at five hundred people. And, they found that those who? Were the warrior type foster CMT activity. They perform slightly this well in a version of the number test, which is where you give people a collection of numbers in medicine, the method recite them back in alphabetical numerical order. And then I did an analysis on this on this data, and about full percents of the of the variability in performance in the test was explained by. so again you know more than ninety five percent. Ju To everything else that the plays into cognitive function. But when you really dig into this and this is. One of My favorite personal stories as the genetics. I was looking at. How do we know? About? SNIPS and how they affect the gene function. And there's one original paper which everybody sites back to and they took the brains of cadavers. And they look to the Gina Type, and then they extracted com t from the brain and they look today. In Test Tube. And those who had the warriors type had on average thirty eight percent. Greater activity than the warriors. But interestingly, if you then try and reconstruct a full day set, the describes the full variability but like I like I've done in the paper for the fierceness as well. What you see. Is that actually? The dates that they present. Is Inaccurate in the paper because? The they don't tell you what the Arabs are. They just give you a groff, and then an Arab until you with Arab are is. But, if you sort of like by you know sort of deduction, you can figure out the the way the described the dates set. Is Inaccurate because they're assuming that it's distributed when it isn't. This vast very busy. If you try and reconstruct, states set the the the random number generator the US once said to be negative numbers, which is impossible to to make the way make the day to fit the way. It's described in the paper. And this makes perfect sense. If you try and understand it, if you if you do understand how these studies at done, so if you have to take cadavers, and is it going to be a certain amount of time? Before you. Get access to the tissues and we sent them out of time. If you process it, look at it, you know. All of that is going to result in huge variability in the data. And that's just to be expected. If you do those kinds of studies, so so the the original study that everybody sites back to say that this snip associated with x percent change in function of Sierra, Mt. Basically because of the way the study was done. Really Trust the data. And so like, but but nobody really thinks about. So so even like if I tell you, that is a thirty eight percent difference function. The pro, even true, but that's that's again. These myths propagated. Forwards because this sort of helps us tell a story. But Hey. The original data probably isn't trustworthy and be. If you then do look at snips in Congress a function. They don't really make any difference. Exactly. And I I have patients who believe that this is the single cause of their you know their depression or the anxiety for their mental illness and that alone as we talked about earlier is enough to affect the biochemistry so sitting. And that kind of ties in with the crib one which I just want to have us, talk, about couple of these athletic type snips so crab won the endurance. gene and was what was interesting about this that you wrote. Is that if you? If you think you don't have the endurance gene, this actually affects your performance regardless of the actual. Gino types can you talk about? One endurance. Yeah this. This is a a brilliant paper that came out in nature, even behavior yeah! Two thousand nine hundred. And they they took people and they made them do. A treadmill test? and. They looked at their performance on standardized tests, and then they took their. Know they? They mentioned that gene talk of this gene, a crab one, which is a associated with improved aerobic performance. And then they told the participants, either they had the good version of of the gene so that you know they were going to be have a good version of the aerobic gene, or they had the by version rights, a two copies of the Bat Bush of the aerobic gene. And, then they retested them. And they found that those who were told they had the good version did about the same as they did on the first test treadmill test? Those who told they had the pad version did was. So being told that they want genetically good. Aerobic endurance made them perform less well. And they're. Just dramatically increasing number of examples of of of this being told that there's something about your physiology will is is going to have a much bigger effects thinking that you're going to have an effect is much bigger than the effect itself so that those those effects on people's performance happened regardless of what their actual gina type, watts and in in the same paper. They told people about their. MTO SNIPS again the obesity risk. And Ben they did standard meals. An look to their society, and if they were told that they had the high risk, the lowest unit type that actually changed the the hormone levels that gop one and their with one of the increase in the Gut, associated with society signaling, and their actual feelings of SOC- society off to the same meal, so being told that you have sent units hyper Galveston the jeans she has you actually have. Changes hormonal signaling, it changes levels of hormones associated with that process. And you'll see this again again, I am just bring this up is a tangent, but just because I was reading these the other day. There were two recent studies that look sleep trackers. And they randomized people to tell them whether they had good or poor. Sleep the night before and regardless of how they actually slept those who told that they had poor sleep. Performed less well in cognitive tests and felt sleepy during the day, even though it had nothing to do with how well they actually slept, so there were all these things that you do in the sort of functional medicine space. That if they don't the the US, you have a much bigger effects based on what you tell the patient raw than what is actually going on either that genetic or Pull, on C. Sleep tracking, you can have your muscle, and you're much more likely to have a negative effects than have a positive effect you know like like with the insurance gene to being told that you have the good gene makes you perform just as well right, so can never get better. You just get worse based on on what what what people are telling you based on genetic, so this huge amount harm that you can do when you talk about. That Eugene isn't working properly. This is the language this this used around H. Afar, and similarly watching a video. Somebody sent me on obesity day, and those those doctor saying that seventy percent. Of struggling with the beastie is genetic, and that's incredibly disempowering. You'll basically telling somebody that there's nothing they can do about it because it's a wooden there in is, it's all in their genes, which you know, even if there isn't effect of genes, is all driven by the environment which you do, have control over right is a huge amount that you can empower yourself if you look at it from the right. But that's not what most people. My listeners know that I have a deep interest in psycho, neuro immunology, and so this doesn't necessarily surprise me. Actually 'cause I could bring up a few examples. In, for example, the pain literature. If a doctor and authority figure you know shows you an MRI or an x Ray, and says you know you have this. You're going to have it. You know for the rest of your life. That actually has a significant impact on the patient's pain level going forward. Just being told that they have a problem. And they see it on the film, and they're told that by an authority figure, and then people were given Two tubes of of cream and had the exact same cream in it, but one one tube was labeled cream, and the other one was labelled a cold cream and they all reported. feeling you know a burning or a hot feeling from the one labeled hot, even though it was the exact same as the cold. And and the people had the cold to. said that they actually feel cold. From the cream, even though the cream had no no impact on temperature. So. Many studies like that about what we believe. Effects are biochemistry. From allergies to health, and then these things that you're talking about with. Durrance, so it's just a really fascinating. Field to to look into. Act N three is the other kind of athletic Snip to talk about can. Other any, is there anything you want to talk about a and three? Yeah, absolutely so. There are. I mean at this point. There are dozens of snips that people talk about in terms of say response to exercise or train a bit of CEO, and then use. It's try and give you some. You're just like people. Using snips teddy how to eat switch certainly is an evidence base that, during the same things for training and this again I, I have a story behind this because like you mentioned in the beginning I work with some some Formula One drivers and It's it's very popular, or if you, if you have some kind of device, protest or something, and you can get it in the hands of Formula One, driver It's it's great. Feel Marketing, right? There are these A. By various metrics, the best motorsports drivers in the world, and they're only ever twins you all the time, so these are very rare individuals in terms of being able to work within this and his great. If you can say, Oh, yeah. So and so person. Driving used by tests or use my device or whatever? So I was sent the results by the coach of one of the drivers of genetic training. Tests, so so they. They tested this guy's genetics and they gave him a report. And one of the things that came up. was you know they looked to three or four genes on muscle fiber type? And One he he, he had two copies of this snip and the men of the ACTONEL for three gene. And In his report? This is a big red light. This this bad. And, then it says proportion of five is low than the general population which recalls Utah Lower Response to strength training. Now bear in mind. This is one of like the fittest people you know a in motorsports, but also compared to the general population just incredibly fit. Talk Point something something. And so you know. To begin with that doesn't make any sense, but but then know there's no references attached to that. But what really bothers me is in line the other things that we. Talked about is that. You'll telling. An elite athlete that's their training isn't going to work for them, so you're telling them that. They're not going to respond well to training, which is then going to affect that performance right and that performance involves driving a concrete wall at two hundred miles an hour. And as soon as you start trying to introduce non evidence, based thoughts into that process I do have a big problem with that. And? When you look at the statements, there's no references of course anywhere in the report so then I'll go and dig into this and look and see what I can find. And one main study. That looked at act. N. Gina Type and response the training. and had. About Sixty people. Hoffman Hof women. And they did see. A statistical trend in terms of response to training in Dhaka peak power change in terms after a chunk of training. So, it wasn't significant, but there was a statistical trend between those who are two copies of good versions copies of the bat version. But this was in a group of older men and women over sixty five doing training training three times a week, doing four to five sets of ten leg extensions. Which is just not relevant? A toll to the athlete who is who is being told that they're not going to respond to strength training. You know this this athlete. And there's no studies in a population that might be relevant to him. And again, if I, if I eat, so I use this data, even though isn't great. Trying to the same thing and then ACN type may explain you know five or six percent of your response to strain so again it's tiny fraction compared to all these other things, which actually even in Formula One driver. All the other lifestyle environment factors are going to play a much bigger. Oh, because these guys are in a different time zone every week. traveling continuously high stress so there are all these other things that you are going to be so much more important. I'm so not only. Have you negatively affected so the cognitive aspects of the training? You also the you know everything else is going to be so much more important. And I know people who are tailoring their entire exercise routine around these once they find out some I've known people who quit running and just change to running sprints based on this and also completely changing their. Their Rep skiing and you know the amount of weight, lifting and things like that. If they're fast, twitch versus slow, twitch The an so there was one study that came out sponsored by a company called DNA Fay in the. UK came out few years ago. Now the the randomized people based on their genetics to. A different training methodology based on where they were largely endurance or strength type, and then they looked at their Both Training Both training. Programs Sort of resistance base than they looked at various different performance metrics and muscle game. and for those who had like a synchronous like they're that Gina hype and the and the training program they were randomized to lined up. Seem to do the best however. I mean you you, you think. Wow, you know that's. That's really important. You know this is. This is going to be something that we're gonNA. See a lot more of. Nobody has been able to reproduce those results. There is no other study the randomized to training methodologies based on their genetics and then sees you know then then they see benefit from. Tailoring based on genetics, so you know there was this one paper that made me super excited about. This is a possibility back when I also had more faith in in snip testing as as a as a personalization method anyway. But it just hasn't been. Nobody's been able to do the same. Nobody's mount. You know there's published anything similar so so there's really again no evidence to support that approach. And the same thing with eating correct so the fat versus the Carb Gino type. Can you talk a little bit about that yeah yeah. There's a number of snips the supposedly associated with. Your best responses to too low carb versus high carb diets. And actually right at the beginning of of me getting into all this that was Saute I had a very well known functional medicine practitioner to say. I said I'm a I'm a low CARB GINA type, but my partner is a high Cobb gene. It's up or something like that and I. was you know immediately? I was like okay. This is something I need to to here and. When when you look at the data that exists again. So you have these Genome Wide Association Studies. And not only of the Genome Wide Association studies flawed in their own ways that we talked about earlier. It doesn't mean they shouldn't be done, but it just means that there's. Some caveats to that, and then you introduce another factor, which was nutritional epidemiology, which is. Basically nonsense I'm most of the time because you just don't know what people are eating despite what they tell you that everything, and then you sort of into those and out pops some jeans, supposedly going to be better. Tell you whether you should eat low cobble fat. and. There are no interventional trials that show that there is a meaningful effect there I. Think the best one that's been done to date was the Diet fits trial that people may have had a Christopher Gardner is sort of a a very well known researcher in that space, and they randomized people to either low Kabul low fat diets. On whole foods in general, so they dramatically improve food quantity, and then after like a certain amount of restriction than people were told you know, find a level of Kabul fat intake is sustainable for you. And what then they did a post doc analysis like a secondary analysis of of the results, so the initial results said that it doesn't matter if you're fat, if you improve quality and find something sustainable, then weight loss is the same. And then they looked at people's genetics, and they separated people into being a low kaci his. A low fat genotype or a mixture of the two? It wasn't really a clear signal, one way or the other. And regardless GINA type, and regardless of of which diet you a randomized to everybody the same amount of weight. So so there's really nothing again that says Oh. Yes, you'll. Somebody should be more cop, so you'll. Somebody should be beating more fat based on your genes. Yeah, Exactly, and there's two more snips. I just wanted to squeeze in. You and I had exchanged some emails this past week about these the VR. The vitamin D receptor. the the current understanding among a lot of practitioners. Is that if you have? The vitamin D, receptor polymorphism. You're at an increased risk of autoimmune disease. And what? What did you find in your analysis of that Yeah I spent some time looking at this the. Yesterday in fact. there. They're full video snips. The sort of talked about faulk. BE SM APA and tack and. Unlike most other snips these are actually. Named based on a bacterial restriction enzyme cleavage site, so this is kind of the the old old school method of trying to figure out types of of gene typing I wish people may have learned with if they lent by chemistry in in in College and so these are the full. They've looked at in terms of association with ultimate disease and Hashimoto's Thyroiditis, a particular property. You know 'cause. Common. People are very interested in the section with with Vitamin D and BITs mathie metabolism so. Looking at three math analyses so again, not just looking at single study looking it multiple generations. Multiple different data sets The so massive I found said that TAC was associated with decreased risk in. An African populations bsn was associated with a decreased risk in African and European populations, but an increased risk in Asian populations. An APA was associated with an increased risk and African populations. So that's one. Increase, the risk, st embrace any seemed to play a role. Then the next maximalists says well as an increased risk with tact, but not with APA and Faulk, and then the next man's says well fuck is associated with increased risk in Asians, but not any other population, and there's no effect of the other ones. So, if you you know if you're gonNA do a method analysis in reality does no overall discernible effect here. And this is you know. The more you look at these various studies. Certainly you might be able to find an effect in a certain population, and maybe that becomes important depending on the patient in front of you but overall. I would say that there's no discernible by meaningful. The fact of any of these snaps on risk of say Hush macy's. Excellent. And then the last one is the glutathione. S transferase salute the claim by some practitioners? Is that if they have this GST SNIP? They will have difficulty producing glutathione if they supplement with an Acetyl, sistine or something like a quarter. And again just kind of anecdotal reports from practitioners, practices, and things like that that you find anything that substantiates that claim that someone should just take glutathione on its own if they have the snip as opposed to say NBC. So I think it's an interesting claim to make because just T- isn't involved in the synthesis of boots. thion is involved in the use of Lutheran right so it's the conjugation of goods thion to a molecule that contains a free radical There are two main. GST snips that the people talk about the m one and the t one null mutation you might read about, and they are associated with a decreased level and function of GST enzyme. And depending on the study may be may increase your risk of certain cancers. If you smoke, it may increase your risk of copd a property just because you're not quite as good at. A falling into the trap of ten to be good at this. But you know the cause of the function of the enzyme you might be able to clear as much of the radicals, but will that again at the end. Is Worth saying these are very very common snips. So, more than fifty percent of all the GST feels in European populations. M One though us that means that more than fifty percent of people have or around fifty percent of people have one copy and twenty five percent of people on average will have. Two copies in East Asian populations. Nearly fifty percent off t. one, though both very common depending on the country in African populations. You might have twins to fifty percent of each in different ratios, so you know again. Probably the majority of people are going to have at least one copy of one of these snips. So. When you then look at? Studies of of whether people with GNC snips respond to knack. Which is the specific question? Actually you find almost the opposite. So. Knack does seem to reduce the risk of mortality in people with AIDS accuse for she digestion there in intensive care units. And there was another study that looked a changes in hearing based on noise exposure, and again those in with either one or two null snip copies of gs John that she did better on Mackerel. They were the ones that responded to knack. So. There's no evidence to suggest that. If you have a GST, snip, you won't respond to that. And I and I have not seen any evidence that glues thion is better than knack for any important outcome nakas very well studied very understood And you know so so then that. May Be a case to say yes, people you know with these snips, which again very common. Maybe the majority of people compared to the the minority of people don't have these snips. Yes, you may have an increased susceptibility talks to distress bots, you know the advice is going to be the same in terms of nutrient status minimizing exposures maximizing the healthy of the antioxidant system through all metric exposures like exercise you know all of that is gonNA. Be the same regardless of snip, so so yes, maybe a biochemical function, but does that change your advice? Now it doesn't and I think that's the important thing Excellent. So as I said earlier, this is you know it's? It's difficult to navigate for practitioners because you know, we go to functional medicine conferences, and there's a bunch of labs. They're that that offer. Genetic testing and it's presented in a very neat and tidy model where you just run the test. And, then the patient is supposed to take all of these supplements to address their genes. So I think that's one of the reasons why it's taking off. 'cause there's just there's a Lotta money to be made in genetic testing and selling supplements to address The individual snips and that's that's a problem and I am worried about it. I've been worrying about it for a long time, and that's why I'm so glad you were able to come on here and talk about the real science behind it. I think we've covered a lot today. Is there anything else you wanted to add that? You really think practitioners, order or the layperson should know about regarding. GENETIC SNIP testing. I think that that gives a sort of like got a nice broad overview of where the evidence really stands. The most important thing to me is is The if people think this is important. And they want to use it in that practice like a don't necessarily have a problem with that, but you, but you should understand the evidence. That exists behind your recommendations. And like I said if you link to the paper and the tools to really dig into this all off Beth for anybody who's willing to invest invest the time. and it's important because you basically a likely more likely to do harm than good with the current state of the science and I think that's you know I think most practitioners want to do good. They want to help They WANNA help that patients and you know the the the possibility of doing of doing home. Of disempowering the patient by by the these tests, and also incurring unnecessary costs for the tests and supplements I think that's the way we need to step back and say. Is this really worth us? Doing and the vast majority of of evidence suggests that the recommendations should stay the same regardless of of snips regardless of Gina Type. You know that's the way we re really are the moment, and maybe that will change. You know in US fine, but that radio where we are right now, so so I think it's just it's just thinking about how. communicates these things we could. Patience is going to is going to affect their physiology. You know regardless of what the actually does. and so just just thinking about that and really digging into the SNIPS. You think you think they're important so so great. Find the papers you know. Dig into the data. Take into account things like ethnicity which. Play, a big role in terms of overall fina type based on Gina Type, and In general. The the research is very sort of European centric, and similarly more than seventy percent of of the genus types in twenty three. It means database. I'll take it from from white. People so so When when you then try and apply that information to those. Who are black or have you know a other different backgrounds? You know that the data even if it's a small, even if there is a small effect, it becomes even less meaningful so taking all those things into account, really taking the time to sort of understand I. think is really important, and it's just because it's going to. It's going to affect. The outcome of your patients, we should tree believe people are trying to improve. exactly and. Like what he said. You know you do risk doing more harm than good in some individuals and that's that's really kind of the core. Tenant of practice is the last thing you want to do is. Is Do harm. And, so we have to be really careful and prudent about what we choose to do, and and what kind of interventions we want to to use with patients, so. Dr would where would you like people to find you online? The easiest way is probably to follow me on instagram. At doctor, tell me Word on Instagram There's usually I'll place of my own science publications that, but then also you know some some more general training, so some training stuff because that's something that I'm interested in, and you'll see pictures of my boxes My my dogs pop up frequently as well I am at Dr, a g on twitter. Now is my middle name. And I also have a website. Dot Com, although that's kind of falling behind in terms of updates. SO-SO instagram's per probably the best place. Excellent. Well. This has been great. Thank you again for coming on. And for all the listeners go to Dr Hedberg DOT COM. If you want to read a full transcript of this. And we'll have links to Dr Woods paper as well as links to anything else that we talked about. We'll take care everyone Dr Hedberg and I will talk to you next time. If you enjoy the doctor Hedberg show. 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