Podcast Transcript

Episode: 62: Unlocking the DNA of Eating Disorders: Identifying Genetic Mutations to Tailor Treatment with Dr. Michael Lutter, PhD, MD

[Bouncy theme music plays.]

Sam: Hey, I’m Sam.

Ashley: Hi, I’m Ashley, and you’re listening to All Bodies. All Foods. presented by The Renfrew Center for Eating Disorders. We want to create a space for all bodies to come together authentically and purposefully to discuss various areas that impact us on a cultural and relational level.

Sam: We believe that all bodies and all foods are welcome. We would love for you to join us on this journey. Let’s learn together.

Sam: You’ve probably heard people say it’s in your genes, but what does that really mean when it comes to eating disorders? How much of this complex and often misunderstood diagnosis can be traced back to our DNA? To answer these questions, we’re joined by Dr. Michael Lutter. He’s a psychiatrist in private practice at Precision Psychiatry and a physician scientist who has worked in the fields of eating disorders, depression and anxiety since 2007.

After completing combined MD and PhD training and psychiatry residency at UT Southwestern, he ran a research program on the genetic and neurobiological basis of eating disorders from 2008 to 2016 before transitioning to full-time clinical care. In 2019, he started Precision Psychiatry to help bring innovative treatments to patients with eating disorders and related conditions. He has published one book, 30 original research papers, and written eight review articles. Ashley and I had our minds blown by this episode. He breaks down the cutting-edge genetic research and shares thought provoking novel theories about eating disorder symptoms. He helped us understand that not all genetic mutations are created equal. Some mutations can be more serious than others. And it’s so important that we all take the time to understand the role of genetics in mental health care. Dr. Lutter uses an advanced strategy known as exome sequencing, a process that allows him to pinpoint serious,  often overlooked genetic mutations in your DNA. These mutations can affect so many processes, like how someone metabolizes certain components in food or how their body regulates appetite and digestion. These mutations seem to explain, at least in part, why symptoms like restricting, binging, and purging can be so hard to stop, and why some people struggle to eat their meal plan or struggle to make progress in treatment no matter how hard they try. But with exome sequencing, Dr. Lutter tailors every treatment plan based on a patient’s unique genetic makeup, offering them a more individualized approach to recovery that actually fits with their biology. By altering meal plans, supplementing for specific deficiencies, and modifying medications, he helps his patients overcome the biological barriers that are interfering with treatment so that they can finally make progress and more easily engage in the emotional, relational, and cognitive work that’s necessary for a sustainable change. If you’ve ever wondered how genetics might shape the course of an eating disorder, or if you’re someone who struggled to find a treatment that truly works, this episode will provide new insights and hopefully some hope. So stay with us as we dive into the cutting edge science behind eating disorders  and how personalized genetic care  might just be the future of treatment.

Hello and welcome back to another episode of All Bodies, All Foods. I’m Sam. I’m here with Ashley and boy, do we have an episode for you. I’m so excited for this one. And we’re really going to dig into a lot of new ideas and speculation. We have Dr. Lutter here with us today. Welcome to the show.

Dr. Lutter: Oh, thank you so much for having me.

Sam: I read your book.  I have it right here, actually. It’s called Genetic Information for Treating Eating Disorders.  And I have to say, I’ve obviously read quite a few books, especially being on this podcast. We have lots of authors on and I always appreciate, I mean, all the books I’ve read, I’ve appreciated them so much. I’ve learned so much and it’s really been enriching. But this book, your book, changed my perspective completely on eating disorders.

Dr. Lutter: Well, thank you.

Sam: Yeah. And I mean that and that’s why I couldn’t wait to get you on the show because I have a million questions for you and I can’t wait to dig in. But before we do, I’d love to get to know you a little more. You’re a psychiatrist. You’re a scientist. What got you into this field? Why eating disorders? Why do you think we all need to understand genetics and eating disorders, why is this important? 

Dr. Lutter: So, I mean, my background story is not all that interesting.  I was at MD-PhD. So I did a combined program to train medical scientists. So you do two years of medical school and then you do your PhD and then you do the last two years of medical school, which are the clinical portion. And my PhD, this would make sense at the end, but was on this like, very basic biochemistry of mitochondria, which are the part of the cell that are involved in like metabolism.  So then I left my PhD and then I did two years of medical school where you, I mean, you did everything. I delivered like 10 babies, you help with surgeries, you go to family practice, you go to psychiatry, internal medicine, you kind of see this broad spectrum of human biology.  And I just thought psychiatry had the best questions remaining. I thought we had the most interesting questions left to answer, like what is a mood, what’s a memory, how memories formed, what’s an emotion. So I decided to go into that. So I did a psychiatric residency and I had the first two years of that to then rotate through all the psychiatry clinics and wards and just kind of see everything, you know, schizophrenia, and we worked in the emergency room, and depression, and bipolar, and personality disorders and all that. And I was just most fascinated by my time on the eating disorder unit. You know, I worked at the old Presbyterian unit in Dallas when it was still around.  And I was just fascinated.  I knew a little bit about metabolism and appetite regulation.  And it just seemed to me so clearly that there was a biological component to it, you know, not to diminish the psychological part, but that there had to be a biological component as well. And there was just, you know, at that time, you know 2004, there’s just nothing known, you know, that’s 20 years ago, 21 years ago now. So, you know, scientists, we run into the darkness, right? We go toward where there’s, you know, the best questions are where we don’t know anything. And fairly naively, I’m just like, okay, I’m just going to go study this. You know, it seems really interesting and important and we don’t know much about it. So I started studying it and everybody’s like, “oh, you know, you did your PhD on, you know, the mitochondria, you know, you’re going have to learn all this new stuff because it’s not relevant.” And you have 20 years later and almost everything I’ve done has taken me back to the mitochondria. Like most of what I do now is just based on mitochondrial biochemistry and how, you know, problems with metabolism, especially in the mitochondria lead to all these like psychiatric disorders. It turned out to be a really good education, but at the time you would never have guessed it.

Sam: Right. Who knew? Well, thank you for running into the darkness because now we have your book and we’re going to have this episode and I’m just so thrilled to get into it.

Ashley:  So Dr. Lutter, when you are working with patients and their families, I’m imagining that people come in with all sorts of ideas about genetics, and I’m curious what some of the biggest myths and misconceptions are that folks might come in with, in regards to genetics and mental health, but also genetics and eating disorders. I feel like, yeah, this is something that is asked a lot about in our field. 

Dr. Lutter: Yeah. I to be very, I spend a lot of time on, you know, psychoeducation because you have to be very careful. You know, there is a strong genetic component, you know,  I estimate, you know, it’s probably 50-50, you know,  environmental and stress and trauma and then psychology, and then the other half, know, biologic of which genetic  is a part.  And so I try to explain to families, you know, that there is a genetic component and yes, you know, likely some of these genes were passed along by family members, but it’s not your fault. You’re not to blame. Nobody does this intentionally. You know, if people without any genetic disorders were the only people have kids, you know, nobody would have any kids, right? You’re not to blame, but there is a genetic component. And if we can understand that a little bit better, maybe it’ll give us some insights, some new treatment opportunities.  The numbers  are interesting. If you say the risk of developing an eating disorder is about 50% genetic,  then you say that a first degree family member of a person with an eating disorder is about five times more likely to have an eating disorder, that’s still only about 5% of the population, right? I’m talking about anorexia, I should say, should clarify, not all eating disorders, but with anorexia, you’re about five times more likely to have anorexia if you have a first degree family member. So, the majority of people still don’t have an eating disorder. 95% of people still don’t get it. So, you are a little bit more likely to develop an eating disorder if you have a first degree relative, but it’s not absolute. It’s not guaranteed that that’s going to happen. So, you know, trying to explain to people that, you know, we’re really just using this as an opportunity to learn more and try to do treatment. And we’re not like placing blame on anybody and nobody needs to feel guilty about anything that they pass along to their child. It’s kind of usually where I start off, trying to explain the value of understanding the genetic component. 

Sam: That’s so important, because I do think that the guilt, the fear, all of that can really get in the way of someone supporting a loved one in recovery. And sometimes even like their willingness to start a family, you know, I know there’s people who are scared to pass on their eating disorder, and there are some people who think there’s like an eating disorder gene and you know, we often have to explain, well, there’s many, many genes at play and these genes are very common  and the environment plays a role as well. It’s not just the genes. So yeah, I think there’s a lot of misconceptions out there about eating disorders, genetics, and mental health.

Dr. Lutter: Yeah, exactly. It can be very hard to explain a lot of the background because like you said, it’s a combination of how did the genetics make you vulnerable to this environmental stress? Right. How do those two interact with each other? A lot of people ask me the question, “did the eating disorder cause the mutation?” I’m like, no, you’re born with the mutation. are passed along through generations. They’ve probably been passed through many generations. It has nothing to do with the eating disorder or, you know, with your food that led to mutation, you know, these mutations or this risk. And there is some risk of passing along to your child. But like I said, you know, even if you do have an eating disorder, there’s a 95% chance that, you know, your child is not going to have one. So I always tell people, you know, be aware of it, but don’t let that be the deciding factor on whether you have children or not.

Sam: Right, right. And there’s also so many protective factors that we can put in place to protect mental health and reduce risk, and so we try to educate families on that as well.  I would love to dig into just what we know so far from the genome-wide association studies. I got really into this. This was like fascinating to me when the PGCED came out with, they  partnered with Angie and they came out with a paper in 2019.  The PGCE is the Psychiatric Genomics Consortium for anyone who is wondering what that acronym is. And Angie is the Anorexia Nervosa Genetics Initiative. So they kind of got together and we’re learning a lot very quickly. So I was hoping we could just start there with the basics. What are the genome-wide association studies? What have we learned so far from them about anorexia? But I think more importantly, what are some of the limitations to the research?

Dr. Lutter: Right. So as you mentioned, it’s not just one anorexia gene, but was, we would have found it a long time ago. There are, you know, thousands of mutations in hundreds of different genes, all of which can increase your risk. The important thing, the first thing I would like to clarify is that not all mutations are created equally, right? There is a spectrum of mutations. So some mutations give a very small amount of risk, but they’re very common in the population. You know, it’s 10, 20, 30, 40% of the population. Some of them are very damaging, they give you a much higher risk, but they’re barely rare. You know, it’d be like one in a hundred thousand, one in a million. So the example most people would understand would be the breast cancer genes, BRCA1 and  BRCA2, BRCA1 and BRCA2. So mutations in those genes give you about a 40 to 70% chance of having breast or ovarian cancer, but it accounts for only about 1 to 2% of all cancers, breast cancers. So the risk is high if you have that mutation, but most of the cancers are not caused by that, right? So those would be the sort of the rare, highly damaging variant. So that’s what I’m interested in. That’s what I look at. What the GWAS studies do are they look for those common variants that give a small amount of risk. Okay. So the ones that are generally found throughout the population, but maybe only increase your risk a small amount. So what a GWAS study essentially does is collects thousands of cases of people and compares them and looks  all along,  all these markers all along your DNA and asked the question,  which of the  variations in the DNA are more commonly found in people with a condition, in this case anorexia versus the general population?  And they go through millions and millions and millions of different DNA variants and they find the ones that are more commonly found in people who have it, in this case anorexia, so they can say statistically you are more likely to have the diseases you have this variant. So this was the study that came out in 2019. I’ve got a pulled up here. This was out of the like you said the Angie group.  These studies are  gigantic. They’re very, because it takes so many people and so much computers and computational and all of this. These are gigantic studies. They’re millions of dollars. They’ve got all of the authors that are involved. So these are huge undertaking. You know, my hats off to these people. These are genetic large groups of people who do that. And when they did it, they found eight genetic variants, so changes in the DNA, that if present are associated with a higher risk of having anorexia. So the value of these studies are, they are common. You know, most of these variants, like I said, are in like 10, 20, 30, 40. You know, one is even in like 90% of the population. The downsides are each one individually only accounts for a very small percentage of the risk, the genetic risk of developing anorexia.  And from my perspective, the other limitation is it’s hard to tell which genes are being influenced by these mutations because only about 1% of all of your DNA encodes for genes. The genes are the parts of the DNA that make your proteins. And most of these variants are in between genes, so it can sometimes be difficult to identify exactly which gene is being influenced by this specific mutation. It can be, you know, there are all these tricks you can do to try to figure it out, but it can be a little  difficult to figure out exactly what the biology is. Like how is this variant, like what is it doing on a biological level to increase your risk? But they were able to find these eight variants and then you can do what’s called a polygenic risk score where you like add it up and if people have like, based upon the number of these variants you have, you can sort of predict, you know, how likely somebody is to have an eating disorder. And you can do  different types of studies  by combining a lot of these different variants.

Sam: So the more of the eight that you have, the more, the higher your risk of developing anorexia. Right.  We should add that the GWAS, people with anorexia were the only ones included. Isn’t that right?

Dr. Lutter: In this specific study.

Sam: Yeah, exactly. So I just want to make sure our audience knows that this is actually just for people with anorexia.

Dr. Lutter: Anorexia one was the first one. Bulimia, no, binge eating, I’m sorry, binge eating GWAS that came out from the Veterans Affairs study. That came out last year. And then I believe the same group that did the Angie group, I think they are working on a binge eating or bulimia study as well. So that should be out hopefully relatively soon. The other real strength of this is because you’ve got so many people with all these different variants, you can then compare it to other conditions and see  what associations there are between the genetic risk for anorexia and then other conditions or measures or things like that.  So they found a positive correlation, so meaning that people who have this risk for anorexia also share risk for OCD, which is not terribly surprising. We’ve known for long time that people with anorexia are more likely to have  OCD or obsessive personalities.  Major depression, schizophrenia, anxiety, not terribly surprising, neuroticism, higher levels of education, college completion.  And then they did some what are called anthropometric, so just measurement type of thing. So less likely to have insulin resistance, lower fasting insulin levels, less likely to have type 2 diabetes, higher HDL cholesterol, lower body fat, lower body mass,  just in general.  From those observations, the theory came about that anorexia  is  what I’ve determined is what, Psycho-metabolic disorder, I believe, in which  metabolism  in part is what  underlies some of this  risk of developing anorexia. It’s not just purely psychological that there are likely metabolic disturbances as well that increase your risk of having the disorder.

Sam: Right. And this was kind of groundbreaking because it sort of gives us some evidence that these are not just psychological disorders, but they’re also rooted in these metabolic factors. And, you know, for example, it seems like folks with anorexia, correct me if I’m wrong, folks with anorexia are more likely to have a smaller body to begin with?

Dr. Lutter: Yes.

Sam: Yes. And so there’s something about the symptoms of anorexia, restricting, that makes it more likely they’re going to get to very low weight.

Dr. Lutter: Yes. They seem to have a genetic risk of just being at a lower body weight, being unable to sustain a higher body mass. 

Sam: Right.Right, so there’s these metabolic factors that are genetically built in that makes someone at elevated risk  of having anorexia.  And maybe even it helps explain why some folks with anorexia tend to return to lower weights  and  relapse because they’re sort of working against their own biology and recovery.

Dr. Lutter: I think that’s true. I think it is harder for these folks to maintain their weight.  And I can’t remember the study, but I believe there was a study a few years ago that the people who settle into long-term recovery tend to be a little bit under, you know, ideal, quote unquote, ideal body weight. So they do have this tendency to kind of settle in a little bit less than you would expect just based upon the typical methods used to estimate ideal body weight.

Sam: Right, right. You know, this study, this 2019 paper really fascinated me. And then I really feel like you have insights that take it even a step further. You talk about these variants that are common and they’re responsible for some amount of risk, but then there are these variations that are much more rare,  but end up creating  more serious issues. I think you used a really good analogy in your book. I can’t remember it off the top of my head. I think was it like shards of glass?

Dr. Lutter: Yeah. Yeah. So the analogy I use was, you know, like a large chandelier, like crashing to the floor, right?  You could either get hit by like lots of tiny little cuts, like little slivers, you know, flying and cause like a lot of small cuts. That would be like th  risk that you’d get from a GWAS.  Or you might get hit by like a single large cut, right? A single large slice of glass like coming and hitting you. And  if it hits you, you’re in big trouble, but if it misses you, you’re completely fine. That’s a little bit how it goes with some of these rare variants. If one of your parents happens to have one of these rare variants that dramatically increases your risk of having the disorder, it really is kind of 50-50, whether or not you inherited or not.

Sam: Right. So we’re going to dig into those bigger shards of glass in just a minute. Yes.

Ashley: I am fascinated right now.  Just taking all of this in and saying what you said, thinking about the folks we’ve worked with anorexia fighting against their biology, that I mean, that puts things into a little bit of a different perspective for me,  and kind of understanding  this and what our clients may be experiencing, and so Dr. Lutter, I’m curious, in your book you write that anorexia remains one of the most poorly understood illnesses in medicine. I’m curious why you think that is.

Dr. Lutter: Oh, we can dive into, I mean, the simple answer is it gets, eating disorders in general get less funding for research than almost any other field of medicine. I don’t know if it’s still the case, but if you look at the NIH, the National Institute of Health, I think we’re like second to last in terms of diseases, in terms of funding.  If I had looked at that before I decided to go into research, I probably would have picked a different field, but there’s  very little  money that goes into the research. It’s like one-tenth, like literally like one-tenth of schizophrenia, one-tenth of autism,  even though we’re probably 10 times more likely or more prevalent than those disorders.  So there’s just a lack of  research and to  a lesser extent, think, you know, it’s still considered,  you know, not within our circles, but in the general population, I think it’s still considered largely a disease of choice. You know, it’s a behavioral condition.  A lot of people still think, you know, it’s just young women trying to be thin to get attention, which, you know, obviously, no, it’s not the case.  But I think there’s a lot of that.  So, for whatever reason, the eating disorder field has not been able to advocate  with politically for funding the way other groups have, you know you look at like autism, that field has really  exploded in the last 20 years in terms of their funding.  The Eating disorder population is not really, or community’s, really not been able to rally together to be effective in increasing funding for whatever reason. 

Sam: Well, I mean, I feel like we’re lucky to have the research that we do. I mean, we  have Twin Studies, Family  Studies, now have  the GWAS studies and I guess we can just hope that  research will continue to be funded because this is really important stuff. I mean, one of the things that came out of the 2019 paper that really stuck with me was this idea that maybe we’re going to get to the point where we’re going to be able to identify many different subtypes of anorexia.  And I’ve always had a hunch about this. You know, just working in the field, you start to realize that no two cases look the same. And especially with anorexia, there just seems to be  way more, I don’t know, differences between clients. You know, some folks, it seems to be really rooted in obsessive thoughts and compulsive behaviors. And then for other people, just, seems to be something different that’s happening. And I can never really put my finger on it, but when I read that, you know, about these different subtypes, and then you actually, in your book, talk about, you also think there are many different subtypes of anorexia. How many do you think are out there?

Dr. Lutter: That’s a good question.  With binge eating and bulimia, there’s clearly four major genetic clusters that I’ve found, and maybe a little bit of a fifth. With anorexia, you know, the most common pathway that I find involved in restriction is metabolism of fats, of lipids. That’s about 40-45% of patients have a mutation in a gene related to metabolizing fat. And then it’s about 25% amino acids, so proteins, few small percentage of people with carbohydrates. And then there’s a few other pathways I found. There’s a subgroup of patients I have who have mutations in genes related to synthesizing dopamine. So they have deficits in making dopamine and serotonin or norepinephrine. They tend to have a very dense depression. They tend to be mostly depressed, don’t respond very well to traditional antidepressants.  They don’t eat much, so oftentimes they’ll end up in eating disorder treatments, but they don’t have that sort of the classic drive for thinness. It’s much more like apathy, and they respond much better to different types of interventions. There’s at least five groups that I find, I’m sure there’s much more, it depends on how much you want to drill down on it.

Sam: So you just dropped some major bombs right now. Let’s back up. Okay so there’s one, there’s a group of people that you believe, out of all the people who have anorexia, there’s a group of people who cannot metabolize a certain amino acid.

Dr. Lutter: Yeah. So it’s mainly the essential amino acids, right? So there’s, so the proteins in your body are made up of 20 amino acids. There are nine essential amino acids. So,  meaning dietary essential. 

Sam: That you have to get from food.

Dr. Lutter: That you have to get from the food that you eat. So patients with anorexia are much more likely than the general population have mutations in genes related to metabolizing or breaking down those amino acids. So, you can use the amino acids to make proteins and if you have extra or if you’re like fasting, then your body can break down protein and use that as energy. So that would be  things like the branch chain amino acids, is isoleucine and baleine. And then the other common ones I see are lysine and tryptophan. So mutations in those pathways are all much more common in people with restricted type eating disorders.  And this is anecdotally, but  you said I was welcome to speculate. Anecdotally, people with  a higher burden of mutations in genes related to metabolizing amino acids tend to be more vegan or vegetarian. They tend to really avoid really high protein meals. They tend to get much more, especially animal sources of protein. They tend to be much more like the data for plant sources of protein.

Sam: Well, that would make sense because eating those amino acids make them feel awful, I imagine.

Dr. Lutter: Yeah. My new view of anorexia and ARFID is that people create aversions to foods that their body cannot metabolize effectively.  You  know, it’s sort of like intuitive eating, but in sort of like  a different way, like, you know, the body knows what it can’t break down, can’t metabolize. And it’s somehow that message gets back to the brain, like, okay, don’t eat that, you know. Because a lot of these intermediate products are like toxic, you know, things like luteric acid, you know, which are like, which is like a brain toxin, you know. So if you can’t metabolize some of these factors, they actually build up as these products that are like toxic to neurons.

Ashley: That is so like, that’s mind blowing.

Sam: Like mind blown, right?

Ashley: I’m thinking of folks with like celiac and just how they respond, you know, to the gluten, to the wheat  and how it just like really hurts their stomach and the rest of their functioning in their body, how this  actually like a certain protein might make them feel a certain way, like you said, and to where they develop this aversion and, and they may not even, you know, cognitively know where that’s coming from. But that I, I’m just thinking of our sweet clients that are like, this doesn’t feel good. This is hurting me. This doesn’t feel good. And how that could be the case for them.

Dr. Lutter: Yeah, I feel incredibly guilt because I worked for four years at the University of Iowa, you know, and I attended when they still had a program. We were very proud that we would give them bacon every Wednesday morning. know, Iowa obviously, big pork.  And it was like every Wednesday morning, like everybody got bacon and you know, was bacon Wednesday and everybody had to eat it. And I’m thinking back now like, oh my gosh, know, what were we doing? Like maybe bacon was  not the best option for them.

Sam: Right. These like fear food challenges that end up actually making recovery a lot harder for them.

Dr. Lutter: Yeah. I mean, like I know the standard is to, you know, the fear foods and exposures. And I want to be very clear that I don’t know if that is good or bad anymore. Right. Like I’m not saying don’t exposures anymore. You know, the evidence is not out there, but it is an interesting thought that the fear foods people develop may have a biological basis, you know, and they may really make them sick.  I re-think everything now.

Ashley: We thought when people would say this, it is so subjective. Is it really harming you? How do we know?

Sam: Right. Is this a medical issue or is this really rooted in the eating disorder? According to all of your work, Dr. Lutter, just seems like there is a small segment of the anorexia population that may have this mutation. And in those very specific cases, treatment really does need to be tailored, especially the meal plans.

Dr. Lutter: Potentially, yeah. Potentially.

Sam: I know we’re speculating. We’re not there yet.

Dr. Lutter:  It could very well be that we will have macronutrient selective  meal plans in the future. Right now, I’m working on helping. So Guido Cromer is doing a ketogenic diet study out of University of California, San Diego. And I’m helping a little bit with it, to analyze the genetics of these folks.  So I have not seen the data. I have no idea if it works or not, but the idea that  eliminating carbohydrates or fats or whatever or low protein diet may be  a potential treatment is very different than what the current standard is. 

Sam: Right. So there’s this very specific variation that has to do with breaking down amino acids that really could be approached the same way we would approach celiac disease. You know we always say all foods fit, except if there’s a medical issue.  And in these cases, I mean, there is a medical issue. There’s a variation.

Dr. Lutter: There could be.

Sam: And so you also talked about there being a variation that affects the ability to break down carbohydrates? 

Dr. Lutter: There is.  So there’s a disease called citrine deficiency in a disease. So we did a talk on this. I work with the Citrine Foundation. There’s a foundation that works on this. It’s a rare and inherited metabolic disorder. So last March they did a presentation on this. And those folks have difficulty breaking down carbohydrates and then large amounts of protein as well. So they tend to have a very strong aversion to carbohydrates and alcohol. And the treatment there is just to have less carbohydrates. There’s a couple of other things you can do, but basically it’s backing off the carbohydrates. I found a couple of cases of citrine deficiency in the patients that I work with. So it’s not like super common, but it’s not rare either. 

Sam: Wow. OK. So we have two subtypes. What were the other? 

Dr. Lutter: So the most common problem in people with restriction is in metabolizing fats, especially long chain fatty acids.

Sam: Long chain fatty acids. 

Dr. Lutter: So I’ve looked at this in two different genetic cohorts now. It’s about 17 to 18 percent of patients, so a little less than one in five patients that I look at have mutations in one of five genes that are involved in importing long-chain fatty acids into the mitochondria to be metabolized down into energy. So it’s what’s called the carnitine pathway.  There’s a series of proteins that are involved in moving fats into the mitochondria to be turned into energy.  People with restrictive eating disorders are much more likely to have rare highly damaging mutations in those genes.

Sam: I remember there was an animation that you had to help explain this. Where what happens is  the brain sort of mistakenly thinks that the body has enough nutrients?

Dr. Lutter: Possibly. I don’t know the exact mechanism. You can clearly see in these patients that they impairments in metabolizing long-chain fatty acids. So there are all these special machinery, all these special proteins that are involved in holding onto the fats and escorting them into the mitochondria to be turned into energy. Patients with restriction are much more likely to have mutations in these genes.  And you can see the buildup of these byproducts.  There’s a pathway that the body has to get rid of these toxic fats called omega oxidation. And it creates these types of fats that can then be like excreted through the urine.  And those levels are much higher in people with restriction.  So you can actually see that it’s more common for people with restriction to have impairments in this beta oxidation process of breaking down fats. So that part is very clear. What I don’t know is then how that stress signal goes back to the brain to stop eating  fat.  That part I’m still working out. It’s not got a theory but I don’t know for sure but you can observe these very clearly and people with restriction and some of the in some of the cases you can actually treat it you can get back things like a carnitine acetyl carnitine and that will, you know, somebody just can’t make enough of it. And that will improve the functioning of the system and people’s, I wouldn’t say they’d become asymptomatic, but you know, they have a lot more energy, less brain fog, they tend to have lower levels of eating disorder thoughts, a little bit better, you know, like meal planning, completion and variety. So you can sometimes actually go in and intervene in the system to kind of make it work better. People do get better. But again, this is speculation, we need to really do large scale studies to prove whether or not this is an effective treatment or not.

Yeah, so then there’s a couple of other pathways. It’s not just metabolisms. So I estimate about 77% of my patients, you know, who are mostly of European descent,  have a mutation in one of these genes that involved in metabolism. So that’s the most common pathway I see. But then there’s this subgroup of folks who have problems with making dopamine.  That’s not that common. I have five to 10 patients like that. And then the other one are circadian rhythms. I see a lot of circadian rhythm patients. So there’s a lot, there’s a much higher rate of what’s called delayed sleep phase syndrome that I really appreciated,  especially working in a treatment center in which you force everybody onto the same schedule. So it’s very common for people to have these disorders where they tend to be night owls. You know, they tend to be people who prefer to go to sleep at like one, two, three, four, five in the morning, and then sleep until like noon. So they’re usually missing breakfast. They usually have very low appetite for breakfast. First meal of the day is around noon. Then they’ll have dinner with their family. And then a lot of them will have a third meal on their own, like 10, 11 o’clock at night, and then go to bed at like one or two in the morning. So their circadian rhythms are shifted. A lot of these times when you’re in high school or something like that, and you’re forced to get up early in the morning, you just don’t want to eat breakfast. It would be like me waking up at like one in the morning and like having my breakfast. Like I’d be like, no thanks.  So they look like restrictors because they eat very, they skip breakfast, they eat a very small lunch and then they come home and they eat all these calories, you know, in the evening and at night. And they sometimes get labeled, you know, like binge eater.

Sam: It sounds like night eating syndrome. Or night eating, yes.

Dr. Lutter: But a lot of times it’s just like misalignment of the circadian clock. There are some treatments that you can do, some behavioral treatments you can do to better align the circadian rhythms, but those tend to be a little bit harder to treat.

Sam: Wow. OK, so did we hit those big shards, the ones that we wanted to, those rare mutations that seemed to affect?

Dr. Lutter: Yeah, I think that covers most I’ve seen.

Sam: Really mind blowing stuff.

Ashley: Yeah, that was great. Thank you so much for sharing. I’m curious, so we have the diagnoses like bulimia and binge eating  that were not included in the genome  wide association studies that we were discussing earlier.  And what we have learned so far about these diagnosis based on family and twin studies that have been conducted. What are your thoughts  on the role of genetics and their impact on the  symptoms such as bingeing and purging? 

Dr. Lutter: So bulimia and binge eating. That’s a great question. So there is one GWAS study, like I said, it came out last year from the FAERS study. And that, what they linked was iron metabolism. They found iron metabolism was associated with increased mutations in genes that are typically associated with iron metabolism or associated with higher risk of binge eating.

Sam: Interesting. Meaning that they’re not absorbing iron?

Dr. Lutter: I don’t know.  I don’t know what the link is.  It’s a great question. You know, it’s one of the beautiful things about genetic studies are they’re completely unbiased, right? Like you can look at everything, you look at all 20,000 genes and you have no idea what’s going to come out of it.  It was a fascinating  finding. Then like I said, I think the ANG group is working on a  binge eating study.  There have been, you know, we’ve done some smaller studies, family-based studies, which we found a few things. Back in 2017, reported the most, in that study we reported we sequenced all the DNA of, or all the genes of 100 patients with eating disorders. And the most common mutation we found in bulimia was in GLP-1 receptor. So four out of the 39 patients with bulimia had a mutation either GLP-1 or GLP-1 receptor. The funny thing is back when I started, first started giving these talks, I had to explain to everybody what GLP-1 was. Now I don’t have to explain.

Sam: Not anymore. That’s a hot topic.

Ashley: Commonplace.

Dr. Lutter: So, you know, obviously that’s gotten a lot of attention. I think there’s clearly a subgroup of patients with binge eating and bulimia and have low levels of GLP-1. We’ve known that since 2012. The first paper showing low levels of GLP-1 in patients with bulimia came out in 2012. There was a second study, I believe, that came out later that showed the same thing. So we’ve known almost 12, 13 years now that patients with binge eating, bulimia tend to have lower levels of GLP, or a subset of them have lower levels of GLP-1.

Ashley: Dr. Lutter, could you just explain what that would look like? Like, what does that mean if they have a lower level of GLP-1?

Dr. Lutter: So GLP-1 is a satiety hormone. It’s released by a specialized set of cells in your intestines that sense the presence of mainly fat, you know carbohydrates and proteins. So in the presence of nutrients, GLP-1 gets released. And it has a number of functions involved in metabolism. So it increases insulin release from the pancreas and it sensitizes the action of insulin, so that’s where you get the diabetes treatment part. It goes back to the stomach to slow  gastric emptying. So it makes you feel more physically full. And then it goes to the brain where it has many effects.  It is, the GLP-1 receptor is present in the brainstem and then into the dopamine neurons.  So it’s thought to have very powerful effects on, I guess the term I’ve seen now is called anti-hedonics.  It decreases pleasure seeking by the dopamine system,  you know? And  it seems like maybe it suppresses  pleasure seeking in response to a number of different things, not just food.  So  that’s how the system works. So people who have mutations in the system in response to food have wanted release of GLP. So they don’t release as much of it. So they don’t feel as full or satisfied as somebody who has a higher level of the hormone.

Ashley: And they might be more pleasure seeking.

Dr. Lutter:  Right. They don’t feel full. They don’t feel satisfied. And they want to continue  even if they’re like physically very uncomfortable.

Sam: Which is that’s right with the criteria of binge eating disorder and binge eating episodes, you know, feeling like maybe eating to the point of feeling so full that that’s really the only message that you have that maybe you had enough.  This is really fascinating and there are probably people in the audience who are thinking,  well, I have binge eating disorder or I have bulimia and if this is a GPL1 issue,  should I just get on a semi-glutide? Should I just do that? And I was hoping you could say a little bit about some of the risks.

Dr. Lutter: I know it’s very controversial.

Sam: Yeah. And there’s a difference between taking the medication at a high dose to pursue weight loss and taking it to actually correct an issue with GLP-1.

Dr. Lutter: Right. So I have prescribed it for people who have mutations in the system, in their system. You can’t measure GLP-1, you know, like you could like thyroid hormone or insulin or smoke.

Sam: Right. Because it’s only like in your system for like what? A couple minutes?

Dr. Lutter: Yeah, the half life is like one minute. So you can’t go in there and check it quick. So the only people who can measure it are like these specialized labs and universities who can like immediately like, you know, stabilize it and, you know, stop the degrading process. So you can’t go and measure it, you know, which would be ideal, but, they’re very powerful medication. So in the people who have these mutations where they don’t make enough GLP one or don’t release it,   the medications have worked  amazingly well. They work, you know, really very quickly and people have symptom of leave at very low doses very quickly. But there are risks.  That  is what I would call a physiological dose of the medication, right? So you’re taking somebody who’s low and you’re getting them back up into the normal range.  So that’s what you would do with say type 1 diabetes or  hypothyroidism. What the pharmaceutical companies are doing is they’re giving massive doses. They’re giving  what we call a pharmacologic dose or a supraphysiological dose. So they’re pushing the system, they’re giving much, much higher levels than you would see in somebody naturally and they’re creating this pharmacological effect. That I don’t know as much about. I know that there are risks at the higher doses. Gastroparesis, severe constipation, it can cause tachycardia, so racing heart. I will say that there’s a number of people I’ve seen who have this apathy syndrome. So really high doses, they don’t report being sad, but they report being very apathetic. They have no motivation. They don’t want to do anything. 

Sam: Well, that makes sense if it’s suppressing dopamine.

Dr. Lutter: Yeah. You know, if it’s anti-hedonic, you know, so like probably serious, but I probably took more people off GLPs last year than I started on GLP. I had a lot of people who came in who got started on these medications, you know, and then they’re like, I’m coming in for depression. And I talked to them and, you know, this started like right after they got put on, you know, like a maximum dose of  something, and we pull them on the dose and all of a sudden they can focus and concentrate again and have motivation. So there are definitely risks.  Unfortunately, we don’t have the tools really to identify who would benefit from these medications versus who would not.  Maybe in the future we’ll be able to measure levels after a meal, like a glucose tolerance test, something similar to that, but it’s not available yet.

Sam: Right, right. I mean, maybe one day it could be a very useful medication for people to target, very specifically target people who have those mutations and affect GLP-1 hormones. Okay, let’s talk about what you do. I want to make sure I’m saying this right. Exome sequencing?

Dr. Lutter: Exome, yeah. So basically, I look at that 1% of all of your DNA that codes for the genes.

Sam: Your clients come in and you sit them down and you explain to them, I’m going to look at your DNA and figure out what mutations you have so you can individualize the treatment plan for them.

Dr. Lutter:  I try to, yeah.

Sam: You try to. You’re very humble.  I appreciate that.  But this is really cool. I mean, so how do you go about this? How do you look at someone’s DNA?

Dr. Lutter: So technically it’s very easy. It’s a cheek cell swab. So it’d be similar to like a COVID test, except you don’t even go into the throat or the nose. It’s just the cheek.

Sam: Wow, no blood.

Dr. Lutter: No blood. And then you send that off to a lab. So there’s enough information in your DNA to fill a book that would be like 400,000 pages long, right?

Sam: Yeah, I thinking to myself, how do you kind of come through all of that? It’s amazing.

Dr. Lutter: What they essentially do is it would be like the equivalent of taking a book, several thousand copies of a book that is 400,000 pages long and putting it through a wood chipper. And then you have a supercomputer  read  millions and millions of fragments of paper and recreate the book by lining up sentences, right? That’s essentially what they do is they just read millions of fragments of DNA and then recreate it by overlapping it, overlap, overlap, overlap, overlap. And then you’ll get like a hundred letter, you know, each position all along, you’ll get like a hundred letters or whatever. And they recreate everybody’s DNA based upon reading tiny fragments. And then they analyze it and compare it what’s called the reference.  The reference is just what is the most common letter at each position along the DNA. And then they flag that. They flag any time that you have a DNA change from what is the most common. And then they put that into a spreadsheet that’s a few hundred thousand lines long, and they send that to me. And then that’s what I analyze.

Sam: And then you can find the smaller pieces of glass and those big shards?

Dr. Lutter: I don’t find the small pieces, but I can find the shards.

Sam: You can find the shards. And then that tells you…

Dr. Lutter: Yeah.  So if there’s a mutation that’s running through a family, I can usually find it now.

Ashley: Wow. Is that something that’s available everywhere, Dr. Lutter? So you’re in Dallas, I’m an hour north of Nashville.

Dr. Lutter: I don’t know if anybody else is doing it for eating disorders. It’s becoming more common for autism.  It’s almost the standard of care now for autism.  There are some other places that are doing it. I don’t know of anybody doing it for eating disorders, so probably will be soon.

Sam: See, Ashley, I’m like looking at you and your mind is getting blown the way.  Like now you’re experiencing the mind blown effect.  So, yeah. So just quickly to give an example. Let’s say someone comes to you and they’ve been diagnosed with anorexia and they’ve tried treatment, nothing seems to work. They’ve sort of been labeled as this severe and enduring case.  How might your exome sequencing help them? What would you maybe change to their treatment as usual?

Dr. Lutter: What’s something we would find? Okay, so this would be the best case scenario. The  most common mutation I have found in anorexia is in the gene called B-Box1, B-B-O-X1. And this mutation is in about,  I can’t remember the exact percentage of population, but it’s less than 1% of the population, but it’s close to about 5 to 7% of people with restriction have this mutation.

Sam: 5 to 7 %?

Dr. Lutter: Yeah, it’s involved in making carnitine. Carnitine, we talked about earlier, is that molecule that’s involved in helping metabolize long-chain fatty acids and then certain amino acids, right? And there’s a paper out in Japan that came out recently that showed something like 40 percent of patients with  eating disorders are deficient in carnitine. So they have low carnitine, right? So people who are deficient in carnitine just have less ability to break down long-chain fatty acids and certain types of amino acids. And you can measure this. It’s pretty easy to measure carnitine, although it’s a little bit tricky on sort of interpreting the data sometimes.

Sam:  I was going to say, is this like in routine lab work  or?

Dr. Lutter: No, not in routine lab work, but you can order it. Yeah, it’s a you got to especially order it, but you can order it and then analyze it.  So the best case scenario is somebody comes in, they have a B box mutation or there’s a couple other genes, TMLHE and  ALDH9A1. So if they have one of these mutations, you can measure, you can look at the carnitine, the carnitine is low, and then you just give it back as a supplement. You know, they take 500 grams twice a day. It’s dirt cheap. It’s pretty safe. And you can see improvements in their metabolism. You can see some of these toxic byproducts decreasing  and people tend to report, like I said, better energy, less brain fog. I wouldn’t say the eating disorder  thoughts go away, but they’re sort of quieter.  That would be like the best case scenario.

Ashley: Wow. Can we send everybody here? 

Sam: How many of these can you do a day, Dr. Lutter?

Dr. Lutter: I can do about two a week.

Sam: We have more than that.  Wow.

Dr. Lutter:  It’s not covered by insurance yet.  I’m trying to get an IRB approved so I can go back retrospectively and then anonymously report some of the findings because it’s much worse. It’s going better than I thought. This is the thing that has really blown my mind from the DNA.  The other thing besides just the fact that people can’t metabolize fat, is about four to five percent of the patients I sequenced,  I wouldn’t say don’t have an eating disorder, but they have a genetic disorder that probably explains their eating issues better, right? So, citrine deficiency would be one of the examples. But I found a few other like really like rare cases of, you know, of metabolism, metabolic disorders, genetic disorders.  I found a case of suspected cystic fibrosis that they didn’t know about. That hasn’t been confirmed yet, but that was another thing that we found. So probably 4to 5 % of patients coming out of,  know, getting treatment, coming out of treatment centers, probably have a medical disorder that mimics anorexia or at least significantly affects the course of the…

Sam: Contributes to it, yeah.

Dr. Lutter: And that’s not even counting the, you know, the immunological component, you know, the mast cell activation syndrome, you know, the celiac disease, things like that. It could be, you know, five to 10 % of patients have an undiagnosed medical condition that’s really impacting their treatment. That was the other really big surprise that has come out of this. it’s not as tricky for me to find other things that are contributing to the eating disorder. Sam:  So there’s a lot of benefits to getting this done because it just will reveal things about you biologically that maybe you didn’t know.

Dr. Lutter: And there are cases where I can’t find anything.

Sam: But that also gives you an answer.  I was thinking to myself,  know, worst case scenario, I guess someone comes in and pays for this and nothing really comes back. That still does give some information because  then we know maybe this is, you know, we can approach this  more from an emotional perspective, more from a psychological viewpoint  to rule it out, at least, has value.

Dr. Lutter: I think that I don’t think the patients think that. 

Sam: I mean, yeah, I’m sure it’s really validating to, you know, find out that you have.

Dr. Lutter: It can be very validating.

Sam: Yeah, or variation and it can be maybe a letdown when you discover that there isn’t really a genetic explanation.  And at the same time,  you’re getting important information either way. 

Ashley: Yeah. I’m just in on taking it all in right now.

Dr. Lutter: When it works is amazing. I feel really bad, you know, like there’s a lot of cases I just can’t do anything and I’m like, you know, like treatment as usual, you know, but, there are, I find a lot of new things that a lot of times it’s very simple things like riboflavin deficiency is like surprisingly common. You know, riboflavin is B2, vitamin B2 and it’s very important for metabolism, especially like fat, fats and fatty acids. That turns out to be way more common than you’d realize.

Ashley: And  what does that do in someone if they have that deficiency? 

Dr. Lutter: So riboflavin is involved in sucking the electrons out of food to create energy, right? So if you don’t have that, again, you can’t metabolize food and you can’t build up these products like gluteric acid.  So you can give back riboflavin. A lot of the B vitamins are deficient.  A lot of these cofactors are deficient. It might turn out that this is like uniquely suited toward treating anorexia because a lot of these cases are just deficiencies in  vitamins or cofactors that can be easily replaced.  It’s not like a cure. There aren’t many cases where it completely goes away, but a lot of times it helps, so, kind of doing a series of talks this year and one of the things I’ve done is just, one of the most common things I found, deficiencies in and then like how do you go and measure those and then how do you treat them, right? So that you don’t need to be able to read DNA exomes, right? Because it took me like 10 years to figure out how to do this. But most dieticians would be able to, you know, read a metabolic study and see where the deficiencies are and be able to go and correct those deficiencies. So I’m trying to come up with a way that’s much, you know, that I can teach.

Sam: More accessible. Yeah.

Ashley: That’s awesome.

Sam: I know. my gosh. What are your hopes, Dr. Lutter, in the next five to 10 years? I mean, what do you hope all of this information, this genetic information, where do you hope we land a decade from now?

Dr. Lutter: A decade.

Sam: Or maybe sooner, you know, hopefully.

Dr. Lutter: I hope it inspires a new generation of researchers to come in, you know, and really look, you know, are there certain macronutrients that people with eating disorders can’t metabolize, you know, are there deficiencies that we can go in and treat and can we tailor meal plans? You know, there’s a lot of work that’s going to go into that. It’s going to be very hard work. But that would be my hope is I think,  I think from a biologic angle, we’ll be able to go in and do a lot of things that will really help  the patients  as well as like on the psychological side, you know, that just help the psychotherapy be much more effective.

Sam: Right. And I think that’s such an important point that eating disorders aren’t just genetic. I mean, even when you have these mutations that are found,  I mean, there’s still an emotional relational component. There’s still a cognitive component. I mean, all of these things, of course it’s all connected. And at the same time, eating disorders are complex. There isn’t one cure. There’s one thing we can point to say, okay, this is going to, you know, guarantee recovery. And so it’s oftentimes interdisciplinary and it’s a really you know, complicated approach because it’s a complicated disorder.

Dr. Lutter: Yeah, what I tell people is what I mainly do is I try to target treatment interfering symptoms, right? I try to target the symptoms that prevent people from doing the work and therapy and with their diet to really heal from all of this.  And that’s really my goal is to try to use the biological stuff to kind of help keep people in treatment and help them be able to kind of go through the work that they need to do in order to really get better from this.

Ashley: Well, Dr. Lutter, I just want to thank you for your work. And I want to shout it from the rooftops that we need  more research in our field.  That was even kind of shocking to hear you say that we,  you know, have some of the lowest  funded research  out there. So  whoever  the powers are that be, they want to come support you and all the work that you’re doing. Come on.

Dr. Lutter: What’s funny is I don’t have any research money. This is all self-funded.  I spend  tens of thousands of dollars of my own money a year doing this stuff.

Ashley: Yes. Wow. That’s amazing. Thank you. Thank you for your contribution. It’s incredible. 

Dr. Lutter: But yeah, it’s much better than applying for NIH money. So I’m much happier.

Sam: The book is called Genetic Information for Treating Eating Disorders by Dr. Michael  Lutter. Wow.  Thank you for writing this book.  I really appreciated it and it really changed the way I think about eating disorders. So thank you.

Dr. Lutter: Oh, well, thank you. That’s kind words.  And I appreciate you having me on and look forward to catching up with you all again here in the future sometime. Okay. 

Sam: Thank you so much.

Ashley: Thank you for listening with us today on All Bodies. All Foods. presented by the Renfrew Center for Eating Disorders.

Sam: We’re looking forward to you joining us next time as we continue these conversations.

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