Episode 286: Dr. Laura Buchanan and Nick Norwitz

Welcome to the Low Carb MD podcast. No one is beyond help. No one is beyond hope.

As we have always said, we are bringing you medical information and cutting-edge science, but none of this is medical advice. Please seek out input from your own doctor. Welcome to the Low Carb MD podcast. I'm joined today with Dr. Laura Buchanan and Dr. Nick Norwitz. And I'll make their introductions in a bit. Today we're going to be talking about anorexia, which is something very important to me. In fact, I've been very open and vocal about me having anorexia as an adolescent, and it's something that I think many people take for granted, the, the impact of relationship to food on particularly young men and women, the associated weight stigma, the restricting of diet, the deep involvement of mental health. And so this is a very vulnerable population. There are very few eating disorder licensed, you know, social workers and therapists, and it's a very vulnerable group of people. And so I'm— this is something very important to me, something very meaningful to me, and, uh, this podcast is, is very special. A little bit about Nick Norwitz: we've had him on several times. I think he's the most, uh, recurring guest at this point. Uh, he's— he did his undergraduate at, uh, Dartmouth, he did his PhD at Oxford, and he is finishing his medical degree at Harvard. He's written, I think, over 20 papers now on a ketogenic diet. And I'm also joined today by my partner in crime, Dr. Laura Buchanan. You guys, if you don't know her, well, here she is again. She's a family medicine doctor, obesity medicine doctor, and she's on the board of the SMHP. Guys, thank you for joining us. We're going to be talking about a paper that Nick co-authored with Michelle Hearn, who is a dietitian who focuses on a ketogenic diet and eating disorders. And their, uh, the paper, uh, which was a case series on 3 patients in anorexia, was published in the Journal of Insulin Resistance in June, and it's 2023. So guys, very happy to have you here. This is exciting. This is exciting work.

Thank you. Great to be here and super excited about this case series that was published and the great work you're doing, Nick.

So, Nick—

Thanks. Thank you both for having me.

Yeah, let's get started, Nick. So, help me understand, you know, how did this project and how did this paper come about? You know, we hear a lot about ketogenic diets for weight loss, for diabetes. So how did it come out? You know, what sparked your interest in writing this paper on anorexia?

Yeah, I guess to kind of step back and take the 50,000-foot view, maybe even 500,000-foot view, a ketogenic diet is a therapeutic intervention that's being used for at least 100 years, originally in epilepsy. But as you know, it's being broadened in its clinical use for a lot of different conditions, including mental health and neurological disorders, and of course, obesity, diabetes, et cetera, et cetera. But more recently, I've seen it be used with great success in a variety of mental health disorders. So you, as you know, and as probably a lot of your audience knows, there was a fantastic 31-patient trial for like schizophrenia, major depression, and bipolar. And I— we've seen it used for other eating disorders as well. So there's definitely an advancement in terms of its, uh, clinical interest in ketogenic diets. And I think what we need to do now is really run larger-scale trials to make this potentially standard of care. That said, admittedly, I don't have the time or resources to be doing that myself right now, so Practically speaking, what I want to do is whatever I can to contribute. And one thing that I thought would be interesting is to highlight what might be the most counterintuitive and provocative use case for a ketogenic diet, which is a ketogenic diet for anorexia. It's something I'd heard of, something I'd seen, but not something I'd ever actually seen highlighted in the literature. That said, there are two prior reports, but both were multimodal interventions where ketogenic diet was used for anorexia, but combined with ketamine therapy. So we had the opportunity when I became aware of these and some other cases of people with not just anorexia, but severe treatment-resistant, um, terminal anorexia. These patients had, um, BMIs as low as 10.7 and, um, disease courses as long as 30 years. Complicated by things like blindness from fat atrophy around the optic nerve, liver damage by starvation, immobility, osteoporosis. These were severe, severe cases. And, uh, common knowledge around anorexia clearly is, you know, eat more calories, don't restrict. This is a restrictive eating disorder, so you don't want to put or push restrictive dieting on these patients. And also, ketogenic diets are known for weight loss, so there's this interesting juxtaposition where you have a diet that is used for weight loss, but really at its core is a potent neuromodulatory intervention, with the common knowledge that anorexia is a disease of dietary restrictions. So patients shouldn't restrict. All foods fit. They should just refeed and focus on non-restrictive dieting. And so, you know, what happens when you actually put this to the test in the clinical setting, or at least in the case series? Well, That's what we wanted to highlight here, to kind of, in a respectful, responsible, but productively provocative manner, stir the pot a little bit and get discussion going around the potential for ketogenic diets in this particular condition.

So one of the biggest criticisms I've seen about, uh, in the eating disorder space, particularly around anorexia, bulimia, and binge eating, is that, uh, you don't want a restrictive diet. When I looked into the literature about this roughly 2 years ago, I looked into the interventions that have been shown to prevent eating disorders in college-age women. One of those is Healthy Weight Program. There's a number of sort of eating disorder prevention programs where they took in at-risk adolescent women or college-age women and they talked to them about weight stigma, weight bias, and educated them on nutrition. And what struck me as odd was that these programs had restrictive diets built in. They were educated on healthy snacks, right? They were educated on healthy, sort of full, you know, real food eating, right? And we know that, uh, depression and anxiety responds to quote-unquote real food, healthy eating. These have been shown in interventional trials. So, uh, it struck me as odd that these anorexia prevention programs actually had a form of restrictive dieting because specifically, you know, highlighting the healthful value of, you know, healthy snacks and real snacks versus modern sort of junk food. And it struck me as odd because it's the most efficacious programs in the literature for anorexia prevention. And yet they specifically restrict junk. And it's not counterintuitive, it makes sense, it fits with all the literature. And, and yet, uh, there's been strong criticism against this case report because it's restrictive in that it restricts carbohydrates. So help me understand, do you think that this, this idea of, uh, not promoting restrictive diets makes sense in the anorexia literature.

It's actually interesting to hear you say— So just let me clarify. The intervention you were talking about focusing on healthy eating was, in effect, some form of restriction, but from a generalist standpoint, maybe not as restrictive as the ketogenic diet, but still some form of restriction, correct?

Yeah. I mean, it's not saying, "Hey, go have Oreos," right? The Healthy Weight Program was not, "Go have Oreos and go have Doritos and just have it in moderation." Certainly wasn't that. And then we've had— oh geez, why am I blanking on her name? Professor Felicia— oh geez— from Australia. She did the interventional study on depression, which is often a comorbidity of anorexia, that showed sort of real food eating decreased depression scores, which is— and real food eating is a form of restriction. We're restricting modern processed food. So, you know, it always struck me as odd that the anorexia community would be so against sort of this concept of restricting things. Maybe there are certain foods that should be restricted.

Yeah, well, actually, that's interesting because I guess what we're setting up is not just a duality, but a spectrum of possible interventions, because a lot of what our patients were exposed to, and I think a lot of patients are, a completely non-restrictive form. So we had our patient dietitians telling our patients like, be able to eat normal foods, quote, normal foods being pizza and ice cream. So effectively junk food. It sounds like there are other people focusing on a, quote, balanced diet, but healthful foods. And I think, you know, the spirit behind that might be, I can only imagine, you know, you wanna really renourish the body and renourish the mind in order to set people up for long-term success, which I really applaud. That's the philosophy that I would take. And I think potentially a ketogenic diet could just take that one step further. And we can talk about mechanistically why that might be in a little bit. But I think one of the reasons, well, there are many reasons I think this might be a very, a subject that requires a lot of nuance. And one thing I definitely wanna highlight because I think it's a criticism that we need to get ahead of, well, a couple things. One, nobody here is advocating for prescribing an animal-based ketogenic diet at this time and pushing it on a patient. These were all patients who self-adopted it as an option they wanted to experiment with. Additionally, if somebody's in an acute critical care state, like they are dying of anorexia in an inpatient setting, clearly refeeding at all costs should be the priority. But we really want— and what is missing in the, um, uh, in terms of like medical care and good patient outcomes is an intervention that facilitates long-term remission. You can force-feed somebody to get them to gain weight and prevent them from dying, but in the end, what you want is something that the patient can sustain for themselves over the course of years. And anorexia, not only does it have an incredibly high mortality rate, but its relapse rate is off the charts. So if there were a standard of care intervention right now that was doing a great job, there wouldn't be a need for something new, something else. As a matter of fact, there isn't something that is really doing a fantastic job at a population level. So we need to kind of think outside the box. And, you know, what we have here is something that is a little bit outside the box. It's not proven, but I think what we have here is our cases that are interesting enough to go, hmm, maybe there's something to this.

Can you describe— oops, sorry, sorry, one more thing here before you edge in, Dr. Laura. Can you describe for the viewer an idea of where these patients were before they had adopted the ketogenic diet and where they are now and sort of their clinical course? The picture, guys, if you're a listener right now and you haven't seen sort of the videos and the pictures, please go to the Journal of Insulin Resistance, uh, and read this article, and we'll include it in the show notes. But, but for the listener, uh, Nick, can you just describe a little bit about— because I think that's so powerful to hear where they were and where they are now and how long they've been in remission.

Yeah, um, like I said, these, these were pretty severe cases. Um, all these patients had anorexia for years. The third patient had anorexia 30 years. Their BMIs were 10.7, 11.8, and 13 at the lowest. 2 males, 1 female— I mean, 2 females, 1 male. And aside from just the numbers, which are striking— if you don't know what a BMI of 10 looks like, it's, it's on death's door, basically. Um, these patients— that patient didn't have enough muscle mass to basically move around. They were losing so much fat that you can actually get blindness because your optic nerve starts to atrophy. You can get bowel obstructions from something called like Superior Mesenteric Artery Syndrome, where like the fat is so depleted in your abdominal area, the vessels just like collapse on top of each other. You can get— they had starvation-induced hepatitis, the bones started to degenerate, patients were refined, like, um, resigned to wheelchairs. Um, it was, um, really striking. And that on top of just other mental health comorbidities, obsessive-compulsive disorder, all the struggled with some form of anxiety. Some heard voices, suicidality, self-mutilation. Um, these were, uh, alarming, um, cases. And, uh, all of them had tried some form or another of standard intervention, um, basically, you know, multiple times, multiple inpatient hospitalizations. Um, they all wanted to get better and they all kept on trying, but no intervention allowed them to sustain remission. Um, the second case, the male case, I thought was— we had a paragraph that was pretty telling, and I just want to kind of highlight it because I think it speaks to the mental health aspect of that, which, you know, is even more important than the weight. One thing, you know, he got to a point where he was, um, just doing everything he possibly could to try to gain weight at points in time. Um, he really wanted to get better, and so he'd go on these binge-restrict cycles, which actually is a pretty common phenomenon. For patients in recovery where, you know, they get moments of awareness of how severe their condition is. They then want to refeed. And based on the guidance he was getting, he would go eat like pints of ice cream, 10 pancakes. He'd eat tons and tons of calories and sugar in an attempt to get better. But what would inevitably happen is he'd panic, feel like he was gaining weight, and then relapse into restriction. And this really, you know, impacts quality of life, not just because you're not physically capable. But he would eat, um, like by himself on a second floor just so he could run up and down the stairs during mealtime because he couldn't sit still. Or he would intentionally forget utensils downstairs so when he went upstairs he would have excuses to run up and down stairs. Like, it completely wrecked all these patients' lives. One of the patients had kids. She couldn't do anything with her son. She was resigned to a wheelchair while he would be like playing next to her with his fire truck. And at 4, he'd just look up at her That was his normal, his mom in a wheelchair with tubes in her nose. So he'd kind of stick his fire hose from his toy truck in his nose to mimic her. Um, these patients did not have good quality of life, and the universal motif for all their stories is, um, not through proper medical guidance but just out of desperation and exploration based on internet resources, they came across the idea of a ketogenic diet. And like I said, all these patients were trying to get better. They were trying a lot of different things. So they gave this a go. And for all of them, the first thing that happened was a sense of profound mental clarity and a decrease in anxiety around food. And I really want to emphasize that because this isn't just, "Oh, they ate meat, gained weight, and got better." This was, they were trying lots of things that didn't really work. Then they tried this approach and their mind state changed. One patient talked about looking in the mirror for the first time in years, in decades, and seeing herself truly for the first time, having that clarity, refeeding and feeling for the first time no anxiety around food. The compulsion to count calories kind of went away. And not only did these patients gain weight, but they felt okay about it and have been able to sustain it. That is pretty remarkable, especially when juxtaposed to what they've been told about their disease, which was, look, you can manage it, but those voices in your head telling you not to eat this, not to eat that, that are nagging you, they're going to be there your whole, your whole life, and you're just going to have to cope with them. That's what they were told. And they're each now at a point where they're reporting no anxiety around food and that those voices are basically gone. So, you know, based on not only BMI criteria but also mental health criteria, and we did some screenings, These people are, you could say, in remission. You could also, I think, effectively say cured.

Yeah, that, that is just incredible. I mean, those types of results and the improvement in those people's lives, there's no medication or anything could do that. And what's so kind of surprising to me, or just, I don't know how you either rationalize it or what your thoughts are, is when people on social media see those results and say that you're going to harm people in the future. Or when you see how far these individuals have come and you just start seeing people on Twitter basically attacking this, what are your thoughts?

Yeah. Well, I mean, a few things. First, I'll highlight that while each of us actually highlighted some of the contrarians. I was surprised by how little negative pushback there was. I'd say 99% of it has been incredibly positive. But we knew that there would be people that have a strong reaction to this because combining ketogenic diets, particularly animal-based ketogenic diets and anorexia, those concepts, is playing with fire, which was the point, in effect, of a case series. It's not going to change standard of care, but it can stir the pot, start discussions. So This is something that I anticipated, and actually I anticipated would be a lot, um, stronger in the pushback. The pushback's been very meek so far, so that's actually interesting. That said, the results speak for themselves. We're not prescribing anything or recommending anything. I don't have the qualifications to do that yet. I'm not an MD, I'm a PhD and a medical student. All I can do though is show up and describe what happened for these patients, and if you, you know, don't have issue with, you know, what was shared, you don't think there were any major omissions, which, I mean, we gave complex social histories, we did screenings, we gave the data, and I will provide more data if people ask for it and I have access to it, and you believe that we're actually accurately reporting, then that's all we're doing. We're not really making recommendations, we're starting a discussion. Um, I haven't— maybe you have— I haven't seen accusations that we might be doing harm because I don't think we are making recommendations, but there certainly have been responses that were or are just emotional reactions based on the common knowledge logic that we already laid out. Oh, this is a restrictive diet, so you shouldn't give it for a restrictive, uh, eating disorder. That said, um, I haven't seen anything with any substance. Every single reply has revealed in the quality of response that they never actually read the manuscript. So If you want to come out with the response, as one person did, "No, no, no!" And that is how you started, exclamation point, something, something, something, blah, blah, blah.

That was a senior reporter. That was a senior reporter from the BBC who said, "No, no, no!" by the way.

Yeah, well, we've had some back and forth. Her last comment, I think, was something very brief as like, "Restricting carbs is doing harm." to which I just replied with pictures from the patients because it's like, do you really think this is doing harm? This person who's had a 30-year history of anorexia, was on death's door, now is happy and healthy. Like, you know, just because she gained the weight with steak and not pasta, is that doing harm? And quite honestly, we were talking with Ken Berry yesterday and talking about, you know, the, the argument which I think is the root of You know, the no, no, no response is that by providing a ketogenic diet, you're trading one eating disorder for another. One, I think that's kind of a flawed analogy because if you're using an intervention as a medical intervention, it's not an eating disorder. If a kid adopts a ketogenic diet for epilepsy, do they have an eating disorder because they have a fear of carbs? No, they're adopting a medical intervention. But playing devil's advocate, let's say a ketogenic diet by virtue of being, quote, fearful of carbs is an eating disorder. If you have a choice— remember, this is a treatment-resistant patient, we have 3 of them for years with anorexia— if you have a choice between having an emaciated body, osteoporosis, fatigue, anxiety, OCD, and that's eating disorder A, and eating disorder B is, you know, I'm scared, quote, of carbs, but I have a healthy body, happy mind, which eating disorder are you going to choose? Because I'll choose B, even if you want to label it an eating disorder, whatever. The titles don't really matter to me. So of course we're going to get emotional pushback, and the emotional pushback I think just makes the, uh, topic more enticing and encourages people to engage. So I really applaud and thank the emotional reactions and the trolls because they're really just helping amp up the engagement, which was always, you know, an aim of this, to start discussion via engagement. So please keep coming with the shallow attacks. I really, um, encourage it.

I want to, I want to highlight some things. You know, our work with Shabani Sethi and Eric Westman and Laura Saslow, you know, back in 2019, we showed that low-carb diets can help with binge eating and food addiction symptoms. And what you described sort of as anorexia in remission, having these restriction and binging cycles. You know, we know in that setting that there's some data that low-carb diets can, can help, some early data. But this, this data is actually even more sort of provocative but nonetheless predicted. Agnes Aiton and her partner in crime in the UK, Ali Ibrahim, have talked about this. In fact, Agnes Aiton wrote a brilliant paper several years ago, about 5 years ago, called "The Blind Spot in Western Medicine," and she highlighted sort of this unifying pathway to, to disordered eating where our modern diet sort of can worsen mental health issues. And if there are sort of weight issues or weight gain that occurs, it may lead to that binge sort of binge-restrict cycle you talked about, presents as binge eating, food addiction, bulimia. And those patients may be normal weight, may be underweight, may be wildly overweight or obese. And then there's like the second type that sort of battles against this, the modern food, with restriction. And the harm there is that there's certainly some stability that happens with a ketogenic diet or fasting, right? So as the body makes ketones, right? I suspect those patients are experiencing some sort of stability that they, that they want and they don't want to lose, right? And then the harm comes when they become so malnourished, the stress hormones increase, some of the health complications arise, um, and they end up eating again. And as you said, the modern field promotes inclusive eating of junk. And that just leads them to feel horrible and they lose that ketosis. And so it's interesting to me, this concept to use ketosis as sort of a mood-stabilizing agent to basically give them, likely, you know, what caused them to restrict in the first place, which is ketones, stable glycemia, and a sense of control. So I think it's an interesting idea and I think it certainly needs warrant. And the other part that I find that the naysayers haven't really brought up is, you know, these groups that are in severe anorexia, they're often very calorie- and fat-phobic, right? So now, literally, I wouldn't view it as a carbohydrate restriction. I would view it as fat inclusionism, right? And fat promotion, a ketogenic diet. It's not necessarily carb restriction, you know, for this group as much as it is, you know, a fat inclusionism. In fact, these people are often very low-calorie, very low-fat. In diets in general. And I think we know the mental health implications of having a low-fat diet. So, you know, I view it as interesting, and I think it's been predicted that this would be beneficial. And in my own practice, I can count probably 3 to 5 patients who were formerly anorexic and now multi-year stable on a low-carbohydrate diet. So you can add another couple there, you know, to your case series from our group.

Yeah, I think there are probably a lot of people. I mean, in the past 24 hours alone, since we had a YouTube with Ken, I've gotten about 8 replies, DMs, or emails about people saying that they had anorexia and have used a low-carbohydrate diet of some form to improve it, including from people inside Harvard. I won't name names, but Um, I think there are probably a lot of people suffering and improving using this methodology, more so than we appreciate. But, you know, getting people to talk about it opens up resources for people. It's not prescribing it, but when people are super desperate and they're looking for options, things to try, having examples to— I'm not even going to say follow, but even reached out to you for guidance is super cool. I think all of our patients requested— I'm very careful about patient confidentiality— but they're requesting to divulge their identity. So they're going to do this. One already has of their own volition. I have no control over whether or not they want to choose to do that. But in so doing, they become kind of— I think they want to be resources, what is what I'm saying. The reason I mentioned this is because if there is anybody listening who is struggling, you know, the great thing about this day and age, while social media has its ups and downs, is it does democratize information, make people accessible. So, um, yeah. And just to circle back to something you said earlier, because I don't want to, uh, miss it, you mentioned, um, correct me if I'm wrong, a hypothesis whereby one of the etiologies of anorexia might be some sort of self-medication and the euphoria gained through ketosis and fasting. Is that correct?

Yeah. Yeah.

Yeah.

But, but it led to an extreme that, you know, which then leads to stress hormones and high cortisol and nutrient depletion, which then causes inflammation and sort of a need to, or push to eat.

Yeah.

It's, and then the recommendation is the modern food, you know, modern food environment, which is toxic.

Yeah. It's an interesting hypothesis. I think I, and I mentioned this earlier today on Twitter, like the, The brain is such a black box, and right now, because it is, and we have such limited tools to really examine what's going on neurometabolically in these conditions, we kind of just brush it off and internalize it as a disorder of the mind in society. But in effect, the brain's an organ. Something's going on metabolically. We just don't know what it is. But psychologically, building on your point, I think something to emphasize that's really important is that sense of control. That, you know, for our patients, and I think a lot of patients, food restriction becomes something in their life they can control when they often can't control a lot else. So while I definitely think that there is a component of ketones fixing something, um, neurologically in the brain, there also might be a psychological component of shifting the spotlight of focus from focusing on calorie restriction to focusing on restriction, let's say, in the form of an animal-based ketogenic diet. So you know, practicing that restriction in and of itself might have some therapeutic modality. And I don't think that's actually anything to scoff at. Now, I don't think that's the whole picture, otherwise other restrictive diets would work. Some of these patients tried veganism. If it was just restriction, that should work too. But, um, restriction has become a dirty word, and I think that's a little bit of an oversimplification because I think there actually might be something therapeutic to the restriction, provided it's focused in an adaptive manner, if that makes any sense.

Yeah, no, well, the harm of food restriction and anorexia, as I said, is nutrient depletion, uh, sort of sarcopenia, osteopenia. Basically the body's saying, I'm not getting enough, and the stress hormones and inflammation associated with that, uh, you know, they can develop arrhythmias from, from mineral depletion, etc. But, you know, if The, the, I suspect the impetus to, to restrict comes from the benefit of ketosis as an initiator, right? I suspect that that would be my hypothesis, and that hypothesis was echoed by Agnes Hayden in her paper, The Blind Spot of Western Medicine. The Western diet, sorry. And I know, you know, Ali Ibrahim has similar feelings. Not to say that they support ketogenic diets for anorexia. I'm not talking for them. I'm not saying that. But I suggest everybody read that paper. It's a great paper. Now, personally speaking, having been somebody who, you know, I had anorexia as a, you know, 13-year-old. I basically did not eat for several weeks, upwards of 6 weeks. And certainly I've sort of seen both ends of the spectrum. I can tell you from a personal anecdote that there is a mood-stabilizing effect of ketogenic diet. And you see this play out in the seizure literature. You see it play out in some of the bipolar depression literature, as you mentioned. And I think that that unifies sort of how it both can help in obesity and anorexia, that the unifying mechanism is our mind. So what say you?

I say it kind of contradicts with satiety per calorie, doesn't it? Sorry, I had to. No, I think, I think that it makes the point that ketogenic diet is not a weight loss diet. It's a diet that, you know, it has a lot of effects depending on what your use case is. But, you know, with respect to food intake, I think it normalizes hunger signals. It lets you hear your body's hunger signals, which are going to be elevated if you're malnourished and depressed if you have excess adiposity, and allows you to therefore maintain or achieve a healthy weight because, you know, your body is trying to achieve a weight homeostasis or will try to achieve, provided you're not screwing up the signals. And standard American diets do screw up the signals. And if, you know, you're restricted on a standard American diet or if you're overweight on a standard American diet, nevertheless, you know, it's about being able to hear your, your body's hunger cues. And that will just drive you to whatever your, quote, healthy weight is. That will be my hypothesis.

Dr. Laura, what say you?

I think I don't know if I have anything to add additional to that. I like that hypothesis.

You know, I'm going to, I'm going to throw another one at you, Nick. I think, you know, one of the things I thought about this, about this paper is, well, let's, let's talk about it. How can a ketogenic diet be both a weight gain diet and a, and a weight loss diet? Right. So this is, You know, we've heard for the last probably 15 years more and more that a ketogenic diet can be used in both diabetes remission and for help with weight loss. And over the last 5 years, this area, this field of ketogenic diet for mental health has really blossomed. And here we have an example of a ketogenic diet for anorexia treatment, or I shouldn't say treatment, sorry, case reports of a ketogenic diet being used to support weight gain in anorexia. So, you know, what do you say to people who are confused? You know, certainly the, you know, the energy balance model proponents will say, well, how can a ketogenic diet be both weight gain and weight loss? So, you know, how do you break that down?

I mean, there's a lot of ways to break it down. I'm gonna adapt my answer based on the audience, which you've set up as the energy balance model crowd. So I'm gonna put this in energy balance model terms. And I guess the obvious analogy for me would be exercise, which can be both a weight loss and a weight gain intervention in a sense, right? If you go eat very little and you run a marathon every day, you're gonna lose weight. 'Cause your energy balance is negative, right? Versus if you're just lifting a bunch, you know, and you're, you're putting your body in an anabolic state and you're eating to compensate, then you're gonna gain weight. It's the same way with the ketogenic diet. If you're overweight and you're eating in a way that, you know, reduces hunger signals, stabilizes insulin, and your energy intake is lower than your energy output in the end because thermodynamics holds, then you're gonna lose weight versus if you are malnourished, and you're eating in a way that fixes your neural metabolism and allows you to eat without major anxiety, you're going to be hungry and you're going to eat more than your needs, which our patients did. Our patients were eating— one portion patients self-reported, and we didn't actually include this, a reviewer told us to take the sentence out because they couldn't believe it, but the patient was saying they were eating 8,000, 9,000 calories a day and just tons and tons and tons of fat. So the people that are losing weight on a ketogenic diet, they're not eating that form of ketogenic diet. There are different forms of ketogenic diet and the body's going to be driven to consume that which serves it best when it's allowed to respond to, you know, signals. So again, it comes back to the misunderstanding arises based on the presupposition, the incorrect presupposition that a ketogenic diet is simply a weight loss diet, which it is not.

Do you think there's a role for, you know, help me understand because I don't recall I don't know if this was mentioned, maybe it was and I'm just not remembering. Do you think there's a role for ketone supplementation in a use case of, say, migraine, seizures, and potentially anorexia or binge eating?

Yeah, that's a tricky one. I actually brought this up yesterday when I was kind of going through a thought puzzle of if one had a randomized control trial for anorexia and you had a standard American diet, a whole food diet that's higher in carbs, a plant-based ketogenic diet, an animal-based ketogenic diet, or a standard diet with ketone supplementation? What would generate the best results? My impression is that ketosis is probably, I don't even want to say necessary but not sufficient, but kind of along those lines. I think it's a major contributing factor, but I don't think it's the be-all end-all. And, you know, I think it would be undermining the intervention to try to do exogenous ketosis on top of an otherwise unhealthy diet. So I don't think ketones alone will be sufficient. I could be wrong, but all we can really do is speculate. So could it have a role?

Maybe.

Would it alone be optimal? Probably not. Again, that's just my gut feeling. Obviously, there's no data to point to.

Speaking of gut feeling, you know, do you think it's the ketones, the micronutrients, or the microbiome? If I had to press you on one of those.

I think it's the micronutrients and the ketones for sure have some effect. I don't— the microbiome may be long-term, but I don't think over the short term. And the reason being, these patients were reporting pretty immediate effects of eating this way, faster than the microbiome could adapt. Plus, the dysbiosis that occurs, you know, at least is associated with restrictive eating, I think is pretty persistent, which might actually be one of the reasons why animal-based ketogenic diet might, and this is just me speculating, have benefit over a plant-based ketogenic diet, simply because these are patients with or presumably who have, or who are more likely to have some form of dysbiosis whereby fermentable fibers might actually cause some GI distress. And at least one patient reported that where she's like, I'm not afraid of vegetables, but I tend not to eat them because they just cause like IBS. So because restricting can lead to dysbiosis and IBS, I, I would think that sometimes maybe plants could be irritating. Not bad for them, but irritating. So I don't know. I don't even know if that's answering your question. I might have just wanted to let you know.

Yeah.

Well, have you— are you familiar with— I'm sure you're familiar with this— some of the data showing that the seizure prevention could very well be from the microbiome. Do you think when it comes to a ketogenic diet, do you think that that's I mean, well, that's an accurate representation of the data. And do you think that that's how potentially the effects on the central nervous system are in general? You know, is that the mechanism? Is it through the microbiome?

I don't think so. I mean, there are two papers, at least, no, I think one is in Nature. First author's name begins with an S, I think. And yeah, they were mouse studies. And they did the whole like, you know, treat and then do the fecal matter transplant to germ-free mice kind of thing. And they're cool studies. These are studies that I often like, the type I will cite a lot. I think they're pretty cool. But in a human context, speaking broadly, I don't think it can be the whole picture. Ketones have such potent direct neuromodulatory effects. I can only imagine that it has a large part to do with the direct effects of ketones on the brain. I'd need to go back and look over those papers for the exact methodology, but again, it's 2 papers out of a sea of thousands and just animal models when we do actually have, you know, human data, including like brain scan level data suggesting that, you know, ketones themselves have powerful functions on on brain metabolism. So I think there is a direct effect of ketones. I'm not ruling out the possibility of a microbiome contribution, but in this particular context, the response was so immediate that I don't think the microbiome could be the complete answer. But, you know, the only way to really answer this will be like longer-term, larger trials with longitudinal multiomics. And I alluded to that earlier today on Twitter where it's like, I, I think Right now the brain's a black, black box, but we're moving to a point where we have more sophisticated technology to not only look at the brain, but, um, this concept of longitudinal multiomics, which is longitudinal over time multiomics, lots of omics, microbiome, transcriptome, proteome, and looking using like machine learning, AI, how all these things are interconnected and contribute to disease to really understand the metabolic fingerprints of all these sorts of conditions, be it sugar addiction, anorexia, um, Schizophrenia, obesity, diabetes, whatever, they're all going to have unique metabolic signatures. And by understanding these, we can start to address the root causes of disease. So this is, this is the new frontier. This is why I find this so exciting.

I'm curious, did any of the patients use biofeedback? I don't, I don't— did I use— did I see that in the literature? Uh, did I see that in your case report? I forgot. You know, did they— were any of them using biofeedback?

No, um, there wasn't any, um, additional intervention of the— that for all those patients, all they changed at that particular point in time was a ketogenic diet. Now these patients, one patient had a 30-year history when she— we had a 2-hour interview to kind of go over the details, ask further questions. I'm sure she didn't tell me everything that happened over the last 30 years, so maybe she tried it once, once upon a time, but it wasn't It wasn't reported. I am not aware of it.

No.

No, no. Have they used biofeedback in their latest sort of, you know, do they use ketone measurements, ketone urine strips, CGMs?

The second patient was measuring ketones. I don't think he was per se reflecting on mental health status and ketone level correlation. And he was primarily using urine strips. None of these patients had like Keto-Mojos on hand. So even the term ketogenic diet is a little bit artificial because other than one patient, we don't have proof of that. But we've seen their dietary journals. They're eating next to zero carbs. So one can presume.

Yeah, presume. Yeah. I wonder how much the biofeedback would empower patients that vulnerable, you know, sort of involve them in their treatment course.

Yeah, I don't know. I mean, we have now continuous— I'm looking for mine. Ketone meters that are coming to market.

Have you actually used one yet?

I haven't put it on just because things have been so crazy and then I was not super well, but I'm going to put it on at the end of this week. CGM, CKM system, SiBio. So we got to see how it is.

We got to bring you on back to take a look at it.

Yeah.

Any final words, Dr. Laura? And then Dr. Nick.

Yeah, I just— so I think going back to something Nick said earlier about restriction and that being a negative term, and I think sometimes it's either just taken out of context or going back to your example of eating disorder A versus eating disorder B, you know, I would choose eating disorder B as well. It like makes perfect sense. To think of another kind of analogy or just something we see in medicine, when I've admitted patients to the hospital for diabetes, when they're coming in for a foot amputation, I would try to put them on a low-carb or ketogenic diet, and I was told, 'Oh no, that's too restrictive,' and I wasn't allowed to do that as a resident. But that patient is coming in and they're going to lose their leg. Like, what is more restrictive, them losing their leg or going on a low-carb ketogenic diet? And I think just thinking about things like that, or someone who is suffering from bipolar or schizophrenia or anorexia, and they're having these types of change in their lives, like, what is truly more or less restrictive?

Amen. Yeah, I agree. That's a— I'm guessing there's no answer to that question. It's a rhetorical question.

Yeah.

Well, the answer is clear. I'll take restricting carbs and keeping leg for 500, Alex.

Yeah.

Yeah. Do you want to give us some parting words? Nick Norwitz.

Yeah, I, I think my parting words will be an appeal to humility in my position. And just to kind of clarify, because now I'm speaking more to the contrarians, for lack of a better term. I realize what I am right now, which is an early career researcher and a medical student. I'm not a psychiatrist. I am not even a physician, and I'm not here trying to recommend something. I'm here to report, describe, and, um, you know, ask questions. So, um, you know, with this report, it's something that, you know, I did, you know, not just to— just to stir the pot, or not to try to influence people to do it off the bat. It's something that, you know, I'm looking forward to a career in medicine and what the healthcare system is right now and what it could be, what the flaws are within it. And I have certain perspectives and opinions. I thought this was a way to kind of promote discussion around that, try to push it in a positive direction. And it was a really fun process for me to do in the context of being someone who, yeah, I'm entrenched in academia and I'm entrenched in low-carb Twitter and I'm entrenched in Harvard Medical School. And I did this while I was on a Harvard Medical School psychiatry rotation. The senior author is, was my attending on the floor. And so to get feedback from him and other psychiatrists, other dietitians as part of my learning experience was I think very fruitful. And I hope that I look back on this in, in time and, and think of it as a worthwhile project. But I just wanna emphasize this isn't, a project of grandiosity, anybody trying to, to change standard of care right now. But I think it's worth asking hard questions, um, particularly in the context where you have an incredibly high mortality condition and patients aren't being served very well. So that's my last two cents.

I 100% agree. This is early data. You know, if you're— if you have somebody in your family who has anorexia, or if you're suffering from anorexia, Talk to your clinical team, you know, include them. This is not meant to be medical advice. I echo Nick and Laura's sentiment. We should challenge the sort of the orthodoxy and the dogma, but we eventually need to present very compelling data. You know, ultimately, I say this to my patients, you know, your own personal data is the best clinical trial that you have. But you need a great clinical team to be able to track and monitor and make things are done sort of in the safest way possible. So I express the same caution that Nick here is expressing.

Yeah.

Guys, thank you so much. Thank you for coming, Dr. Laura. Thank you, Nick, as always.

Yeah, thanks, Brad.

Special shout out to Michelle who couldn't make it here today, but we'll certainly have her on very soon. Yeah, thanks, guys.

Awesome. Thanks.