#224 – How the keto diet may ease depression in bipolar disorder and other mental health conditions | Iain Campbell, Bret Scher & Dominic D’Agostino

The ketogenic diet may help reduce depression and other symptoms in bipolar disorder. The ketogenic diet also helps metabolic health and reduces the risk for cardiometabolic diseases. The risk for cardiometabolic diseases is elevated in people with bipolar disorder when compared to the general population. Dr. Iain Campbell, Dr. Bret Scher, and Dr. Dominic D’Agostino discuss how the state of ketosis has beneficial effects on brain neurotransmitters and how those benefits have been life-changing physically and mentally for Dr. Campbell, who has bipolar disorder.

Helpful Links:

Metabolic Mind: https://www.metabolicmind.org

Bipolar Keto Study: https://www.bipolarketostudy.com

BipolarCast on YouTube: https://www.youtube.com/channel/UCDB-iMvEJ-HeHqpamIN5JWw/videos

Diet Doctor podcast: https://lowcarbcardiologist.com/boundless-health-podcast/

Iain Campbell, MD, PhD, on Twitter: https://twitter.com/IainCampbellPhD

Bret Scher, MD: https://lowcarbcardiologist.com

Bret Scher, MD, on Twitter: https://twitter.com/bschermd/

Bret Scher, MD, on Instagram: https://www.instagram.com/drbretscher/

Dominic D’Agostino, PhD: https://www.dominicdagostino.org

Dominic D’Agostino, PhD, on Twitter: https://twitter.com/DominicDAgosti2

Dominic D’Agostino, PhD on Instagram: https://www.instagram.com/dominic.dagostino.kt/

5:40 — Dr. Iain Campbell explains how a ketogenic diet improved his mental health

For Dr. Campbell, the ketogenic diet has provided dramatic relief for symptoms of bipolar 2.

I’m the Baszuki Brain Research Fellow in Metabolic Psychiatry at Edinburgh University. I have a PhD in Global Health from the University of Edinburgh. I also am diagnosed with bipolar (type 2), and I’ve been using ketogenic metabolic therapy for seven years now. And this was something that is a real pleasure to be on this podcast because I originally found out about ketogenic metabolic therapy through listening to podcasts like you were doing, Dom, and promoting this as a therapy for cancer and for neurological disorders like epilepsy and other conditions. And I had no idea at the time it would have an effect on my mental health, but it was more effective than any treatment I’d ever tried in my life in ameliorating the symptoms of bipolar. It was such a dramatic turnaround for me after having tried many things that haven’t worked. I felt I need to spend as much time as I can the rest of my life trying to tell other people about this and try to explore it and understand how many people this could help.

9:02 — Dr. Campbell explains his pilot trial on the ketogenic diet and bipolar disorder

Dr. Campbell’s pilot trial investigated whether 8 to 10 weeks of the ketogenic diet produced mental health changes in 27 participants with bipolar disorder.

And what we saw was quite interesting, because there’s a significantly increased cardiovascular risk with bipolar disorder. In fact, in the UK, over 70% of people die of physical preventable illness with serious mental illness, and there’s two to three times the risk of Type 2 diabetes and there’s a very strong energy component to bipolar disorder. That’s kind of underrecognized in the research, and ketosis speaks to all of these mechanisms, but it’s also a therapy used for epilepsy, and anticonvulsants are used to treat bipolar disorders. So we share medications with epilepsy. And now this other effective therapy for epilepsy is coming into focus for bipolar. So there’s a lot of scientific background as to why we want to conduct this study… People are reporting remission of symptoms, substantial benefits. So we want to try and understand under a bit more of a microscope of what’s really happening, and we’ll be publishing a paper in the next couple of months. But we found substantial changes in their metabolic profile, alongside their psychiatric symptoms, alongside their brain imaging.

16:20 — The ketogenic diet is often misunderstood

Dr. Bret Scher explores some myths about the ketogenic diet regarding cholesterol and heart health.

I think people need to realize that we’re talking about ketogenic therapies, and we can’t extrapolate generic, so-called low-carb data to that. So that’s the first point. And then the second point is just educating people that for the majority of the people, LDL doesn’t go up… We have to get over the preconceived notions that by definition this is a harmful diet for your heart where LDL is going to go up—because that’s not the case for the vast majority of the people. And even if LDL goes up a little bit, overall calculated cardiac risk goes down because of all the metabolic improvements. So there’s definitely a lot of education that needs to go on, especially in groups that maybe aren’t as familiar with ketogenic therapies.

18:10 — Elevated lactate is a biomarker in bipolar disorder

Although lactate can’t be used to diagnose bipolar disorder, elevation of this biomarker is associated with the mental health condition.

The biomarker is very difficult to isolate in bipolar disorder because you’re trying to measure the activity in the brain, and of course you’re getting a signal from the serum, but we’re never sure how reliable it is. But the systematic reviews have consistently, for around 70 years now, highlighted elevated lactate as being a significant biomarker as the most significantly altered biomarker in bipolar disorder in the serum. And this is also reflected in brain magnetic resonance spectroscopy. And so lactate is considered a biomarker in bipolar disorder. You can’t use it to diagnose anything, but there’s definitely elevated lactate. And this has been related to the literature on mitochondrial dysfunction—the hypothesis being that this is glycolysis running on overdrive. And I think this fits with metabolic dysfunction in general—that there’s mitochondrial dysfunction, increased glycolysis. I think it also ties in with what you’re saying about insulin resistance in the brain. And we’ve always known that insulin resistance causes havoc with the whole rest of the body.

24: 37 — Circadian rhythm disruption affects bipolar disorder

Dr. Campbell explains how sleep-wake cycles can impact bipolar disorder symptoms.

During mania they have unlimited energy and they work all day and night. And you can actually take someone who’s depressed and you can even do things, like keep them up till two or three in the morning, and this will help them to feel better. And then if you take someone and do the opposite and you have someone who’s manic and disrupt their sleep, they can become worse. So there’s a really strong circadian aspect. And obviously when you wear a CGM, this becomes really apparent to you with the dawn effect. And I did this for a year myself, wearing a CGM, and this cortisol rise that you described in the morning is significant. I think it’s also correlated. We were seeing in the blood levels of people in our study that glucose and ketones correlate to their psychiatric symptoms. So it’s something that’s happening in real time. It’s not just like the extended effects of cortisol over time, but also the daily effects of cortisol surges and glucose surges, I think could be really interesting to study.

30:33 — Morning exercise can help blunt the dawn glucose rise

Dr. Campbell explains how running in the morning helps him mitigate bipolar symptoms, which he notes, that for him, tend to be worse in the morning. He correlates this reduction in symptoms to a blunting of the natural rise in glucose that occurs upon waking (i.e. the dawn rise).

I think that combining exercise and diet is an absolute nobrainer for mental health. And I think, just anecdotally, I am a different person if I exercise, if I do a run in the morning and bring down my glucose levels. And one of the most important things to help me realize that was looking at a CGM and seeing the surge in the morning and seeing something is happening with my metabolism in the morning that makes the symptoms much worse in the morning if you don’t manage it. So going for a run I can kind of flatten a lot of that glucose curve and feel much, much better throughout the whole rest of the day. And I think that this is something that could be revealed by more people wearing CGMs and examining this.

38:48 — The ketogenic diet has effects on brain neurotransmitters

While low-carb diets in general have some metabolic health benefits, Dr. Scher explains that the specifics of the ketogenic diet—in which the body enters a state of ketosis—is what produces the beneficial effects on neurotransmitters.

It’s actually a ketogenic medical intervention that does these amazing things of changing your neurotransmitters in the brain. So I just want to make sure people understand that very important concept as we’re talking about the sort of the deep science here… We have to look at it from two different aspects, and one is improve metabolic health, and one is changing the fuel source for the brain. And so when it comes to improving metabolic health, then yes, a low-carb, 75-gram fibrous carbohydrate diet, combined with exercise and sleep, it is going to improve metabolic health for just about everybody. And it may not be the most powerful intervention, but it’s going to be a powerful intervention that’s going to help people improve their metabolic health. I think you will see benefits for mental health. Then the next question is, Well, is there more? And I think the more is changing the fuel source for the brain from using glucose to using ketones, bypassing absolutely any potential insulin resistance that exists in the brain. And then you see decreased neuroinflammation. You see a balancing of the neurotransmitters with increased GABA, decreased glutamate, and I just don’t think you’re going to see those things with simply improving your metabolic health; that requires this metabolic shift and fuel shift from glucose to ketones.

43:34 — Dr. Campbell explains ketosis helps him combat depression

Dr. Campbell shares about the deep states of depression he’s experienced with bipolar disorder and how the ketogenic diet has helped him reduce depressive episodes.

I think you hear again and again when you speak to people with bipolar is that the early morning is the worst time. It’s when you wake up and you’re faced with this state of depression and the state of depression is not really so much feeling sad—it’s like a state of physiological crisis that the body plunges into where people go into catatonic states of depression where they can’t move and there’s increased lactate in their blood and they feel like they’ve run a marathon even though they’ve not even moved an inch. And it really is that state of complete physical exhaustion that happens for no apparent reason. And it just comes over people during these episodes. And so it’s extremely unfortunate: this makes people very hopeless… Even if they have a family that they care about more than anything in the world or friends or a job, they can’t physically summon the energy to interact. And it’s very discouraging for people. So if anyone is experiencing that, I would say that I’ve been through that for many, many years and it took me a very, very long time to realize that metabolism has anything to do with that state. And now if I maintain ketosis, I don’t have to experience that state of physical exhaustion that happens. We’re still trying to understand why that happens and what this benefit provides. But I think that for me, maintaining ketosis is something that is the only thing that’s ever turned the dial on these severe depressive episodes. I come out of them when I go into ketosis.

46:42 — Dr. Campbell describes why he went on the ketogenic diet

Although Dr. Campbell turned to the ketogenic diet for physical health benefits, he also found that it had major mental health benefits for him.

When I first learned about this, I did it to lose weight. I was experiencing suicidal depressions and I really was aware at a certain point that I wasn’t going to survive this condition much longer. I had a wife and a family, and I wanted to do lots of things, and I realized this just wasn’t going to happen. And so I just told myself, “At least I’m going to try and be as physically healthy as possible. “This is my last sort of go at this. And so I actually did an Atkins diet. I got the Atkins Diet book, and I did a very strict version of it. That, I realized, put me in ketosis. And when I saw the weight loss—I lost about 50, 60 pounds of weight. And I saw that at the same time my psychiatric symptoms were going away, which to me was completely remarkable after trying this. And the resource I had available was just really listening to your podcast and listening to your shows… You’re the person that was telling people about this for physical health, but it was really affecting my brain as well. And so when I was reading your research, I was like, ‘Oh, this has to do with epilepsy and neurons and membrane potentials. And it really spoke to me as someone who researched bipolar disorder scientifically. So, at the time, I wish I could have done it with support from a psychiatrist who understood metabolic psychiatry and these aspects of it.

Iain Campbell (00:00:06):

When I first learned about this, I did it to lose weight. I was experiencing suicidal depressions and I really was aware at a certain point that I wasn’t going to survive this condition much longer. I just told myself, at least I’m going to try and be as physically healthy as possible. This is my last go at this. What I’d love in the future is for people to get this feedback and as early as possible when someone’s having their first episode, maybe we can prevent a large course of the illness by introducing this early on. Just like with some people with epilepsy, including as someone who has kids that are susceptible to bipolar is that we can put people on this as early as possible and potentially avoid the whole course of the illness. I think that would be the best possible outcome.

Ben Grynol (00:00:52):

I’m Ben Grynol, part of the early startup team here at Levels. We’re building tech that helps people to understand their metabolic health. Along the way, we have conversations with thought leaders about research backed information so you can take your health into your own hands. This is a whole new level. What is the connection between metabolic health and mental health? Something that we’ve talked about on this podcast before with Dr. Chris Palmer. This episode is part of a three-part series between the cross section of mental health and metabolic health. We’re doing it in association with Metabolic Mind and our great friend, advisor and mentor, Dr. Dom D’Agostino is hosting the series.

(00:01:45):

In this episode, Dom sat down with Dr. Iain Campbell and Dr. Bret Scher. They talked about how metabolic health and mental health are tightly related. They talked about things like how can dietary and nutritional interventions be taken as a step to mitigate and improve mental health disorders. How can CGM help with things like data insight and accountability for some of these dietary interventions to improve metabolic health. They also discussed how there are other biomarkers associated with mental health conditions, increases in cortisol, increases in lactate, glucose, insulin. These can all show signs of insulin resistance and mitochondrial dysfunction in the body, which ultimately, leads to poor metabolic health. We know over time this can lead to poor brain health.

(00:02:29):

Dr. Iain Campbell was recently awarded the first Metabolic Psychiatry Research Fellow at Baszucki Group, investigating the science and application of ketogenic metabolic therapy for bipolar disorder. Dr. Iain Campbell is one of the few scientists in the world researching bipolar disorder, who also lives with the condition. After personally sending his illness into remission using ketogenic therapies, he dedicated his career to furthering mental health research in the emerging field of metabolic psychiatry. Dr. Bret Scher is the director of Metabolic Mind and a board-certified cardiologist, lipidologist and leading expert in therapeutic uses of metabolic therapies, including the ketogenic diet.

(00:03:11):

He’s practiced for more than 20 years as a preventative cardiologist and was the medical director of dietdoctor.com for more than three years. Last but not least, Dom D’Agostino. Dr. D’Agostino is a friend, advisor and mentor to many of us at Levels. DOM is an associate professor in the department of Molecular Pharmacology and Physiology at the University of South Florida. Dom’s Labs have developed and tested metabolic-based strategies for targeting CNS oxygen toxicity, seizures, epilepsy, and neurodegenerative diseases. The main focus of this lab over the last 12 years has been investigating the neuroprotective mechanism of the ketogenic diet and metabolic health. Anyway, no need to wait. Here’s a great conversation about the cross section of mental health and metabolic health with Dom, Bret and Iain.

Dominic D’Agostino (00:04:07):

I am honored to be among Dr. Bret Scher and Dr. Iain Campbell. I thought before we begin, maybe both of you guys could just discuss a little bit briefly your background and what you do and how both of you are really spearheading this whole movement, advancing the science application advocacy of metabolic psychiatry.

Bret Scher (00:04:33):

I’ll jump in. Because I’d love to transition and introduce Iain a little bit too. I’m Bret Scher. I’m actually a cardiologist by training, but in my cardiology practice I really focused on cardiometabolic health and how metabolic health related to so many other disease issues. Really, did deep dives on metabolic health and about nutritional therapy, lifestyle interventions, to improve metabolic health with ketogenic therapies being a big part of that. From then, with my focus on metabolic health, then started to transition to this connection between metabolic health and mental health. That’s when I met the Baszuckis and was fortunate enough to meet Iain Campbell and hear his story as well. Just really became enthralled with this opportunity within mental health, within psychiatry to focus on metabolic health and metabolic therapies as potential treatments for psychiatric illnesses.

(00:05:27):

I really have to give a lot of credit to someone like Iain or Iain himself and Matt Baszucki and others who’ve shared their stories and are, like Ian’s doing, helping further the science. That’s what got me connected with Metabolic Mind where I’m now the director, where we’re really focusing on putting forth this education about this connection between metabolic and mental health and metabolic therapies as treatment for mental illness. I’m real happy to be here today to share this with your listeners and Dr. Iain Campbell has been a shining light for me as an example of someone who’s lived with mental illness, who’s treated it with nutritional therapies and who’s sharing his story with the world to help educate and inspire others while also doing the research. It’s just such a great combination. I’ll turn it over to you, Iain, to give a little bit of your own intro there.

Iain Campbell (00:06:16):

Thank you. Yes, I’m the Baszucki Brain Research Fellow in Metabolic Psychiatry at Edinburgh University. I have a PhD in global health in the University of Edinburgh. I also am diagnosed with bipolar type two and I’ve been using ketogenic metabolic therapy for seven years now. This was something that it’s a real pleasure to be on this podcast. Because I originally found out about ketogenic metabolic therapies through listening to podcasts like you were doing Dom and promoting this as a therapy for cancer and for neurological disorders, like epilepsy and other conditions. I had no idea at the time it would have an effect on my mental health, but it was more effective than any treatment I’d ever tried in my life in ameliorating the symptoms of bipolar. It was such a dramatic turnaround for me after having tried many things that haven’t worked. I felt I need to spend as much time as I can the rest of my life trying to tell people about this and try to explore and understand how many people this could help.

Dominic D’Agostino (00:07:13):

Iain, you’re, you’re really like the poster child for this. Because you live with a disorder, you’ve more or less managed it or maybe even described as putting it into remission to some extent with ketone metabolic therapies. We’ll get into that a little bit about how you do that, your personal story, but also, the research that you’re doing through the fellowship and also, the advocacy and the education outreach that you’re doing. Really, what we’re here to discuss, the link between metabolic health and mental health. Levels has an immense appreciation for that. They’ve even funded a collaborative study at University of South Florida with Dr. Allison Hall. We’re looking at CGM and low-carb diets in the context of looking at normal healthy people. Even a low-carb diet or ketogenic diet implemented in normal healthy people without bipolar depression improves scores on things like PHQ-9 and GAD-7 and a variety of others.

(00:08:18):

What we’re talking about here today for our listeners is not strictly about bipolar depression, I mean a heavy emphasis towards that, but just towards the link really in the general population of metabolic health and mental health. I think we have the two leading experts here that could talk through personal experience and through research and advocacy. My intro into Levels was actually through the Baszuckis, through Jen Baszucki. I think she’s a CGM user, a Levels user. I think it was Casey or Josh, connected me. Things like devices, emerging technologies like continual glucose monitoring is a very valuable tool. Iain, I think maybe you could talk a little bit about the research that you’re doing through your fellowship and how you’re designing that protocol, specifically ketone metabolic therapies or dietary therapies and the different things that you’re looking at.

Iain Campbell (00:09:20):

We just conducted a pilot trial with 27 participants with bipolar disorder going on a ketogenic diet for eight to 10 weeks with a two-week washout periods. We were assessing feasibility and acceptability of the diet for preparation for a future randomized controlled trial. We were also looking at outcome measures, psychiatric outcome measures, metabolic outcome measures. What we saw was quite, it was very interesting because there’s a significantly increased cardiovascular risk with bipolar disorder. In fact, in the UK, over 70% of people die of physical preventable illness with serious mental illness.

(00:09:55):

There’s two to three times the risk of type two diabetes and there’s a very strong energy component to bipolar disorder that’s under recognized in the research. Ketosis speaks to all of these mechanisms, but it’s also a therapy used for epilepsy and anticonvulsants are used to treat bipolar disorders. We share medications with epilepsy. Now, this other effective therapy for epilepsy is coming to focus for bipolar. There’s a lot of scientific background to why we want to conduct this study. Also, many patients, many like myself, like Matt Baszucki, are coming forward with help of Bret sharing this in Metabolic Mind and these channels. It’s a real patient movement to raise awareness about this because the people are reporting remission of symptoms, substantial benefits. We want to try and understand under a bit more of a microscope of what’s really happening and we’ll be publishing a paper in the next couple of months.

(00:10:44):

We found substantial changes in their metabolic profile alongside their psychiatric symptoms, alongside their brain imaging and other parameters that we looked at that would be considered very beneficial for bipolar disorder. It speaks to many of the aspects of bipolar pathophysiology that are important, like glutamate in the brain, serum lactate levels, the psychiatric symptoms associated with bipolar. We’re very excited to share these results. We presented this at ISBD conference. I was there with Bret a couple of weeks ago in Chicago. We presented alongside Shebani Sethi’s work at Stanford and Georgia Ede’s study with Dr. Danan. I think it was the first time people really saw this as a serious scientific area for bipolar disorder that we would want to study this and then look at the mechanism shared with anticonvulsants.

Bret Scher (00:11:33):

I wanted to add being in the crowd for that presentation at this international bipolar meeting and to see people’s attention and to hear them talking after the fact. Because for a lot of people, it was a new introduction to ketogenic therapies. It was pretty remarkable, because the data presented was impressive and it really got people’s attention. It’s such an important step, because we can talk about it all we want. We can share stories all we want, but for the treating physician who’s maybe a little skeptical, they need data, they need studies, and that’s what they now have. The reaction in the room was really dramatic. I think we’re going to see this take off in large work because of what Iain and Dr. Shebani Sethi and Albert Danan and Georgia Ede because of what they’re doing, not just clinically, not just from an education standpoint, but from a research standpoint. It’s so impressive to see.

Dominic D’Agostino (00:12:26):

Have there ever been any kind of dietary therapy clinical trials presented at ISBD? That’s a massive step in the direction of hitting mainstream for this disorder. Was everybody in shock that something like nutritional intervention can have an effect? Iain, it wasn’t at ISBD, but I saw probably a similar presentation at Keto Live in Switzerland.

Iain Campbell (00:12:55):

It was really remarkable because we were showing, and keeping in mind we’re in a small sample size. We were trying to present this as a feasibility and acceptability study, but we’re also sharing the outcomes they were measuring in psychiatric symptoms, metabolic symptoms. Alongside Shebani and Georgia’s data, we’re showing very substantial changes in psychiatric symptoms, beneficial changes in brain imaging and metabolomics. The profile of benefits speaks to the whole gamut of what goes wrong in bipolar disorder.

(00:13:25):

I think for people watching this, a lot of people were very surprised and very excited and lots of psychiatrists who were previously I know to be skeptical, came up afterwards and were really saying, “We want to launch research in this area.” I think actually the main thing I wanted to point out was that this makes complete scientific sense. We’re using these anticonvulsants to treat bipolar, and here’s another anticonvulsant therapy that’s showing effectiveness. Let’s try to explore the mechanisms of this and understand more about it. It was really, we received a very warm response and a very open response, and people were wanting to jump in and get involved in this, which is all you can ask for with these conferences. It’s fantastic.

Bret Scher (00:14:02):

Dom, you asked if there’ve been presentations about dietary intervention. Well, there was a big focus on this increased cardiometabolic risk for patients with bipolar disorder. Whether it’s from the underlying cause itself or from the medications or a combination of both, it’s clear they’re at higher risk. There was some discussion about nutrition in general and lifestyle in general to counteract or to address that increased cardiometabolic risk. Here’s an intervention, nutritional ketosis, ketogenic therapy that cannot only address that increased cardiometabolic risk, but could also looks like it also addresses the psychiatric symptomatology. You get a dual effect rather than just trying to say, okay, we use drugs for the bipolar and then try and counteract the increased cardiometabolic risk with lifestyle. Here’s a lifestyle and that can do both. That’s something that really get a lot of people’s attention and rightly so.

Dr. Casey Means (00:15:08):

This is Dr. Casey Means, co-founder and Chief Medical Officer of Levels. If you’ve heard me talk on other podcasts before, you know that I believe that tracking your glucose and optimizing your metabolic health is really the ultimate life hack. We know that cravings, mood instability, and energy levels and weight are all tied to our blood sugar levels. Of course, all the downstream chronic diseases that are related to blood sugar are things that we can really greatly improve our chances of avoiding if we keep our blood sugar in a healthy and stable level throughout our lifetime. I’ve been using CGM now on and off for the past four years since we started Levels, and I have learned so much about my diet and my health. I’ve learned the simple swaps that keep my blood sugar stable like flax crackers instead of wheat-based crackers.

(00:16:00):

I’ve learned which fruits work best for my blood sugar. I do really well with pears and apples and oranges and berries, but grapes seem to spike my blood sugar off the chart. I’m also a notorious night owl and I’ve really learned with using Levels, if I get to bed at a reasonable hour and get good quality sleep, my blood sugar levels are so much better. That has been so motivating for me on my health journey. It’s also been helpful for me in terms of keeping my weight at a stable level much more effortlessly than it has been in the past. You can sign up for Levels at levels.link/ podcast. Now, let’s get back to this episode.

Dominic D’Agostino (00:16:45):

There is an appreciation then and discussion about things like insulin resistance and the development of metabolic health problems. Is that, I mean, we are privy to that in our little niche of a community of metabolic psychiatry, but within the scope and the breadth of the individuals at this conference is this, was this completely all new to them and did they actually, high fat diets have been associated with cardiovascular risk? I mean, was there a little bit of pushback or I was wondering if there was a Q question answer session sort of after the presentation of the data, when people maybe look up what a ketogenic diet is and the macronutrient ratios as Bret as a cardiologist, lipidologist, that is what you have been kind of a voice of reason when it comes to discussing the cardiometabolic implications of these dietary therapies.

Bret Scher (00:17:45):

You’re spot on. There definitely was some concern. Oh, well, we see that low-carb diets increase your risk of death and high-fat diets increase your risk of heart disease and LDL is going to go through the roof. There definitely were those concerns. There’s probably the most discussion of LDL ever at a psychiatry conference is my guess. That’s why I’m glad I was there and I was able to speak up and point out that we have to realize that the “studies” that show low-carb being harmful or increased risk of heart disease have 40% of their calories from carbs. That’s their definition of low-carb, which is completely different from a ketogenic intervention. We really are talking about two completely separate things. The physiologic changes that occur with a ketogenic intervention are dramatically different from just the 40% carbs or even one study that showed 20% carbs, still not ketogenic.

(00:18:43):

I think people need to realize that we’re talking about ketogenic therapies and we can’t extrapolate generic so called low-carb data to that. That’s the first point. Then the second point is just educating people that for the majority of the people, LDL doesn’t go up. I think Iain, you presented data, and Shebani and Georgia, all present presented data about LDL and cardiac risk. In general, LDL doesn’t go up and Shebani even presented her evidence that cardiac risk was the same or went down. Those are the other we have to get over the preconceived notions that this is by definition a harmful diet for your heart where LDL is going to go up. Because that’s not the case for the vast majority of the people. Even if LDL goes up a little bit, overall calculated cardiac risk goes down because of all the metabolic improvement. There’s definitely a lot of education that needs to go on, especially in groups that may be aren’t as familiar with ketogenic therapies.

Dominic D’Agostino (00:19:42):

It’s an aggregate of cardiometabolic biomarkers, like blood pressure medication. Hemoglobin A one C and other things like continuous glucose monitoring, which is looking at things like glycemic variability and then of course, ketone levels. If you’re using a ketogenic intervention. Iain and Bret, was there any discussion or general consensus with everyone presenting on the biomarkers that we should be paying attention to in regards to mental health bipolar, specifically?

Iain Campbell (00:20:14):

I was just going to say it was fantastic. If there’s anyone who could speed dial at that moment when they asked about cardiometabolic risk, it would be Bret. The fact that we are able to actually give quite robust feedback on that was fantastic. Because it’s a major topic of any bipolar conference is the physical and cardiometabolic aspect of bipolar. The biomarker, it’s very difficult to isolate biomarkers in bipolar disorder. Because you’re trying to measure the activity in the brain and of course, you’re getting a signal from the serum, but we’re never sure how reliable it is.

(00:20:42):

The systematic reviews have consistently for around 70 years now, highlighted elevated lactate as being a significant biomarker is the most significantly altered biomarker in bipolar disorder in the serum. This is also reflected in brain magnetic resonance spectroscopy. Lactate is considered a biomarker in bipolar disorder. You can’t use it to diagnose anything, but there’s definitely elevated lactate. This has been related to the literature on mitochondrial dysfunction and the hypothesis being that this is glycolysis running an overdrive. I think this fits with metabolic dysfunction in general, that there’s a mitochondrial dysfunction increased glycolysis. I think it also ties in with what you’re saying about insulin resistance in the brain, and we’ve always known that insulin resistance causes havoc with the whole rest of the body.

(00:21:29):

For some reason, we’ve assumed that the brain wasn’t affected in some way. I think the scientific understanding has evolved to the point where we now understand that insulin is extremely important in the brain. If you look at the mechanisms of action of some of the bipolar medications, they act on insulin signaling mechanisms. The primary target of lithium is the phosphatidyl and acetol cycle, and there’s been untold amount spent on studying this mechanism for pharmaceutical intervention. It’s actually a key component of insulin signaling as are many of the other drug targets like GSK-3 studied in bipolar disorder. I think the actual way we treat this at the moment does speak to these metabolic aspects.

Dominic D’Agostino (00:22:06):

Bret, do you want to comment on that? Maybe follow up on the lactate perhaps as a mitochondrial metabolic biomarker that could be implicated here? That’s a new one for the community too and something we’re actually very interested in.

Bret Scher (00:22:22):

Well, I want to answer the question by focusing on the word that you said, was there a consensus? Definitely, no. There’s not a consensus. A lot of the presentations, we’re still using fasting glucose as the measurement, which we know is just such a misleading metric. Things like CGM looking at your average daily glucose, your glycemic variability is so much more informative than just a fasting glucose. There’s definitely some education that needs to go on. There was one talk, talking about insulin and home IR and even mentioned CGMs, which is certainly a step in the right direction, but that was one out of many. There definitely needs to be some education from that standpoint. I think lactate is a fascinating marker that we should be following. That’s going to take some time to adopt as well as people get familiar with it and learn how to use it.

(00:23:14):

I think it’s clear we’re on the cutting-edge of learning more about how to monitor metabolic health and that what we have been doing with fasting glucose is woefully inadequate. We’re going to keep learning more and getting more comfortable with things like lactate and CGMs and of course, blood pressure and A1C and fasting insulin and home IRs. Using all of those together to assess metabolic health and then using that as the broader picture of cardiometabolic health. There also was a lot of discussion about LDL. As we know, we have to go way past LDL to assess cardiovascular risk as well and look at the whole picture. It’s clearly emerging and groups like Levels are certainly lead leading the way when it comes to getting beyond just fasting glucose and getting more intensive measurements of glycemic control.

Dominic D’Agostino (00:24:11):

Do you think there’s an opportunity to look at stress hormones, for example, maybe catecholamines or maybe more importantly, cortisol? Because cortisol in myself and many others, we’re looking at a big data set now for Dexcom. That dawn response is ubiquitous among healthy individuals and across the board and people who have dysregulated cortisol or hypercortisolemia, maybe at higher risk. Is that something we should be looking at in this population?

Bret Scher (00:24:44):

It certainly makes sense. As you know, I’m sure you know with cortisol, the timing of measurement makes a difference and how you measure it makes a difference. A lot of those things need to be worked out and consistent. Certainly, makes sense. As a society, I think we can say we’re not very good at managing our stress. It’s clear that, that impacts our health, our metabolic health and our mental health. I think that, that does make a lot of sense to focus on.

Dominic D’Agostino (00:25:10):

Especially, in the context of this population. I think maybe anxiety disorders are on the rise and maybe that’s a contributing factor for triggering an event. Bipolar disorder, maybe Iain can talk about this is very cyclic and maybe it’s from seasonal circadian. There’s different things that can trigger the disorder including anxiety and maybe it could follow some kind of stress biomarker. I think that’s a fruitful area for research that remains untapped and I’ve been personally interested in. Because we’ve done some research in the military and with NASA and looking at operationally how these stress biomarkers can be elevated. Then when we go back and look at the cardiometabolic biomarkers, we see that they’re dysregulated too. It’s like, is the cortisol impacting that or are there other factors? Just the nature of the operational activity impacting cardiometabolic biomarker or is it being driven by the stress hormones? Something to look at.

Iain Campbell (00:26:17):

Absolutely. There’s two major things I think CGM could be really used for in bipolar disorder and schizophrenia and major depression is, there’s bipolar disorder. It’s one of the most well-known features going back to the 60s when Jean Falret was talking about fully circular madness. It was very much pointing out this circadian aspect. When you disrupt someone’s circadian rhythm, they’ll have episodes and if you improve someone’s circadian rhythm, they’ll have less. It’s almost like the body’s energy regulation is being dysregulated bipolar. He was sitting with patients in hospital observing them. He was saying that his depression is especially conspicuous and during mania they have unlimited energy and they work all day and night and you can actually take someone who’s depressed and you can even do things like keep them up till 2:00 or 3:00 in the morning and this will help them to feel better.

(00:27:13):

Then if you take someone and do the opposite and you have someone who’s manic and disruptor their sleep, they can become worse. There’s a really strong circadian aspect. Obviously, when you wear a CGM, this becomes really apparent to you with the dawn effect. I did this for a year myself wearing a CGM and this cortisol rise that you described in the morning is significant. I think it’s also correlated, we were seeing in the blood levels of people in our study that glucose and ketones correlate to their psychiatric symptoms. It’s something that’s happening in real time. It’s not just like the extended effects of cortisol over time, but also, the daily effects of cortisol surges and glucose surges I think could be really interesting to study.

Dominic D’Agostino (00:27:51):

Bret and Iain, we know that stress plays a huge role in mental health and the management of mental health and perhaps bipolar. It leads to the question of stress biomarkers that we can measure. Cortisol in particular, which we’ve done some research on maybe catecholamines, and this is influenced profoundly by situationally but also, circadian variability and also sleep. Maybe a little bit of insight into that and also if we know if metabolic therapies can impact stress in that way.

Iain Campbell (00:28:27):

The circadian aspect of bipolar has been recognized right from the start of bipolar since the earliest clinical observations by Emil Kraepelin, who was seeing patients be very active at nighttime and sleep during the day. This was reflected in even the earliest papers on bipolar by Jean Falret, where he was calling it circular insanity where it follows this pattern of circadian dysregulation. You can help people with bipolar through light therapies that realign their circadian rhythm. People can also have episodes brought in by circadian rhythm disruption. I think the main thing I noticed, the morning experience using CGM was what you described about the dawn effect, the cortisol surge in the morning. We also measured daily ketone and glucose levels in our patients and we were looking at the correlation with their psychiatric symptoms measured daily.

(00:29:13):

We found these positive correlations with the things you’d want to improve, like better mood, better energy and negative correlations with things like anxiety and impulsivity. I think this speaks to a really important point about bipolar, which is in the euthymic state, there’s actually a huge degree of variation on a daily basis in someone’s symptoms. Even people that are euthymic, the attempted suicide rates for bipolar between 25 and 60% for people at the moment. Even though we’re saying in studies that a lot of people are achieving clinical euthymia, they don’t want to live. That’s not an outcome that I think any of us feel as good as patients or clinicians. Then we want to try and understand what is this variation and the so-called euthymic state? CGM could give us a great deal of potential information about that through cortisol and metabolic parameters. I think it’d be really interesting for future research.

Bret Scher (00:30:04):

I think the question of stress is really fascinating. One of the amazing parts of Iain’s data that he presented was this correlation between ketone levels and psychiatric symptoms. As we know, ketone levels can change throughout the day and there are a number of different things that could impact that. Stress hormones certainly could be one of them. I’d be fascinated to learn more about the role of changing stress hormones and altering ketone levels and then how that impacts symptoms of mental illness or even mental clarity and executive function and thought process and energy levels and how all that is intertwined.

(00:30:45):

You can think of different interventions. If you know your ketones drop at a certain point, well, then you do certain interventions to try and raise them. Whether that’s managing stress hormones or whether that’s taking an exogenous ketone or taking an MCT oil or doing some other type of intervention to raise those ketones back up in a circular pattern. How does that impact your cognitive function, your mental health? I think that’s a really fascinating area of discovery. Iain, was I think the first to really show this data that there is this direct correlation between ketone level and symptoms of mental health.

Dominic D’Agostino (00:31:25):

Maybe looking at stress too. Maybe normal stress response, which we want is an elevation of cortisol in the morning, but not so much in the evening. Maybe that could be indicative. Another thing that you brought up, Bret, is just other things that could be used to modulate or augment metabolic physiology to improve these things, including an elevation of ketones. I know exercise is a big lever that we can pull. Not everybody’s going to do it, but I know Iain, that you’re a huge advocate of exercise, strength training, exercise in general. In addition to sleep and diet, I think of exercise as a metabolic therapy. In regards to your participants in the study and the feasibility of looking at exercise and perhaps there’s a synergy, a diet, lifestyle exercise synergy going on there where one and one equals three when you combine the two together. Your thoughts maybe personally on how perhaps we could research that or get some insights into that.

Iain Campbell (00:32:33):

How would you feel like to ask you that question? I think that the metabolic therapies are, ketogenic diet is one metabolic therapy, and there’s so many things that affect metabolism, like you’re saying, circadian rhythm, exercise, sleep, are all interrelated. They’re all acting on similar underlying pathways, which are also some of the pathways that we manage through medication in bipolar disorder. I think that combining exercise and diet is an absolute no-brainer for mental health. I think just anecdotally, I am a different person if I exercise, if I do a run in the morning and bring down my glucose levels.

(00:33:09):

One of the most important things that help me realize that was looking at a CGM and seeing this surge in the morning and seeing something is happening with my metabolism in the morning, that it makes the symptoms much worse in the morning if you don’t manage it. Going for a run, I can flatten a lot of that glucose curve and feel much, much better throughout the whole rest of the day. I think that this is something that could be revealed by more people wearing CGMs and examining this.

Dominic D’Agostino (00:33:35):

Potential synergy there. I remember years ago, and Jung Roe was there, cure for epilepsy was there. UCB pharmaceuticals, they make Keppra. They held a meeting in Belgium. They’re very interested in the ketogenic diet and perhaps, synergy with this anti-epileptic drug. We’re discussing here a metabolic therapy that in the context of an adjuvant at least, but also perhaps a replacement for drug therapy along the line. People who are already on pharmacotherapy, maybe these metabolic interventions, there could be some synergy there, but also diet.

(00:34:20):

Exercise is a huge lever that is altering our metabolism. I think you bring up some good points. I know I’m not suffering, at least that I know of, of any mental disorder. I know exercise has always kept me sane, so to speak, in grad school. I self-medicate with exercise and just defaulted to that. I established those early patterns early in life. I think without that, I don’t know where I would be. I see that in other graduate students and people in academia too, that it’s such a powerful therapy in and of itself.

Bret Scher (00:34:55):

I think exercise has a dual therapy effect. One is the endorphins that come from exercise. I don’t know studies on this, but I think it’s clear, some people get them and some people don’t. Some people just feel great with exercise and some people maybe don’t, and from the endorphin side. The other part is the metabolic health side. Like you said, exercise is a metabolic therapy and it’s practically, everybody’s going to get that benefit by maintaining or building lean muscle mass, by doing cardio and improving your blood sugar and your insulin and your glucose sensitivity. That those things are going to improve your metabolic health, which then will translate to some degree to mental health as well. I think there is sort of that dual-pronged approach for exercise for improving people’s overall mental wellbeing.

Dominic D’Agostino (00:35:43):

Brain energy, not just like BDNF. I think Rhonda Patrick had sent me some papers and there was a research scientist and there was a couple of papers sent to me on how we exercise, that elevates circulating levels of lactate in the millimolar concentration. That freely crosses a blood brain barrier via the monocarboxylic acid transporter to restore brain energy. Our brain would have free access to this alternative fuel. I do think lactate is underrated. Actually, before I even started in ketones, I was interested in alpha L polylactate, which as a source of an alternative fuel, I’m still very interested in that. I think exercise does so many different things and muscle is an endocrine organ and it’s releasing myokines and other factors that are altering brain health and maybe stabilizing our mood. The lactate question is something that’s interesting too. At rest, if lactate is elevated, that’s a telltale sign of metabolic mitochondrial dysfunction. It feeds into that mitochondrial etiology of mental health.

Iain Campbell (00:36:49):

It’s so interesting, the lactate question as well, because exercise is also a trigger. It generally improves people in depression states. I’ve definitely experienced this, is that intense exercise can be a trigger for mania people with bipolar disorder. If you do the moderate intensity like below lactate threshold exercise, it appears to be beneficial. Then the higher intensity exercise, people can get manic. I find that really fascinating in the context of what you’re saying about lactate because you’re importing this additional fuel source into the brain and you’re having heightened power and activity of the brain in the EEG studies I’ve seen on that. It’s also importing glutamate alongside the lactate. This glutamate and lactate flooding the brain after exercise, I wonder whether that is a risk factor for manic episodes, but also what does that say about what a manic episode is?

(00:37:42):

I have a paper about this I just published called Metabolic Overdrive, Glutaminolysis and Hyper Glycolysis in Mania and Bipolar Disorder. I think this post-exercise state is a significant risk for mania, but it also reveals an interesting aspect of mania that we were showing a ketogenic diet was improved, which is increased glutamate metabolism in the brain. We’re showing between 11 and 13% reduction in glutamate in the brain of pupil on our pilot study. This is what a marker of response to anticonvulsants as well. I think these unique metabolic states could reveal aspects of the condition that we could use to optimize ketogenic diet intervention.

Dominic D’Agostino (00:38:20):

With the glutamate in, did you also look at GABA? Because work in our animal model show that glutamate can stay the same or go down, but we have correspondingly higher levels of GABA. We do immunocytochemistry or western bots for glutamic acid decarboxylase 65 and 67, and these are always elevated. With diet therapy, but also with a ketone estro therapy, which makes me think that the ketones are altering the enzymatic production of the enzyme and maybe the activity of that enzyme to make more glutamate GABA. This is one of the underlying theories that we’re working on.

Iain Campbell (00:39:00):

Yeah, absolutely. There’s a glutamate GABA balance in the brain, and it appears that glutamate is reduced and that GABA’s increased in ketogenic diet. One of the proposals I made in this paper I just published was that glutamate is also a metabolic substrate in the brain. This was Hans Krebs’ original focus on glutamate in his early papers. If glutamate is used as a metabolic substrate in the brain, this is fulfilling a similar role to ketones. If you provide ketones, it reduces the need for glutamate to be metabolized in this way.

(00:39:29):

What’s interesting about that is that if you have glutamate being used through this as a metabolic substrate in the brain, you get several of the markers of bipolar disorders such as decreased N-acetyl aspartate is using up the aspartate pool. You get this increased level of glutamate. Ketogenic diet, bringing those down in that context would make a lot of sense. I think in the same way we’re looking at the metabolic role, the role of metabolism in psychiatric disorders. We could also look at some of these neurotransmitters that have been focused in bipolar through a metabolic lens to understand some of these states of mania and depression.

Dominic D’Agostino (00:40:04):

I think of glutamine with glutamine synthesis. The astrocytes take up the glutamate from the exercise and then convert the glutamate back to glutamine, and then it gets transported back to the neurons and then glutamate is synthesized. That’s a whole other area that it’s not really even discussed much in neuroscience, but that idea of glutamate being a carbon source really for fuel and for ATP is very interesting.

Bret Scher (00:40:33):

You guys are getting deep into the science here. I wanted to take a step back for the broader perspective. Because I think it brings up such an important point that we’re talking about a nutritional intervention that changes the neurotransmitters of the brain. That in itself is pretty remarkable. Because you talk about, yeah, you can improve your metabolic health by going on a low-calorie Mediterranean diet or just reducing your calories by 500 calories. Those aren’t going to change the physiology of your brain and the neurotransmitters of your brain. That’s why I think it’s so important as we talk about a ketogenic diet in this setting, it’s actually a ketogenic medical intervention that does these amazing things of changing your neurotransmitters in the brain. I want to make sure people understand that very important concept as we’re talking about the deep science here.

Dominic D’Agostino (00:41:24):

Bret, that’s a super important point, like that overarching change in our metabolic physiology impacts brain energy metabolism, brain neuropharmacology. This is an ongoing question, even in this niche here that a low-carb diet or maybe implementing intermittent fasting. I just interviewed someone yesterday about how that changes the whole microbiome. Low-carb intermittent fasting could be equally as powerful. Bret, I’d like to get your thoughts on not necessarily a strict clinical ketogenic diet, but the potential if a low-carb diet defined as under 100 grams of carbs and sticking to fibrous carbs instead of sugars and starches or intermittent fasting could have equal amount. If the benefits are linked to a loss of body weight or changes in body composition, and if you could achieve that through other dietary means, and if that’s one of the things changing our mental health?

Bret Scher (00:42:30):

That’s a great question.

Dominic D’Agostino (00:42:31):

In discerning whether it’s the ketogenic therapy and the elevation of ketones versus just body composition or metabolic markers.

Bret Scher (00:42:40):

I think it’s a fascinating question. I guess to start the answer, is I have to say a lot of this is taking what we have and making best guesses from it, and that we need dedicated studies looking specifically at this question, which haven’t been done, but I’m sure will be done. I think we have to look at it from two different aspects. One is, improve metabolic health and one is changing the fuel source for the brain. When it comes to improving metabolic health, then yes, a low-carb 75-gram fibrous carbohydrate diet combined with exercise and sleep is going to improve metabolic health for just about everybody. It may not be the most powerful intervention, but it’s going to be a powerful intervention that’s going to help people improve their metabolic health. By improving metabolic health, I think you will see benefits from mental health. Then the next question is, well, is there more?

(00:43:36):

I think the more is changing the fuel source for the brain from using glucose to using ketones, bypassing absolutely any potential insulin resistance that exists in the brain. Then you see decreased neuro-inflammation, you see a balancing of the neurotransmitters with increased GABA, decreased glutamate. I just don’t think you’re going to see those things with simply improving your metabolic health. That requires this metabolic shift and fuel shift from glucose to ketones. That’s not to say you’re not going to get any benefit by just focusing on metabolic health with a low-carb diet. I think you will, but I think if you want to optimize or intensify the treatment as the medical treatment, that’s where a ketogenic therapy comes in and changing the fuel source with ketones.

Dominic D’Agostino (00:44:19):

Great points and very well stated. A ketogenic diet is more or less a prescriptive diet therapy or a prescription strength metabolic therapy, as opposed to a low-carb diet. A ketogenic diet truly is, I mean, it is legitimately in action, a prescription strength diet therapy and it’s prescribed in epilepsy. It has a wide track record. It was very interesting as I got more and more into this research, people didn’t know about the epilepsy research, which was like my wheelhouse and the overlap between the anti-epileptic drugs and bipolar too. That may be some common mechanism there. It makes sense that you may need to achieve and sustain that therapeutic ketosis to get that continuing benefit on the brain in this context.

Bret Scher (00:45:10):

I think that’s well said. With that, I’ll put in a selfless plug that we have a number of videos on this topic, and especially that connection between epilepsy and mental health and ketogenic therapies at our Metabolic Mind YouTube channel.

Dominic D’Agostino (00:45:25):

What are some practical steps individuals can take to improve their metabolic health and in turn, positively impact? We’ve been talking largely about psychiatric disorders and bipolar, but through being a researcher and being a patient too, you have a knowledge and a broader context too. What are some actionable things that our listeners can do in regards to dietary approaches or metabolic-based approaches?

Iain Campbell (00:45:55):

I think you hear again and again when you speak to people with bipolar is the early morning is the worst time. It’s when you wake up and you’re faced with this state of depression and the state of depression is not really so much feeling sad, it’s like a state of physiological crisis that the body plunges into where people go into catatonic states of depression where they can’t move and there’s increased lactate in their blood. They feel like they’ve run a marathon even though they’ve not even moved an inch. It really is that state of complete physical exhaustion that happens for no apparent reason. It just comes over people during these episodes. It’s extremely, unfortunately, this makes people very hopeless because they can’t do.

(00:46:37):

Even if they have a family that they care about more than anything in the world or friends or a job, they can’t physically summon the energy to interact with it. It’s very discouraging for people. If anyone is experiencing that, I would say that I’ve been to that for many, many years and it took me a very, very long time to realize that metabolism was anything to do with that state. Now if I maintain ketosis, I don’t have to experience that state of physical exhaustion that happens. We’re still trying to understand why that happens and what this benefit provides. I think that for me, maintaining ketosis is something that is the only thing that’s ever turned the dial on that for me is these severe depressive episodes that I come out of them when I go into ketosis.

(00:47:20):

I’m also someone that like with epilepsy, has to stay on the diet. If I come off of it, I experience those suppressive episodes, so I need to maintain the diet over a long time. I think that ketosis, and like you’re saying, exercise are the one two punch that can make me, someone that’s functional, enable to do things I want to do and look after my family and do my job. If you can find that combination, I think it could be really helpful for people. I don’t recommend it until we have RCTs, and I would prefer people speak to their psychiatrist and a dietician and do this very carefully. Because we need to understand a lot more about this. For me personally, that has been what’s really helped, is the ketosis plus exercise for the depression, especially.

Dominic D’Agostino (00:48:02):

Iain, you stumbled upon this dietary therapy yourself, and then without the use of, from my understanding, a registered dietician or clinician, you just sort of started doing this yourself, more or less mean. Did you have an open communication with your doctor? Because I get so many emails and so many people email me or reach out to me where they’re just looking for resources. It brings up the next question. It’s like, how can healthcare professionals collaborate and ensure that this is where can people get help, essentially? I know you’re working on the metabolic mind front through education, advocacy and research, all three of those things. In addition to being a patient yourself, you’re at the forefront of this. What do we tell our listeners out there who may be dealing with this, where should they go?

Iain Campbell (00:49:02):

Basically, when I first learned about this, I did it to lose weight. I was experiencing suicidal depressions. I really was aware at a certain point that I wasn’t going to survive this condition much longer. I had a wife and a family and I wanted to do lots of things, and I realized this just wasn’t going to happen. I just told myself, at least I’m going to try and be as physically healthy as possible. This is my last go at this. I actually did an Atkins diet. I got the Atkins diet book, and I did a very strict version of it and I realized put me in ketosis. When I saw that the weight loss, I lost about 50, 60 pounds of weight. I saw that at the same time my psychiatric symptoms were going away, which to me was completely remarkable after trying this.

(00:49:42):

The resources I had available were just, it was really listening to your podcast and listening to your shows on Bulletproof Radio and all the person that was telling people about this for physical health. It was really affecting my brain as well. When I was reading your research, I was like, “Oh, this is to do with epilepsy and neurons and membrane potentials.” It really spoke to me as someone who researched bipolar disorder scientifically. At the time, I wish I could have done it with support from a psychiatry who understood metabolic psychiatry and these aspects of it.

(00:50:16):

I was very much doing it just for my physical health and also, experiencing these mental health benefits. What I’d love in the future is for people to get this feedback and as early as possible when someone’s having their first episode, maybe we can prevent a large course of the illness by introducing this early on, just like with some people with epilepsy. That’s my hope, including as someone who has kids that are susceptible to bipolar, is that we can put people on this as early as possible and potentially avoid the whole course of the illness. I think that would be the best possible outcome. I’m not sure how frequent that is in epilepsy, but I do know that it does happen.

Dominic D’Agostino (00:50:49):

I know it’s often overwhelming for people and families when parents reach out to me to prepare a ketogenic diet and put their child on it, and in some conditions they’re just averse to the high fat intake. Was that difficult for you and do you think in this particular patient population that it would be, I think we universally agree that we need to agree on a standardized ketogenic therapy. It’s like when you give a person a drug, you want to make sure that this drug is standardized. If there’s a clinical response and outcomes are measured, you could say that this particular therapy did this particular outcome. If you have a wide range of studies using modified Atkins, clinical diet, low glycemic index diet, I think it’s important to start with a universal ketogenic diet from there.

(00:51:45):

Can people do this themselves? I know there’s certain services that are coming online like Cook Keto, for example. I’m an advisor for them, but they’re not kicked off yet, looking for funding. That will actually make therapeutic clinical ketogenic diets where it could just go to your doorstep. It’s like having a drug delivery to your doorstep. Do you think that’s going to be super important or do you think it’s just education, education from the nutritional front along with monitoring, like continuous glucose monitoring so you can course correct and adjust your diet as you go?

Iain Campbell (00:52:19):

I totally agree. Having some standardization of the diet with epilepsy, like the Charlie Foundation type recommendations. I know that Bret’s work at Metabolic Mind is working towards having this outreach to patients like the Charlie Foundation with epilepsy. It’s making a huge impact already, and we’re seeing people experience the benefits. I think that having meal deliveries would be fantastic. One of the things about going into ketosis is that there is just like we were saying about exercise, the brain is flooded with these metabolites. When you add ketones into the brain, people can become mildly hypomanic in the transition. Chris Palmers talked about this for a long time and Georgia Ede.

(00:52:58):

We find in our pilot study, we could completely manage, we could avoid this by having a two-week or extended adaption period where we gradually introduce the diet. I think that it’d be really interesting to look at the delivery and like you said, the standardization to see what’s best for people with these mental health conditions and how can we do it the most safe way possible and the expertise of dieticians in these parts are Beth Zupec and Helen Grossi. People like this are just completely invaluable for their use of it in epilepsy.

Dominic D’Agostino (00:53:30):

Good points. Iain, maybe talk about the potential for pre-delivered, pre-made whole food ketogenic meals and the need for that, particularly in this community or like the general population. Is that a barrier to entry, I guess? Do you feel like that’s a barrier to entry for people to implement this and really the importance of having a standardized ketogenic therapy so we can make sense of the outcome measures for this?

Iain Campbell (00:54:01):

I definitely think so. Because a lot of the barrier to ketogenic diets, obviously people feel like it might cost more than their normal diet. We saw in our study very high levels of adherence, over 91% adherence as measured by daily ketone levels to the diet. That people are willing to this. People with bipolar when they experience the benefits you can bring, they are willing to stick with this. Just like in epilepsy, if you prefer the diet over seizures, it’s a very powerful motivator. Then still there’s times that people will fall off or they go to a family event and so forth. Having the ability to have pre-prepared meals and delivered meals and snacks and things they could take around, that I think would be a really powerful one.

(00:54:44):

I also want to mention it could be really impactful in low and middle-income countries where people can’t access psychiatric care. My friend, Nomeli, who I spoke to recently lives in Nigeria and she doesn’t have any mental healthcare access of any significant kind. It’s associated with cost and corruption in their government. If you could employ ketogenic diets in low and middle-income countries where the vast majority of people with bipolar live and are suffering much more than people in Western countries, this could be a really impactful intervention I think for people from low incomes in western countries and in low middle-income countries.

Dominic D’Agostino (00:55:24):

I think people in these countries really have no idea about metabolic psychiatry and the potential for dietary therapies to even impact this disorder or other psychiatric disorders, which leads to a lot of the education outreach you’re doing and advocacy. Maybe you could tell people about your efforts too, not only for doing clinical research, but also on the podcast front and creating an educational platform so people really have access to this. Just much like you finding a podcast on the ketogenic diet, me talking on Tim Ferriss or something. That’s maybe the way that we need to reach people. I know this podcast, like podcasts have been instrumental for Levels to get this message out on metabolic control and CGMs.

Iain Campbell (00:56:17):

Absolutely. None of this or none of my research certainly would’ve happened without your outreach and letting people know about ketosis. It wasn’t even something on my radar until you started doing the Tim Ferris interviews and the Bulletproof Radio and so forth. It really was something that I didn’t know could help me and I found about it through physical health. I thought it could help me improve my weight. Then all this came secondary to that. I felt like I just want to do what I can in my small way with my own podcast. I do a podcast called Bipolarcast with Matt Baszucki to bring patients on who want to share their experience. We’ve both shared our own diagnosis and our experience with keto, and we’ve got about 22 interviews now with patients and clinicians. We’re trying to make people aware that this is a possibility, because it’s not on the radar for many people at all.

(00:57:03):

This is made possible by the fellowship that the Baszucki Foundation has given me. This was through their experience with their own son having the same experience with bipolar and ketogenic diet and wanting to outreach. It’s really been a wonderful experience and we’ve started to do fundraisers for people on the podcast. We just got me a fundraising to do Georgia Ede’s ketogenic training course. We’re seeing that a lot of the people that are having this result also want to do their own bit to spread the word and training as dieticians, going back to university to get involved in research, trying to do anything they can. Because we’re like, “Oh, something is really working for us.” That’s not, unfortunately, the normal experience with bipolar disorder. It’s often a long journey of things not working well. People are excited and want to talk about it.

Dominic D’Agostino (00:57:47):

In addition to the podcast front and what you’re doing with Bipolarcast, creating an education platform, for example, where clinicians could get educational credits to further and advance their education on this front, I think that’s going to be instrumental. I look forward to talking to Georgia Ede soon about her program and how she’s working to advance it. Because we’re not going to make inroads until patients can know about it, but they really need a network of people who are knowledgeable on implementing these things to have that support network.

Iain Campbell (00:58:23):

If I could give a shout-out to a press work on Metabolic Mind, Bret is directing this organization to raise awareness about this. He’s really one of the first people to really put his name behind this with all his expertise in ketogenic diet metabolism and to say, this is something that could be really helpful. Like yourself raising awareness about ketogenic diet, I just can’t say enough how much is appreciated by people with mental health conditions. Because we haven’t had new treatments in over 50 years, really. We’ve had very few new treatments and those that are given to us, you have substantial metabolic side effects where you put on 20 or 30 pounds, for example. We need adjunct treatments and therapies that we can use to manage this and prevent this cardiometabolic risk. Metabolic Mind are reaching out to people through Bret’s work and through Bipolarcast we’re intervening patients to talk about what we’re seeing here.

Dominic D’Agostino (00:59:18):

The track record for drug treatment is abysmal. From what I’ve seen so far from your data and other datas emerging, it’s super encouraging to see this will be ultimately available as a therapy, as a choice, and for people to have those choices. Big props to Bret for putting his name behind this movement too, and being at the level that he was. I think we need more advocates like him, like you, and published research scientists, and also, the rare person that has that interplay between academia and influence with the media and stuff too. I think you need that dual thing to really move this, to advance the science application is going to be super important. Well, thank you for everything that you’re doing Iain on the research front, on the advocacy front. Maybe you could tell people, again, you’ve already mentioned it, but maybe you could tell people where they could find you, how they can contribute and how they can learn more about this.

Iain Campbell (01:00:16):

I have a Twitter account, Iain Campbell PhD. You can find Bipolarcast on YouTube if you search Bipolarcast or keto bipolar. Lots of interviews with patients. Metabolicmind.org has lots of information, videos by Bret about ketogenic diets for mental health. They’re fantastic and they’re a great resource if you’re looking into this for the first time.