Dr. Chris Palmer: Diet & Nutrition for Mental Health

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.240 | and I'm a professor of neurobiology and ophthalmology

00:00:13.180 | at Stanford School of Medicine.

00:00:15.020 | Today, my guest is Dr. Chris Palmer.

00:00:17.360 | Dr. Chris Palmer is a medical doctor specializing

00:00:19.900 | in psychiatry at Harvard Medical School.

00:00:22.440 | He is the world expert in the relationship

00:00:24.860 | between metabolic disorders and psychiatric disorders.

00:00:28.160 | He treats a variety of different conditions,

00:00:30.300 | including psychosis, including schizophrenia,

00:00:32.920 | as well as attention deficit hyperactivity disorder,

00:00:35.680 | obsessive compulsive disorder, anxiety disorders,

00:00:38.780 | and depression, among others.

00:00:41.160 | He is best known for understanding the relationship

00:00:43.620 | between how metabolism and these various disorders

00:00:46.520 | of the mind interact.

00:00:48.000 | And indeed, today he describes not only

00:00:50.240 | his own fascinating journey into the field of psychiatry,

00:00:53.520 | but also his clinical and research experience using diet,

00:00:57.760 | that is, different forms of nutrition

00:00:59.520 | in order to treat various psychiatric disorders.

00:01:02.440 | He describes some remarkable case studies

00:01:05.200 | of individuals and groups of people

00:01:07.440 | who have achieved tremendous relief

00:01:09.380 | from the types of psychiatric disorders

00:01:11.460 | that I just mentioned a few moments ago,

00:01:13.620 | as well as new and emerging themes

00:01:16.280 | as to how metabolism and the mind interact

00:01:19.280 | to control things like obesity.

00:01:21.160 | Indeed, he raises the hypothesis that perhaps obesity,

00:01:24.320 | in many cases, is the consequence of a brain dysfunction

00:01:27.840 | as opposed to the consequence of a metabolic dysfunction

00:01:30.760 | that then impacts the brain.

00:01:32.480 | During today's episode, he shares with us

00:01:34.800 | his overriding hypotheses about the critical roles

00:01:37.900 | that mitochondrial function and dysfunction

00:01:40.840 | play in mental health and mental illness,

00:01:43.400 | and how various particular types of diets,

00:01:46.200 | ranging from the ketogenic diet to modified ketogenic diet,

00:01:49.640 | and even just slight adjustments in carbohydrate intake,

00:01:52.720 | can be used in order to change mitochondrial function

00:01:56.420 | and bring relief for various psychiatric illnesses.

00:01:59.440 | He also highlights the essential and important theme

00:02:02.600 | that various diet interventions,

00:02:04.800 | including the ketogenic diet,

00:02:06.660 | were not first developed for sake of weight loss,

00:02:09.000 | but rather were developed as treatments

00:02:11.200 | for neurologic conditions such as epilepsy.

00:02:13.520 | Today, he shares with us how the foods that we eat

00:02:15.760 | alone end in combination, and how fasting,

00:02:19.160 | both intermittent fasting and more lengthy fasts,

00:02:22.360 | can interact with the way that our brain functions

00:02:25.000 | to strongly control the way that we think, feel, and behave.

00:02:28.720 | What's wonderful is that Dr. Palmer

00:02:30.240 | not only explains the science and his clinical expertise,

00:02:33.200 | but also points to various actionable measures

00:02:35.520 | that people can take in order to improve

00:02:37.720 | their mental health.

00:02:38.840 | I'd like to mention that Dr. Palmer

00:02:40.320 | is also the author of a terrific new book.

00:02:42.740 | The title is "Brain Energy, a Revolutionary Breakthrough

00:02:45.720 | "in Understanding Mental Health

00:02:47.080 | "and Improving Treatment for Anxiety, Depression,

00:02:49.840 | "OCD, PTSD, and More."

00:02:52.620 | I've read the book and it is a terrific read.

00:02:55.140 | I came away from this book with a much evolved understanding

00:02:58.920 | of how the various psychiatric disorders

00:03:00.900 | that I just described, as well as ADHD, emerge in people.

00:03:04.480 | And it has completely revised my understanding

00:03:06.800 | about the possible origins of various psychiatric disorders

00:03:09.640 | and the best ways to treat them,

00:03:11.400 | including both with medications,

00:03:13.480 | but also with nutritional approaches.

00:03:16.100 | If you'd like to learn more about Dr. Palmer's work

00:03:18.280 | and the book, please go to chrispalmermd.com.

00:03:22.200 | We also provide links to the book

00:03:24.080 | and to his website in our show note captions.

00:03:26.280 | Before we begin, I'd like to emphasize that this podcast

00:03:28.880 | is separate from my teaching and research roles at Stanford.

00:03:31.800 | It is, however, part of my desire and effort

00:03:33.720 | to bring zero cost to consumer information

00:03:35.560 | about science and science-related tools

00:03:37.620 | for the general public.

00:03:38.960 | In keeping with that theme,

00:03:40.040 | I'd like to thank the sponsors of today's podcast.

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00:07:15.960 | And now for my discussion with Dr. Chris Palmer.

00:07:19.320 | Chris, Dr. Palmer, thank you for being here.

00:07:21.800 | - Thank you, Andrew, for having me.

00:07:23.480 | - I have a lot of questions for you,

00:07:25.520 | and I'm really excited about this topic

00:07:27.080 | because I think most people know what mental illness is,

00:07:30.940 | or they have some idea what that is.

00:07:32.560 | Most people have some idea what nutrition is.

00:07:35.460 | Fewer people certainly know how closely

00:07:39.780 | those things can interact.

00:07:42.500 | And I think everybody is familiar with the feeling

00:07:46.300 | of a food or the ingestion of a food,

00:07:48.640 | making them feel good in the short term.

00:07:51.380 | And we eat a food that tastes delicious to us

00:07:53.100 | or that we associate with something nice

00:07:55.240 | and we feel good mentally and physically.

00:07:58.180 | Whereas when we eat something that gives us food poisoning

00:08:01.220 | or maybe even something that just doesn't taste that great

00:08:03.320 | or that we associate with a bad experience,

00:08:05.880 | we feel less good in the short term.

00:08:07.900 | But I believe that very few people understand

00:08:12.260 | or are familiar with the fact that nutrition

00:08:16.000 | and our mental health interact in this very intimate,

00:08:20.260 | maybe even causal way.

00:08:21.700 | And that is something that occurs

00:08:24.320 | over long periods of time.

00:08:25.760 | Meaning what I ate yesterday, the day before,

00:08:28.000 | maybe even 10 years ago could be impacting the way

00:08:31.280 | that my brain and body are making me feel now.

00:08:34.240 | So if you would, I'd love for you to just tell us

00:08:36.600 | about a little bit of the history,

00:08:38.960 | in particular your history with exploring the relationship

00:08:42.000 | between nutrition and mental health.

00:08:44.680 | And then we can dive into some of the more particulars

00:08:48.040 | of ketogenic diets versus other diets

00:08:50.540 | and some of the truly miraculous findings

00:08:53.960 | that you and others are coming up with

00:08:58.000 | based on real patients and real experiences of people

00:09:01.360 | who suffer and then find relief

00:09:03.480 | by altering their nutrition.

00:09:05.280 | - Sure.

00:09:06.120 | This story really starts with my own personal story.

00:09:11.840 | And I don't need to go into great detail,

00:09:16.240 | but to set the stage, when I was a kid,

00:09:20.040 | I definitely had mental illness.

00:09:22.520 | Started with OCD, a series of events happened in my family.

00:09:27.320 | My mother had a horrible kind of psychotic break

00:09:30.740 | and all sorts of adverse childhood events for me.

00:09:35.960 | She and I were actually homeless together for a while.

00:09:38.840 | I went on to have subsequent depression,

00:09:43.880 | suicidality, all sorts of things.

00:09:46.840 | But somehow or another, I pulled myself together

00:09:50.040 | and got through medical school,

00:09:51.800 | actually did quite well in medical school,

00:09:54.100 | got an award for being one of the top students,

00:09:57.480 | and then was doing my internship and residency at Harvard.

00:10:02.320 | And at that point in time,

00:10:06.820 | I was diagnosed with metabolic syndrome.

00:10:09.120 | So I had high blood pressure, horrible lipids,

00:10:14.480 | and prediabetes.

00:10:16.020 | And I was doing everything right, supposedly.

00:10:18.700 | I was on a low-fat diet and I was exercising regularly.

00:10:23.520 | And year after year,

00:10:24.400 | my doctor kept telling me diet and exercise.

00:10:27.400 | I kept asking him what diet, what exercise.

00:10:30.580 | I was doing everything he kept telling me to do.

00:10:33.380 | Everything was getting worse.

00:10:34.560 | My blood pressure kept going higher.

00:10:36.320 | And at some point, he kind of said,

00:10:41.420 | you're gonna have to go on medication.

00:10:43.960 | I need to put you on something for your prediabetes,

00:10:46.120 | something for your cholesterol,

00:10:47.380 | and something for your blood pressure.

00:10:49.640 | So three pills out of the gate.

00:10:51.880 | And I'm like, I'm only in my 20s.

00:10:53.360 | - Were you overweight?

00:10:54.400 | - No, technically no.

00:10:56.640 | I had a gut, so that's a sign of insulin resistance.

00:11:01.600 | I know now, I didn't know it then.

00:11:03.920 | And he actually kind of leaned in at one point and said,

00:11:10.560 | do your parents have diabetes?

00:11:14.160 | Yeah, do your parents have high blood pressure?

00:11:16.280 | Yeah, are your parents overweight?

00:11:19.000 | Yeah, oh, I'm really sorry, it's genetic.

00:11:23.480 | Basically, you're screwed.

00:11:25.400 | It's your genes.

00:11:26.760 | You're just gonna have to bite the bullet and take meds.

00:11:30.600 | And as a physician, I knew what that meant.

00:11:33.920 | I knew that I'm in my 20s.

00:11:35.760 | If I'm already on three meds for metabolic syndrome,

00:11:39.480 | I'm gonna be screwed by the time I'm 40 or 50,

00:11:42.280 | and I'm probably gonna be having heart attacks.

00:11:45.120 | And I'd heard through the rumor mill

00:11:49.400 | that the Atkins diet could somehow help people

00:11:54.400 | improve their cholesterol and pre-diabetes.

00:11:57.440 | I actually didn't really believe it.

00:12:00.000 | I was highly skeptical.

00:12:01.400 | And I believed everything I was taught in medical school.

00:12:04.720 | Why would my professors lie to me

00:12:07.520 | that they knew what they were talking about?

00:12:09.280 | Low-fat diet was the thing to do.

00:12:11.640 | And the Atkins diet was clearly dangerous and reckless.

00:12:15.280 | And, but I had been trying the medical dogma for years

00:12:20.280 | and it wasn't working for me.

00:12:22.640 | And so for whatever reason,

00:12:23.920 | I decided this is gonna be my last attempt

00:12:27.320 | at something different.

00:12:29.320 | And then I'll just bite the bullet and go on meds.

00:12:32.840 | So I tried the Atkins diet.

00:12:34.760 | I did my own special version of it.

00:12:37.600 | I still avoided red meat

00:12:39.080 | 'cause I was terrified of red meat.

00:12:41.040 | I tried to do a healthy version,

00:12:44.760 | which it's probably more like the South Beach diet.

00:12:47.600 | This was before the South Beach diet was invented.

00:12:50.360 | But within three months,

00:12:53.000 | my metabolic syndrome was completely gone.

00:12:55.680 | - So blood pressure normalized, lipids normalized.

00:12:59.780 | Did your weight change?

00:13:00.880 | Or you mentioned that you were of healthy weight,

00:13:02.800 | but that you had a bit of abdominal fat.

00:13:05.760 | - So I lost the abdominal fat.

00:13:07.680 | I probably lost about 10 pounds through this process.

00:13:12.480 | And, but everything got normal.

00:13:15.160 | And when I went back to my doctor, he was shocked.

00:13:17.720 | He actually said, "What the hell are you doing?"

00:13:19.760 | - During the time before you switched to this new diet,

00:13:23.480 | how was your mental health, if you don't mind me asking?

00:13:25.720 | Because it sounded like you're very clear

00:13:28.080 | that there was metabolic syndrome

00:13:29.880 | or you were headed towards more severe metabolic syndrome.

00:13:32.320 | You mentioned OCD.

00:13:34.040 | I actually am familiar with this.

00:13:35.580 | As a kid, I had a low level kind of Tourette's grunt

00:13:39.260 | and probably obsessive still to some extent,

00:13:43.160 | although not full-blown clinically diagnosed OCD.

00:13:46.120 | So I can relate somewhat if you're willing.

00:13:49.500 | But what was the context of all that

00:13:52.460 | before and after this nutritional switch?

00:13:55.100 | - So before the nutritional switch,

00:14:00.400 | I was still struggling with low-grade depression and OCD.

00:14:05.400 | I, again, it wasn't necessarily interfering

00:14:10.400 | with my ability to function

00:14:13.480 | 'cause I was functioning at a high level.

00:14:16.000 | I mean, anybody looking from the outside,

00:14:18.440 | you're a top student.

00:14:19.360 | You just got into one of the most competitive,

00:14:21.440 | actually at that point,

00:14:22.280 | it was the most competitive residency program

00:14:25.120 | in the country for psychiatry.

00:14:27.200 | So they would have looked at me and said, "You're fine."

00:14:29.600 | But I wasn't, I was actually on medications.

00:14:32.440 | I was trying different medications, trying to figure out

00:14:35.880 | how to feel better, how to stop obsessing so much,

00:14:39.920 | how to not be so depressed.

00:14:42.200 | And I found that those medications,

00:14:44.800 | they actually came with more side effects for me

00:14:50.400 | than benefits.

00:14:52.400 | I was on Prozac for a long time.

00:14:54.200 | It totally messed up my sleep.

00:14:56.640 | And then the psychiatrist was like,

00:14:57.840 | "You need pills to help you sleep now."

00:15:00.200 | And I'm like, that's not really resonating very well with me

00:15:05.000 | and I'm now a psychiatrist, I'm in my psychiatry residency.

00:15:08.440 | And I'm thinking, you know what?

00:15:10.440 | That's just not sitting well with me,

00:15:13.160 | that you're gonna prescribe more and more meds

00:15:15.400 | for all the side effects that you're causing.

00:15:18.320 | And yet at the same time, I wanted to feel better.

00:15:20.320 | And I was learning chemical imbalances.

00:15:23.440 | This is what we do to get rid of depression and OCD.

00:15:26.400 | You're supposed to take your pills and so on and so forth.

00:15:29.160 | Take your pills and so I was taking my pills.

00:15:31.920 | I was in psychotherapy.

00:15:33.320 | I had been in psychotherapy on and off for years.

00:15:36.360 | I had received much more intensive treatment

00:15:39.720 | when I was younger and that was essentially worthless for me.

00:15:44.280 | It actually probably just caused harm at the end of the day.

00:15:48.120 | - Psychoanalysis?

00:15:49.280 | - Various psychotherapies, not psychoanalysis per se,

00:15:54.280 | but some of them were psychoanalytically oriented.

00:15:57.240 | Psychotherapies, I was actually hospitalized at one point,

00:16:00.720 | had been put on lithium and imipramine,

00:16:06.440 | which is a tricyclic antidepressant and other things.

00:16:10.280 | And they were actually horrible.

00:16:14.040 | They were horrible.

00:16:14.880 | They did nothing beneficial for me.

00:16:17.480 | I gave them a decent amount of time to work.

00:16:21.040 | I really wanted to feel better.

00:16:25.360 | So at the time that I tried this diet,

00:16:28.120 | I certainly wasn't impaired in the same way.

00:16:31.480 | I wasn't struggling that much,

00:16:33.480 | but I still have these low grade symptoms,

00:16:36.040 | was trying to feel better.

00:16:37.320 | And the thing that was the most striking to me

00:16:43.320 | after doing the diet for three months

00:16:45.880 | was not the fact that my metabolic syndrome was gone.

00:16:48.760 | That was my goal and it was a seemingly miraculous

00:16:54.040 | achievement because I got rid of everything

00:16:57.320 | with one dietary change.

00:16:59.720 | But the thing that I noticed was dramatic improvement

00:17:02.720 | in my mood, energy, concentration, and sleep.

00:17:06.440 | For the first time in my life,

00:17:10.600 | I started waking up before my alarm went off

00:17:13.360 | and feeling rested.

00:17:15.360 | That never happened to me before.

00:17:17.480 | I was meticulous about planning when my alarm went off

00:17:22.160 | and how many times I could push the snooze button

00:17:25.680 | in order to be on time for wherever I needed to be,

00:17:29.240 | whether it was school or the hospital or whatever.

00:17:32.280 | I had a good system.

00:17:36.120 | I was never late for anything,

00:17:38.360 | but that was shocking to me that I felt so good.

00:17:43.360 | And one of the things that I've often said to people,

00:17:49.320 | prior to the diet, I always felt like there are two types

00:17:53.320 | of people in the world.

00:17:54.480 | There are haves and have nots.

00:17:56.440 | There are these happy peppy people who just are so positive

00:18:01.360 | and they've got energy and they have this saying,

00:18:04.800 | they like to work hard and play hard.

00:18:06.960 | And I always understood working hard.

00:18:11.040 | I totally got that 'cause I was a hard worker

00:18:13.200 | and I understood the value of hard work

00:18:15.160 | and that you gotta do something useful with yourself.

00:18:19.120 | But I never understood who the hell wants to play hard?

00:18:23.520 | Like who's got energy for that?

00:18:25.240 | Like, aren't you tired from working so hard?

00:18:27.800 | How on earth do these people have energy

00:18:30.960 | to go and play hard?

00:18:32.760 | And I assumed that they were just part of the haves

00:18:38.080 | in the world and they were just lucky and privileged.

00:18:41.960 | They either had good genetics

00:18:44.240 | or maybe they had good childhoods or good parents

00:18:48.240 | or something, something that I didn't have.

00:18:50.760 | - The kids with genuine smiles in the yearbooks.

00:18:53.240 | - Yes, exactly.

00:18:55.280 | - Whereas the rest, and by the way,

00:18:58.700 | I really appreciate you sharing some of your personal story

00:19:02.420 | because I think it is very important for people to hear

00:19:07.160 | and understand that people like yourself

00:19:09.380 | who are extremely high functioning and accomplished,

00:19:12.280 | that the road was, from everything I'm hearing

00:19:16.920 | and understanding, very choppy internally at times,

00:19:20.860 | and that you've overcome a lot in order to get there.

00:19:23.000 | And also, I've been going through what sounds like

00:19:25.940 | a very long iterative process of trying to figure out

00:19:28.680 | what works and what doesn't work

00:19:30.000 | to finally arrive at a solution

00:19:32.200 | and then make that the basis of much of the work

00:19:35.180 | that you're doing today for other people.

00:19:36.880 | I think it's very important because I think many people

00:19:39.720 | share with you this notion that there are indeed two groups,

00:19:44.720 | a happy group and then fated to be unhappy group.

00:19:48.060 | And it speaks to the fact that,

00:19:52.240 | your story rather, speaks to the fact that

00:19:54.640 | what we see is not always what's going on internally

00:19:57.260 | with people and that this notion of there just being

00:20:01.400 | two groups, the happy or the haves and the have nots,

00:20:04.400 | can't be the way that it works.

00:20:07.080 | And there are probably many more people suffering

00:20:09.440 | than we realize, and that there is an important need

00:20:13.200 | for tools to overcome that suffering.

00:20:15.800 | So I really just hear even early in our discussion,

00:20:18.600 | I just want to extend a genuine thanks

00:20:20.400 | because so much of what I hear from people is,

00:20:23.620 | questions about health and mental health

00:20:26.360 | and physical health, but that clearly point to the fact

00:20:29.480 | that many people are struggling to varying degrees.

00:20:32.280 | And even the people who are in this category

00:20:34.100 | of great childhood and happiness could do far better

00:20:38.340 | for themselves and then also for other people.

00:20:40.740 | So thank you for that.

00:20:42.580 | I want to know at the point where you realized

00:20:47.440 | that nutrition can play a profound role in how you feel

00:20:51.260 | and operate in a large number of domains,

00:20:54.120 | you were still a student or a resident at that point?

00:20:57.260 | - I was a resident.

00:20:59.060 | - At that point, did you decide that you were going

00:21:00.940 | to explore this in a professional context?

00:21:04.140 | - Not yet.

00:21:04.980 | - Okay, so what was the journey forward

00:21:07.260 | into the work that you're doing now?

00:21:10.340 | - So the next step was that I just had friends and family

00:21:15.340 | who saw me, saw that I had improved my health,

00:21:19.660 | saw that I lost some weight pretty easily.

00:21:22.220 | In particular, I remember like my sister and sister-in-law,

00:21:26.160 | they got really pissed at me one Thanksgiving

00:21:28.940 | because I could resist all the pumpkin pie

00:21:31.340 | and apple pie and everything else.

00:21:33.180 | They were like, how the hell are you doing that?

00:21:34.900 | How are you resisting all of this food?

00:21:37.620 | I said, I don't crave it anymore.

00:21:39.180 | I don't want it, I'm fine.

00:21:40.620 | I'm just, I'm having turkey and green beans

00:21:42.900 | and that's good enough for me.

00:21:44.500 | So I got them to do the diet

00:21:47.600 | and they too noticed dramatic improvement in their moods

00:21:50.820 | and energy and sleep and everything else.

00:21:54.120 | So within a few years,

00:21:55.960 | the primary thing I noticed

00:22:01.040 | is this powerful antidepressant effect.

00:22:04.800 | And now I'm, you know, an attending physician.

00:22:08.800 | I've got all these patients in my clinical practice

00:22:11.200 | with treatment resistant mental illness.

00:22:13.000 | I'm in a tertiary care hospital.

00:22:15.280 | So I almost never get somebody off the street

00:22:19.120 | with their first episode of depression.

00:22:21.640 | Out of the gate as part of my career,

00:22:24.120 | I get treatment resistant mental disorders.

00:22:26.440 | So I get people who've already been

00:22:28.100 | to six plus psychiatrists, therapists.

00:22:31.280 | They've usually tried dozens of different medications.

00:22:34.240 | They've been in decades of psychotherapy.

00:22:36.800 | They've often had ECT and other things

00:22:39.980 | and nothing's working.

00:22:41.800 | And I'm thinking, you know, well,

00:22:43.000 | we're kind of out of options for these other people

00:22:45.560 | and this diet is having this really powerful

00:22:47.980 | antidepressant effect.

00:22:49.840 | I think I'm gonna try it

00:22:50.960 | and just see if any of my patients are game to try it,

00:22:53.900 | to see if it might help them.

00:22:56.560 | Sure enough, it did.

00:22:58.920 | Didn't help everyone and not everybody was interested

00:23:01.800 | and/or able to do it.

00:23:04.040 | But some of the ones who were able to do it

00:23:07.140 | ended up having a remarkable

00:23:09.160 | and powerful antidepressant effect.

00:23:11.540 | One woman actually became hypomanic within a month

00:23:14.880 | and she had been depressed pretty much nonstop

00:23:18.400 | for over five years, chronically depressed,

00:23:20.840 | suicidal, in and out of hospitals.

00:23:23.800 | And I saw her become hypomanic and I'm thinking, wow,

00:23:26.160 | this really is a powerful antidepressant effect.

00:23:29.080 | Like this is amazing.

00:23:30.600 | This is like a medication,

00:23:32.280 | but better because it actually is working for her.

00:23:35.460 | But I laid low at that point,

00:23:40.420 | because at that point we didn't have many clinical trials

00:23:44.360 | of the safety or efficacy of the Atkins diet

00:23:47.280 | for even weight loss or diabetes,

00:23:49.920 | let alone any mental disorders.

00:23:51.880 | And so I really actually felt like I'm on the fringe here

00:23:54.640 | and this is not going to be met with praise by anyone.

00:23:59.640 | So I'm just going to lay low.

00:24:01.800 | I'm going to offer it to patients.

00:24:04.280 | And I went along that way up until 2016.

00:24:09.280 | - And may just ask about the diet.

00:24:14.240 | When you say Atkins diet, so this is low to zero starch.

00:24:19.240 | So low carbohydrate diet, certainly low sugar.

00:24:23.840 | - Yeah.

00:24:25.200 | - And was it traditional Atkins?

00:24:28.240 | Were you tailoring it to the individual patient,

00:24:30.680 | depending on their psychiatric symptoms,

00:24:33.920 | whether or not they were overweight or not overweight?

00:24:36.800 | I'm assuming you're not a nutritionist.

00:24:38.240 | So how did you prescribe a nutrition plan for your patients

00:24:43.240 | and what was involved in making sure

00:24:45.760 | that they adhered to that?

00:24:47.160 | Maybe even some of the things you observed in terms

00:24:50.280 | of who was more willing to try this or not try this.

00:24:53.480 | Any observations or maybe even data.

00:24:56.560 | - So early on I was winging it and I was, you know,

00:24:59.960 | the first few patients, it was try this Atkins diet.

00:25:04.140 | I want to see ketosis.

00:25:05.400 | So I was going for ketones.

00:25:07.920 | - So they were pricking their finger

00:25:09.160 | and they were doing a blood ketone test.

00:25:11.420 | - I didn't know about blood ketone monitors

00:25:15.120 | if they existed back then.

00:25:16.560 | So I was, we were using urine strips.

00:25:18.840 | - Which are not quite as accurate,

00:25:20.500 | but still useful as a general guide from what I understand.

00:25:23.160 | Is that right?

00:25:24.000 | - Absolutely.

00:25:25.160 | And so I was strongly recommending

00:25:30.080 | that patients achieve urinary ketosis.

00:25:34.160 | And the interesting thing is I noticed a pattern

00:25:37.440 | that when they were trying the diet and not getting ketones,

00:25:40.460 | they often did not get a clinical benefit.

00:25:43.320 | It was once they got into ketosis

00:25:45.520 | that I began to notice the clinical benefit

00:25:47.960 | and the powerful antidepressant effect.

00:25:52.080 | So probably any nutrition plan, aka diet,

00:25:57.080 | that elevated ketones in the urine

00:26:01.000 | to the point where you would say this person is in ketosis,

00:26:04.540 | where they would say I'm in ketosis.

00:26:06.560 | That was a step in the right direction,

00:26:08.860 | independent of like exactly what they were eating

00:26:12.420 | or not eating to get there, including fasting.

00:26:16.120 | At that time, probably fasting wasn't as popular.

00:26:18.280 | Now, thanks to the incredible work,

00:26:20.720 | I think it's incredible and he is a former colleague.

00:26:22.920 | And I know there's a lot of controversy about fasting,

00:26:25.000 | but I think for many people, fasting is a powerful tool.

00:26:27.160 | For others, it's a less useful tool,

00:26:29.360 | but of Sachin Panda and others.

00:26:32.400 | But fasting certainly will limit your carbohydrate intake

00:26:37.000 | and get you into ketosis, correct?

00:26:38.720 | - It will.

00:26:39.560 | - Did you have any patients fast

00:26:41.000 | or do intermittent fasting?

00:26:42.380 | - I did.

00:26:43.960 | So, and I had some patients

00:26:47.120 | who did what Atkins had called a fat fast,

00:26:50.880 | where they eat primarily fat.

00:26:53.660 | So they either fast and/or they eat primarily fats

00:26:57.020 | to try to get into a state of ketosis.

00:27:00.080 | So for some patients,

00:27:00.960 | it was actually quite easy to get into ketosis,

00:27:03.080 | especially overweight and obese patients.

00:27:06.600 | They have a lot of fat stores on their body

00:27:08.520 | and actually limiting carbohydrates usually results

00:27:12.080 | in high levels of ketosis for them.

00:27:14.720 | - And they probably feel better too, I imagine,

00:27:16.560 | because when we limit our starch intake,

00:27:19.280 | we start to excrete a lot of water.

00:27:20.680 | People can get some pretty quick weight loss

00:27:24.180 | that even though it may not be fat loss,

00:27:26.120 | makes them feel literally a little lighter

00:27:28.140 | and maybe a little more energetic.

00:27:29.600 | Is that right? - Absolutely.

00:27:32.140 | And as the years went on,

00:27:36.760 | the field was advancing, more research was coming out.

00:27:40.340 | People were getting a little more sophisticated

00:27:43.260 | with blood ketone monitoring, with different versions

00:27:46.640 | of ketogenic diets, and I was evolving my practice.

00:27:51.640 | The thing that completely upended everything

00:27:58.400 | that I knew as a psychiatrist though

00:28:00.280 | was when I helped a patient in 2016 lose weight.

00:28:04.720 | So this was a patient, 33-year-old man

00:28:08.160 | with schizoaffective disorder.

00:28:10.300 | He had been my patient for eight years now.

00:28:12.040 | Could you clarify for people with schizoaffective disorders?

00:28:14.820 | I'm not a clinician, but as I recall,

00:28:16.300 | it's like a low level of schizophrenia.

00:28:20.100 | So there might be some auditory hallucinations.

00:28:22.100 | If I met this person, I might think they're kind of different

00:28:24.580 | quote unquote weird, but they would not seem necessarily

00:28:29.300 | at the scary to me and typically to other people.

00:28:34.300 | And I mean that with respect, of course,

00:28:38.000 | but oftentimes people with schizophrenia can seem

00:28:39.700 | just like you don't even know how to interact with them

00:28:42.200 | because their world seems so altered

00:28:43.900 | because they have all these so-called positive symptoms,

00:28:47.180 | hallucinations, and they're talking to people

00:28:49.080 | that no one else can see, et cetera.

00:28:50.420 | Is that schizoaffective?

00:28:52.500 | - So no, actually.

00:28:53.660 | So schizoaffective is the same as schizophrenia, essentially.

00:28:57.560 | The only difference is it's schizophrenia

00:28:59.620 | with superimposed mood episodes.

00:29:01.800 | - Oh, so it's actually more severe than-

00:29:03.700 | - It can be.

00:29:04.560 | - Okay, so I have it backwards.

00:29:05.880 | - So schizoaffective disorder is essentially schizophrenia

00:29:10.440 | plus some mood episodes.

00:29:11.960 | - Maybe I'm thinking of schizotypal.

00:29:13.840 | - Schizotypal is the low grade kind of mild paranoia

00:29:18.520 | or kind of eccentric beliefs and other things.

00:29:21.880 | - Okay, so folks out there,

00:29:23.640 | I have my nomenclature backwards.

00:29:25.080 | Schizotypal is the quote unquote low level schizophrenia

00:29:29.000 | or schizoid-like.

00:29:31.400 | Schizoaffective is as or more-

00:29:34.000 | - Full blown schizophrenia plus full blown,

00:29:36.560 | usually bipolar symptoms.

00:29:37.800 | - And now it's absolutely clear

00:29:38.920 | who the clinician in the room is.

00:29:41.240 | Thank you for that reminder.

00:29:43.240 | - No worries.

00:29:44.060 | So this man had schizoaffective disorder.

00:29:47.600 | He had daily auditory hallucinations.

00:29:51.640 | He had paranoid delusions.

00:29:53.800 | He could not go out in public without being terrified.

00:29:56.900 | He was convinced that there were these powerful families,

00:30:02.400 | that they had technologies that could control his thoughts.

00:30:05.160 | They could broadcast his thoughts to other people.

00:30:07.560 | They were trying to hurt him.

00:30:08.920 | They had targeted him for some reason.

00:30:11.200 | He wasn't quite sure why.

00:30:12.640 | He had some suspicions and beliefs about

00:30:15.560 | maybe when he did this bad thing when he was 11 years old,

00:30:19.680 | that's why they decided to target him.

00:30:22.040 | This man was tormented by his illness.

00:30:25.760 | Tormented, it ruined his life.

00:30:28.280 | He had already tried 17 different medications

00:30:31.040 | and none of them stopped his symptoms,

00:30:33.480 | but they did cause him to gain a lot of weight.

00:30:35.360 | - These are the medications, as I recall,

00:30:37.840 | for schizophrenia that classical ones

00:30:39.840 | are dopamine receptor blockers,

00:30:42.100 | cause people to huge increases in prolactin.

00:30:45.520 | That's why sometimes men will get breast development

00:30:47.840 | and they'll put on a lot of weight

00:30:49.280 | and they'll be catatonic or movement disorders.

00:30:52.520 | They make you feel like,

00:30:53.960 | I have to imagine given how good

00:30:56.600 | most things that release dopamine make us feel

00:30:58.640 | that blocking dopamine receptors with antipsychotics

00:31:01.840 | makes people feel lousy.

00:31:03.960 | - Horrible.

00:31:05.280 | And it's a huge challenge in our field

00:31:08.880 | because a lot of patients don't want to take them.

00:31:11.440 | And then you get these rebound effects.

00:31:14.060 | If patients are on them for several months

00:31:16.240 | and then they stop them cold turkey,

00:31:18.040 | they can get wildly psychotic and ill,

00:31:20.780 | end up aggressive or hospitalized or sometimes dead.

00:31:27.160 | So that's him, he weighs 340 pounds.

00:31:32.160 | And for whatever reason, he gets it in his head,

00:31:35.320 | I'm never gonna get a girlfriend if I don't lose some weight.

00:31:38.320 | He also recognizes I'm never gonna get a girlfriend

00:31:42.380 | cause I'm a loser, I'm schizophrenic,

00:31:44.520 | I live with my father, I have nothing going for me,

00:31:48.240 | but I could at least try to address

00:31:51.560 | one of these awful, horrible things about myself

00:31:55.260 | and maybe I could lose some weight.

00:31:57.100 | So he asked for my help.

00:31:58.360 | For a variety of reasons, we ended up deciding

00:32:01.620 | to try the ketogenic diet.

00:32:03.700 | Now at this point, I have no anticipation

00:32:08.280 | that the ketogenic diet is gonna do anything

00:32:10.400 | for his psychiatric symptoms.

00:32:12.600 | Because this man has schizoaffective disorder,

00:32:14.540 | that's not depression.

00:32:16.000 | Depression is very different,

00:32:17.540 | they're totally different disorders.

00:32:19.340 | So he decides to give it a try.

00:32:24.500 | Within two weeks, not only does he start losing weight,

00:32:27.800 | but I begin to notice this dramatic antidepressant effect.

00:32:32.280 | He's making better eye contact, he's smiling more,

00:32:35.360 | he's talking a lot more.

00:32:37.300 | I'm thinking like, what's gotten into you?

00:32:38.820 | Like you're coming to life,

00:32:40.640 | I've never heard you talk this much,

00:32:42.040 | I've never seen you so excited or present or alive.

00:32:47.040 | I haven't changed his meds at all.

00:32:49.120 | The thing that upended everything

00:32:53.360 | that I knew as a psychiatrist was six to eight weeks in,

00:32:57.600 | he spontaneously starts reporting,

00:32:59.820 | you know those voices that I hear all the time?

00:33:02.840 | They're going away.

00:33:04.020 | And he says, you know how I always thought

00:33:07.960 | that there were all these families

00:33:09.240 | who were controlling my thoughts and out to get me

00:33:11.920 | and they had targeted me?

00:33:13.100 | And I'm thinking, oh yeah,

00:33:15.320 | we've been talking about that for eight years,

00:33:16.620 | we can talk about that again.

00:33:18.440 | He says, you know what?

00:33:22.960 | Now that I think about it, I don't think that's true.

00:33:26.360 | And now that I say it, it sounds kind of crazy.

00:33:28.280 | It probably never was.

00:33:30.100 | I've probably had schizophrenia all along

00:33:33.660 | like everybody's been trying to tell me.

00:33:35.660 | And I think it's going away.

00:33:38.680 | That man went on, he's now lost 160 pounds

00:33:44.600 | and kept it off to this day.

00:33:46.080 | - Wow.

00:33:47.400 | - He was able to do things he had not been able to do

00:33:50.600 | since the time of his diagnosis.

00:33:52.220 | He was able to complete a certificate program.

00:33:54.760 | He was able to go out in public and not be paranoid.

00:33:58.060 | He performed improv in front of a live audience.

00:34:01.660 | At one point, he was able to move out of his father's home

00:34:04.900 | and live independently.

00:34:07.560 | And that completely blew my mind as a psychiatrist.

00:34:12.560 | And I went on a scientific journey to understand

00:34:18.660 | what in the hell just happened.

00:34:20.800 | - That is indeed mind blowing.

00:34:23.100 | - I'd like to take a quick break

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00:35:37.480 | - I have a couple of questions.

00:35:39.080 | First of all, did he stay on any kind of antipsychotic

00:35:42.840 | or other medication?

00:35:45.400 | If so, were the dosages adjusted, excuse me,

00:35:48.920 | while undergoing this remarkable transition?

00:35:53.280 | Because as we know, it's not an either/or medication

00:35:55.900 | or nutrition changes, it can be both.

00:35:59.760 | And then the other question is one of adherence.

00:36:03.120 | I think about someone with schizoaffective disorder

00:36:05.720 | who's suffering from all the sorts of things

00:36:08.320 | that you described.

00:36:09.280 | How does somebody like that organize themselves

00:36:12.460 | in order to stay on a ketogenic diet?

00:36:15.200 | And I say this with all the seriousness in the world.

00:36:17.880 | I think there are a lot of people who do not have

00:36:20.680 | schizotype or schizoaffective disorder who have trouble,

00:36:24.460 | they claim, adhering to a ketogenic diet.

00:36:29.460 | It's not the easiest diet, certainly in its extreme form.

00:36:33.760 | At first, it's not the easiest diet to stick to.

00:36:37.060 | So how did he do it?

00:36:39.380 | This sounds like a remarkable individual.

00:36:41.900 | And I'd also like to just know your general thoughts

00:36:44.320 | about adherence to things when people are back

00:36:48.700 | on their heels mentally, how do they get motivated

00:36:52.040 | and stick to something?

00:36:53.640 | So the questions were medication, yes or no.

00:36:56.080 | If yes, dosage adjusted, yes or no.

00:36:59.440 | And if people are suffering from depression

00:37:03.300 | or full-blown psychotic episodes,

00:37:05.300 | how does one ensure that they continue to adhere to a diet?

00:37:10.340 | - So in terms of medications, he has remained on medication.

00:37:15.340 | So early on, I wasn't adjusting anything.

00:37:18.660 | I was just in disbelief and shocked that this was happening.

00:37:22.260 | I didn't know what was going on.

00:37:24.840 | Over the years, we have slowly but surely

00:37:27.740 | tried to taper him off his meds.

00:37:29.940 | He has been on meds for decades.

00:37:33.100 | He started medications when he was a young child.

00:37:36.660 | His brain has developed in response

00:37:41.660 | to all sorts of psychiatric medications.

00:37:46.300 | And it has not been easy to try to get him off.

00:37:49.400 | So we continue to try to get him off medication

00:37:52.740 | and it's challenging and difficult.

00:37:55.980 | And I just wanna say for any listeners,

00:37:58.580 | it is getting off your meds is very difficult and dangerous

00:38:02.280 | and you need to do it with supervision,

00:38:04.740 | with a mental health professional or a prescriber

00:38:08.940 | because it is dangerous.

00:38:11.180 | When people reduce their meds too much,

00:38:14.520 | they can get wildly symptomatic.

00:38:17.540 | - Is that true for depression as well?

00:38:19.600 | - It's true for any psychiatric medication.

00:38:22.620 | The brain makes adaptations

00:38:24.540 | in response to psychiatric medications.

00:38:27.140 | And when you stop them cold turkey, some people are fine,

00:38:32.180 | but I wouldn't recommend finding out

00:38:35.740 | because I've seen patients when they stop antidepressants,

00:38:39.560 | I've seen patients get floridly depressed and suicidal

00:38:44.140 | within three months.

00:38:45.140 | I had one patient almost quit her job

00:38:47.780 | because she became convinced that,

00:38:50.540 | well, my life sucks and it's all because of my boss.

00:38:54.120 | And I know that she's just a horrible human being

00:38:58.020 | and she's abusing me.

00:38:59.220 | And I was like, whoa, whoa, whoa,

00:39:01.260 | I think this is related to your medication change.

00:39:03.620 | We got her back on her meds within three days.

00:39:07.740 | She said, oh my God, I can't believe that happened.

00:39:11.140 | Like I almost quit my job.

00:39:13.660 | And that would have been the most illogical

00:39:16.300 | and irrational decision I've ever made in my entire life.

00:39:20.140 | But somehow it seemed so real just several days ago.

00:39:25.060 | And now that I'm back on this medication,

00:39:27.860 | and it doesn't mean that she needs the meds,

00:39:30.740 | but it doesn't mean that he needs the meds.

00:39:32.860 | It means that meds need to be adjusted very safely

00:39:35.980 | and cautiously and gradually.

00:39:37.860 | So that's the medication piece.

00:39:40.300 | The adherence piece was not easy for him

00:39:43.500 | and for other patients.

00:39:44.960 | It is very rare that I have a patient

00:39:48.860 | who I can say, do the ketogenic diet,

00:39:51.060 | come see me in three months and let me know how it's going.

00:39:54.280 | That almost never happens.

00:39:57.140 | It has happened, I think on two occasions.

00:39:59.620 | But that is, if I understand correctly,

00:40:01.900 | what perhaps not you,

00:40:03.500 | but many psychiatrists do with medication.

00:40:06.720 | It's here's your prescription.

00:40:08.460 | Let's talk in a month or three months.

00:40:11.260 | - Yes.

00:40:12.380 | - So that's a variable that is probably worth us

00:40:14.720 | exploring a little bit here as the conversation continues.

00:40:17.460 | - Absolutely.

00:40:18.300 | - You know, that frequent contact

00:40:19.500 | and making micro adjustments or macro adjustments

00:40:22.940 | to medication or nutrition could be meaningful.

00:40:26.340 | - Absolutely.

00:40:27.380 | So with this particular patient,

00:40:29.940 | early on he was actually pretty adherent.

00:40:33.120 | I was seeing him once a week.

00:40:34.740 | And so I could do a lot of education.

00:40:38.300 | I was weighing him.

00:40:39.580 | I was checking his ketones.

00:40:41.220 | I was checking his glucose levels.

00:40:43.620 | At that point I had a blood ketone monitor in my office.

00:40:46.980 | So I knew whether he was compliant or not,

00:40:49.980 | which is so beneficial in doing clinical work

00:40:54.000 | and research on this diet.

00:40:55.740 | It's the only diet where within seconds

00:40:58.700 | I can have an objective biomarker

00:41:00.340 | of compliance or non-compliance.

00:41:02.340 | - Such a key point.

00:41:04.500 | And again, brings to mind for me

00:41:06.960 | the parallel with medication.

00:41:08.660 | I mean, a patient can say they're taking their medication

00:41:12.120 | and unless they're in a hospital setting

00:41:14.340 | where somebody is checking under their tongue

00:41:15.800 | and you know, all of this,

00:41:16.780 | they very well could not be taking it or taking more.

00:41:20.920 | And you and I both know that blood draws

00:41:24.740 | for neurotransmitter levels are complicated

00:41:27.300 | because you want to know what's in the brain

00:41:28.480 | and what's functional in the brain.

00:41:30.040 | So, and I would have to imagine

00:41:31.500 | that most people that are prescribed drugs

00:41:33.420 | for any number of different psychiatric conditions

00:41:36.380 | are not giving blood every time they talk

00:41:37.980 | to their psychiatrist or psychologist.

00:41:39.620 | - No, no.

00:41:40.940 | And when we looked at, you know, on that front,

00:41:43.580 | when we've looked at studies of compliance,

00:41:46.460 | the majority of patients are at least somewhat non-compliant

00:41:51.460 | with prescription medications.

00:41:54.060 | It's not on purpose.

00:41:55.300 | It's, they forgot.

00:41:58.420 | They take it at night.

00:41:59.660 | They were out late.

00:42:01.580 | They were off their routine.

00:42:04.180 | They forgot to brush their teeth

00:42:06.460 | because that's when they take their meds.

00:42:08.300 | And so, because they, you know, it was so late,

00:42:11.360 | they just crashed when they got home.

00:42:13.060 | They forgot to take their meds.

00:42:14.980 | Happens all the time.

00:42:16.660 | If it's a medication that people take more than once a day,

00:42:19.520 | the non-compliance rates are much higher

00:42:22.500 | because it's just easy to forget.

00:42:24.580 | So it's not that people are willfully, you know,

00:42:27.800 | disobeying their doctors or anything else.

00:42:30.060 | It's just hard to remember to take meds

00:42:32.820 | consistently every day.

00:42:34.420 | - When you say measuring ketones,

00:42:36.380 | I want to drill into this a little bit

00:42:38.900 | because it does seem that the presence of ketones

00:42:43.060 | and somebody being quote unquote in ketosis

00:42:45.340 | turns out to be the key variable.

00:42:47.460 | Certainly in your book, that's what I,

00:42:49.620 | one of the major takeaways,

00:42:51.220 | although there were many important takeaways,

00:42:54.180 | that people get into ketosis.

00:42:56.620 | Do they have to stay in ketosis?

00:42:58.660 | So for instance, I've followed the,

00:43:00.740 | I don't any longer, but I've tried in the past,

00:43:02.900 | the so-called cyclic ketogenic diet,

00:43:04.600 | where every third or fourth day,

00:43:06.220 | get some pasta or rice, et cetera.

00:43:08.620 | And that was interesting as an experiment,

00:43:14.280 | but to stay in ketosis,

00:43:17.680 | what sort of blood levels of ketones

00:43:20.020 | do you like to see in your patients?

00:43:22.300 | What is the range that you think most people could aspire to?

00:43:26.760 | - So it really depends on the patient

00:43:28.980 | and what I'm treating, quite honestly.

00:43:31.460 | So, and I don't think every patient

00:43:34.820 | needs the ketogenic diet.

00:43:36.420 | For some patients, simply getting rid of junk food

00:43:38.680 | can make a huge difference in a mood disorder, for instance.

00:43:41.740 | - So a junk food, meaning highly processed food,

00:43:44.180 | food that could last on the shelf a very long time.

00:43:46.420 | - Highly processed foods that are usually high

00:43:49.380 | in both sugar, carbohydrate, carbs, and fats.

00:43:54.380 | Those seem to be the worst foods.

00:43:58.100 | That combination, high sugar, high fat,

00:44:01.580 | seems to be the worst combination for metabolic health.

00:44:06.380 | And lo and behold, we've got emerging data

00:44:09.500 | that suggests, that strongly suggests

00:44:11.860 | it's also bad for mental health.

00:44:13.980 | Depression and anxiety are the most common

00:44:16.460 | mental disorders, and so we have the best data

00:44:18.960 | for those disorders, but we actually have a lot of data

00:44:22.800 | with even bipolar disorder and schizophrenia

00:44:25.380 | that insulin resistance in particular,

00:44:28.260 | and insulin signaling in the brain is impaired

00:44:32.940 | in people with chronic mental disorders,

00:44:36.220 | kind of across the board.

00:44:37.980 | All the way from chronic anxiety, depression,

00:44:40.760 | to bipolar, to schizophrenia, and even Alzheimer's disease.

00:44:44.560 | We know that patients with all of those disorders

00:44:47.300 | have impaired glucose metabolism,

00:44:51.340 | and that the insulin signaling system in the brain,

00:44:54.380 | which is different than insulin signaling in the periphery,

00:44:57.460 | seems to somehow possibly be playing a role.

00:45:02.900 | So to step back from that, so for some patients,

00:45:06.920 | I might just wanna decrease glucose and insulin levels,

00:45:10.300 | and I can do that by getting rid of sweets.

00:45:12.500 | For other patients, like patients

00:45:15.780 | with schizoaffective disorder, or schizophrenia,

00:45:17.900 | or bipolar disorder, especially if it's chronic,

00:45:20.620 | if I'm using it as a brain treatment,

00:45:23.360 | then I do want a ketogenic diet,

00:45:27.340 | and I usually want reasonably high levels of blood ketones.

00:45:31.500 | Usually, for depression, I wanna see at least greater

00:45:35.940 | than probably 0.8 millimole.

00:45:39.340 | For psychotic disorders and bipolar disorder,

00:45:44.420 | I usually wanna see levels greater than 1.5.

00:45:47.900 | That's what I'm shooting for, if at all possible.

00:45:50.600 | And so, yeah, I think that's what I'd go for.

00:45:57.860 | - Yeah, so, and sorry, I didn't mean to imply

00:46:02.300 | that people need to be in ketosis

00:46:04.340 | in order to see some mental health benefits

00:46:06.960 | from changing their diet.

00:46:08.300 | You make very clear in your book,

00:46:11.060 | and we'll go into this in more detail,

00:46:13.580 | that avoiding insulin resistance,

00:46:16.740 | reversing insulin resistance,

00:46:18.460 | and essentially trying to reverse

00:46:20.820 | what earlier described as this metabolic syndrome,

00:46:25.120 | which is a bunch of different things, is the target.

00:46:28.940 | And for some people, getting rid of highly processed foods

00:46:32.360 | and focusing mainly on non-processed

00:46:34.420 | or minimally processed foods will really help.

00:46:36.540 | For others, going straight to the full-blown ketogenic diet

00:46:39.720 | will be of most benefit.

00:46:42.320 | I'd like to back up a little bit in history

00:46:44.700 | and get to something which I find incredibly interesting,

00:46:48.860 | which is epilepsy and the longstanding use

00:46:52.940 | of ketogenic diet and fasting to treat epilepsy.

00:46:56.980 | And the reason I want to kind of rewind

00:46:59.480 | to that point in history is that I think that

00:47:03.080 | for a lot of listeners and people out there

00:47:06.360 | who are familiar with how changing your diet

00:47:10.060 | or changing your exercise can positively impact sleep

00:47:13.140 | and weight and all these things,

00:47:14.280 | and it cascades into feeling better.

00:47:16.660 | That makes perfect sense.

00:47:18.340 | But for a lot of the world still,

00:47:20.240 | the idea that changing or using nutrition

00:47:24.860 | as a dissection tool or as a treatment tool

00:47:29.360 | to understand and treat mental illness

00:47:31.820 | is still a kind of heretical idea.

00:47:34.120 | That to them, it kind of falls in the,

00:47:35.860 | okay, well, that's like woo science or something like that.

00:47:39.600 | Now, obviously you're a board-certified physician

00:47:42.220 | or psychiatrist at arguably one of the finest

00:47:45.980 | medical schools in the world, Harvard Medical School.

00:47:49.020 | You know, even though I'm on the Stanford side,

00:47:50.820 | we acknowledge our East Coast friends.

00:47:53.680 | - You're the Harvard of the West Coast.

00:47:55.460 | - We're not going to talk, we're not going to talk--

00:47:57.460 | - Or we're the Stanford of the East Coast.

00:47:59.320 | - That argument could go back and forth a number of times.

00:48:01.540 | But you know, this is, you're a serious clinician

00:48:04.220 | and a serious scientist and you're a serious thinker.

00:48:09.100 | But for a lot of people out there,

00:48:11.080 | the notion of using diet, they immediately think,

00:48:14.440 | ah, well, that makes perfect sense.

00:48:17.120 | Or I think there's a category of people who think,

00:48:19.380 | well, yeah, didn't Atkins die of a heart attack?

00:48:21.860 | You know, I hear that a lot, you know?

00:48:23.480 | So like, that was crazy.

00:48:25.260 | You know, like people immediately discard the Atkins diet

00:48:29.580 | for that reason, which I do think is throwing the baby out

00:48:32.900 | with the bathwater, but it's an interesting thing nonetheless.

00:48:35.820 | And then I think that the majority of people

00:48:37.340 | sit in the middle and just want to see science and medicine

00:48:41.100 | come up with treatments that work.

00:48:42.840 | And I have to say, I'm very relieved

00:48:45.800 | to hear what you said earlier, which was,

00:48:47.320 | you never said that people should come off their medication

00:48:49.500 | and just become, go on a ketogenic diet

00:48:52.020 | and everything will be cured.

00:48:53.020 | You're certainly not saying that.

00:48:55.300 | And rather you're saying, if I understand correctly,

00:48:58.720 | that nutrition needs to be considered one of the major tools

00:49:02.720 | in the landscape of effective tools,

00:49:05.140 | and that it can be very effective,

00:49:06.580 | evidenced by the story that you shared.

00:49:08.500 | And there are many other stories in there as well,

00:49:12.180 | of truly miraculous transformations.

00:49:15.140 | So let's talk about epilepsy and how the ketogenic diet

00:49:19.180 | is not just used for epilepsy, but is one of the oldest,

00:49:23.580 | if not the oldest examples of the use of nutrition

00:49:26.940 | to treat a condition of the nervous system

00:49:30.260 | that can be incredibly debilitating, even deadly.

00:49:32.900 | - Yeah, and the reality is that this literature

00:49:37.300 | and this clinical history and all of the research we have

00:49:40.900 | was the godsend that I needed

00:49:43.540 | to do the work that I'm doing.

00:49:45.740 | Otherwise I would have been discredited on day one.

00:49:48.500 | Chris Palmer's claiming that a dietary change

00:49:52.260 | can influence schizophrenia or schizoaffective disorder,

00:49:55.500 | that's impossible, and he's a quack.

00:49:58.140 | But the thing that immediately got me credibility

00:50:02.640 | was I didn't focus on it as a diet.

00:50:05.700 | I did a deep dive into the epilepsy literature.

00:50:10.460 | So the ketogenic diet, unbeknownst to most people,

00:50:14.340 | was actually developed 100 years ago, 1921,

00:50:19.340 | by a physician for one and only one purpose,

00:50:23.300 | to treat epilepsy.

00:50:25.140 | It wasn't developed as a weight loss diet.

00:50:27.140 | It wasn't developed as the diet

00:50:29.520 | that all human beings should follow.

00:50:32.620 | And the reason it was developed

00:50:34.020 | is because of this longstanding observation

00:50:38.460 | since the time of Hippocrates

00:50:40.760 | that fasting can stop seizures.

00:50:43.780 | Now fasting is not a healthy diet.

00:50:48.580 | Fasting is the process of no diet.

00:50:51.340 | So we now understand a tremendous amount of science.

00:50:57.240 | Most people think going without food is bad,

00:51:01.120 | and they equate it with starvation.

00:51:04.140 | But in fact, when we go without food,

00:51:06.540 | it causes tremendous shifts in metabolism,

00:51:10.340 | both brain and body metabolism.

00:51:13.300 | And it puts the body into a mode of autophagy

00:51:17.940 | and conservation of resources and all sorts of things

00:51:21.500 | that are beneficial to human health.

00:51:25.420 | And this is why fasting has been used

00:51:27.380 | as a therapeutic intervention in almost every culture

00:51:30.820 | and almost every religion for millennia.

00:51:33.760 | But for the most part,

00:51:36.600 | that was all thought to be religious folklore.

00:51:39.120 | That was just crazy talk.

00:51:40.600 | And those stupid people way back then

00:51:44.000 | thought God cured everything.

00:51:45.460 | And so they fasted and they just assumed

00:51:47.740 | that they were getting better.

00:51:49.740 | Well, in 1921, one physician used intermittent fasting

00:51:54.740 | on a child with seizures and found that,

00:51:58.960 | oh, lo and behold, this religious folklore stuff

00:52:01.260 | has something to it.

00:52:02.100 | It actually worked.

00:52:04.060 | The problem with fasting is that you can only fast

00:52:06.420 | for so long before you starve to death,

00:52:08.160 | and that's not a very effective treatment.

00:52:10.520 | - And this child was ingesting water, correct?

00:52:14.860 | - Yes.

00:52:15.700 | - It was just food elimination fasting.

00:52:16.780 | - Food elimination.

00:52:18.100 | So no special diet.

00:52:19.740 | So it was, but the problem with fasting for epilepsy

00:52:23.740 | is that as soon as people start eating a normal diet again,

00:52:26.460 | their seizures usually come right back.

00:52:28.840 | Oftentimes with a vengeance.

00:52:30.780 | And so it can be a good short-term intervention.

00:52:33.220 | The fasting can take a few days

00:52:36.400 | 'cause it can take a few days to get ketosis.

00:52:39.660 | And then you can get some relief from chronic seizures,

00:52:43.360 | but it's not a good long-term treatment

00:52:45.660 | because again, people will starve to death.

00:52:49.160 | As soon as they start eating, seizures come back.

00:52:51.680 | So it was actually Dr. Russell Wilder at the Mayo Clinic

00:52:55.560 | who developed the ketogenic diet

00:52:57.500 | with one and only one purpose.

00:52:59.300 | He wanted to see, can we mimic the fasting state

00:53:04.300 | using this special diet

00:53:07.720 | to see if it might stop seizures long-term?

00:53:11.740 | And lo and behold, it worked.

00:53:13.780 | Early results were extraordinarily positive.

00:53:17.660 | 50% of patients who use the ketogenic diet

00:53:20.560 | became seizure-free,

00:53:22.340 | and another 35% have a 50% or greater reduction

00:53:26.780 | in their seizure frequency.

00:53:28.540 | So about 85% efficacy rate.

00:53:30.980 | - Sorry to interrupt.

00:53:31.820 | I didn't mean to do that there.

00:53:33.220 | Was it just for pediatric epilepsy

00:53:36.380 | or for adult epilepsy as well?

00:53:37.900 | - So back in the 1920s,

00:53:39.460 | we didn't have many anti-epilepsy treatments

00:53:42.300 | and a lot of adults were struggling as well.

00:53:44.260 | So they were using it on anybody who would do the diet.

00:53:47.120 | By the 1950s, pharmaceuticals were coming out

00:53:52.460 | and we had many more anti-convulsant treatments.

00:53:55.200 | And there's no question they work for a lot of people.

00:53:58.860 | That's great.

00:53:59.900 | And taking a pill is so much easier than doing this diet.

00:54:03.580 | So the diet pretty much fell out of favor

00:54:05.620 | and nobody was using it from the 1950s to about the '70s.

00:54:10.260 | But lo and behold, even to this day,

00:54:13.500 | people with epilepsy, about 30% don't respond

00:54:17.180 | to the current treatments that we have available.

00:54:19.860 | 30% will have treatment-resistant epilepsy,

00:54:22.480 | which means they continue to have seizures

00:54:24.600 | no matter how many anti-convulsants they're taking.

00:54:27.420 | Even if they've had brain surgery,

00:54:29.460 | it just doesn't stop their seizures.

00:54:31.340 | And so in the 1970s, the ketogenic diet was resurrected

00:54:35.600 | at Johns Hopkins for these treatment-resistant cases.

00:54:39.060 | And lo and behold, it works.

00:54:41.220 | Not for all of them, but it works.

00:54:43.420 | And about 1/3 become seizure-free.

00:54:48.420 | And these are people who've tried everything

00:54:50.480 | and nothing's working.

00:54:51.380 | So 1/3 becomes seizure-free.

00:54:53.340 | Another 1/3 get a clinical benefit,

00:54:55.740 | meaning a 50% or greater reduction

00:54:57.600 | in their seizure frequency.

00:54:59.180 | And the other 1/3, it doesn't seem to work.

00:55:01.980 | It's not always clear if that's because of noncompliance

00:55:04.660 | or if that's because the diet's just not working,

00:55:07.320 | but about 1/3, 1/3, 1/3.

00:55:10.040 | Seizure freedom, reduction in seizures,

00:55:12.380 | or it just doesn't work.

00:55:13.720 | And so the reality, the godsend for me

00:55:18.900 | is that we have decades of neuroscience research

00:55:21.860 | on the ketogenic diet and what it is doing to the brain.

00:55:25.020 | We know that the ketogenic diet

00:55:26.620 | is influencing neurotransmitter levels,

00:55:29.180 | in particular glutamate, GABA, adenosine.

00:55:32.540 | It changes calcium channel regulation and calcium levels,

00:55:36.780 | which is really important in the function of cells.

00:55:40.340 | It changes gene expression.

00:55:42.540 | It reduces brain inflammation.

00:55:45.260 | It changes the gut microbiome.

00:55:47.100 | And there are, you know,

00:55:47.940 | gut microbiome's a huge topic right now.

00:55:49.880 | And there are some researchers who argue

00:55:51.380 | that is the primary benefit of the ketogenic diet.

00:55:54.020 | It's changing the gut microbiome in beneficial ways.

00:55:57.140 | So it's doing a lot of things.

00:55:59.820 | It obviously improves insulin resistance,

00:56:03.300 | lowers glucose levels, lowers insulin levels,

00:56:06.260 | which improves insulin signaling.

00:56:08.260 | The key for my research that I've outlined,

00:56:14.660 | the real magic is that this diet

00:56:19.780 | stimulates two processes that relate to mitochondria.

00:56:23.900 | It stimulates a process called mitophagy,

00:56:26.820 | which is getting rid of old and defective mitochondria

00:56:30.140 | and replacing them with new ones.

00:56:32.260 | And it also stimulates a process

00:56:33.840 | called mitochondrial biogenesis,

00:56:36.380 | which means that after people have done the ketogenic diet

00:56:40.060 | for a while, months or years,

00:56:43.260 | many of their cells in their bodies and brains

00:56:47.100 | will have more mitochondria and those mitochondria

00:56:50.860 | will be healthier.

00:56:52.880 | And I believe that is the reason the ketogenic diet

00:56:57.360 | is such a powerful treatment, not only for epilepsy,

00:57:00.960 | but also for people with chronic mental disorders.

00:57:04.100 | - Would you mind listing off a few of the mental disorders?

00:57:09.860 | And I know this is not meant to be inside ball,

00:57:12.740 | but we should distinguish between psychiatric disorders

00:57:15.180 | and neurological symptoms and diseases.

00:57:19.540 | You know, the fields of psychiatry and neurology,

00:57:22.380 | hopefully someday will just merge.

00:57:23.940 | But for instance, typically if somebody is presenting

00:57:28.140 | with something that looks like Alzheimer's, dementia,

00:57:31.220 | they'll talk to a neurologist.

00:57:32.500 | Whereas if somebody is presenting with symptoms

00:57:34.620 | like schizophrenia, bipolar, they'll talk to a psychiatrist.

00:57:37.120 | But if you wouldn't mind wearing a dual hat,

00:57:40.680 | could you just quickly list off some of the neurologic

00:57:44.880 | and psychiatric disorders for which ketogenic,

00:57:48.780 | or let's just say nutrition changes have been shown

00:57:51.760 | to improve symptoms significantly?

00:57:53.720 | And then maybe we can dive into a couple of these

00:57:55.640 | as well as get more deeply into these two

00:57:57.920 | very interesting aspects of mitochondrial function

00:58:01.380 | and repair and turnover.

00:58:02.820 | - Yeah, so the field, you know,

00:58:05.700 | in terms of nutritional psychiatry, it's a broad field

00:58:09.460 | and it's in its infancy is the real answer.

00:58:12.200 | If you're looking for randomized controlled trials,

00:58:14.400 | documenting efficacy in large numbers of patients

00:58:18.500 | with these disorders, we don't have them.

00:58:21.780 | They're underway now, but we don't have them yet.

00:58:25.040 | What we do have are case studies.

00:58:28.940 | We have a lot of mechanistic science papers

00:58:33.940 | by some of the leading neuroscientists and psychiatrists

00:58:37.300 | in the world and neurologists in the world,

00:58:40.780 | kind of outlining this is everything we know

00:58:42.940 | that the ketogenic diet's doing.

00:58:44.840 | These are the problems in the brains of people

00:58:47.580 | with these chronic mental or neurological disorders,

00:58:50.640 | so we know that they should work.

00:58:52.560 | But the disorders range from chronic depression

00:58:56.980 | to we've got a trial underway for PTSD.

00:59:01.980 | We've got one actually decent pilot trial

00:59:08.420 | from the National Institutes of Health

00:59:11.040 | for the ketogenic diet for alcohol use disorder

00:59:13.660 | of all things, and we can go into that a little more.

00:59:16.720 | We've got a couple of pilot trials of the ketogenic diet

00:59:19.760 | for Alzheimer's disease.

00:59:21.800 | We've got, and those are randomized controlled trials.

00:59:24.960 | We've got case studies of the ketogenic diet

00:59:29.180 | for chronic depression, bipolar disorder, and schizophrenia.

00:59:33.520 | The largest study that we've got

00:59:35.240 | in that mental health sphere is a pilot study

00:59:40.320 | of 31 patients admitted to a French hospital.

00:59:43.400 | The 28 of those patients were able to do the diet

00:59:49.880 | and stay on the diet.

00:59:52.720 | So 10% off the bat, non-compliant, couldn't do the diet,

00:59:57.260 | so we need to include that.

00:59:58.920 | But of the 28 patients who were able to do,

01:00:01.020 | and these are 28 patients

01:00:02.180 | with treatment-resistant mental disorders,

01:00:04.180 | chronic depression, bipolar, and schizophrenia.

01:00:07.920 | Of the patients who were able to do the ketogenic diet,

01:00:10.720 | 100% had at least some improvement in symptoms.

01:00:14.480 | 46% had remission of illness.

01:00:18.340 | Remission of illness, that does not happen

01:00:20.760 | with current treatments.

01:00:22.540 | And 64%, I think, were discharged on less medicine

01:00:27.540 | than they went into the hospital on.

01:00:31.540 | So it wasn't that the people were prescribing more medicine,

01:00:35.820 | and that's why they were being discharged

01:00:39.060 | on less medication.

01:00:40.620 | We've got at least, again,

01:00:43.300 | a lot of the hardcore scientists are gonna say,

01:00:45.580 | show us the randomized controlled trials

01:00:47.840 | with hundreds of patients.

01:00:49.980 | And we've got five randomized controlled trials

01:00:53.140 | underway now, funded primarily through philanthropy.

01:00:57.380 | I can tell you that we've talked

01:01:03.400 | about that one index patient,

01:01:05.220 | but at this point, I have now treated dozens of patients,

01:01:08.800 | and I've heard from hundreds of patients

01:01:11.740 | who've been treated by other clinicians, researchers,

01:01:15.320 | or I've just heard from patients from around the world

01:01:18.140 | who have shared stories of complete remission

01:01:22.580 | of long, chronic mental disorders,

01:01:27.300 | like bipolar disorder and schizophrenia,

01:01:30.060 | off of psychiatric meds, some of them, not all of them,

01:01:33.020 | but some of them are able to get off all psychiatric meds

01:01:36.460 | and remain in remission.

01:01:37.700 | Again, I think I didn't say this before,

01:01:44.140 | but it's really important to mention.

01:01:46.620 | For people who might be unfamiliar

01:01:48.940 | with the mental health field

01:01:50.260 | and its connection with epilepsy,

01:01:52.340 | the reason that it's such an important connection

01:01:55.900 | is that we use epilepsy treatments

01:01:57.900 | in psychiatric patients every day

01:02:00.220 | in tens of millions of people.

01:02:03.160 | So a lot of people don't know this,

01:02:05.120 | but I'll list off some names

01:02:07.680 | that a lot of your listeners may have heard of,

01:02:10.800 | and they probably know them as psychiatric drugs,

01:02:13.060 | but in fact, these are epilepsy drugs,

01:02:15.320 | Depakote, Tegretol, Lamictal, Topamax,

01:02:18.360 | Neurontin or Gabapentin, Valium, Klonopin, Xanax.

01:02:23.120 | Those are all medications that stop seizures,

01:02:27.520 | and many of them were developed initially for seizures,

01:02:32.520 | but we in the mental health field quickly steal them

01:02:36.800 | and start using them in tens of millions of people,

01:02:39.000 | even if they're off-label.

01:02:40.760 | So that means we don't have research studies

01:02:43.140 | documenting that they're effective,

01:02:44.960 | but we go ahead and use them anyway

01:02:47.440 | because the reality is far too many patients

01:02:49.920 | aren't getting better with the FDA-approved treatments

01:02:52.680 | that we do have to offer.

01:02:54.360 | So psychiatrists are just winging it in some cases,

01:02:57.440 | and we're just throwing whatever we can at them,

01:03:00.120 | and we absolutely include epilepsy treatments.

01:03:03.240 | So in many ways, using the ketogenic diet

01:03:05.960 | as a treatment for serious mental disorders

01:03:08.160 | is nothing new at all.

01:03:10.080 | It's an established evidence-based treatment for epilepsy.

01:03:13.280 | We use evidence-based treatments for epilepsy

01:03:16.120 | across the board for a wide range of mental disorders,

01:03:19.920 | and so in many ways,

01:03:21.000 | that's all I'm doing with the ketogenic diet.

01:03:23.200 | It just happens to be a diet.

01:03:24.700 | - I love it.

01:03:27.040 | I love it, and I should say I love it

01:03:29.480 | because we had a guest on here early days of the podcast.

01:03:34.040 | He's a colleague of mine at Stanford.

01:03:35.800 | He's a bioengineer and a psychiatrist,

01:03:38.140 | phenomenal scientist and psychiatrist called Diceroth,

01:03:42.000 | who won the Lasker Prize and so on and so forth,

01:03:44.700 | and he made a really important point,

01:03:46.120 | which should have been obvious to me,

01:03:47.720 | but wasn't until he said it,

01:03:50.360 | which was the psychiatrist has tools

01:03:54.720 | just like the surgeon has tools,

01:03:56.120 | but the tools are language and observing behavior.

01:04:00.240 | Those are the dissection tools

01:04:02.560 | for what's going on in someone's brain,

01:04:04.760 | and then as a neuroscientist,

01:04:07.000 | I'm familiar with the neurotransmitters and neuromodulators,

01:04:09.320 | and you mentioned that,

01:04:11.220 | and there are these tools of altering brain chemistry,

01:04:17.440 | which are of the sorts of drugs you just listed off

01:04:20.120 | or antidepressants or antipsychotics

01:04:22.260 | that fall into these major bins of adjusting dopamine

01:04:24.480 | or adjusting serotonin or some combination of dopamine,

01:04:27.520 | serotonin, epinephrine, adenosine, and on and on and on,

01:04:30.800 | and it seems to me it's an incredible field,

01:04:34.600 | but that the field is still very much in its infancy,

01:04:37.440 | that it wasn't but 100 years ago

01:04:39.640 | that people were measuring bumps on the head

01:04:42.520 | as a way to diagnose phrenology

01:04:44.400 | and that there's still so much to learn,

01:04:46.960 | and so when I hear you say adjusting nutrition

01:04:49.920 | or putting people into a ketogenic state

01:04:51.620 | or even just eliminating highly processed foods, sugars, et cetera,

01:04:54.760 | taking care of metabolic syndrome

01:04:56.080 | and then observing tremendous relief

01:04:58.560 | in clinical syndromes or symptoms, rather,

01:05:02.940 | of psychiatric disorders, it makes perfect sense to me.

01:05:06.280 | It's yet another dissection tool

01:05:08.460 | and a tool for altering brain chemistry.

01:05:11.360 | I think that if I think about the landscape,

01:05:13.800 | the sort of sociology out there of,

01:05:15.900 | again, it seemed to be these bins,

01:05:18.100 | like a third of people saying,

01:05:19.000 | "Of course, diet and exercise and social connection

01:05:22.080 | "and limiting stress, that's the good stuff.

01:05:24.660 | "That's the stuff that we know really works."

01:05:26.340 | And then about a third of people are sort of unclear,

01:05:28.180 | and then a third of people think,

01:05:29.140 | "Well, if it's not a prescription drug,

01:05:31.840 | "then it just has no place in medicine."

01:05:34.480 | And hopefully that's changing.

01:05:36.640 | And certainly the work that you're doing

01:05:37.940 | is going to be important in that transition

01:05:41.480 | that I think we will see.

01:05:43.540 | I'd like to talk about mitophagy

01:05:47.980 | and mitochondrial biogenesis.

01:05:49.980 | I think most people learn that the mitochondria

01:05:52.540 | are the energy factories of cells,

01:05:55.620 | and that indeed they are.

01:05:57.100 | As a neuroscientist, what I know about them

01:05:58.780 | is that they are present everywhere in neurons,

01:06:00.740 | not just in the so-called cell body,

01:06:02.500 | but you can find mitochondria

01:06:04.140 | in the furthest little bits of neurons,

01:06:06.460 | and neurons can be quite big, very large, in fact,

01:06:09.500 | meters long or more in some cases,

01:06:12.000 | and some species, including us,

01:06:13.820 | depending on how tall somebody is.

01:06:15.020 | It could be many meters, or several meters, rather.

01:06:17.660 | And then mitochondria do a lot of stuff

01:06:21.820 | besides just produce energy.

01:06:23.780 | 'Cause I think people hear mitochondria, energy,

01:06:25.620 | and they think, "Oh, so these patients felt better.

01:06:27.560 | "They lost weight, they have more energy,

01:06:29.020 | "and then they're doing better."

01:06:30.060 | But here we're talking about remission

01:06:32.180 | of auditory hallucinations, people feeling suicidal,

01:06:37.180 | and then changing their diet,

01:06:39.080 | and feeling like life is something they can deal with,

01:06:41.220 | and maybe even function extremely well, and et cetera.

01:06:44.500 | So maybe we could just talk about mitochondria for a moment,

01:06:47.260 | and then talk about these two major effects.

01:06:49.140 | What are some of the other things

01:06:50.480 | that mitochondria are important for in neurons,

01:06:53.900 | and maybe other cells of the brain?

01:06:56.940 | Because as an access point for all this,

01:06:59.540 | I think it would be great

01:07:00.420 | if people could learn a little mitochondria biology.

01:07:03.140 | - Yeah, no, so I guess the first thing that I'll say

01:07:07.140 | is that this field is one of the most cutting edge fields

01:07:12.140 | in medicine right now.

01:07:14.300 | 20 years ago or so, I think the majority

01:07:19.500 | of research scientists thought of mitochondria

01:07:21.940 | as nothing more than little batteries.

01:07:25.020 | They take food and oxygen and turn it into ATP,

01:07:29.180 | and that's really important.

01:07:30.420 | Yeah, we get that, but they're just little batteries.

01:07:33.740 | That's all they are.

01:07:34.740 | And so one of the reasons that this

01:07:39.220 | work is so important is because it combines

01:07:44.140 | cutting edge research in the metabolic field

01:07:47.580 | and the aging field, and we can start to pair it

01:07:52.180 | with the mental health and neurological health field.

01:07:55.780 | So mitochondria, one scientist gave me this analogy.

01:08:00.780 | He said, "If you think of the cell as a computer,

01:08:05.980 | "a lot of people think of mitochondria as the power cord

01:08:09.260 | "to that computer, 'cause they're providing the power,

01:08:11.620 | "and they are, in fact, the power cord to that computer,

01:08:14.500 | "but actually their real function

01:08:17.020 | "is the motherboard of that computer."

01:08:19.660 | So mitochondria are directing and allocating resources

01:08:23.500 | throughout a cell.

01:08:24.460 | That is their primary function,

01:08:26.660 | and then they happen to be powerhouses as well.

01:08:29.380 | And so to give some clear examples,

01:08:33.100 | mitochondria play a direct role in the production

01:08:36.860 | and release and regulation of some really key

01:08:40.340 | neurotransmitters, including serotonin, dopamine,

01:08:44.780 | glutamate, acetylcholine.

01:08:47.340 | Those are pretty powerful neurotransmitters.

01:08:51.260 | - Yeah, I would consider those the,

01:08:53.500 | I know you listed more than three,

01:08:54.660 | but the sort of primary colors of neurotransmission.

01:08:58.860 | - Yes.

01:08:59.700 | - Any one of those,

01:09:00.540 | in excess or deficiency is going to have profound

01:09:04.460 | negative effects on a nervous system,

01:09:06.500 | or it's going to alter the way that people and animals

01:09:09.820 | feel, think, move, remember, et cetera.

01:09:12.820 | - And so as part,

01:09:13.900 | so mitochondria are providing both some of the building

01:09:18.340 | blocks, if you will, for some of those molecules.

01:09:21.420 | They're part of the Krebs citric acid cycle.

01:09:23.780 | Some of the intermediate products actually go

01:09:27.340 | into making those neurotransmitters, much more importantly,

01:09:31.060 | mitochondria provide the energy for the production

01:09:34.140 | of those neurotransmitters and fascinatingly,

01:09:37.260 | mitochondria are directly related to the release

01:09:40.580 | of neurotransmitters, ATP alone is not enough.

01:09:45.300 | There've been some research studies that have actually found

01:09:48.500 | that mitochondria move along the membrane of the synapse

01:09:54.500 | to release batches of vesicles of neurotransmitters.

01:09:59.500 | And that if the mitochondria are removed from the synapse

01:10:03.420 | and researchers flood that cell with ATP,

01:10:08.420 | neurotransmitters usually are not getting released.

01:10:11.980 | Mitochondria are doing other things.

01:10:14.820 | We don't entirely even understand what all they're doing

01:10:18.100 | or how they're doing it,

01:10:19.540 | but they're doing other things that they're not doing.

01:10:23.140 | They're doing other things than just providing the power.

01:10:28.060 | Another really important example is that mitochondria

01:10:31.060 | are actually the primary regulators of epigenetics.

01:10:35.940 | If you look at any one factor, so one study actually found

01:10:39.500 | that they're responsible for the expression

01:10:42.940 | of about 60% of the genes in a cell.

01:10:46.740 | And so, and mitochondria do this through a lot of ways

01:10:51.380 | known for years and sometimes decades.

01:10:53.700 | So mitochondria are directly related to the levels

01:10:56.580 | of reactive oxygen species in a cell.

01:10:59.780 | They are managing calcium regulation in cells.

01:11:04.540 | And we know that those things play a role

01:11:06.740 | in epigenetic expression.

01:11:08.340 | We know the levels of ATP to ADP or AMP also play a role.

01:11:13.340 | And mitochondria are doing those things.

01:11:17.020 | But it turns out mitochondria are actually doing

01:11:18.620 | much more sophisticated things than even those

01:11:21.220 | in terms of gene expression.

01:11:22.900 | Mitochondria at least play a role in all of the aspects

01:11:27.500 | of the human stress response.

01:11:30.220 | So when humans are stressed either physically

01:11:33.020 | or psychologically, there are several things that happen.

01:11:38.020 | Increased cortisol, increased adrenaline, noradrenaline,

01:11:43.740 | inflammation, and gene expression in particular

01:11:46.940 | in the hippocampus occur with the stress response.

01:11:50.980 | And one group of researchers actually genetically

01:11:53.380 | modified mitochondria in four different ways

01:11:55.900 | and found that all of the stress response,

01:11:58.300 | all those four buckets of stress response were impacted

01:12:03.100 | in one way or another, implying that mitochondria

01:12:07.140 | are somehow playing a role in those.

01:12:11.140 | In terms of their role in cortisol,

01:12:14.060 | we know that mitochondria actually have the enzyme required

01:12:17.820 | for the synthesis of steroid hormones.

01:12:21.660 | So that includes cortisol, estrogen, testosterone,

01:12:25.100 | and progesterone, some names that maybe everybody's heard of.

01:12:28.780 | And so that means that if mitochondria are in short supply

01:12:33.780 | or dysfunctional, the production of those hormones

01:12:39.620 | may become dysregulated.

01:12:44.460 | Mitochondria play a direct role in inflammation,

01:12:48.340 | and they turn the inflammatory system both on,

01:12:53.340 | or they at least play a role in turning

01:12:55.980 | the inflammatory system both on and off.

01:12:58.780 | I think I'm not gonna be able to quote

01:13:00.380 | the exact study and author, but one paper in Cell

01:13:03.940 | actually identified mitochondria as the key regulator

01:13:07.780 | in turning certain inflammatory cells off.

01:13:10.900 | And that when you inhibit mitochondrial function,

01:13:13.260 | those cells don't turn off.

01:13:15.540 | Mitochondrial levels of reactive oxygen species

01:13:18.620 | are a key signaling process

01:13:22.620 | to turn the inflammatory cell process off.

01:13:26.220 | Another study found that macrophages,

01:13:28.860 | so macrophages are an important immune cell

01:13:32.180 | that play a role in healing.

01:13:33.500 | So if you cut yourself, your body will send inflammation

01:13:38.380 | that way and send immune cells that way

01:13:42.300 | to try to heal your skin.

01:13:44.580 | And macrophages play an important role in that healing.

01:13:48.100 | One group of researchers tried to figure out

01:13:50.580 | how do macrophages know to switch

01:13:53.780 | between the different phases of wound healing?

01:13:56.620 | 'Cause the macrophages do different things

01:13:59.060 | in the different phases of wound healing.

01:14:01.940 | And the conclusion of all of their research

01:14:04.700 | was that it's mitochondria.

01:14:06.260 | Mitochondria are sending the essential signals

01:14:10.300 | that change the state of the macrophages

01:14:13.260 | to induce these different phases of wound healing.

01:14:17.060 | So I've just talked about neurotransmitters, hormones,

01:14:22.060 | epigenetic expression, inflammation.

01:14:25.580 | For anybody familiar with the mental health field,

01:14:30.060 | they know these are like some of the key variables

01:14:36.300 | that researchers have been struggling with for decades

01:14:40.100 | trying to figure out how do these fit together?

01:14:42.980 | We know that all of those buckets can be disrupted

01:14:47.980 | in people with mental disorders.

01:14:50.580 | And our field has struggled to understand

01:14:54.820 | but how do they fit together?

01:14:56.820 | How can we make sense of this disruption?

01:15:00.660 | And I believe once you understand

01:15:03.540 | the science of mitochondria,

01:15:07.020 | you can actually connect all of the dots

01:15:09.620 | of the mental illness puzzle.

01:15:11.500 | I'd like to take a brief break

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01:15:34.380 | The problem with a lot of blood and DNA tests out there,

01:15:36.460 | however, is that you get data back about metabolic factors,

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01:15:56.980 | hormones, lipids, and other things

01:15:58.780 | that impact your immediate and long-term health

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01:16:23.200 | - Super interesting little sub-cellular goodies

01:16:27.060 | these mitochondria are.

01:16:28.800 | I come from a field where people are often divided

01:16:33.500 | into lumpers and splitters,

01:16:35.260 | and I'm somewhere in between.

01:16:37.540 | For those of you who don't know,

01:16:39.860 | lumpers are people that like to make things really simple,

01:16:42.220 | lists of no more than three functions

01:16:44.500 | or dividing brain areas into no more than three splitters

01:16:47.760 | are people that like to subdivide into a ton of detail.

01:16:51.740 | There's a history of scientists being splitters

01:16:53.800 | in order to be able to name things after themselves

01:16:55.900 | because there's more territory to go around

01:16:58.860 | if you're splitting than if you're lumping.

01:17:00.980 | But we are doing neither here.

01:17:02.460 | What I'm hearing is that mitochondria,

01:17:06.700 | in addition to being important sources

01:17:08.700 | of energy production and output in cells,

01:17:11.580 | which of course they are, probably have other roles

01:17:16.340 | and that maybe someday what we call mitochondria

01:17:20.420 | will actually be two or three different

01:17:22.380 | little sub-cellular organelles.

01:17:23.780 | There may be little bits in there

01:17:24.920 | that are controlling gene expression

01:17:26.100 | and little bits in there that are controlling

01:17:27.980 | neurotransmitter production.

01:17:29.740 | At least for now, the name is mitochondria

01:17:32.220 | and thank you, by the way, for illustrating

01:17:34.500 | some of the other things that they do

01:17:35.940 | because in the landscape of science education,

01:17:40.020 | oftentimes people think, okay, energy production,

01:17:42.900 | there'll be a picture or a cartoon of mitochondria

01:17:44.620 | like flexing its muscles.

01:17:45.980 | People go, okay, energy, mitochondria, mighty mitochondria

01:17:48.580 | and then they'll think, oh, you know,

01:17:49.740 | they're just sort of like a dumb jock portion of the cell.

01:17:53.060 | They're not doing anything sophisticated

01:17:55.020 | and everything you listed off is that they are doing

01:17:57.580 | many sophisticated, intricate things within cells.

01:18:01.140 | So I think how things are cartooned and discussed

01:18:03.820 | actually has an impact and not just on the general public,

01:18:06.700 | but on the medical field and on the science fields.

01:18:09.260 | Anyway, that's more science sociology.

01:18:11.180 | But now that everyone is well aware

01:18:14.220 | that mitochondria are doing a large number

01:18:16.500 | of very important things in a very regulated way,

01:18:20.700 | let's talk about mitophagy.

01:18:22.100 | You know, a few years ago,

01:18:22.980 | because a Nobel Prize was given for autophagy,

01:18:26.300 | sometimes called autophagy, look, people,

01:18:28.620 | you can say it either way.

01:18:29.580 | People will know, hopefully what it means is more important,

01:18:32.300 | which is the gobbling up of one's own cells

01:18:35.300 | that are dead or injured.

01:18:37.340 | And this idea of autophagy, of cells being eaten up

01:18:43.860 | or within a system, nervous system or other system,

01:18:48.400 | has come up again and again.

01:18:50.060 | I actually wasn't aware that mitophagy

01:18:52.900 | could be such an important lever.

01:18:54.780 | So tell us about mitophagy, which I have to presume

01:18:57.060 | is the intentional, or not, gobbling up of mitochondria,

01:19:02.060 | presumably to replace them

01:19:04.600 | with newer, healthier mitochondria, is that right?

01:19:06.660 | - It is.

01:19:07.500 | So in many ways, mitophagy is a subset of autophagy,

01:19:12.020 | but it's got its own name

01:19:15.260 | because it is specific to mitochondria.

01:19:18.220 | There do appear to be some unique regulators of mitophagy

01:19:24.280 | compared to autophagy more broadly.

01:19:27.300 | Mitochondria actually are playing a role in autophagy itself.

01:19:31.800 | And this makes sense because one of,

01:19:34.820 | so the global picture of autophagy is stimulated

01:19:38.560 | by fasting states or fasting-mimicking states.

01:19:43.560 | So when your body senses that you don't have enough food,

01:19:49.600 | it actually hunkers down and starts to recycle

01:19:54.600 | dead old parts in this kind of carefully orchestrated way.

01:20:00.620 | And it takes them to lysosomes, they get degraded,

01:20:06.160 | and then those degradation products get used

01:20:10.100 | for either energy or to build new things.

01:20:13.420 | Autophagy is always occurring at a low level,

01:20:17.500 | but you can really hyper-stimulate the process

01:20:20.680 | through fasting, calorie restriction,

01:20:23.140 | fasting-mimicking diets, other things.

01:20:25.640 | And this is why fasting and calorie restriction

01:20:28.640 | is so kind of such hot topics in the medical field now

01:20:32.480 | is because they've been shown to induce longevity,

01:20:36.060 | and we think it's probably through that process

01:20:39.200 | that you're stimulating the body to kind of become lean

01:20:47.160 | and conservative in terms of its allocation of resources.

01:20:52.080 | And the body doesn't just destroy the healthiest tissue

01:20:56.620 | along with the old dead stuff.

01:20:58.280 | It has these processes that identify

01:21:00.800 | the old and defective parts first, and they go first,

01:21:04.100 | and that's what's beautiful about the whole thing,

01:21:06.480 | and that's why fasting is so important.

01:21:09.520 | So mitophagy we know plays a really important role

01:21:15.880 | because so there's this term called mitochondrial dysfunction

01:21:20.880 | which some researchers are actually wanting to get rid of

01:21:25.200 | and move away from because as you just said,

01:21:27.840 | mitochondria do so many different things,

01:21:30.040 | and different mitochondria even within the same cell

01:21:32.520 | may very well be specializing in different tasks,

01:21:35.720 | and mitochondria from one cell to another

01:21:37.520 | are sometimes doing very different things.

01:21:39.880 | Like not all mitochondria can produce cortisol.

01:21:43.080 | That's specific to specific cells.

01:21:46.420 | Where those genes are getting turned on.

01:21:48.660 | So it's not like all mitochondria are producing cortisol.

01:21:51.380 | Just the ones in your adrenal gland, for instance,

01:21:54.460 | are producing cortisol.

01:21:56.060 | But there is this term mitochondrial dysfunction,

01:22:00.940 | and it has long been known for decades

01:22:05.620 | that mitochondrial dysfunction is associated

01:22:09.260 | with everything that ails us essentially.

01:22:13.660 | So in the 1950s we had a theory of aging

01:22:18.660 | that was based on reactive oxygen species,

01:22:25.220 | and that essentially,

01:22:26.340 | and that's where all the inflammation is bad for you

01:22:28.540 | comes from.

01:22:29.380 | - And where all the noise about antioxidants.

01:22:34.380 | - Yes.

01:22:35.720 | - Like in the 90s it was like it contains antioxidants.

01:22:38.180 | Not to say antioxidants are bad,

01:22:39.760 | but they are certainly not the be all end all of health.

01:22:42.220 | - They are not, but that's exactly

01:22:44.260 | where that research came from.

01:22:45.860 | Is that researchers were narrowing in

01:22:48.460 | on these reactive oxygen species

01:22:50.620 | are highly, highly correlated with all of the diseases

01:22:55.520 | of aging and poor health outcomes.

01:22:58.740 | Turns out they're also highly, highly correlated

01:23:01.720 | with all chronic mental disorders, interestingly.

01:23:05.660 | And so researchers used antioxidants to see if,

01:23:09.900 | well maybe if we can stop, somehow tame

01:23:12.860 | these reactive oxygen species,

01:23:14.280 | we'll improve health outcomes.

01:23:15.580 | Doesn't seem to work.

01:23:16.980 | By the 1970s our understanding of mitochondria

01:23:20.360 | and their role in the production

01:23:21.540 | of reactive oxygen species expanded,

01:23:23.840 | and that led to the mitochondrial theory of aging.

01:23:27.100 | So in the 1970s we had this mitochondrial theory of aging,

01:23:30.440 | based primarily and exclusively on reactive oxygen species.

01:23:34.220 | Fast forward a couple of decades,

01:23:37.360 | that was disproven because we now know reactive oxygen

01:23:40.160 | species aren't all bad.

01:23:41.680 | They actually serve a signaling process.

01:23:43.960 | They're a normal part of human functioning

01:23:46.280 | and cellular function.

01:23:48.000 | So they're not all bad, but we still know high levels

01:23:51.760 | of reactive oxygen species are bad for you.

01:23:55.220 | Fast forward to just, I think maybe last year,

01:23:59.400 | with this expanded role of all of the different things

01:24:02.000 | mitochondria are doing.

01:24:03.660 | So David Sinclair published a paper

01:24:07.420 | in one of the Cell journals, I think,

01:24:09.380 | saying that oh, mitochondria are actually the unifying link

01:24:14.380 | of everything that we know about aging.

01:24:17.220 | Mitochondria are the cause, or defective mitochondria,

01:24:21.220 | or defective mitochondrial function,

01:24:23.640 | mitochondrial dysfunction,

01:24:25.540 | is possibly the unifying cause of aging

01:24:30.020 | and all of the aging-related disorders.

01:24:33.640 | So mitophagy is trying to address all that,

01:24:38.640 | is trying to say, okay, this is bad.

01:24:40.720 | We don't want defective mitochondria,

01:24:42.700 | and how can we get rid of old ones or defective ones

01:24:46.580 | and replace them with new ones?

01:24:49.460 | And I think the most powerful signal and tool

01:24:54.460 | that we have right now is in fact related to diet.

01:25:01.820 | It's calorie restriction.

01:25:03.480 | That is the oldest, truest, kind of best-proven way

01:25:08.480 | to prevent aging in a wide variety of animal species.

01:25:15.040 | Fasting and intermittent fasting,

01:25:18.100 | and again, you can only do those things for so long,

01:25:20.920 | and then fasting-mimicking diets

01:25:23.280 | can also stimulate this process of mitophagy.

01:25:29.060 | Before we talk about mitochondrial biogenesis,

01:25:31.700 | if, and I certainly accept the idea

01:25:36.520 | that mitochondria are extremely important

01:25:39.500 | in physical health and mental health.

01:25:41.340 | That's, for me, is a straightforward conclusion

01:25:44.880 | at this point, based on what you've said,

01:25:46.800 | what I've read elsewhere, et cetera.

01:25:48.940 | And if various diets, including ketogenic diet,

01:25:54.680 | including fasting, reducing sugar intake, et cetera,

01:25:58.200 | can assist in mitochondrial function and mitophagy,

01:26:01.800 | and that's at least one of the levers

01:26:04.100 | by which diet can positively impact mental health

01:26:07.480 | and physical health, can we conclude

01:26:11.420 | that there's something special

01:26:12.980 | about low blood glucose in the brain, right?

01:26:16.420 | I mean, the sort of common pathway of all of those things,

01:26:19.260 | fasting, ketogenesis, for some people,

01:26:22.400 | maybe some people have great insulin management,

01:26:26.180 | so just removing sweets, you know, refined sugars,

01:26:29.700 | you know, brings down their blood glucose levels

01:26:32.260 | substantially, they don't need to go on a ketogenic diet

01:26:34.340 | in order to relieve a low-level depression

01:26:36.100 | or something like that.

01:26:37.140 | It seems like the common theme here

01:26:39.420 | is that glucose levels in the brain need to be reduced,

01:26:43.900 | which for me is surprising because neurons love glucose.

01:26:48.900 | I mean, there are some really nice studies,

01:26:51.780 | one that I can think of recently

01:26:53.580 | that was published in Neurons.

01:26:54.540 | If you just look at the tuning of a neuron,

01:26:56.240 | how well a neuron in the brain

01:26:58.820 | represents some visual image in the environment

01:27:01.980 | in terms of, here we can just generalize

01:27:03.620 | in saying more action potentials,

01:27:05.420 | more electrical signals from the neuron

01:27:06.960 | generally correlates with better,

01:27:08.840 | high-fidelity representation.

01:27:10.580 | It's like sort of, you know,

01:27:11.600 | if every time someone says shout

01:27:13.780 | and then someone shouts, the neuron is like

01:27:15.900 | the one responding to the order,

01:27:17.900 | and these neurons, just when there's high glucose,

01:27:20.100 | they are faithful representatives

01:27:22.440 | of what's out there in the world.

01:27:24.380 | But then when you fast an animal,

01:27:26.300 | they become less faithful representatives

01:27:28.220 | of what's out there.

01:27:29.540 | And yet, when I've done intermittent fasting

01:27:31.740 | and I do a kind of modified version of it,

01:27:33.760 | my mental clarity is far better

01:27:35.280 | than when I've had a big bowl of pasta,

01:27:37.180 | probably for other reasons related to serotonin

01:27:40.180 | and tryptophan, and so I think for the typical listener

01:27:44.980 | out there, I have to imagine

01:27:45.820 | it's got to be a little confusing, right?

01:27:47.100 | We hear neurons love glucose, they live on glucose.

01:27:50.980 | And here we're saying, let's deprive them of some glucose,

01:27:54.020 | or let's just bring glucose levels down,

01:27:56.280 | or let's switch the fuel source of the brain

01:27:58.160 | from glucose to ketones,

01:28:00.820 | and now the brain really works the way it's supposed to.

01:28:03.980 | So this raises a little bit of a just-so-story question,

01:28:06.500 | like why would it be the case that neurons love glucose,

01:28:11.500 | and yet, if there's too much glucose around,

01:28:13.540 | they become sick?

01:28:14.500 | And of course, with any why-would-it-be story,

01:28:19.480 | as I always say, you know, I wasn't consulted

01:28:21.220 | at the design phase, and I'm going to presume

01:28:22.940 | that you weren't consulted at the design phase either,

01:28:25.660 | and that if any of us say that we are,

01:28:27.020 | then we are probably the patients that need evaluation.

01:28:29.780 | So I think there's a name for that, right?

01:28:31.460 | There's delusion, right?

01:28:32.480 | Okay, throughout my first correct clinical assessment

01:28:35.180 | of myself.

01:28:36.060 | So how do I get my head around this, right?

01:28:40.040 | You've got me sold on mitochondria,

01:28:41.700 | not that I needed to be sold, but that's an easy,

01:28:43.900 | like yes, yes, absolutely yes.

01:28:46.060 | The idea that diet can impact mental health

01:28:47.860 | and physical health, yes, absolutely,

01:28:49.580 | by way of mitochondria, at least in part, great.

01:28:53.340 | But then neurons love glucose.

01:28:55.460 | So what's going on, or what do you think is going on?

01:28:58.540 | - I am not convinced that glucose is the real story.

01:29:05.640 | Glucose may in fact be a symptom.

01:29:17.180 | So we know that parts of the brain,

01:29:20.140 | you know, there have been a couple of studies

01:29:22.340 | that just came out in the last couple of weeks, I think,

01:29:25.900 | documenting that actually astrocytes in the hypothalamus

01:29:30.900 | play a key role in glucose regulation throughout the body.

01:29:37.180 | And it appears to be a metabolic role,

01:29:43.420 | which in my mind implies that the mitochondria

01:29:48.060 | in those astrocytes are probably playing a key role,

01:29:51.580 | because we know mitochondria play a key role

01:29:54.480 | in sensing glucose levels.

01:29:57.180 | They play a key role in the release of insulin

01:30:01.180 | from the pancreas.

01:30:02.780 | But mitochondria in the brain is also playing a role

01:30:09.240 | in kind of balancing how much glucose is around.

01:30:14.240 | And so it's a difficult question,

01:30:20.060 | because I think in some cases, high glucose levels

01:30:24.000 | are actually a symptom of metabolic dysfunction

01:30:28.780 | somewhere in the body or brain.

01:30:31.600 | And when I think about, well, what does that mean?

01:30:37.000 | In my mind, most of the evidence currently is pointing

01:30:41.500 | to mitochondrial dysfunction somewhere in the body or brain

01:30:46.500 | that is the most likely cause

01:30:49.580 | of that dysregulation of glucose levels.

01:30:52.980 | But we know that if you consume massive amounts

01:31:00.780 | of junk food, sugar, and other things,

01:31:04.980 | that you can get dysregulation of glucose levels.

01:31:09.820 | The conundrum though is that that's not a universal response.

01:31:17.400 | - And what about the typical person?

01:31:19.160 | I've never really liked junk food that much.

01:31:21.040 | Maybe as a kid, I can recall liking candy,

01:31:23.640 | but I was a sandwich for lunch person for a long time.

01:31:27.120 | And as I've changed that out for salad

01:31:30.200 | and maybe a small piece of meat with my salad

01:31:33.660 | or something like that, I feel far better during the day,

01:31:36.020 | far more alert, but I do eat carbohydrates.

01:31:37.880 | I eat starches typically at night,

01:31:39.280 | but I tend to do some very hard training

01:31:41.580 | at some point during the day.

01:31:42.920 | So I imagine I have some glycogen to repack.

01:31:45.320 | Okay, that's me.

01:31:46.400 | I only mentioned that because I'm not in ketosis

01:31:49.720 | as far as I know.

01:31:50.560 | I haven't, unless you brought the strips,

01:31:52.320 | I haven't done the blood glucose test today.

01:31:54.840 | So what about the typical person who's an omnivore

01:32:00.000 | eating some rice, some pasta, pasta salads,

01:32:05.000 | people that are eating not junk food,

01:32:08.300 | massive amounts of sugar,

01:32:09.980 | but have blood glucose that's in kind of moderate range.

01:32:13.380 | Do you think, and here feel free to speculate,

01:32:16.400 | do you think that those people might feel far better

01:32:20.780 | or even a little bit better

01:32:22.020 | if they were in a lower glucose state?

01:32:26.800 | And I asked this because I think there are a lot of people

01:32:29.880 | out there who suffer from full-blown depression,

01:32:31.920 | but there are also a lot of people who suffer

01:32:33.500 | from like moodiness and feeling not so great,

01:32:36.880 | subclinical depression.

01:32:38.440 | - Yes, burnout is what I would call it.

01:32:40.380 | - Yeah, and just feeling like some days are great

01:32:42.880 | and then other days they feel lousy

01:32:44.280 | for reasons they don't understand.

01:32:46.440 | - Yeah.

01:32:47.520 | - And those make for less dramatic case studies.

01:32:50.140 | And yet I have to assume that that description

01:32:52.880 | will net a large fraction of the general public.

01:32:57.640 | - So the way that I kind of break this field,

01:33:02.160 | and I'm probably getting too nerdy right now,

01:33:04.280 | but I kind of break this field into cause,

01:33:07.200 | what's the actual root cause,

01:33:11.200 | and what are effective treatments?

01:33:14.520 | And I really see them as two separate things.

01:33:16.960 | Just because the ketogenic diet is an effective treatment

01:33:22.960 | does not imply that the cause of the problem

01:33:26.400 | was eating carbohydrates.

01:33:29.040 | And I think that's a really important distinction.

01:33:32.320 | There are many people who disagree with me on that.

01:33:34.660 | There's no doubt about it.

01:33:35.760 | And everybody's heard people say,

01:33:37.660 | sugar is the cause of everything that ails you,

01:33:40.560 | or carbs are the cause of everything that ails you.

01:33:42.840 | If everybody does a low carb diet or a ketogenic diet,

01:33:46.320 | and then they go to,

01:33:47.880 | so it must be sugar that was the cause.

01:33:51.740 | I don't see it as clearly black and white as that.

01:33:56.500 | The calorie restriction, ketogenic diet,

01:34:01.220 | carbohydrate restriction are inducing metabolic changes

01:34:06.220 | in the brain and body.

01:34:08.560 | And regardless of what the person was eating,

01:34:13.860 | they are inducing metabolic changes

01:34:16.400 | that can be really beneficial to brain health.

01:34:19.540 | So let me just give a clear black and white example of this.

01:34:23.480 | And then I can speak to the broader topic

01:34:26.440 | that you brought up about just the general population.

01:34:29.560 | The easy example of the ketogenic diet

01:34:32.260 | being an effective intervention

01:34:34.480 | for somebody who was not following a bad diet

01:34:37.660 | is an infant with epilepsy.

01:34:39.480 | There are lots of infants who have uncontrollable seizures.

01:34:44.840 | They are drinking breast milk.

01:34:47.360 | To the best of our knowledge,

01:34:48.580 | that is the primary most beneficial food source

01:34:53.320 | an infant could be consuming.

01:34:56.100 | Now some might say, well, maybe the mother's,

01:34:59.120 | you know, whatever, I don't buy that.

01:35:02.560 | The mother's breast milk is in fact

01:35:04.320 | the optimal food source for that infant.

01:35:07.920 | And yet that infant is still seizing.

01:35:10.380 | If we put that infant on a ketogenic diet,

01:35:12.720 | a lot of those infants' seizures will stop.

01:35:16.020 | It doesn't mean that the cause of the infant's seizures

01:35:19.200 | was a bad diet, but it means a dietary intervention

01:35:23.240 | can change brain metabolism

01:35:25.240 | and improve symptoms in that person.

01:35:29.880 | So going to your broader question about adults modern day,

01:35:33.980 | the real answer is, you know,

01:35:36.960 | there was just this conference in London,

01:35:41.000 | the Royal College of Obesity Medicine

01:35:43.680 | or something like that.

01:35:44.840 | That's not the name, but it's something along those lines.

01:35:48.020 | The conclusion of that conference,

01:35:51.940 | it invited the greatest minds in obesity medicine.

01:35:56.440 | The overarching conclusion of that conference was,

01:35:58.860 | we don't know what causes obesity.

01:36:01.220 | It's really important that we sit with that.

01:36:08.520 | We don't know what causes obesity.

01:36:11.140 | - They don't think excess caloric intake

01:36:12.920 | beyond one's daily metabolic needs is causing obesity.

01:36:17.740 | - Some will argue that, and so some will say yes,

01:36:22.280 | it's all energy balance,

01:36:24.800 | but why do we have an epidemic of obesity?

01:36:27.960 | - Well, that's the gazillion dollar question.

01:36:32.040 | - And junk, some will say it's all the junk food,

01:36:35.440 | but we had junk food in the 1970s.

01:36:37.480 | When I was growing up, I grew up on Kool-Aid

01:36:40.200 | and Twinkies and King Dongs and Ho-Hos and-

01:36:43.520 | - Oh, I'm rewatching the Mad Men series now.

01:36:46.800 | I love that series and I'm rewatching it.

01:36:48.480 | And I happen to know someone who worked on that series.

01:36:51.360 | They research everything for the props and the costumes,

01:36:54.320 | everything, but right down to diet.

01:36:55.620 | And if you look at the diet, it was terrible.

01:36:57.920 | It was mostly, yes, there was a lot of excessive amounts

01:37:00.340 | of drinking and cigarette smoking,

01:37:01.720 | but the diets were terrible.

01:37:03.680 | It was prepackaged foods.

01:37:05.240 | It was frozen dinners.

01:37:06.500 | I mean, that really came to prominence

01:37:08.080 | in the '70s and '80s.

01:37:09.960 | But even in the '50s and from what I've been reading,

01:37:14.160 | even in the '30s and '40s,

01:37:16.000 | people were not eating grass-fed meat and Brazil nuts

01:37:21.200 | with a little bit of broccoli rabe on the side.

01:37:23.920 | That is not the typical intake.

01:37:27.160 | So something out there or maybe multiple things

01:37:30.780 | are at play to increase obesity.

01:37:33.820 | - And at the end of the day, I believe,

01:37:38.280 | some will call this speculative,

01:37:39.920 | but I actually think we've got a tremendous amount

01:37:41.920 | of evidence that continues to point in this direction.

01:37:45.440 | I believe that mitochondria are the key

01:37:48.080 | to the obesity epidemic,

01:37:50.400 | that there is something in our environment.

01:37:54.460 | So that is either our food, environmental toxins,

01:37:59.120 | stress levels, poor sleep, not getting adequate sunlight,

01:38:04.240 | whatever you want to speculate on, all of the above.

01:38:08.440 | All of those things are known

01:38:11.400 | to impair mitochondrial function.

01:38:14.080 | And if parts of your brain that regulate metabolism

01:38:19.080 | and that regulate eating behaviors

01:38:23.600 | are not metabolically healthy,

01:38:27.160 | it means that they will not stop you from eating,

01:38:30.620 | or it means that your metabolism will not rise

01:38:34.220 | to the challenge of 10 donuts,

01:38:38.200 | because some people can eat 10 donuts

01:38:40.160 | and go on staying thin and healthy.

01:38:42.880 | - Although I totally agree,

01:38:44.520 | although I would just like to say that it seems to me

01:38:47.800 | that compared to when I was growing up,

01:38:49.280 | and again, I haven't run the statistics,

01:38:51.100 | there are fewer and fewer of those individuals around now.

01:38:53.860 | Just as when I was growing up,

01:38:55.300 | it was one or two kids in class that were quite overweight,

01:39:00.440 | and then there were some that were mildly overweight,

01:39:02.740 | but most were of healthy weight.

01:39:05.100 | Nowadays, that's dramatically altered.

01:39:08.560 | The landscape is dramatically altered in the other direction.

01:39:11.560 | It is rare when I encounter one of those

01:39:15.200 | can eat anything type people.

01:39:17.020 | I know one, he's actually an employee at Stanford.

01:39:18.920 | He's on our media team at Stanford.

01:39:20.460 | And this guy, when I take him to lunch, it's like,

01:39:23.020 | and he's in his early 70s, and he can eat,

01:39:26.960 | and he's incredibly lean.

01:39:28.040 | He exercises a little bit,

01:39:29.200 | but he's one of these mutants that just can eat,

01:39:33.320 | and eat, and eat, and he's lean, and he's vital,

01:39:36.240 | and it's wild, and he's an expensive lunch.

01:39:40.520 | But those people seem rare,

01:39:45.240 | and even those kids are now seem rare.

01:39:47.440 | - They're getting increasingly rare.

01:39:49.000 | And that leads me to think it may be epigenetic factors

01:39:53.940 | in the womb environment,

01:39:55.640 | so that kids are actually coming out predisposed

01:39:58.960 | to obesity.

01:40:00.180 | - Well, let me ask you about that,

01:40:01.160 | because I had a note here to ask this later,

01:40:03.000 | but I'm going to interrupt you now

01:40:04.120 | in order to capture this moment.

01:40:06.540 | My understanding is that,

01:40:08.840 | well, as everyone knows, we inherit DNA.

01:40:10.560 | We get genes from both of our parents, and they mix.

01:40:12.880 | Although there are incredible data

01:40:14.880 | from Catherine Dulock's lab at Harvard,

01:40:16.600 | and others showing that we actually have

01:40:18.520 | entire regions of our brain that carry neurons

01:40:22.600 | that are purely of mom's or of dad's DNA,

01:40:26.740 | depending on the brain region.

01:40:27.720 | This is a wild finding, but it's accurate,

01:40:30.760 | and this has actually been known about

01:40:31.880 | in terms of heritability of disease, et cetera.

01:40:34.360 | Maternal DNA, DNA from mom, genes from our mother,

01:40:40.800 | not to place blame on mothers at all,

01:40:43.220 | my understanding is that the mitochondrial DNA

01:40:46.300 | come exclusively through the maternal side.

01:40:48.800 | Is that true?

01:40:50.440 | - So it's a great question,

01:40:51.680 | and I've been asked this before,

01:40:52.920 | and yeah, psychiatrists are known for blaming mothers,

01:40:56.280 | and some might say that I'm trying to redo

01:40:58.760 | that whole thing and blame mothers again.

01:41:00.980 | - The data or the data, I'm not trying to blame mothers here.

01:41:04.560 | Mothers play an essential role in everything,

01:41:08.880 | but if it is true that mitochondria

01:41:11.920 | are the linchpin of all this,

01:41:13.160 | and maternal DNA is what determines the mitochondrial DNA,

01:41:15.920 | I think it's an important place to look.

01:41:17.480 | - It's an important question,

01:41:18.640 | and the answer is unequivocally no.

01:41:21.440 | That's not the way it works.

01:41:23.480 | - Vindication for anyone that was asserting that.

01:41:25.720 | - And so let me explain it.

01:41:26.840 | So mitochondria have 36 genes unto themselves.

01:41:31.160 | 13 of those genes code for some of the mitochondrial

01:41:34.560 | machinery of making ATP, and the other 36 play roles

01:41:38.920 | in epigenetic regulation, play roles in whole body

01:41:43.300 | metabolism and other things.

01:41:45.800 | So that is what you're inheriting from your mom,

01:41:48.800 | is the mitochondria and those 36 genes for the most part.

01:41:54.340 | But the majority of proteins that make up mitochondria,

01:41:59.340 | over I think 1,300 genes that make up mitochondria

01:42:03.140 | are actually encoded in the nuclear DNA.

01:42:06.900 | And so you inherit a copy from both your mother

01:42:09.780 | and your father.

01:42:11.100 | So the majority of people who have mitochondrial defects

01:42:14.600 | or rare mitochondrial diseases actually could inherit them

01:42:20.340 | from either mom or dad, because it can be a defect

01:42:24.600 | in the nuclear genes that code for proteins

01:42:29.600 | that make up mitochondria.

01:42:31.000 | The much bigger issue, so when I talk about

01:42:36.360 | mitochondrial dysfunction being a primary driver

01:42:40.520 | of mental illness, metabolic illness,

01:42:43.800 | it's not that people inherit a defective mitochondrion

01:42:50.120 | or mitochondria from mom, and then that just ruins

01:42:54.520 | their life forever.

01:42:56.200 | That's actually not the way it works.

01:42:58.560 | The beautiful thing about this theory is that it connects

01:43:03.520 | all of the risk factors that we already know play a role

01:43:07.760 | in mental health, but also metabolic health.

01:43:12.320 | Sleep disruption impairs mitochondria

01:43:15.680 | and mitochondrial function.

01:43:17.800 | Stress, high levels of stress and trauma

01:43:20.320 | impair mitochondrial function.

01:43:22.780 | Drug and alcohol use.

01:43:24.760 | Alcohol, tobacco definitely in terms of the smoke,

01:43:29.760 | and marijuana, THC in particular,

01:43:33.600 | all impair mitochondrial function.

01:43:35.840 | - THC directly or the smoke?

01:43:39.360 | - THC directly, those studies have been done.

01:43:42.400 | And so mitochondria actually have CB1 receptors, right?

01:43:48.000 | On them, and various researchers, a couple of studies

01:43:53.000 | from Nature actually documented this,

01:43:56.200 | that the mitochondrial CB1 receptors are primary,

01:44:01.200 | kind of primary points of the influence of marijuana

01:44:08.640 | on human behaviors and effects.

01:44:12.600 | So because when they remove CB1 receptors

01:44:16.200 | in animal models, these changes don't happen.

01:44:20.120 | So the CB1 receptors, we've got some large studies

01:44:24.960 | of adolescents who use a lot of marijuana,

01:44:27.700 | and the areas where the mitochondria have the greatest number

01:44:31.200 | of CB1 receptors are areas of their brains

01:44:34.460 | that actually are atrophied or shrunk

01:44:38.560 | compared to normal healthy controls.

01:44:40.960 | So that means their brain tissue is aging prematurely,

01:44:43.840 | it's shrinking prematurely, but the CB1 receptors

01:44:48.840 | on mitochondria also seem to play a role

01:44:51.440 | in the memory impairment that can be induced from THC,

01:44:55.320 | and they also play a role in the kind of lack of motivation,

01:45:01.920 | the behavioral amotivational state from THC.

01:45:07.640 | Now again, for people who want to chillax,

01:45:11.200 | that's what they're looking for.

01:45:12.960 | They don't want to remember anything.

01:45:14.680 | They don't want to think.

01:45:16.360 | They want to be spaced out.

01:45:18.580 | They want to relax.

01:45:20.380 | That's great, but it's important that they know

01:45:24.560 | that they're actually harming the mitochondria

01:45:26.800 | in their brain cells,

01:45:28.600 | and that although there's always an opportunity

01:45:34.080 | to repair mitochondria and always an opportunity

01:45:36.960 | to stimulate mitochondrial biogenesis

01:45:39.160 | so you can get it back, but if you keep doing it chronically

01:45:42.520 | you're probably not helping your overall mental

01:45:46.000 | or metabolic health.

01:45:47.120 | - Yeah, I'm glad you brought up THC.

01:45:48.520 | We did an episode on Canvas.

01:45:49.880 | We also did one on alcohol.

01:45:51.620 | Probably lost some friends from that one.

01:45:54.020 | I mean, when you look at the data, it's very clear.

01:45:55.700 | I mean, I'm not arguing that people dislike the effects

01:45:59.040 | of these compounds when they take them,

01:46:02.060 | but it is clear that, at least to me, based on the data,

01:46:06.100 | that regardless of what people have read about red wine,

01:46:08.280 | that not drinking any alcohol is going to be healthier

01:46:10.720 | than drinking alcohol, and that the thresholds for alcohol

01:46:12.840 | ingestion before people start to negatively impact

01:46:15.220 | their health is about one or two per week.

01:46:17.440 | And then THC, because of the very high concentrations

01:46:19.960 | of THC that are present in a lot of products now,

01:46:23.120 | vaping and smoking THC and even edibles,

01:46:26.100 | that it can be problematic.

01:46:28.440 | You mentioned adolescence, you know,

01:46:29.880 | predisposition of brain atrophy, psychosis, et cetera.

01:46:33.040 | In any case, because you mentioned alcohol

01:46:36.280 | and because it is a commonly used substance,

01:46:40.400 | I heard you give a talk in which,

01:46:42.560 | I think I have this right, in which alcohol

01:46:46.320 | can disrupt the way that the brain uses fuels of all kinds,

01:46:52.320 | which may disrupt one's response to alcohol,

01:46:57.520 | make alcohol seem more rewarding to those that drink alcohol.

01:47:02.940 | So drinking alcohol makes alcohol more rewarding

01:47:06.000 | to the brain's alcohol drinkers.

01:47:08.980 | But that it also might alter glucose metabolism,

01:47:12.800 | that basically alcohol is not good for our brains.

01:47:16.680 | Do I have that correct?

01:47:17.800 | - You do have that correct.

01:47:18.900 | - Okay.

01:47:19.740 | What happens if you take an alcoholic

01:47:23.780 | or somebody that just drinks, you know,

01:47:26.060 | two to four nights a week, a couple of drinks,

01:47:28.740 | which I think is pretty common out there,

01:47:31.420 | and you put them on a ketogenic diet,

01:47:33.620 | has that experiment been done?

01:47:35.220 | - That experiment has been done.

01:47:36.980 | And led by none other than a woman named Nora Volkow,

01:47:41.980 | who is one of the leading neuroscientists

01:47:45.100 | and addiction researchers in the world.

01:47:47.600 | She is the director of the National Institute of Drug Abuse.

01:47:51.220 | She's been hot on the trail of metabolic abnormalities

01:47:54.820 | in the brains of people with alcohol use disorder,

01:47:57.740 | which I will just refer to as alcoholics,

01:48:00.140 | because that's what everybody knows it as.

01:48:03.020 | So she's been hot on this trail for many, many years.

01:48:06.980 | And as you said, it turns out that the reward pathways

01:48:11.980 | in particular are metabolically compromised in alcoholics.

01:48:17.840 | And the metabolic compromise essentially in a nutshell

01:48:20.500 | means they aren't getting enough fuel from glucose.

01:48:24.100 | The interesting thing is that when people drink alcohol,

01:48:27.920 | your liver converts alcohol into a molecule called acetate.

01:48:32.260 | That acetate travels up to the brain

01:48:34.820 | and fuels brain cells, in particular,

01:48:37.820 | some of these reward pathway cells more than others.

01:48:41.060 | And so chronic alcoholics have this chronic deprivation

01:48:46.060 | of energy in these cells.

01:48:49.580 | And so Nora Volkow and other researchers

01:48:52.380 | at National Institutes of Health did a study

01:48:55.780 | in which they set out to see if we can change

01:49:00.340 | this brain metabolic problem in alcoholics.

01:49:04.900 | Will that affect clinical symptoms of alcoholism

01:49:08.820 | and will it do anything that's clinically useful?

01:49:13.420 | And so they actually did a pilot randomized controlled trial,

01:49:18.420 | admitted alcoholics to a detox unit.

01:49:22.020 | Half of the patients got a ketogenic diet.

01:49:24.520 | The other half got the standard American diet.

01:49:27.340 | And then everybody else, all of them got the same detox protocol.

01:49:32.140 | The patients who got the ketogenic diet

01:49:35.580 | required fewer benzodiazepines for their detox.

01:49:40.280 | Despite that, they had fewer withdrawal symptoms

01:49:44.620 | from the alcohol.

01:49:46.240 | They reported fewer cravings for alcohol.

01:49:49.700 | And the researchers did brain scans

01:49:53.100 | which showed improved brain metabolism

01:49:56.220 | in these key areas that they were looking at.

01:49:59.480 | And their brains showed reduced levels of neuroinflammation

01:50:05.580 | which was also something they were really interested in.

01:50:09.300 | And so that one study says to us

01:50:13.460 | that even though most people would think

01:50:16.860 | alcoholism has nothing to do with diet,

01:50:19.820 | alcohol is just drinking too much.

01:50:22.180 | It's a matter of willpower.

01:50:24.340 | Or it's somebody who's addictive.

01:50:25.860 | They've got an addictive personality.

01:50:27.820 | And it's that simple.

01:50:29.260 | You come out of the womb with an addictive personality

01:50:32.500 | and those people are novelty seekers

01:50:36.020 | and they're impulsive and they have no patience.

01:50:39.420 | They have no discipline.

01:50:40.740 | They can't sustain any kind of rewarding experience.

01:50:45.480 | - Or childhood trauma.

01:50:47.020 | There's a story there, which they're very well maybe.

01:50:51.580 | - And there may be.

01:50:53.020 | But what that research study strongly suggests,

01:50:57.780 | and again, yes, maybe we need larger controlled trials,

01:51:01.300 | but this is one of the leading neuroscientists in the world

01:51:03.780 | who's hot on this trail.

01:51:04.780 | This is what she believes and this is what I believe,

01:51:08.300 | is that if we can correct the brain metabolic defects

01:51:11.860 | from chronic alcohol use,

01:51:13.980 | we might be able to help people be sober

01:51:17.500 | and give them a fighting chance or give them an edge up

01:51:21.500 | or pull a lever that we can use in their favor

01:51:25.940 | for their benefit.

01:51:27.660 | There's one caution to all of this research

01:51:29.560 | that I really do want to highlight.

01:51:31.220 | And so now I'm going to get hate mail

01:51:33.220 | from all the keto community.

01:51:35.320 | - That's okay.

01:51:36.160 | I mean, anytime I admire you

01:51:37.540 | for talking about nutrition at all,

01:51:38.940 | because anytime one talks about nutrition,

01:51:41.580 | you're going to get hate mail from somebody, but.

01:51:44.680 | - So the caveat to all of this is that

01:51:48.700 | as part of the research that those researchers were doing,

01:51:53.700 | they actually wanted to see what will happen

01:51:57.180 | to alcohol levels

01:51:59.780 | if an animal consumes alcohol while on a ketogenic diet.

01:52:04.780 | So they didn't do this in humans yet.

01:52:08.240 | This is a fairly easy study to do.

01:52:10.260 | So I'm hoping somebody will do this study soon.

01:52:13.000 | But they instead put rats, half of them on a standard diet

01:52:17.460 | and half of them on a ketogenic diet.

01:52:19.180 | And then they expose them

01:52:20.200 | to the exact same amount of alcohol.

01:52:22.840 | The rats who were on the ketogenic diet

01:52:25.060 | had a five-fold increase in blood alcohol levels.

01:52:28.920 | Five-fold increase.

01:52:31.380 | - Meaning they drank more or it was metabolized differently?

01:52:34.720 | - It was metabolized differently.

01:52:36.540 | The rats all got the same amount of alcohol.

01:52:39.220 | - So for people out there who are ketogenic,

01:52:42.500 | I'm a little chuckling, but who are not alcoholics,

01:52:44.500 | please alcoholics, please do something about it

01:52:46.400 | 'cause it's so detrimental.

01:52:47.460 | But I guess, does this mean that they can drink less

01:52:50.240 | in order to get the effect of alcohol

01:52:52.080 | that most people are seeking?

01:52:53.240 | - Cheap dates.

01:52:54.660 | Cheap date is what you call that.

01:52:56.300 | You only need a half a drink instead of three drinks.

01:52:59.740 | - I would think the keto community would thank you for this

01:53:01.740 | unless they somehow have a stake in the alcohol industry.

01:53:05.240 | - The reason that I put it as a caution

01:53:09.460 | is that if anybody is struggling with alcoholism

01:53:12.280 | and thinks, "Hey, I need an edge up.

01:53:14.300 | I need a lever to pull because I'm really struggling

01:53:16.880 | to give this stuff up."

01:53:18.560 | I just find myself going back.

01:53:20.220 | And if you're telling me my brain metabolism is messed up

01:53:23.540 | and this might help it, I'm all in favor of that.

01:53:27.540 | And yes, that's what the researchers are pursuing.

01:53:29.840 | And that's what I'm saying with the following caveat,

01:53:34.120 | that if you relapse while on a ketogenic diet,

01:53:37.780 | you better not drink the same amount of alcohol

01:53:40.340 | that you think you can drink.

01:53:43.240 | - Could be deadly.

01:53:44.340 | - It could be deadly and/or it could be really deadly

01:53:49.100 | to you or someone else because unfortunately,

01:53:51.420 | a lot of times when people drink,

01:53:53.180 | they get behind the wheel and they think

01:53:55.580 | that they can handle two drinks safely.

01:53:58.420 | And they think, "Well, I can go out for dinner

01:54:00.780 | and have two glasses of wine and drive home safely."

01:54:04.040 | I know myself.

01:54:05.540 | If you go to a ketogenic diet,

01:54:08.480 | please don't drive with the same two drinks

01:54:11.500 | because it means your blood alcohol level,

01:54:13.740 | if it models anything that we found in the rat study,

01:54:18.160 | your blood alcohol levels may be five times higher

01:54:20.660 | than they would normally be.

01:54:22.320 | And that means you are really wasted

01:54:25.200 | and you're probably not safe to be driving.

01:54:27.440 | - Probably the same is true for drinking

01:54:28.840 | on an empty stomach, right?

01:54:30.300 | - Yeah. - Yeah.

01:54:31.360 | No, that's a very important point

01:54:32.920 | and thank you for raising that.

01:54:34.900 | I mean, I hear this again about mitochondria,

01:54:40.920 | about blood glucose.

01:54:42.960 | You mentioned astrocytes.

01:54:44.060 | And for those of you who heard that earlier,

01:54:46.140 | astrocytes are a non-neuron cell type in the brain,

01:54:49.460 | a glial cell type that my postdoc advisor

01:54:53.020 | was known for popularizing the modern science of glia,

01:54:56.620 | which include astrocytes.

01:54:57.620 | And I'd be remiss if I didn't say that they do,

01:55:00.740 | they are considered the cells

01:55:03.180 | that hold everything together in the brain

01:55:04.580 | and are kind of passive observers,

01:55:06.260 | but they do many things actively there.

01:55:09.400 | I think now people appreciate the astrocytes

01:55:11.720 | as at least as important as the neurons.

01:55:14.720 | And certainly for disease,

01:55:16.260 | they are often implicated in warding off of disease, et cetera.

01:55:20.820 | Everything that you're telling me about,

01:55:22.420 | the fact that the brain can regulate things

01:55:24.340 | that are happening in the body, metabolism, et cetera,

01:55:27.060 | organ health, obesity, et cetera.

01:55:29.660 | To me as a neuroscientist, that's not surprising.

01:55:32.260 | All of it just screams hypothalamus, hypothalamus,

01:55:35.240 | hypothalamus, 'cause here you're telling me

01:55:37.020 | it's regulating these basal functions like metabolism.

01:55:40.360 | It's regulating how much we crave things.

01:55:42.880 | And of course, hypothalamus is involved

01:55:44.800 | in motivation and craving.

01:55:45.960 | There are other areas too,

01:55:47.480 | other areas of the brain too, of course.

01:55:49.400 | But I would imagine that someone ought to,

01:55:52.960 | or has mapped out where the receptors

01:55:57.960 | for all this business are in the brain.

01:56:00.280 | And I guess that raises the question

01:56:03.480 | of when one goes on a ketogenic or low blood glucose diet

01:56:07.880 | or FAS, has anyone observed changes in the brain?

01:56:12.360 | Has anyone had neuroimaging of humans and their brains

01:56:15.700 | under conditions of ingesting one diet or another,

01:56:19.480 | whether or not they're suffering

01:56:21.280 | from a psychiatric disorder or not?

01:56:23.400 | I would think that's where the gold is.

01:56:26.540 | - We do have some of those studies.

01:56:29.500 | So, and they've, when you do a neuroimaging study,

01:56:33.540 | you can measure a lot of different things.

01:56:35.180 | So one thing, with a PET scan,

01:56:37.180 | you can measure glucose metabolism.

01:56:39.580 | So a researcher, Steven Cunane, is doing that research,

01:56:43.740 | in particular in Alzheimer's disease patients

01:56:47.620 | and Alzheimer's disease models, but in humans.

01:56:51.220 | And that's because we know that, again,

01:56:56.220 | a common finding in patients with Alzheimer's disease

01:56:59.380 | is this glucose hypo metabolism.

01:57:02.900 | Some people are attributing it

01:57:04.420 | to insulin signaling impairment.

01:57:07.300 | And so some people are calling it type three diabetes.

01:57:10.340 | The end of the day, I think the clearest signal

01:57:14.200 | that we have is that cells aren't getting enough energy

01:57:17.740 | from glucose as a fuel source.

01:57:20.100 | That is something that I think I can confidently say

01:57:23.540 | that's backed by numerous research studies.

01:57:26.780 | There's debate in the research field

01:57:28.300 | about whether that's a primary driver of the illness.

01:57:31.740 | I happen to believe it is.

01:57:33.660 | And if you ask the question,

01:57:35.340 | well, why would cells not be getting enough fuel

01:57:37.640 | from glucose, you have to focus on mitochondria

01:57:40.780 | 'cause they're the ones producing the fuel

01:57:43.020 | from that glucose.

01:57:44.020 | So somehow you have to implicate mitochondria

01:57:46.500 | in that process one way or another.

01:57:48.480 | Others will say, no, that's just a side effect

01:57:52.660 | of whatever's causing Alzheimer's disease.

01:57:55.500 | So Steven Cunane has done studies

01:57:57.300 | where he even gives ketone supplements.

01:57:59.780 | - So these are liquid ketone esters?

01:58:01.580 | - So yeah, ketone esters or ketone salts.

01:58:04.980 | And it has actually found

01:58:06.660 | that these brain metabolism deficits can be corrected

01:58:11.460 | at least short term by giving a ketone supplement.

01:58:16.200 | - Is this in the context of people

01:58:18.180 | also ingesting some carbohydrate?

01:58:20.080 | Because I confess, I've tried the ketogenic diet.

01:58:23.740 | I probably did it wrong.

01:58:24.860 | This was years ago and then the cyclic ketogenic diet.

01:58:27.140 | But in the last year or so,

01:58:30.100 | I've started using liquid ketone esters.

01:58:33.380 | And I do eat some carbohydrates each day,

01:58:36.180 | usually in proportion

01:58:37.920 | to how much high intensity exercise I'm doing.

01:58:40.220 | Those liquid ketone esters for me, at least subjectively,

01:58:46.260 | I feel like greatly increase my energy levels

01:58:48.740 | and my ability to focus mentally.

01:58:51.680 | And they improve my sleep.

01:58:53.020 | This is my observation, tracking some data,

01:58:55.580 | but just again, subjectively.

01:58:57.380 | So in this example,

01:58:58.900 | are you talking about people taking ketone esters

01:59:01.040 | or ketone salts on a backdrop of a ketogenic diet

01:59:04.780 | or on the backdrop of a more typical diet?

01:59:07.900 | - So he's done both.

01:59:09.900 | So he's done studies where patients

01:59:14.140 | aren't doing anything special with the diet.

01:59:15.940 | So they're eating whatever they normally eat,

01:59:18.280 | absolutely non-ketogenic,

01:59:20.380 | giving them a ketone salt or ester,

01:59:23.620 | and then noticing immediate and direct changes

01:59:26.820 | in the metabolism of these

01:59:29.460 | metabolically compromised brain cells

01:59:32.460 | as measured by pet imaging.

01:59:35.240 | - These are not household pets, by the way.

01:59:38.180 | I'm sorry, you have to just pee,

01:59:40.380 | positron emission tomography, not pets.

01:59:42.500 | Although I'm sure that there are people out there

01:59:44.340 | who have their dogs or cats or whatever,

01:59:46.420 | or their pet kangaroos,

01:59:48.220 | whatever you might own on ketogenic diets.

01:59:50.280 | Okay.

01:59:51.120 | - Absolutely.

01:59:51.940 | And so he's actually moved further.

01:59:53.900 | He's done a pilot trial in a nursing home, actually,

01:59:56.720 | where he did not put the patients on a ketogenic diet.

02:00:00.320 | He simply reduced carbohydrate consumption

02:00:04.500 | at breakfast and lunch.

02:00:07.060 | They still got the same dinner as everyone else.

02:00:09.900 | And simply reducing carbohydrate consumption

02:00:12.660 | at breakfast and lunch

02:00:14.600 | resulted in cognitive improvement

02:00:16.780 | in a statistically significant way

02:00:19.820 | in some of those subjects.

02:00:21.420 | - I love that result.

02:00:22.500 | I'm sorry, I just have to highlight this.

02:00:23.760 | I'm a huge believer in directing carbohydrates

02:00:27.460 | to specific portions of the day

02:00:28.860 | when one needs to be less focused and alert

02:00:31.940 | and yet can replenish glycogen.

02:00:34.020 | Limiting carbohydrates most of the time during the day

02:00:38.700 | for me has been a game changer

02:00:40.380 | in terms of maintaining alertness, et cetera.

02:00:42.900 | I'm not aware that I have age-related cognitive decline,

02:00:45.860 | but then again, people around me may argue otherwise.

02:00:48.940 | - Let me say, you are Andrew Huberman.

02:00:50.940 | There is no way you have cognitive impairment.

02:00:54.020 | - Although you didn't know me as a six-year-old.

02:00:54.860 | - If you have cognitive impairment, we're all screwed.

02:00:57.420 | - Well, I have plenty of flaws and impairments,

02:00:59.700 | well over 3,000 documented by people very close to me.

02:01:02.900 | But this is very interesting, I think,

02:01:07.640 | in the context of everything we've been talking about

02:01:09.460 | because could it be that supplementing with liquid ketones

02:01:14.460 | or prescribing liquid ketones

02:01:17.860 | to people who are challenged with mood disorders

02:01:22.300 | or things of that sort could be beneficial

02:01:24.180 | even if they are not willing or able

02:01:26.980 | to adhere to a ketogenic diet?

02:01:29.180 | - That is the million dollar question right now

02:01:31.300 | and we don't have good trial data to say yes or no.

02:01:36.300 | My speculation, my hunch,

02:01:42.020 | having tried that clinically with patients

02:01:46.000 | is it doesn't seem to work.

02:01:48.480 | It's not the same thing.

02:01:50.080 | The bigger reason for my feeling confident in saying that

02:01:56.760 | is that we've had ketone salts and esters available

02:02:01.360 | for over a decade now.

02:02:03.580 | We have tens of thousands of children and adolescents

02:02:08.100 | who are following a strict,

02:02:10.140 | ridiculously strict ketogenic diet

02:02:12.820 | to control their epilepsy.

02:02:15.620 | Those kids would love to be off the ketogenic diet.

02:02:19.920 | Their parents would love to have them off

02:02:23.280 | the ketogenic diet. - Yeah, no birthday cake,

02:02:24.880 | no ice cream.

02:02:25.720 | - There is not one case report of any child

02:02:30.720 | controlling his or her seizures using exogenous ketones

02:02:35.740 | without also doing the ketogenic diet.

02:02:38.640 | I just find it hard to believe

02:02:41.780 | that at least some of those people haven't tried it out

02:02:45.220 | to see.

02:02:46.680 | I do know some patients with bipolar disorder

02:02:50.320 | and even schizophrenia

02:02:52.660 | who are doing extraordinarily well on a ketogenic diet.

02:02:57.460 | They have tried to switch off the ketogenic diet

02:03:00.540 | using exogenous ketones.

02:03:02.780 | Their symptoms came back

02:03:04.920 | and so they found that it just wasn't effective.

02:03:08.460 | Again, those are anecdotes.

02:03:11.640 | My scientific speculation about why

02:03:15.360 | is because the ketogenic diet

02:03:17.360 | is actually not necessarily about ketones themselves.

02:03:22.360 | Ketones are one of a multifaceted story there.

02:03:27.800 | When people do a ketogenic diet,

02:03:31.900 | they're also lowering glucose levels.

02:03:35.420 | They're improving insulin signaling.

02:03:38.740 | They're ramping up mitochondrial biogenesis

02:03:42.760 | in particular in the liver

02:03:45.420 | because mitochondria actually make ketones.

02:03:49.280 | That's where they're made

02:03:50.300 | and they're primarily made in the liver mitochondria.

02:03:53.720 | So when somebody's in a fasting state

02:03:56.640 | or on a ketogenic diet,

02:03:58.020 | their liver mitochondria go through the roof

02:04:02.460 | because they're being called to action.

02:04:04.460 | It's like, hey, body's in starvation mode, get to work.

02:04:07.980 | And so the mitochondria, the cell senses,

02:04:11.460 | we need more mitochondria to process fat,

02:04:14.700 | to turn it into ketones

02:04:16.100 | so that those ketones can get up to the brain

02:04:18.180 | and keep the brain fueled

02:04:19.980 | because fatty acids can't fuel the brain.

02:04:23.540 | Only ketones can.

02:04:25.880 | Now, so my sense is that,

02:04:29.220 | and the gut microbiome changes and everything,

02:04:31.500 | the changes in hormones.

02:04:32.960 | So if you're eating a lot of donuts

02:04:37.040 | and drinking a bottle of ketones,

02:04:39.620 | the donuts are going to prevent your body

02:04:42.760 | from lowering glucose levels.

02:04:44.900 | You're still gonna have the high glucose levels

02:04:46.640 | from the donuts.

02:04:47.780 | You're still gonna probably have

02:04:48.920 | the impaired insulin signaling.

02:04:50.940 | You're probably still going to possibly have

02:04:53.700 | some inflammation from the inflammatory effects

02:04:57.140 | of that food.

02:04:58.400 | And so just drinking ketones alone won't be enough.

02:05:04.460 | I think for people who are metabolically healthy,

02:05:09.060 | I'll include you in that,

02:05:10.840 | I think ketones can play a really beneficial role, no doubt.

02:05:15.020 | I think exogenous ketones may in fact

02:05:19.800 | prove invaluable in clinical use

02:05:23.420 | for patients who maybe can't follow

02:05:25.060 | a super strict ketogenic diet

02:05:26.760 | but maybe could do a low carb diet.

02:05:29.480 | And then given the research that's happening

02:05:31.180 | with alcohol use disorder,

02:05:34.160 | I could imagine a situation,

02:05:36.020 | here's the million dollar tip

02:05:39.380 | to whoever wants to go out and get this

02:05:41.120 | if it actually turns out to be true.

02:05:43.580 | I could imagine a scenario

02:05:45.380 | where we use exogenous ketones with alcoholics

02:05:48.860 | and that every time they have a severe craving for alcohol,

02:05:52.020 | they drink ketones instead.

02:05:54.220 | - Which sort of tastes like alcohol.

02:05:56.640 | The ketone esters, when I take them,

02:05:59.180 | I drink them straight.

02:06:00.300 | Sometimes I'll put them in seltzer

02:06:01.560 | and I'm not a big drinker, as I mentioned.

02:06:03.020 | I might have an alcoholic drink every once in a while.

02:06:05.720 | I just don't ever crave it.

02:06:07.100 | I just do it every, maybe,

02:06:09.380 | I think 2020 was the last time I had a drink of alcohol.

02:06:14.260 | So obviously I'm not a good representative example.

02:06:17.620 | But the ketones taste good to me

02:06:19.880 | and they obviously don't get you drunk.

02:06:21.860 | They do seem to flick on my alertness pretty quickly.

02:06:26.180 | And my understanding is that they

02:06:30.120 | are the brain's preferred fuel source,

02:06:33.520 | meaning they are going to be the first fuels

02:06:36.320 | used by the brain

02:06:38.080 | when there's a buffet of fuels available.

02:06:43.080 | If there's glucose in my bloodstream,

02:06:45.320 | there's circulating liquid ketones,

02:06:47.560 | that ketones would be used first or preferentially.

02:06:50.340 | Is that true?

02:06:51.180 | - I think it's a complex question.

02:06:55.320 | I mean, some research that we have

02:06:58.680 | suggests that there are brain areas or brain cells

02:07:03.160 | that require glucose and cannot use ketones.

02:07:07.560 | So 100% of the brain cannot be fueled with ketones,

02:07:11.200 | as far as we can tell.

02:07:12.940 | So there are some areas that require glucose

02:07:16.660 | and that's probably the reason we have gluconeogenesis

02:07:19.280 | is to keep the body going

02:07:21.040 | and to keep the brain going no matter what.

02:07:23.200 | But when ketones are available,

02:07:28.320 | especially if ketones are high,

02:07:30.520 | the way I think about it is not that ketones

02:07:35.860 | are like the preferred fuel source

02:07:37.540 | and glucose goes to the wayside.

02:07:39.860 | But the way I think about it is that you have a range

02:07:43.400 | of cells with varying degrees of metabolic health.

02:07:48.400 | And some of those cells are gonna be extraordinarily healthy

02:07:51.720 | with appropriate healthy abundant mitochondria.

02:07:57.200 | And those cells are probably going to continue

02:07:59.360 | to use glucose as a fuel source.

02:08:02.040 | But if ketones happen to be there,

02:08:03.840 | sure, they'll use that too, like why not?

02:08:06.160 | But the real money is metabolically compromised tissues,

02:08:10.900 | whether it's brain cells or other tissues

02:08:14.440 | but we're talking about the brain.

02:08:16.240 | So if you've got metabolically compromised brain cells,

02:08:19.840 | 'cause it's not across the board,

02:08:21.460 | like with Alzheimer's brain scans,

02:08:24.040 | there are specific regions

02:08:25.720 | that are more metabolically compromised than others.

02:08:28.200 | And that's why we see patterns of atrophy

02:08:31.800 | in specific brain regions is because those regions

02:08:36.680 | are dysfunctional metabolically for whatever reason.

02:08:40.160 | And we can get into why that might be.

02:08:43.000 | But my sense is that if you've got

02:08:45.620 | a metabolically compromised cell,

02:08:47.480 | that cell is sending out a distress signal.

02:08:51.080 | That cell is calling resources from the body,

02:08:56.000 | like feed me, give me something.

02:08:59.120 | And if it can't use glucose effectively,

02:09:01.520 | it is gonna suck up those ketones

02:09:04.160 | and then start running on all cylinders or closer to it.

02:09:08.500 | And that process is so critical

02:09:13.500 | because what it means is that if that cell

02:09:17.600 | was barely getting by on 60% of its real ATP requirement,

02:09:22.600 | it means that it doesn't have enough energy

02:09:27.320 | for maintenance and repair functions.

02:09:30.720 | As soon as you give that cell 100% energy or close to it,

02:09:35.720 | even if you get it up to 90%

02:09:37.720 | of its preferred energy amount,

02:09:41.780 | it can start to repair itself.

02:09:44.840 | I mean, that's the beauty of the human body

02:09:47.800 | and living organisms is that they have a priority list

02:09:51.280 | of what they're gonna do.

02:09:53.360 | And if that cell senses that there are defective molecules,

02:09:58.360 | defective proteins in this cell that need to be replaced,

02:10:04.900 | once it gets enough fuel,

02:10:07.540 | it will start repairing itself and doing that work.

02:10:12.280 | - That makes sense.

02:10:13.200 | Thank you for that clarification.

02:10:14.880 | I'd like to talk about Alzheimer's

02:10:18.900 | and age-related cognitive decline generally.

02:10:22.400 | I know many people out there are just terrified

02:10:25.880 | of losing their memory for the obvious reasons,

02:10:29.280 | memory sets context, et cetera.

02:10:31.600 | And many people have relatives that suffer from Alzheimer's

02:10:35.520 | or other forms of dementia.

02:10:36.900 | I've heard that the ketogenic diet and diets like it

02:10:42.080 | can be very effective for helping to offset

02:10:46.760 | some of the symptoms of Alzheimer's

02:10:48.820 | and age-related cognitive decline.

02:10:50.420 | In fact, I even have a friend I won't out him by institution

02:10:54.160 | who's the chair of cardiology

02:10:56.880 | who contacted me of all people,

02:10:59.240 | asking whether or not I was aware of any studies

02:11:03.240 | or whether or not I knew of anybody

02:11:05.080 | who had benefited from ketogenic diet for Alzheimer's.

02:11:09.320 | And I thought, well,

02:11:10.160 | why don't you ask one of your colleagues in neurology?

02:11:12.280 | But his response was really interesting.

02:11:14.400 | He said, there are many books out there

02:11:17.440 | for the general public.

02:11:18.400 | There are a lot of online discussions about this.

02:11:21.100 | There are a lot of assertions about this

02:11:22.520 | and some animal studies.

02:11:24.480 | But again, these are his words.

02:11:26.540 | There are very few, if any,

02:11:31.120 | controlled clinical trials exploring the role

02:11:33.600 | of the ketogenic diet for the treatment or reversal

02:11:37.300 | of Alzheimer's and age-related cognitive decline.

02:11:39.820 | I'm hoping that statement was incorrect

02:11:41.760 | or soon will be incorrect because those trials are ongoing.

02:11:45.040 | But he said, yeah, you know,

02:11:46.000 | the people who are most popular for telling us

02:11:50.560 | about the important role and positive role

02:11:53.700 | of being in ketosis for Alzheimer's,

02:11:56.460 | for some reason, they just won't do a clinical trial.

02:11:59.480 | And that's been frustrating to the community.

02:12:02.360 | So this is a very educated, very accomplished person

02:12:05.040 | who's a physician of heart medicine

02:12:07.900 | as opposed to something else related to the brain.

02:12:12.160 | But what is the story there?

02:12:14.400 | And for goodness sake, why aren't there clinical trials

02:12:18.160 | on ketogenic diet and Alzheimer's?

02:12:20.320 | I don't expect you to be responsible for that fact,

02:12:25.320 | but goodness, I would think this would be

02:12:28.100 | like the obvious thing for NIH.

02:12:31.080 | I'm on the study section, you know,

02:12:32.520 | but not for these sorts of experiments.

02:12:34.920 | Why isn't money just avalanching into this area

02:12:38.140 | based on all the anecdotal evidence

02:12:40.340 | that people are talking about?

02:12:42.340 | - So we've got a couple of small pilot clinical trials.

02:12:47.100 | The best one was a randomized controlled trial.

02:12:50.580 | I think it only included 26 subjects, something like that.

02:12:54.540 | Randomized to 12 weeks of a low fat diet, 10 week washout,

02:12:59.540 | 12 weeks of ketogenic diet.

02:13:04.420 | Some of the participants got keto first and then low fat.

02:13:07.900 | Other participants got low fat, then keto.

02:13:11.140 | And that trial actually found

02:13:13.820 | that when patients were in ketosis,

02:13:18.740 | they had statistically significant improvement

02:13:24.340 | in activities of daily living and quality of life.

02:13:29.060 | And they did have improvement in cognitive function,

02:13:32.420 | but it didn't reach statistical significance.

02:13:34.980 | That improvement did not.

02:13:36.480 | We've got other trials.

02:13:40.780 | We've got several animal models showing

02:13:44.020 | that the ketogenic diet can improve biomarkers

02:13:47.520 | of Alzheimer's disease in Alzheimer's models.

02:13:51.180 | So it can reduce plaques and tangles,

02:13:53.700 | can even improve cognitive impairment in animal models.

02:13:58.240 | We've got a couple of other small pilot trials

02:14:03.240 | of ketogenic diet in humans showing

02:14:06.440 | that it improves biomarkers compared to, say,

02:14:09.320 | the low fat diet or the American Heart Association diet.

02:14:12.620 | So we've got those.

02:14:13.940 | I think one of the biggest challenges

02:14:16.820 | that I'll just share openly,

02:14:18.820 | and this is, I'm somebody who's pretty passionate

02:14:21.540 | about this research and I believe it has a lot of potential,

02:14:26.480 | but Johns Hopkins researchers attempted

02:14:30.580 | to do exactly this kind of a study.

02:14:33.700 | Alzheimer's patients, ketogenic diet versus the,

02:14:39.200 | I think American Academy of Aging or something like that,

02:14:42.220 | diet is the control diet.

02:14:44.580 | - Which presumably has starches in there.

02:14:46.340 | I think that's the key variable.

02:14:47.580 | - Probably lots of, yeah, lots of whole grains,

02:14:50.260 | lots of whole grains.

02:14:51.100 | - Yeah, some potatoes.

02:14:53.220 | And they spent, I believe, over three years,

02:14:58.220 | they screened over 1300 participants,

02:15:02.560 | 1300 people who expressed interest.

02:15:06.680 | The end of the day, I think they only got 27 people

02:15:10.680 | to enroll and only 14 of those people completed the study.

02:15:15.680 | Despite that, what they found was that the subjects

02:15:21.420 | who achieved ketosis had cognitive improvement.

02:15:25.920 | But people on study section are gonna look at a study

02:15:30.540 | like that and say, even if the science is there,

02:15:35.540 | if you can't get people to do this diet,

02:15:39.900 | why would we spend money on researchers trying

02:15:43.660 | to get people to do this diet?

02:15:45.340 | - I should mention study section is this closed door panels

02:15:49.880 | of 40 or so people, there are many of these panels,

02:15:53.620 | different divisions of the National Institutes of Health

02:15:58.040 | use different panels and then grants are evaluated

02:16:01.100 | and in a very small, because of the size

02:16:04.100 | of the federal budget for research,

02:16:05.360 | a very small percentage, usually about 10% of these studies

02:16:10.360 | are funded, the rest generally don't end up happening.

02:16:16.720 | That is very informative.

02:16:20.000 | What you just described is very informative

02:16:21.780 | because now it makes sense to me that there's no conspiracy.

02:16:26.660 | It's not like big pharma, I don't think is trying

02:16:29.260 | to suppress trials of ketogenic diets on Alzheimer's

02:16:33.780 | because I would imagine the first thing that pharma

02:16:35.940 | would want to do is to see that study done

02:16:37.860 | so they didn't have to and then the moment it was done,

02:16:40.340 | if it showed a positive effect,

02:16:41.420 | they'd probably want to isolate the molecule

02:16:43.200 | and wrap it up in something that people would take, right?

02:16:45.740 | - Yes.

02:16:46.580 | - So I don't think there's any active suppression by pharma.

02:16:48.160 | I think pharma would probably be cheering from the sidelines

02:16:51.000 | because they could capitalize on it

02:16:52.720 | because ultimately the studies are done by scientists,

02:16:54.800 | but the treatments are generally doled out

02:16:56.880 | by pharmaceutical companies and/or physicians.

02:16:59.540 | So I don't believe there's a conspiracy there.

02:17:01.720 | That is very interesting and it's kind of amazing

02:17:04.880 | given our discussion of earlier,

02:17:07.680 | which is that you had a patient

02:17:09.740 | that was having schizophrenic symptoms

02:17:12.340 | who managed to stay on this diet.

02:17:14.240 | So is there something special about Alzheimer's patients

02:17:18.280 | and people with age-related cognitive decline?

02:17:20.200 | Presumably they're very dependent on others

02:17:22.820 | to cook for them and shop for them.

02:17:26.560 | I think that this is an almost perfect controlled environment

02:17:29.420 | for getting this study done.

02:17:30.760 | - I think that is the key issue.

02:17:33.800 | So again, I get patients with bipolar disorder,

02:17:38.480 | schizophrenia, extraordinarily impaired people.

02:17:44.320 | To do this diet and stay with it,

02:17:46.560 | but it's because I'm providing a weekly session for them.

02:17:51.400 | And I imagine this study did not provide

02:17:56.000 | that kind of intensive support.

02:17:58.400 | So I think in the pilot trial that I described to you,

02:18:01.760 | they actually got, I think, over 90% compliance

02:18:04.680 | with the different dietary interventions.

02:18:07.560 | So some of it is gonna be dependent on the research group,

02:18:12.120 | and does the research group understand

02:18:14.360 | that this is not, it's not like prescribing a pill.

02:18:18.340 | Here, take this pill and take it every day

02:18:21.260 | and come back in three weeks.

02:18:23.420 | And even then, we don't know for sure

02:18:25.360 | that the patient took the pill every day.

02:18:27.280 | We just assume they took the pill every day

02:18:29.440 | and studies say they probably didn't.

02:18:32.380 | But so I think when we think about a dietary intervention,

02:18:35.720 | we need to think about more intensive support and education.

02:18:41.200 | And that support could be a health and wellness coach.

02:18:44.360 | It could be a dietician.

02:18:46.120 | It could be education of the family.

02:18:48.620 | It might even be providing them with dietary, like meals,

02:18:53.620 | that maybe for six months,

02:18:57.880 | we actually provide them with ketogenic meals once a week,

02:19:02.880 | put them in your freezer, microwave them when needed

02:19:07.840 | to make this diet as easy and doable as possible.

02:19:12.720 | Because if we can get people to do the diet,

02:19:17.000 | if we can get them through the first couple of months,

02:19:19.880 | most people can learn how to do this diet.

02:19:23.340 | More importantly, I didn't mention this before,

02:19:27.080 | but the number one reason I am so successful

02:19:30.380 | at getting patients to stay on this diet for years

02:19:34.960 | is because of the consequences to them when they go off

02:19:38.200 | of it.

02:19:39.040 | That is the reason I can get schizophrenic patients

02:19:43.340 | and bipolar patients to do this diet,

02:19:45.640 | whereas other people can't get an everyday human being

02:19:49.160 | to do it for weight loss.

02:19:50.920 | Because the weight loss patient doesn't experience

02:19:54.280 | devastating tormenting symptoms when they break the diet.

02:19:59.280 | Oftentimes they are rewarded.

02:20:02.400 | They eat something they really enjoy,

02:20:05.200 | and they get a little bit of a dopamine rush from it,

02:20:07.560 | and they're off to their aces.

02:20:08.960 | They're like, I'm gonna, oh, I've already cheated.

02:20:11.200 | I'll cheat again.

02:20:12.060 | I'll get back on it someday.

02:20:13.560 | And they never get around to it.

02:20:15.940 | My patients, when they go off the diet,

02:20:19.300 | they start hallucinating within 24, 48 hours,

02:20:24.080 | and they quickly realize that was a really stupid thing

02:20:27.320 | to do.

02:20:28.200 | That piece of cake was not at all worth the torment

02:20:32.260 | that I'm experiencing now.

02:20:34.440 | So they get back on the diet.

02:20:36.420 | I suspect with Alzheimer's disease,

02:20:38.380 | we might notice something similar.

02:20:41.220 | These people, some of these people have very mild symptoms,

02:20:44.880 | so maybe they won't have that kind of a reinforcement,

02:20:49.280 | negative reinforcing kind of experience.

02:20:52.640 | But I think some of them will.

02:20:54.500 | Some of them recognize that they are impaired cognitively.

02:21:00.840 | And if this diet could help them remember better,

02:21:04.360 | if this diet could help them function better,

02:21:07.320 | and again, that's what the pilot trial showed

02:21:08.780 | is activities of daily living.

02:21:10.480 | That means these people are able to go to the bathroom

02:21:12.500 | on their own.

02:21:13.460 | They're able to get themselves dressed,

02:21:15.540 | whereas they needed help with those things before.

02:21:18.980 | Those are actually really important things

02:21:22.900 | to both the patient and the caregiver.

02:21:26.020 | And if they go off the diet and then quickly revert

02:21:30.460 | into a more symptomatic state,

02:21:33.780 | that might be reinforcing enough for them

02:21:37.780 | to figure out a way to do the diet on their own.

02:21:41.500 | And if we think about, you know,

02:21:42.740 | if this really is an effective intervention,

02:21:44.740 | and yes, we need longer trials, larger trials, all that,

02:21:48.060 | 'cause there are plenty of stories in the medical field

02:21:51.900 | where pilot trials looked really spectacular

02:21:55.580 | and promising, and then larger trials

02:21:57.720 | just failed to show the benefits.

02:22:00.620 | I believe based on all the science of metabolism,

02:22:05.260 | mitochondria, glucose, hypometabolism, all of that,

02:22:08.320 | I believe the science makes this an obvious treatment

02:22:13.320 | that has real potential.

02:22:15.960 | So, you know, people will call me biased.

02:22:19.180 | That's fine, I've got my bias.

02:22:20.740 | - No, based on clinical observation

02:22:22.780 | and extensive clinical observation at that.

02:22:25.560 | I think biases that are simply because we want to feel

02:22:28.780 | a certain way or believe something are worth critiquing,

02:22:33.500 | but bias based on observation.

02:22:36.780 | Here, I should mention that, you know,

02:22:38.440 | most of what we know about human memory

02:22:42.260 | was sparked by one patient, a famous HM,

02:22:45.100 | who I think was living in Harvard Medical,

02:22:48.780 | in one of the hospitals around there,

02:22:50.020 | many hospitals on Longwood campus, but one patient.

02:22:54.940 | I mean, the reason we associate the hippocampus with memory

02:22:57.360 | is because we knew that HM's hippocampus was damaged,

02:23:01.120 | intentionally damaged for epilepsy treatment, right?

02:23:04.380 | So this idea that everything has to be

02:23:06.820 | a randomized clinical trial to me is crazy.

02:23:09.580 | I mean, of course that's a gold standard and it's essential,

02:23:14.020 | but there's so much information in textbooks,

02:23:17.400 | medical textbooks in particular,

02:23:19.080 | that are gleaned from single patient case studies

02:23:21.860 | or from three patient neurostimulation in the brain

02:23:25.300 | or something of that sort.

02:23:26.420 | So to me, I'm still perplexed as to, you know,

02:23:30.860 | why there's this insistence on only one form of evidence.

02:23:35.860 | Clearly what you're doing,

02:23:39.740 | the important work that you're doing clinically

02:23:41.500 | and in the research side and in public communication

02:23:43.860 | is assisting this.

02:23:45.140 | I have a question about, or more of a statement/question

02:23:49.420 | about the ketogenic diet.

02:23:51.600 | Based on everything that we've talked about,

02:23:53.840 | seems to me that the ketogenic diet for weight loss

02:23:57.660 | is a very interesting aspect of the diet

02:24:00.280 | as is intermittent fasting for weight loss,

02:24:03.160 | even though it might just be by way of caloric restriction

02:24:06.100 | that occurs with fasting.

02:24:08.060 | But then in some ways,

02:24:09.540 | the effects of the ketogenic diet on weight loss

02:24:13.220 | are a bit of a decoy for most people.

02:24:15.360 | That's where their mind goes.

02:24:16.560 | This person lost X amount of weight.

02:24:18.240 | Maybe that made them feel better.

02:24:19.320 | Maybe that actually made them underweight.

02:24:20.680 | I think you've talked about it for some people

02:24:22.160 | that can actually bring them underweight.

02:24:24.700 | But I'm glad that we got the chance to dive

02:24:28.280 | into the description of ketogenic diet for epilepsy,

02:24:30.700 | because it really is a medical intervention

02:24:33.560 | that has a side effect of weight loss

02:24:36.280 | or could be used to treat obesity and induce weight loss.

02:24:40.180 | But it's really about far more than that.

02:24:44.180 | And that raises a question for me, which is,

02:24:46.380 | you know, we've been talking about the ketogenic diet

02:24:49.980 | as one thing,

02:24:51.120 | but I've heard you discuss this before where, you know,

02:24:54.760 | just as a physician will prescribe different dose,

02:24:57.960 | dosage ranges of a given drug,

02:25:00.680 | you can prescribe different dosage ranges

02:25:03.240 | of a nutritional plan, a diet.

02:25:05.540 | It's not one thing.

02:25:06.680 | It's not necessarily zero carbohydrates

02:25:09.180 | or a hundred grams or 50 grams.

02:25:10.660 | It depends on the patient and a lot of other factors.

02:25:14.200 | I've heard you list off various things, classic keto.

02:25:16.760 | Maybe you could just briefly tell us what that typically is.

02:25:19.540 | 'Cause I think most people think it means eating

02:25:22.060 | a lot of meat and not carbohydrates,

02:25:24.760 | but might not be that fasting.

02:25:28.020 | And then some of the other, you mentioned Atkins earlier.

02:25:30.940 | We don't have to go into each of these in detail.

02:25:32.500 | And I know in your book,

02:25:33.340 | you talk about not just the science and clinical background,

02:25:36.020 | but also some actionable steps that people could consider.

02:25:39.220 | So they can refer there for more detail.

02:25:41.500 | But for somebody who let's say is depressed,

02:25:44.980 | they've had some rounds of depression.

02:25:46.740 | Maybe they're on antidepressants, maybe not.

02:25:48.980 | And they want to try something like this.

02:25:51.400 | Obviously this has to be done in concert

02:25:53.340 | with a physician observing all this.

02:25:56.300 | But what is the typical thing that you probe with first?

02:26:00.260 | Just like with a drug,

02:26:01.100 | you'd might probe with 20 milligrams of a drug.

02:26:03.160 | What's your typical initial dietary intervention probe?

02:26:08.160 | Terrible languaging, I realize.

02:26:09.620 | And I'm criticizing myself for that,

02:26:11.920 | but I think people get the idea.

02:26:14.180 | - The real answer is that I don't have a one size fits all

02:26:17.620 | recommendation for any person.

02:26:19.620 | So the first thing that I'm going to assess with the patient

02:26:22.020 | is what symptoms are they having?

02:26:24.580 | What is their current diet like?

02:26:26.580 | And what are they willing to do?

02:26:28.760 | I try to meet them where they're at.

02:26:30.760 | So if somebody, you know, and I want to point out,

02:26:34.700 | like you mentioned the all meat version of this diet,

02:26:38.120 | which is often referred to as the carnivore diet.

02:26:41.220 | - A very controversial diet.

02:26:42.620 | - There is no doubt that exists.

02:26:44.340 | And for some people, some people swear by it.

02:26:45.940 | They swear that they've tried other versions of ketogenic

02:26:48.340 | diets and only when they went to a carnivore diet,

02:26:50.460 | did they get benefits.

02:26:52.220 | But there are vegetarian and vegan versions of the

02:26:55.100 | ketogenic diet.

02:26:56.180 | So in my mind,

02:26:57.640 | this is not at all about the diet wars of animal source

02:27:01.580 | versus plant source foods.

02:27:03.460 | It's about inducing a state of ketosis,

02:27:06.860 | which is mimicking the fasting state.

02:27:09.120 | That is what it's about.

02:27:10.580 | And you can do that by not eating anything by fasting and,

02:27:14.380 | or intermittent fasting and you get your results.

02:27:17.260 | So no diet is a ketogenic diet.

02:27:21.700 | So it's not about the foods or the types of foods that

02:27:24.780 | you're eating.

02:27:25.620 | It's about inducing a state of ketosis.

02:27:28.300 | The first variable I'm going to look at when I recommend

02:27:30.820 | this or prescribe this is the person's current weight.

02:27:34.500 | If somebody is obese versus somebody who's thin,

02:27:39.500 | I'm going to use different dietary strategies for those two

02:27:42.240 | situations.

02:27:43.220 | In the obese patient,

02:27:44.580 | they have tons of fat stores on their body already.

02:27:48.380 | Usually it is a goal of theirs to tap into some of those and

02:27:52.140 | they'd like to lose some weight if they're going to try a

02:27:54.900 | ketogenic diet for brain health anyway.

02:27:57.860 | And so I'm going to use that.

02:27:59.900 | So that person really,

02:28:01.820 | the diet is carbohydrate restriction and that usually is a

02:28:05.860 | sufficient intervention,

02:28:07.460 | both simple carbohydrates, meaning sugars and fructose.

02:28:11.180 | Also fructose, definitely.

02:28:13.380 | So no added sugars essentially.

02:28:16.780 | You can have added natural sweeteners like Stevia or monk

02:28:20.660 | fruit.

02:28:21.540 | You might use artificial sweeteners.

02:28:24.260 | I'd probably years after of doing this,

02:28:28.280 | I'd probably recommend steer away from them if you can,

02:28:30.780 | because I think they tend to stimulate cravings for high

02:28:33.300 | carb foods.

02:28:35.100 | So if you can kind of get through a couple of weeks without

02:28:40.540 | sweet things,

02:28:41.820 | your cravings for those will go down and it'll make the diet

02:28:44.820 | easier and a little more sustainable.

02:28:46.420 | But let's say you can have your artificial sweeteners,

02:28:49.700 | if that's what you really want.

02:28:51.260 | So I'm going to say less than 20 grams of carbs a day for

02:28:55.300 | those people.

02:28:57.000 | They can have all the protein they want.

02:28:59.120 | They can have vegetables and they can have all the fat they

02:29:01.960 | want, but I'm not going to push fat on those people.

02:29:05.080 | I'm not going to tell them eat a lot of fat at the same time,

02:29:07.820 | because I want to use the fat on their body as the fat

02:29:11.700 | source, at least early on.

02:29:14.340 | - Are you encouraging healthy fats like mono and saturated

02:29:16.700 | fats like olive oil or are you encouraging people to eat a

02:29:21.380 | little less butter, et cetera?

02:29:24.380 | - I, I, I tend to,

02:29:27.340 | I tend to encourage again,

02:29:30.740 | a wide range of fats and it's going to depend on the person.

02:29:33.420 | A lot of times people come to me with very specific ideas,

02:29:37.320 | but I'm going to tend to encourage olive oil, avocados,

02:29:41.420 | nuts,

02:29:42.540 | which are usually considered even by the American Heart

02:29:45.060 | Association, healthy sources of fat.

02:29:47.420 | The more controversial thing are things like coconut oil or

02:29:51.320 | coconut cream,

02:29:52.460 | which the American Heart Association might say is not a

02:29:55.140 | healthy fat.

02:29:56.240 | I kind of disagree with that and don't think it's unhealthy

02:30:00.300 | at all actually.

02:30:01.160 | And when you look at the epidemiological studies of

02:30:04.880 | saturated fat causing heart disease or causing adverse

02:30:09.220 | outcomes at best,

02:30:11.380 | maybe increases your risk 10 to 15% at best.

02:30:14.500 | - How much coconut oil can people ingest anyway,

02:30:17.420 | before they either develop diarrhea, no joke,

02:30:20.700 | or, or just sort of get tired of coconut oil.

02:30:23.460 | But anyway, your point is taken,

02:30:27.180 | but they can eat meat if they like meat or eggs,

02:30:30.900 | or if they don't like meat and eggs,

02:30:32.360 | they could eat sardines or things of that sort.

02:30:34.300 | I mean, I personally can't, I can't even stomach the,

02:30:36.420 | I don't even like the word sardine.

02:30:38.540 | I have nothing against the actual fish, but that's just me.

02:30:41.700 | But obviously people have,

02:30:42.940 | I say this because people have different preferences, right?

02:30:45.580 | - Yes.

02:30:46.420 | - I'll eat a steak, but I'm not going to eat a sardine.

02:30:47.880 | - And I'm going to go with that.

02:30:49.100 | And again,

02:30:49.940 | there are vegan sources of protein that people can eat tempeh

02:30:53.780 | and, you know, other things.

02:30:55.340 | So that's the obese person is carb restriction is the primary

02:31:01.960 | initial phase.

02:31:04.660 | The thin person is going to need to eat a lot of fat because

02:31:07.760 | they don't have a lot of fat stores on their body.

02:31:10.500 | And if I want them in ketosis, clinical ketosis,

02:31:14.040 | I'm going to have to feed them fat.

02:31:15.640 | So that's the person that I'm going to say,

02:31:18.420 | make sure you get in avocados, olive oil, butter,

02:31:22.840 | maybe a cream, heavy cream.

02:31:25.680 | So heavy cream is delicious.

02:31:27.020 | It's a delicious way to get your fats in and have one

02:31:30.660 | patient who just drinks it straight to just try to get it in

02:31:33.360 | other people.

02:31:34.200 | - I get it.

02:31:35.040 | I like, I've never had an appetite for sweets.

02:31:37.200 | I absolutely love savory, fatty food.

02:31:41.420 | And I, when I was in high school, I was, I was thin.

02:31:44.460 | So I was able to do this, but I used to drink half and half.

02:31:48.160 | Sometimes I wake up in the middle of the night and drink it

02:31:49.920 | just cause it tastes so, so good.

02:31:51.700 | - It does taste good.

02:31:52.880 | So, so if they're on a ketogenic diet,

02:31:55.020 | I'm going to push them away from half and half and toward

02:31:58.380 | heavy whipping cream and, and so you can whip that up.

02:32:03.120 | You can freeze it.

02:32:04.040 | It turns into ice cream.

02:32:05.380 | You can add vanilla.

02:32:06.360 | You can add cocoa powder.

02:32:07.680 | You can add all sorts of things.

02:32:08.960 | And you you're off to the races with shakes and ice cream

02:32:12.160 | and mousse and all sorts of things that you can have.

02:32:15.120 | With any of these patients,

02:32:20.040 | the beauty of this diet is I have objective biomarkers.

02:32:24.100 | I'm going to have them measuring ketones and I'm going to

02:32:26.740 | adjust the diet based on their state of ketosis and,

02:32:30.520 | or the clinical benefits that I'm looking for.

02:32:32.820 | If it's an average person who is not currently under

02:32:37.260 | psychiatric care, not taking prescription medicines,

02:32:41.760 | but is saying I'm burned out, I'm exhausted.

02:32:45.980 | I want some of that brain energy that Andrew Huberman's

02:32:48.680 | talking about, he talks about feeling good.

02:32:51.280 | I want some of that.

02:32:53.240 | I'm probably actually going to recommend the protocol you

02:32:55.600 | described, which is,

02:32:57.340 | let's see if we can just carb restrict for a while

02:33:01.200 | and see if that produces clinical benefit.

02:33:04.480 | I have one, he's not even a patient,

02:33:07.240 | just somebody who read my book.

02:33:11.660 | I didn't tell him anything.

02:33:13.660 | And he came away from it saying he was ready to start an

02:33:16.960 | antidepressant or an antidepressant for his anxiety,

02:33:20.080 | had chronic anxiety, was trying meditation,

02:33:22.560 | was trying all sorts of things.

02:33:23.800 | Nothing, nothing, those things weren't enough.

02:33:27.640 | He was ready to go on prescription medicine.

02:33:30.320 | He read an early copy of the book.

02:33:32.240 | He took it upon himself without consulting with me to

02:33:34.840 | restrict carbohydrates alone.

02:33:36.600 | He did not go ketogenic.

02:33:38.480 | He is a vegetarian.

02:33:40.760 | He restricted carbs within three weeks said,

02:33:45.360 | I don't need prescription medicine.

02:33:47.280 | I can't believe how much better I feel.

02:33:49.980 | And all I did was cut out some of the high carb foods

02:33:53.560 | in my diet.

02:33:55.240 | So I think for some people it can be that simple.

02:33:58.420 | For people with serious mental disorders,

02:34:02.360 | if they are chronically depressed,

02:34:04.100 | if they're on lots of prescription meds,

02:34:06.040 | if they're disabled by their symptoms,

02:34:07.940 | and certainly if you're bipolar or have schizophrenia

02:34:12.200 | or something, those are the people I really do want them

02:34:15.280 | to work with a medical professional,

02:34:17.120 | because meds may need to be adjusted.

02:34:20.440 | They really need, they need a real shot at this diet.

02:34:25.440 | It's not like weight loss.

02:34:28.140 | Weight loss, everybody wings it.

02:34:30.480 | And either you're successful or you aren't.

02:34:32.320 | You look on the internet or you read a book or you do,

02:34:35.840 | even the colleague that you mentioned,

02:34:37.640 | he's probably just reading,

02:34:39.120 | who knows whether it's credible information or not.

02:34:43.120 | And just winging it and seeing whether it works or not.

02:34:50.000 | For people with serious mental disorders,

02:34:53.120 | I want you to treat it like you have epilepsy.

02:34:56.400 | 'Cause you do have a serious brain disorder.

02:35:01.080 | Like it's impairing your ability to function in the world.

02:35:04.160 | It's impairing your health and happiness.

02:35:06.700 | You deserve a competent medical treatment.

02:35:09.680 | And we have that.

02:35:10.760 | We have a hundred year evidence base.

02:35:14.300 | We've got dieticians who know this

02:35:17.000 | like the back of their hand.

02:35:18.780 | They can monitor your level of ketosis.

02:35:22.300 | They can help look for vitamin and nutrient deficiencies

02:35:27.080 | that can be a consequence of the diet

02:35:29.480 | and make sure that you're not developing those.

02:35:31.960 | They can help tweak the diet if needed.

02:35:34.960 | They can give you ideas

02:35:35.920 | if you're getting bored with eggs every morning.

02:35:38.060 | They can give you ideas for what else you might have.

02:35:40.840 | And if you're using it to treat a serious disorder,

02:35:45.180 | I think you need serious help.

02:35:48.300 | - Couple of questions, a little more detailed,

02:35:51.220 | but I think a lot of people will have this on their mind.

02:35:54.180 | Is it ever the case that you'll prescribe somebody

02:35:58.200 | the ketogenic diet in conjunction with intermittent fasting?

02:36:01.640 | So eat keto, but eat between the hours of whatever,

02:36:04.980 | 11 a.m. and 8 p.m. or something like that.

02:36:08.160 | That's the first question.

02:36:09.080 | - Absolutely.

02:36:09.920 | So, and I have one patient with type two diabetes

02:36:13.300 | and chronic depression,

02:36:14.580 | and he will try to follow the ketogenic diet

02:36:18.220 | and sometimes his blood sugars are still very high.

02:36:22.760 | And sometimes I will ask him

02:36:24.680 | to do either intermittent fasting

02:36:26.340 | or even a three or four day water fast.

02:36:30.140 | And it is shocking.

02:36:32.980 | When he does a three or four day water fast,

02:36:36.580 | the first day or two, he feels like crap.

02:36:38.840 | I'll just say upfront,

02:36:40.900 | don't do it if you've got an important meeting

02:36:43.020 | or business trip or any, like don't be--

02:36:45.060 | - So this is just consuming water?

02:36:46.740 | - This is just consuming water.

02:36:48.060 | - No black coffee?

02:36:49.140 | - I usually tell him he can have

02:36:52.420 | plain black coffee or tea, but--

02:36:56.340 | - You have mercy after all.

02:36:58.260 | - I have a tiny ounce of mercy.

02:37:00.360 | But when he does it,

02:37:04.260 | his blood sugars plummet in a good way.

02:37:07.780 | Like his blood sugars are normalizing.

02:37:10.700 | But the last time he did it,

02:37:12.660 | he actually got to seven days at one point.

02:37:16.220 | And he said, I feel great, I want to keep going.

02:37:18.540 | I can't believe that I'm not hungry,

02:37:20.820 | but I am not hungry at all.

02:37:22.780 | I don't miss food at all.

02:37:25.020 | And at seven days, I kind of cut the cord.

02:37:27.180 | I was like, no, no, we're done, you got to eat.

02:37:30.540 | - Well, I find it really interesting

02:37:31.740 | that the intermittent fasting, of course,

02:37:33.220 | controversial at some level,

02:37:35.700 | but as to whether or not it's just beneficial

02:37:39.340 | by way of caloric restriction,

02:37:40.820 | 'cause it is one way to achieve caloric restriction,

02:37:43.400 | whether or not it has additional benefits.

02:37:45.180 | But I'm very interested in the neural side of it.

02:37:49.180 | And it does seem that the fasted state

02:37:51.200 | can start to take on its own rewarding properties

02:37:54.020 | where people get dopamine release,

02:37:57.040 | not from eating as most everyone does,

02:37:59.380 | but from abstaining from food.

02:38:01.380 | Now this can be pathologic

02:38:02.940 | and in the sort of example of anorexia nervosa,

02:38:06.460 | which is both know as the most deadly psychiatric illness.

02:38:10.540 | But for non-anorexics, I think it's interesting to note

02:38:14.200 | that eventually not eating

02:38:15.940 | can have its own rewarding properties to it

02:38:18.560 | that aren't just related to weight loss,

02:38:20.580 | but in the short term, feeling, in other words,

02:38:22.480 | feeling really good by way of abstaining from eating.

02:38:25.120 | - Yes. - Yeah.

02:38:25.960 | - Well, and that's actually, it raises an important risk

02:38:29.760 | that I haven't mentioned yet,

02:38:32.000 | but at least in psychiatric patients,

02:38:33.820 | but even in some patients who just use the keto diet

02:38:36.460 | for weight loss, I have seen definite hypomania.

02:38:41.100 | - So these are people that aren't sleeping very much.

02:38:43.480 | They're, are they also getting kind of delusional thinking?

02:38:47.940 | They're gonna run for president.

02:38:49.500 | - No, so the distinction between hypomania and mania,

02:38:53.460 | so mania, you might become psychotic and delusional.

02:38:56.820 | Mania by definition is problematic.

02:38:59.700 | It's causing a problem in some way or another.

02:39:02.100 | And if you have psychotic symptoms,

02:39:03.760 | it's definitely called mania, full-blown mania.

02:39:06.700 | Hypomania, for better or worse,

02:39:09.620 | is something every human being probably craves.

02:39:12.760 | So it is feeling extraordinarily good.

02:39:17.580 | It's getting by on less sleep, but you don't need to sleep.

02:39:20.500 | Who needs sleep?

02:39:21.380 | I've got things to do.

02:39:22.780 | I am, my brain is running on all cylinders.

02:39:27.780 | I feel so creative.

02:39:31.320 | There've been lots of famous people through the ages

02:39:35.300 | who have been bipolar, you know, probably bipolar,

02:39:38.960 | and some of their most productive periods of time,

02:39:42.640 | whether it's art or creating scientific models

02:39:47.040 | or what have you, were probably during hypomanic episodes.

02:39:51.100 | - So what do you do in that case?

02:39:52.460 | I mean, I'm obsessed with getting sufficient quality sleep.

02:39:56.260 | It's a kind of a repeating theme in our podcasts

02:39:59.140 | and many of my social media posts.

02:40:01.780 | And I always recommend behavioral tools first,

02:40:05.380 | then, you know, exercise, viewing sunlight, et cetera,

02:40:09.020 | the appropriate times, avoiding late night,

02:40:11.140 | artificial light exposure, et cetera.

02:40:13.040 | And occasionally for people who are doing all that

02:40:16.800 | and still struggle with sleep supplementation,

02:40:19.380 | one of the things that I've seen some data on

02:40:22.660 | is that for people who are following a low carbohydrate diet

02:40:25.720 | that inositol in particular can be helpful

02:40:28.400 | for getting it into sleep,

02:40:31.120 | probably because it's a bit of an,

02:40:32.640 | has a bit of an anti-anxiety effect.

02:40:34.980 | But presumably there are other things out there too.

02:40:36.800 | The magnesiums will generally do that.

02:40:38.400 | A hot bath will do that too, for that matter.

02:40:40.940 | But what you're talking about is people who are going,

02:40:42.920 | what, a day and a half without sleep,

02:40:44.800 | or they're just, you know, two hours of sleep a night?

02:40:47.600 | - I have, so the worst case I saw

02:40:50.240 | was actually a mental health professional

02:40:51.920 | who didn't recognize it initially.

02:40:53.840 | He went six months with two to four hours

02:40:57.260 | of sleep every night.

02:40:58.420 | - Because they were on a ketogenic diet.

02:40:59.860 | - He was on a ketogenic diet,

02:41:01.720 | was getting by on two to four hours of sleep every night,

02:41:04.820 | did not initially recognize that this was a problem.

02:41:08.300 | He was feeling great.

02:41:10.820 | He was feeling that keto high.

02:41:14.440 | And he was actually waking up and like at 4 a.m.

02:41:19.040 | going for 10 to 20 mile runs most days.

02:41:23.280 | He finally stopped the ketogenic diet after about six months

02:41:26.200 | because he said, I can't maintain my weight.

02:41:28.840 | So I'm losing too much weight.

02:41:30.720 | - Sorry, I didn't mean to drop.

02:41:31.600 | So what do you, I was just thinking there's some

02:41:33.000 | social media personalities associated with nutrition

02:41:36.080 | that might be hypomanic.

02:41:38.460 | I'll let you do the clinical evaluation.

02:41:42.460 | So what does somebody do in that case?

02:41:43.780 | So I don't know that I've ever been hypomanic,

02:41:47.260 | but as I mentioned earlier,

02:41:49.000 | unless I've done a very high intensity workout

02:41:51.640 | early in the day and I need to replenish carbohydrates,

02:41:53.600 | I typically eat meat, fruit, and vegetables

02:41:57.200 | throughout the day, minimum amounts of fruit, but some.

02:42:00.720 | And then at night I switch over to mainly carbohydrate.

02:42:03.680 | It really helps me sleep.

02:42:04.840 | It replenishes glycogen stores.

02:42:06.760 | I sleep really well, wake up the next morning, repeat.

02:42:09.460 | And of course this goes against a lot of the dogma that,

02:42:12.680 | oh, you're not supposed to eat carbohydrates

02:42:13.900 | late in the day.

02:42:14.740 | And this is what works for me.

02:42:17.420 | And so I do it.

02:42:19.140 | For somebody like this mental health professional

02:42:23.060 | who was hypomanic, would going off the ketogenic diet

02:42:26.680 | entirely be the best idea?

02:42:28.560 | Or could it be that adjusting when they eat

02:42:31.760 | their carbohydrates would be advantageous

02:42:34.380 | in order to make sure that they felt alert and great

02:42:36.880 | during the day, maybe not hypomanic,

02:42:38.440 | but then we could have a four to eight hours a night sleep

02:42:43.440 | as opposed to a two to four hours a night,

02:42:45.960 | which is really very little sleep.

02:42:47.560 | - Yeah.

02:42:48.400 | - It can't be healthy.

02:42:49.300 | - It's not healthy.

02:42:50.340 | - Even if you can do it and feel great,

02:42:51.840 | I imagine that the brain is suffering.

02:42:53.760 | - It is.

02:42:54.600 | And the body is suffering.

02:42:55.880 | - And your friends and family are suffering.

02:42:57.420 | - The body is repairing itself with sleep.

02:42:59.880 | And so yeah, if it's somebody who is not a patient,

02:43:04.880 | they're not a mental health patient,

02:43:09.260 | they're not using the ketogenic diet

02:43:11.180 | as a mental health treatment,

02:43:12.600 | they're simply doing it for whatever.

02:43:14.640 | I actually start with everything you've just outlined.

02:43:20.640 | Let's start with behavioral measures first.

02:43:24.180 | And the first intervention is education.

02:43:27.600 | You need at least six hours of sleep a night, period.

02:43:31.760 | End of story, that's non-negotiable.

02:43:34.560 | If you're not getting at least six hours of sleep a night,

02:43:37.580 | we need to consider this a problem.

02:43:39.880 | So figure out a way to get six hours of sleep.

02:43:42.640 | For some people, that's enough.

02:43:44.120 | Just the education.

02:43:45.080 | They don't get out of bed at 3 a.m.

02:43:49.320 | It might take them an hour to fall back to sleep.

02:43:51.300 | They fall back to sleep.

02:43:53.620 | For most people, if you can get three nights of decent sleep

02:43:58.280 | in a row, the hypomania goes away.

02:44:00.480 | That is the way to extinguish it.

02:44:04.640 | And then they still go on feeling a high from it.

02:44:08.500 | They feel great.

02:44:10.340 | Their brain feels good in terms of memory,

02:44:14.300 | concentration, motivation, all of those things.

02:44:17.420 | But they're not hypomanic anymore.

02:44:21.420 | And then I might use supplements, melatonin,

02:44:24.120 | others that you mentioned.

02:44:26.520 | Magnesium is a big one.

02:44:28.080 | And for some, I will recommend exactly what you're doing.

02:44:33.040 | Eat some carbohydrates in the evening

02:44:36.060 | before you're going to bed.

02:44:37.680 | Either have them at dinner,

02:44:39.400 | and then wait a few hours before you're gonna go to bed,

02:44:41.560 | or have them right before you're gonna go to bed,

02:44:43.920 | just to try to calm your body down and get it going.

02:44:50.540 | When I'm using this as a clinical intervention,

02:44:52.780 | especially with patients with serious mental illness,

02:44:55.780 | I actually want them in a state of ketosis long-term.

02:45:01.020 | So I'm not gonna do the carbohydrate intervention.

02:45:03.740 | I'm gonna try all the other ones.

02:45:05.960 | But if they still can't sleep,

02:45:07.840 | even with supplements, over-the-counter supplements,

02:45:10.280 | then I'm probably gonna go with prescription

02:45:13.700 | sleeping medicines as a temporary stop-gap

02:45:18.880 | to try to get them three to seven days of decent sleep

02:45:23.880 | that usually breaks the hypomanic cycle.

02:45:26.480 | And then they stay on the ketogenic diet

02:45:29.760 | because it ends up resulting

02:45:31.640 | in all of these other improvements that I've described.

02:45:34.840 | Their illness can sometimes go into full remission.

02:45:37.780 | - Is it low-dose trazodone as a first-line prescription?

02:45:43.280 | - I would not use trazodone.

02:45:44.960 | I would actually specifically avoid trazodone

02:45:47.200 | because it's an antidepressant

02:45:49.680 | and they're already hypomanic.

02:45:51.280 | And I certainly don't wanna push that further.

02:45:54.040 | So as long as it's somebody without a history of addiction,

02:45:58.520 | I'm gonna use a benzodiazepine,

02:46:01.400 | or either commonly called the Z medicines for sleep,

02:46:06.400 | zolpidem or Ambien or something like that.

02:46:09.280 | - Let's tap into the opioid pathway.

02:46:11.080 | Gabba, gabba. - Gabba, gabba.

02:46:12.960 | So I'm probably, I usually start with something

02:46:15.360 | like Ativan or Klonopin or something like that.

02:46:17.840 | Probably Ativan 'cause it's shorter acting.

02:46:20.520 | And again, I'm only looking to use it short-term.

02:46:23.160 | I let them know that up front.

02:46:25.080 | We're looking for three to seven days of decent sleep

02:46:27.800 | and then we're gonna try to get them off that medicine.

02:46:31.040 | And usually people are off to the races

02:46:33.660 | and can sustain it well.

02:46:35.700 | - A question about hormones.

02:46:39.220 | Many of the Huber and Lab podcast listeners will ask,

02:46:44.480 | anytime we're talking about something like exercise

02:46:46.800 | or drug treatment or behavioral treatment,

02:46:49.440 | people say, what about the menstrual cycle?

02:46:52.320 | How is that impacted by this and how does this impact,

02:46:55.900 | how does the menstrual cycle impact its efficacy, et cetera?

02:46:59.080 | Carbohydrates and caloric restriction have been implicated

02:47:04.940 | in different interaction,

02:47:07.040 | are known to interact with the endocrine system.

02:47:10.260 | So what do you do if you have a patient

02:47:13.400 | who is depressed or could have psychotic symptoms,

02:47:18.400 | but let's go with depression

02:47:20.040 | 'cause that's probably a bit more familiar to most people.

02:47:23.120 | And then they're on a low carbohydrate

02:47:25.220 | or full ketogenic diet, but their menstrual cycles cease.

02:47:30.220 | How do you deal with those adjustments?

02:47:33.680 | And I guess we could expand this conversation and say,

02:47:35.900 | what about male fertility also?

02:47:37.840 | Because sub caloric diets seem to,

02:47:41.680 | my understanding is that sub maintenance caloric diets,

02:47:46.280 | so weight loss diets will improve testosterone,

02:47:52.000 | estrogen ratios in males that are obese,

02:47:55.000 | but for someone that's not obese to go on a sub caloric diet,

02:48:00.000 | that it can start to impair testosterone levels

02:48:02.680 | and probably not make, render them infertile,

02:48:05.560 | but certainly adjust that whole axis.

02:48:08.900 | So what about interactions between ketosis,

02:48:11.920 | diets, et cetera, and the endocrine system?

02:48:16.120 | - The real answer is I don't think anybody knows

02:48:18.660 | and there's not a one size fits all answer.

02:48:21.520 | 'Cause I've seen examples and I'm aware of science

02:48:26.520 | to back up the whole or opposite conclusions.

02:48:31.580 | So the first general observation that I'll make,

02:48:36.120 | I know so many couples, husbands and wives,

02:48:40.360 | boyfriends and girlfriends, heterosexual couples,

02:48:44.700 | who have tried the ketogenic diet to lose weight together.

02:48:48.480 | - And end up with a baby.

02:48:49.580 | - Almost universally, the men have a much easier time

02:48:54.200 | with it than the women.

02:48:55.440 | It's not across the board, but I know so many examples

02:49:01.320 | where the women say, I couldn't tolerate that diet.

02:49:05.360 | It did not make me feel better.

02:49:07.880 | It actually made me feel worse.

02:49:10.320 | And I think in those cases,

02:49:11.960 | it probably does relate to hormones.

02:49:15.800 | I'm aware of animal models of, you know,

02:49:18.800 | mice in particular, ketogenic diet and mouse models.

02:49:23.240 | One researcher shared with me,

02:49:25.760 | the thing that was striking is that the female mice

02:49:29.240 | never got pregnant on the ketogenic diet.

02:49:33.760 | Whereas the mice on the standard diet

02:49:35.880 | were just having babies right and left.

02:49:37.980 | And it was just shocking the difference.

02:49:41.020 | On the surface, it makes sense.

02:49:45.060 | The ketogenic diet is mimicking the fasting state.

02:49:48.380 | Women who are trying to reproduce should not be fasting.

02:49:53.460 | If your body is in a fasting state,

02:49:57.800 | it probably does not want to expend resources,

02:50:02.480 | metabolic resources, calories, nutrients, and other things

02:50:07.040 | to creating a baby because your very life

02:50:10.440 | is being threatened by quote unquote fasting or starvation.

02:50:15.440 | That even though the ketogenic diet

02:50:18.700 | is a sustainable non-starvation diet,

02:50:21.620 | we're really using that diet to trick the body

02:50:24.180 | into thinking that it is in a fasting or starvation state.

02:50:29.320 | And so just from a kind of evolutionary stance,

02:50:33.440 | it makes sense that women's bodies

02:50:36.360 | may actually have significant changes

02:50:39.040 | in hormonal status to prevent pregnancy

02:50:42.520 | because a woman should not be having a baby

02:50:45.680 | when she's starving to death.

02:50:47.740 | I know of examples of women who are the opposite though,

02:50:55.720 | who have benefited dramatically and tremendously

02:50:59.960 | from the ketogenic diet,

02:51:01.640 | have put schizophrenia, bipolar disorder into full remission.

02:51:05.240 | And I do actually know of one case, at least one case,

02:51:09.020 | a woman, infertile, she and her husband

02:51:12.040 | had been trying for three years, no pregnancy,

02:51:15.280 | she went keto, within four months she was pregnant.

02:51:18.660 | How do I make sense of that?

02:51:22.620 | I don't know.

02:51:23.600 | And unfortunately I don't think we really have

02:51:26.320 | good controlled data on what does the ketogenic diet do

02:51:31.320 | to male hormonal systems, what does the ketogenic diet do

02:51:36.240 | to female hormonal systems.

02:51:38.400 | But clearly I think changes are happening

02:51:44.360 | and I don't have a way to predict it at least

02:51:48.440 | if somebody else has great insights, I welcome them,

02:51:51.360 | but I haven't seen them published.

02:51:53.240 | - It's a terrific answer because when things are

02:51:56.120 | all over the place and bi-directional,

02:51:57.680 | depending on one circumstance or the other,

02:51:59.820 | I think it screams for controlled studies

02:52:03.280 | and more descriptions of case studies

02:52:05.920 | and anecdotal data too.

02:52:07.400 | So I think it's an excellent answer.

02:52:09.560 | It also calls to mind the important

02:52:12.500 | public service announcement that

02:52:14.400 | because of these bi-directional effects that you described,

02:52:17.200 | please don't use fasting or the ketogenic diet

02:52:19.440 | as a reliable form of contraception.

02:52:22.400 | - Yes, please don't.

02:52:24.080 | - I have a final question which relates to something

02:52:27.840 | that is very much starting to get buzz now

02:52:32.460 | and maybe more so for people that hang out

02:52:34.560 | in the Twitter space or the nutrition space.

02:52:37.080 | But there's a new class of drugs that I think initially

02:52:40.280 | were developed to treat diabetes,

02:52:44.020 | but are now being evaluated for their efficacy

02:52:47.900 | to treat obesity.

02:52:49.400 | And these are the semaglutide drugs

02:52:54.400 | that are involved in,

02:52:57.000 | they tap into these glucagon related JLP1 pathways.

02:53:01.960 | And as is a story that we've talked about

02:53:04.920 | a little bit on the podcast before,

02:53:06.320 | but many people I imagine

02:53:07.640 | probably haven't heard that conversation.

02:53:09.640 | I would just simply like to know

02:53:10.800 | what you think about these drugs.

02:53:13.480 | They obviously adjust the way that glucose and insulin

02:53:17.160 | are managing energy, both in the body and the brain

02:53:20.960 | and can produce weight loss.

02:53:22.880 | So that to me, when I look at the data,

02:53:25.220 | you know, it's impressive, but a good, you know,

02:53:30.220 | a good logical shift in diet and exercise

02:53:32.700 | could achieve similar weight loss,

02:53:34.240 | but a lot of people just won't do that.

02:53:35.940 | So the question I have is,

02:53:37.880 | what are your thoughts on semaglutide and other GLP?

02:53:41.000 | I think I might've said GLT before, excuse me,

02:53:42.800 | GLP1 related compounds.

02:53:46.280 | And do you ever prescribe these

02:53:49.120 | in conjunction with these dietary shifts?

02:53:51.520 | Because it seems to me they would fall right in

02:53:53.760 | with the catalog of other approaches

02:53:56.360 | that you have available.

02:53:57.600 | - The real answer is I am not at all an expert

02:54:02.000 | on these medications.

02:54:05.000 | - But what are your thoughts about them?

02:54:06.520 | I mean, they seem to be weight loss drugs,

02:54:08.400 | not unlike the Fen-Fen drugs of the nineties

02:54:11.360 | that then were banned

02:54:12.320 | because a few people didn't handle them well.

02:54:14.880 | - They are, and you know, and we had Fen-Fen

02:54:19.880 | and even before that in the 1950s and sixties and seventies,

02:54:24.160 | Dexedrine.

02:54:25.240 | - Amphetamine.

02:54:26.320 | - Amphetamine.

02:54:27.160 | - Mother's little helper.

02:54:28.000 | - Was yes, was the treatment of choice for women

02:54:31.640 | across the United States to keep their slim figures.

02:54:36.000 | And we created addicts and all sorts of problems,

02:54:40.360 | but they were widely used in probably millions of women

02:54:44.000 | because they work.

02:54:45.240 | - Because they kill appetite.

02:54:47.920 | - They kill appetite.

02:54:49.280 | My overall thoughts are this.

02:54:56.760 | There is zero doubt in my mind

02:54:59.560 | that the obesity epidemic is a threat to human health

02:55:04.560 | and potentially the human species.

02:55:08.640 | If it keeps going at the rate it's going,

02:55:11.600 | it is a threat to our species.

02:55:13.960 | We have to figure out what on earth is happening

02:55:18.680 | and what can we do about it.

02:55:20.200 | These medications in early studies are highly effective

02:55:28.160 | over a year or two.

02:55:33.160 | That's promising.

02:55:35.520 | I am worried though that we're not attacking

02:55:41.520 | the root cause of obesity.

02:55:43.680 | And if the root cause of obesity ends up being some kind

02:55:50.440 | of poisoning of the metabolic machinery in the brain

02:55:55.880 | or body, and I would argue that probably relates

02:56:00.760 | to mitochondrial health and mitochondrial function.

02:56:03.800 | I have every reason to believe that taking a medication

02:56:09.880 | that helps you lose weight may not be addressing

02:56:14.600 | that problem, and therefore may not be addressing

02:56:19.600 | all of the negative health consequences

02:56:23.640 | of what we call obesity.

02:56:26.080 | I actually, so obesity in and of itself,

02:56:29.320 | we know that excess fat can become inflammatory

02:56:33.560 | and can cause problems in and of itself,

02:56:36.280 | but I actually see obesity as a symptom.

02:56:40.400 | I see obesity as a symptom of metabolic derangement

02:56:44.480 | in the body or brain, and that is why people become obese.

02:56:49.480 | And that if we're really going to get anywhere,

02:56:52.760 | we need to identify what is causing

02:56:54.920 | that metabolic derangement.

02:56:56.600 | Using a symptomatic treatment like a GLP-1 medication

02:57:03.000 | to the best of my knowledge is not addressing

02:57:08.000 | that core problem, and we're just ignoring it.

02:57:12.360 | Maybe I'll be wrong, and maybe these will be

02:57:16.000 | the wonder drug that saved the human species,

02:57:18.800 | and everybody will be thin and healthy forever and ever.

02:57:22.440 | I'm not hopeful, 'cause we've had so many promising drugs

02:57:28.920 | come along, and I'm not sure if we'll be able

02:57:32.800 | to get FEN-FEN, Dexogen, and other things.

02:57:35.520 | We've had so many promising drugs.

02:57:37.560 | And at the end of the day, when you try to muck

02:57:41.880 | with human metabolism using a single processed molecule,

02:57:46.480 | man-made, I can't think of even one example

02:57:51.000 | where it's been great for large numbers of people.

02:57:56.000 | I mean, certainly manufacturing insulin is life-saving

02:58:02.040 | for people with type 1 diabetes,

02:58:04.200 | so that would be an example.

02:58:06.520 | But giving massive doses of insulin to people

02:58:09.000 | with type 2 diabetes actually is a downward spiral.

02:58:12.400 | I would much rather see people with type 2 diabetes

02:58:16.040 | control their diabetes through diet and lifestyle,

02:58:19.080 | and that might be a ketogenic diet, or a low-carb diet,

02:58:21.840 | or exercise, or good sleep, or all of the other things,

02:58:25.800 | all of it.

02:58:27.500 | I'd much rather see that, because when people try

02:58:29.760 | to control their type 2 diabetes with a molecule,

02:58:32.120 | even though it's a natural molecule, insulin,

02:58:34.920 | we know that that results in really poor health consequences,

02:58:39.560 | results in higher rates of cardiovascular disease,

02:58:42.160 | higher rates of mental disorders,

02:58:44.000 | higher rates of premature mortality.

02:58:46.720 | Do I think GLP-1 molecules are gonna be different?

02:58:51.520 | No, I don't have any reason to think they are going to be.

02:58:55.440 | So that would be buying two cents, but we'll see, time will tell.

02:59:00.440 | - Time will tell.

02:59:01.680 | Meanwhile, I want to thank you for doing what is,

02:59:06.200 | without question, pioneering work.

02:59:08.920 | I mean, again, I'm not a clinician,

02:59:12.200 | but I've been around this space long enough

02:59:15.760 | to know that, indeed, there are no wonder drugs, right?

02:59:19.480 | There are drugs that certainly can help alleviate symptoms

02:59:22.120 | in some individuals, but that lifestyle,

02:59:27.120 | and in case of your work, in particular,

02:59:29.320 | in the discussion today, diet, and the ketogenic diet,

02:59:32.600 | in particular, it's clear, can have incredible effects,

02:59:37.600 | miraculous effects in some individuals,

02:59:40.200 | and positive effects in others that might not be

02:59:43.240 | of the same magnitude, but nonetheless,

02:59:44.800 | are extremely important.

02:59:46.800 | So I, on behalf of myself and the listeners,

02:59:50.080 | and certainly just on behalf of everybody out there,

02:59:53.240 | because everyone does need to be concerned

02:59:56.080 | about mental health issues, whether or not they have them

02:59:58.800 | in their family, themselves, or otherwise,

03:00:00.960 | because they impact everybody,

03:00:02.640 | just really want to thank you for doing the work

03:00:04.080 | that you're doing, because it really is pioneering,

03:00:07.360 | and it's brave, and I can see now,

03:00:11.000 | based on our discussion, why it would work.

03:00:15.520 | You've given us a lot of hints

03:00:18.040 | into the underlying mechanisms that suggest,

03:00:19.840 | as to why it would work, and you've given us examples

03:00:23.320 | as to how it has worked in patients that you've worked with,

03:00:26.880 | and this field is expanding fast.

03:00:29.120 | I think this is an area of psychiatry and medicine

03:00:31.840 | in general, meaning behavioral nutritional interventions

03:00:34.400 | that is expanding very fast.

03:00:36.280 | So thank you for being brave, and for taking this on,

03:00:40.280 | and doing it in such a structured way,

03:00:42.120 | and for communicating it here today,

03:00:44.040 | and with the general public through your book,

03:00:45.760 | and your online presence.

03:00:47.000 | We will certainly point people in the direction

03:00:48.720 | of those valuable resources.

03:00:51.080 | Thanks so much, I really appreciate it.

03:00:53.080 | - Thank you, Andrew, for being brave,

03:00:54.840 | and having me on here, so, and-

03:00:57.400 | - It's been a pleasure.

03:00:58.240 | - And for a great conversation.

03:01:01.100 | - Thank you for joining me for my discussion

03:01:02.560 | with Dr. Chris Palmer.

03:01:03.980 | I hope you found it to be as informative, actionable,

03:01:06.920 | and exciting in terms of the various treatments

03:01:09.680 | that we can now think about when considering treatments

03:01:12.960 | for psychiatric disorders.

03:01:14.400 | Once again, if you're interested in his work,

03:01:16.240 | or his new book, "Brain Energy,"

03:01:18.400 | I encourage you to go to his website,

03:01:19.980 | that's chrispalmermd.com.

03:01:21.880 | You can also find the book "Brain Energy" by Chris Palmer

03:01:24.320 | on Amazon, and other sites where books are sold,

03:01:26.600 | and we provide links to the book,

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03:03:37.040 | [upbeat music]

03:03:39.620 | you

Dr. Chris Palmer: Diet & Nutrition for Mental Health | Huberman Lab Podcast #99

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