How Ketogenic Diet Improves Brain Function | Dr. Chris Palmer & Dr. Andrew Huberman

00:00:00.000 | Does ketogenic diet improve mitochondrial function?

00:00:05.180 | And if so, how does that work?

00:00:06.740 | The quick summary story for people who don't know ketogenic...

00:00:10.800 | So ketogenic diet is a 100-year-old evidence-based treatment for epilepsy.

00:00:14.600 | It can stop seizures even when medications fail to.

00:00:17.680 | We have over a dozen controlled trials of ketogenic diets

00:00:24.200 | in children, in particular, with treatment-resistant epilepsy.

00:00:28.400 | We have two Cochrane reviews that came out positive.

00:00:32.340 | So Cochrane reviews are the gold standard in the medical field for meta-analyses.

00:00:37.720 | Very rigorous.

00:00:39.680 | And they analyzed the data that exists and came to the conclusion that ketogenic diet...

00:00:45.400 | If somebody has treatment-resistant epilepsy, compared to treatment as usual,

00:00:51.340 | which is try another anti-epileptic medication,

00:00:53.800 | the ketogenic diet is six times more likely to result in seizure freedom.

00:00:58.260 | ...than just trying yet another epilepsy pill.

00:01:01.400 | So the ketogenic diet is a powerful anti-convulsant treatment.

00:01:06.340 | We use anti-convulsant treatments in psychiatry every day in tens of millions of people.

00:01:11.780 | Lots of these medications are used.

00:01:15.200 | So at this point, we now have over 50 published pilot trials, case series, case reports,

00:01:25.880 | other lines of evidence of the ketogenic diet for psychiatric disorders.

00:01:33.920 | Schizophrenia, bipolar disorder, depression, anxiety, anorexia, nervosa, surprisingly.

00:01:40.400 | These 50 reports represent over 1,900 people.

00:01:46.320 | And on balance, the ketogenic diet appears to be an effective treatment,

00:01:54.140 | sometimes an extraordinarily effective treatment,

00:01:58.540 | like in able to induce remission of schizophrenia or bipolar

00:02:03.840 | in people who otherwise had treatment-resistant disorders.

00:02:08.040 | And they're going off medication simultaneously?

00:02:10.180 | Some of them are.

00:02:11.680 | So there are, you know, I have heard probably from thousands of people around the world

00:02:20.000 | since my work has become more public.

00:02:23.600 | And actually, our first podcast together, hands down, the most cited reason people know who I am.

00:02:32.340 | As they should.

00:02:33.620 | Well, I know about you, but it's Huberman, that Huberman Lab podcast.

00:02:38.440 | Well, I'm just a runway for people to, incredible messages to take off.

00:02:44.920 | Thank you again for the opportunity to disseminate this word.

00:02:48.880 | And because at the end of the day, I'm hearing from thousands of people who simply listened

00:02:54.300 | to that podcast, made changes, started a ketogenic diet for their schizophrenia

00:02:59.760 | or other treatment-resistant mental disorder, reach out to me.

00:03:05.080 | You saved my life.

00:03:08.100 | I can't tell you how many times I've gotten handwritten notes, emails, messages from people

00:03:14.540 | who use those words.

00:03:17.200 | You saved my life.

00:03:18.620 | I never met this person.

00:03:19.860 | All I did was share this knowledge.

00:03:23.760 | And then they saved their own lives with knowledge.

00:03:29.740 | Coming back to your question now, in a roundabout way, does the ketogenic diet impact mitochondrial

00:03:36.240 | health?

00:03:36.720 | We have strong evidence that it does.

00:03:41.240 | And so it appears, so the ketogenic diet is mimicking the fasting state.

00:03:47.900 | And I just want to say that again.

00:03:53.400 | The ketogenic diet mimics the fasting state.

00:03:57.140 | What does that mean?

00:03:58.460 | It means the ketogenic diet is mimicking no food consumption.

00:04:02.780 | So is the ketogenic diet the healthiest diet that everybody should follow?

00:04:09.000 | No, that's not the way I think about it.

00:04:11.040 | The ketogenic diet is an intervention.

00:04:13.180 | It is shifting metabolism.

00:04:16.500 | It is shifting countless kind of systems, signaling pathways, other things, gene expression in the

00:04:25.660 | human body and brain.

00:04:26.200 | And that results in effects.

00:04:30.820 | And the good news is these effects appear to be life-changing and life-saving sometimes.

00:04:37.740 | So they're highly beneficial effects.

00:04:42.260 | Again, dose and the way you do it matter because fasting, the extreme version of fasting is starvation

00:04:50.580 | and that results in death.

00:04:52.520 | So that is not at all a good thing.

00:04:54.200 | Not feasible.

00:04:54.640 | So let's make sure that if you're going to do a ketogenic diet or a fasting regimen that

00:04:59.440 | you're not depriving yourself of essential nutrition, that you're getting enough calories, you're

00:05:06.120 | getting enough nutrients, that you're doing it in a medically sound way so that you're optimizing

00:05:11.760 | your health and not hurting your health.

00:05:16.960 | We have, you know, it's hard to measure this in humans in vitro because we can't like do

00:05:28.400 | an intervention to a human and then dissect their brain and like biopsy it and look at

00:05:32.140 | the mitochondria under the microscope.

00:05:34.020 | So we mostly have animal data that supports this, but animal data strongly supports that ketogenic

00:05:43.040 | interventions improve mitophagy, so getting rid of these old and defective mitochondria.

00:05:50.520 | So you're kind of cleaning house, you're getting rid of the bad, and then you're replacing them

00:05:58.340 | with new fresh ones, mitochondrial biogenesis, so that at the end of the day, the cell

00:06:04.000 | will have more healthy mitochondria.

00:06:06.060 | Now, some researchers have really hyper-focused on the ketogenic diet might be working through

00:06:11.920 | the gut microbiome, this gut-brain connection, and we have some evidence that that is true.

00:06:18.600 | So researchers actually took feces from human children with epilepsy before starting a ketogenic

00:06:30.160 | ketogenic diet, and then afterward while they were stable on a ketogenic diet, and then they

00:06:36.760 | transferred these fecal samples to mice who were predisposed to epilepsy or predisposed to

00:06:44.700 | seizures.

00:06:45.000 | When they took the feces from the children while the children still had or seizing, the mice

00:06:52.800 | were more likely to seize when they took the feces from the children doing the ketogenic diet and

00:07:02.160 | transferred it to the mice, the mice were less likely to have seizures.

00:07:06.380 | Interesting.

00:07:07.360 | Even though the mice were not on ketogenic diets.

00:07:09.920 | So there's something in the feces of children with epilepsy doing ketogenic diets that has an

00:07:21.540 | anti-seizure effect.

00:07:22.620 | What could that something be?

00:07:24.520 | It could be the gut microbiome, but it could be molecules, neurotransmitters, neuropeptides,

00:07:32.360 | other things that those microbes are producing, or it could be neuropeptides and other factors

00:07:40.500 | that the gut cells are producing.

00:07:42.760 | So we really don't know for sure what exactly is it.

00:07:47.060 | So on the surface, there's something in the feces.

00:07:49.900 | There's a gut microbiome, a gut-brain connection thing.

00:07:54.000 | What does that have to do with mitochondria?

00:07:56.120 | So another research group did that same model, got mice to have an anti-seizure effect from

00:08:06.240 | a ketogenic diet, and then dissected their brains looking for what changed in the brain.

00:08:14.820 | How exactly is a ketogenic diet having an anti-seizure effect in the brain?

00:08:21.240 | Because that's the pathology, the pathological finding seizure is occurring in the brain.

00:08:28.260 | And when they analyzed genetic changes, up-regulation, down-regulation, it all centered on mitochondria.

00:08:40.240 | That the changes in the gut were resulting in mitochondrial changes in the brain, which means

00:08:48.620 | brain energy metabolism in the brain.

00:08:51.620 | And so again, it's an umbrella theory doesn't replace what we know.

00:08:59.180 | It's not gut microbiome or serotonin.

00:09:02.800 | It's not gut microbiome or mitochondria.

00:09:05.540 | It's both.

00:09:06.560 | Both of them are true, and it's all interconnected.

00:09:10.260 | So I do think we've got more than enough data that ketogenic therapies impact brain metabolism,

00:09:21.580 | which then impacts neurotransmitters.

00:09:24.520 | That's really what I hope will become one of many really important studies published by Ian

00:09:36.140 | Campbell and colleagues in the UK, that they just did a pilot trial, 20 patients with bipolar

00:09:43.240 | disorder, put on ketogenic diets, and they found wide-ranging improvements in metabolic health

00:09:51.100 | biomarkers, like weight, blood pressure, other things.

00:09:53.660 | But they also found a reduction in brain glutamate activity, which is often associated with bipolar

00:10:02.720 | disorder and hyperexcitability and seizures.

00:10:05.280 | And so that helps us understand, again, it's not metabolic or glutamate, a neurotransmitter.

00:10:13.240 | It's both.

00:10:13.960 | It's putting it together.

00:10:16.100 | Yeah, the Campbell study is really interesting.

00:10:18.300 | We will link to that in the show note captions.

00:10:20.500 | And incidentally, we will also link to this American Heart Association appalling quote-unquote

00:10:28.360 | testimony.

00:10:29.080 | Sorry, AHA.

00:10:30.100 | I'm not sorry.

00:10:31.940 | I'm not sorry.

00:10:34.260 | But then again, I'm not a physician, so I don't have to worry about that.

00:10:38.300 | Well, maybe I do.

00:10:39.060 | Anyway.

00:10:41.000 | I'm not a cardiologist.

00:10:43.580 | Is there any rationale for people who don't have epilepsy or don't suffer from bipolar or

00:10:50.220 | schizophrenia, but like myself, would like to keep our mitochondrial function as strong as

00:10:57.860 | possible for doing a brief ketogenic intervention?

00:11:02.380 | Yes.

00:11:03.300 | The answer is yes.

00:11:05.320 | Can intermittent – so I'm going to lump ketogenic with other fasting-mimicking diets and fasting

00:11:12.880 | itself.

00:11:13.400 | So can intermittent fasting or can cycles of fasting have health-improving qualities or health-improving

00:11:23.160 | effects?

00:11:23.900 | Absolutely.

00:11:26.060 | So interestingly, before I talk about even some of the science on this, and it's not

00:11:33.960 | super robust.

00:11:35.060 | Why?

00:11:35.680 | Because again, we don't fund diet studies.

00:11:38.380 | There's no money to be made from dietary interventions.

00:11:42.460 | Really?

00:11:43.260 | There's no patent on it.

00:11:44.620 | Nobody cares about dietary interventions.

00:11:47.620 | But there are a lot of studies on exercise interventions.

00:11:50.240 | But even those are – they're not huge randomized controlled trials with 10,000 participants.

00:11:57.880 | They're not – you know, like even the federal government will fund large-scale medication

00:12:05.760 | trials, statin studies, and others.

00:12:09.740 | But they often don't.

00:12:12.760 | I mean, there have been a few – the Women's Health Initiative funded a massive dietary intervention

00:12:17.540 | study, and unfortunately, that was a huge disappointment to the field because it was negative.

00:12:22.400 | They randomized women to just keep doing the diet you're eating or go on a low-fat diet,

00:12:29.860 | and the low-fat diet didn't do anything for their heart health or other objective kind of outcome

00:12:39.780 | measures.

00:12:41.480 | And put another way, just to really close this for people, it means a low-fat diet is

00:12:48.320 | no better than the standard American diet.

00:12:51.020 | A low-fat diet is equivalent.

00:12:53.620 | You get equivalent health effects from a low-fat diet to a standard American diet.

00:13:00.720 | That's really bad.

00:13:02.900 | So low-fat diets need to go away, and people who promote low-fat diets need to stop promoting.

00:13:10.040 | They need to come up to speed with the science and just, like, move on.

00:13:14.080 | Like, at least acknowledge there are healthy fats.

00:13:16.680 | Even though fat has more calories, don't worry about those calories.

00:13:20.440 | Worry about the health effects, the long-term health effects.

00:13:24.940 | Yeah.

00:13:25.420 | You got to get those monounsaturated fats, and you got to get your omega-3s, and you have

00:13:28.880 | to – you know, and I'm a believer in eating some butter here and there.

00:13:32.240 | You were asking me about intermittent ketogenic diets or intermittent fasting.

00:13:36.760 | Intermittent fasting.

00:13:37.700 | So I'll just say that we have a long history in multiple cultures on Earth for thousands

00:13:46.300 | of years.

00:13:47.140 | Fasting has been part of healing rituals.

00:13:55.020 | India, India, China, Christian – fasting has been a part of rituals.

00:14:02.240 | And, you know, most people just assume it's religious folklore or just silliness or whatever.

00:14:08.660 | But I actually think millennia of humans were not all stupid idiots.

00:14:14.260 | And that some people along the way actually noticed this seems to do something useful.

00:14:20.080 | And that's probably why it found its way in every culture and persisted for thousands of

00:14:26.940 | years, because there was actually something meaningful happening.

00:14:33.160 | .

00:14:35.160 | you

How Ketogenic Diet Improves Brain Function | Dr. Chris Palmer & Dr. Andrew Huberman

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