Episode 99: Dr. Chris Palmer – Diet & Nutrition For Mental Health | Huberman Lab

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Key Takeaways

  • Nutrition and mental health interact intimately and even causally in some cases
  • Processed foods rich in fat, carbohydrates, and sugar are the worst for metabolic health and mental health
  • Insulin resistance is impaired in people with chronic mental disorders
  • A ketogenic diet has shown beneficial effects in the treatment of chronic depression, PTSD, Alzheimer’s, alcohol use disorder, bipolar disorder, schizophrenia, epilepsy
  • The beauty of the ketogenic diet for intervention is you can measure with objective biomarkers
  • “Once you understand the science of mitochondria, you can actually connect all the dots of the mental health puzzle.” – Dr. Chris Palmer
  • Calorie restriction, ketogenic diet, and carbohydrate restriction are inducing metabolic changes in the brain and body that can be beneficial to brain health – it’s not just about villainizing sugar or carbohydrates alone
  • Just like medication, dose the diet: for some people, symptoms can be reduced without fully being on a ketogenic diet; just cutting highly processed foods rich in carbohydrates, fat, and sugar is sufficient
  • The obesity epidemic is really a mystery though we want to believe it’s diet; it’s not as simple as energy balance or food – we had junk food and highly processed diets in the 70s – it’s likely mitochondrial health deficits
    • Sleep disruption, stress, trauma, drug and alcohol use, tobacco, and THC impair mitochondria and mitochondrial dysfunction
  • “I see obesity as a symptom of metabolic derangement in the body or brain…and if we’re really going to get anywhere we need to identify what is causing metabolic derangement.” – Dr. Chris Palmer
  • Exogenous ketones or supplementing with ketones while on a standard diet isn’t enough
    • The ketogenic diet isn’t just about ketones, people on the diet are also lowering glucose levels, improving insulin signaling, ramping up mitochondrial biogenesis (particularly in the liver), gut microbiome changes, hormones are repaired, etc.  


Chris Palmer, MD (@ChrisPalmerMD) is the director of the Department of Postgraduate and Continuing Education at McLean Hospital and an assistant professor of psychiatry at Harvard Medical School. For over 20 years, Dr. Palmer’s clinical work has focused on treatment-resistant cases, and recently he has been pioneering the use of the ketogenic diet in psychiatry, especially treatment-resistant cases of mood and psychotic disorders.

In this episode, Andrew Huberman & Chris Palmer dive into the applications of diet for neurological and mental health disorders. They review the role of the mitochondria in mental health, the impact of a low-carb diet on the gut microbiome and weight loss, the validity of the ketogenic diet for various conditions, and much more.

Host: Andrew Huberman (@hubermanlab)

Book: Brain Energy by Christopher M. Palmer, MD

Context & Dr. Palmer’s Personal Experience

  • Throughout much of his early adulthood, Dr. Palmer was in therapy and dealing with depression, and suicidal ideation, and struggled with successful treatment
  • In his 20s (during residency), Dr. Palmer struggled with metabolic syndrome and was told it was genetic and there was nothing he can do
  • What started it all: 3 months into the low-carb (modified Atkins diet), Dr. Palmer’s metabolic syndrome was cured
  • After changing his diet, Dr. Palmer noticed a dramatic improvement in mood, energy, cognition, and sleep
  • He began anecdotally offering a modified Atkin’s diet or keto diet to patients and the antidepressant success was remarkable when patients achieved ketosis as measured by urine
  • In 2016 he successfully treated a case of schizoaffective disorder with the ketogenic diet – the patient no longer hears voices, lost significant weight, started a successful career, and has maintained health
    • Note, diet is not a substitute for medication – the patient was on medication consistently but prior to the ketogenic diet no medication regimen was working for him

Addressing Diet & Medication Adherence

  • As we know, adherence is difficult with any diet
  • Most patients are not compliant 100% of the time with medication, usually not on purpose – it’s hard to remember to take medication every day
  • The ketogenic diet is particularly great as a treatment protocol because you can measure and know with certainty whether someone is adherent (unlike other diets and medication)
    • For depression, the recommended range is around 0.8 mmol
    • For psychotic disorder and bipolar, the recommended range is around 1.5 mmol  
  • For some, measured ketosis isn’t necessary – just cutting highly processed foods rich in carbohydrates, fat, and sugar is sufficient
  • Important distinction: “Just because the ketogenic diet is an effective treatment, does not imply that the cause of the problem was eating carbohydrates.” – Dr. Chris Palmer
  • Intensive support (coach, education of family, providing meals, etc.) is necessary to make the diet as easy and doable as possible, at least for 6 months
  • Negative reinforcement is a big reason people are able to adhere to the ketogenic diet – the piece of cake isn’t worth the hallucination
  • The first variable to look at when prescribing diet is current weight – in this case, the first line of attack is carb restriction; start with no added sugar and low carb (<20g), encourage healthy sources of fat so the body uses fat stores
    • A thin person needs a lot of fat

Origins Of Ketogenic Diet For Epilepsy

  • In 1920 there was an observation that fasting can stop seizures
  • Fasting puts the body into a mode of autophagy and conservation of resources which are beneficial to health
  • The problem with fasting is (1) you eventually need food; (2) as soon as the patient ate again, the seizures came back
  • The ketogenic diet was developed in 1921 as a treatment for epilepsy because it mimics a fasting state – 50% became seizure-free and 35% saw a reduction in seizures
  • 30% of people have treatment-resistant epilepsy which resurrected the ketogenic diet in the 70s with success rates of about 1/3
  • Benefits of the ketogenic diet: influences neurotransmitter levels (particularly glutamate, GABA, adenosine), changes calcium channel regulation, changes gene expression, reduces brain inflammation, improves the health of the gut microbiome, improves insulin resistance and signaling
  • A ketogenic diet is now an established treatment for epilepsy

Importance Of Mitochondrial Health & How To Achieve It

  • Mitochondria are the energy factories of cells, present everywhere in neurons – think of mitochondria as not just power cord for computer but motherboards, directing and allocating resources to cells
  • Mitochondria provide energy for the production of neurotransmitters and the release of neurotransmitters (ATP alone is not enough)
  • “Mitochondria play at least a role in all of the aspects of human stress response” – Dr. Chris Palmer
  • If mitochondria are in short supply, a function may be dysregulated
  • Mitochondria play a role in inflammation, playing a key role in turning inflammatory processes off
  • It’s a myth! Maternal DNA is not solely responsible for mitochondrial health
  • A ketogenic diet has two critical benefits for mitochondrial health: (1) stimulates mitophagy (like autophagy for mitochondria); (2) stimulates mitochondrial biogenesis (increases the number and health of mitochondrial cells)
  • Mitophagy: gobbling up dead cells in mitochondria to replace them with newer, healthier cells
    • Autophagy is stimulated by fasting or fasting-mimicking states
    • Mitochondrial dysfunction is associated with nearly every physical and mental health disorder and disorder of aging
  • On mitophagy: “The most powerful signal and tool we have right now is related to diet – it’s calorie restriction…fasting and intermittent fasting…and fasting mimicking diets” – Dr. Chris Palmer
  • Glucose doesn’t tell the full story – high glucose levels are often a symptom, maybe of mitochondrial dysfunction somewhere in the brain and body
    • It is true that consuming large amounts of junk food and processed foods can lead to dysregulation of glucose levels, but this isn’t true of everyone

Alcohol Use & Disorder

  • Alcohol disrupts the way the brain uses all fuels
  • Reward pathways are metabolically compromised in alcoholics
  • When people drink alcohol, the liver converts alcohol into acetate which travels to the brain and fuels brain cells differentially – fueling reward centers more than other centers
  • Patients in the rehab center who were assigned to the ketogenic diet needed fewer benzodiazepines than the non-ketogenic group
    • The keto group also had improved brain metabolism, reduced inflammation, and reported fewer withdrawal symptoms
  • “If we can correct brain metabolic defects from chronic alcohol use, we might be able to help people be sober” – Dr. Chris Palmer
  • The ketogenic diet increases the metabolism of alcohol which means your blood alcohol level is up to 5x higher than on a standard diet so if you relapse on the ketogenic diet, it could be deadly

Alzheimer’s Disease

  • A marker of Alzheimer’s disease is glucose hypermetabolism
  • With Alzheimer’s specific regions are more metabolically compromised than others so we see patterns of atrophy  
  • Cells aren’t getting enough fuel from glucose as an energy source
  • Brain metabolism supplements can be corrected in the short-term by using exogenous ketones, even on a standard diet – but it’s unlikely that supplementing with liquid ketones could be the answer even if not adherent to the ketogenic diet
    • Exogenous ketones may be useful for alcoholics during a craving (instead of drinking) and for people who are otherwise healthy and have difficulty adhering to the ketogenic diet
  • Timing of carbohydrates: reducing carbohydrates at breakfast and lunch (not dinner) resulted in cognitive improvement
  • The ketogenic has been shown to improve biomarkers (as well as cognition and activities of daily living) in patients with Alzheimer’s disease but adherence to the diet is difficult and the studies have a small sample size of completion

Some Cautions About Fasting

  • A fasted state can induce dopamine rewards where the person feels good by abstaining from eating (which can be a slippery slope to an eating disorder)
  • Hypomania: almost euphoric feeling – for example, not sleeping much because you don’t feel like you need sleep since you feel so good
    • Hypomania can go away with three days of good sleep, at least 6 hours

Hormone Considerations

  • Almost universally, men seem to have an easier time losing weight on a ketogenic diet than women
    • Men also report feeling better while women feel worse
  • A ketogenic diet is mimicking fasting state in the body – women trying to reproduce should not be in a fasted state
  • There isn’t good control data about what is happening to hormonal systems by sex
  • Semaglutide and GLP-1 agonists are addressing the symptom (obesity) but not the underlying problem
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