Essentials: Diet & Nutrition for Mental Health | Dr. Chris Palmer
In a Nutshell
Dr. Chris Palmer discovered that the ketogenic diet can dramatically improve severe mental illness by targeting mitochondrial dysfunction in the brain. His landmark case involved a patient with treatment-resistant schizoaffective disorder who achieved complete symptom resolution, lost 160 pounds, and regained independent functioning after years of failed medications and therapy. The mechanism involves stimulating mitophagy to replace defective mitochondria, which regulate neurotransmitter production, hormone synthesis, inflammation, and stress responses—functions that directly impact mental health symptoms.
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Andrew Huberman welcomes Dr. Chris Palmer to discuss the relationship between nutrition and mental health. Most people understand that food can affect mood in the short term, but fewer recognize that nutrition and mental health interact in an intimate, possibly causal way over long periods of time.
Dr. Palmer's exploration of nutrition and mental health began with his own experience. As a child, he had OCD, depression, and suicidality. During his internship and residency at Harvard, he was diagnosed with metabolic syndrome despite following a low-fat diet and exercising regularly. His doctor recommended medication for pre-diabetes, cholesterol, and blood pressure.
After hearing rumors that the Atkins diet could improve cholesterol and pre-diabetes, and frustrated with conventional treatments, Dr. Palmer tried the Atkins diet. Within three months, his metabolic syndrome completely resolved, and he experienced dramatic improvements in mood, energy, concentration, and sleep. For the first time, he woke up before his alarm feeling rested.
As an attending physician treating treatment-resistant mental illness at a tertiary care hospital, Dr. Palmer began offering the ketogenic diet to patients who had already tried multiple medications, decades of psychotherapy, and ECT without success. Some patients experienced remarkable antidepressant effects. One woman became hypomanic within a month after years of chronic depression and suicidality.
Due to lack of clinical trials on the safety and efficacy of the Atkins diet for mental disorders, Dr. Palmer kept a low profile, offering the diet to willing patients until 2016.
In 2016, Dr. Palmer treated a 33-year-old man with schizoaffective disorder who had been his patient for eight years. The patient had daily auditory hallucinations, paranoid delusions, weighed 340 pounds, and had tried 17 different medications without symptom relief. The patient decided to try the ketogenic diet to lose weight.
Within two weeks, the patient began losing weight and showed dramatic improvements in eye contact, smiling, and engagement. After 6-8 weeks, the patient spontaneously reported that his auditory hallucinations were diminishing and his paranoid delusions about families controlling his thoughts were disappearing. He recognized that these beliefs had likely been symptoms of schizophrenia rather than reality.
The patient lost 160 pounds and maintained the weight loss. He completed a certificate program, performed improv in front of a live audience, moved out of his father's home, and lived independently. Tapering medications has been challenging due to decades of medication use since childhood.
Dr. Palmer adjusts ketone level targets based on the condition being treated. For some patients, simply eliminating junk food can significantly improve mood disorders. Highly processed foods high in both sugar and fat appear worst for metabolic and mental health.
For depression, he targets blood ketone levels greater than 0.8 mmol. For psychotic disorders, schizophrenia, and bipolar disorder, he aims for levels greater than 1.5 mmol when using the diet as a brain treatment.
The ketogenic diet was developed in 1921 by Dr. Russell Wilder at the Mayo Clinic specifically to treat epilepsy, not for weight loss. It was created to mimic the metabolic state of fasting, which had been observed since Hippocrates to stop seizures. The problem with fasting is that seizures typically return when normal eating resumes.
Early results showed 50% of patients became seizure-free and another 35% had 50% or greater reduction in seizure frequency. By the 1950s, anticonvulsant medications largely replaced the diet, but approximately 30% of epilepsy patients remain treatment-resistant. The diet was resurrected at Johns Hopkins in the 1970s for these cases, with about one-third becoming seizure-free, another third experiencing clinical benefit, and one-third showing no response.
Decades of neuroscience research have documented the ketogenic diet's effects on the brain, including:
- Influencing neurotransmitter levels (glutamate, GABA, adenosine)
- Changing calcium channel regulation and calcium levels
- Altering gene expression
- Reducing brain inflammation
- Modifying the gut microbiome
- Improving insulin resistance and insulin signaling
The diet stimulates mitophagy (removal of old and defective mitochondria) and mitochondrial biogenesis (creation of new, healthier mitochondria). Dr. Palmer believes these mitochondrial effects are central to the diet's efficacy for both epilepsy and chronic mental disorders.
Mitochondria serve as the "motherboard" of the cell, directing and allocating resources, not merely providing power. They play direct roles in:
- Production, release, and regulation of neurotransmitters including serotonin, dopamine, glutamate, and acetylcholine
- Providing building blocks and energy for neurotransmitter synthesis
- Moving along synaptic membranes to facilitate neurotransmitter vesicle release
- Regulating the stress response (cortisol, adrenaline, noradrenaline, inflammation, gene expression in hippocampus)
- Synthesizing steroid hormones including cortisol, estrogen, testosterone, and progesterone
- Regulating inflammatory processes, including turning inflammatory cells on and off
- Directing macrophage function during wound healing phases
These functions connect to key variables disrupted in mental disorders: neurotransmitters, hormones, epigenetic expression, and inflammation.
Mitophagy is a specific form of autophagy targeting mitochondria, involving removal of old and defective mitochondria to be replaced with new ones. There appear to be unique regulators of mitophagy compared to general autophagy.
Mitochondria play a role in autophagy itself. The global picture of autophagy is stimulated by fasting states or fasting mimicking states. When the body senses that it doesn't have enough food, it hunkers down and starts to recycle dead old parts in a carefully orchestrated way, taking them to lysosomes where they get degraded, and those degradation products get used for either energy or to build new things. Autophagy is always occurring at a low level, but it can be hyper-stimulated through fasting, calorie restriction, fasting mimicking diets, and other things. This is why fasting and calorie restriction are hot topics in the medical field now—they've been shown to induce longevity, and researchers think it's probably through that process. The body becomes lean and conservative in terms of its allocation of resources.
The body doesn't just destroy the healthiest tissue along with the old dead stuff. It has processes that identify the old and defective parts first, and they go first. That's what's beautiful about the whole thing, and that's why fasting is so important.
Mitophagy plays a really important role because there's the term called mitochondrial dysfunction, which some researchers are wanting to get rid of and move away from because mitochondria do so many different things, and different mitochondria, even within the same cell, may be specializing in different tasks. Mitochondria from one cell to another are sometimes doing very different things. Not all mitochondria can produce cortisol—that's specific to cells where those genes are getting turned on. It's not like all mitochondria are producing cortisol, just the ones in the adrenal gland, for instance, are producing cortisol.
It has long been known for decades that mitochondrial dysfunction is associated with everything that ails us, essentially. David Sinclair published a paper in one of the cell journals saying that mitochondria are actually the unifying link of everything we know about aging. Defective mitochondria or defective mitochondrial function, mitochondrial dysfunction, is possibly the unifying cause of aging and all of the aging-related disorders.
Mitophagy is trying to address all that—saying, "Okay, this is bad. We don't want defective mitochondria, and how can we get rid of old ones or defective ones and replace them with new ones?" The most powerful signal and tool available is related to diet: calorie restriction. That is the oldest, truest, best-proven way to prevent aging in a wide variety of animal species. Fasting and intermittent fasting also work, and fasting mimicking diets can stimulate the process of mitophagy.
For the typical person who's an omnivore eating rice and pasta, they might feel far better or even a little bit better if they were in a lower glucose state. There are a lot of people who suffer from full-blown depression, but there are also a lot of people who suffer from moodiness and feeling not so great—subclinical depression, which can be called burnout. Some days are great, and then other days they feel lousy for reasons they don't understand.
There is a distinction between what's the actual root cause and what are effective treatments—these are two separate things. Calorie restriction, ketogenic diet, and carbohydrate restriction are inducing metabolic changes in the brain and body. Regardless of what the person was eating, they are inducing metabolic changes that can be really beneficial to brain health.
For an average person who is not currently under psychiatric care, not taking prescription medicines, but is saying they're burned out, exhausted, and want brain energy, the recommendation is to try carb restriction for a while and see if that produces clinical benefit.
There is an example of a person who is not even a patient—just somebody who read the book. He had chronic anxiety, was trying meditation, was trying all sorts of things, and was ready to go on prescription medicine. He read an early copy of the book and took it upon himself without consulting anyone to restrict carbohydrates alone—he did not go ketogenic. He is a vegetarian. He restricted carbs. Within 3 weeks, he said he didn't need prescription medicine and couldn't believe how much better he felt. All he did was cut out some of the high-carb foods in his diet.
For some people it can be that simple. For people with serious mental disorders—if they are chronically depressed, if they're on lots of prescription meds, if they're disabled by their symptoms, and certainly if they're bipolar or have schizophrenia—those are the people who need to work with a medical professional because meds may need to be adjusted. They need a real shot at this diet.
It's not like weight loss. Weight loss, everybody wings it. Either you're successful or you aren't. You look on the internet or you read a book and see whether it works or not. But if you're using it to treat a serious disorder, serious help is needed.
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