Diet and Nutrition for Mental Health: Ketogenic Diets, Metabolism, and Insights From Dr. Chris Palmer

Most people recognize that food can change how they feel in the short term. A meal can leave us energized, sleepy, satisfied, or uncomfortable. The more consequential question is whether nutrition can change the biology underlying our mental health over weeks, months, or years.

That question reaches well beyond weight loss. It connects diet to brain metabolism, neurotransmitters, inflammation, hormones, and the function of mitochondria. It also raises an important clinical possibility: nutritional interventions may help some people whose psychiatric symptoms have not improved with conventional treatment.

In my discussion with psychiatrist Dr. Chris Palmer, we explored both the striking clinical observations driving this field and the limits of what those observations establish. Nutrition deserves consideration as a treatment tool, but that is not the same as saying that a ketogenic diet cures mental illness or replaces medication. Understanding that distinction is essential.

Table of Contents

• How a Metabolic Problem Opened a New Question About Mental Health
• Low-Carbohydrate Diets in Treatment-Resistant Depression
• A Schizoaffective Disorder Case That Changed the Direction of the Work
• Not Everyone Needs a Ketogenic Diet
• Why Epilepsy Provides an Important Scientific Foundation
• How a Ketogenic Diet May Affect the Brain
• Mitochondria Do Much More Than Produce Energy
• Autophagy, Mitophagy, and Mitochondrial Renewal
• What This Means for Everyday Mood, Anxiety, and Burnout
• Nutrition Belongs in Mental Health Care, With Appropriate Guardrails

How a Metabolic Problem Opened a New Question About Mental Health

Palmer’s interest in nutrition began with his own health. As a child and young adult, he experienced obsessive-compulsive symptoms, depression, and suicidality. He nevertheless completed medical school and went on to internship and residency training at Harvard.

During that training, while still in his twenties, he was diagnosed with metabolic syndrome. His blood pressure was elevated, his blood lipids were poor, and he had prediabetes. He was exercising regularly and following the low-fat dietary advice he had been taught, yet his metabolic health continued to worsen.

Eventually, his physician recommended medications for blood pressure, cholesterol, and prediabetes. Before starting that regimen, Palmer decided to try the Atkins diet, despite his skepticism about its safety and its departure from the nutritional guidance he had received.

He reports that within three months, after losing approximately 10 pounds, his metabolic measurements returned to normal. But the more surprising change was psychological: his mood, energy, concentration, and sleep improved dramatically.

For the first time, he regularly woke before his alarm feeling rested. The difference challenged an assumption he had carried for years: that energetic, consistently positive people simply had better genes, better childhoods, or some other advantage he lacked.

This was a personal observation, not a controlled experiment. Still, it prompted a question that would shape his clinical work: Could a dietary intervention that changed metabolism also help people with persistent psychiatric symptoms?

Low-Carbohydrate Diets in Treatment-Resistant Depression

As an attending psychiatrist in a tertiary care setting, Palmer was treating people with unusually difficult illnesses. Many had already seen numerous psychiatrists and therapists, tried dozens of medications, spent years in psychotherapy, and undergone treatments such as electroconvulsive therapy without sufficient relief.

With conventional options running out for some patients, he began offering a low-carbohydrate approach modeled on the diet he had used himself.

The results varied. Some people were not interested, some could not sustain the diet, and some did not improve. Others experienced what he described as a substantial antidepressant effect.

One woman who had been chronically depressed and suicidal for more than five years became hypomanic within about a month. That response suggested a powerful effect on mood, but it also underscores why a large change in energy or mood should not automatically be interpreted as healthy recovery. Hypomania is clinically important and requires professional assessment.

Palmer also noticed a pattern: patients who restricted carbohydrates but did not produce detectable ketones often did not experience the same benefit as those who entered ketosis. At the time, he encouraged patients to check urinary ketones.

That observation helped distinguish two related but different interventions:

• Carbohydrate restriction: Reducing carbohydrate intake without necessarily reaching ketosis.
• A ketogenic diet: Changing the diet sufficiently to produce a sustained state of ketosis.

These early experiences were not proof of efficacy. Palmer emphasized that, at the time, there were few clinical trials even addressing the safety and effectiveness of these diets for weight loss or diabetes, much less psychiatric disorders.

A Schizoaffective Disorder Case That Changed the Direction of the Work

A particularly consequential case began in 2016. Palmer had been treating a 33-year-old man with schizoaffective disorder for eight years. The patient experienced daily auditory hallucinations, paranoid delusions, and intense fear of going out in public.

He had tried 17 medications without resolution of his symptoms. He also weighed 340 pounds and wanted to lose weight, partly because he hoped to pursue a relationship and build a more independent life.

They decided to try a ketogenic diet. Initially, weight loss was the goal.

Changes in Mood Came First

Within two weeks, Palmer noticed more than a change on the scale. His patient made better eye contact, smiled more, spoke more, and appeared increasingly engaged and hopeful. His medications had not been changed during that initial period.

Then, approximately six to eight weeks into the diet, the patient began reporting that the voices he heard were fading. He also started questioning longstanding beliefs that other people were controlling his thoughts and targeting him.

That shift was especially striking because it involved not only fewer symptoms, but greater insight into experiences he had previously understood as real external threats.

Functional Improvements Mattered as Much as Symptom Changes

Palmer reported that the patient eventually lost 160 pounds and maintained that loss through the time of our discussion. He completed a certificate program, could go into public without the same paranoia, performed improvisational comedy before a live audience, and, for a period, lived independently outside his father’s home.

Those are meaningful changes in daily function, not merely changes in a symptom score. They are also observations from one person’s treatment, not evidence that every person with schizophrenia or schizoaffective disorder will respond similarly.

Medication remained part of the clinical picture. Palmer described a slow, difficult attempt to taper medications after many years of exposure, beginning in childhood.

Do not stop or taper psychiatric medication on your own. Palmer was explicit that medication withdrawal can be difficult and dangerous and must be managed with a prescribing clinician or mental health professional.

Not Everyone Needs a Ketogenic Diet

One of the most useful points in this discussion was that nutritional treatment is not an all-or-nothing choice between an unrestricted diet and therapeutic ketosis.

For some people, Palmer begins with reducing highly processed foods, particularly foods that combine substantial amounts of sugar or refined carbohydrate with fat. He described that combination as especially concerning for metabolic health and pointed to emerging evidence connecting these dietary patterns with mental health as well.

For someone with a mood concern, simply reducing sweets and improving food quality may be enough to produce a meaningful change. In other situations, he may aim to lower glucose and insulin through carbohydrate restriction without requiring ketosis.

For chronic, disabling disorders such as schizophrenia, schizoaffective disorder, or bipolar disorder, he takes a more structured approach when using nutrition as a brain-directed treatment.

The Ketone Levels Palmer Uses Clinically

Palmer described different blood ketone targets depending on the patient and condition:

• Depression: He generally aims for blood ketones above approximately 0.8 mmol/L.
• Psychotic disorders and bipolar disorder: He generally aims for blood ketones above approximately 1.5 mmol/L, when feasible.

These are targets from his clinical practice, not established universal treatment thresholds. They should not be interpreted as instructions to pursue those numbers without supervision.

The broader point is that using a diet to treat a serious psychiatric disorder is different from experimenting with a diet for weight loss. The intervention, symptom response, medication regimen, and clinical monitoring all matter.

Why Epilepsy Provides an Important Scientific Foundation

The use of a ketogenic diet for brain disorders did not begin with psychiatry or weight loss. Its medical history stretches back to 1921, when it was developed to treat epilepsy.

Long before that, fasting had been observed to reduce seizures in some people. The practical problem was obvious: fasting cannot continue indefinitely. Once a person resumed a conventional diet, seizures could return.

Dr. Russell Wilder at the Mayo Clinic developed the ketogenic diet to address that problem. The goal was to reproduce aspects of fasting metabolism while allowing people to continue eating.

Palmer described early epilepsy reports in which approximately half of patients became seizure-free and another 35% experienced at least a 50% reduction in seizure frequency. Those historical results should not be treated as a prediction for an individual patient today.

As anticonvulsant medications became more available, a pill was generally easier to use than a demanding dietary treatment. Yet, as Palmer noted, roughly 30% of people with epilepsy continue to have seizures despite available treatments.

He described renewed use of ketogenic treatment at Johns Hopkins for difficult cases beginning in the 1970s. In the treatment-resistant groups he discussed, approximately one-third became seizure-free, another third had at least a 50% reduction in seizures, and the remaining third did not appear to benefit.

The Epilepsy Foundation’s overview of ketogenic dietary therapy provides additional context on its established role in epilepsy care.

Evidence that a diet treats epilepsy does not establish that it treats depression or schizophrenia. What epilepsy research does provide is a long clinical history and a substantial body of neuroscience showing that this dietary intervention can change brain function.

How a Ketogenic Diet May Affect the Brain

Palmer outlined several biological effects studied in connection with ketogenic diets:

• Changes in neurotransmitter systems, including glutamate, GABA, and adenosine.
• Changes in calcium regulation, which is important for cellular signaling.
• Changes in gene expression and brain inflammation.
• Changes in the gut microbiome.
• Lower glucose and insulin levels and improved insulin signaling.

Different researchers emphasize different mechanisms. Some focus heavily on the microbiome. Palmer places particular emphasis on mitochondria and two processes involved in maintaining them: mitophagy and mitochondrial biogenesis.

His proposal is that improving mitochondrial function may help explain benefits across both neurological and psychiatric conditions. That is a mechanistic framework, not a settled explanation.

At the time of our discussion, large randomized controlled trials establishing psychiatric efficacy were not yet available, although trials were underway. Clinical cases can motivate that research, but they cannot replace it.

Mitochondria Do Much More Than Produce Energy

Mitochondria are usually introduced as the powerhouses of cells. That description is correct, but incomplete.

Palmer used a useful computer analogy: mitochondria are not simply the power cord. In important respects, they also help perform the coordinating functions of a motherboard, directing resources and influencing cellular behavior.

That broader role matters because many of the systems implicated in mental illness depend on mitochondrial activity.

Neurotransmitter Production and Release

Mitochondria contribute to the production, regulation, and release of neurotransmitters, including serotonin, dopamine, glutamate, and acetylcholine.

Some intermediate products of the Krebs, or citric acid, cycle supply building blocks used in neurotransmitter production. Mitochondria also provide energy for that production.

But their involvement extends beyond supplying ATP. Palmer described experiments in which removing mitochondria from synaptic regions impaired neurotransmitter release even when researchers supplied ATP. The implication is that mitochondria support neurotransmission through additional functions, some of which are not yet fully understood.

Stress Responses and Hormone Production

Mitochondria also participate in the response to physical and psychological stress. Palmer discussed research in which genetically altering mitochondrial function affected cortisol responses, adrenaline-related responses, inflammation, and stress-related gene expression in the hippocampus.

They are involved in steroid hormone synthesis as well. Relevant hormones include cortisol, estrogen, testosterone, and progesterone.

This does not mean every mitochondrion makes every hormone. Function depends on the cell and the genes expressed there. Mitochondria in cortisol-producing adrenal cells, for example, have a different context from mitochondria in other tissues.

Inflammation and Immune-Cell Behavior

Mitochondrial signaling can help regulate both the activation and resolution of inflammatory processes. Palmer described research identifying mitochondrial signals, including reactive oxygen species, as important in switching off certain inflammatory cell responses.

He also discussed macrophages, immune cells involved in wound healing. Their work changes across the stages of healing, and mitochondrial signals help coordinate those shifts.

The significance for psychiatry is the overlap. Neurotransmission, hormones, inflammation, and gene regulation have all been implicated in mental disorders. Palmer’s hypothesis is that mitochondria may help connect findings that otherwise appear separate.

That makes mitochondrial biology a promising organizing framework. It does not mean that a single mitochondrial defect has been proven to cause every mental illness.

Autophagy, Mitophagy, and Mitochondrial Renewal

To understand Palmer’s emphasis on mitochondrial health, it helps to distinguish three related processes.

• Autophagy: A cellular recycling process that breaks down components and reuses their materials.
• Mitophagy: A more specific process that removes mitochondria, including those that are old or defective.
• Mitochondrial biogenesis: The production of new mitochondria.

Autophagy occurs continuously at a baseline level. Under certain conditions, including fasting or calorie restriction, cells increase recycling activity. Components are delivered to lysosomes, broken down, and their materials can be reused for energy or rebuilding.

This is not simply indiscriminate destruction. Cellular quality-control systems help identify damaged components for removal.

Palmer’s interest is in coupling that removal with renewal. He described ketogenic diets as potentially stimulating both mitophagy and mitochondrial biogenesis, helping cells replace defective mitochondria and, over time, increase their supply of healthier mitochondria.

Why “Mitochondrial Dysfunction” Is a Broad Term

Because mitochondria do so many jobs, calling them “dysfunctional” can conceal important differences. One mitochondrial function might be impaired while another is preserved. Mitochondria can also differ across cell types and may specialize even within a single cell.

That complexity matters when connecting mitochondrial research to psychiatric symptoms. There is unlikely to be one simple measure that captures everything mitochondria are doing.

The Connection to Aging Research

Palmer also linked this discussion to aging. Mitochondrial dysfunction is associated with many age-related conditions, and calorie restriction has extended lifespan across a wide range of animal models.

One proposed explanation involves improved cellular maintenance and resource allocation, including autophagy and mitophagy. However, animal longevity findings do not establish that fasting or a ketogenic diet will extend a particular person’s life.

Nor does the biological appeal of fasting make prolonged food restriction an appropriate self-treatment for psychiatric illness. The historical reason for developing ketogenic therapy was precisely that fasting itself is not a sustainable long-term treatment.

What This Means for Everyday Mood, Anxiety, and Burnout

Not everyone struggling with energy or mood has a severe psychiatric disorder. Many people feel exhausted, anxious, inconsistent, or burned out without being under psychiatric care.

For someone in that situation who is not taking prescription medication, Palmer said he might begin with a period of carbohydrate restriction to see whether it helps, rather than immediately pursuing a strict ketogenic diet.

He described a vegetarian reader of his book who had persistent anxiety despite trying meditation and other approaches. The person reduced high-carbohydrate foods without entering ketosis and reported substantial improvement within three weeks.

That is another anecdote, not proof that carbohydrate restriction treats anxiety broadly. It does, however, illustrate that any useful nutritional change need not look identical for every person.

A Treatment Response Does Not Prove the Original Cause

Palmer made a distinction worth keeping in mind: identifying an effective treatment is different from identifying the root cause of an illness.

If carbohydrate restriction helps someone feel better, that does not prove that carbohydrates caused the problem. A dietary intervention may induce a metabolic state that is beneficial regardless of how the symptoms began.

This helps avoid a common mistake in health discussions: turning a possible treatment benefit into a universal claim about which foods cause disease.

Nutrition Belongs in Mental Health Care, With Appropriate Guardrails

The central lesson is not that everyone should enter ketosis. It is that the brain’s metabolic environment deserves serious attention in mental health care.

For some people, improving food quality and reducing highly processed foods may be a useful starting point. Others may benefit from carbohydrate restriction. For people with chronic, disabling psychiatric symptoms, a medically supervised ketogenic intervention is an area of active clinical investigation.

The guardrails are essential:

• Do not assume a dramatic case report predicts your own outcome. Responses vary, and some people do not benefit.
• Do not replace psychiatric treatment with an unsupervised diet experiment. Serious symptoms require coordinated care.
• Do not change medication independently. Dietary treatment may require clinical monitoring and medication adjustments by a prescriber.
• Keep mechanisms and outcomes separate. A plausible biological explanation is not the same as demonstrated clinical efficacy.

For additional background on Palmer’s work, his clinical and educational resources offer a starting point.

What makes this field compelling is the combination of meaningful patient experiences, established neurological uses of ketogenic therapy, and testable biological hypotheses. The task now is to determine who benefits, under what conditions, and with what risks. Nutrition should neither be dismissed as irrelevant nor presented as a universal cure.