CGPR: Can you start by telling us about your work and your theory connecting metabolism to mental health?
Dr. Palmer: My work explores how metabolism underlies mental health, proposing that mental disorders are metabolic disorders affecting the brain. Viewing mental illness through this lens connects biological, psychological, and social factors shared with conditions like obesity, type 2 diabetes, and cardiovascular disease.

CGPR: How do you incorporate metabolic health into your psychiatric assessments and treatment planning? 
Dr. Palmer: I do standard mental health assessments and assess metabolic markers (eg, weight, blood pressure, glucose regulation, inflammatory biomarkers). These are frequently abnormal in older psychiatric patients, and growing evidence suggests they are not merely comorbid conditions or side effects of psychiatric medications but may be foundational to mental illness pathophysiology (Chourpiliadis C et al, JAMA Netw Open 2024;7(4):e244525). If a patient is overweight, has type 2 diabetes, and experiences chronic depression, I don’t automatically reach for the next antidepressant. Instead, I consider a comprehensive lifestyle medicine intervention addressing diet, nutrition, exercise, sleep regulation, and relationships to target all three conditions simultaneously. Depression can hinder motivation, so start small: a short walk or one dietary change (eg, adding vegetables or cutting back on sugary drinks) to build momentum. If a patient’s weight and their blood sugars improve, their depression will likely also improve.

CGPR: Which biomarkers guide your interventions? 
Dr. Palmer: In older adults, I routinely measure weight, BMI, blood pressure, and waist circumference. I typically obtain fasting glucose and lipids, particularly HDL cholesterol and triglycerides. I also assess insulin resistance by obtaining fasting glucose and insulin simultaneously to calculate Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), a broad measure of insulin resistance. Two patients can have the same fasting glucose but different insulin levels: High insulin suggests resistance, low insulin suggests normal function. Both insulin resistance and type 2 diabetes increase Alzheimer’s disease (AD) risk, as insulin signaling problems in the brain play a profound role in AD development and progression (De Felice FG et al, Nat Rev Neurosci 2022;23(4):215–230). Brain glucose hypometabolism, where the brain struggles to generate sufficient energy from glucose, is a hallmark feature of AD.

CGPR: How do you think through dietary interventions for older adults with different metabolic needs? 
Dr. Palmer: Dietary interventions fall into several categories, often requiring opposite recommendations. First, being overweight or obese can contribute to metabolic dysfunction, and weight loss may improve both physical and mental health. But conversely, people with eating disorders, depression, or cancer may be severely malnourished and require weight restoration. Both scenarios reflect metabolic imbalance; metabolism requires balance, not extremes. Next, micronutrient deficiencies, like low vitamin B12 or folate, may require supplementation. Biological variability matters: Whole grains help most but harm those with celiac disease.

CGPR: Please tell us about where ultra-processed foods and diets come in. 
Dr. Palmer: There’s growing concern about ultra-processed foods. While many foods are processed in basic ways for safety and storage (like pasteurizing milk or freezing vegetables), ultra-processed foods are different. They’re made mostly from refined ingredients and additives, and research shows they’re linked to poor physical and mental health outcomes (Lane MM et al, BMJ 2024;384:e077310). The gut microbiome is another area where diet influences brain health. I use nutritional interventions to modulate the gut microbiome and thereby brain activity. For example, the ketogenic diet alters the gut microbiome (Ang QY et al, Cell 2020;181(6):1264–1275). In an older adult with long COVID, I may consider the ketogenic diet for its anti-inflammatory and immune-modulating effects, even when poor diet wasn’t the original cause.

CGPR: Can you discuss the MIND diet and the latest research for cognitive impairment and dementia? 
Dr. Palmer: The MIND diet combines the Mediterranean and DASH diets. It includes leafy greens, nuts, berries, beans, whole grains, fish, poultry, olive oil, and wine, while limiting red meat, butter, margarine, cheese, pastries, sweets, and fried food. Epidemiological studies suggest greater adherence to the MIND diet reduces risk for neurodegenerative disorders, particularly AD (Chen H et al, JAMA Psychiatry 2023;80(6):630–638). But there are two red flags. First, a large RCT of more than 600 overweight or obese older adults found no significant cognitive benefit after three years, despite modest improvements in metabolic health (Barnes LL et al, N Engl J Med 2023;389(7):602–611). Though critics argue the trial was too short, researchers believed three years was sufficient based on prior data. Both groups lost weight and improved diet quality, which likely diluted the effect. Second, the MIND diet was developed through statistical modeling combining DASH and Mediterranean diet elements after neither showed strong standalone benefits. While this doesn’t invalidate the diet, it raises questions about its scientific grounding. Despite these challenges, the MIND diet is still promoted as our best hope for preventing neurodegeneration.

CGPR: How do you counsel patients who ask what they should eat for optimal brain health and to prevent cognitive decline? 
Dr. Palmer: I focus on biomarkers and dietary and lifestyle modifications to improve them. If a patient presents with high blood pressure, abnormal lipids, type 2 diabetes, and obesity, I look for interventions addressing all conditions simultaneously. Various dietary patterns work. If the MIND diet suits them, I support it. But I often use ketogenic and low-carbohydrate diets, which can be life-changing for people with insulin resistance, type 2 diabetes, and mental illness. Treatment should be individualized; something the patient is capable and willing to do. And it shouldn’t just be diet. We must address all lifestyle medicine pillars. Are they getting adequate sleep and physical activity? Do they have social connections and purpose? When someone says, “I’m profoundly lonely. I don’t know why I’m alive,” changing their diet is futile. Instead, I focus on restoring sleep, rebuilding purpose, and strengthening connections. Once these factors improve, their blood sugars, blood pressure, and lipids might improve.

“Treat the ketogenic diet as a medical intervention, not a fad. There is extensive science behind ketogenic therapy, including how to monitor labs, electrolytes, and vitamin levels, as well as how to identify and address nutrient deficiencies.”

Christopher Palmer, MD 

CGPR: You mentioned the ketogenic diet. How does it work for patients with mental illness? 
Dr. Palmer: The ketogenic diet is high-fat, very low-carbohydrate, and moderate-protein. It shifts the body’s metabolism into ketosis so the body burns fat for energy instead of glucose, producing ketone bodies, an alternative fuel for the brain. This 100-year-old evidence-based epilepsy treatment was developed to stop seizures, not for weight loss. We regularly use epilepsy treatments (eg, valproic acid, lamotrigine, gabapentin, benzodiazepines [BZDs], implants, vagal nerve stimulators) for mental illnesses. The keto diet can stop seizures when multiple medications fail, so we are exploring its psychiatric potential, including in neurodegeneration and comorbid symptoms like depression, anxiety, rumination, and psychosis. The mechanisms are complex, but we know more about the ketogenic diet’s brain effects than any other dietary intervention. It modulates neurotransmitters, reduces neuroinflammation, regulates ion channels, alters the gut microbiome, and affects mitochondria through mitophagy and mitochondrial biogenesis.

CGPR: Are there patients who would not benefit from a ketogenic diet?
Dr. Palmer: Not all patients are candidates. It can be risky for those with inborn errors of metabolism affecting fatty acid oxidation, a history of pancreatitis, severe kidney or liver dysfunction, or active eating disorders.

CGPR: What evidence is there for the ketogenic diet for neurocognitive disorders? 
Dr. Palmer: For neurocognitive disorders, the evidence is preliminary but promising. Preclinical studies in AD models show the ketogenic diet reduces amyloid plaques, reduces neuroinflammation, and prevents neurodegeneration (Xu Y et al, CNS Neurosci Ther 2022;28(4):580–592). We have human trial data from small pilot trials. The best one randomized 26 patients with AD to both a low-fat diet for 12 weeks and a ketogenic diet for 12 weeks, separated by a 10-week washout. On the ketogenic diet, patients showed statistically significant improvement in quality of life and activities of daily living (ADLs); although cognition improved, it didn’t reach statistical significance compared to the low-fat diet (Phillips MCL et al, Alzheimers Res Ther 2021;13(1):51). In AD, quality of life and ADLs are probably more important management metrics than whether the person remembers yesterday’s meal. Larger trials are underway, and ketone supplements might produce benefits as a more modest intervention (Avgerinos KI et al, Ageing Res Rev 2020;58:101001).

CGPR: For clinicians wanting to help patients start a ketogenic diet, what advice and implementation pearls can you offer?
Dr. Palmer: Treat the ketogenic diet as a medical intervention, not a fad. Extensive science supports ketogenic therapy, including how to monitor labs, electrolytes, and vitamin levels, as well as how to identify and address nutrient deficiencies. Multiple versions exist—vegan, vegetarian, omnivore, carnivore—with varying fat compositions. Without guidance, most patients will fail. Partner with a dietitian to identify which biomarkers and interventions to target. Importantly, ketogenic diets have objective biomarkers of compliance. Use urine, blood, or breath tests to confirm ketosis and adjust the “dose” as needed.

CGPR: What should clinicians watch for in terms of the medical side effects of the ketogenic diet? 
Dr. Palmer: The first week can be challenging, particularly for older adults taking diabetes or blood pressure medications. Because the diet rapidly lowers glucose and blood pressure, medications like metformin, insulin, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and antihypertensives may need adjustment or discontinuation. Many patients experience “keto flu” in the first one or two weeks. They can feel nauseous, lightheaded, dizzy, or weak as their body transitions from using carbohydrates to fats and ketones. This transition takes days to weeks, as cells need enzymes, receptors, and transport molecules to run on fats and ketones versus glucose. For patients with brain glucose hypometabolism, symptoms may worsen before improving.

CGPR: What psychiatric side effects do you see most commonly in the first few weeks after starting the ketogenic diet?
Dr. Palmer: The most common is hypomania. The diet can be highly energizing. Some patients develop a reduced need for sleep. I rarely discontinue the diet, instead using sleep hygiene, short-term sleep medications (three to five days), or adjustments to existing medications. After a few nights of adequate sleep, symptoms usually resolve, and many patients describe improved mood, energy, and memory.

CGPR: Can you share an example where you saw significant changes with the ketogenic diet? 
Dr. Palmer: I often share Doris’s story with her full permission because it illustrates the remarkable potential for metabolic interventions. Doris had a severely traumatic childhood and was diagnosed with schizophrenia at 17. Over the decades, she tried numerous antipsychotics, mood stabilizers, antidepressants, and BZDs, none of which worked. By her late 60s, she had a PACT team, was under guardianship, and had been hospitalized multiple times following suicide attempts. At 70, weighing 330 pounds, her PCP referred her to a weight loss clinic using the ketogenic diet. Within two weeks, Doris began losing weight and reported spontaneous resolution of her long-standing hallucinations and delusions. Within a month, her schizophrenia was in complete remission. Within six months, she had tapered off all antipsychotic medications and remained in remission.

CGPR: Do you think metabolic interventions really improve functioning in neurocognitive disorders if introduced earlier in life?
Dr. Palmer: While Doris’s case highlights severe schizophrenia, the condition includes cognitive and functional impairment. With neurodegenerative disorders, the challenge is neuron death, not just atrophy. Once neurons die, no intervention, including the ketogenic diet, can bring them back. Still, metabolic interventions may offer powerful benefits: improving quality of life, reducing symptoms, and slowing progression. If we use metabolic lifestyle interventions early enough, these interventions might delay the onset of neurodegeneration, allowing people to live out their lives. They might pass away from something else first.

CGPR: Thank you for your time, Dr. Palmer.