Metabolic Psychiatry: Bridging Brain and Metabolic Health

By Maya Shetty, BS

Metabolic Psychiatry: Bridging Brain and Metabolic Health

In recent years, a groundbreaking field known as Metabolic Psychiatry has emerged at the intersection of metabolic and brain health. Spearheaded by Shebani Sethi, MD, a Clinical Associate Professor in the Department of Psychiatry and Behavioral Sciences at Stanford University, this innovative field sheds light on the powerful connection between our metabolic health and mental well-being.

As rates of mental illnesses like Alzheimer’s, bipolar disorder, and schizophrenia rise alongside metabolic conditions such as obesity, diabetes, and cardiovascular disease, researchers are uncovering how these seemingly distinct issues may be intertwined. A Stanford study found that developing a metabolic disorder like insulin resistance can double your risk of depression, even if you’ve never experienced mental illness before. As such, emotional and metabolic disorders often occur together, with over forty percent of individuals with severe mental illnesses also experiencing metabolic syndrome.

It’s easy to see how mental illness could lead to conditions such as obesity or diabetes because someone struggling emotionally might be unable to eat well or exercise. However, it’s becoming increasingly apparent that metabolic disorders have a distinct role in the onset and progression of mental illnesses.

“Many psychiatric diseases have underpinnings in metabolic dysfunction,” explains Dr. Sethi. “We are seeing insulin and glucose handling differences in the brain in patients with psychiatric conditions.”

These metabolic issues in the brain are present even at the early stages of disease detection and progression. Dr. Sethi explains that patients diagnosed with a first episode of schizophrenia—before any treatment with medications—already show disrupted energy metabolism in the brain. Similarly, Alzheimer’s disease has been referred to as type III diabetes due to its strong link to disrupted insulin signaling in the brain.

Dr. Sethi has been a trailblazer in this area since 2015, founding the first academic Metabolic Psychiatry Clinic focused on treating patients with both mental health and metabolic disorders. Metabolic Psychiatry examines how improving metabolic health through nutritional interventions can significantly enhance brain health and mitigate the symptoms of severe psychiatric conditions.

How Metabolic Health Impacts Brain Health

Many psychiatric diseases are characterized by metabolic dysfunctions, which impair the brain’s ability to function properly. These dysfunctions occur when chemical processes are disrupted, hindering the body’s ability to produce and utilize energy efficiently.

A well-known example is insulin resistance, where the body’s cells don’t respond appropriately to insulin—the hormone that allows glucose to enter cells and be metabolized for energy. The brain, one of the most metabolically active organs, requires large amounts of energy to function. It is highly dependent on glucose due to its limited flexibility to use other energy sources. This dependence makes metabolic conditions like insulin resistance particularly harmful, as any disruption in glucose supply puts the brain at risk for cognitive decline and neuronal degeneration.

“If you don’t have optimal metabolic functioning in the brain, then you won’t process and create energy as efficiently as a healthy brain,” states Dr. Sethi. “The brain will have all this glucose around it, but you can’t actually use it properly. This is called cerebral glucose hypometabolism, and it’s very common in psychiatric and neurodegenerative diseases.” 

Other metabolic abnormalities commonly seen in psychiatric conditions include oxidative stress, mitochondrial dysfunction, and neurotransmitter imbalances, which all have downstream effects on synapse connection and neuronal excitability.

“We don’t know for sure what the primary drivers for these metabolic dysfunctions are, but it is likely a combination of factors influencing one another,” says Dr. Sethi. “For example, insulin resistance is correlated with higher inflammation levels and oxidative stress in the brain, which in turn exacerbates mitochondrial and neurotransmitter dysfunction.”

Chronic inflammation disrupts brain activity and undermines the integrity of the brain’s protective mechanisms. The blood-brain barrier (BBB), a critical structure that protects the brain from harmful substances in the blood, becomes compromised. This “leaky” BBB allows inflammatory molecules, pathogens, and toxins to enter the brain from the bloodstream, exacerbating the inflammatory response within the brain and creating a self-perpetuating cycle of neuroinflammation. “We see significantly more inflammation in the brains of people with mental illness, especially in treatment-resistant patients, than in healthy people,” states Dr. Sethi.

How Nutrition Can Improve Brain Health

Dr. Sethi’s metabolic approach to brain health not only enhances our understanding of psychiatric conditions but also opens up new avenues for treatment, such as nutritional interventions. Studies have shown that nutritional interventions can impact the balance of neurotransmitters in the brain, which is crucial for regulating mood and behavior.

By targeting metabolic dysfunctions such as insulin resistance, oxidative stress, and improper energy utilization, nutritional interventions can help restore brain function and reduce inflammation. This comprehensive approach addresses the symptoms of psychiatric conditions while tackling their underlying causes, offering a more effective and holistic treatment strategy.

The Stanford Metabolic Psychiatry group, led by Dr. Sethi, is investigating whether dietary changes, such as adopting a ketogenic diet, can stabilize brain health. The ketogenic diet, which is high in fat and low in carbohydrates, encourages the brain to use fat and ketone bodies as primary fuels instead of glucose. This metabolic shift helps counteract issues related to glucose metabolism and insulin resistance. The diet adopted in the study focuses on consuming whole, unprocessed foods, including protein and non-starchy vegetables, without restricting fats.

“The ketogenic diet is a strong, powerful metabolic intervention. It can improve neurological and psychiatric conditions by making changes in the brain through these pathways,” says Dr. Sethi. “By providing ketones as an alternative energy source, the ketogenic diet reduces glucose dependency, which is beneficial in counteracting glucose hypometabolism.”

In Dr. Sethi’s study among participants with schizophrenia consuming a ketogenic diet, there was a 32 percent reduction in Brief Psychiatric Rating Scale scores. There was also increased life satisfaction and enhanced sleep quality among participants.

The ketogenic diet can also have a positive influence on brain aging for everyone and has been experientially understood to help normalize the brain for centuries. Dating back to roughly 500 BC,  fasting (which mimics the ketogenic diet) was used to treat epilepsy. Current research shows that the destabilization of brain networks might indicate early signs of reduced metabolism, which is linked to dementia. By increasing the use of ketones for energy, dietary interventions like the ketogenic diet can provide more energy to the brain and potentially protect against aging-related cognitive decline.

Dr. Sethi warns, however, that “the ketogenic diet is very specific and may not be suitable for everyone. It can be incredibly beneficial for people with insulin resistance, obesity, or diabetes, but it may not be feasible or appropriate for all individuals.”

Future studies will reveal further dietary interventions that benefit brain health. For example, Dr. Sethi and her team plan to conduct a randomized controlled trial with the ketogenic diet versus the Mediterranean diet in cases of serious mental illness. Whichever diet one chooses, Dr. Sethi recommends the reduction of sugar, ultra-processed foods, and refined carbohydrates to promote both metabolic and brain health.

“Our diet provides the precursors for neurotransmitters and other vital cellular structures in the brain, while also impacting inflammation levels. If we have deficiencies in our diet, we’re not going to be able to create the components and environment we need for optimal brain function and regulation of mood,” states Dr. Sethi.