Recent data from the Centers for Disease Control and Prevention more than shows that 40% of American adults are classified as obese and 36% report symptoms of anxiety, depression, or both. Corresponding Shebani SethiMD, a clinical assistant professor of psychiatry and behavioral sciences, the two epidemics are closely linked.
Sethi is licensed in both Psychiatry and Obesity Medicine and is the founder of Stanford Medicine’s Department of Metabolic Psychiatrythe first academic clinic to focus on treating patients with mental and metabolic disorders – conditions such as insulin resistance or prediabetes, high cholesterol, high blood pressure, and being overweight or obese.
Sethi coined the term “metabolic psychiatry” in 2015 after noticing a high prevalence of metabolic disorders in her treatment-resistant psychiatric patients and realizing that she needed to address both issues simultaneously to ensure adequate mental health care.
She spoke to us about how metabolic disorders affect the brain and how treating mental illness through nutrition can bring new hope to patients.
1. How do you define metabolic psychiatry?
Metabolic psychiatry is a new subspecialty focused on the treatment and management of metabolic disorders to improve mental health outcomes. A growing body of evidence points to a link between mental illness and altered metabolism in the brain; Therefore, treating this dysfunction can improve treatment outcomes.
Metabolic disease rates are already very high in the general population. A study found that up to 88% of American adults have poor metabolic health, and rates are higher in people with psychiatric disorders. As a matter of fact, research out Stanford medicine Colleagues suggest that developing a metabolic disorder like insulin resistance can double your risk of depression even if you have no history of mental illness.
The good news is that in our clinic we have seen encouraging improvements in mental health after treatment of metabolic diseases by non-pharmacological methods (including diet and lifestyle changes) in combination with medication. research shows that patients with treatment-resistant bipolar disorder did better when insulin resistance was addressed.
For a long time, doctors mostly viewed diet as a secondary therapy, an adjunct to medications that might lower blood pressure or improve diabetes. But we have recognized that metabolic nutritional therapy can serve as an important medical intervention in mental illness that can alter brain structure and function. We learn from our neuroscientists who recognized the connections between brain and body metabolism over a century ago, leading to the successful treatment of pediatric epilepsy with the ketogenic diet, before the advent of the first anti-seizure drug.
2. It’s easy to see how mental illness can lead to conditions like obesity or diabetes because someone struggling mentally may not be able to eat well or exercise. But you say the opposite is also true. How does this work?
We don’t know all the mechanisms, but we do know that patients who are diagnosed with a first episode of schizophrenia – even before they are treated with drugs – already have impaired insulin and glucose metabolism in the brain.
When insulin resistance develops, the brain becomes ‘more impermeable’, meaning more substances can cross the blood-brain barrier and get into brain tissue. This leads to an accumulation of toxic substances and increased inflammation. We see significantly more inflammation in the brains of people with mental illness, especially treatment-resistant patients, than healthy people.
A lot has also happened research in the last century regarding metabolism and mitochondrial dysfunction and how this affects brain activity in mental illness. Mitochondria are the site of energy production and consumption in the cell. When they’re not working properly, the communication and connections between brain cells — also known as neural networks — are less stable, affecting cognition and worsening mental health.
We are investigating whether dietary changes, specifically a ketogenic diet, can improve this instability in the brain. In collaboration with a UC San Francisco neuroscientist colleague, Judith Ford, we are recruiting patients diagnosed with either bipolar disorder or schizophrenia in a randomized control study investigating the effects of a ketogenic diet on insulin resistance and neural network stability as measured by functional MRI.
3. Can you tell us more about the ketogenic diet and why it might be beneficial for some patients with serious mental illnesses?
I want to stress that a ketogenic diet isn’t for everyone. It should actually be called a therapy rather than a diet because it is a metabolic procedure that should be carried out under medical supervision.
However, a ketogenic diet is a very low-carb, high-fat, moderate-protein diet. Patients on this diet avoid bread, rice, pasta, and grains while consuming whole foods such as eggs, avocado, nuts, fish, and chicken. Vegetarians can also go ketogenic, but food choices can be limited.
Restricting carbohydrates forces the body to burn fat for energy and prompts the liver to make compounds called ketones, which can be used to fuel brain cells instead of glucose. At our clinic, we try to support patients in what is known as “nutritional ketosis,” which means that their body gets all the nutrients it needs while keeping blood ketone levels between 0.5 and 5 millimolar. (This is very different from ketoacidosis, a dangerous condition of 50 millimolar ketones or higher.)
Although ketogenic diets sometimes get a bad rap, lumped together with fad diets that can be dangerous or difficult to stick to, ketogenic diets have been used to treat pediatric epilepsy and other neurodegenerative diseases for decades. There is a lot of research showing that ketogenic diets increase mitochondrial growth and reduce inflammation and oxidative stress in the brain, but until now, no one has studied the effect of a ketogenic diet specifically on mental illness.
4. They recently completed a pilot study involving patients with severe mental illness who tried the ketogenic diet for four months. Can you describe some of your preliminary results?
In this pilot studywe taught 22 patients with severe bipolar disorder or schizophrenia how to follow a ketogenic diet. It was all real, meaning that instead of controlling food intake in a temporary inpatient setting and delivering meals, we taught patients how to buy and prepare their own food. Despite the severity of their mental illness, our patients were able to successfully implement the ketogenic diet as a lifestyle change. However, there is a selection bias as those who participated in the study may have been a more motivated population.
After four months, our preliminary results were very encouraging: they included a 30 percent reduction in central abdominal fat, an 11 percent decrease in BMI, and a 17 percent decrease in heart inflammation as measured by a marker called highly sensitive C-reactive protein. Perhaps most importantly, we saw a 30 percent improvement in our patients’ total clinical impression inventory, which is the gold standard of psychiatric assessment we use to assess symptoms of mental illness. We also saw improvements in sleep.
We are analyzing the rest of the data and will present our findings at the International Society for Bipolar Disorders conference next June. We are also enrolling patients in randomized controlled trials to compare a ketogenic diet to diets based on the USDA standard Dietary Guidelines. It’s one step at a time, but if we’re able to alter the structure and function of the brain through non-pharmacological methods like diet, that’s a very positive step forward for chronic mental illness.
5. Can you give an example of a patient that could be treated in your clinic? How is your approach different from treating just her mental illness or just her metabolic disorder?
I treat patients who have either only psychiatric illness or psychiatric illness and metabolic problems, including patients with eating disorders. After performing a physical examination, collecting a complete medical and psychiatric history, and reviewing metabolic biomarkers, I assess the patient’s eating behavior and medications to see what metabolic interventions might be appropriate.
I rely heavily on non-pharmacological interventions and do a lot of nutritional counseling, which I find very satisfying. Oftentimes, my patients have a misconception about what’s healthy and what’s not, so I start from scratch and teach them “Nutrition 101” using a science-based approach. I also evaluate whether certain therapies or medications might be helpful: are they an emotional eater or not?
Although medications can be life-saving, some psychiatric drugs can contribute to metabolic disorders, so I work with my patients’ other doctors to adjust their medications whenever possible — and avoid medications that lead to weight gain or insulin resistance. Finally, in our Hippocratic Oath, we pledge to use all available measures for the benefit of our patients, including diet plans.
For additional resources and information on enrolling in current clinical trials, visit Stanford Medicine’s Metabolic Psychiatry community page.