Recent data from the Centers for Disease Control and Prevention reveals that more than 40% of American adults are classified as obese and 36% report symptoms of anxiety, depression, or both. According to Shebani SetiMD, clinical assistant professor of psychiatry and behavioral sciences, the two epidemics are closely linked.
Board certified in both psychiatry and obesity medicine, Sethi is the founder of Stanford Medicine’s Metabolic Psychiatry Clinicthe first academic clinic focused on treating patients with mental illness and metabolic disorders, such as insulin resistance or prediabetes, high cholesterol, hypertension, and overweight or obesity.
Sethi coined the term “metabolic psychiatry” in 2015 after seeing a high prevalence of metabolic disorders among his treatment-resistant psychiatric patients and realizing that in order to provide adequate psychiatric care, he needed to address the two issues simultaneously.
He talked to us about how metabolic disorders affect the brain and how treating mental illness with nutrition can offer patients new hope.
1. How do you define metabolic psychiatry?
Metabolic psychiatry is a new subspecialty focused on detecting and treating metabolic dysfunction to improve mental health outcomes. Mounting evidence points to a connection between mental illness and altered metabolism in the brain; therefore, treatment that addresses this dysfunction may improve patient outcomes.
Rates of metabolic conditions are already very high in the general population. A study found that up to 88% of American adults have poor metabolic health, and in people with psychiatric illnesses, the rates are higher. In fact, research of Stanford Medicine colleagues suggests that developing a metabolic disorder such as insulin resistance can double your risk of depression, even if you don’t have a history of mental illness.
The good news is that at our clinic we have seen encouraging improvements in mental health after treating metabolic conditions through non-pharmacological methods (including dietary and lifestyle changes) in combination with medication. Research shows that people with treatment-resistant bipolar disorder did better when insulin resistance was addressed.
For a long time, doctors have thought of nutrition primarily as a secondary therapy, an adjunct to medications that might lower blood pressure or improve diabetes. But we have realized that nutritional metabolic therapy can serve as a significant medical intervention for mental illness, which can change the structure and function of the brain. We took lessons from our neurology colleagues who recognized the links between metabolism in the brain and the body more than a century ago, leading to the successful treatment of pediatric epilepsy with ketogenic diets before the advent of the first anti-seizure drug.
2. It’s easy to see how mental illness could lead to conditions like obesity or diabetes because someone who has mental problems might not be able to eat right or exercise. But you are saying that the opposite is also true. How does it 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 have been treated with medication, already have altered insulin and glucose metabolism in the brain.
As insulin resistance develops, the brain becomes more “leaky,” meaning more substances can cross the blood-brain barrier and reach brain tissue. This results in a buildup of toxic substances and increased inflammation. We see significantly more inflammation in the brains of people with mental illnesses, especially treatment-resistant patients, than in healthy people.
there has also been a lot research over the past century regarding metabolism and mitochondrial dysfunction, and how that affects brain activity in mental illness. Mitochondria are the site for energy production and consumption in the cell. If they don’t work properly, the communication and connections between brain cells, also known as neural networks, are less stable, affecting cognition and worsening mental health.
We are studying whether a change in diet, particularly a ketogenic diet, can improve this instability in the brain. Working together with a neuroscientist colleague from UC San Francisco, Judith Ford, we are recruiting patients who have been diagnosed with bipolar disorder or schizophrenia in a randomized control trial which explores the effects of a ketogenic diet on insulin resistance and neural network stability, as measured by fMRI.
3. Can you tell us more about the ketogenic diet and why it might be beneficial for some patients with severe mental illness?
I want to emphasize that a ketogenic diet is not for everyone. It really should be called a therapy rather than a diet, because it is a metabolic intervention meant to be carried out under medical supervision.
With that being said, a ketogenic diet is a very low carb, high fat diet with moderate protein intake. Patients on this diet avoid bread, rice, pasta, and cereals, and consume whole foods such as eggs, avocado, nuts, fish, and chicken. Vegetarians can also follow a ketogenic diet, but food options may be limited.
Restricting carbohydrates forces the body to burn fat for energy and causes the liver to produce compounds called ketones, which can be used to fuel brain cells instead of glucose. At our clinic, we try to keep patients in what we call “nutritional ketosis,” which means their bodies get all the nutrition they need while keeping blood ketone levels between 0.5 and 5 millimolar. (This is quite different from ketoacidosis, a dangerous state of ketones of 50 millimolar or higher.)
Although ketogenic diets sometimes get a bad rap, lumped in with fad diets that can be dangerous or difficult to maintain, ketogenic diets have been used for decades to treat pediatric epilepsy and other neurodegenerative conditions. There is plenty of research showing that ketogenic diets increase the growth of mitochondria 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. He recently completed a pilot study of patients with severe mental illness who tried the ketogenic diet for four months. Can you describe some of your preliminary results?
In this pilot study, we taught 22 patients with severe bipolar disorder or schizophrenia how to maintain a ketogenic diet. It was all from the real world, meaning we didn’t monitor food intake in a hospice setting and we didn’t deliver meals, but instead taught patients how to buy and prepare their own food. Despite the severity of their mental illness, our patients were able to successfully adopt the ketogenic diet as a lifestyle change. However, there is a selection bias, as those who entered the study may have been a more motivated population.
After four months, our preliminary results were very encouraging: they included a 30% reduction in central abdominal fat, an 11% reduction in BMI, and a 17% reduction in cardiac inflammation, as measured by a marker called high sensitivity C-reactive protein. . Perhaps most importantly, we saw a 30% improvement in our patients’ Clinical Global Impressions Inventory, which is the gold standard psychiatric assessment we use to assess symptoms of mental illness. Also, we saw improvements in sleep.
We are analyzing the rest of the data and will present our results at the International Society for Bipolar Disorders conference next June. Additionally, we are recruiting patients for randomized controlled trials to compare a ketogenic diet with diets based on the USDA standard. Dietary guidelines. It’s one step at a time, but if we’re able to change the structure and function of the brain through non-drug 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 your mental illness or just your metabolic disorder?
I treat patients who have a psychiatric condition alone or a psychiatric condition in addition to a metabolic problem, including patients with eating disorders. After performing a physical exam, taking a complete medical and psychiatric history, and reviewing metabolic biomarkers, I assess the patient’s eating pattern 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. My patients often have misconceptions about what is healthy and what is not, so I start from scratch and teach them “Nutrition 101” using a science-based approach. I also assess whether certain types of therapy or medications may be helpful: Are they emotional eaters or not?
Although medications can save lives, some psychiatric medications can contribute to metabolic dysfunction, so I work with my patients’ other doctors to adjust their medications when possible, avoiding medications that cause weight gain or insulin resistance. After all, in our Hippocratic Oath, we pledge to use all available measures to benefit our patients, including dietary regimens.
More resources and information about enrolling in current clinical trials can be found at Stanford Medicine’s Metabolic Psychiatry. community page.
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