The brain is the body’s most energy-intensive organ. Despite making up just 2 percent of the body’s mass, it consumes about 20 percent of its energy. Typically, the brain is mostly fueled by glucose that is produced by the breakdown of carbohydrates. But when there isn’t enough glucose to go around, the brain starts consuming fat-derived compounds called ketone bodies for fuel.
This shift, ketosis, is what happens when you follow a ketogenic diet, or keto diet, an eating regimen that is high in fat and low in carbs. Scientists have been studying how ketosis changes the brain since the early 1920s, when the diet was introduced as a therapy for treatment-resistant epilepsy in children. Some studies have also suggested it could help treat symptoms of Alzheimer’s disease.
And now results from several small trials bolster the case that the keto diet can help treat mental health conditions that include depression, bipolar disorder, schizophrenia and anorexia nervosa. The results are preliminary—randomized controlled trials are underway to better evaluate who might be helped by the diet and how much it might benefit them. But together, the findings support a theory of some mental illnesses as metabolic disorders, in which the brain’s ability to derive energy from its preferred sources becomes compromised.
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This understanding of the keto diet has “really forced me to rethink how I understand mental illness,” says Chris Palmer, a psychiatrist who studies metabolism at Harvard Medical School.
The Energy Connection
The idea that mental illnesses and metabolism are connected makes sense, regardless of the potential effects of the keto diet. “Metabolism is basically the backbone of physiology,” says Isaac Marin-Valencia, a neurologist studying metabolic diseases at the Icahn School of Medicine at Mount Sinai. “Without metabolism, life wouldn’t be possible. So it’s not surprising that pretty much any human disease [has] some metabolic component.”
Scientists already knew that people with psychiatric conditions such as depression, bipolar disorder and schizophrenia are at higher risk of metabolic diseases such as diabetes, obesity and polyendocrine metabolic ovarian syndrome, or PMOS (formerly polycystic ovary syndrome, or PCOS). The reverse is also true: people with metabolic disorders are more likely to have psychiatric illnesses as well. Serious mentalillnesses also often involve disruptions to glucose metabolism in the brain. In bipolar disorder, for example, people whose brains were inefficient at turning glucose into energy showed earlier and more frequent symptoms.
This may explain why the ketogenic diet, which bypasses glucose by providing an alternate fuel source, shows promise for treating these diagnoses. In a randomized controlled trial with 88 participants that was published in February, people with treatment-resistant depression who followed a strict keto diet experienced a small improvement in their symptoms compared with a control group. Other, smaller pilot trials found that keto improved bipolar disorder and schizophrenia symptoms; importantly, participants in the studies remained on their medications to treat those conditions. At least five randomized controlled trials are currently underway to test the effects of the diet more rigorously.
“These research results are early; they’re preliminary. But it definitely gives us a signal that we should explore further,” says Shebani Sethi, a metabolic psychiatrist at Stanford University.
One big unanswered question is how the keto diet is doing this at all. The effect is likely driven by multiple factors beyond just providing the brain with a source of alternate fuel, Palmer says. Ketosis may affect the balance of two of the brain’s essential neurotransmitters, glutamate and gamma-aminobutyric acid (GABA), which excite and inhibit neuronal firing, respectively. This regulating effect helps explain how the keto diet can treat epilepsy, and it could also explain why the diet might be useful in other conditions, too. Ketosis also supports the overall function of mitochondria, the powerhouses of a cell, which create the molecules that brain cells use as energy. The diet also appears to reduce inflammation throughout the body, a factor that is also intertwined with many mental illnesses; it is possible that tamping down on inflammation can indirectly improve symptoms of these disorders.
A Potential Treatment for Anorexia Nervosa
The keto diet may have benefits for other types of mental illness, too. A small study published this month found that the diet improved eating disorder symptoms in people with anorexia nervosa who were either mildly underweight or had managed to get back to a healthy weight.
The idea that a highly restrictive diet could help treat a highly restrictive eating disorder such as anorexia nervosa seems counterintuitive. “It’s kind of paradoxical,” says the study’s lead author Guido Frank of University of California, San Diego. But while the keto diet limits the food groups that people can eat, it doesn’t necessarily restrict the calories they consume. The participants in the trial didn’t experience clinically significant weight loss while on the diet.
Study co-author Caroline Beckwith, a wellness coach who acted as a counselor for participants in the study, had herself recovered from anorexia nervosa after she was treated with the keto diet. Before following the diet, “I was so scared of eating fat. That was a whole food group I didn’t eat,” she says. But when she didn’t gain weight on keto, she felt encouraged to keep it up. Within weeks, she says, she experienced the first day in many years in which she wasn’t preoccupied with food restriction and exercise. “I realized, at the end of the day, that was hours and hours of not having any anorexic thoughts,” Beckwith adds.
Both Palmer and Sethi stress that anyone who wants to try a ketogenic diet for mental illness must talk to their doctor first. The diet can interact with psychiatric medications in unpredictable ways. It can also trigger episodes of mania, including in people with no psychiatric history, which may be destabilizing. “Please don’t attempt to do this on your own,” Palmer says.
That a single intervention could help treat conditions as varied as anorexia nervosa, depression and Alzheimer’s disease is tantalizing. And there are a few reasons why a common treatment could show some utility for these seemingly disparate conditions. Alzheimer’s and depression often occur together, which suggests some of the same biological mechanisms could underlie both; other pairs of these conditions have similar relationships. Plus, certain conditions may be more similar than current diagnostic categories account for—bipolar disorder and schizophrenia, for example, may be part of a single spectrum of conditions.
More broadly, metabolism is increasingly being linked to an array of health conditions, suggesting that metabolic treatments—whether they are diets, drugs or exercise regimens—may affect many systems in the body. Glucagonlike peptide 1 (GLP-1) medications, for example, primarily target metabolism and weight, but they affect the brain, too, helping reduce the risk of substance use and some eating disorders.
“Metabolism affects every cell, tissue and organ in your body,” Palmer says. A therapy that addresses metabolic dysfunction, he adds, “can end up being a powerful treatment.”
