Q&A: Keto diet may improve symptoms of severe mental illness

Key takeaways:

• Psychotropic medications can cause adverse metabolic effects such as weight gain.
• The ketogenic diet may help restore metabolic health and improve psychiatric symptoms in patients receiving these medications.

Results of a small pilot study suggest that the ketogenic diet may help counter adverse metabolic effects of psychotropic medications and improve mental health among adults with schizophrenia or bipolar disorder.

Psychotropic medications can have “undesirable side effects” such as changes in weight and metabolism, leading many patients to discontinue treatment, according to Shebani Sethi, MD, an associate professor of psychiatry and behavioral sciences at Stanford Medicine, and colleagues.

In addition, previous studies indicate that psychiatric diseases “may have underpinnings in metabolic dysfunction,” the researchers wrote in Psychiatry Research.

“While research on [ketogenic diets] for psychiatric illnesses is in its early stages, with only case reports and observational studies being reported to date, the well-established use of [ketogenic diets] in the treatment of neurological conditions suggests that it would be worthy of exploration in the treatment of psychiatric disorders through carefully planned robust clinical trials,” they wrote.

Sethi and colleagues conducted a proof-of-concept study to investigate the impact of the ketogenic diet on metabolic health and psychiatric symptoms among 21 adults with schizophrenia or bipolar disorder. All the participants were currently receiving psychotropic medications and had at least one metabolic abnormality like insulin resistance, hypertriglyceridemia, dyslipidemia or impaired glucose tolerance.

For 4 months, the participants were instructed to consume approximately 10% of their calories from carbohydrates, 30% of their calories from protein and 60% of their calories from fat. The researchers monitored participants’ adherence to the ketogenic diet through weekly measurements of blood ketone levels.

Overall, 14 patients were fully adherent to the ketogenic diet, six were semiadherent and one was not adherent.

At baseline, 29% of participants met criteria for metabolic syndrome, which the researchers defined as having three or more of the following conditions:

• abdominal obesity;
• elevated triglyceride levels;
• low HDL cholesterol;
• elevated BP; and
• elevated fasting glucose.

After 4 months of the ketogenic diet, none of the participants had metabolic syndrome, according to Sethi and colleagues.

On average, the researchers observed a 10% decrease in body weight and 11% decrease in waist circumference, as well as reductions in BP, BMI, triglycerides, blood glucose and insulin resistance.

“We’re seeing huge changes,” Sethi, who is also the founder and director of the Metabolic Psychiatry Clinic at Stanford, said in a press release. “Even if you’re on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, the insulin resistance. I think that’s very encouraging for patients.”

In addition, there was a 31% improvement on the Clinical Global Impressions scale, with 79% of participants experiencing clinically meaningful improvement.

“The participants reported improvements in their energy, sleep, mood and quality of life,” Sethi said in the release. “They feel healthier and more hopeful.”

We spoke with Sethi to learn more about the study findings and the implications for primary care providers.

Healio: What led you to conduct this research?

Sethi: As a medical student, I observed a patient with treatment-resistant schizophrenia experience significant relief in an obesity clinic at Duke University School of Medicine through the ketogenic diet. Understanding the influence of the ketogenic diet on the brain from epilepsy research, I witnessed beneficial effects in serious mental illnesses like bipolar or schizophrenia. This inspired me to focus on this population clinically and to conduct research at Stanford, studying the relationship between metabolism and mental health.

Healio: Did anything in the findings stand out to you in particular?

Sethi: Our 4-month study revealed that 100% of the patients who started with metabolic syndrome no longer had it by the end of the study. Furthermore, 79% were in psychiatric remission with a one point or more increase on the Clinical Global Impression scale. We also observed more significant improvements in the adherent group compared with the semiadherent group, indicating a potential dose-response relationship with the ketogenic therapy.

Healio: What are some potential reasons for the associations between improved mental health and the keto diet?

Sethi: Evidence from the field of epilepsy with the ketogenic diet has revealed changes in metabolic deficits, oxidative stress, stabilization of neuronal membranes and neuro- inflammation of the brain. These concepts could be applied for other brain health conditions, including psychiatric conditions.

Healio: What are the implications for PCPs?

Sethi: PCPs and psychiatrists can refer patients with mental health conditions for additional support in metabolic psychiatry treatment to help support their patients further.

References:

• Pilot study shows ketogenic diet improves severe mental illness. https://med.stanford.edu/news/all-news/2024/04/keto-diet-mental-illness.html. Published April 1, 2024. Accessed April 29, 2024.
• Sethi S, et al. Psychiatry Res. 2024;doi:10.1016/j.psychres.2024.115866.