Promising research results linking keto diets to treating severe mental illness

08 Apr 2024 --- A new clinical trial links keto diets to “dramatic improvements” in metabolic function and psychiatric symptoms in patients diagnosed with either bipolar disorder or schizophrenia who were also overweight or met criteria for metabolic abnormalities, such as insulin resistance or impaired glucose tolerance.

According to the researchers, the dual improvements found in the trial are rare in mental health care, as treatments often lead to significant comorbidities, such as weight gain, obesity, dyslipidemia (imbalance of lipids, such as cholesterol) and cardiometabolic disease. 

After the four-month single-arm pilot trial, 79% of participants showed clinically meaningful psychiatric improvement with at least one point change on the Clinical Global Impression scale. In addition, 75% of study participants were in recovery or a recovered state on a Clinical Mood Monitoring Scale. 

“These results are encouraging and suggest that a ketogenic diet intervention could serve as a valuable adjunctive treatment for individuals living with serious mental illness,” says the study’s lead researcher, Shebani Sethi, founding director of the Stanford Metabolic Psychiatry Clinic and clinical associate professor of psychiatry.  

“The dual metabolic and psychiatric improvements observed in our study represent novel findings in psychiatry, warranting further investigation.”

Benefits of a keto diet 
Commonly used for fast weight loss, keto diets have been linked to improvements in obesity, type 2 diabetes, epilepsy and psychiatric illness. This diet, consisting of a daily intake of 10% carbohydrates, 30% protein and 60% fat, aims to achieve ketosis — a metabolic state where the body burns fat for energy instead of glucose. 

The study, published in Psychiatry Research, is the first US-based clinical trial to examine the impact of the low carbohydrate dietary intervention for serious mental illness since 1965. It was led by the Stanford University School of Medicine and funded by the Baszucki Group, a private lender and advocacy group aiming to transform mental health outcomes. 

Patients consumed 20 g of carbohydrates, one cup of vegetables, two cups of salad and eight glasses of water daily.“After we witnessed ketogenic therapy send our son’s ‘treatment resistant’ bipolar disorder into complete and lasting remission, we immediately started funding metabolic psychiatry studies like Dr. Sethi’s,” says Jan Ellison Baszucki, co-founder and president of Baszucki Group. 

“This pilot study, the first of its kind, offers hope to those living with bipolar illness and has successfully paved the way for larger trials that could establish ketogenic therapy as a safe and effective adjunctive or even first-line treatment for bipolar disorder and other serious mental illnesses.”

The trial was completed by 21 participants, each receiving a full medical and psychiatric evaluation, a fasting blood test and training on implementing a keto diet. The researchers encouraged them to consume 20 g of carbohydrates, one cup of vegetables, two cups of salad and eight glasses of water daily. 

Metabolic and psychiatric results 
The study concludes that a ketogenic nutritional intervention was safe and feasible with a high adherence rate — measured through blood ketone levels. Of the 21 participants, 14 were fully adherent (achieving ketosis in 80–100% of times measured), and six were semi-adherent (50–79% of times measured). 

Participants who wholly adhered to the diet achieved a recovered state — defined by Clinical Mood Monitoring — at the end of the study, which the researchers explain demonstrates a correlation between the frequency of reaching ketosis and how well their symptoms improved. 

These patients also showed significant reductions in weight (12%), body mass index (12%), waist circumference (13%) and visceral adipose tissue (36%). In addition, this group also showed more significant biomarker benefits, with a 27% increase in insulin resistance and a 25% decrease in triglyceride levels — the main constituents of body fat. 

Moreover, 100% of patients with metabolic syndromes were in remission by the end of the study. 

Addressing metabolic issues may complement psychiatric treatment to enhance patients’ well-being.Patients with schizophrenia showed an average 32% improvement on a brief psychiatric rating scale. In comparison, 69% of participants with bipolar showed an improvement of at least one point as measured by the Clinical Global Impression. 

Psychiatric outcomes in all participants included increased life satisfaction (17%) and enhanced sleep quality (19%). 

Integrated psychiatric care 
The researchers underscore that mental and physical health are interconnected, and addressing metabolic issues may complement psychiatric treatment to enhance the well-being of patients. 

The study’s outcomes highlight the potential for a more comprehensive and integrated approach to psychiatric care and “open opportunities for further research into the relationship between mental health and metabolic health,” reveals the report. 

For example, interventions would benefit from an increased understanding of the mechanism and potential synergies between psychiatric treatment and metabolic improvements.  

At the same time, the authors note that the small sample size and selection bias may have influenced the study’s outcomes. Other limitations that may have impacted the study’s outcomes include not accounting for participants’ socioeconomic status, a short study duration, implementation during COVID-19 and lack of a control arm of the study. 

According to the report, several randomized clinical trials are underway, which will also evaluate cognition, recommending that such trials are needed to assess the impact of keto interventions in people with bipolar or schizophrenia. 

By Jolanda van Hal