Ketogenic diet improves health in schizophrenia and bipolar disorder

In a recently published study in the journal Psychiatry Research, a team of researchers assessed the effects of the ketogenic diet (KD) on metabolic and psychiatric health in people with schizophrenia or bipolar disorder who had existing metabolic abnormalities.

Millions of people worldwide suffer from severe mental illnesses such as schizophrenia (24 million) and bipolar disorder (50 million). Current treatments often result in resistance or metabolic side effects, leading to treatment abandonment. Traditional antipsychotics may shorten life expectancy despite their long-term benefits in schizophrenia. The ketogenic diet, effective in the treatment of epilepsy, offers an alternative energy source for the brain by reducing neuronal excitability and inflammation. Emerging evidence suggests that metabolic dysfunction underlies psychiatric diseases. Given the high risk of metabolic syndrome in people with severe mental illness, further research into the potential of KD to improve metabolic and psychiatric markers is urgently needed.

The study involved 23 people aged 18 to 75 years, all taking psychotropic medications and meeting criteria for being overweight or having metabolic abnormalities. Twenty-one people (5 with schizophrenia and 16 with bipolar disorder) completed the study. Participants received educational materials, cookbooks, resources, and a personal trainer.

The KD consisted of 10% carbohydrate, 30% protein, and 60% fat, with the goal of achieving blood ketone levels of 0.5 to 5 mM. Dietary compliance was monitored by ketosis levels. Blood samples were analyzed to assess metabolic markers, and vital signs, body composition, and psychiatric assessments were recorded at baseline, two months, and four months. Remote participants self-reported data and visited local facilities for assessments. The study also assessed potential adverse effects of the KD compared with psychiatric medications and was approved by the Stanford University Institutional Review Board and registered with ClinicalTrials.gov (NCT03935854).

Statistical analysis was performed using standard methods in Microsoft Excel, and data were recorded in Research Electronic Data Capture (REdCap). Paired t-tests were used to compare baseline and endline measurements, and McNemar's test and chi-square analysis were used for nominal data. The study was exploratory in nature and was not powered for significance, but p values < 0.05 were considered significant. Analysis included percentage changes in metabolic and psychiatric variables, providing information on the potential benefits of KD for people with severe mental illness.

The data analysis included twenty-three participants, of whom 5 had schizophrenia and 16 had bipolar disorder. Fourteen participants fully adhered to the CD, 6 partially, and one did not.

At baseline, 29% of participants met criteria for metabolic syndrome. By the end of the study, none of the participants met these criteria (p < 0.05). The main metabolic outcomes included a mean weight loss of 10% (p < 0.001), a decrease in waist circumference of 11% (p < 0.001), a decrease in systolic blood pressure of 6.4% (p < 0.005), a decrease in fat mass index of 17% (p < 0.001), and a decrease in body mass index (BMI) of 10% (p < 0.001). Visceral adipose tissue decreased by 27% (p < 0.001), high-sensitivity C-reactive protein (hsCRP) by 23%, triglycerides by 20% (p < 0.02), and small dense low-density lipoprotein (LDL) by 1.3%. Increases in LDL (21%) and high-density lipoprotein (HDL) (2.7%) were noted. Hemoglobin A1c (HbA1c) decreased by 3.6% (p < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) by 17% (p < 0.05). There was no significant change in 10-year risk of atherosclerotic cardiovascular disease (ASCVD) for the entire cohort, but dieters experienced an 11% improvement (p < 0.01).

Psychiatric outcomes showed a 31% improvement in the Clinical Global Impressions severity scale (p < 0.001). The recovery rate increased from 33% at baseline to 75% by the end of the study, with 100% recovery in the full adherent group. Overall, 43% of participants achieved recovery (50% among full adherents, 33% among partial adherents), and 79% showed a significant improvement in symptom severity (92% among full adherents, 50% among partial adherents). Among participants with bipolar disorder, 69% showed an improvement in severity of more than 1 point, and the recovery rate increased from 38% to 81%. All full adherent participants with bipolar disorder had recovered or were in recovery by the end of the study. Psychiatric improvements included a 17% increase in life satisfaction (p < 0.002), a 17% improvement in global assessment of functioning (p < 0.001), and a 19% improvement in sleep quality (p < 0.02). Participants with schizophrenia experienced a 32% decrease in Brief Psychiatric Symptom Scale scores (p < 0.02).

Common side effects of KD such as headache, fatigue and constipation were reported early on but decreased to minimal levels after the third week. Qualitative feedback from participants highlighted significant improvements in anxiety, mood stabilization and overall quality of life, with some expressing profound personal transformations.

A study of people with schizophrenia and bipolar disorder receiving KD along with psychiatric treatment showed significant improvements in psychiatric and metabolic outcomes. Psychiatric outcomes showed a 31% improvement in mental illness severity, with 79% of symptomatic participants showing significant improvement, particularly among those on the diet. Metabolic outcomes included reductions in weight, waist circumference, systolic blood pressure, fat mass index, BMI, visceral adipose tissue, HbA1c, and triglycerides. Overall side effects of KD were reduced after three weeks. These results suggest that KD is a viable and effective adjunctive treatment for improving psychiatric and metabolic health in this population.