Case Report: Metabolic, inflammatory, and neurological improvements after a ketogenic diet in a woman with treatment-resistant schizophrenia and metabolic syndrome

We report the case of a 48-year-old woman with treatment-resistant schizophrenia (TRS) and metabolic syndrome who completed a 5-week medical ketogenic diet (KD) in an inpatient setting. The patient was initially started on a 2.5:1 ratio of fat to combined carbohydrate and protein in grams, but her diet was modified on two occasions due to difficulty reaching consistent ketosis (βHB ≥0.5 mmol/L). Ketosis became more consistent throughout the study but was only fully maintained the last 5 days. Despite this, the patient had many clinically meaningful improvements including a 69% decrease in insulin-resistance (HOMA-IR), 41% decrease in C-peptide, and a 64% decrease in fasting insulin, despite minimal weight loss. Importantly, insulin-resistance moved from pre-diabetic to optimal levels. Fingerstick glucose also decreased. CRP reduced by 61%, suggesting movement from high to average cardiac risk. Extrapyramidal side effects (i.e., pseudoparkinsonism) improved dramatically (80% decrease), reaching almost full resolution. Global psychopathology ratings were not improved; however, the participant had only a few days consistently in ketosis and was facing significant personal stressors nearing the endpoint, which may have eclipsed clinical benefits. Despite this, we saw a hint of improvement in negative symptoms, which we point out as these are particularly problematic in TRS. These results are congruent with emerging data suggesting various health benefits of KD for people with schizophrenia, and we report for the first time its impact in TRS with long-term use of antipsychotic medications (clozapine, olanzapine) that contribute to metabolic syndrome, parkinsonian-like symptoms, and cardiac risk. Our results suggest that despite TRS, dual antipsychotic treatment and limited time in ketosis, a KD can reverse insulin resistance, greatly improve antipsychotic-associated pseudoparkinsonism, and reduce cardiac risk and inflammation. Thus, this diet may be a beneficial treatment alongside antipsychotic medication. We also suggest that well-controlled clinical trials longer than 5 weeks and with consistent ketosis are needed. Additionally, lower calories or a higher ratio of fat to combined protein and carbohydrate may be necessary to maintain ketosis for individuals with metabolic dysfunction who are taking antipsychotic medication.