Ketogenic metabolic therapy in schizophrenia spectrum and bipolar disorders: population descriptors and feasibility outcomes from a randomized, controlled clinical trial

Background Schizophrenia, schizoaffective disorder, and bipolar disorder are associated with significant metabolic comorbidity and reduced life expectancy. Ketogenic metabolic therapy (KMT) has emerged as a promising dietary intervention targeting the bioenergetic abnormalities implicated in the pathophysiology of these conditions. No randomized controlled trial data exists to establish the feasibility of implementing KMT in this population. This paper reports on the feasibility outcomes of the North Queensland Dietary Intervention Trial (NQDIT). Methods This was a randomized, parallel group, controlled clinical trial comparing KMT with the Australian Guide to Healthy Eating (AGTHE) in adults with schizophrenia, schizoaffective disorder, or bipolar disorder, recruited from Townsville, Queensland, Australia between January 2024 and October 2025. Participants received individualized dietary advice and practical support to shop for, prepare, and cook meals, delivered through weekly dietitian contact throughout the trial. Feasibility outcomes included recruitment and retention rates, dietitian attendance, dietary adherence, daily ketone levels, and change in body mass index (BMI) as an indicator of dietary compliance. Results Of 96 participants assessed for eligibility, 71 were enrolled and 52 completed the 12-week intervention (AGTHE n = 26; KMT n = 26). The cohort had a mean age of 46.14 ± 12.10 years and was predominantly female (62%). Dietitian attendance was high in both arms (AGTHE 85%; KMT 92%). In the AGTHE arm, 61.5% of participants achieved moderate to high dietary adherence. Participants in the KMT group spent 70.06% of the intervention period in nutritional ketosis, with all 26 completers achieving blood ketone levels ≥0.5 mmol/L. Overall, 96.2% of KMT completers achieved at least semi-adherence, with 73.1% achieving full adherence. Both arms demonstrated BMI reductions (AGTHE: −2.70 ± 4.06%; KMT: −6.50 ± 4.73%), supporting compliance with the allocated diet. Conclusion KMT is a feasible and safe therapeutic dietary intervention for individuals with serious mental illness when delivered with appropriate clinical and dietetic support. Notably, high adherence was achieved in a real-world self-prepared meal model, without reliance on delivered, standardized food provision. Clinical Trial Registration https://anzctr.org.au , ACTRN12623000854639