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Peer-reviewedCC BYFrontiers in Nutrition

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

  • Calogero Longhitano1
  • Calogero Longhitano2
  • Calogero Longhitano3
  • Calogero Longhitano4
  • Jaymee-Leigh Swift2
  • Jaymee-Leigh Swift4
  • Jaymee-Leigh Swift5
  • Sabine Finlay2
  • Sabine Finlay4
  • Beena Suvarna2
  • Beena Suvarna4
  • Shaileigh Gordon1
13 more authors
  • Shaileigh Gordon4
  • Omer Shareef1
  • Omer Shareef4
  • Isabella Peachey2
  • Isabella Peachey3
  • Donna Rudd3
  • Iain Campbell6
  • Shebani Sethi7
  • Christopher Palmer8
  • Zoltan Sarnyai2
  • Zoltan Sarnyai4
  • Zoltan Sarnyai3
  • Zoltan Sarnyai9
9 affiliations
  1. 1Townsville University Hospital and Health Service, Mental Health Service Group, Queensland Health, Townsville, QLD, Australia
  2. 2Laboratory of Psychiatric Neurosciences, Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia
  3. 3College of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia
  4. 4Margaret Roderick Centre for Mental Health Research, James Cook University, Townsville, QLD, Australia
  5. 5Department of Psychology, Townsville University Hospital and Health Service, Queensland Health, Townsville, QLD, Australia
  6. 6Center for Clinical Brain Sciences, Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom
  7. 7Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, United States
  8. 8McLean Hospital, Harvard Medical School, Belmont, MA, United States
  9. 90Department of Cognitive Science and Neuropsychology, University of Szeged, Szeged, Hungary
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Abstract

BackgroundSchizophrenia, 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).MethodsThis 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.ResultsOf 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.ConclusionKMT 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 Registrationhttps://anzctr.org.au, ACTRN12623000854639

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Cite

BibTeXRIS
BibTeX
@article{longhitano2026ketogenic,
  title = {{Ketogenic metabolic therapy in schizophrenia spectrum and bipolar disorders: population descriptors and feasibility outcomes from a randomized, controlled clinical trial}},
  author = {Calogero Longhitano and Calogero Longhitano and Calogero Longhitano and Calogero Longhitano and Jaymee-Leigh Swift and Jaymee-Leigh Swift and Jaymee-Leigh Swift and Sabine Finlay and Sabine Finlay and Beena Suvarna and Beena Suvarna and Shaileigh Gordon and Shaileigh Gordon and Omer Shareef and Omer Shareef and Isabella Peachey and Isabella Peachey and Donna Rudd and Iain Campbell and Shebani Sethi and Christopher Palmer and Zoltan Sarnyai and Zoltan Sarnyai and Zoltan Sarnyai and Zoltan Sarnyai},
  journal = {Frontiers in Nutrition},
  year = {2026},
  month = nov,
  doi = {10.3389/fnut.2026.1962072},
  url = {https://doi.org/10.3389/fnut.2026.1962072},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Ketogenic metabolic therapy in schizophrenia spectrum and bipolar disorders: population descriptors and feasibility outcomes from a randomized, controlled clinical trial
AU  - Calogero Longhitano
AU  - Calogero Longhitano
AU  - Calogero Longhitano
AU  - Calogero Longhitano
AU  - Jaymee-Leigh Swift
AU  - Jaymee-Leigh Swift
AU  - Jaymee-Leigh Swift
AU  - Sabine Finlay
AU  - Sabine Finlay
AU  - Beena Suvarna
AU  - Beena Suvarna
AU  - Shaileigh Gordon
AU  - Shaileigh Gordon
AU  - Omer Shareef
AU  - Omer Shareef
AU  - Isabella Peachey
AU  - Isabella Peachey
AU  - Donna Rudd
AU  - Iain Campbell
AU  - Shebani Sethi
AU  - Christopher Palmer
AU  - Zoltan Sarnyai
AU  - Zoltan Sarnyai
AU  - Zoltan Sarnyai
AU  - Zoltan Sarnyai
PY  - 2026
DA  - 2026/11/04
JO  - Frontiers in Nutrition
DO  - 10.3389/fnut.2026.1962072
UR  - https://doi.org/10.3389/fnut.2026.1962072
AB  - BackgroundSchizophrenia, 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).MethodsThis 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.ResultsOf 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.ConclusionKMT 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 Registrationhttps://anzctr.org.au, ACTRN12623000854639
SN  - 2296-861X
ER  -