Efficacy of an Anti-Inflammatory Dietary Pattern on Global Functioning, Gut Microbiome, and Health in Patients with Psychiatric Disorders and Neurodegenerative Diseases: Protocol for a Randomized Controlled Crossover Trial
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Background
Psychiatric disorders and neurodegenerative diseases, including bipolar disorder (BD), schizophrenia spectrum disorders (SSD), Parkinson’s disease (PD), and Alzheimer’s disease (AD), are associated with substantial impairments in functioning and quality of life. Increasing evidence suggests that low-grade systemic inflammation and gut microbiome dysregulation are shared mechanisms across these brain disorders, providing a rationale for transdiagnostic interventions targeting the gut–brain axis.
Objective
This study was designed to evaluate the efficacy of an anti-inflammatory dietary pattern (AIDP), termed the BrAIN diet, on global functioning and a comprehensive set of secondary clinical, cognitive, inflammatory, and gut-health outcomes across relevant patient populations.
Methods
We designed an open-label, randomized controlled, two-period crossover trial with 12-week intervention periods, a 24-week washout period and 12-week follow-up. We aimed to enrol 100 adult outpatients (25 per diagnosis: BD, SSD, PD, and AD) aged 18–80 years, recruited through outpatient clinics and patient organisations in the northern Netherlands. Participants were randomized 1:3 to either start the BrAIN diet immediately (Group 1, BrAIN/diet-as-usual [DaU] sequence) or after 36-weeks (Group 2, DaU/BrAIN sequence). The BrAIN diet is based on Shivappa’s Dietary Inflammatory Index, components of the MIND diet, and Dutch dietary guidelines, and is delivered through weekly home-delivered food boxes, recipes, and weekly dietitian counselling. The primary outcome is global functioning measured with the Outcome Questionnaire-45 (OQ-45). The treatment effect is estimated from the timepoint × treatment interaction in a linear mixed-effects model that uses all observed timepoints, with participant as a random intercept and period and sequence as fixed effects. Secondary outcomes include Global Assessment of Functioning (GAF), cognition (Brief Assessment of Cognition, Stroop, Trail Making), quality of life (EQ-5D), fatigue (FSS), gastrointestinal symptoms (GSRS), gut-permeability biomarkers, faecal microbiome composition, inflammatory and metabolic markers, and disease-specific symptom scales. Assessments occur at weeks 0 (V1, baseline period 1), 12 (V2, end of period 1), 24 (V3, mid-washout), 36 (V4, baseline period 2), 48 (V5, end of period 2), and 60 (V6, follow-up). The trial protocol was developed in 2021 and approved by the accredited Medical Research Ethics Committee on 11 January 2022. The trial is reported in accordance with the SPIRIT 2013 guideline in effect at the time of protocol development.
Results
The trial received favourable ethical opinion from Medical Research Ethics Committee BeBo Assen (NL78755.056.21) on 11 January 2022 and was registered prospectively at OMON (NL-OMON52339). Recruitment commenced in February 2022; the first participant was enrolled on 7 March 2022 and the last on 6 May 2024. Follow-up was completed on 5 September 2025. A total of 107 participants were enrolled. Data analysis is ongoing; primary results are expected to be submitted for publication in summer 2026.
Conclusions
This study provides evidence on whether an anti-inflammatory dietary intervention targeting shared inflammatory and gut–microbiome pathways can improve global functioning and a broad set of clinical and mechanistic outcomes in psychiatric and neurodegenerative populations. The crossover design ensures all participants ultimately receive the intervention while serving as their own controls, maximising statistical power within a heterogeneous patient population. If effective, the BrAIN diet could provide a safe, accessible adjunct to standard care in neuropsychiatric and neurodegenerative populations.
Trial Registration
OMON NL-OMON52339; https://onderzoekmetmensen.nl/en/trial/52339
