The effect of simultaneous application of plant-rich ketogenic diet and intermittent fasting on early-to-mid-stage Alzheimer's disease: a randomised controlled trial

INTRODUCTION: This study evaluates the effect of simultaneous application of plant-rich ketogenic diet and intermittent fasting as an individualized adjunct to standard treatment on cognitive function in early/mid-stage Alzheimer's patients. METHODS: This assessor-blinded, randomized controlled trial enrolled 60 Alzheimer's disease (AD) patients (CDR 1-2; aged 55-85), randomized to intervention (n = 30; intervention + standard care) or control (n = 30; standard care). Cognition and brain structure were assessed at baseline and 6 months. Individual cognitive changes were analyzed using Reliable Change Index (RCI). RESULTS: Cognitive change scores differed significantly between groups (p < 0.001). The mean Mini Mental State Examination (MMSE) score increased by +0.9 in the intervention group, while a decrease of -1.5 points was observed in the control group. RCI analysis indicated stability in 93% of intervention and 70% of control participants, with cognitive improvement in 7% and 3.3%, respectively. DISCUSSION: The intervention method has the potential to stabilize cognitive decline in AD and promote improvement at the individual level. The response to the intervention is closely related to the individual's metabolic phenotype and structural brain integrity. ETHICAL APPROVAL: Istanbul Medipol University Non-Interventional Clinical Research Ethics Committee on March 6, 2025, under number 242 and the study was carried out in accordance with the Declaration of Helsinki and its later amendments. CLINICALTRIALS: gov ID: NCT06898424.