A three-week Ketogenic Diet increases Global Cerebral Blood Flow and Brain-Derived Neurotrophic Factor

Abstract Purpose The beneficial effects of a ketogenic diet (KD) on neurodegenerative conditions such as mild cognitive impairment (MCI) and Alzheimer’s disease (AD) are increasingly acknowledged, with potential implications for the general population as well. Thus, our study aimed to explore the effect of a KD on cerebral blood flow (CBF) and Brain-Derived Neurotrophic Factor (BDNF) in healthy individuals. We hypothesized that a KD would increase CBF and BDNF, thereby presenting itself as an approach to prevent cognitive decline. Methods In total, 11 cognitively healthy individuals with overweight participated in a randomized, crossover trial consisting of two three-week interventions: 1) a KD and 2) a standard diet. Each diet period concluded with a positron emission tomography (PET) study day, accompanied by a separate magnetic resonance imaging (MRI) scan. Blood samples were collected prior to the PET scan to measure β-hydroxybutyrate (β-OHB) and BDNF levels. CBF was assessed using a [15O]H2O PET scan co-registered with an MRI scan. Results A KD led to increased basal plasma β-OHB levels compared to the SDD (647 (418-724) vs. 50 (50-60) μmol/l, p<0.05), increased CBF by 22% (p=0.02), and elevated BDNF levels by 47% (p=0.04). Moreover, a correlation was observed between β-OHB levels and CBF measurements across the two diets (R2=0.54, p<0.001). Conclusion Implementing a KD improved CBF and raised BDNF levels in cognitively healthy individuals, indicating that a KD should be assessed for as a potential treatment for conditions associated with reduced CBF.