A 3-Week Ketogenic Diet Increases Global Cerebral Blood Flow and Brain-Derived Neurotrophic Factor

Abstract

Context: The beneficial effects of a ketogenic diet (KD) on neurodegenerative conditions such as mild cognitive impairment (MCI) and Alzheimer disease (AD) are increasingly acknowledged, with potential implications for the general population as well.

Objective: 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 2 different 3-week interventions: (i) a KD; and (ii) a standard diet (SDD). 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 < .05), increased CBF by 22% (P = .02), and elevated BDNF levels by 47% (P = .04). Moreover, a correlation was observed between β-OHB levels and CBF measurements across the 2 diets (R2 = 0.54, P < .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.

Keywords: brain-derived neurotrophic factor; cerebral blood flow; ketogenic diet; ketosis; positron emission tomography.