Abstract
Ketones represent an important alternative fuel for the brain under glucose hypo-metabolic conditions induced by neurological diseases or aging, however their metabolic consequences in healthy brain remain unclear. Here we report that ketones can increase the redox NAD+/NADH ratio in the resting brain of healthy young adults. As NAD is an important energetic and signaling metabolic modulator, these results provide mechanistic clues on how nutritional ketosis might contribute to the preservation of brain health.
Highlights
Brain relies on blood glucose as its predominant energy source
We first determined the blood ketones pharmacokinetics produced by the ingestion of 10 g of medium chain triglycerides (MCT) contained in a complete liquid diet
A “keto-index” ratio of 61 μM.h/g was determined and was similar with other MCT formulations tested in analogous conditions [3, 14, 24]
Summary
While brain glucose utilization decreases in mild cognitively impaired elderly and in Alzheimer’s disease patients, ketone metabolism remains intact [1]. The two main ketones, beta-hydroxybutyrate (BHB) and aceto-acetate (AcA), are actively transported to the brain by the monocarboxylic transporter 1 (MCT1), resulting in brain levels directly proportional to their blood concentrations [3]. They are further metabolized to Acetyl-CoA and enter the Krebs cycle to generate ATP [2]. In Alzheimer’s disease patients, it has been recently shown that an increase in blood ketones can restore part of the brain glucose energy deficit [4]. Under healthy homeostatic conditions, an increase in brain ketones proportionally decreases brain glucose utilization [5]
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