Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study.
Level 4 - case-series / case-control
Single-arm before-and-after interventional study without a separate control group
PubMed 27629100 · doi:10.1177/0271678X16669366
What was done
Ten healthy adults (mean age 35 ± 15 years) followed a 4-day very high-fat ketogenic diet (4.5:1 lipid to protein plus carbohydrate ratio). Cerebral metabolic rates of acetoacetate (CMRa) and glucose (CMRglc) were measured before and after the diet using dual-tracer positron emission tomography (PET) with 11C-acetoacetate and 18F-fluorodeoxyglucose.
What was found
During the ketogenic diet, plasma ketones increased 8-fold (p = 0.005) while plasma glucose decreased by 24% (p = 0.005). CMRa increased 6-fold (p = 0.005), and CMRglc decreased by 20% (p = 0.014). Plasma ketones correlated with CMRa (r = 0.93; p < 0.0001). CMRa accounted for 17% of whole-brain energy requirements (12-24% across brain regions), and total cerebral ketone metabolism was estimated to represent approximately 33% of brain energy requirements.
Why it matters
This study quantifies the human brain's rapid shift to ketone utilization during acute dietary ketosis, demonstrating that ketones can supply approximately one-third of adult cerebral energy demands.
Limits
The sample size was very small (n = 10), there was no control group, and the intervention lasted only four days. The findings from healthy adults cannot be directly generalized to older adults or individuals with chronic cerebral glucose hypometabolism, and β-hydroxybutyrate utilization was estimated rather than directly measured.
Cited by
- supports Experiments by Stephen Cunnane and others show that when brain cells are given both glucose and ketones, they choose to burn a mixture of the two.