A New Way to Produce Hyperketonemia: Use of Ketone Ester in a Case of Alzheimer's Disease
Overview
Psychiatry
Affiliations
Background: Providing ketone bodies to the brain can bypass metabolic blocks to glucose utilization and improve function in energy-starved neurons. For this, plasma ketones must be elevated well above the ≤ 0.2 mM default concentrations normally prevalent. Limitations of dietary methods currently used to produce therapeutic hyperketonemia have stimulated the search for better approaches.
Method: Described herein is a new way to produce therapeutic hyperketonemia, entailing prolonged oral administration of a potent ketogenic agent--ketone monoester (KME)--to a patient with Alzheimer's disease dementia and a pretreatment Mini-Mental State Examination score of 12.
Results: The patient improved markedly in mood, affect, self-care, and cognitive and daily activity performance. The KME was well tolerated throughout the 20-month treatment period. Cognitive performance tracked plasma β-hydroxybutyrate concentrations, with noticeable improvements in conversation and interaction at the higher levels, compared with predose levels.
Conclusion: KME-induced hyperketonemia is robust, convenient, and safe, and the ester can be taken as an oral supplement without changing the habitual diet.
β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.
Madhavan S, Diaz S, Peralta S, Nomura M, King C, Ceyhan K Cell Chem Biol. 2024; 32(1):174-191.e8.
PMID: 39626664 PMC: 11741930. DOI: 10.1016/j.chembiol.2024.11.001.
Ketogenic Diet: A Review of Composition Diversity, Mechanism of Action and Clinical Application.
Malinowska D, Zendzian-Piotrowska M J Nutr Metab. 2024; 2024:6666171.
PMID: 39463845 PMC: 11511599. DOI: 10.1155/2024/6666171.
Meer N, Fischer T J Nutr Metab. 2024; 2024:9672969.
PMID: 38715705 PMC: 11074881. DOI: 10.1155/2024/9672969.
Imada T, Katakami N, Watanabe H, Nishina S, Sasaki S, Takahara M J Diabetes Investig. 2024; 15(7):843-850.
PMID: 38459768 PMC: 11215694. DOI: 10.1111/jdi.14179.
Sastriques-Dunlop S, Elizondo-Benedetto S, Arif B, Meade R, Zaghloul M, Luehmann H Sci Rep. 2024; 14(1):1438.
PMID: 38228786 PMC: 10791699. DOI: 10.1038/s41598-024-51996-7.