A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer's disease

Alzheimers Dement. 2015 Jan;11(1):99-103. doi: 10.1016/j.jalz.2014.01.006. Epub 2014 Oct 7.


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.

Keywords: Brain insulin resistance; Fasting; Ketogenic diet; Ketone bodies; Ketone monoester; Medium-chain triglyceride; Pyruvate dehydrogenase; β-Hydroxybutyrate.

Publication types

  • Case Reports

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Alzheimer Disease / drug therapy*
  • Dietary Supplements
  • Glucose / deficiency
  • Glucose / metabolism
  • Humans
  • Hydroxybutyrates / administration & dosage
  • Hydroxybutyrates / therapeutic use*
  • Ketone Bodies / administration & dosage
  • Ketone Bodies / therapeutic use
  • Ketosis / chemically induced
  • Male
  • Middle Aged


  • (R)-3-hydroxybutyl (R)-3-hydroxybutyrate
  • Hydroxybutyrates
  • Ketone Bodies
  • Glucose
  • 3-Hydroxybutyric Acid