Diet-induced ketosis improves cognitive performance in aged rats

Adv Exp Med Biol. 2010:662:71-5. doi: 10.1007/978-1-4419-1241-1_9.


Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1alpha levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions.

MeSH terms

  • Aging / pathology*
  • Animals
  • Behavior, Animal
  • Blotting, Western
  • Capillaries / cytology
  • Capillaries / metabolism
  • Cell Count
  • Cerebral Cortex / metabolism
  • Cognition*
  • Diet, Ketogenic*
  • Glucose Transporter Type 1 / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Ketosis / pathology*
  • Male
  • Rats
  • Rats, Inbred F344


  • Glucose Transporter Type 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Slc2a1 protein, rat