Effects of β-hydroxy-β-methyl butyrate on working memory and cognitive flexibility in an animal model of aging

Emily R. Hankosky, Luke K. Sherrill, Lauren A. Ruvola, Rachel M. Haake, Taehyeon Kim, Lindsey R. Hammerslag, Daniel G. Kougias, Janice M. Juraska, Joshua M. Gulley

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Objectives: Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) on working memory and cognitive flexibility. Methods: Beginning ∼12 months of age, male and female Long–Evans rats were given twice daily access to sipper tubes containing calcium HMB (450 mg/kg) or vehicle (285 mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. Results: Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. Discussion: Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process.

Original languageEnglish
Pages (from-to)379-387
Number of pages9
JournalNutritional Neuroscience
Issue number7
StatePublished - Aug 9 2017

Bibliographical note

Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.


  • Aging
  • Cognitive flexibility
  • Prefrontal cortex
  • Working memory
  • β-Hydroxy-β-methyl butyrate

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Neuroscience
  • Nutrition and Dietetics


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