The effect of D-serine administration on cognition and mood in older adults

Oncotarget. 2016 Mar 15;7(11):11881-8. doi: 10.18632/oncotarget.7691.


Background: D-serine is an endogenous co-agonist of the N-Methyl D-Aspartate Receptor (NMDAR) that plays a crucial role in cognition including learning processes and memory. Decreased D-serine levels have been associated with age-related decline in mechanisms of learning and memory in animal studies. Here, we asked whether D-serine administration in older adults improves cognition.

Results: D-serine administration improved performance in the Groton Maze learning test of spatial memory and learning and problem solving (F(3, 38)= 4.74, p = 0.03). Subjects that achieved higher increases in plasma D-serine levels after administration improved more in test performance (r2=-0.19 p = 0.009). D-serine administration was not associated with any significant changes in the other cognitive tests or in the mood of older adults (p > 0.05).

Methods: Fifty healthy older adults received D-serine and placebo in a randomized, double blind, placebo-controlled, crossover design study. We studied the effect of D-serine administration on the performance of cognitive tests and an analogue mood scale. We also collected blood samples to measure D-serine, L-serine, glutamate and glutamine levels.

Conclusions: D-serine administration may be a strategy to improve spatial memory, learning and problem solving in healthy older adults. Future studies should evaluate the impact of long-term D-serine administration on cognition in older adults.

Keywords: D-serine; Gerotarget; aging; cognition; glutamate metabolism; mood.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Cognition Disorders / drug therapy*
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mood Disorders / drug therapy*
  • Prognosis
  • Serine / administration & dosage*
  • Serine / blood


  • Serine