Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study

Psychopharmacology (Berl). 2002 May;161(3):248-54. doi: 10.1007/s00213-002-1045-y. Epub 2002 Mar 22.


Rationale: Phosphatidylcholine (PtdCho) in brain cell membranes decreases with age. Evidence from both animal and in vitro studies indicates that CDP-choline (citicoline) administration may increase phosphatidylcholine (PtdCho) synthesis and might reverse PtdCho loss.

Objectives: We investigated whether oral citicoline can increase PtdCho synthesis in the brains of older subjects by measuring levels of phosphorus-containing metabolites using proton-decoupled phosphorus magnetic resonance spectroscopy ((31)P-MRS) before and after citicoline treatment.

Methods: All subjects took 500 mg citicoline once orally each day for 6 weeks, then took either citicoline or placebo once orally per day for a second 6-week period. Subjects underwent a (31)P-MRS scan at baseline and following 6 and 12 weeks of treatment.

Results: Treatment with citicoline for 6 weeks was associated with a 7.3% increase from baseline levels in brain phosphodiesters ( P=0.008), including an 11.6% increase in glycerophosphoethanolamine ( P=0.002) and a 5.1% increase in glycerophosphocholine ( P=0.137). Subjects who continued to take citicoline for the second 6-week period did not show significant additional increases in the levels of these metabolites. No changes were seen in other phosphorus-containing metabolites. There was a correlation between improvement on the California Verbal Learning Test and increase in phosphodiesters.

Conclusions: The increases in phosphodiesters seen in this study indicate that phospholipid synthesis and turnover were stimulated by 6 weeks of oral citicoline. These results in humans support previous in vitro and animal studies and suggest that the administration of oral citicoline may be of use in reversing age-related changes in the brain.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Aged
  • Aging / physiology
  • Analysis of Variance
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Chemistry
  • Cytidine Diphosphate Choline / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Ethanolamines / metabolism
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Middle Aged
  • Nootropic Agents / pharmacology*
  • Phosphatidylcholines / metabolism*
  • Phosphorylcholine / metabolism
  • Time Factors
  • Verbal Learning / drug effects


  • Ethanolamines
  • Nootropic Agents
  • Phosphatidylcholines
  • Phosphorylcholine
  • Cytidine Diphosphate Choline
  • phosphorylethanolamine