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Psychopharmacology (Berl). 2002 May;161(3):248-54. Epub 2002 Mar 22.

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

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  • 1Consolidated Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.



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.


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.


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.


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.


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.

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