Eftect of oral CDP-choline on plasma choline and uridine levels in humans

Twelve mildly hypertensive but otherwise normal fasting subjects received e ach of four treatments in random order: CDP-choline (citicoline; 500, 2000, and 4000 mg) or a placebo orally at 8:00 a.m. on four different treatment days. Eleven plasma samples from each subject, obtained just prior to treat ment (8:00 a.m.) and 1-12 hr thereafter, were assayed for choline, cytidine , and uridine. Fasting terminated at noon with consumption of a light lunch that contained about 100 mg choline. Plasma choline exhibited dose-related increases in peak values and areas under the curves (AUCs), remaining sign ificantly elevated, after each of the three doses, for 5, 8, and 10 hr, res pectively. Plasma uridine was elevated significantly for 5-6 hr after all t hree doses, increasing by as much as 70-90% after the 500 mg dose, and by 1 00-120% after the 2000 mg dose. No further increase was noted when the dose was raised from 2000 to 4000 mg. Plasma cytidine was not reliably detectab le, since it was less than twice blank, or less than 100 nM, at all of the doses. Uridine is known to enter the brain and to be converted to UTP; more over, we found that uridine was converted directly to CTP in neuron-derived PC-12 cells. Hence, it seems likely that the circulating substrates throug h which oral citicoline increases membrane phosphatide synthesis in the bra ins of humans involve uridine and choline, and not cytidine and choline as in rats. BIOCHEM PHARMACOL 60;7:989-992, 2000. (C) 2000 Elsevier Science In c.