Single- and repeated-dose oral toxicity studies of citicoline free-base (choline cytidine 5'-pyrophosphate) in Sprague-Dawley rats.
The dietary supplement Citicoline free-base (choline cytidine 5'-pyrophosphate) was toxicologically evaluated in Sprague-Dawley rats using oral gavage. In an acute 14-day study, 2000 mg/kg was well tolerated. In a 90-day study, 100, 350, and 1000 mg/kg/day doses resulted in no mortality. In males, slight significant increases in serum creatinine (350 and 1000 mg/kg/day), and decreases in urine volume (all treated groups) were observed. In females, slight significant increases in total white blood cell and absolute lymphocyte counts (1000 mg/kg/day), and blood urea nitrogen (BUN) (100 and 350, but not 1000 mg/kg/day) were noted. A dose-related increase in renal tubular mineralization, without degenerative or inflammatory reaction, was found in females (all treated groups) and two males (1000 mg/kg/day). Renal mineralization in rats (especially females) is influenced by calcium:phosphorus ratios in the diet. A high level of citicoline consumption resulted in increased phosphorus intake in the rats, and likely explains this result.
Schauss
A G
AG
Natural and Medicinal Products Research, AIBMR Life Sciences, Inc, 4117 S. Meridian, Puyallup, WA 98373 USA. alex@aibmr.com
Somfai-Relle
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S
Financsek
I
I
Glavits
R
R
Parent
S C
SC
Endres
J R
JR
Varga
T
T
Szücs
Z
Z
Clewell
A
A
D000284:Administration, Oral; D000818:Animals; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D002114:Calcinosis / Q000139:chemically induced / Q000473:pathology; D003404:Creatinine / Q000097:blood; D003566:Cytidine Diphosphate Choline / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D007928:Lethal Dose 50; D008297:Male; D018697:Nootropic Agents / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014563:Urodynamics / Q000187:drug effects
D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline; D003404:Creatinine