Citicoline (cytidine diphosphocholine, CDP-choline) is a novel nutrient with a broad spectrum of benefits for conditions associated with symptoms of neurological dysfunction.

Abstract
Introduction
Citicoline Versus Choline
Bioavailability/Pharmacokinetics
Mechanism of Action
Clinical Applications
Alzheimer’s Disease and Dementia
Parkinson’s Disease
Stroke and Cerebral Ischemia
The results of this trial found no benefits for stroke recovery associated with citicoline intake at 500 mg/day, unlike earlier studies. A significant confounding factor may have impacted the analysis.
Traumatic Head Injuries
Eye Health and Visual Function
Glaucoma
Ischemic Optic Neuropathy
Substance Abuse
Infectious Disease
Appetite Control and Satiety
Mental Health
Safety and Dosing
Conclusions
References
1. Secades JJ, Lorenzo JL. Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Clin Pharmacol. 2006;28 Suppl B:1-56.
2. Jambou R, El-Assaad F, Combes V, Grau GE. Citicoline (CDP-choline): What role in the treatment of complications of infectious diseases. Int J Biochem Cell Biol. 2009;41(7):1467-1470.
3. Higdon J, Drake VJ. Linus Pauling Institute at Oregon State University. Choline. Available at: http://lpi.oregonstate.edu/infocenter/othernuts/choline. Accessed April 6, 2010.
4. Weiss GB. Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life Sci. 1995;56(9):637-660.
5. D’Orlando KJ, Sandage BW. Citicoline (CDP-choline): mechanisms of action and effects in ischemic brain injury. Neurol Res 1995;17(4):281-284.
6. Dinsdale JR, Griffiths GK, Rowlands C, et al. Pharmacokinetics of 14C CDPcholine. Arzneimittelforschung. 1983;33(7A):1066-1070.
7. Agut J, Font E, Sacristán A, Ortiz JA. Bioavailability of methyl-14C CDP-choline by oral route. Arzneimittelforschung. 1983;33(7A):1045-1047.
8. Agut J, Font E, Sacristán A, Ortiz JA. Radioactivity incorporation into different cerebral phospholipids after oral administration of 14C methyl CDP-choline.
Arzneimittelforschung. 1983;33(7A):1048-1050.
9. Babb SM, Appelmans KE, Renshaw PF, Wurtman RJ, Cohen BM. Differential effect of CDP-choline on brain cytosolic choline levels in younger and older
subjects as measured by proton magnetic resonance spectroscopy. Psychopharmacology (Berl). 1996;127(2):88-94.
10. Wurtman RJ, Regan M, Ulus I, Yu L. Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochem Pharmacol. 2000;60(7):989-992.
11. Babb SM, Wald LL, Cohen BM, et al. Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic
resonance spectroscopy study. Psychopharmacology (Berl). 2002;161(3):248-254.
12. Silveri MM, Dikan J, Ross AJ, et al. Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy. NMR Biomed. 2008;21(10):1066-1075.
13. Secades JJ, Frontera G. CDP-choline: pharmacological and clinical review. Methods Find Exp Clin Pharmacol. 1995;17 Suppl B:1-54.
14. Drago F, Mauceri F, Nardo L, et al. Effects of cytidine-diphosphocholine on acetylcholine-mediated behaviors in the rat. Brain Res Bull. 1993;31(5):485-489.
15. Adibhatla RM, Hatcher JF, Dempsey RJ. Citicoline: neuroprotective mechanisms in cerebral ischemia. J Neurochem. 2002;80(1):12-23.
16. Adibhatla RM, Hatcher JF. Citicoline decreases phospholipase A2 stimulation and hydroxyl radical generation in transient cerebral ischemia. J Neurosci Res. 2003;73(3):308-315.
17. Rema V, Bali KK, Ramachandra R, et al. Cytidine-5-diphosphocholine supplement in early life induces stable increase in dendritic complexity of neurons
in the somatosensory cortex of adult rats. Neuroscience. 2008;155(2):556-564.
18. Petkov VD, Mosharrof AH, Kehayov R, et al. Effect of CDP-choline on learning and memory processes in rodents. Methods Find Exp Clin Pharmacol.
1992;14(8):593-605.
19. Petkov VD, Kehayov RA, Mosharrof AH, et al. Effects of cytidine diphosphate choline on rats with memory deficits. Arzneimittelforschung. 1993;43(8):822-828.
20. Teather LA, Wurtman RJ. Dietary cytidine (5’)-diphosphocholine supplementation protects against development of memory deficits in aging rats. Prog. Neuropsychopharmacol Biol Psychiatry. 2003;27(4):711-717.
21. Teather LA, Wurtman RJ. Dietary CDP-choline supplementation prevents memory impairment caused by impoverished environmental conditions in rats.
Learn Mem. 2005;12(1):39-43.
22. de la Morena E. Efficacy of CDP-choline in the treatment of senile alterations in memory. Ann NY Acad Sci. 1991;640:233-236.
23. Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Citicoline improves verbal memory in aging. Arch Neurol. 1996;53(5):441-448.
24. Alvarez XA, Laredo M, Corzo D, et al. Citicoline improves memory performance in elderly subjects. Methods Find Exp Clin Pharmacol. 1997;19(3):201-210.
25. Franco-Maside A, Caamaño J, Gómez MJ, Cacabelos R. Brain mapping activity and mental performance after chronic treatment with CDP-choline in Alzheimer’s disease. Methods Find Exp Clin Pharmacol. 1994;16(8):597-607.
26. Caamaño J, Gómez MJ, Franco A, Cacabelos R. Effects of CDP-choline on cognition and cerebral hemodynamics in patients with Alzheimer’s disease. Methods Find Exp Clin Pharmacol. 1994;16(3):211-218.
27. Fernández-Novoa L, Alvarez XA, Franco-Maside A, Caamaño J, Cacabelos R. CDP-choline-induced blood histamine changes in Alzheimer’s disease. Methods Find Exp Clin Pharmacol. 1994;16(4):279-284.
28. Cacabelos R, Alvarez XA, Franco-Maside A, Fernández-Novoa L, Caamaño J. Effect of CDP-choline on cognition and immune function in Alzheimer’s
disease and multi-infarct dementia. Ann NY Acad Sci. 1993;695:321-323.
29. Cacabelos R, Caamaño J, Gómez MJ, et al. Therapeutic effects of CDP-choline in Alzheimer’s disease. Cognition, brain mapping, cerebrovascular hemodynamics, and immune factors. Ann NY Acad Sci. 1996;777:399-403.
30. Alvarez XA, Mouzo R, Pichel V, et al. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer’s disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods Find Exp Clin Pharmacol. 1999;21(9):633-644.
31. Ramaker C, Marinus J, Stiggelbout AM, Van Hilten BJ. Systematic evaluation of rating scales for impairment and disability in Parkinson’s disease. Mov Disord. 2002;17(5):867-876.
32. Martí Massó JF, Urtasun M. Citicoline in the treatment of Parkinson’s disease. Clin Ther. 1991;13(2):239-242.
33. Eberhardt R, Birbamer G, Gerstenbrand F, Rainer E, Traegner H. Citicoline in the treatment of Parkinson’s disease. Clin Ther. 1990;12(6):489-495.
34. Cubells JM, Hernando C. Clinical trial on the use of cytidine diphosphate choline in Parkinson’s disease. Clin Ther. 1988;10(6):664-671.
35. Agnoli A, Ruggieri S, Denaro A, Bruno G. New strategies in the management of Parkinson’s disease: a biological approach using a phospholipid precursor (CDPcholine). Neuropsychobiology. 1982;8(6):289-296.
36. Tazaki Y, Sakai F, Otomo E, et al. Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke. 1988;19(2):211-216.
37. Clark WM, Warach SJ, Pettigrew LC, Gammans RE, Sabounjian LA. A randomized dose-response trial of citicoline in acute ischemic stroke patients. Citicoline Stroke Study Group. Neurology. 1997;49(3):671-678.
38. Clark WM, Williams BJ, Selzer KA, et al. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke. 1999;30(12):2592-2597.
39. Clark WM, Wechsler LR, Sabounjian LA, Schwiderski UE. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients.
Neurology. 2001;57(9):1595-1602.
40. Hazama T, Hasegawa T, Ueda S, Sakuma A. Evaluation of the effect of CDPcholine on poststroke hemiplegia employing a double-blind controlled trial.
Assessed by a new rating scale for recovery in hemiplegia. Int J Neurosci. 1980;11(3):211-225.
41. Piccoli F, Battistini N, Carbonin P, et al. CDP-choline in the treatment of chronic cerebrovasculopathies. Arch Gerontol Geriatr. 1994;18(3):161-168.
42. Warach S, Pettigrew LC, Dashe JF, et al. Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators. Ann Neurol. 2000;48(5):713-722.
43. Iranmanesh F, Vakilian A. Efficiency of citicoline in increasing muscular strength of patients with nontraumatic cerebral hemorrhage: a double-blind randomized clinical trial. J Stroke Cerebrovasc Dis. 2008;17(3):153-155.
44. Overgaard K, Meden P. Citicoline--the first effective neuroprotectant to be combined with thrombolysis in acute ischemic stroke? J Neurol Sci. 2006;247(2):119-120.
45. Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database Syst Rev. 2005;(2):CD000269.
46. Calatayud Maldonado V, Calatayud Pérez JB, Aso Escario J. Effects of CDPcholine on the recovery of patients with head injury. J Neurol Sci. 1991;103
Suppl:S15-18.
47. Levin HS. Treatment of postconcussional symptoms with CDP-choline. J Neurol Sci. 1991;103 Suppl:S39-42.
48. Lozano R. CDP-choline in the treatment of cranio-encephalic traumata. J Neurol Sci. 1991;103 Suppl:S43-47.
49. Campos EC, Schiavi C, Benedetti P, Bolzani R, Porciatti V. Effect of citicoline on visual acuity in amblyopia: preliminary results. Graefes Arch Clin Exp
Ophthalmol. 1995;233(5):307-312.
50. Campos EC, Bolzani R, Schiavi C, Baldi A, Porciatti V. Cytidin-5’-diphosphocholine enhances the effect of part-time occlusion in amblyopia. Doc Ophthalmol. 1996;93(3):247-263.
51. Campos EC, Fresina M. Medical treatment of amblyopia: present state and perspectives. Strabismus. 2006;14(2):71-73. 52. Fresina M, Dickmann A, Salerni A, De Gregorio F, Campos EC. Effect of oral CDP-choline on visual function in young amblyopic patients. Graefes Arch Clin Exp Ophthalmol. 2008;246(1):143-150.
53. Parisi V, Manni G, Colacino G, Bucci MG. Cytidine-5’-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma. Ophthalmology. 1999;106(6):1126-1134.
54. Parisi V. Electrophysiological assessment of glaucomatous visual dysfunction during treatment with cytidine-5’-diphosphocholine (citicoline): a study of 8
years of follow-up. Doc Ophthalmol. 2005;110(1):91-102.
55. Grieb P, Rejdak R. Pharmacodynamics of citicoline relevant to the treatment of glaucoma. J Neurosci Res. 2002;67(2):143-148.
56. Parisi V, Coppola G, Ziccardi L, Gallinaro G, Falsini B. Cytidine-5’-diphosphocholine (Citicoline): a pilot study in patients with non-arteritic ischaemic optic
neuropathy. Eur J Neurol. 2008;15(5):465-474.
57. O’Leary G, Weiss RD. Pharmacotherapies for cocaine dependence. Curr Psychiatry Rep. 2000;2(6):508-513.
58. Renshaw PF, Daniels S, Lundahl LH, Rogers V, Lukas SE. Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in
cocaine-dependent subjects: a preliminary report. Psychopharmacology (Berl). 1999;142(2):132-138.
59. Lukas SE, Kouri EM, Rhee C, Madrid A, Renshaw PF. Effects of short-term citicoline treatment on acute cocaine intoxication and cardiovascular effects. Psychopharmacology (Berl). 2001;157(2):163-167.
60. Brown ES, Gorman AR, Hynan LS. A randomized, placebo-controlled trial of citicoline add-on therapy in outpatients with bipolar disorder and cocaine dependence. J Clin Psychopharmacol. 2007;27(5):498-502.
61. Killgore WDS, Ross AJ, Kamiya T, et al. Citicoline affects appetite and corticolimbic responses to images of high-calorie foods. Int J Eat Disord. 2010;43(1):6-13.
62. Salvadorini F, Galeone F, Nicotera M, Ombrato M, Saba P. Clinical evaluation of CDP-choline (Nicholin): efficacy As antidepressant treatment. Curr Ther Res Clin Exp. 1975;18(3):513-520.
63. Deutsch SI, Schwartz BL, Schooler NR, et al. First administration of cytidine diphosphocholine and galantamine in schizophrenia: a sustained alpha7 nicotinic agonist strategy. Clin Neuropharmacol. 2008;31(1):34-39.
64. Schauss AG, Somfai-Relle S, Financsek I, et al. Single- and repeated-dose oral toxicity studies of citicoline free-base (choline cytidine 5’-pyrophosphate) in Sprague-Dawley rats. Int J Toxicol. 2009;28(6):479-487.
65. Cho H, Kim YJ. Efficacy and safety of oral citicoline in acute ischemic stroke: drug surveillance study in 4,191 cases. Methods Find Exp Clin Pharmacol.
2009;31(3):171-176.