Overview
CDP-choline (Citicoline) — reversing nerve damage at the molecular level
CDP-choline (Citicoline) is a form of the B-vitamin choline. It is used by the body to make cell membranes and also to make the neurotransmitter acetylcholine.
CDP-choline began to be used in the 1960s as a treatment for brain injuries, and interest in it has grown with the realization that it offers a degree of protection against various kinds of damage to the nervous system (including the retina and optic nerve).
CDP-choline has been the focus of countless experiments using cell culture and lab animals, and many thousands of human volunteers and patients have participated in clinical studies of this compound. There is now considerable evidence that CDP-choline has neuro-protective and neuro-regenerative effects that can ameliorate the following conditions:
- glaucoma-related damage to the eye
- amblyopia (poor vision in one eye; “lazy eye”)
- Alzheimer’s Disease
- Parkinson’s Disease
- age-related learning and memory disorders
- traumatic brain injury
- stroke
- drug addiction.
The brain-bioavailability of CDP-choline is low, because the majority of the consumed dose is used outside of the brain. Fortunately the substance is not terribly expensive and so the low brain-bioavailability can be compensated for by using fairly large doses — 1000 mg/day, for example. The lack of toxicity of the supplement makes this possible without causing significant side effects.
Read CDP-Choline (Citicoline) Monograph
CDP-choline is a form of the B-vitamin choline. It is an intermediate in the synthesis of components of cell membranes and of the neurotransmitter acetylcholine. It also is a precursor of betaine, which is involved in gene regulation.
The biochemistry of CDP-choline has been studied since the 1950s and its clinical use began in the 1960s as a treatment for brain injuries.1 Progress has been very slow, perhaps because the potential applications of the substance were patented and were then subjected to financial and legal game-playing by the patent owner and licensees. Development was further plagued by clinical studies that sometimes reached conflicting results. Even now there is not yet a consensus on optimum dosages for various conditions. Nevertheless, interest in this supplement remains high; and there is general agreement that it offers a degree of protection against various kinds of damage to the nervous system (including the retina and optic nerve).
The neuroprotective effects of CDP-choline may derive from its ability to increase the synthesis of phosphatidylcholines in injured nervous tissue.2 Phosphatidylcholines are major components of cell membranes.
What we can’t tell you
In the U.S. and some other industrialized countries, government agencies like the U.S. Food and Drug Administration have adopted censorship as a method for intensifying their control over the supplement industry and its customers. Thus, FDA regulations prohibit us from telling you that any of our products are effective as medical treatments, even if they are, in fact, effective.
Accordingly, we will limit our discussion of CDP-choline to a brief summary of relevant research, and let you draw your own conclusions about what medical conditions it may be effective in treating.
CDP-choline has been the focus of countless experiments using cell culture and lab animals, and many thousands of human volunteers and patients have participated in clinical studies of this compound.3 There is now considerable evidence that CDP-choline has neuroprotective and neuro-regenerative effects that can ameliorate the following conditions:3,4
- glaucoma-related damage to the eye15,7
- amblyopia (poor vision in one eye; “lazy eye”)14,7
- Alzheimer’s Disease6,7
- Parkinson’s Disease7,8,9
- age-related learning and memory disorders10
- traumatic brain injury2
- stroke5
- drug addiction11,12,13
CDP-choline as a treatment for visual problems
Two kinds of vision problems have been shown to be improved by CDP-choline supplementation. Both are problems stemming from damaged nerves.
Glaucoma results from damage to nerve cells which transmit information from the retina into the brain. Treatment of glaucoma patients with oral CDP-choline (1600 mg/day for 60 days) resulted in “Improvement of retinal function (objectively evaluated by pattern electroretinogram recordings) and of neural conduction along visual pathways…”15
Amblyopia (a.k.a. “lazy eye”) is a visual disorder in which one eye has poor vision despite having no significant defect in the eye itself. It is thought to be caused by damage to the brain's visual centers or to the optic nerve. CDP-choline has been tested in children with amblyopia and found to improve visual acuity, contrast sensitivity, and strength of visual responses.16 When combined with patching, it leads to more stable benefits than those achieved with patching alone.14
CDP-choline for Alzheimer’s and Parkinson’s
When CDP-choline was administered to early-to-mid-stage Parkinson’s patients it led to significant improvement in symptoms. Advanced Parkinson’s patients appeared not to benefit from the treatment.8,9
A number of clinical trials have demonstrated an ability of CDP-choline to reverse the cognitive symptoms of Alzheimer’s Disease. For example, in 1999 Spanish researchers reported that 1000 mg/day of CDP-choline “…Improves cognitive performance, cerebral blood perfusion and the brain bioelectrical activity pattern in AD patients.” The treatment was more effective in some types of Alzheimer’s Disease than in others.6
CDP-choline’s action against Alzheimer’s symptoms may be due in part to its ability to keep nerve cells alive under conditions that normally would cause them to self-destruct. Some of the damage done to the brain by Alzheimer’s Disease is thought to be due to the triggering of cell suicide (“apoptosis”) by the plaques of amyloid protein that are a hallmark of the disease. A study in 1999 implanted amyloid protein in various parts of rats’ brains. Those rats that were also treated with CDP-choline suffered less neurodegeneration and performed better in cognitive tests than rats that received no CDP-choline.17
Other age-related cognitive problems
Phosphatidylcholine — a major component of brain cell membranes — is produced by the body in decreasing amounts as one ages. It is thought that this decline lowers the efficiency of signaling between nerve cells, and therefore impairs the processing of information in the brain.18
Supplementation in “older subjects” with CDP-choline (500 mg/day for 6 weeks) has been shown to promote synapse formation and efficiency, and to improve performance on the California Verbal Learning Test.19,18,10
Traumatic brain injury
The toll taken by traumatic brain injury is enormous — every year, approximately 1.4 million Americans sustain such an injury, of which 50,000 die, another 235,000 are hospitalized, and 80,000–90,000 people suffer permanent disability.2
At long last, a major clinical trial has been organized to find out whether CDP-choline’s benefits in stroke and dementia can be translated into a treatment for traumatic brain injury. The trial, called COBRIT, started in 2007 but is still recruiting participants (as of April 2010); it is scheduled to be completed in December 2010.20 We eagerly await the results, which we anticipate will catapult CDP-choline into a first-line treatment for such injuries.
Stroke
CDP-choline as a treatment for stroke has received a considerable amount of research attention. The evidence suggests that if stroke patients are treated with 2000 mg of CDP-choline within the first 24 hours after having the stroke, their probability of complete recovery at 3 months will be increased by about 8%.5
Schizophrenia
In a recent collaboration between LifeLink and researchers at Georgetown University and the U.S. Department of Veterans Affairs, a new application for CDP-choline has been shown: treatment of schizophrenia. Researchers previously had suspected that at least some aspects of schizophrenia may be caused by a defect in a molecular channel in nerve cell membranes — specifically, a defect in the alpha7 nicotinic acetylcholine receptor located in this channel. That suspicion has now been confirmed by a 12-week-long clinical trial in which patients were given a combination of CDP-choline (supplied by LifeLink) and the drug galantamine; the trial showed that 5 out of 6 subjects receiving this treatment experienced a “reduction in Clinical Global Impressions severity scores and Positive and Negative Syndrome Scale total scores.”22
Side effects
CDP-choline typically is without side effects. Rarely a few users experience digestive intolerance, gastrointestinal discomfort or restlessness.3
Bioavailability
When taken orally CDP-choline is converted in the intestine into cytidine and choline, both of which are efficiently absorbed into the bloodstream.21 These components are then transported throughout the body where they are utilized in various biosynthetic pathways.4 A small fraction of the cytidine and choline pass through the blood-brain barrier and are converted in the brain back into CDP-choline.4
The brain-bioavailability of CDP-choline is therefore low, since the majority of the consumed dose is used (or wasted) outside of the brain. Fortunately the substance is not prohibitively expensive and the low brain-bioavailability can be compensated for by using fairly large doses — 1000 mg/day, for example. The lack of toxicity of the supplement makes this possible without causing significant side effects.
Conclusion
Are CDP-choline supplements useful for the conditions and
purposes mentioned above? We aren’t allowed to tell you, so you
should take a look at some of the references cited here, and
then decide for yourself.
References
[1] [EXPERIMENTAL AND CLINICAL STUDIES ON CDP-CHOLINE THERAPY FOR BRAIN INJURIES.] Kumamoto Igakkai Zasshi. 1964 Mar 25; 38:145-76 Tanakamaru S
[2] The citicoline brain injury treatment (COBRIT) trial: design and methods. J Neurotrauma. 2009 Dec; 26(12):2207-16 Zafonte R, Friedewald WT, Lee SM, Levin B, Diaz-Arrastia R, Ansel B, Eisenberg H, Timmons SD, Temkin N, Novack T, Ricker J, Merchant R, Jallo J
[3] Cytidine 5'-diphosphocholine (CDP-choline) in stroke and other CNS disorders. Neurochem Res. 2005 Jan; 30(1):15-23 Adibhatla RM, Hatcher JF
[4] Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. Altern Med Rev. 2004 Mar; 9(1):17-31 Conant R, Schauss AG
[5] Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke. 2002 Dec; 33(12):2850-7 Dávalos A, Castillo J, Alvarez-Sabín J, Secades JJ, Mercadal J, López S, Cobo E, Warach S, Sherman D, Clark WM, Lozano R
[6] 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 Nov; 21(9):633-44 Alvarez XA, Mouzo R, Pichel V, Pérez P, Laredo M, Fernández-Novoa L, Corzo L, Zas R, Alcaraz M, Secades JJ, Lozano R, Cacabelos R
[7] CDP-choline: pharmacological and clinical review. Methods Find Exp Clin Pharmacol. 1995 Oct; 17 Suppl B:1-54 Secades JJ, Frontera G
[8] Citicoline in the treatment of Parkinson’s disease. Clin Ther. 1991 Mar-Apr; 13(2):239-42 MartíMassó JF, Urtasun M
[9] Clinical trial on the use of cytidine diphosphate choline in Parkinson’s disease. Clin Ther. 1988; 10(6):664-71 Cubells JM, Hernando C
[10] 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 Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, Yurgelun-Todd DA, Renshaw PF
[11] Effects of short-term citicoline treatment on acute cocaine intoxication and cardiovascular effects. Psychopharmacology (Berl). 2001 Sep; 157(2):163-7 Lukas SE, Kouri EM, Rhee C, Madrid A, Renshaw PF
[12] Decreased activity of brain phospholipid metabolic enzymes in human users of cocaine and methamphetamine. Drug Alcohol Depend. 2002 Jun 1; 67(1):73-9 Ross BM, Moszczynska A, Peretti FJ, Adams V, Schmunk GA, Kalasinsky KS, Ang L, Mamalias N, Turenne SD, Kish SJ
[13] Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: a preliminary report. Psychopharmacology (Berl). 1999 Feb; 142(2):132-8 Renshaw PF, Daniels S, Lundahl LH, Rogers V, Lukas SE
[14] Effect of oral CDP-choline on visual function in young amblyopic patients. Graefes Arch Clin Exp Ophthalmol. 2008 Jan; 246(1):143-50 Fresina M, Dickmann A, Salerni A, DeGregorio F, Campos EC
[15] Evidence of the neuroprotective role of citicoline in glaucoma patients. Prog Brain Res. 2008; 173:541-54 Parisi V, Coppola G, Centofanti M, Oddone F, Angrisani AM, Ziccardi L, Ricci B, Quaranta L, Manni G
[16] Cytidine-5'-diphosphocholine improves visual acuity, contrast sensitivity and visually-evoked potentials of amblyopic subjects. Curr Eye Res. 1998 Feb; 17(2):141-8 Porciatti V, Schiavi C, Benedetti P, Baldi A, Campos EC
[17] Citicoline protects hippocampal neurons against apoptosis induced by brain beta-amyloid deposits plus cerebral hypoperfusion in rats. Methods Find Exp Clin Pharmacol. 1999 Oct; 21(8):535-40 Alvarez XA, Sampedro C, Lozano R, Cacabelos R
[18] Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses. Alzheimers Dement. 2008 Jan; 4(1 Suppl 1):S153-68 Cansev M, Wurtman RJ, Sakamoto T, Ulus IH
[19] Use of phosphatide precursors to promote synaptogenesis. Annu Rev Nutr. 2009; 29:59-87
[20] Study of Citicoline for the Treatment of Traumatic Brain Injury (COBRIT) ClinicalTrials.gov website
[21] Bioavailability of methyl-14C CDP-choline by oral route. Arzneimittelforschung. 1983; 33(7A):1045-7 Agut J, Font E, Sacristán A, Ortiz JA
[22] First administration of cytidine diphosphocholine and galantamine in schizophrenia: a sustained alpha7 nicotinic agonist strategy. Clin Neuropharmacol. 2008 Jan-Feb; 31(1):34-9 Deutsch SI, Schwartz BL, Schooler NR, Rosse RB, Mastropaolo J, Gaskins B
