Everything You Need to Know About Citicoline

General Information

Scientific Name: Cytidine diphosphate-choline (CDP-Choline) and Cytidine 5′-diphosphocholine

Any Other Names: Sold as brand names: Cebroton, Ceraxon, Cidilin, Citifar, Cognizin, Difosfocin, Hipercol, NeurAxon, Nicholin, Sinkron, Somazina, Synapsine, Startonyl, Trausan, Xerenoos, and others.

Primary Constituents: Cytidine-diphosphocholine (CDP-choline)

Country or Region of Origin: Cytidine and Choline [naturally occurring in human beings and animals]

Known Uses: Cognitive Enhancer, Improved Memory, Neuroprotective Effects, Vision, Neurodegenerative Diseases, Bipolar Disease, and More

General History & Introduction

Citicoline is a naturally occurring chemical present in human and animal tissue, especially within the organs. It is available as an over-the-counter supplement in nearly a hundred countries around the world and is sold under a variety of brand names (Wisher, 2012). One of the reasons Citicoline is a sought-after nootropic is its ability to increase neurotransmitter levels in the central nervous system (Iulia et al., 2017).  It achieves this manipulation of neurotransmitters through interactions with the synthesis of phospholipid cellular membranes (2017). The supplement is well-studied for its ability to improve cognitive impairment (Gareri et al., 2015).

Nootropic Benefits of Citicoline

Cognitive Enhancer

Citicoline has been proven to activate an improved brain metabolism, through the various level manipulations of neurotransmitters (Secades & Lorenzo, 2006). The supplement also has documented, empirical evidence that it improves cognitive rating scales (2006). Some studies have revealed Citicoline’s potential to slow the advancing of the neurodegenerative, mild cognitive impairment (Grieb, 2014). There are studies which indicate Citicoline can modulate the activity and expression of some ‘neuronal-death’-associated protein kinases in the central nervous system (Gareri et al., 2015). The theory behind Citicoline’s ability to enhance brain function starts with its ability to increase phosphatidylcholine levels in the brain (Conant & Schauss, 2004).  Phosphatidylcholine is one of the brain chemicals responsible for efficient brain function, and the regulation of certain chemical communications within the brain (2004).

Improved Memory

Many studies have revealed CDP-choline’s potential to improve the density of dopamine receptors (Gimenez et al., 1991).  A few studies have purported that the supplement may improve learning and memory performance (Secades & Lorenzo, 2006). Citicoline supplements have been well-studied when it comes to their effect on memory.  One study suggested the supplement could be used to directly combat normal memory loss as an effect from aging (Nakazaki et al., 2020). The same study suggested Citicoline could be used to improve overall memory performance as well (2020).

Neuroprotective Effects

There are several preclinical studies which have shown Citicoline’s capability to offer significant neuroprotective properties, especially for various central neurodegenerative diseases (Grieb, 2014). Citicoline provides benefits to neuroendocrine cells, which are critical in sending and receiving messages from the nervous system and producing hormones in response (Secades & Lorenzo, 2006). The supplement also provides neuroimmunomodulation and neurophysiological benefits (2006).

Vision

Citicoline could improve the retinal and postretinal visual pathways through their stimulation of the dopaminergic system (Iulia et al., 2017). The same research actually proved the supplement’s ability to favorably impact contrast sensitivity, visual acuity, and visual evoked responses (2017).  Citicoline has been shown in a few studies to slow the progression of the neurodegenerative disorder glaucoma (Grieb, 2014). The neuroprotective effects the substance has in the treatment of glaucoma is impressive considering the benefits exist even alongside incredible intraocular pressure (Iulia et al., 2017). The use of Citicoline in the treatment of lazy eye (amblyopia) has been proven to offer significant benefits to visual acuity (Pawar et al., 2014).

Other Uses

Citicoline has been proven to offer significant neuroprotective effects in patients suffering from Alzheimer’s disease, Parkinson’s disease, and stroke (Iulia et al., 2017).  The supplement has been proven useful in treating amblyopia, drug addictions, and even alcoholism (Secades & Lorenzo, 2006). It is also possible that the supplement could have positive effects in the treatment of cerebral vascular disease, head trauma (HT), and other cognitive disorders (2006).

Important Note: Although some studies have suggested the nootropic could be useful in recovering ischemic stroke patients, a very large, recent study proposed the supplement offered no benefit in the treatment of ischemic strokes (Grieb, 2014).

Dosing and Usage Information

Adults are typically advised to take around 400 to 600 mg a day of Citicoline, which is also around the amount found offered as a daily serving in most Citicoline supplement brands. The supplement form of citicoline undergoes a process in the body called hydrolyzation, by which choline and cytidine are produced in the intestines (Wurtman et al., 2000). Following these chemicals as they make it through the blood-brain barrier, they reform to create citicoline once again through use of the rate-limiting enzyme (CTP-phosphocholine cytidylyltransferase) found in phosphatidylcholine synthesis (Alvarez et al., 1999).

Side Effects

Although it has been reported as having a low toxicity profile in humans, Citicoline has only been sufficiently studied at doses of up to 2000 mg per day (Conant & Schauss, 2004). There are some minor adverse reactions in some rare cases including stomach pain and diarrhea (2004). Citicoline may have a potential to exacerbate psychotic episodes, or adversely interact with anti-psychotic prescription medication, although there are not sufficient studies to solidify these claims (Tardner, 2020). In general, the moderate doses found in most Citicoline supplements appear to be safe.

Conclusion

Overall, Citicoline is a relatively safe, neuroprotective supplement (Gareri et al., 2015). One of Citicoline’s most exciting pieces of empirical data include the clear indication that the supplement can improve mental performance (Franco-Maside et al., 1994). That same study also revealed the supplement’s ability to improve brain electrical activity (1994). The versatile usage of the supplement is impressive, and the plethora of clinical trials and empirical data supporting the substance’s many applications is growing.  Whether it is being used as a cognitive and memory enhancer, or for its ability to combat many neurodegenerative conditions, the supplement seems to have a very promising future!

Sources:

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Conant, R. and Schauss, A. (2004). Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. Alternative Medicine Review. Vol. 9(1). Pp. 17–31. PMID 15005642

Franco-Maside, A., Caamaño, J., Gómez, M., and Cacabelos, R. (1994). Methods Find Exp. Clin Pharmacol. Vol. 16(8). Pp. 597-607.

Gareri, P., Castagna, A., Cotroneo, A. M., Putignano, S., De Sarro, G., & Bruni, A. C. (2015). The role of citicoline in cognitive impairment: pharmacological characteristics, possible advantages, and doubts for an old drug with new perspectives. Clinical interventions in aging. Vol. 10. Pp. 1421–1429. DOI: https://doi.org/10.2147/CIA.S87886

Giménez, R., and Aguilar, J. (1998). Effects of CDP-choline administration on brain striatum platelet-activating factor in aging rats. European Journal of Pharmacology. Vol. 344(2–3). Pp. 149-152. DOI: https://doi.org/10.1016/S0014-2999(98)00035-1.

Grieb P. (2014). Neuroprotective properties of citicoline: facts, doubts and unresolved issues. CNS drugs. Vol. 28(3). Pp. 185–193. DOI: https://doi.org/10.1007/s40263-014-0144-8

Iulia, C., Ruxandra, T., Costin, L., Liliana-Mary, V. (2017). Citicoline – a neuroprotector with proven effects on glaucomatous disease. Rom J Ophthalmol. Vol. 61(3). Pp. 152-158. DOI: 10.22336/rjo.2017.29. PMID: 29450391; PMCID: PMC5710031.

Nakazaki, E., Mah, E., Citrolo, D., Watanabe, F. (2020). Effect of Citicoline on Memory Function in Healthy Order Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Current Developments in Nutrition. Vol. 4(2). Pp. 1227. DOI: https://doi.org/10.1093/cdn/nzaa057_043

Pawar, P., Mumbare, S., Patil, M., & Ramakrishnan, S. (2014). Effectiveness of the addition of citicoline to patching in the treatment of amblyopia around visual maturity: a randomized controlled trial. Indian journal of ophthalmology. Vol. 62(2). Pp. 124–129. DOI: https://doi.org/10.4103/0301-4738.128586

Secades, J. and Lorenzo, J. (2006). Citicoline: pharmacological and clinical review. Methods Find Exp Clin Pharmacol. Suppl Vol. B. Pp. 1-56. PMID: 17171187.

Tardner, P. (2020). “The use of citicoline for the treatment of cognitive decline and cognitive impairment: A meta-analysis of pharmacological literature. International Journal of Environmental Science & Technology”. International Journal of Environmental Science & Technology. Vol. 08(30).

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Wurtman, R., Regan, M., Ulus, I., Yu, L. (Oct 2000). “Effect of oral CDP-choline on plasma choline and uridine levels in humans”. Biochemical Pharmacology. Vol. 60(7). Pp. 989–92. DOI:10.1016/S0006-2952(00)00436-6