Citicoline is the name of a chemical compound also known as CDP-choline or cytidine diphosphate choline (1). It is an intermediate in the synthesis of phosphatidylcholine, a type of phospholipid that is an important component of cell membranes.

Chemical Industrial Synthesis Process

• Synthesis of cytidine. Cytidine is synthesized from uridine orotate through various chemical steps including methylation and phosphorylation.
• Synthesis of phosphocholine. Phosphocholine is synthesized by alkylating choline with an alkylating agent, such as ethylene oxide, followed by phosphorylation.
• Condensation of cytidine and phosphocholine. Cytidine and phosphocholine are condensed in the presence of a condensing agent, such as N,N'-dicyandiamide, to form citicoline.
• Purification. Crude citicoline is purified through crystallization or chromatography techniques to remove impurities and enhance the purity of the product.
• Quality control. Samples of the final product are tested to ensure they meet purity, stability, and biological activity standards.
• Sterilization. The final product is sterilized by heat treatments or filtration to ensure microbiological safety before use in pharmaceutical or supplement applications.

What it is used for and where

Citicoline is a compound that plays a crucial role in the biochemistry of nerve cells. It is used as a dietary supplement and pharmaceutical agent to support brain function, particularly in cases of neurodegenerative diseases such as Alzheimer's disease and dementia. Citicoline works by increasing the availability of phosphatidylcholine for the maintenance of cell membranes and for neurotransmitter production, thus contributing to neuronal health and improved cognitive functions. Additionally, it has been studied for its potential benefits in recovery from brain injuries and stroke, as it can help reduce tissue damage and promote neuronal repair.

Anti-aging Properties. It contributes to the synthesis of phospholipids in the cell membrane, supporting skin regeneration and reducing signs of aging such as fine lines and wrinkles.

Neuronal Protection. Citicoline is known for its neuroprotective properties (2). When applied to the skin, it can help protect skin cells from oxidative stress and enhance their functionality. It can improve cognitive decline (3).

Improvement of Skin Elasticity. It promotes the production of phosphatidylcholine, an important component of cell membranes, which can improve skin elasticity and smoothness.

Hydration. It can help enhance the skin barrier and increase the skin's ability to retain moisture, resulting in healthier, more hydrated skin.

Repair Effects. It stimulates cell regeneration, contributing to the repair of damaged skin and promoting a clearer and more even complexion.

Versatile Applications. Citicoline can be used in a variety of cosmetic formulations, including serums, creams, and lotions, due to its benefits for improving skin health and appearance.

Molecular Formula   C₁₄H₂₆N₄O₁₁P₂

Molecular Weight    488.32 g/mol

CAS   987-78-0

UNII    536BQ2JVC7

EC Number   213-580-7

Synonyms:

citicholine

cytidine 5'-diphosphocholine

CDP-choline

References_____________________________________________________________________

(1) Secades JJ, Gareri P. Citicoline: pharmacological and clinical review, 2022 update. Rev Neurol. 2022 Nov 30;75(s05):S1-S89. doi: 10.33588/rn.75s05.2022311. PMID: 36544369; PMCID: PMC10548481.

Abstract. This review is based on the previous one published in 2016 (Secades JJ. Citicoline: pharmacological and clinical review, 2016 update. Rev Neurol 2016; 63 (Supl 3): S1-S73), incorporating 176 new references, having all the information available in the same document to facilitate the access to the information in one document. This review is focused on the main indications of the drug, as acute stroke and its sequelae, including the cognitive impairment, and traumatic brain injury and its sequelae. There are retrieved the most important experimental and clinical data in both indications.

(2) Świątkiewicz M, Grieb P. Citicoline for Supporting Memory in Aging Humans. Aging Dis. 2023 Aug 1;14(4):1184-1195. doi: 10.14336/AD.2022.0913. 

Abstract. Citicoline is the generic name of CDP-choline, a natural metabolite presents in all living cells. Used in medicine as a drug since the 1980-s, citicoline was recently pronounced a food ingredient. When ingested, citicoline breaks down to cytidine and choline, which become incorporated into their respective normal metabolic pathways. Choline is a precursor of acetylcholine and phospholipids; these is a neurotransmitter pivotal for learning and memory and important constituents of neuronal membranes and myelin sheaths, respectively. Cytidine in humans is readily converted to uridine, which exerts a positive effect on synaptic function and supports the formation of synaptic membranes. Choline deficiency has been found to be correlated with memory dysfunction. Magnetic resonance spectroscopy studies showed that citicoline intake improves brain uptake of choline in older persons, suggestive of that it shall help in reversing early age-related cognitive changes. In randomized, placebo-controlled trials of cognitively normal middle-aged and elderly persons, positive effects of citicoline on memory efficacy were found. Similar effects of citicoline on memory indices were also found in patients suffering from mild cognitive impairment and some other neurological diseases. Altogether, the aforementioned data provide complex and unambiguous evidence supporting the claim that oral citicoline intake positively influences memory function in humans who encounter age-related memory impairment also in the absence of any detectable neurological or psychiatric disease.

(3) Bermejo PE, Dorado R, Zea-Sevilla MA. Role of Citicoline in Patients With Mild Cognitive Impairment. Neurosci Insights. 2023 Feb 16;18:26331055231152496. doi: 10.1177/26331055231152496. 

Abstract. The term mild cognitive impairment (MCI) defines an intermediate state between normal aging and dementia. Vascular cognitive impairment refers to a decline in cognitive function that is caused by or associated with vascular disease and comprises all the spectrum of cognitive impairments, from MCI of vascular origin to vascular dementia. One of the available treatments for cognitive impairment is cytidine diphosphate-choline (CDP-Choline), or citicoline. The objective of the present manuscript is to provide complete evidence about the efficacy of citicoline for MCI, especially of vascular origin, but also due to other neurodegenerative disorders. Citicoline is a pharmaceutical product constituted by the combination of 2 natural molecules (cytidine and choline) and is marketed as a food supplement. It has been proposed to provide neuroprotective effects through diverse mechanisms of action. Taking into account the available literature, citicoline has shown a consistent improvement in cognitive function in patients with MCI, especially of vascular origin. Moreover, it provides beneficial effects on vascular, Alzheimer, and mixed dementias, stroke sequelae, intracerebral hemorrhages, traumatic brain injuries, and neurodegenerative diseases. Long-term treatment with citicoline has also been demonstrated to be well-tolerated and has not been associated with severe adverse events. Citicoline is a safe, well-tolerated, and promising agent with evidenced neuroprotective properties. © The Author(s) 2023.

Almeria M, Alvarez I, Molina-Seguin J, Besora S, Buongiorno M, Romero S, Casas L, Cano C, Castejon J, Arribas S, Krupinski J. Citicoline May Prevent Cognitive Decline in Patients with Cerebrovascular Disease. Clin Interv Aging. 2023 Jul 19;18:1093-1102. doi: 10.2147/CIA.S409994. PMID: 37489128; PMCID: PMC10363355.