Citicoline

Citicoline, also known as CDP-choline, is a compound that the body produces in small amounts and can also be taken as a supplement. It is made up of choline and cytidine (which the body converts to uridine), two nutrients involved in brain health.

Its main role is to serve as a precursor in the synthesis of phospholipids, which form neuron membranes, and acetylcholine, a neurotransmitter related to memory and attention.

Due to these functions, it has been studied as a support for memory, cognitive decline, brain injuries, and eye health.

How does it work?

• Neuronal Support: provides choline and uridine to produce phosphatidylcholine, a key component of neuronal membranes.
• Neurotransmission: promotes the synthesis of acetylcholine, involved in learning and memory processes.
• Brain Energy: some neuroimaging studies show it can improve bioenergetics in the frontal areas of the brain.

Benefits According to Science

Acute Stroke

Dávalos and collaborators in 2012 conducted a trial with over 2,000 patients who had suffered a stroke and received 2,000 mg of citicoline daily in the early hours. The study concluded that there were no benefits compared to placebo in neurological recovery.

Traumatic Brain Injury

That same year, Zafonte and his team evaluated over 1,200 patients with moderate or severe traumatic brain injury, treated with 2,000 mg daily for 90 days. They also found no improvements in memory, attention, or functional recovery compared to placebo.

Memory in Older Adults

A trial in older adults with memory complaints, using 500 mg daily for 12 weeks, observed modest improvements in episodic memory compared to placebo. However, the European Food Safety Authority (EFSA) in 2024 concluded that the evidence is insufficient to approve the claim of “support for memory”.

Attention and Mental Speed

McGlade and his team in 2015 worked with adolescents and young adults. After 28 days with doses between 250 and 500 mg daily, small improvements were detected in sustained attention and in information processing speed.

Glaucoma

Rossetti and collaborators in 2023 conducted a trial in glaucoma patients using oral citicoline (between 500 and 1,600 mg per day) and in 2% eye drops. They found better quality of life and slower progression of certain visual parameters, although the authors themselves note that larger studies are needed to confirm this.

Dosage and Forms of Consumption

• Memory and Attention: between 250 and 500 mg per day for 1 to 3 months.
• After a Stroke: in some studies, 1,000 mg daily has been used for several months, although results have been variable.
• Acute Stroke or Trauma: higher doses, up to 2,000 mg per day, were tested without clear results.
• Glaucoma: used both orally (500–1,600 mg daily) and in 2% eye drops.

Note

Favorable memory results come from studies with well-defined doses of citicoline. Not all supplements available on the market guarantee the same purity or bioavailability, so effects may vary.

Safety and Potential Side Effects

• Generally well-tolerated in healthy adults.
• Side effects are infrequent and mild: headache, digestive discomfort, or temporary insomnia.
• EFSA considers its intake as a supplement up to 500 mg per day to be safe.
• There is insufficient data during pregnancy or breastfeeding, so its use without medical supervision is not recommended during these stages.

Conclusions

Citicoline is a supplement with good safety and studies supporting small improvements in short-term memory and attention.

However, large trials in acute stroke and traumatic brain injury showed no efficacy, limiting its role in severe conditions. In glaucoma and post-stroke recovery, there are positive signals that require confirmation.

In summary, it can be considered for occasional support for cognitive health, always with realistic expectations and under the supervision of a healthcare professional.

References

1. Alvarez-Sabín J, Ortega G, Jacas C, Santamarina E, Maisterra O, Ribo M, Molina C, Roman GC. Long-term treatment with citicoline may improve poststroke vascular cognitive impairment. Cerebrovasc Dis. 2013;35(2):146-54. doi: 10.1159/000346602. Epub 2013 Feb 7. PMID: 23406981.
2. Alvarez-Sabín J, Santamarina E, Maisterra O, Jacas C, Molina C, Quintana M. Long-Term Treatment with Citicoline Prevents Cognitive Decline and Predicts a Better Quality of Life after a First Ischemic Stroke. Int J Mol Sci. 2016 Mar 16;17(3):390. doi: 10.3390/ijms17030390. PMID: 26999113; PMCID: PMC4813246.
3. Dávalos A, Alvarez-Sabín J, Castillo J, Díez-Tejedor E, Ferro J, Martínez-Vila E, Serena J, Segura T, Cruz VT, Masjuan J, Cobo E, Secades JJ; International Citicoline Trial on acUte Stroke (ICTUS) trial investigators. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet. 2012 Jul 28;380(9839):349-57. doi: 10.1016/S0140-6736(12)60813-7. Epub 2012 Jun 11. PMID: 22691567.
4. EFSA CEP Panel (EFSA Panel on Food Contact Materials, Enzymes and Processing Aids), Turck, D., Bohn, T., Castenmiller, J., De Henauw, S., Hirsch-Ernst, K. I., Knutsen, H. K., Maciuk, A., Mangelsdorf, I., McArdle, H. J., Naska, A., Pentieva, K., Thies, F., Tsabouri, S., Vinceti, M., Bresson, J.-L., Fiolet, T., & Siani, A. (2024). ‘Citicoline’ and support of the memory function: Evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA Journal, 22(7), e8861. https://doi.org/10.2903/j.efsa.2024.8861
5. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013. Scientific Opinion on the safety of “citicoline” as a Novel Food ingredient. EFSA Journal 2013; 11 (10):3421, 22 pp. doi:10.2903/j.efsa.2013.3421
6. McGlade E, Agoston AM, DiMuzio J, Kizaki M, Nakazaki E, Kamiya T, Yurgelun-Todd D. The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males. J Atten Disord. 2019 Jan;23(2):121-134. doi: 10.1177/1087054715593633. Epub 2015 Jul 15. PMID: 26179181.
7. Nakazaki E, Mah E, Sanoshy K, Citrolo D, Watanabe F. Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Nutr. 2021 Aug 7;151(8):2153-2160. doi: 10.1093/jn/nxab119. PMID: 33978188; PMCID: PMC8349115.
8. Rossetti L, Goni F, Montesano G, Stalmans I, Topouzis F, Romano D, Galantin E, Delgado-Gonzales N, Giammaria S, Coco G, Vandewalle E, Lemmens S, Giannoulis D, Pappas T, Manni G. The effect of citicoline oral solution on quality of life in patients with glaucoma: the results of an international, multicenter, randomized, placebo-controlled cross-over trial. Graefes Arch Clin Exp Ophthalmol. 2023 Jun;261(6):1659-1668. doi: 10.1007/s00417-022-05947-5. Epub 2023 Jan 14. PMID: 36639525; PMCID: PMC10199108.
9. Zafonte RD, Bagiella E, Ansel BM, Novack TA, Friedewald WT, Hesdorffer DC, Timmons SD, Jallo J, Eisenberg H, Hart T, Ricker JH, Diaz-Arrastia R, Merchant RE, Temkin NR, Melton S, Dikmen SS. Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA. 2012 Nov 21;308(19):1993-2000. doi: 10.1001/jama.2012.13256. PMID: 23168823.