Citicoline is the drug and supplement name for cytidine-5’-diphosphocholine (CDP-choline), a molecule every cell makes on the way to building phosphatidylcholine, the main fat in cell membranes. Taken by mouth, it is broken down into choline and a pyrimidine nucleoside (cytidine, which in humans circulates mainly as uridine), and both parts are reused by the body. It has been a prescription drug for stroke, head injury and cognitive decline in many countries since the 1970s, while in the US and the EU it is sold as a food or dietary supplement for memory and focus.
The single most important fact is that the large, modern trials were negative. The ICTUS trial of 2,298 stroke patients was stopped for futility, and the COBRIT trial of 1,213 patients with traumatic brain injury found no benefit. Evidence in cognitive impairment is more favorable but of low quality, and only one industry-funded trial in healthy older adults has shown a memory effect. In 2024 the European Food Safety Authority concluded that a memory benefit has not been established.
This page summarizes what the clinical trials, systematic reviews and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Endogenous nucleotide; intermediate in phosphatidylcholine synthesis; choline and uridine donor |
| Other names | CDP-choline, cytidine diphosphocholine; Somazina (drug brand); Cognizin (Kyowa Hakko supplement ingredient) |
| Formula | C₁₄H₂₆N₄O₁₁P₂, 488.32 g/mol (free form); the sodium salt is C₁₄H₂₅N₄NaO₁₁P₂, 510.31 g/mol |
| Route | Oral; intravenous in hospital stroke trials such as ICTUS |
| Studied doses | 250–500 mg/day in supplement trials; 500–2,000 mg/day in stroke, brain injury and dementia trials |
| Half-life | No single value. Plasma choline stays raised 5–10 h and uridine 5–6 h after one oral dose; excretion of a radiolabeled dose has a fast phase (≈3–7 h) and a slow phase (≈19–71 h) |
| Status outside the US | Prescription drug in many countries (approved for brain injury in 59 countries, per the COBRIT authors); authorized as a novel food in the EU |
| US status | Not an FDA-approved drug; sold as a dietary supplement |
| WADA status | Not named on the 2026 Prohibited List |
What it is
CDP-choline is a nucleotide built from cytidine (a ribose sugar plus the base cytosine), two phosphate groups and choline (PubChem). Eugene Kennedy and Samuel Weiss described the role of cytidine nucleotides in phospholipid synthesis in 1956 (Kennedy and Weiss, J Biol Chem 1956), and the route is still called the Kennedy pathway. In it, CDP-choline is formed from phosphocholine, and that step is the rate-limiting one for making phosphatidylcholine (Secades and Gareri, Rev Neurol 2022).
“Citicoline” is the name used when the same molecule is given as a drug (Fioravanti and Yanagi, Cochrane 2005). Both the “inner salt” (the free form) and the sodium salt have been used as prescription drugs; the inner salt is the form accepted as a food ingredient in the US and EU (Świątkiewicz and Grieb, Aging Dis 2023).
The rationale for taking it rests on three ideas:
- Membrane repair. In animal models of brain injury and ischemia (loss of blood flow), citicoline was proposed to speed rebuilding of membrane phospholipids and limit their breakdown into free fatty acids (Fioravanti and Yanagi, Cochrane 2005). These are animal and laboratory findings.
- Choline supply. Choline is the raw material for acetylcholine, the neurotransmitter involved in attention and memory. Citicoline raises blood choline for several hours (Wurtman et al., Biochem Pharmacol 2000).
- Uridine supply. The cytidine half is converted to uridine. Uridine enters the brain and is converted to UTP, and in cultured neuron-derived cells it was also converted to CTP, the cytidine nucleotide used to make CDP-choline (Wurtman et al., Biochem Pharmacol 2000).
Citicoline is one of several “choline donors” sold as nootropics. Alpha-GPC is the other common one; it delivers choline with a glycerophosphate backbone instead of a nucleotide, so it supplies no uridine.
How it works in the body
After ingestion, citicoline is well absorbed and rapidly broken down into choline and cytidine. Blood cytidine is quickly converted to uridine, and choline and uridine then enter cells and join their normal metabolic pathways (Świątkiewicz and Grieb, Aging Dis 2023).
In a crossover study of 12 adults, single oral doses of 500, 2,000 and 4,000 mg each raised plasma choline and uridine (Wurtman et al., Biochem Pharmacol 2000):
| Dose | Plasma choline | Plasma uridine |
|---|---|---|
| 500 mg | Raised significantly for 5 h | Raised for 5–6 h, peak up 70–90% |
| 2,000 mg | Raised for 8 h | Raised for 5–6 h, peak up 100–120% |
| 4,000 mg | Raised for 10 h | No further rise over 2,000 mg |
Plasma cytidine was below the detection limit at every dose. The authors concluded that in humans the circulating products of oral citicoline are choline and uridine, not choline and cytidine as in rats. In this study the uridine rise did not increase further above 2,000 mg.
A 2022 review written by a scientist at Ferrer, the company that markets the drug, summarizes older pharmacokinetic work (Secades and Gareri, Rev Neurol 2022):
- Absorption. In rats, oral bioavailability of radiolabeled citicoline was close to that of intravenous dosing, with almost no label left in the feces.
- Brain uptake. In rats, label from the choline and cytidine halves appeared in brain phospholipids and nucleotides and stayed there for at least 48 h.
- Elimination in people. After an oral radiolabeled dose in 6 healthy volunteers, the label left the body slowly in exhaled carbon dioxide, urine and feces:
| Route of excretion | First-phase half-life | Second-phase half-life |
|---|---|---|
| Exhaled CO₂ | 2.6 h | 56 h |
| Urine | 6.6 h | 71 h |
| Feces | Not reported | 19 h |
These half-lives describe the radioactive label as it moves through normal choline and nucleotide metabolism, not intact citicoline. After a 30-minute intravenous infusion in healthy people, CDP-choline itself was almost undetectable in plasma by the end of the infusion (Secades and Gareri, Rev Neurol 2022).
Regulatory status
Prescription drug in other countries
Citicoline has been used in medicine since the 1970s as a prescription drug for acute and chronic neurological conditions such as stroke, brain and spinal cord injury and Parkinson’s disease (Świątkiewicz and Grieb, Aging Dis 2023). Specific sourced data points:
- The ICTUS investigators noted it is approved in some countries for acute ischemic stroke (Dávalos et al., Lancet 2012).
- The COBRIT investigators stated it was approved for traumatic brain injury in 59 countries (Zafonte et al., JAMA 2012).
- The 2005 Cochrane review called it a frequently prescribed drug for cognitive impairment in several European countries, especially when cerebrovascular disease is involved (Fioravanti and Yanagi, Cochrane 2005).
- In South Korea, a post-marketing study followed 4,191 stroke patients treated under the locally approved regimen (Secades and Gareri, Rev Neurol 2022).
Supplement status in the US and EU
No citicoline product appears in FDA’s database of approved drugs (Drugs@FDA). It is sold as a dietary supplement ingredient: the NIH Dietary Supplement Label Database lists more than 400 US product labels that contain citicoline (search in October 2026) (NIH DSLD). FDA’s GRAS (generally recognized as safe) notice inventory returned no entry for citicoline in the same search (FDA GRAS notices). Because it is not an approved drug, no US citicoline product has gone through FDA review of efficacy for any condition.
In the EU, citicoline is authorized as a novel food ingredient after an EFSA safety evaluation (EFSA NDA Panel, EFSA J 2024). A 2023 review gives the recommended maximum intake of the inner salt as 500 mg/day in food supplements and 1,000 mg/day in foods for special medical purposes (Świątkiewicz and Grieb, Aging Dis 2023).
In 2024, EFSA rejected a proposed EU health claim that citicoline supports memory in middle-aged and older adults with subjective memory complaints. The panel found that a cause-and-effect relationship had not been established (EFSA NDA Panel, EFSA J 2024).
What the research shows
Acute ischemic stroke: early promise, then a null trial
Stroke is where citicoline was studied most. An early pooled analysis of 4 oral trials (1,372 eligible patients) used individual patient data and found complete recovery at 3 months in 25.2% on citicoline vs 20.2% on placebo (OR 1.33, 95% CI 1.10–1.62). The 2,000 mg/day dose gave the largest difference (Dávalos et al., Stroke 2002). The trials were drawn partly from Ferrer’s own bibliographic database, and the author list included Ferrer scientist J.J. Secades.
ICTUS was designed to confirm this result (Dávalos et al., Lancet 2012):
| Feature | ICTUS trial |
|---|---|
| Design | Randomized, double-blind, placebo-controlled, sequential; 59 hospitals in Spain, Portugal and Germany; funded by Ferrer |
| Patients | 2,298 with moderate-to-severe acute ischemic stroke, treated within 24 h of onset |
| Dose | 1,000 mg IV every 12 h for 3 days, then 1,000 mg orally every 12 h, for 6 weeks in total |
| Primary outcome | Global recovery at 90 days (NIHSS ≤1, modified Rankin ≤1, Barthel Index ≥95) |
| Result | Stopped for futility; OR 1.03 (95% CI 0.86–1.25), p = 0.364 |
| Safety | No significant differences in safety outcomes or adverse event rates |
The investigators concluded that citicoline is not effective in moderate-to-severe acute ischemic stroke under the conditions of the trial.
Later meta-analyses split along predictable lines:
| Review | Trials, patients | Main finding |
|---|---|---|
| Secades et al., J Stroke Cerebrovasc Dis 2016 (Ferrer-affiliated authors) | 10 double-blind RCTs | Higher rate of independence, OR 1.56 (95% CI 1.12–2.16) random effects; the authors called the benefit “limited” on top of clot-dissolving therapy (rtPA) |
| Martí-Carvajal et al., Cochrane 2020 (independent) | 10 RCTs, 4,281 patients | No difference in mortality (RR 0.94, 95% CI 0.83–1.07), disability (RR 1.11, 95% CI 0.97–1.26), Barthel ≥95 (RR 1.03) or NIHSS ≤1 (RR 1.08); all trials at high risk of bias; six were drug-company sponsored |
The Cochrane review rated the evidence low-certainty and noted that its trial sequential analysis suggested more trials may not be needed for the main outcomes. It also found that harms were poorly reported.
Traumatic brain injury: COBRIT
COBRIT was a phase 3, double-blind trial at 8 US trauma centers. It randomized 1,213 patients with complicated mild, moderate or severe traumatic brain injury to 2,000 mg/day citicoline or placebo for 90 days (Zafonte et al., JAMA 2012). Favorable improvement on the Glasgow Outcome Scale–Extended was 35.4% vs 35.6%. The global odds ratio was 0.98 (95% CI 0.83–1.15) at 90 days and 0.87 (95% CI 0.72–1.04) at 180 days, with no benefit in either severity subgroup.
Cognitive impairment and dementia
The evidence here is older, smaller and more heterogeneous.
- Cochrane 2005. The review included 14 double-blind, placebo-controlled trials in older people, ranging from subjective memory complaints to vascular cognitive impairment and mild-to-moderate dementia. Seven of the 14 lasted only 20–30 days and one lasted 12 months. It found no effect on attention, some evidence of benefit on memory and behavior in the short to medium term, stronger evidence on global clinical impression, and good tolerability (Fioravanti and Yanagi, Cochrane 2005). The lead reviewer had been an investigator in some of the included trials.
- Meta-analysis 2023. A review of studies from 2010–2022 found seven eligible studies in mild cognitive impairment, Alzheimer’s disease and post-stroke dementia, of which only two were randomized trials. Pooled standardized mean differences ranged from 0.56 (95% CI 0.37–0.75) to 1.57 (95% CI 0.77–2.37) depending on assumptions, and the authors judged the overall quality poor, with significant risk of bias in favor of citicoline (Bonvicini et al., Nutrients 2023).
Individual studies show the same pattern of positive open-label results and a negative blinded one:
| Study | Design, n | Dose, duration | Result |
|---|---|---|---|
| IDEALE, Cotroneo et al. 2013 | Open-label, untreated control group; 349 adults ≥65 with mild vascular cognitive impairment | 500 mg twice daily, 9 months | MMSE stable on citicoline (22.4 to 22.9) and different from controls; no difference in daily-living scores |
| Alvarez-Sabín et al. 2013 | Open-label RCT; 347 first-ever stroke patients | 1,000 mg/day, 12 months | Less decline in attention-executive function (OR 2.38 at 12 months) and temporal orientation; functional outcome not significantly different (57.3% vs 48.7%) |
| Cohen et al. 2003 | Double-blind RCT; 30 patients with vascular dementia | 500 mg twice daily, 12 months | No difference in neuropsychological performance or MRI brain volume; both groups declined |
MMSE (Mini-Mental State Examination) is a 30-point screening test of cognition.
Healthy adults and age-related memory complaints
Only a handful of placebo-controlled trials have tested citicoline in people without a neurological diagnosis.
| Trial | Participants | Dose, duration | Main result |
|---|---|---|---|
| Spiers et al., Arch Neurol 1996 | 95 adults aged 50–85; then a 32-person crossover subgroup with “relatively inefficient” memory | 1,000 mg/day for 3 months; 2,000 mg/day for 2 months in the crossover | No overall effect in the first study; better delayed recall only in the weaker-memory subgroup. In the crossover, 2,000 mg/day improved immediate and delayed story recall |
| Nakazaki et al., J Nutr 2021 | 100 healthy adults aged 50–85 with age-associated memory impairment | 500 mg/day (Cognizin), 12 weeks | Primary outcome (Spatial Span) not different between groups; secondary episodic memory (Paired Associates) and a composite memory score improved more than placebo |
| McGlade et al., J Atten Disord 2019 | 75 healthy adolescent boys | 250 or 500 mg/day (Cognizin), 28 days | Better attention (p = 0.02) and psychomotor speed (p = 0.03) than placebo |
| Bruce et al., Int J Food Sci Nutr 2014 | 60 healthy adults | One drink with 250 mg citicoline plus caffeine; tested 30 min later | Faster reaction times and fewer errors on attention tasks; the effect of citicoline cannot be separated from caffeine |
Three caveats apply. The Nakazaki and McGlade trials were sponsored by or co-authored with employees of Kyowa Hakko Bio, the maker of Cognizin (Nakazaki et al., J Nutr 2021; McGlade et al., J Atten Disord 2019). The positive results are mostly secondary outcomes from small samples. And when EFSA weighed the healthy-adult evidence, it noted that the 500 mg/day episodic memory effect was not seen in the 1,000 mg/day Spiers trial or supported by dementia data, and found no convincing mechanism (EFSA NDA Panel, EFSA J 2024).
For comparison, other compounds marketed for cognition with pages in this library include alpha-GPC, Bacopa monnieri, Ginkgo biloba, L-theanine, Lion’s mane, Rhodiola rosea and the prescription wakefulness drugs modafinil and armodafinil.
Doses used in studies
| Setting | Daily dose studied | Source |
|---|---|---|
| Healthy adolescents | 250 or 500 mg oral | McGlade et al. 2019 |
| Healthy older adults | 500 mg oral | Nakazaki et al. 2021 |
| Older adults, memory | 1,000–2,000 mg oral | Spiers et al. 1996 |
| Vascular cognitive impairment, post-stroke cognition | 1,000 mg oral | Cotroneo et al. 2013; Alvarez-Sabín et al. 2013 |
| Acute ischemic stroke | 500–2,000 mg oral and/or IV | Martí-Carvajal et al. 2020 |
| Traumatic brain injury | 2,000 mg oral or enteral | Zafonte et al. 2012 |
| Recommended maximum as a food supplement (inner salt) | 500 mg | Świątkiewicz and Grieb 2023 |
Side effects and risks
Tolerability in trials
Across decades of trials, citicoline has been well tolerated, and no large trial found a safety signal. The 2,298-patient ICTUS trial reported no significant differences from placebo in safety outcomes or adverse events (Dávalos et al., Lancet 2012). The 12-week Nakazaki trial reported no serious adverse events (Nakazaki et al., J Nutr 2021).
Specific findings:
- Headache. In 12 healthy volunteers given 600 mg/day and 1,000 mg/day for 5 days each, transient headaches were the only adverse event: 4 and 5 people on the two doses vs 1 on placebo (Dinsdale et al., Arzneimittelforschung 1983).
- Digestive upset and restlessness. A manufacturer-authored review describes occasional digestive intolerance and, in the first days, excitability or restlessness. In an uncontrolled series of 2,817 patients given a mean 600 mg/day for 15–60 days, 5.0% reported side effects, mostly digestive (3.6%) (Secades and Gareri, Rev Neurol 2022).
- Stroke-trial adverse events. In the pooled US oral stroke trials, anxiety (13.7% vs 10.0%) and limb edema (9.8% vs 6.5%) were reported slightly more often with citicoline, while depression and falls were more frequent with placebo (Secades and Gareri, Rev Neurol 2022).
Limits of the safety data
The independent Cochrane stroke review found that adverse events were poorly reported and harms may have been underestimated. It concluded that the safety profile “remains unknown” in the strict sense of well-reported trial data (Martí-Carvajal et al., Cochrane 2020). Most trials enrolled older adults or hospitalized patients for weeks to months, so long-term use by healthy young people has not been studied.
Interactions and who should be cautious
No clinically important drug interactions are documented in the sources reviewed here. Citicoline has been used as an add-on treatment in Parkinson’s disease (Fioravanti and Yanagi, Cochrane 2005) and studied alongside the dementia drug rivastigmine (Bonvicini et al., Nutrients 2023), but these studies were not designed to detect interactions. None of the sources reviewed here report data in pregnancy or breastfeeding.
Sports and anti-doping
Citicoline is not named on the WADA 2026 Prohibited List (WADA 2026 Prohibited List). Products that combine it with stimulants should be judged on their other ingredients.
Key takeaways
- A choline and uridine donor. Oral citicoline is split into choline and cytidine, which humans convert to uridine; both raise blood levels for roughly 5–10 h after a dose.
- Drug abroad, supplement in the US. It is a prescription drug in many countries and a novel food in the EU, but it has no FDA drug approval and is sold in the US as a dietary supplement.
- The big trials were negative. ICTUS (2,298 stroke patients) was stopped for futility, COBRIT (1,213 brain-injury patients) found no benefit, and the independent 2020 Cochrane review found no effect on death or disability after stroke.
- Cognitive-impairment evidence is positive but weak. Cochrane found some short-term benefit on memory and behavior but not attention; a 2023 meta-analysis found larger effects but mostly from non-randomized, high-bias studies.
- Healthy-adult evidence is thin. One industry-funded 12-week trial at 500 mg/day showed better episodic memory on secondary outcomes, and EFSA judged a memory benefit unproven in 2024.
- Well tolerated in trials. Headache, digestive upset and restlessness are the main reported effects, but harms were poorly reported in many trials.
Sources
- National Center for Biotechnology Information. Citicoline (CID 13804) and citicoline sodium (CID 36605). PubChem. PubChem.
- Kennedy EP, Weiss SB. The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem. 1956;222(1):193–214. PubMed.
- 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. PubMed.
- Secades JJ, Gareri P. Citicoline: pharmacological and clinical review, 2022 update. Rev Neurol. 2022;75(s05):S1–S89. PubMed; PMC. (Spanish-language; first author employed by Ferrer.)
- Świątkiewicz M, Grieb P. Citicoline for supporting memory in aging humans. Aging Dis. 2023;14(4):1184–1195. PubMed.
- EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T, et al. ‘Citicoline’ and support of the memory function: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA J. 2024;22(7):e8861. PubMed.
- US Food and Drug Administration. Drugs@FDA: FDA-approved drugs. Drugs@FDA.
- US Food and Drug Administration. GRAS notices inventory. FDA GRAS notices.
- National Institutes of Health, Office of Dietary Supplements. Dietary Supplement Label Database: citicoline. NIH DSLD.
- Dávalos A, Castillo J, Alvarez-Sabín J, et al. Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke. 2002;33(12):2850–2857. PubMed.
- Dávalos A, Alvarez-Sabín J, Castillo J, et al. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet. 2012;380(9839):349–357. PubMed.
- Secades JJ, Alvarez-Sabín J, Castillo J, et al. Citicoline for acute ischemic stroke: a systematic review and formal meta-analysis of randomized, double-blind, and placebo-controlled trials. J Stroke Cerebrovasc Dis. 2016;25(8):1984–1996. PubMed.
- Martí-Carvajal AJ, Valli C, Martí-Amarista CE, Solà I, Martí-Fàbregas J, Bonfill Cosp X. Citicoline for treating people with acute ischemic stroke. Cochrane Database Syst Rev. 2020;8(8):CD013066. PubMed.
- Zafonte RD, Bagiella E, Ansel BM, et al. Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA. 2012;308(19):1993–2000. PubMed.
- 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. PubMed.
- Bonvicini M, Travaglini S, Lelli D, Antonelli Incalzi R, Pedone C. Is citicoline effective in preventing and slowing down dementia? A systematic review and a meta-analysis. Nutrients. 2023;15(2):386. PubMed.
- Cotroneo AM, Castagna A, Putignano S, et al. Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study. Clin Interv Aging. 2013;8:131–137. PubMed.
- Alvarez-Sabín J, Ortega G, Jacas C, et al. Long-term treatment with citicoline may improve poststroke vascular cognitive impairment. Cerebrovasc Dis. 2013;35(2):146–154. PubMed.
- Cohen RA, Browndyke JN, Moser DJ, Paul RH, Gordon N, Sweet L. Long-term citicoline (cytidine diphosphate choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes. Cerebrovasc Dis. 2003;16(3):199–204. PubMed.
- Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Citicoline improves verbal memory in aging. Arch Neurol. 1996;53(5):441–448. PubMed.
- 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;151(8):2153–2160. PubMed.
- McGlade E, Agoston AM, DiMuzio J, et al. The effect of citicoline supplementation on motor speed and attention in adolescent males. J Atten Disord. 2019;23(2):121–134. PubMed.
- Bruce SE, Werner KB, Preston BF, Baker LM. Improvements in concentration, working memory and sustained attention following consumption of a natural citicoline-caffeine beverage. Int J Food Sci Nutr. 2014;65(8):1003–1007. PubMed.
- Dinsdale JR, Griffiths GK, Castelló J, Maddock J, Ortiz JA, Aylward M. CDP-choline: repeated oral dose tolerance studies in adult healthy volunteers. Arzneimittelforschung. 1983;33(7A):1061–1065. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List. In force January 1, 2026. WADA.