Citicoline

updated

Citicoline (CDP-choline) is sold as a Kennedy pathway intermediate that improves memory and cognition. An openFDA query on 9 October 2026 located no FDA-approved citicoline drug, its large stroke and brain injury trials failed, and EFSA concluded in 2024 that a cause-and-effect relationship with memory has not been established.

Cytidine diphosphate-choline, a phosphatidylcholine precursor

  • An openFDA query on 9 October 2026 for citicoline or citicoline sodium returned no application; trial authors state it is approved in some countries for stroke and in 59 countries for traumatic brain injury, but those are not regulator records.
  • ICTUS (2298 patients with acute ischemic stroke) stopped for futility; 90-day global recovery was similar (OR 1.03, 95% CI 0.86 to 1.25).
  • COBRIT (1213 patients with traumatic brain injury): no difference in functional and cognitive status at 90 days (global OR 0.98) or 180 days (OR 0.87).
  • A 2020 Cochrane review of 10 stroke trials (4281 participants, all at high risk of bias) found little or no difference on any outcome.
  • EFSA's Panel concluded in 2024 that a cause-and-effect relationship between citicoline and memory has not been established.
  • After single oral doses in 12 adults, plasma choline and uridine rose and cytidine was not reliably detectable.

What is citicoline, and is it an approved drug?

Citicoline (CDP-choline) is a molecule the body makes itself. An openFDA query on 9 October 2026 found no FDA-approved citicoline drug. Trial authors state it is approved as a drug in some other countries, but those statements are not regulator records.

Citicoline (CDP-choline, cytidine 5'-diphosphocholine) is C14H26N4O11P2 (488.32 g/mol, CAS 987-78-0). Citicoline sodium is C14H25N4NaO11P2 (510.31 g/mol, CAS 33818-15-4). Products use either the inner salt or the sodium salt, so label milligrams are not identical amounts of citicoline.

An openFDA Drugs@FDA query on 9 October 2026 for citicoline or citicoline sodium (brand, generic and active-ingredient fields) returned no application, so no FDA-approved citicoline drug was located. The ICTUS report says citicoline is approved in some countries for acute ischemic stroke, and the COBRIT report says it is approved for traumatic brain injury in 59 countries. Those are the trial authors' statements, not regulator records, so approval abroad is not established here. US supplement status is not established here either.

PubChem: citicoline and citicoline sodium identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 13804 (citicoline, CDP-choline, cytidine 5'-diphosphocholine) and CID 36605 (citicoline sodium).

Citicoline (CDP-choline, cytidine 5'-diphosphocholine): C14H26N4O11P2, 488.32 g/mol, CAS 987-78-0. Citicoline sodium: CID 36605, C14H25N4NaO11P2, 510.31 g/mol, CAS 33818-15-4. Products use either the inner salt or the sodium salt, so label milligrams are not identical amounts of citicoline.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source
openFDA query, 9 October 2026: no citicoline application

Regulatory record

U.S. Food and Drug Administration. openFDA Drugs@FDA query for citicoline or citicoline sodium (brand, generic and active-ingredient fields), run on 9 October 2026.

The query returned no application, so no FDA-approved citicoline drug was located. Trial reports describe approvals elsewhere: the ICTUS report says citicoline is approved in some countries for acute ischemic stroke, and the COBRIT report says it is approved for traumatic brain injury in 59 countries. Those are the trial authors' statements, not regulator records.

Participants / model
FDA application database, not a clinical population
Treatment
Exact substance-name query
Follow-up
Query run on 9 October 2026
Study design
Dated US approval-record query
Funding
not stated in the source

A negative query on one date is not proof about every product or jurisdiction. Approvals outside the United States were not confirmed with a regulator record, and US supplement status is not established here.

Read the original source
ICTUS: 2298 patients with acute ischemic stroke, stopped for futility

Randomized controlled trial

Dávalos A et al. Lancet. 2012;380(9839):349-57. PMID 22691567.

The trial was stopped for futility. 90-day global recovery was similar (OR 1.03, 95% CI 0.86 to 1.25), with no differences in safety variables.

Participants / model
2298 patients with moderate-to-severe acute ischemic stroke in Germany, Portugal and Spain
Treatment
Intravenous then oral citicoline (2000 mg/day, 6 weeks in total) or placebo, started within 24 hours of onset
Follow-up
6 weeks of treatment; 90-day outcome
Study design
Randomized placebo-controlled trial, stopped for futility
Funding
Ferrer Grupo

Funded by Ferrer Grupo.

Read the original source
COBRIT: 1213 patients with traumatic brain injury, no benefit at 90 or 180 days

Randomized controlled trial

Zafonte RD et al. JAMA. 2012;308(19):1993-2000. PMID 23168823.

Functional and cognitive status did not differ at 90 days (global OR 0.98, 95% CI 0.83 to 1.15) or at 180 days (OR 0.87, 95% CI 0.72 to 1.04).

Participants / model
1213 patients with complicated mild, moderate or severe traumatic brain injury at 8 US level 1 trauma centers
Treatment
Citicoline 2000 mg/day (enteral or oral) or placebo
Follow-up
90 days of treatment; outcomes at 90 and 180 days
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The COBRIT report says citicoline is approved for traumatic brain injury in 59 countries; that is the authors' statement, not a regulator record.

Read the original source

What did the memory and cognition studies find?

Memory results are small and short. EFSA's 2024 opinion found a cause-and-effect relationship with memory has not been established, and the positive healthy-volunteer trials are small, partly industry-affiliated or limited to a post hoc subgroup.

EFSA's Panel on Nutrition evaluated a proposed EU health claim for citicoline inner salt and memory in middle-aged or older adults with age-associated subjective memory impairment. Of 3 pertinent studies in healthy people, only one randomized trial (500 mg/day for 12 weeks) showed an episodic-memory benefit. Another at 1 g/day for 3 months did not, and data in dementia at 1 g/day did not support it. The Panel concluded that a cause-and-effect relationship has not been established.

In 100 healthy adults aged 50 to 85 with age-associated memory impairment, citicoline 500 mg/day (n=49) versus placebo (n=51) for 12 weeks improved episodic memory (mean 0.15 versus 0.06) and a composite memory score (3.78 versus 0.72). Both were secondary outcomes, and the abstract does not report the primary outcome result. The abstract names a branded product (Cognizin), and the authors are affiliated with Kyowa Hakko Bio, Kyowa Hakko USA and Biofortis Innovation Services.

In 95 volunteers aged 50 to 85 screened free of dementia, citicoline 1000 mg/day for 3 months improved delayed logical-memory recall only in a subgroup with relatively inefficient memory, identified after the data were analyzed. In a follow-up crossover in 32 of those people, 2000 mg/day improved immediate and delayed recall. In 75 healthy adolescent males, citicoline 250 or 500 mg/day for 28 days improved attention (p=0.02) and psychomotor speed (p=0.03); the abstract names the same branded product, and 3 co-authors are affiliated with Kyowa Hakko Bio or Kyowa Hakko USA.

A Cochrane review of 14 heterogeneous double-blind trials in older people with chronic cerebral disorders, from subjective memory complaints to vascular cognitive impairment and dementia, found some evidence of benefit on memory and behavior in the short to medium term, no benefit on attention, and good tolerability. Most trials lasted 20 days to 3 months, and the principal reviewer had been an investigator in some included studies.

EFSA opinion, 2024: cause-and-effect between citicoline and memory not established

Regulatory record

Turck D et al. EFSA J. 2024;22(7):e8861. PMID 38966137.

EFSA's Panel on Nutrition evaluated a proposed EU health claim for citicoline inner salt and memory in middle-aged or older adults with age-associated subjective memory impairment. Of 3 pertinent studies in healthy people, only one randomized trial (500 mg/day for 12 weeks) showed an episodic-memory benefit; another at 1 g/day for 3 months did not, and data in dementia at 1 g/day did not support it. The Panel found no convincing mechanism by which citicoline or its components, beyond their own synthesis in the body, could affect memory, and concluded that a cause-and-effect relationship has not been established.

Participants / model
Middle-aged and older adults with age-associated subjective memory impairment (evidence reviewed)
Treatment
Oral citicoline inner salt
Follow-up
12 weeks and 3 months across the studies covered
Study design
Regulator scientific opinion on a health-claim application
Funding
not stated in the source

A health-claim opinion, not a drug approval decision.

Read the original source
Healthy older adults: 100 people, 12 weeks, secondary memory outcomes improved

Randomized controlled trial

Nakazaki E et al. J Nutr. 2021;151(8):2153-2160. PMID 33978188.

The citicoline group improved more on episodic memory (mean 0.15 versus 0.06) and on a composite memory score (3.78 versus 0.72). Both were secondary outcomes; the abstract does not report the primary outcome result.

Participants / model
100 healthy adults aged 50 to 85 with age-associated memory impairment (49 citicoline, 51 placebo)
Treatment
Oral citicoline 500 mg/day or placebo
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The abstract names a branded product (Cognizin), and the authors are affiliated with Kyowa Hakko Bio, Kyowa Hakko USA and Biofortis Innovation Services. The memory outcomes were secondary and used computerized tests.

Read the original source
Older volunteers: 95 people, benefit confined to a post hoc subgroup

Randomized controlled trial

Spiers PA et al. Arch Neurol. 1996;53(5):441-8. PMID 8624220.

Citicoline 1000 mg/day for 3 months improved delayed logical-memory recall only in a subgroup with relatively inefficient memory, identified after the data were analyzed. In a follow-up crossover in 32 of those people, 2000 mg/day improved immediate and delayed recall. The benefit was confined to a post hoc subgroup.

Participants / model
95 volunteers aged 50 to 85 screened free of dementia; 32 in the crossover
Treatment
Oral citicoline 1000 mg/day, then 2000 mg/day in the crossover
Follow-up
3 months
Study design
Randomized trials, with a post hoc subgroup analysis
Funding
not stated in the source

The benefit was confined to a post hoc subgroup.

Read the original source
Healthy adolescent males: 75 people, 28 days, attention and psychomotor speed improved

Randomized controlled trial

McGlade E et al. J Atten Disord. 2019;23(2):121-134. PMID 26179181.

Citicoline improved attention (p=0.02) and psychomotor speed (p=0.03).

Participants / model
75 healthy adolescent males
Treatment
Oral citicoline 250 or 500 mg/day (n=51) or placebo (n=24)
Follow-up
28 days
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The abstract names a branded product (Cognizin), and 3 co-authors are affiliated with Kyowa Hakko Bio or Kyowa Hakko USA.

Read the original source
Cochrane 2005: 14 trials, short-term memory and behavior signal, good tolerability

Systematic review and meta-analysis

Fioravanti M et al. Cochrane Database Syst Rev. 2005;2005(2):CD000269. PMID 15846601.

The review of 14 heterogeneous double-blind trials, most lasting 20 days to 3 months, found some evidence of benefit on memory and behavior in the short to medium term, no benefit on attention, and good tolerability. It describes CDP-choline as an essential precursor for phosphatidylcholine synthesis that the body also makes itself.

Participants / model
Older people with chronic cerebral disorders, from subjective memory complaints to vascular cognitive impairment and dementia
Treatment
CDP-choline at varying doses and routes
Follow-up
Most trials 20 days to 3 months
Study design
Systematic review and meta-analysis of 14 double-blind trials
Funding
not stated in the source

The principal reviewer had been an investigator in some included studies.

Read the original source

What did the stroke and brain injury trials find?

The large trials failed. ICTUS (2298 patients with acute ischemic stroke) stopped for futility, COBRIT (1213 patients with brain injury) found no benefit, and a 2020 Cochrane review found little or no difference on any stroke outcome.

ICTUS randomized 2298 patients with moderate-to-severe acute ischemic stroke in Germany, Portugal and Spain to citicoline or placebo within 24 hours of onset. It was stopped for futility, and 90-day global recovery was similar (OR 1.03, 95% CI 0.86 to 1.25), with no differences in safety variables. It was funded by Ferrer Grupo.

COBRIT randomized 1213 patients with complicated mild, moderate or severe traumatic brain injury at 8 US level 1 trauma centers to citicoline 2000 mg/day or placebo for 90 days. Functional and cognitive status did not differ at 90 days (global OR 0.98, 95% CI 0.83 to 1.15) or at 180 days (OR 0.87, 95% CI 0.72 to 1.04).

A Cochrane review of 10 randomized trials (4281 participants, all at high risk of bias, 6 company-sponsored) found little or no difference in all-cause mortality (17.3% versus 18.5%; RR 0.94, 95% CI 0.83 to 1.07), disability or dependence, serious cardiovascular adverse events, Barthel recovery or NIHSS recovery, all at low certainty.

Two analyses were more positive. An individual-patient pooling of 4 trials of oral citicoline started within 24 hours of moderate-to-severe ischemic stroke (1372 eligible patients) reported 3-month recovery of 25.2% versus 20.2% (OR 1.33, 95% CI 1.10 to 1.62). A meta-analysis of 10 trials, whose corresponding author's listed email is at ferrer.com, reported higher independence (random effects OR 1.56, 95% CI 1.12 to 2.16) and concluded citicoline offers limited benefit on top of rtPA. Its conclusion differs from the Cochrane review.

ICTUS: 2298 patients with acute ischemic stroke, stopped for futility

Randomized controlled trial

Dávalos A et al. Lancet. 2012;380(9839):349-57. PMID 22691567.

The trial was stopped for futility. 90-day global recovery was similar (OR 1.03, 95% CI 0.86 to 1.25), with no differences in safety variables.

Participants / model
2298 patients with moderate-to-severe acute ischemic stroke in Germany, Portugal and Spain
Treatment
Intravenous then oral citicoline (2000 mg/day, 6 weeks in total) or placebo, started within 24 hours of onset
Follow-up
6 weeks of treatment; 90-day outcome
Study design
Randomized placebo-controlled trial, stopped for futility
Funding
Ferrer Grupo

Funded by Ferrer Grupo.

Read the original source
COBRIT: 1213 patients with traumatic brain injury, no benefit at 90 or 180 days

Randomized controlled trial

Zafonte RD et al. JAMA. 2012;308(19):1993-2000. PMID 23168823.

Functional and cognitive status did not differ at 90 days (global OR 0.98, 95% CI 0.83 to 1.15) or at 180 days (OR 0.87, 95% CI 0.72 to 1.04).

Participants / model
1213 patients with complicated mild, moderate or severe traumatic brain injury at 8 US level 1 trauma centers
Treatment
Citicoline 2000 mg/day (enteral or oral) or placebo
Follow-up
90 days of treatment; outcomes at 90 and 180 days
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The COBRIT report says citicoline is approved for traumatic brain injury in 59 countries; that is the authors' statement, not a regulator record.

Read the original source
Cochrane 2020: 10 trials, 4281 participants, little or no difference

Systematic review and meta-analysis

Martí-Carvajal AJ et al. Cochrane Database Syst Rev. 2020;8(8):CD013066. PMID 32860632.

The review found little or no difference with citicoline in all-cause mortality (17.3% versus 18.5%; RR 0.94, 95% CI 0.83 to 1.07), disability or dependence, serious cardiovascular adverse events, Barthel recovery or NIHSS recovery, all at low certainty. Harms were poorly reported and the authors say the safety profile remains unknown.

Participants / model
4281 patients with acute ischemic stroke across 10 randomized trials (all at high risk of bias, 6 company-sponsored)
Treatment
Oral, intravenous or combined citicoline, 500 to 2000 mg/day
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 10 randomized trials
Funding
not stated in the source

All included trials were at high risk of bias and 6 were company-sponsored.

Read the original source
Pooled analysis: 4 trials, 1372 patients, 3-month recovery 25.2% versus 20.2%

Systematic review and meta-analysis

Dávalos A et al. Stroke. 2002;33(12):2850-7. PMID 12468781.

3-month recovery was 25.2% versus 20.2% (OR 1.33, 95% CI 1.10 to 1.62), with the largest difference at the highest dose. Safety was similar to placebo.

Participants / model
1372 patients with moderate-to-severe acute ischemic stroke (eligible from 1652 randomized)
Treatment
Oral citicoline 500, 1000 or 2000 mg/day, started within 24 hours of stroke
Follow-up
3 months
Study design
Individual-patient pooling of 4 randomized placebo-controlled trials, drawn from MEDLINE, Cochrane and Ferrer Group databases
Funding
not stated in the source

The pooled data include the Ferrer Group database. The later ICTUS trial did not confirm the result.

Read the original source
Stroke meta-analysis: 10 trials, higher independence, corresponding author at ferrer.com

Systematic review and meta-analysis

Secades JJ et al. J Stroke Cerebrovasc Dis. 2016;25(8):1984-96. PMID 27234918.

The meta-analysis reported higher rates of independence with citicoline (random effects OR 1.56, 95% CI 1.12 to 2.16; fixed effects OR 1.20, 95% CI 1.06 to 1.36) and concluded citicoline offers limited benefit on top of rtPA. Its conclusion differs from the Cochrane review.

Participants / model
Patients with acute ischemic stroke across 10 randomized double-blind trials
Treatment
Citicoline started within 14 days of onset
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 10 randomized double-blind trials
Funding
not stated in the source

The corresponding author's listed email is at ferrer.com.

Read the original source

Does citicoline improve memory and cognition?

Not established in healthy adults. EFSA found no cause-and-effect relationship in 2024, and the supporting trials are small, short and partly industry-run.

Sellers describe citicoline as a Kennedy pathway intermediate (CDP-choline) that improves memory and cognition. The molecule's role as a precursor for phosphatidylcholine synthesis is real, and the body also makes it itself. That role has not been shown to translate into a memory benefit in healthy adults.

EFSA's Panel found no convincing mechanism by which citicoline or its components, beyond their own synthesis in the body, could affect memory, and concluded in 2024 that a cause-and-effect relationship has not been established. The healthy-volunteer trials behind the claim include a 100-person trial whose primary outcome result is not reported in the abstract, a 95-person trial with a benefit only in a post hoc subgroup, and an adolescent trial, two of them with authors from Kyowa Hakko.

EFSA opinion, 2024: cause-and-effect between citicoline and memory not established

Regulatory record

Turck D et al. EFSA J. 2024;22(7):e8861. PMID 38966137.

EFSA's Panel on Nutrition evaluated a proposed EU health claim for citicoline inner salt and memory in middle-aged or older adults with age-associated subjective memory impairment. Of 3 pertinent studies in healthy people, only one randomized trial (500 mg/day for 12 weeks) showed an episodic-memory benefit; another at 1 g/day for 3 months did not, and data in dementia at 1 g/day did not support it. The Panel found no convincing mechanism by which citicoline or its components, beyond their own synthesis in the body, could affect memory, and concluded that a cause-and-effect relationship has not been established.

Participants / model
Middle-aged and older adults with age-associated subjective memory impairment (evidence reviewed)
Treatment
Oral citicoline inner salt
Follow-up
12 weeks and 3 months across the studies covered
Study design
Regulator scientific opinion on a health-claim application
Funding
not stated in the source

A health-claim opinion, not a drug approval decision.

Read the original source
Healthy older adults: 100 people, 12 weeks, secondary memory outcomes improved

Randomized controlled trial

Nakazaki E et al. J Nutr. 2021;151(8):2153-2160. PMID 33978188.

The citicoline group improved more on episodic memory (mean 0.15 versus 0.06) and on a composite memory score (3.78 versus 0.72). Both were secondary outcomes; the abstract does not report the primary outcome result.

Participants / model
100 healthy adults aged 50 to 85 with age-associated memory impairment (49 citicoline, 51 placebo)
Treatment
Oral citicoline 500 mg/day or placebo
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The abstract names a branded product (Cognizin), and the authors are affiliated with Kyowa Hakko Bio, Kyowa Hakko USA and Biofortis Innovation Services. The memory outcomes were secondary and used computerized tests.

Read the original source
Older volunteers: 95 people, benefit confined to a post hoc subgroup

Randomized controlled trial

Spiers PA et al. Arch Neurol. 1996;53(5):441-8. PMID 8624220.

Citicoline 1000 mg/day for 3 months improved delayed logical-memory recall only in a subgroup with relatively inefficient memory, identified after the data were analyzed. In a follow-up crossover in 32 of those people, 2000 mg/day improved immediate and delayed recall. The benefit was confined to a post hoc subgroup.

Participants / model
95 volunteers aged 50 to 85 screened free of dementia; 32 in the crossover
Treatment
Oral citicoline 1000 mg/day, then 2000 mg/day in the crossover
Follow-up
3 months
Study design
Randomized trials, with a post hoc subgroup analysis
Funding
not stated in the source

The benefit was confined to a post hoc subgroup.

Read the original source
Healthy adolescent males: 75 people, 28 days, attention and psychomotor speed improved

Randomized controlled trial

McGlade E et al. J Atten Disord. 2019;23(2):121-134. PMID 26179181.

Citicoline improved attention (p=0.02) and psychomotor speed (p=0.03).

Participants / model
75 healthy adolescent males
Treatment
Oral citicoline 250 or 500 mg/day (n=51) or placebo (n=24)
Follow-up
28 days
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The abstract names a branded product (Cognizin), and 3 co-authors are affiliated with Kyowa Hakko Bio or Kyowa Hakko USA.

Read the original source
Cochrane 2005: 14 trials, short-term memory and behavior signal, good tolerability

Systematic review and meta-analysis

Fioravanti M et al. Cochrane Database Syst Rev. 2005;2005(2):CD000269. PMID 15846601.

The review of 14 heterogeneous double-blind trials, most lasting 20 days to 3 months, found some evidence of benefit on memory and behavior in the short to medium term, no benefit on attention, and good tolerability. It describes CDP-choline as an essential precursor for phosphatidylcholine synthesis that the body also makes itself.

Participants / model
Older people with chronic cerebral disorders, from subjective memory complaints to vascular cognitive impairment and dementia
Treatment
CDP-choline at varying doses and routes
Follow-up
Most trials 20 days to 3 months
Study design
Systematic review and meta-analysis of 14 double-blind trials
Funding
not stated in the source

The principal reviewer had been an investigator in some included studies.

Read the original source

How does citicoline work, and what does blood show after a dose?

After an oral dose, blood shows rises in choline and uridine, not cytidine. A Cochrane review calls CDP-choline an essential precursor for phosphatidylcholine synthesis, and EFSA found no convincing mechanism for a memory effect.

In 12 mildly hypertensive but otherwise normal fasting adults given single oral doses of 500, 2000 or 4000 mg citicoline or placebo in random order, plasma choline rose with dose and stayed elevated for 5, 8 and 10 hours. Plasma uridine rose 70 to 90% after 500 mg and 100 to 120% after 2000 mg, with no further rise at 4000 mg, while cytidine was not reliably detectable.

The authors conclude the circulating substrates through which oral citicoline could raise brain phosphatide synthesis in humans are likely uridine and choline. A Cochrane review describes CDP-choline as an essential precursor for phosphatidylcholine synthesis that the body also makes itself, and EFSA's Panel found no convincing mechanism by which citicoline or its components could affect memory beyond their own synthesis in the body.

Single-dose PK: 12 adults, plasma choline and uridine rose, cytidine not detectable

Human study

Wurtman RJ et al. Biochem Pharmacol. 2000;60(7):989-92. PMID 10974208.

Plasma choline rose with dose and stayed elevated for 5, 8 and 10 hours at the three doses. Plasma uridine rose 70 to 90% after the lowest dose and 100 to 120% after the middle dose, with no further rise at the highest dose, while cytidine was not reliably detectable. The authors conclude the circulating substrates through which oral citicoline could raise brain phosphatide synthesis in humans are likely uridine and choline.

Participants / model
12 mildly hypertensive but otherwise normal fasting adults
Treatment
Single oral citicoline doses of 500, 2000 or 4000 mg, or placebo, in random order
Follow-up
Single doses
Study design
Randomized crossover pharmacokinetic study
Funding
not stated in the source

A single-dose study in 12 adults; it measures blood substrates, not memory or cognition.

Read the original source
Cochrane 2005: 14 trials, short-term memory and behavior signal, good tolerability

Systematic review and meta-analysis

Fioravanti M et al. Cochrane Database Syst Rev. 2005;2005(2):CD000269. PMID 15846601.

The review of 14 heterogeneous double-blind trials, most lasting 20 days to 3 months, found some evidence of benefit on memory and behavior in the short to medium term, no benefit on attention, and good tolerability. It describes CDP-choline as an essential precursor for phosphatidylcholine synthesis that the body also makes itself.

Participants / model
Older people with chronic cerebral disorders, from subjective memory complaints to vascular cognitive impairment and dementia
Treatment
CDP-choline at varying doses and routes
Follow-up
Most trials 20 days to 3 months
Study design
Systematic review and meta-analysis of 14 double-blind trials
Funding
not stated in the source

The principal reviewer had been an investigator in some included studies.

Read the original source
EFSA opinion, 2024: cause-and-effect between citicoline and memory not established

Regulatory record

Turck D et al. EFSA J. 2024;22(7):e8861. PMID 38966137.

EFSA's Panel on Nutrition evaluated a proposed EU health claim for citicoline inner salt and memory in middle-aged or older adults with age-associated subjective memory impairment. Of 3 pertinent studies in healthy people, only one randomized trial (500 mg/day for 12 weeks) showed an episodic-memory benefit; another at 1 g/day for 3 months did not, and data in dementia at 1 g/day did not support it. The Panel found no convincing mechanism by which citicoline or its components, beyond their own synthesis in the body, could affect memory, and concluded that a cause-and-effect relationship has not been established.

Participants / model
Middle-aged and older adults with age-associated subjective memory impairment (evidence reviewed)
Treatment
Oral citicoline inner salt
Follow-up
12 weeks and 3 months across the studies covered
Study design
Regulator scientific opinion on a health-claim application
Funding
not stated in the source

A health-claim opinion, not a drug approval decision.

Read the original source

What side effects and warnings are reported?

ICTUS found no differences in safety variables and a Cochrane review of older people reported good tolerability. A 2020 Cochrane stroke review found harms poorly reported and says the safety profile remains unknown.

ICTUS found no differences in safety variables, and the pooled analysis of 4 stroke trials reported safety similar to placebo. A Cochrane review of CDP-choline in older people with chronic cerebral disorders reported good tolerability.

The 2020 Cochrane stroke review found harms poorly reported, and the authors say the safety profile remains unknown. No primary source gives adverse-event rates for healthy-adult supplement use beyond the trial summaries above, so those rates are not established here.

ICTUS: 2298 patients with acute ischemic stroke, stopped for futility

Randomized controlled trial

Dávalos A et al. Lancet. 2012;380(9839):349-57. PMID 22691567.

The trial was stopped for futility. 90-day global recovery was similar (OR 1.03, 95% CI 0.86 to 1.25), with no differences in safety variables.

Participants / model
2298 patients with moderate-to-severe acute ischemic stroke in Germany, Portugal and Spain
Treatment
Intravenous then oral citicoline (2000 mg/day, 6 weeks in total) or placebo, started within 24 hours of onset
Follow-up
6 weeks of treatment; 90-day outcome
Study design
Randomized placebo-controlled trial, stopped for futility
Funding
Ferrer Grupo

Funded by Ferrer Grupo.

Read the original source
Pooled analysis: 4 trials, 1372 patients, 3-month recovery 25.2% versus 20.2%

Systematic review and meta-analysis

Dávalos A et al. Stroke. 2002;33(12):2850-7. PMID 12468781.

3-month recovery was 25.2% versus 20.2% (OR 1.33, 95% CI 1.10 to 1.62), with the largest difference at the highest dose. Safety was similar to placebo.

Participants / model
1372 patients with moderate-to-severe acute ischemic stroke (eligible from 1652 randomized)
Treatment
Oral citicoline 500, 1000 or 2000 mg/day, started within 24 hours of stroke
Follow-up
3 months
Study design
Individual-patient pooling of 4 randomized placebo-controlled trials, drawn from MEDLINE, Cochrane and Ferrer Group databases
Funding
not stated in the source

The pooled data include the Ferrer Group database. The later ICTUS trial did not confirm the result.

Read the original source
Cochrane 2020: 10 trials, 4281 participants, little or no difference

Systematic review and meta-analysis

Martí-Carvajal AJ et al. Cochrane Database Syst Rev. 2020;8(8):CD013066. PMID 32860632.

The review found little or no difference with citicoline in all-cause mortality (17.3% versus 18.5%; RR 0.94, 95% CI 0.83 to 1.07), disability or dependence, serious cardiovascular adverse events, Barthel recovery or NIHSS recovery, all at low certainty. Harms were poorly reported and the authors say the safety profile remains unknown.

Participants / model
4281 patients with acute ischemic stroke across 10 randomized trials (all at high risk of bias, 6 company-sponsored)
Treatment
Oral, intravenous or combined citicoline, 500 to 2000 mg/day
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 10 randomized trials
Funding
not stated in the source

All included trials were at high risk of bias and 6 were company-sponsored.

Read the original source
Cochrane 2005: 14 trials, short-term memory and behavior signal, good tolerability

Systematic review and meta-analysis

Fioravanti M et al. Cochrane Database Syst Rev. 2005;2005(2):CD000269. PMID 15846601.

The review of 14 heterogeneous double-blind trials, most lasting 20 days to 3 months, found some evidence of benefit on memory and behavior in the short to medium term, no benefit on attention, and good tolerability. It describes CDP-choline as an essential precursor for phosphatidylcholine synthesis that the body also makes itself.

Participants / model
Older people with chronic cerebral disorders, from subjective memory complaints to vascular cognitive impairment and dementia
Treatment
CDP-choline at varying doses and routes
Follow-up
Most trials 20 days to 3 months
Study design
Systematic review and meta-analysis of 14 double-blind trials
Funding
not stated in the source

The principal reviewer had been an investigator in some included studies.

Read the original source

Why does citicoline sit in C tier?

The Kennedy-pathway role is real, but the large trials failed and the positive signals come from small, short or sponsor-linked studies.

The C reflects a compound with a real biochemical role and a consistent but small short-term memory signal in older people with cerebral disorders, whose large trials failed. ICTUS (2298 patients) stopped for futility in acute stroke, COBRIT (1213) found no benefit in brain injury, and the 2020 Cochrane review found little or no difference on any stroke outcome.

The positive signals come from a pooled analysis and a meta-analysis with sponsor links, a Cochrane review of small short trials in older people with cerebral disorders, and small healthy-volunteer trials, two with authors from Kyowa Hakko. Memory and cognition benefits in healthy adults are not established.

ICTUS: 2298 patients with acute ischemic stroke, stopped for futility

Randomized controlled trial

Dávalos A et al. Lancet. 2012;380(9839):349-57. PMID 22691567.

The trial was stopped for futility. 90-day global recovery was similar (OR 1.03, 95% CI 0.86 to 1.25), with no differences in safety variables.

Participants / model
2298 patients with moderate-to-severe acute ischemic stroke in Germany, Portugal and Spain
Treatment
Intravenous then oral citicoline (2000 mg/day, 6 weeks in total) or placebo, started within 24 hours of onset
Follow-up
6 weeks of treatment; 90-day outcome
Study design
Randomized placebo-controlled trial, stopped for futility
Funding
Ferrer Grupo

Funded by Ferrer Grupo.

Read the original source
COBRIT: 1213 patients with traumatic brain injury, no benefit at 90 or 180 days

Randomized controlled trial

Zafonte RD et al. JAMA. 2012;308(19):1993-2000. PMID 23168823.

Functional and cognitive status did not differ at 90 days (global OR 0.98, 95% CI 0.83 to 1.15) or at 180 days (OR 0.87, 95% CI 0.72 to 1.04).

Participants / model
1213 patients with complicated mild, moderate or severe traumatic brain injury at 8 US level 1 trauma centers
Treatment
Citicoline 2000 mg/day (enteral or oral) or placebo
Follow-up
90 days of treatment; outcomes at 90 and 180 days
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The COBRIT report says citicoline is approved for traumatic brain injury in 59 countries; that is the authors' statement, not a regulator record.

Read the original source
Cochrane 2020: 10 trials, 4281 participants, little or no difference

Systematic review and meta-analysis

Martí-Carvajal AJ et al. Cochrane Database Syst Rev. 2020;8(8):CD013066. PMID 32860632.

The review found little or no difference with citicoline in all-cause mortality (17.3% versus 18.5%; RR 0.94, 95% CI 0.83 to 1.07), disability or dependence, serious cardiovascular adverse events, Barthel recovery or NIHSS recovery, all at low certainty. Harms were poorly reported and the authors say the safety profile remains unknown.

Participants / model
4281 patients with acute ischemic stroke across 10 randomized trials (all at high risk of bias, 6 company-sponsored)
Treatment
Oral, intravenous or combined citicoline, 500 to 2000 mg/day
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 10 randomized trials
Funding
not stated in the source

All included trials were at high risk of bias and 6 were company-sponsored.

Read the original source
Pooled analysis: 4 trials, 1372 patients, 3-month recovery 25.2% versus 20.2%

Systematic review and meta-analysis

Dávalos A et al. Stroke. 2002;33(12):2850-7. PMID 12468781.

3-month recovery was 25.2% versus 20.2% (OR 1.33, 95% CI 1.10 to 1.62), with the largest difference at the highest dose. Safety was similar to placebo.

Participants / model
1372 patients with moderate-to-severe acute ischemic stroke (eligible from 1652 randomized)
Treatment
Oral citicoline 500, 1000 or 2000 mg/day, started within 24 hours of stroke
Follow-up
3 months
Study design
Individual-patient pooling of 4 randomized placebo-controlled trials, drawn from MEDLINE, Cochrane and Ferrer Group databases
Funding
not stated in the source

The pooled data include the Ferrer Group database. The later ICTUS trial did not confirm the result.

Read the original source
Stroke meta-analysis: 10 trials, higher independence, corresponding author at ferrer.com

Systematic review and meta-analysis

Secades JJ et al. J Stroke Cerebrovasc Dis. 2016;25(8):1984-96. PMID 27234918.

The meta-analysis reported higher rates of independence with citicoline (random effects OR 1.56, 95% CI 1.12 to 2.16; fixed effects OR 1.20, 95% CI 1.06 to 1.36) and concluded citicoline offers limited benefit on top of rtPA. Its conclusion differs from the Cochrane review.

Participants / model
Patients with acute ischemic stroke across 10 randomized double-blind trials
Treatment
Citicoline started within 14 days of onset
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 10 randomized double-blind trials
Funding
not stated in the source

The corresponding author's listed email is at ferrer.com.

Read the original source
Cochrane 2005: 14 trials, short-term memory and behavior signal, good tolerability

Systematic review and meta-analysis

Fioravanti M et al. Cochrane Database Syst Rev. 2005;2005(2):CD000269. PMID 15846601.

The review of 14 heterogeneous double-blind trials, most lasting 20 days to 3 months, found some evidence of benefit on memory and behavior in the short to medium term, no benefit on attention, and good tolerability. It describes CDP-choline as an essential precursor for phosphatidylcholine synthesis that the body also makes itself.

Participants / model
Older people with chronic cerebral disorders, from subjective memory complaints to vascular cognitive impairment and dementia
Treatment
CDP-choline at varying doses and routes
Follow-up
Most trials 20 days to 3 months
Study design
Systematic review and meta-analysis of 14 double-blind trials
Funding
not stated in the source

The principal reviewer had been an investigator in some included studies.

Read the original source
Healthy older adults: 100 people, 12 weeks, secondary memory outcomes improved

Randomized controlled trial

Nakazaki E et al. J Nutr. 2021;151(8):2153-2160. PMID 33978188.

The citicoline group improved more on episodic memory (mean 0.15 versus 0.06) and on a composite memory score (3.78 versus 0.72). Both were secondary outcomes; the abstract does not report the primary outcome result.

Participants / model
100 healthy adults aged 50 to 85 with age-associated memory impairment (49 citicoline, 51 placebo)
Treatment
Oral citicoline 500 mg/day or placebo
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The abstract names a branded product (Cognizin), and the authors are affiliated with Kyowa Hakko Bio, Kyowa Hakko USA and Biofortis Innovation Services. The memory outcomes were secondary and used computerized tests.

Read the original source
Healthy adolescent males: 75 people, 28 days, attention and psychomotor speed improved

Randomized controlled trial

McGlade E et al. J Atten Disord. 2019;23(2):121-134. PMID 26179181.

Citicoline improved attention (p=0.02) and psychomotor speed (p=0.03).

Participants / model
75 healthy adolescent males
Treatment
Oral citicoline 250 or 500 mg/day (n=51) or placebo (n=24)
Follow-up
28 days
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The abstract names a branded product (Cognizin), and 3 co-authors are affiliated with Kyowa Hakko Bio or Kyowa Hakko USA.

Read the original source
EFSA opinion, 2024: cause-and-effect between citicoline and memory not established

Regulatory record

Turck D et al. EFSA J. 2024;22(7):e8861. PMID 38966137.

EFSA's Panel on Nutrition evaluated a proposed EU health claim for citicoline inner salt and memory in middle-aged or older adults with age-associated subjective memory impairment. Of 3 pertinent studies in healthy people, only one randomized trial (500 mg/day for 12 weeks) showed an episodic-memory benefit; another at 1 g/day for 3 months did not, and data in dementia at 1 g/day did not support it. The Panel found no convincing mechanism by which citicoline or its components, beyond their own synthesis in the body, could affect memory, and concluded that a cause-and-effect relationship has not been established.

Participants / model
Middle-aged and older adults with age-associated subjective memory impairment (evidence reviewed)
Treatment
Oral citicoline inner salt
Follow-up
12 weeks and 3 months across the studies covered
Study design
Regulator scientific opinion on a health-claim application
Funding
not stated in the source

A health-claim opinion, not a drug approval decision.

Read the original source

Studies and sources

PubChem: citicoline and citicoline sodium identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 13804 (citicoline, CDP-choline, cytidine 5'-diphosphocholine) and CID 36605 (citicoline sodium).

Citicoline (CDP-choline, cytidine 5'-diphosphocholine): C14H26N4O11P2, 488.32 g/mol, CAS 987-78-0. Citicoline sodium: CID 36605, C14H25N4NaO11P2, 510.31 g/mol, CAS 33818-15-4. Products use either the inner salt or the sodium salt, so label milligrams are not identical amounts of citicoline.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source
openFDA query, 9 October 2026: no citicoline application

Regulatory record

U.S. Food and Drug Administration. openFDA Drugs@FDA query for citicoline or citicoline sodium (brand, generic and active-ingredient fields), run on 9 October 2026.

The query returned no application, so no FDA-approved citicoline drug was located. Trial reports describe approvals elsewhere: the ICTUS report says citicoline is approved in some countries for acute ischemic stroke, and the COBRIT report says it is approved for traumatic brain injury in 59 countries. Those are the trial authors' statements, not regulator records.

Participants / model
FDA application database, not a clinical population
Treatment
Exact substance-name query
Follow-up
Query run on 9 October 2026
Study design
Dated US approval-record query
Funding
not stated in the source

A negative query on one date is not proof about every product or jurisdiction. Approvals outside the United States were not confirmed with a regulator record, and US supplement status is not established here.

Read the original source
EFSA opinion, 2024: cause-and-effect between citicoline and memory not established

Regulatory record

Turck D et al. EFSA J. 2024;22(7):e8861. PMID 38966137.

EFSA's Panel on Nutrition evaluated a proposed EU health claim for citicoline inner salt and memory in middle-aged or older adults with age-associated subjective memory impairment. Of 3 pertinent studies in healthy people, only one randomized trial (500 mg/day for 12 weeks) showed an episodic-memory benefit; another at 1 g/day for 3 months did not, and data in dementia at 1 g/day did not support it. The Panel found no convincing mechanism by which citicoline or its components, beyond their own synthesis in the body, could affect memory, and concluded that a cause-and-effect relationship has not been established.

Participants / model
Middle-aged and older adults with age-associated subjective memory impairment (evidence reviewed)
Treatment
Oral citicoline inner salt
Follow-up
12 weeks and 3 months across the studies covered
Study design
Regulator scientific opinion on a health-claim application
Funding
not stated in the source

A health-claim opinion, not a drug approval decision.

Read the original source
Single-dose PK: 12 adults, plasma choline and uridine rose, cytidine not detectable

Human study

Wurtman RJ et al. Biochem Pharmacol. 2000;60(7):989-92. PMID 10974208.

Plasma choline rose with dose and stayed elevated for 5, 8 and 10 hours at the three doses. Plasma uridine rose 70 to 90% after the lowest dose and 100 to 120% after the middle dose, with no further rise at the highest dose, while cytidine was not reliably detectable. The authors conclude the circulating substrates through which oral citicoline could raise brain phosphatide synthesis in humans are likely uridine and choline.

Participants / model
12 mildly hypertensive but otherwise normal fasting adults
Treatment
Single oral citicoline doses of 500, 2000 or 4000 mg, or placebo, in random order
Follow-up
Single doses
Study design
Randomized crossover pharmacokinetic study
Funding
not stated in the source

A single-dose study in 12 adults; it measures blood substrates, not memory or cognition.

Read the original source
Pooled analysis: 4 trials, 1372 patients, 3-month recovery 25.2% versus 20.2%

Systematic review and meta-analysis

Dávalos A et al. Stroke. 2002;33(12):2850-7. PMID 12468781.

3-month recovery was 25.2% versus 20.2% (OR 1.33, 95% CI 1.10 to 1.62), with the largest difference at the highest dose. Safety was similar to placebo.

Participants / model
1372 patients with moderate-to-severe acute ischemic stroke (eligible from 1652 randomized)
Treatment
Oral citicoline 500, 1000 or 2000 mg/day, started within 24 hours of stroke
Follow-up
3 months
Study design
Individual-patient pooling of 4 randomized placebo-controlled trials, drawn from MEDLINE, Cochrane and Ferrer Group databases
Funding
not stated in the source

The pooled data include the Ferrer Group database. The later ICTUS trial did not confirm the result.

Read the original source
ICTUS: 2298 patients with acute ischemic stroke, stopped for futility

Randomized controlled trial

Dávalos A et al. Lancet. 2012;380(9839):349-57. PMID 22691567.

The trial was stopped for futility. 90-day global recovery was similar (OR 1.03, 95% CI 0.86 to 1.25), with no differences in safety variables.

Participants / model
2298 patients with moderate-to-severe acute ischemic stroke in Germany, Portugal and Spain
Treatment
Intravenous then oral citicoline (2000 mg/day, 6 weeks in total) or placebo, started within 24 hours of onset
Follow-up
6 weeks of treatment; 90-day outcome
Study design
Randomized placebo-controlled trial, stopped for futility
Funding
Ferrer Grupo

Funded by Ferrer Grupo.

Read the original source
Cochrane 2020: 10 trials, 4281 participants, little or no difference

Systematic review and meta-analysis

Martí-Carvajal AJ et al. Cochrane Database Syst Rev. 2020;8(8):CD013066. PMID 32860632.

The review found little or no difference with citicoline in all-cause mortality (17.3% versus 18.5%; RR 0.94, 95% CI 0.83 to 1.07), disability or dependence, serious cardiovascular adverse events, Barthel recovery or NIHSS recovery, all at low certainty. Harms were poorly reported and the authors say the safety profile remains unknown.

Participants / model
4281 patients with acute ischemic stroke across 10 randomized trials (all at high risk of bias, 6 company-sponsored)
Treatment
Oral, intravenous or combined citicoline, 500 to 2000 mg/day
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 10 randomized trials
Funding
not stated in the source

All included trials were at high risk of bias and 6 were company-sponsored.

Read the original source
Stroke meta-analysis: 10 trials, higher independence, corresponding author at ferrer.com

Systematic review and meta-analysis

Secades JJ et al. J Stroke Cerebrovasc Dis. 2016;25(8):1984-96. PMID 27234918.

The meta-analysis reported higher rates of independence with citicoline (random effects OR 1.56, 95% CI 1.12 to 2.16; fixed effects OR 1.20, 95% CI 1.06 to 1.36) and concluded citicoline offers limited benefit on top of rtPA. Its conclusion differs from the Cochrane review.

Participants / model
Patients with acute ischemic stroke across 10 randomized double-blind trials
Treatment
Citicoline started within 14 days of onset
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 10 randomized double-blind trials
Funding
not stated in the source

The corresponding author's listed email is at ferrer.com.

Read the original source
COBRIT: 1213 patients with traumatic brain injury, no benefit at 90 or 180 days

Randomized controlled trial

Zafonte RD et al. JAMA. 2012;308(19):1993-2000. PMID 23168823.

Functional and cognitive status did not differ at 90 days (global OR 0.98, 95% CI 0.83 to 1.15) or at 180 days (OR 0.87, 95% CI 0.72 to 1.04).

Participants / model
1213 patients with complicated mild, moderate or severe traumatic brain injury at 8 US level 1 trauma centers
Treatment
Citicoline 2000 mg/day (enteral or oral) or placebo
Follow-up
90 days of treatment; outcomes at 90 and 180 days
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The COBRIT report says citicoline is approved for traumatic brain injury in 59 countries; that is the authors' statement, not a regulator record.

Read the original source
Cochrane 2005: 14 trials, short-term memory and behavior signal, good tolerability

Systematic review and meta-analysis

Fioravanti M et al. Cochrane Database Syst Rev. 2005;2005(2):CD000269. PMID 15846601.

The review of 14 heterogeneous double-blind trials, most lasting 20 days to 3 months, found some evidence of benefit on memory and behavior in the short to medium term, no benefit on attention, and good tolerability. It describes CDP-choline as an essential precursor for phosphatidylcholine synthesis that the body also makes itself.

Participants / model
Older people with chronic cerebral disorders, from subjective memory complaints to vascular cognitive impairment and dementia
Treatment
CDP-choline at varying doses and routes
Follow-up
Most trials 20 days to 3 months
Study design
Systematic review and meta-analysis of 14 double-blind trials
Funding
not stated in the source

The principal reviewer had been an investigator in some included studies.

Read the original source
Healthy older adults: 100 people, 12 weeks, secondary memory outcomes improved

Randomized controlled trial

Nakazaki E et al. J Nutr. 2021;151(8):2153-2160. PMID 33978188.

The citicoline group improved more on episodic memory (mean 0.15 versus 0.06) and on a composite memory score (3.78 versus 0.72). Both were secondary outcomes; the abstract does not report the primary outcome result.

Participants / model
100 healthy adults aged 50 to 85 with age-associated memory impairment (49 citicoline, 51 placebo)
Treatment
Oral citicoline 500 mg/day or placebo
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The abstract names a branded product (Cognizin), and the authors are affiliated with Kyowa Hakko Bio, Kyowa Hakko USA and Biofortis Innovation Services. The memory outcomes were secondary and used computerized tests.

Read the original source
Older volunteers: 95 people, benefit confined to a post hoc subgroup

Randomized controlled trial

Spiers PA et al. Arch Neurol. 1996;53(5):441-8. PMID 8624220.

Citicoline 1000 mg/day for 3 months improved delayed logical-memory recall only in a subgroup with relatively inefficient memory, identified after the data were analyzed. In a follow-up crossover in 32 of those people, 2000 mg/day improved immediate and delayed recall. The benefit was confined to a post hoc subgroup.

Participants / model
95 volunteers aged 50 to 85 screened free of dementia; 32 in the crossover
Treatment
Oral citicoline 1000 mg/day, then 2000 mg/day in the crossover
Follow-up
3 months
Study design
Randomized trials, with a post hoc subgroup analysis
Funding
not stated in the source

The benefit was confined to a post hoc subgroup.

Read the original source
Healthy adolescent males: 75 people, 28 days, attention and psychomotor speed improved

Randomized controlled trial

McGlade E et al. J Atten Disord. 2019;23(2):121-134. PMID 26179181.

Citicoline improved attention (p=0.02) and psychomotor speed (p=0.03).

Participants / model
75 healthy adolescent males
Treatment
Oral citicoline 250 or 500 mg/day (n=51) or placebo (n=24)
Follow-up
28 days
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The abstract names a branded product (Cognizin), and 3 co-authors are affiliated with Kyowa Hakko Bio or Kyowa Hakko USA.

Read the original source

Why is Citicoline in C tier?

C fits a compound with a real biochemical role and a small, short-term memory signal in older people with cerebral disorders, but with failed large trials. The healthy-adult memory claim rests on small, short trials, some with industry-affiliated authors, and EFSA found no cause-and-effect relationship.