Peptides›Cognitive›Citicoline

Citicoline

/ CDP-choline (small molecule, nucleotide-choline conjugate)

TIER 2 · TranslationalN = 0 · TESTING PENDINGMW 488.32 g·mol⁻¹

ALIAS · CDP-choline · Cytidine 5'-diphosphocholine · Somazina (trade) · Ceraxon (trade) · Cognizin (supplement brand)

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequence— sequence not captured —

MW · 488.32CLASS · CDP-choline (small molecule, nucleotide-choline conjugate)CATEGORY · Cognitive

Tier 2. Approved in many EU countries and Japan for ischemic stroke and post-stroke cognitive recovery; sold in the US as a dietary supplement (Cognizin and other brands). The pivotal ICTUS Phase 3 trial (2012) was negative for the primary endpoint in acute ischemic stroke.

§ B · Mechanism of action

Citicoline (cytidine 5'-diphosphocholine) is an endogenous intermediate in the Kennedy pathway of phosphatidylcholine biosynthesis. Exogenous citicoline is hydrolysed to cytidine and choline, which cross the blood-brain barrier and are reincorporated into CDP-choline within neurons. Proposed neuroprotective mechanisms include support of membrane phospholipid synthesis after ischemic injury, reduction of free fatty acid release, and downstream cholinergic and dopaminergic effects.

§ C · Human clinical evidence

Tier 2. The ICTUS Phase 3 trial (Davalos and colleagues, Lancet 2012) randomised approximately 2,300 acute ischemic stroke patients to citicoline or placebo and found no improvement in 90-day functional outcomes; this trial ended European regulatory enthusiasm for the acute-stroke indication. The IDEALE trial (Cotroneo and colleagues 2013) in mild vascular cognitive impairment reported modest cognitive measure differences. The supplement literature in healthy adults is heterogeneous and underpowered.

§ D · Primary literature

PubMed22691567Davalos A et al. — Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial) · The Lancet · human-phase-3-rctCiticoline did not improve 90-day modified Rankin Scale outcomes versus placebo in acute ischemic stroke; the trial was stopped for futility.Limitations: Single Phase 3 trial; standardised stroke care during the trial may have raised the floor for incremental benefit.2012

PubMed23403474Cotroneo AM et al. — Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study · Clinical Interventions in Aging · human-phase-2Open-label citicoline 1000 mg/day for 9 months was associated with stable MMSE scores in the treated group versus decline in untreated controls in mild vascular cognitive impairment.Limitations: Open-label, non-randomised treatment allocation; substantial confounding by indication; modest absolute differences.2013

§ F · Safety signal

Generally well-tolerated across decades of European clinical use. Reported adverse events include gastrointestinal upset, headache, and insomnia. The drug has a long safety record at gram-scale daily doses.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The negative ICTUS trial is a load-bearing fact: prior smaller positive trials had supported European approval, but the rigorous large Phase 3 did not replicate efficacy in acute stroke. The compound persists in clinical use in some jurisdictions and as a dietary supplement marketed for cognition in healthy adults, but the supportive evidence in non-stroke populations is limited.