Citicoline (CDP-Choline)

Fioravanti and Yanagi (Cochrane Database Syst Rev, 2005; PMID 15846601): meta-analysis of 14 trials of CDP-choline for cognitive and behavioral disturbance in chronic cerebral disorders of the elderly, reporting benefit on memory and behavior and no evidence of benefit on attention; the trials were heterogeneous in dose, route of administration, inclusion criteria and outcome measures, and seven of them lasted 20 to 30 days. The review declares that its principal reviewer was an investigator in some of the included studies. The grade rests on this review. Bonvicini et al. (Nutrients, 2023; PMID 36678257): later meta-analysis of six studies in mild cognitive impairment, Alzheimer's disease or post-stroke dementia, positive in every analysis, with the authors rating the overall quality of the studies poor and the risk of bias in favor of the intervention significant. Spiers et al. (Arch Neurol, 1996; PMID 8624220): NIH-funded randomized trial in 95 healthy volunteers aged 50 to 85 at 1,000 mg/day for 3 months; verbal memory improved only in a subgroup identified after the data were analyzed as having relatively inefficient memories, and a crossover at 2,000 mg/day in 32 of those subjects improved immediate and delayed recall. Cotroneo et al. (Clin Interv Aging, 2013; PMID 23403474) is the IDEALE study in mild vascular cognitive impairment at 500 mg twice daily; it is an open multicenter study with a non-randomized control group, and is context rather than evidence. A 2016 review by Secades (Rev Neurol; PMID 28417449) is linked on this page for readers who go looking for it, and is not counted toward the grade: it was authored from the company that manufactures citicoline. Nakazaki et al. (J Nutr, 2021; PMID 33978188) is linked on the same terms and is also not counted. It is the randomized trial most often cited for citicoline in healthy older adults with age-associated memory impairment, and two things in its own record keep it off the grade: the improvements it reports for episodic and composite memory are labeled secondary outcomes in the abstract, with no primary endpoint reported as met, and its first author's listed affiliation is the company that manufactures the citicoline ingredient supplied to supplement makers. That is two independent manufacturer-affiliated papers behind the use this compound is most sold for, which is why both are shown rather than omitted. Against: Cohen et al. (Cerebrovasc Dis, 2003; PMID 12865605), the only 12-month double-blind trial (30 patients with vascular dementia, 500 mg twice daily), found no difference from placebo on cognition or MRI, and EFSA Panel on Nutrition (EFSA J, 2024; PMID 38966137) concluded a cause-and-effect relation with memory in older adults was not established.