Citicoline (also known as CDP-choline; cytidine 5'-diphosphocholine) is a naturally occurring compound that serves as a precursor for essential cellular nutrients, including choline, which is used in the production of cell membranes, and acetylcholine, a brain chemical important for memory. Insufficient brain levels of choline may contribute to memory loss and the breakdown of cell membranes in Alzheimer’s disease. Citicoline is considered the form of choline best absorbed by the brain. It is a common ingredient in supplements marketed for brain support, but there is no evidence to date that it can prevent dementia. No serious safety issues have been reported with citicoline treatment.
Clinical trials testing citicoline have been small with possible benefits depending on different factors. Large confirmatory randomized clinical trials are needed.
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Short-term treatment with citicoline has shown benefits in individuals with lower cognition at the beginning of studies, but due to discrepancies across studies, there is insufficient evidence that it is beneficial in healthy people with otherwise good cognition.
Citicoline supplementation improved speed in cognitive tasks in teenage boys [1], and reaction time in young adults in their 20s [2; 3]. However, another small study in young men found that while performance on measures of processing speed, memory, and executive function improved following supplementation in low performers, it declined slightly in those with high performance at baseline [4]. Similarly, improvements in memory in healthy elderly adults have primarily been observed in those with memory problems [5]. One study in healthy middle-aged women reported that citicoline improved attention [6], while another study in healthy middle age to older adults found a small effect on memory but no effects on attention [7]. Reduction in markers of oxidative stress have also been observed with citicoline supplementation [3].
No studies have examined whether citicoline can prevent dementia, but studies to date have shown little to no benefit regarding protection against stroke or brain injury-related cognitive impairment. Citicoline has not shown benefits in ischemic stroke relative to the current standard of care [8; 9; 10]. In traumatic brain injury, modest neuroprotection has been observed with intravenous citicoline, while no clear benefits have been observed with other forms of administration [11].
The impact of APOE4 on the effects of citicoline is unclear. One small pilot study in people with the APOE4 variant reported that citicoline treatment for three months improved cognition compared to patients on a placebo [12], another study reported that APOE4 carriers showed less benefit [13], while a third study indicated that cognitive benefits were independent of APOE4 status [14]. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.
Pilot studies suggest that citicoline may provide cognitive benefits in patients with Alzheimer's disease, but no large randomized controlled trials have been conducted [12; 15; 16; 17]. Five case-control observational studies reported cognitive benefits when citicoline is added to standard-of-care symptomatic treatments for Alzheimer’s disease relative to those receiving the standard-of-care alone. The modest effects on cognition generally required citicoline treatment for at least nine to 12 months [18; 19; 20; 21; 22]. Some studies also suggest citicoline may be beneficial for patients with vascular cognitive impairment [14; 23; 24], and may allow for lower levodopa doses in patients with Parkinson’s disease [25].
No serious safety issues have been reported with citicoline treatment [26]. In a meta-analysis of trials for cerebral dysfunction in elderly people, citicoline tended to be more tolerable than the placebo [23]. Longer term treatment, up to three years, shows a similar safety profile as short-term supplementation. Drug interactions with citicoline are not well studied, though it may interact with Parkinson's drugs such as levodopa (drugs.com).
NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.
Citicoline is available as a single supplement or as one ingredient in some supplements marketed to promote brain health. Typical doses are 250–1,000 mg/day. According to the European Food Safety Authority, the recommended maximum daily dose of citicoline is 500 mg/day for supplements and 1,000 mg/day for medical foods in middle-aged to elderly adults [27]. For healthy individuals, lower doses (e.g. 250 mg/day) may provide more benefit than higher doses [6], while most clinical studies in patients with neurological disease used doses of 1,000 mg/day. In dementia patients, treatment for at least 12 months was generally required to see evidence of cognitive benefit.
Full scientific report (PDF) on Cognitive Vitality Reports
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