CYTICHOLINE

CYTICHOLINE

MECHANISM OF ACTION AND LITERATURE

Choline is an important nutrient known to positively influence brain development and have anti-aging functions. Choline is essential for various biological functions of cells. For example, choline metabolites acetylcholine and phosphatidylcholine, respectively, contribute to proper signaling functions for normal cholinergic neurotransmission and the structural integrity of cell membranes. Brain choline uptake decreases in older adults, and low extracellular choline supply may contribute to age-related cognitive decline. Unsurprisingly, higher dietary choline is associated with better cognitive performance in older individuals. One method of increasing dietary choline intake is supplementation with citicoline (CDP-choline or cytidine-5-diphosphate choline). Compared to the choline portion obtained from other dietary sources such as phosphatidylcholine, it has been suggested that the choline in citicoline is less prone to conversion to trimethylamine (TMA) and trimethylamine N-oxide (TMAO), which are involved in the pathogenesis of cardiovascular disease. Citicoline is a mononucleotide composed of naturally occurring components of cytosine, ribose, pyrophosphate, and choline. Citicoline is produced by the body as an intermediate product of phosphatidylcholine and sphingomyelin biosynthesis. Citicoline's neuroprotective effects include activating the biosynthesis of structural phospholipids in neuronal membranes, increasing cerebral metabolism, norepinephrine and dopamine levels in the central nervous system, preventing cardiolipin loss, and protecting cell membranes by accelerating phospholipid resynthesis. Unsurprisingly, citicoline supplementation has demonstrated beneficial effects on memory function and behavior in populations with a wide range of disorders, such as those with mild to moderate vascular cognitive impairment, vascular dementia, or senile dementia.

PUBLICATIONS ON THE SUBJECT:

** Nutr. 2021 Aug 7;151(8):2153-2160.doi: 10.1093/jn/nxab119.
Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349115/pdf/nxab119.pdf

** J Neurochem. 2002 Jan;80(1):12-23.doi: 10.1046/j.0022-3042.2001.00697.x.
Citicoline: neuroprotective mechanisms in cerebral ischemia
https://onlinelibrary.wiley.com/doi/epdf/10.1046/j.0022-3042.2001.00697.x

** Clin Interv Aging. 2013;8:131-7.doi: 10.2147/CIA.S38420.
Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569046/pdf/cia-8-131.pdf

** J Pharmacol Sci. 2011;116(2):232-7. doi: 10.1254/jphs.11013fp.
Neuroprotective effects of citidine-5-diphosphocholine on impaired spatial memory in a rat model of cerebrovascular dementia
https://pubmed.ncbi.nlm.nih.gov/21613753/

** Clin Interv Aging. 2012;7:113-8.doi: 10.2147/CIA.S29366.
Retrospective and observational study to assess the efficacy of citicoline in elderly patients suffering from stupor related to complex geriatric syndrome
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3363302/pdf/cia-7-113.pdf

** Clin Interv Aging. 2015;10:1421–1429.doi: 10.2147/CIA.S87886
The role of citicoline in cognitive impairment: pharmacological characteristics, possible advantages, and doubts for an old drug with new perspectives
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562749/pdf/cia-10-1421.pdf