Citicoline Emerges as a Key Nutrient for Brain Health

Citicoline is an endogenous nucleotide that serves as a pivotal intermediate in the synthesis of phosphatidylcholine, the principal phospholipid of human cell membranes. As an extensively used dietary supplement, its benefits for cognition and behavior have been clinically validated, yet the precise neuroprotective mechanisms remain to be fully elucidated.

Modulating neuronal activity

At the cellular level, citicoline modulates neuronal activity in a clearly dose-dependent manner. Using a tri-culture system derived from human induced pluripotent stem cells (iPSC) that comprises cortical neurons, astrocytes, and microglia, investigators observed statistically significant differences in cell-activity parameters after citicoline treatment compared with controls. Micro-electrode array recordings and RNA-sequencing revealed that citicoline influences cellular function by regulating specific molecular pathways within neuronal network models, providing crucial clues to its neuroprotective actions.

A superior choline source

Relative to other choline donors, citicoline offers distinct metabolic-safety advantages. On a molar basis, its acute toxicity is markedly lower than that of choline. More importantly, citicoline is not readily hydrolyzed in the gut to trimethylamine (TMA), thereby limiting formation of its oxidized metabolite trimethylamine-N-oxide (TMAO)—a molecule implicated in cardiovascular disease, cognitive decline, and other disorders. These properties make citicoline a safer form of choline supplementation.

Enhancing cognitive function

Citicoline’s advantages are most pronounced in cognitive protection. Epidemiological studies show that choline intake correlates strongly with cognitive performance in both adults and the elderly, and citicoline outperforms ordinary choline or phosphatidylcholine in improving cognition. Clinical trials confirm that it can heighten attention and psychomotor speed in adolescents, ameliorate symptoms in patients with vascular cognitive impairment, and even potentiate the effects of cholinesterase inhibitors in dementia. These effects are likely linked to its role as a phosphatidylcholine precursor in membrane synthesis and its facilitation of acetylcholine production.

Although citicoline’s potential to sustain brain health has been preliminarily validated, its detailed molecular mechanisms still need further dissection. Continued advances in research technologies will deepen our understanding of its roles in modulating neuroinflammation, stabilizing neuronal networks, and more, thereby providing a stronger scientific foundation for its use in preventing and ameliorating neurodegenerative diseases.

References:

• 1. Nakazaki E, Lili L, Zhang B, et al. Investigating specific molecular and functional impacts of citicoline on brain health. Curr Dev Nutr. 2024;8(Suppl 2):103221.
• 2. Synoradzki K, Grieb P. Citicoline: a superior form of choline? Nutrients. 2019;11(7):1569.

*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.

by GSHWORLD

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