Side effects of Citicoline

Citicoline，also known as CDP-choline or cytidine-5-diphosphatecholine,is a naturally occurring endogenousnucleoside. Citicoline functions as an intermediate in threemajor metabolic pathways:

(1)synthesis of phosphatidylcholine (lecithin), one of themajor cell membrane phospholipids with an important rolein lipoprotein formation.Citicoline formation is the rate-limiting step in the synthesis of phosphatidylcholine.

(2)Synthesis of ACh: citicoline by providing choline for thisneurotransmitter could limit choline availability for mem-brane synthesis.

(3) Oxidation to betaine,a methyl donor. The main components of citicoline, cholineand cytidine, are readily absorbed in the gastrointestinaltract and cross the BBB.As adietary supplement, choline is part of the vitamin-B group.A related product, choline alphoscerate, has also been usedless frequently.

Uses

Citicoline has been used in a number of trials in AD patients showing consistent moderate improvement of memory and behaviour.

Side effects

Citicoline has a very low toxicity profile in animals and humans. Clinically, doses of 2000 mg per day have been observed and approved. Minor transient adverse effects are rare and most commonly include stomach pain and diarrhea.There have been suggestions that chronic citicoline use may have adverse psychiatric effects. However, a meta-analysis of the relevant literature does not support this hypothesis.At most, citicoline may exacerbate psychotic episodes or interact with anti-psychotic medication.

Synthesis

In vivo

Phosphatidylcholine is a major phospholipid in eukaryotic cell membranes. Close regulation of its biosynthesis, degradation, and distribution is essential to proper cell function. Phosphatidylcholine is synthesized in vivo by two pathways

The Kennedy pathway, which includes the transformation of choline to citicoline, by way of phosphorylcholine, to produce phosphatidylcholine when condensed with diacylglycerol.

Phosphatidylcholine can also be produced by the methylation pathway, where phosphatidylethanolamine is sequentially methylated.

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