Citicoline for Supporting Memory in Aging Humans

Abstract

Citicoline is the generic name of CDP-choline, a natural metabolite presents in all living cells. Used in medicine as a drug since the 1980-s, citicoline was recently pronounced a food ingredient. When ingested, citicoline breaks down to cytidine and choline, which become incorporated into their respective normal metabolic pathways. Choline is a precursor of acetylcholine and phospholipids; these is a neurotransmitter pivotal for learning and memory and important constituents of neuronal membranes and myelin sheaths, respectively. Cytidine in humans is readily converted to uridine, which exerts a positive effect on synaptic function and supports the formation of synaptic membranes. Choline deficiency has been found to be correlated with memory dysfunction. Magnetic resonance spectroscopy studies showed that citicoline intake improves brain uptake of choline in older persons, suggestive of that it shall help in reversing early age-related cognitive changes. In randomized, placebo-controlled trials of cognitively normal middle-aged and elderly persons, positive effects of citicoline on memory efficacy were found. Similar effects of citicoline on memory indices were also found in patients suffering from mild cognitive impairment and some other neurological diseases. Altogether, the aforementioned data provide complex and unambiguous evidence supporting the claim that oral citicoline intake positively influences memory function in humans who encounter age-related memory impairment also in the absence of any detectable neurological or psychiatric disease.

Figure 1.

Major metabolic pathways of citicoline following ingestion. 1. Hydrolysis and dephosphorylation of citicoline occur in blood and yield choline and cytidine (in humans converted to uridine) that enter brain. 2. In the brain cytidine is activated by phosphorylation to cytidine-triphosphate (CTP). Choline, which concomitantly enters the brain, follows three major paths: 3. activation by phosphorylation to phosphocholine; 4. conversion to betaine (N,N,N-trimethylglycine); 5. conversion to acetylcholine (a neurotransmitter). 6. CTP and phosphocholine rejoin to yield CDP-choline, which 7. is used to synthesize phosphatidylcholine, utilized to support membrane integrity and myelin metabolism.