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Citicoline Overview:

citicolineCDP-choline, also known as citicoline, is a bioavailable form of choline that is absorbed in the gut and quickly broken down to it’s constituent parts cytidine and free choline. Both compounds then cross the blood brain barrier. Inside the brain, choline is required for the production of the neuotransmitter acetylcholine and for cell membrane synthesis.

After absorption the nucleoside cytidine is converted to uridine which subsequently lends a hand in cell membrane synthesis via the kennedy cycle. CDP-choline’s potency as a choline source and nootroopic is often placed on par with Alpha GPC, however there are distinct differences between the compounds as noted below.

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Other names:

Cytidine Diphosphocholine, Citicoline, CDP-Choline, cytidine 5′-diphosphocholine.

Important Information

Dosing Citicoline

Typical dosing in clinical research has varied from 500mg-2000mg per day (4).

For nootropic uses, including memory and attention enhancement , most healthy adult users would find 250-1000mg per day sufficient with one study noting 250mg just as effective as 500mg per day for enhanced attention span(5). Higher doses (1000mg/day) have been with the elderly (6)(7).

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Citicholine Absorption

Citicoline is water soluble and over 95% of an oral dose is absorbed (1).  After gastrointestinal absorption, citicoline is split into its constituent molecules; choline and cytidine.  CDP-choline has been noted to raise plasma levels of choline and uridine in humans, but has not been found to raise plasma cytidine. (2). This is due to cytidine’s rapid conversion to uridine within the body (3).

While CDP choline is a naturally occurring intermediary for the creation of PC, it’s oral administration results in it being quickly broken down into it’s constituent parts, choline and cytidine (converted to uridine). One study demonstrates that 30 minutes following direct infusion of CDP into the bloodstream, it’s levels are undetectable, while plasma uridine and choline have been elevated (20)  This confirms that CDP does not cross the blood brain barrier directly, but rather it’s constituent parts do.

Editors Note: Though CDP-choline is essentially choline and the nucleoside cytidine, it doesn’t raise cytidine levels, but rather uridine levels due to rapid conversion. This makes CDP-choline both a potent choline supplement and uridine prodrug.

Citicholine Benefits

Supporting Memory, Attention and Preventing Cognitive Decline.

As a nootropic, cdp-choline can be thought of as both a bioavailable choline source and a source of uridine (2). In the elderly CDP-choline has been noted to improve memory performance (6) and prevent cognitive decline (7). One study involving 60 healthy adult women aged between 40-60 show enhanced attention performance vs placebo. Doses used were both 250mg and 500mg, with both being equally effective (5).

Researchers attribute the cognitive enhancement to choline’s ability to support synthesis of phosphatidylcholine (PC) and acetylcholine within the brain. The increase in plasma uridine following citicoline consumption also lends a hand in PC formation within the brain via the Kennedy cycle. (8).

Editors Note: Choline and uridine work in synergy to create PC within the brain, making CDP choline both a bioavailable choline supplement and a uridine prodrug.

Drug Addiction

Citicoline has been shown in one clinical study to mildly reduce drug craving and lead to a lower intake of cocaine in addicted individuals.  One study involving 14 males with a history of cocaine dependence were given 500mg of citicoline twice per day for two weeks. Participants we’re noted to report a decrease in cocaine cravings. (11). Another study involving 500mg, twice daily failed to show any benefits on cocaine intake, though self reported alcohol intake was modestly reduced(12). Finally a randomised placebo controlled study of  44 bipolar outpatients with cocaine addiction found citicoline treated individuals were less likely to use cocaine when instructed not to. Cocaine use was assessed through urine screens (13).

Editors Note: The mixed evidence suggests that citicoline may be of positive benefit. Further research needs to be done before firm conclusions can be drawn.

Citicholine Safety and Side Effects

Citicoline has a very good safety record with one study involving 2817 showing 95% of patients tolerated treatment well (9). The most noted side effects in the remaining side effects were digestive disturbances, occurring in over 3% of individuals.

Research has noted a minor appetite suppressing effect of citicoline at 2000mg/day, however there was no significant change in participants body weight suggesting that food intake was not sufficiently altered.(10). Any appetite suppressive effect at higher doses appears to be minor.

Editors Note: Citicoline is a well tolerated nootropic. Digestive issues are unlikely though can likely be offset by splitting doses up throughout the day, or reducing total intake.

Citicoline vs. Alpha GPC

While both citicoline and Alpha GPC are bioavailable choline supplements which raise plasma levels of choline which then crosses the blood brain barrier (2)(14). Both CDP and GPC choline are naturally occurring forms of choline found during the creation and breakdown of PC , notably GPC choline is a catabolic byproduct of PC breakdown, whereas CDP is a building block for PC (see diagram).

Synthesis of choline from citicoline

Editors Note: As noted in the diagram above, GPC choline (glycerophosphocholine) is created when phosphatidylcholine (PC) stores are broken down. This can occur when the body stores of choline are running low. It seems the brain priorities acetylcholine needs over PC needs. CDP choline on the other hand is created when the brain is rich in choline and wishes to synthesise cell membranes. This would suggest that CDP choline is something created when choline is abundant, while GPC choline is created when choline is scarce.

Both GPC and CDP choline will raise the free choline pool which subsequently allows for acetylcholine and PC creation, however GPC choline has been shown to enhance growth hormone secretion (15) and improve peak bench press force (16). CDP choline on the other hand has the added benefit of raising plasma uridine (2), which is crucial for PC synthesis.

Editors note: In short it would appear GPC would be geared more towards exercise enthusiasts while CDP more for those looking for a PC booster, though research indicates both supplements will raise free choline and subsequently allow for PC creation and ACh creation. Both seeem excellent choices as a choline supplement.

Choline Content Differences

Alpha-GPC contains far more choline per gram than citicoline does. The molecular masses are as follows;

Choline: 104.17g /mol (17)

GPC: 257.221g /mol (18) – therefore 40% approximate choline or 400mg per gram.

CDP: 510.31g /mol (19) – therefore 20% approximate choline or 200mg per gram.