What is citicoline?

Citicoline (cytidine 5-diphosphate choline, CDP-choline) is essential for the production of phospholipids such as phosphatidylcholine. These molecules build cell membranes and protective nerve coatings in the body [1]. Citicoline is a more complex molecule than regular choline, or even alpha-GPC, but it is the same substance that is naturally produced in the brain. To avoid confusion, scientists decided to call it "citicoline" when it is used as a treatment and "CDP-choline" when it is produced in the body [2]. Once ingested, it releases two compounds: cytidine and choline. After they cross the blood-brain barrier, neurons in the brain use them to make citicoline and other phospholipids [3]. Choline boosts acetylcholine and other neurotransmitters to keep the nervous system running smoothly. The body converts citicoline into many other beneficial compounds. Therefore, citicoline may have more benefits and fewer side effects than ordinary choline [4,5,3].

How it works

Citicoline increases the production of neurotransmitters and cell building blocks. In addition to acetylcholine, it boosts norepinephrine and dopamine in the brain [4,6]. It can enhance brain blood flow and stimulate mitochondria to produce more energy [4,5,2]. Adequate levels of CDP choline protect phosphatidylcholine and sphingomyelin, which build a protective nerve membrane called myelin. Citicoline also inhibits the inflammatory enzyme phospholipase A2 and enhances the main antioxidant glutathione [7,8]. In summary, citicoline functions by balancing neurotransmitters and protecting the nervous system from oxidation and age-related damage [9,10,1].

Dietary source

The body syntheses citicoline from cytidine and choline. The best way to increase citicoline levels through food is to consume adequate food sources that provide both. Choline-rich foods include [11,12] : Organ meat (liver) eggs chicken fish Whole grains Cytidine is an RNA nucleoside most concentrated in meat (especially organ meat); It is also found in colostrum [13,14]. Citicoline supplements (Cognizin, Somazina) are another potential source of additional choline, in addition to: choline alpha-GPC phosphatidylcholine lecithin

The health benefits of citicoline may be valid

1) Cognitive enhancement

Age-related cognitive decline Cognitive abilities tend to decline with age due to decreased blood flow to the brain or for other reasons. A review of 14 clinical trials concluded that CDP-choline can improve memory and behavior in patients with mild to moderate cognitive impairment, including those with poor brain circulation [9]. Based on data from more than 2,800 elderly patients, after receiving citicoline treatment, memory problems disappeared in 21% of patients and memory improved in 45% of patients. This study lacked placebo controls, so we should take the results with a grain of salt [18]. Citicoline (1000mg for 9 months) was beneficial in 350 elderly patients with mild cognitive impairment because it was able to [19] : Strengthen the nerve membranes to increase norepinephrine and dopamine levels to prevent oxidative damage In three studies of 210 patients with dementia and poor brain circulation, CDP-choline improved memory, reaction speed, and behavior. The higher the dose of citicoline (2000mg), the better the effect [20,21,22]. Many people use citicoline to improve thinking, enhance memory, and prevent cognitive decline. Let's see what science has to say about its role as a puzzle... In two clinical trials in 135 healthy adults, citicoline (250-500mg) improved attention and mental clarity [23,24]. A drink containing caffeine and CDP choline (250 mg) enhanced cognitive performance and reduced reaction time in 60 volunteers. Caffeine is a known stimulant and it may have contributed to the results [25]. In 24 healthy adults, higher doses of citicoline (500 or 1000mg) improved various cognitive markers - processing speed, working and verbal memory, executive function - but only in those with poorer cognitive ability [26]. In the same study, supplements had no effect on intermediate performers and even slightly impaired cognitive ability in high performers. [26] Cannabis abuse impaired cognitive ability. In a study of 19 chronic marijuana smokers, citicoline (2,000 mg per day for 8 weeks) reduced impulsive responses and improved cognitive performance. All participants wanted to quit smoking, and the researchers suggest that the effects of citicoline may help steer them in that direction [27,28]. According to preliminary research, citicoline can enhance attention and mental clarity, especially in people with poor cognitive abilities.

2) Stroke rehabilitation

Cutting off the blood supply to a specific brain region can kill neurons and cause severe brain damage. Citicoline may help by strengthening nerve membranes and blocking free radical production [29,30]. According to a meta-analysis of four clinical trials (more than 1,300 patients), taking 2000mg of citicoline within 24 hours after a stroke increased the odds of a full recovery by 38% [10]. Data from more than 4,000 stroke survivors show that citicoline improves outcomes and AIDS recovery; Higher doses (2000-4000mg) are more effective. There was no placebo control in this study, so no definitive conclusions could be drawn [31]. Two studies of more than 3,000 patients found no significant benefit of CDP-choline for acute stroke [32,33]. Clot-busting drugs remain the first choice for acute stroke. Two combined reviews concluded that citicoline may provide additional benefits or help patients who are unable to receive their preferred treatment [34,35]. Timely administration of citicoline may improve stroke recovery, but research is limited. Clot-busting drugs remain the first choice for acute stroke.

3) Vision problems

Like protecting nerves in the brain and spinal cord, citicoline may have the same beneficial effect on the optic nerve. It may reverse damage to retinal neurons and help treat eye diseases such as [1] : Optic neuropathy Glaucoma Amblyopia Glaucoma Increased eye pressure and other factors can damage the optic nerve and lead to glaucoma, sometimes leading to complete blindness [36]. In two clinical trials in 80 glaucoma patients, long-term oral citicoline repaired nerve damage, improved vision, and slowed disease progression [37,38]. Citicoline eye drops showed the same results in two other clinical trials (68 patients) [39,40]. Amblyopia, or "lazy eye," occurs when the eyes and brain don't communicate well. It can cause blurred vision in one eye. [41] In three clinical trials of 190 children, oral citicoline improved standard amblyopia treatment (eye patch) [42,43,44]. Injection of CDP choline (1000mg daily) healed the optic nerve and improved vision in 10 adults with amblyopia. The study had a small sample size and lacked placebo controls, so the results are questionable [45]. Optic neuropathy Optic neuropathy is another type of optic nerve injury that may interfere with vision. In 26 patients with optic neuropathy, citicoline (1600mg/ day for 2 months) improved vision by repairing nerve damage [46]. Insufficient evidence There is no valid clinical evidence to support the use of citicoline for the treatment of any of the disorders in this section. The following is a summary of recent animal studies, cell-based studies, or low-quality clinical trials that should trigger further investigation. However, you should not interpret them as supporting any health benefits.

4) Brain injury

Oxidative stress, autoimmune reactions, and environmental toxins can cause severe brain cell damage. Citicoline protects the brain and spinal cord from these stresses by protecting the myelin sheath of cells and enhancing important neurotransmitters. Alzheimer's disease In three clinical trials, Citicoline (1000mg daily for 1-3 months) improved symptoms of Alzheimer's disease [47,48,49] : Improved mental performance stimulated blood flow to the brain reduced levels of inflammatory molecules (histamine and IL1B) However, the lack of placebo controls in both studies made the results questionable. In a third study, patients with a genetic predisposition to Alzheimer's disease (APOE-e4 carriers) experienced even greater benefits. This is an important finding because APOE-e4 carriers respond differently (and often worse) to various interventions [48,50]. Citicoline enhanced the effect of drug therapy for Alzheimer's disease and slowed the progression of two observational trials (more than 600 patients) [51,52]. In rats with Alzheimer's disease, citicoline protects nerves from protein mutations and reduces blood flow. As a result, the rats had fewer cognitive impairments and improved memory [53]. Citicoline may help treat Alzheimer's disease and improve standard care, but existing clinical evidence is weak. Parkinson's disease The destruction of dopamine neurons in Parkinson's disease causes muscle stiffness, tremors, and other symptoms. In rats with Parkinson's disease, citicoline relieves muscle stiffness by increasing dopamine levels in the brain. It also enhances the effect of standard treatment [54,55]. Multiple sclerosis Inflammatory destruction of the myelin sheath of the external nerve sheet can trigger multiple sclerosis, accompanied by severe physical and cognitive impairment. In animals with multiple sclerosis, scientists have observed the potential of citicoline to enhance myelin recovery and motor coordination [56,57].

5) Mental disorders and drug addiction

Depression In a study of 50 patients, adding citicoline to an antidepressant (citalopram) improved depressive symptoms and recovery [58]. In rats, CDP-choline increases norepinephrine, dopamine, and serotonin levels in the brain's memory, mood, and movement centers [59,60]. Methamphetamine and cocaine addicts Citicoline reduced depressive symptoms in 60 methamphetamine (meth) addicts, but had no effect on drug use (2000 mg/day for 3 months). In another study of 31 methamphetamine addicts, citicoline protected the brain and reduced drug use [61,62]. In more than 130 cocaine addicts with bipolar disorder, citicoline (500-2,000 mg for 3 months) reduced drug use but did not affect mood. However, in a trial of 20 heavy cocaine users, it produced no effect [63,64,65]. A review of nine trials concluded that citicoline may have a slight benefit on substance addiction, particularly cocaine, but highlighted the need for stronger clinical evidence [66]. Citicoline enhanced the effect of standard treatment in 66 patients with schizophrenia. It improves so-called "negative" symptoms such as emotional dullness, poor communication, and stiffness. These are particularly difficult to treat with conventional drugs [67]. In 24 healthy adults, CDP-choline enhances cognition by stimulating the nicotinic acetylcholine receptor, which is generally underactive in schizophrenia [26]. Preliminary studies are promising, but there is not enough evidence to support the use of citicoline to treat mental disorders and drug addiction.