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Citicoline is a naturally occurring nutrient in the human body, and it is used in the synthesis of phosphatidylcholine (it forms 30% of the gray matter in the brain tissue). Intake of citicoline supplements enhances the production of acetylcholine and restoration of phospholipid content within the brain, and this two positively affect memory and various brain activities. This compound is a necessary precursor in the synthesis of phosphatidylcholine (an important component of the cell membranes). The sodium salt in the naturally occurring citicoline is synthesized for therapeutic application. When a person is suffering from ischemia, phosphatidylcholine is broken down into free fatty acids; these are then utilized to generate free radicals that potentiate ischemic injury. It is water soluble compound that belongs to the cholinergic class.

Citicoline is also referred to as CDP-choline, cytidine 5'-diphosphocholine, Citicolina, CDPC., etc. The chemical formula for Citicoline is C14-H26-N4-O11-P2. This compound has various brand names, and it is widely used as a cognitive enhancer. Scientific and clinical studies have indicated that it is efficient in boosting mental performance and energy and also protects the brain against oxidative stress. It is also used to increase the positive effects of other nootropics especially the racetams. Citicoline is a very popular brain supplement, and this can be attributed to its high efficacy and its high safety levels. It helps enhance both general brain health and cognitive function. Some of the mental processes that Citicoline boosts are learning, memory, focus and logical reasoning. Citicoline is also effective when stacked since it enhances the effectiveness of other nootropic agents. Citicoline is mostly used by elderly people who are seeking to prevent Alzheimer's and also stroke survivors although recently younger people are increasingly using it to boost their memory and performance at school or work.


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Citicoline is a naturally occurring substance in the human body, but it was first developed (synthetically) in Japan as a therapeutic drug for the treatment of a certain type of stroke. Its initial synthesis was in 1993 by Ferrer, a pharmaceutical company that was seeking to help stroke victims. Its marketing and manufacturing rights within U.S. and Canada would later be transferred from Ferrer and licensed to Interneuron, a nootropic supplement company in 1993. Interneuron went forward and patented Citicoline for its application in the reduction of cerebral infarct volume by 1993 and later in 1998 it acquired another patent for its role in the protection of brain tissue after stroke.

In various European nations, it was first offered as a prescription drug and currently, in most of these nations it is prescribed for thinking conditions that are linked to circulation problems within the brain. This substance is mainly marketed as a dietary supplementary. Citicoline has indicated that it can nourish the nerves and enhance blood circulation in the brain. Over the years since its first development, various scientific and clinical studies have been carried out to evaluate the effects of citicoline on the brain. However, more research is necessary to prove the links between the effects of Citicoline in those suffering from degenerative brain conditions and cognitive enhancement.


A clinical trial was performed in 394 patients to determine whether citicoline could help reduce central nervous system ischemic injury through stabilization of cell membranes and lowering the generation of free radicals. The trial was double-blind, 33-centered, randomized, placebo-controlled, and efficacy trial that lasted 6 weeks with an additional 6-week follow-up after completion of the treatment. Citicoline was administered in 267 patients and 127 patients received the placebo at doses fixed at 500mg per day all through the six-week treatment. The observations showed that Citicoline was safe but had no clinical efficacy in enhancing the conditions and symptoms in patients suffering from an acute ischemic stroke who were studied. However, post hoc analysis suggests that there might be a subgroup of patients suffering from moderate to severe strokes that might experience positive effects.

In many studies, Citicoline has been observed to have therapeutic efficacy in the treatment of memory disorders in patients with cerebrovascular pathogenesis. When a metanalysis was carried out on the entire database of results from clinical trials that had been conducted with Citicoline, it confirmed the experimental observations in animal studies. Animal studies had time and again shown that multiple biological actions of this substance in repairing lipid cell structures and various neurotransmitter functions.

In a rat-based study, the effects of Citicoline on cognitive deficit were evaluated in young rats that had been subjected to impoverished environmental conditions and had developed hippocampal-dependent memory impairments that were related to those exhibited in aging rats. The male Sprague –Dawley rats that had been raised for 3 months under enriched environmental (EC) or impoverished environment (IC) were all administered with either the Citicoline supplement or the control diet at approximately 500mg/kg every day. After 3 months of treatment, the rodents were taught to perform cued and spatial versions of the Morris water maze while contrasting their rates of acquisition and retention. IC rats showed a selective deficit in their hippocampal dependent spatial memory that could be improved by supplementing them with citicoline. In the EC rats, citicoline did not exhibit any memory enhancing effects. In IC rats, when citicoline supplements were administered for only the first or final months and not for the entire 3 month treatment period, citicoline did not prevent their memory impairment. Based on these results, it was concluded that long-term administration of Citicoline supplements could ameliorate the hippocampal-dependent memory impairment resulting from impoverished conditions in rats. It was suggested that long-term Citicoline consumption enhances membrane phosphatide synthesis and this how citicoline was able to improve cognition.

In an animal modeled study, researchers contrasted citicoline and epinephrine in their ability to improve the outcome of cardiac arrest. The randomized study involved administration of asphyxia in 45 rats to induce cardiac arrest and the resuscitated rats were then assigned to three groups that were treated with 250 mg/kg of citicoline, 100 μg/kg of epinephrine, or 2 mL/kg of saline. The researchers observed the hemodynamic parameters for 2 hours post-resuscitation and then examined cardiac function after 2 hours post-resuscitation using echocardiography. After the examination, the rats' hearts were harvested, and a histological evaluation was performed. Both epinephrine and citicoline were observed to increase the rate of return of blood pressure and spontaneous circulation throughout cardiopulmonary resuscitation but the post-resuscitation cardiac function in citicoline and placebo-treated groups were higher than that observed in the epinephrine group. By use of electron microscopy, researchers observed minimal mitochondrial and myocardial injury in citicoline and placebo groups compared to epinephrine group. Citicoline and placebo were also observed to protect connexin 43 when contrasted with epinephrine. The study concluded that citicoline was able to increase the rate of return of spontaneous circulation when administered in resuscitation just like epinephrine, but it did not amplify the severity of both myocardial injury and post-resuscitation myocardial dysfunction while epinephrine was observed to be harmful.

A human-based study was conducted to evaluate the effects of citicoline on unipolar and bipolar depression and methamphetamine dependence in 60 patients (adults). The trial was double-blind, randomized, and placebo-controlled. Citicoline and the placebo were randomized at doses of 2000mg per day used for 12 weeks. The researchers used Depressive Symptomatology-Clinician Version (IDS-C) to evaluate mood and Hopkins Auditory Verbal Learning Test (HVLT) to evaluate cognition. Urine drug screens were employed in the analysis of the drug use. The 28 patients who received citicoline treatment showed statistically and significantly higher improvements in IDS-C scores compared to the 20 patients who received the placebo. The study results indicated that citicoline might have antidepressant properties and has no tolerance problems. Another human-based study observed the effects of CDP-choline (citicoline) on memory performance when administered to elderly patients. Citicoline was administered orally alone at dosages of 1000mg and 500mg per day, or it was administered in combination with nimodipine in 4 weeks of monitoring memory performance in elderly subjects who had memory deficits. The study involved 24 patients who were aged above 60 years. Compared to the placebo, citicoline was observed to significantly enhance memory in free recall tasks but no improvements were observed in recognition tests. At doses in the range of 300-1000mg per day, citicoline indicated to have memory improving properties. After administration of citicoline, researchers also observed a drop in systolic blood pressure and some slight changes in lymphocyte cell counting in the aged subjects. These results were similar to the vasoregulatory and neuroimmune actions of citicoline and indicate that this nootropic agent can enhance memory through acting on mechanisms of brain cerebrovascular and neurotropism regulation. Based on these results, the researchers concluded that citicoline is appropriate for use in the treatment of memory deficits in seniors.

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