Citicoline: A Unique Source of Choline For Brain Health
You may have heard of choline—a micronutrient that helps support lipid metabolism and liver health. Choline is also a critical nutrient for brain health due to the many metabolic pathways it feeds into.
For instance, choline is a precursor for phosphatidylcholine (in cell membranes), acetylcholine (in the brain), sphingomyelin (in the myelin sheath of nerve cells), and betaine (in the methylation cycle).
The major contributors of choline in the American diet are eggs, meat, poultry, fish, dairy foods, pasta, rice, and egg-based dishes as well as liver and peanuts. Yet, data from the National Health and Nutrition Examination Survey shows that only 8 percent of Americans consume the recommended amount of this vital nutrient. Consequently, many people may benefit from supplementation to help fulfill their metabolic demand for choline.
Most nutritional supplements deliver choline as choline bitartrate or phosphatidylcholine. However, there’s also a lesser-known source called citicoline.
Citicoline is unique because it’s a nutritional source of both choline and cytidine. Emerging research suggests that citicoline provides all of the benefits of choline but also works via distinct mechanisms of its own. Because of this, citicoline might be a better option than other forms of supplemental choline for many people.
Here’s what you need to know to appropriately educate yourself on this unique nutrient.
WHAT IS CITICOLINE?
Citicoline is the ingredient name for a compound that’s chemically identical to cytidine-diphosphocholine (CDP-choline). The only difference is that CDP-choline is naturally occurring in humans, and citicoline is the form found in nutritional supplements.
CDP-choline is a nucleotide composed of choline, cytosine, ribose, and pyrophosphate and is present in every cell of the human body as well as naturally occurring in foods. However, the only foods that contain any appreciable amount of CDP-choline are liver, brain, and other organ meats.
CDP-choline was discovered in 1955 and scientists developed the synthetic version of the molecule shortly after that. The earliest form of citicoline was marketed as a prescription medication and not a nutritional supplement. While physicians in Europe and Japan have been prescribing citicoline since the 1970s, it was not introduced in the United States as a dietary supplement until the 1980s.
HOW CITICOLINE WORKS IN THE BRAIN
Citicoline works best when it is taken orally and has a bioavailability of approximately 92 percent. It’s first broken down in the small intestines and liver to cytidine and choline. The cytidine is then metabolized into uridine which, along with choline, are both free to cross the blood-brain barrier.
Once inside the central nervous system, uridine and choline can recombine to form CDP-choline. They are also each available to enter other metabolic pathways independently.
The choline component of citicoline accounts for many of its mechanisms. Choline is a precursor for acetylcholine—a brain neurotransmitter that helps support focus, attention, learning, and memory. Choline is also a precursor for phosphatidylcholine—a structural component of cell membranes of the neurons in the brain.
However, the choline component doesn’t explain all of citicoline’s mechanisms of action. For example, citicoline supports dopamine levels in the brain. It also supports mitochondrial function and brain energy production as well as the protein expression of sirtuin 1 (SIRT1), an enzyme that supports the health of nerve cells.
All of this opens up endless possibilities for brain health. Clinical studies of citicoline continue to unfold, but already show promise for its ability to support attention, memory, satiety, and vision.*
CITICOLINE FOR FOCUS AND ATTENTION
One relevant result of citicoline studies is that it supports energy production in the brain specific to areas of the frontal lobe that are dedicated to focus and attention.*
A team of researchers led by Erin McGlade at the University of Utah have conducted two double-blind, placebo-controlled trials that have evaluated citicoline for focus and attention in healthy subjects. The first study involved 60 healthy women, and the second involved 75 teenaged boys. Both studies randomized the participants into three groups for 28 days. One group took 500 mg of citicoline per day, another group took 250 mg of citicoline per day, and the third group took a placebo.
Results of both studies revealed that citicoline helped support attention and cognition in healthy women, and helped support attention, motor speed and caution in teens.*
CITICOLINE FOR MEMORY
Because of its role as a precursor for acetylcholine and as a building block for neuronal cell membranes, citicoline has been studied extensively for its role in supporting memory and cognitive function.*
Some of the earliest studies of citicoline found that it supports cognition in healthy older adults. In these studies, citicoline was particularly helpful for healthy people who didn’t have any cognitive disorders, but who were beginning to notice some age-related memory concerns.*
Other studies evaluated citicoline in people with cognitive concerns. A 2005 Cochrane review of 14 of these studies concluded: “There is some evidence that CDP-choline provides modest but consistent improvement of memory and behavior in these patients.”
One of the most recent clinical trials of citicoline for memory was the IDEALE study. This 2013 study was unique in that it administered citicoline for nine months—significantly longer than earlier studies. Results showed that oral supplementation with 1,000 mg of citicoline per day supported cognitive function.*
CITICOLINE FOR SATIETY
Many studies have linked dopamine, norepinephrine, and serotonin to human moods and cravings. Citicoline’s ability to support the synthesis of these neurotransmitters has led to research examining its effects in people struggling with addictions and other cravings.
The results of these studies have been mixed. Although citicoline consistently supports memory, attention, and mood in these studies, it doesn’t consistently help to reduce cravings. For example, a study published in 2019 found that citicoline had no effect on alcohol intake in people struggling with unhealthy use of alcohol.
Despite conflicting results in studies of cravings, there may be a potential role for citicoline to support appetite control in healthy adults. A study published by Killgore and colleagues in 2010 showed that oral citicoline supplementation supported healthy brain patterns in response to high-calorie foods and healthy appetite control.*
CITICOLINE FOR HEALTHY VISION
Until recently, citicoline research has concentrated on memory, focus, and brain health. The eyes, however, are undeniably an extension of the brain. The optic nerve is cranial nerve II, and the retina is packed with specialized nerve cells called retinal ganglion cells.
Therefore, regardless of the inherent health of a person’s eyes, one foundational way to support healthy vision is to support the healthy structure and function of the retina and optic nerve. Damage to these critical components of eye health can lead to vision loss over time.
Research on citicoline’s role in supporting eye health and vision is accelerating quickly. Some of the earliest studies evaluated citicoline in children who use an eye patch to improve vision. The combination of citicoline with patching was more effective for supporting healthy vision than patching alone.
In a 2013 study published in Ophthalmologica, researchers showed that oral supplementation with citicoline supported healthy vision in patients with an existing eye condition. A 2019 study published in PLoS ONE reported that oral citicoline supported visual function, retinal ganglion function, and neural conduction along visual pathways.*
Eye drops containing citicoline have been evaluated in Italy, with preliminary evidence suggesting that the topical application of citicoline may also support retinal and visual health.
CITICOLINE IN PRACTICE
Citicoline is produced in two different forms: citicoline salt and citicoline freebase. Citicoline salt is available by prescription in some countries and citicoline freebase is available in dietary supplements in the U.S.
Japanese company Kyowa Hakko produces citicoline freebase by using a patented and natural fermentation process. It goes by the brand name Cognizin and can be found in supplements sold by numerous manufacturers.
Citicoline is considered to have an excellent safety profile. Some mild adverse effects have been observed, such as gastrointestinal discomfort or irritability and no serious adverse effects have been reported.
Citicoline is approved for a maximum intake of 1,000 mg per day by European agencies. U.S. supplements containing citicoline typically provide 250 to 500 mg per day and this amount is consistent with studies of citicoline to help support attention or memory in healthy adults and teens.*