Citicoline Helps Protect Brain Function

Citicoline May Help Keep You Sharp

Citicoline Helps Protect Brain Function
Precursor to vital brain lipids may help preserve and improve learning and memory
By Aaron W. Jensen, Ph.D.

ature knows how important your brain is to you, so it does its best to protect it from injury. Most obvious, of course, is the thick, protective bone structure of the skull, which shields the fragile brain from external trauma. Inside the skull, between bone and brain, is a series of membranes called meninges, which cushion the brain and protect it from infection. Further shielding is provided by the cerebrospinal fluid, a clear fluid that fills spaces within the brain and between the skull, meninges, and brain. Together, these features provide a protective environment that keeps your brain out of harm’s way—most of the time.

But physical protection of the brain is not sufficient to shield it from other kinds of threats that it faces daily. It also needs to be protected from injuries that can come from within, such as damage from infection (thanks, meninges), free radicals, and nutrient deprivation. You may think that this type of internal protection is beyond your control—but it isn’t, really. You can do a lot to protect your brain by supplying it with the nutrients it needs on a daily basis. And if you do it right, you can help to ensure healthy cognition, learning, and memory all the days of your life—which may be longer as a result. In many ways, the health of your brain determines the health of your body.

Lipids Are Vital for Brain Health

The brain is in constant need of nutrients, such as glucose and oxygen for energy production, and lipids and amino acids for building new cellular structures. Lipids (fats and fatty compounds) are central to brain activity in two respects: structure and function. They contribute to the formation of healthy neuronal (nerve-cell) membranes, and they help to insulate the neurons and facilitate the conduction of electric impulses throughout the brain’s neural circuitry. A particularly important class of lipids for optimal brain function is phospholipids (so called because they contain one or more phosphate groups), such as phosphatidylcholine (which accounts for over half of all the brain’s phospholipids) and phosphatidylserine.

Citicoline May Help Reverse Brain Aging

Researchers have recently found that a phospholipid precursor compound—citicoline—increases the level of phosphorus-containing metabolites in the brain.1 This result suggests that citicoline (a shorthand term for cytidine-5’-diphosphocholine, or CDP-choline) may help boost the levels of certain key brain phospholipids and has led the researchers to suggest that “the administration of oral citicoline may be of use in reversing age-related changes in the brain.”

“The administration of oral
citicoline may be of use in
reversing age-related
changes in the brain.”

As our brains age, metabolic and biochemical changes occur that generally lead to loss of cognitive abilities. Among such changes is an alteration of neuronal membrane structure, which leads to a loss of neuronal function. In addition, changes in glucose metabolism may make neurons work less efficiently. Together, these changes impair our ability to process information, and they may result in a loss of memory, a decreased ability to learn, and an impaired ability to execute specific skills. As it turns out, many such changes in brain function can be correlated with the levels of phosphorus-containing metabolites (phosphometabolites) in the brain.

Citicoline Maintains Phosphometabolites

Because citicoline helps to modulate the level of brain phospholipids, researchers at Harvard Medical School recently investigated its effect on cognition in 19 elderly individuals (average age 70.3 years).1 All the subjects were tested at the beginning of the study to determine the levels of phosphometabolites in their brain tissue, and they were also subjected to neuropsychological analysis. They were then given 500 mg of citicoline daily for 6 weeks, at which time the tests were repeated. The levels of certain phosphometabolites of interest increased by 7.3% during this period.

When the subjects were scored
using a verbal learning test, it was
clear that memory had improved in
the group that had taken
citicoline for all 12 weeks.

The patients were then divided into two groups: one group continued to receive 500 mg/day of citicoline for an additional 6 weeks, while the other group received a placebo. Subsequent tests showed that the levels of the brain phosphometabolites remained elevated in the citicoline group, whereas they began to fall in the control group. Thus, while continued administration of citicoline did not result in further increases in the phosphometabolites, it ensured that these compounds remained at elevated levels so that they could continue to support the synthesis of new brain phospholipids.

Citicoline Improves Cognitive Performance

An increase in phosphometabolites would be of limited interest unless it correlated with improved cognition—and that is exactly what the researchers found. At week 12 of the study, when the subjects were scored using a verbal learning test, it was clear that memory had improved in the group that had taken citicoline for all 12 weeks. Some improvement was also noted in the other group (6 weeks of citicoline followed by 6 weeks of placebo), but the change was not statistically significant.

It is interesting to note that the greatest increase in phosphometabolites correlated with the greatest increase in verbal test scores. The researchers reported that improvements in other cognitive measures were also observed when citicoline was administered, but they have not yet published these results (when they do, we will report on it).

Citicoline Is a Neuroprotective Compound

Citicoline was first identified as an intermediate in phosphatidylcholine synthesis about 50 years ago. Since then, its role in neural protection has gradually been revealed, and currently it is thought to play many roles in maintaining brain health and function.2 One such role is to safeguard the presence of other brain lipids (such as cardiolipin, sphingomyelin, and ceramide), perhaps by preventing the decomposition of these essential compounds.

Citicoline is also thought to stimulate the presence of glutathione, a vital cellular antioxidant that protects the brain’s cellular structures from free radical damage. And it helps to reduce lipid peroxidation, thus possibly reducing the risk of neuronal membrane damage. Finally, there is evidence that citicoline supports normal ion-channel function, the process by which metallic ions such as sodium and potassium conduct electric impulses across neuronal membranes.

Citicoline Helps Glaucoma Patients

Glaucoma is the term used for a number of related eye diseases caused by the buildup of hydrostatic pressure in the eyeball. Excessive pressure damages the optic nerve head in the center of the retina at the back of the eye. The optic nerve transmits visual images to your brain in the form of electric signals conducted by millions of individual neurons. For this process to work optimally, the neurons in your optic nerves and your brain must be healthy.

Damage to the optic nerve in glaucoma is caused by the death of cells called retinal ganglion cells in the optic nerve head. When these cells die, they may deprive neighboring neurons of important growth factors. A recent study in Poland has suggested, however, that neuroprotectants such as citicoline may inhibit this cell death in glaucoma patients.1 Oral administration of citicoline (500 mg twice daily for two 2-week periods with a 2-week break in between) was found to improve visual pathway function in 21 patients.

When the neural performance (called visual evoked potential, or VEP) of the glaucomatous eyes was measured at the end of the study, it was clear that citicoline had improved the visual pathway function in the affected eyes. The authors concluded that oral citicoline may be valuable in the treatment of glaucoma.

  1. Rejdak R, Toczolowski J, Krukowski J, et al. Oral citicoline treatment improves visual pathway function in glaucoma. Med Sci Monit 2003; 9:PI24-8.

Citicoline Reduces Brain Damage Following Stroke

According to Steven Warach of the National Institute of Neurological Disorders and Stroke in Bethesda, MD, citicoline greatly reduces the volume of the infarct (dead brain tissue) following a stroke. Presenting his findings at the 27th International Stroke Conference held in San Antonio in February 2002, Dr. Warach reported that the neuroprotectant activity of citicoline depends on the dosage. Stroke patients were given either citicoline (500 mg/day or 2000 mg/day) or placebo for 6 weeks starting immediately after their stroke. The infarct volume was measured by MRI on day one and again after 12 weeks (i.e., after 6 weeks of treatment followed by 6 weeks of nontreatment).

The results were dramatic: over the 12-week period, infarct volume increased by 85% in the control group, by 34% in the group taking 500 mg/day of citicoline, and by only 2% in the group taking 2000 mg/day of citicoline. Oddly, however, there was no significant difference in clinical improvement between the control group and the pooled citicoline group. (For more on strokes, see the sidebar “Strokes Increase the Risk for Dementia.”)

Strokes Increase the Risk for Dementia

A stroke, or “brain attack,” is usually caused by blocked blood flow to a small, localized region of the brain. Impaired blood flow—even for a short time—can cause brain cells to die quickly, leaving an infarct. This will impair brain function to some degree, and additional impairment may result from the release of toxic compounds from the infarct into nearby regions of the brain. Depending on the location and extent of tissue damage, a stroke may impact a number of different functions—e.g., speech, movement, and cognition—to varying degrees.

Many stroke victims, however, may not even be aware that they have had a stroke—or even multiple strokes. These “silent strokes,” which can occur while one is awake or asleep, lack the usual outward symptoms associated with a stroke because they occur in relatively unimportant areas of the brain. Nonetheless, they do cause tissue damage, which can be cumulative and lead to noticeable functional impairment over time.

Researchers in The Netherlands have recently demonstrated that elderly individuals who have had silent strokes (documented by MRI brain scans) have a greatly increased risk for dementia and also suffer from more rapid cognitive failure as they age.1 The risk of silent strokes, and thus the risk of dementia, can be reduced by simple, common-sense lifestyle changes, such as weight control, maintaining good cardiovascular health, not smoking, and visiting a physician regularly to monitor overall (especially cardiovascular) health.

  1. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215-22.

Protect Your Brain from the Inside Out

It pays to take good care of your brain. Nature has done its best to protect your brain by enclosing it in a lightweight, cushioned, carry-along helmet, but you need to do your part as well, by providing it with nutrients that optimize its structure and function from the inside. You’re probably planning to keep your brain for a long time, so you want to take good care of it. Make sure that you arm it with all the molecules it needs to make your journey through this life an exciting and carefree one.


  1. Babb SM, Wald LL, Cohen BM, et al. Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacology 2002;161:248-54.
  2. Adibhatla RM, Hatcher JF, Dempsey RJ. Citicoline: neuroprotective mechanisms in cerebral ischemia. J Neurochem 2002;80:12-23.

Dr. Jensen is a cell biologist who has conducted research in England, Germany, and the United States. He has taught college courses in biology and nutrition and has written extensively on medical and scientific topics.

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