Citicoline: A Multifunctional Ingredient for Brain Health

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Citicoline: A Multifunctional Ingredient for Brain Health

by F. Renshaw, M.D., Ph.D.

10/14/2008

http://www.naturalproductsinsider.com/articles/citicoline--a-

multifunctional-ingredient-for-.html

Citicoline, the generic name for CDP-choline when used as a

nutritional supplement, has a variety of effects relevant for the

maintenance of brain health. It is a multi-functional ingredient that

appears to facilitate neurotransmission by increasing levels of

critical neurotransmitters, such as dopamine and acetylcholine;1

enhance cellular integrity by increasing phospholipid synthesis;2 and

support cellular activity by increasing levels of adenosine

triphosphate (ATP).3

In many parts of the world, citicoline is available as a

pharmaceutical agent for the treatment of stroke and closed head

injury.4 The mechanism of action for these indications is thought to

be a decrease in free fatty acids and their toxic intermediates, due

to an increase in the rate of phospholipid synthesis. Citicoline has

also been extensively evaluated as a treatment of dementia and

appears to be effective as a therapy for memory loss due to cerebral

infarction.5 In North America, citicoline is available as a

nutritional ingredient (Cognizin® Citicoline, from Kyowa Hakko).

In addition to memory, citicoline has a number of other health

benefits. Citicoline serves as a source of choline and supplies

cytidine, which is converted to uridine in the gut before absorption

into the blood. Uridine readily crosses the blood-brain barrier,

where it can be interconverted to CDP-choline.6

The pyrimidines, cytidine and uridine, have positive and distinct

effects on the brain relative to the effects of other brain

nutrients. For example, both cytidine and uridine have antidepressant

effects in animal models,7,8 and in humans with bipolar depression.9

These effects are most likely due to an increase in brain levels of

dopamine and norepinephrine.10

Increases in brain dopamine are also relevant to other brain-related

conditions. For example, citicoline administration has been shown to

improve the symptoms of Parkinson's disease, a disorder characterized

by low brain dopamine levels.11,12 Similarly, the use of a number of

different drugs, including alcohol and nicotine, has been linked to a

release of dopamine within the brain. Thus, it is interesting that

citicoline appears to reduce use of a wide range of drugs.13

The pyrimidines also have positive effects on mitochondrial function.

When given to humans with bipolar disorder, subjects treated with

pyrimidines demonstrated an increase in brain pH and a reduction in

brain glutamate levels.14,15 Taken together, these findings are

consistent with an improvement in mitochondrial function.16

Intriguingly, it appears administration of citicoline to healthy

volunteers increases levels of the high energy phosphate, adenosine

triphosphate (ATP) in the frontal cortex.17 This observation is also

consistent with a treatment-related improvement in mitochondrial

function.

While some other brain nutrients do not significantly cross the blood-

brain barrier in older adults,18 citicoline has significant effects

on brain phospholipid metabolism after single or multiple doses.19

F. Renshaw, M.D., Ph.D., is the USTAR Investigator and Director

of Magnetic Resonance Imaging, The Brain Institute of the University

of Utah, and professor of psychiatry at the University of Utah School

of Medicine.