Citicoline: A Multifunctional Ingredient for Brain Health

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

Perry 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.

References on the next page...

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