How CDP Choline (Citicoline) Defends Your Brain

How CDP Choline (Citicoline) Defends Your Brain

Authored by Jamie Witherby • 
November 11, 2019
 • 10 min read
supplementscognitionnootropics

Finding your purpose isn’t easy.

Take the adventurous protagonist for example—they wish for more, struggle through every rock bottom, fall in and out of love in cringe-worthy romance scenarios, and end up on a completely different path than originally intended. But always, their purpose is found.

This epic tale follows a naturally-occurring compound, cytidinediphosphocholine (also known as cytidine 5’-diphosphocholine, cytidine diphosphate choline, and cytidine diphosphate-choline). But we can just call it CDP choline (or its generic pharmaceutical name: citicoline) for short. We’ll explore CDP choline’s journey through various systems of your body to find its ultimate purpose: to fight for your brain function.

Supplementing with this compound can increase cognitive function and memory performance, protect the brain from damage and disease, and reduce inflammation.

CDP Choline: Becoming Citicoline

You can find CDP choline in every single cell in your body, especially your brain. It’s a binding of a choline molecule to a cytidine molecule.1

Choline

Choline is a molecule best metabolized twice. Both times occur within our cell powerhouses, also known as the mitochondria. First, choline is metabolized by choline oxidase and once more by betaine aldehyde dehydrogenase. The result? Trimethylglycine, which is a plant-based amino acid found in sugar beets, spinach, quinoa, and other nourishing nibbles.2

More importantly, it’s a cofactor in the mandatory mammalian process known as methylation; methylation is when our cells donate methyl groups to other processes of the body. Donating is perhaps too soft of a term for this required action. The recipient processes include synthesizing essential neurotransmitters like dopamine and serotonin.2

You can find choline in foods like eggs, liver, and other meats but you can also purchase choline supplements as well. The National Academy of Sciences designated choline as essential in 1988, suggesting dietary intake.

Wondering about other essential nutrients?

Subscribe now and we'll fill you in on all the exclusive research behind the natural compounds in our products.

Cytidine

Cytidine is a nucleoside molecule formed through a bonding of cytosine to a ribose ring. If that doesn’t ring a bell, consider the word ribose. You know it. In fact, the answer is hiding in your DNA. Give up? Cytidine is a major component of ribonucleic acid (RNA).3

Though not the same as DNA, RNA is still involved in genetics. RNA’s job is to convert the genetic code in your DNA to a more friendly format for protein production.3

It stands to reason that cytidine is found in foods with a high RNA content. Think animal products, especially organ meats. If you need a drink pairing, consider a nice beer to go with it; brewer’s yeast is another great natural source.

Choline + Cytidine

When choline and cytidine are together as CDP choline, they can be found hiding in the foods you’re probably consuming frequently: brain and liver. For non-zombie or non-offal-loving groups, some CDP choline can be synthesized from choline-rich foods such as eggs, poultry, and beef.4 And by egg, we mean the full egg.

While egg whites are a proper protein-rich breakfast food, they do not contain the choline. Only the delicious yolk does.

Like any good main character starved for attention, CDP choline decided it wasn’t present enough through food. This is true—to enjoy the full potential of CDP choline’s brain and body benefits, you’ll need to assist your body’s natural production by supplementing with its chemically identical stunt double, citicoline.5

An illustration of a DNA strand, showing what CDP choline is, and how it become citicoline

Citicoline Origin Story

Now a common oral supplement, citicoline was first synthesized in the 1970s in Japan as a prescription-only medication to help stroke patients and those with Parkinson’s disease. It was later prescribed in Europe for a range of cognitive impairments such as memory deficits, which is where its brain-enhancing talents were discovered.5 These talents have shown promise in treating a vast array of neurological conditions, including the aforementioned ischemic stroke and dementia conditions,6 such as age-associated memory impairment, Alzheimer’s disease, and Parkinson’s disease.7 Citicoline then took its first steps out on the market as a dietary supplement.

Body Armor: Mission in the Bloodstream

Once ingested, citicoline immediately faces an identity crisis. It gets broken down and appears in your bloodstream as two separate chemicals: choline and uridine. The compound won’t see the other side of itself until both parts are reunited in the brain as citicoline once more.8

Until then, citicoline has a job do in your blood.

Free Radical Agent

Citicoline travels vigorously through the body to slay any foes daring to cross its path.

While most of your favorite fictional heroes meander from quest to quest, citicoline moves with purpose throughout the body, squelching the free radicals that attack the brain.

Citicoline becomes an agent of change for another character in the story: glutathione (GSH). Residing in the kingdoms of plants, animals, bacteria, and fungi, glutathione is a very powerful antioxidant.9 It can directly scavenge excess free radicals to protect cells and tissues from oxidative damage.

When a plethora of free radicals roam your body unattended, these unattached oxygen molecules take electrons from lipid cell membranes (also called lipid peroxidation) and trigger inflammation, which accelerates cell deterioration and aging. Worse yet, this damage contributes to the development of the terrifying trifecta of diseases: diabetes, cancer, and heart disease.9

Brain cells and tissues are especially susceptible to oxidative damage because of the brain’s elevated use of oxygen. Citicoline boosts levels of glutathione to hold back the free radical attack on brain cells.10,11 This allows your cells to better protect themselves from future harm as well as assist with making a complete recovery from a brain injury.

An image of an atom, with an illustration of boxing gloves, showing how citicoline fights free radicals

To the Center of the Brain

Battling free radicals is all in preparation of citicoline’s arrival in the brain. Recall that it has been traveling in the bloodstream as two separate chemicals, choline and uridine, which are reunited in the brain as citicoline. Now that they’re back together, they can begin to work their magic on your body’s control center.

Strengthening Your Defenses

Citicoline doesn’t stop to celebrate when it reaches the brain; it gets straight to work as a precursor for the synthesis of two important components in brain cells: phosphatidylcholine (substance found in cell membranes) and acetylcholine (a neurotransmitter).12

Acetylcholine and Phosphatidylcholine

Acetylcholine is the major neurotransmitter responsible for activating muscles in both the sympathetic and parasympathetic nervous system. It’s also involved in encoding our memories.13

Acetylcholine can be found in all motor neurons, and it serves a number of critical functions. Blink, and you may miss them. Or, blink, and you may experience them; acetylcholine is responsible for the muscle contractions of your eyelids by transmitting the signals between your motor nerves and your muscles.14

In the brain, acetylcholine is a neuromodulator, meaning that it acts on a variety of neurons rather than directly engaging in specific synaptic transmission between neurons. This neuromodulator plays a heavy role in areas of the brain responsible for motivation, attention, and even arousal.14

When acetylcholine function is interrupted, your body can undergo some serious changes. Here’s a cheery example: when a black widow spider bites, her venom causes a dangerous rise in acetylcholine levels. Best case scenario? Severe muscle contractions followed by spasms. Worse case scenario? Spasms ending in sudden paralysis, followed by death.15

Phosphatidylcholine on the other hand is an essential part of stabilizing brain cell membranes and participating in neuronal activity.16

Your body uses choline to synthesize acetylcholine, but that can leave your choline stores shortchanged for other functions.

Guess what else you need choline for? Synthesizing the six-syllable tongue twister, phosphatidylcholine. Supplementing with citicoline gives your body enough choline to assist with both productions, so you can enjoy muscle activation and strong brain cells to help protect against Alzheimer's, vascular dementia, and cerebrovascular disease.17

Rebuilding After Attacks

With phospatidylcholine abound, your brain cells can not only enjoy mild strengthening but also repair from long-term and short-term damage.

Recall that citicoline was originally used as a medication for ischemic stroke patients because it can repair neuronal membranes damaged from the lack of oxygen to the brain.5 An acute ischemic stroke quickly cuts off blood flow to the brain, meaning it doesn't get enough oxygen to function properly. In a study of 272 stroke patients, 54% showed improvements in brain function in as little as two weeks when supplementing with citicoline.18

A meta-analysis of over a thousand ischemic stroke patients and their magnetic resonance imaging scans found that 25% experienced a complete recovery from their brain injury after supplementing with citicoline for twelve weeks.19

While clinical trials have demonstrated citicoline's recovery mechanisms of action through increased blood flow, in vitro studies have examined citicoline's attenuation of cell death. When the enzyme phospholipase A2 is activated, it tells your cells to die. Phospholipase A2 is activated for its damaging deeds after brain injuries or trauma, such as an acute ischemic stroke. But citicoline has been able to modulate the activation of phospholipase A2 to reduce its cell-slaying effects.20

Neurological damage can manifest itself in other ways, including declines in neurotransmitter activity.

Dopamine, a neurotransmitter heavily involved in regulating mood, can suffer a reduction if dopaminergic neurons have been damaged. Citicoline can be quite the dopaminergic neuron booster. Citicoline potentiates the production of dopamine to attenuate recent declines in the mood boosting chemical.21

Citicoline’s dopaminergic activity is likely related to its uridine component.

Recall that as citicoline travels through your bloodstream, it does so as uridine and choline. In fact, supplementing with citicoline can significantly increase plasma uridine concentrations.8 Similar to cytidine, uridine is a nucleotide base also commonly taken as a dietary supplement and cognitive booster. Uridine is generally used to increase the synthesis of cellular membranes and a greater density of synapses in the brain,22 especially in combination with choline and DHA. Uridine augments potassium-evoked dopamine release.23

While citicoline may not directly influence dopamine concentrations, it appears to increase dopamine transporters by increasing the quantity of dopamine released from a stimulated neuron, potentially by increasing the overall health of neuronal membranes.21

Focusing and Remembering

If increased dopamine doesn’t get your attention, citicoline can. Our noble neuroprotectant has been shown to improve attention by reducing focus-based errors, including errors of omission as well as incorrect information.24

But even if you do omit information, citicoline may be able to help. In a study on spatial memory tasks using animal models, citicoline was shown to have a protective effect against the impairment of hippocampal-dependent long-term memory, particularly for those susceptible to memory loss or memory problems: elderly animals.25

Even elderly humans enjoyed improvements in short-term memory recall and verbal memory after oral supplementation of citicoline for four weeks.7

Memory boosts and defense against memory loss in clinical trials situate citicoline as a promising possible treatment for Alzheimer's disease.

In patients with Alzheimer's disease, citicoline treatment increased blood flow to the brain and bioelectrical activity patterns.26 Increased blood flow in the brain may assist with recovery from brain injury and offer neuroprotective effects against cerebrovascular disease.

But supplementing with citicoline isn’t reserved for elderly people; the positive effect of citicoline can be enjoyed by anyone.

Nootropics that contain citicoline act as daily memory and mood enhancers, stress reducers, and cognitive catch-alls to support long-term cognitive resilience. When you’re ready to improve your reaction times,27 lower your cortisol levels,28 and protect and strengthen your neurons,29 the supplements may be able to get you back in top form quicker.

A model of the human brain in a skull, showing the impact of citicoline on the brain

Battling Against Addiction

For many people, citicoline’s journey in the brain may end with memory boosts and increased attention. For those battling with cocaine addiction, however, citicoline has one final job to do. Before we can send citicoline back out the battlefield, we need to arm ourselves with some basic knowledge about the mechanisms of addiction.

The current basis of pharmocological therapy establishes that the mesocortical and mesolimbic dopaminergic systems play major roles in addiction.

One of the four main dopamine pathways in our brains, the mesocortical dopaminergic system connects the prefrontal cortex to the ventral tegmentum. It’s heavily involved in our emotional responses and motivation. It’s also closely associated with the mesolimbic pathway, which connects our ventral tegmental area in the midbrain to the ventral striatum in the forebrain. This dopamine pathway is commonly referred to as the reward pathway because it facilitates reinforcement and reward-based learning.30 Another reward? This pathway may be involved in our subjective feelings of pleasure.

Cocaine floods these pathways with dopamine, allowing the user to tap into those extra sensations of pleasure, motivation, and reward. But the brain adjusts quickly to these higher dopamine levels so that when they dip below the new normal, the user begins to experience withdrawal symptoms: restlessness, exhaustion, muscle aches, difficulty concentrating, increased appetite, and an inability to feel pleasure.

Combine difficult symptoms with a reward feedback loop easily controlled by a stimulus (cocaine), and you get cocaine addiction.31

In a double-blind outpatient study, researchers wanted to examine citicoline’s safety in elevating dopamine levels in the central nervous system after they’ve been depleted by cocaine dependency. After two weeks, citicoline treatment was linked with reductions in subjects’ reported mood states associated with cocaine cravings.32

In other words? How about their own: subjects felt more in control over their use of cocaine (or lack thereof), less of an immediate urge to use it, and a reduction in overall desire to use it as compared to the placebo group.32

A longer study in 2007 observed the administration of citicoline to test for its effects on cognitive performance. The individuals had not only a cocaine addiction but also bipolar disorder. Of all the psychiatric disorders, bipolar disorder is linked to the highest rates of substance abuse. Cocaine is often the drug of choice. Both bipolar disorder and cocaine use are associated with symptoms related to mood and cognitive decline.

After twelve weeks of supplementation, the citicoline group showed two areas of significant improvement: improvements in declarative memory, and better yet, improvements in cocaine use. By the end of the study, the placebo group was about 6.4 times more likely to test positive for cocaine than the citicoline group.33

While it would not be accurate to say that citicoline is a cure for cocaine addiction, it would be accurate to say that there are studies showing that citicoline may be able to have a helpful intervention. Further research in these mechanisms has been strongly encouraged.

Supplementing with Citicoline

In both cocaine addiction studies, citicoline was tolerated very well, and no one discontinued the use of medication for its effects. As for side effects? None were reported.

While side effects for this med are uncommon, minor effects may include headaches, digestive problems, insomnia, and changes in blood pressure.

Citicoline is highly bioavailable and well absorbed with few side effects.

While there is no Recommended Dietary Allowance (RDA), clinical reviews of daily oral doses suggest 250mg to 2,000mg a day, with high doses recommended for optimal cognitive benefits.

If you're looking for a daily dose of citicoline, nootropic supplements are a great source that can be packed with other brain-boosting ingredients.

Because citicoline has been reported to influence blood pressure, talk to your doctor before combining the supplement with blood pressure medication. As always, talk to your healthcare provider before taking any new dietary supplements.

Reflecting on Purpose

You should be flattered by how much citicoline is willing to endure for the sake of defending you.

It has to fight rising aggressive free radicals, not to mention build extra levels of defense on your brain cells to insure them for future attacks to promote brain health. Even after all that, citicoline finds the strength to help you improve your long-term memory and cognitive function.

Show your gratitude for citicoline’s journey by using its boost to embark on your own.

Journey into your mind

We'll keep you up to date on all the latest tips and tricks to optimize your cognitive performance. Sign up now to start treating your brain to the best.

Scientific Citations

1.Bracken BK, Penetar DM, Rodolico J, Ryan ET, Lukas SE. Eight weeks of citicoline treatment does not perturb sleep/wake cycles in cocaine-dependent adults. Pharmacol Biochem Behav. 2011;98(4):518-24.
2.Lin, CS. & Wu, RD. J Protein Chem (1986) 5: 193. https://doi.org/10.1007/BF01025488
3.Cansev M. Uridine and cytidine in the brain: their transport and utilization. Brain Res Rev. 2006;52(2):389-97.
4.Patterson KY, Bhagwat SA, Williams JR, Howe JC, Holden JM. USDA Database for the Choline Content of Common Foods. U.S. Department of Agriculture. Published January 2008. Accessed March 2019.
5.Grieb P. Neuroprotective properties of citicoline: facts, doubts and unresolved issues. CNS Drugs. 2014;28(3):185-93.
6.Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Citicoline improves verbal memory in aging. Arch Neurol. 1996;53(5):441-8.
7.Alvarez XA, Laredo M, Corzo D, et al. Citicoline improves memory performance in elderly subjects. Methods Find Exp Clin Pharmacol. 1997;19(3):201-10.
8.Wurtman RJ, Regan M, Ulus I, Yu L. Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochem Pharmacol. 2000;60(7):989-92.
9.Masella R, Di benedetto R, Varì R, Filesi C, Giovannini C. Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J Nutr Biochem. 2005;16(10):577-86.
10.Adibhatla RM, Hatcher JF, Dempsey RJ. Effects of citicoline on phospholipid and glutathione levels in transient cerebral ischemia. Stroke. 2001;32(10):2376-81.
11.Barrachina M, Domínguez I, Ambrosio S, Secades J, Lozano R, Ferrer I. Neuroprotective effect of citicoline in 6-hydroxydopamine-lesioned rats and in 6-hydroxydopamine-treated SH-SY5Y human neuroblastoma cells. J Neurol Sci. 2003;215(1-2):105-10.
12.Kim JH, Choi BY, Kho AR, et al. Acetylcholine precursor, citicoline (cytidine 5'-diphosphocholine), reduces hypoglycaemia-induced neuronal death in rats. J Neuroendocrinol. 2018;30(1)
13.Amenta F, Tayebati SK. Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction. Curr Med Chem. 2008;15(5):488-98.
14.Hasselmo ME. The role of acetylcholine in learning and memory. Curr Opin Neurobiol. 2006;16(6):710-5.
15.Kuo IY, Ehrlich BE. Signaling in muscle contraction. Cold Spring Harb Perspect Biol. 2015;7(2):a006023. Published . doi:10.1101/cshperspect.a006023
16.Kanno K, Wu MK, Scapa EF, Roderick SL, Cohen DE. Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2. Biochim Biophys Acta. 2007;1771(6):654-62.
17.Dixon CE, Ma X, Marion DW. Effects of CDP-choline treatment on neurobehavioral deficits after TBI and on hippocampal and neocortical acetylcholine release. J Neurotrauma. 1997;14(3):161-9.
18.Tazaki Y, Sakai F, Otomo E, et al. Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke. 1988;19(2):211-6.
19.Alvarez-Sabín J, Román GC. The role of citicoline in neuroprotection and neurorepair in ischemic stroke. Brain Sci. 2013;3(3):1395-414. Published 2013 Sep 23. doi:10.3390/brainsci3031395
20.Adibhatla RM, Hatcher JF. Citicoline decreases phospholipase A2 stimulation and hydroxyl radical generation in transient cerebral ischemia. J Neurosci Res. 2003;73(3):308-15.
21.Giménez R, Raïch J, Aguilar J. Changes in brain striatum dopamine and acetylcholine receptors induced by chronic CDP-choline treatment of aging mice. Br J Pharmacol. 1991;104(3):575-8.
22.Wurtman RJ. A nutrient combination that can affect synapse formation. Nutrients. 2014;6(4):1701-10. Published 2014 Apr 23. doi:10.3390/nu6041701
23.Wang L, Pooler AM, Albrecht MA, Wurtman RJ. Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci. 2005;27(1):137-45.
24.Mcglade E, Locatelli A, Hardy J, Kamiya T, Morita M, Morishita K, Sugimura Y, Yurgelun-Todd D. Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women. Food and Nutrition Sciences (2012) 03. 10.4236/fns.2012.36103.
25.Teather LA, Wurtman RJ. Dietary cytidine (5')-diphosphocholine supplementation protects against development of memory deficits in aging rats. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27(4):711-7.
26.Alvarez XA, Mouzo R, Pichel V, et al. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods Find Exp Clin Pharmacol. 1999;21(9):633-44.
27.Stough C, Lloyd J, Clarke J, et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl). 2001;156(4):481-4.
28.1
29.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 (Berl). 2002;161(3):248-54.
30.Pulvirenti L, Koob GF. Dopamine receptor agonists, partial agonists and psychostimulant addiction. Trends Pharmacol Sci. 1994;15(10):374-9.
31.Nestler EJ. The neurobiology of cocaine addiction. Sci Pract Perspect. 2005;3(1):4-10.
32.Renshaw PF, Daniels S, Lundahl LH, Rogers V, Lukas SE. Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: a preliminary report. Psychopharmacology (Berl). 1999;142(2):132-8.
33.Brown ES, Gorman AR, Hynan LS. A randomized, placebo-controlled trial of citicoline add-on therapy in outpatients with bipolar disorder and cocaine dependence. J Clin Psychopharmacol. 2007;27(5):498-502.
Editor's Choice
Emails worth reading.

Once a week, we'll send you the most compelling research, stories and updates from the world of human enhancement.

H.V.M.N. Co-founders Michael Brandt and Geoffrey Woo

These statements have not been evaluated by the FDA. Our products are not intended to diagnose, treat, cure, or prevent any disease.

© 2019 HVMN Inc. All Rights Reserved. H.V.M.N.®, Health Via Modern Nutrition™, Nootrobox®, Rise™, Sprint®, Yawn®, Kado™, and GO Cubes® are registered trademarks of HVMN Inc. ΔG® is a trademark of TΔS® and used under exclusive license by HVMN Inc.

H.V.M.N.
38 Mason St, 3rd Floor, San Francisco, CA 94102
Email us: care@hvmn.com

These statements have not been evaluated by the FDA. Our products are not intended to diagnose, treat, cure, or prevent any disease.

© 2019 HVMN Inc. All Rights Reserved. H.V.M.N.®, Health Via Modern Nutrition™, Nootrobox®, Rise™, Sprint®, Yawn®, Kado™, and GO Cubes® are registered trademarks of HVMN Inc. ΔG® is a trademark of TΔS® and used under exclusive license by HVMN Inc.