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Golden Thinker ® – Encyclopedia of Substances – Citicoline (CDPC)

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Citicoline (CDPC)
What is Citicoline?

Citicoline (CDP-choline; formally known as Cytidine Diphosphate Choline or cytidine 5′-diphosphocholine) is a naturally occurring molecule which is present in every cell of the body. The molecule is highly enriched in the brain and is vital for many key neuronal functions.

Choline is the vital precursor molecule required for the synthesis of the neurotransmitter acetylcholine (Ach). This chemical messenger is one of the predominant neurotransmitters responsible for learning, memory and cognition. Choline is also a key player in the production of phosphatidylcholine, which helps to build cell membranes.

Without choline, many functions of the brain and body wouldn’t be possible.

Our bodies can produce some choline and we can get a small amount from foods such as organ meats. However, we use up this essential nutrient far quicker than we produce it, meaning that most of us can benefit from supplementing with citicoline.

After digestion, citicoline is converted into choline and cytidine. Both of these molecules have key functions within the body, but choline is particularly important for brain function. Importantly, these molecules are small enough to cross the blood-brain barrier easily. Once arriving in the brain, the molecules are converted back into citicoline, allowing them to effectively assist in the production of acetylcholine and repair of cell membranes.

Citicoline has gathered a lot of attention from neuroscientists, and it’s potentially one of the most powerful nootropic compounds we’re aware of. In fact, citicoline has been used in many countries as a prescription drug to aid with memory, cognition and mental function during stroke recovery.

Citicoline is top of the list when it comes to choline-related supplemented because of its high bioavailability and ability to easily cross the blood-brain-barrier. Citicoline also appears to raise choline levels more quickly and effectively than other types of choline supplements.

Citicoline has been widely studied in the scientific literature, with some fairly impressive results. Here is a quick overview of the key benefits of citicoline supplementation:

  • Enhances and speeds up the formation of cell membranes
  • Boosts cognition, mental focus and learning capacity
  • Boosts cognitive performance and memory in patients with Alzheimer’s
  • May provide an effective rehabilitation medication to offset the damaging consequences of stroke
  • Improves vascular health and blood flow to the brain
  • Boosts the production of acetylcholine
  • Improves eye health and prevents vision loss in conditions such as glaucoma
Brain Benefits and Mode of Action

Let’s dig in to some of the most important scientific findings regarding the brain benefits of citicoline supplementation…

Boosts Cognition, Memory and Mental Energy

Numerous human studies have shown that supplementation with citicoline improves cognitive performance.

One study investigated the effects of 500mg and 250mg citicoline supplementation versus a placebo control in 40-60-year-old women. The study found that women who were supplemented with citicoline for 28 days outperformed placebo controls on cognitively-demanding tasks. These women made significantly fewer errors and completed the task with more ease. Interestingly, there also appeared to be a dose-response curve, with women supplementing with 500mg citicoline outperforming both the placebo and 250mg citicoline group.

One of the primary functions of citicoline is its ability to raise acetylcholine levels in the brain. This neurotransmitter underpins attention, alertness and a range of cognitive functions. Importantly, acetylcholine has been shown to optimise the detection of relevant signals during information processing, and modulate synapse formation and strength accordingly. This means that neuronal synapses are optimised for efficient memory storage and cognitive processing.

In animal models of stroke, researchers have found that long-term treatment with citicoline increased neuronal plasticity after stroke-related injury. They found that citicoline promotes increase plasticity and functional connectivity throughout the brain. This means that new synapses could be made and strengthen more easily. Synapses are vital for memory and information transfer. Hence, any modulation in their activity can have a huge effect on brain function.

It’s clear the citicoline holds potential therapeutic benefits. However, citicoline’s ability to increase neuronal plasticity may underlie some of its memory and cognitive enhancing effects in healthy people too.

A widely reported effect of citicoline supplementation is an enhancement to mental energy and focus. Various studies have shown that citicoline supplements can aid blood flow to the brain and improve vascular health. Research has also demonstrated that citicoline can increase the efficiency of glucose uptake and use in neurons, which may be one of the mechanisms which underlie this boost in mental energy.

Mode of action: A 2008 study found that citicoline enhanced frontal lobe energetics. In particular, researchers found this effect in the anterior cingulate cortex, a brain region which is responsible for many ‘higher order’ cognitive tasks such as attention, impulse control, decision-making and memory. The researchers found heightened levels of cellular energy in the form of phospholipids and ATP. This indicates that citicoline enhanced activity in these regions, which may constitute the underlying mechanism of citicoline’s ability to improve cognition and memory. This effect may also contribute to the improvements in mental energy and focus. This increase is phospholipid turnover is also thought to be one of the protective mechanisms which aid in mitigating age-related cognitive decline.

How to Use

Long-term supplementation with citicoline is considered safe and well-tolerated for most people.

Citicoline is water-soluble and highly bioavailable in either capsule or powder form.

It’s important to remember that while the compound is considered non-toxic at the correct dosage levels, taking too high a dose can lead to toxicity. Although these cases are very rare, you should stop supplementing with citicoline if you experience symptoms such as headaches, blood pressure changes, nausea, blurred vision, chest pain or diarrhoea.

Recommended Dose: 250 – 500mg daily

We recommend a dose a daily dose of 250-500mg per day to yield the best energy boosting and cognition enhancing effects. This dose is well within the safe upper limit of around 1000-2000mg which has been used in therapeutic settings. If you intend on taking a higher dose to address specific health conditions, we recommend consulting a medical professional to ensure high levels of the supplement are safe for your condition.

Stacks well with Pramiracetam: Citicoline stacks well with any other nootropic within the ‘racetam’ group. Racetam compounds, such as Pramiracetam, increase the uptake of acetylcholine in the brain. This increase in the uptake of acetylcholine will further enhance mental focus, cognition and alertness. Combining these two may also yield even better effects on memory.

Classification: Energy, Cognition, Memory

We’ve classified citicoline as an energy booster because of its ability to boost the production of cellular energy and acetylcholine. Boosting these molecules reduce mental fatigue, sharpens focus and increase mental energy.

Citicoline is also and cognition and memory enhancer. Supplementing with citicoline can improve our cognitive ability and aid us with learning, decision making and keep our thinking ‘sharp’. Citicoline can also improve memory, and has been shown to help protect against age-related impairments to memory.

References
  1. Agnoli A, Fioravanti M, and Lechner H. Efficacy of CDP-Choline in chronic cerebral vascular diseases (CCVD). In: Zappia V, Kennedy EP, Nilsson BI, and Galletti PV. Novel Biochemical, Pharmacological, and Clinical Aspects of Cytidinediphosphocholine. New York: Elsevier Science;1985.
  2. Demedio G, Trovarelli G, Piccinin G, and et al. The effect of cytidine-diphosphate choline (cdp-choline) on brain lipid changes during aging. Journal Of Neuroscience Research 1984;11(1):49-58.
  3. Parisi, V., Barbano, L., Di Renzo, A., Coppola, G., & Ziccardi, L. (2019). Neuroenhancement and neuroprotection by oral solution citicoline in non-arteritic ischemic optic neuropathy as a model of neurodegeneration: A randomized pilot study. PloS one, 14(7), e0220435. https://doi.org/10.1371/journal.pone.0220435
  4. Bruhwyler J, Liegeois J-F, and Geczy J. Facilitatory effects of chronically administered citicholine on learning and memory processes in the dog. Progress in Neuro-Psychopharmacology & Biological Psychiatry 1998;22(1):115-128.
  5. Rejdak R, Toczolowski J, Krukowski J, et al. Oral citicoline treatment improves visual pathway function in glaucoma. Med Sci Monit 2003;9:PI24-8.
  6. Clark W.M. “Efficacy of citicoline as an acute stroke treatment.” Expert Opinion on Pharmacotherapy. 2009 Apr;10(5):839-46.
  7. Dempsey RJ, Raghavendra Rao VL. Cytidinediphosphocholine treatment to decrease traumatic brain injury-induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats. J Neurosurg 2003;98:867-73.
  8. Silveri M.M. et. al. “Cognizin® Citicoline Increases Brain Energy (ATP) by 14% and Speeds up Formation of Brain Membranes by 26% in Healthy Adults” Society for Neuroscience San Diego, CA
  9. O. Hurtado, A. Cárdenas, J.M. Pradillo, J.R. Morales, F. Ortego, T. Sobrino, J. Castillo, M.A. Moro, I. Lizasoain, A chronic treatment with CDP-choline improves functional recovery and increases neuronal plasticity after experimental stroke,Neurobiology of Disease, Volume 26, Issue 1, 2007, Pages 105-111,ISSN 0969-9961, https://doi.org/10.1016/j.nbd.2006.12.005.
  10. De Bruin N.M., Kiliaan A.J., De Wilde M.C., Broersen L.M. “Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats.” Neurobiology of Learning and Memory. 2003 Jul;80(1):63-79.
  11. Wang L., Pooler A.M., Albrecht M.A., Wurtman R.J. “Dietary uridine-5′-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats.” Journal of Molecular Neuroscience 2005;27(1):137-45.
  12. Watanabe S., Kono S., Nakashima Y., Mitsunobu K., Otsuki S. “Effects of various cerebral metabolic activators on glucose metabolism of brain.” Folia Psychiatr Neurol Jpn. 1975;29(1):67-76.
  13. McGlade E., Agoston A.M., DiMuzio J., Kizaki M., Nakazaki E., Kamiya T., Yurgelun-Todd D. “The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males.” Journal of Attention Disorders 2015 Jul 15. pii: 1087054715593633.
  14. Spiers PA, Myers D, Hochanadel GS, et al. Citicoline improves verbal memory in aging. Arch Neurol 1996;53:441-8.
  15. Zweifler RM. Membrane stabilizer: Citicoline. Curr Med Res Opin 2002;18:s14-s17.
  16. Secades, Julio J. et al. Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials. Journal of Stroke and Cerebrovascular Diseases, Volume 25, Issue 8, 1984 – 1996
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