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Citicoline: Benefits, Dosage, Side Effects, and More!

By Dr. Ramon Velazquez Ph.D. | |

Citicoline is a brain supplement (also known as a nootropic) linked to multiple cognition-enhancing effects in human randomized controlled trials. Its benefits may include support for focus, recall, attention and overall brain health. It is one of the best nootropics known to science. In this article we explain why as well as give recommendations on the best supplements that supply this nutrient.

What Is Citicoline?

Citicoline (also known as cytidine-5-diphosphocholine, cytidine diphosphate choline or CDP-choline) is a naturally occurring compound in the human body. Citicoline is a 2-in-1 brain booster because after it is consumed, it breaks down into two distinct nootropic compounds:

  1. Choline, a nutrient related to "good fats" and B-vitamins that is regarded as one of the most important nootropics for brain health and sharp cognition;(1)

  2. Cytidine, a compound that is metabolized into uridine, which is another nootropic associated with memory function, brain plasticity, and healthy brain cell membranes (2)

Citicoline’s two nootropic compounds promote brain health in several pathways. The end result is a single whole-brain optimizer nootropic that can boost brainpower across all age groups and lifestyles -- making it the ideal core ingredient for a brain supplement called Mind Lab Pro.

 

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  • 11 brain supplements in 1 formula

  • 250 mg of citicoline per serving

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Benefits of Citicoline

Citicoline's benefits as a supplement can be broadly placed into two categories: brain health support, and nootropic cognitive enhancement.

The following lists show some of the evidence-backed benefits associated with citicoline.

Brain Support

  • Optimizes brain cells' mitochondria for healthy energy metabolism

  • Raises brain levels of neural building-block phosphatidycholine

  • Supports brain chemicals acetylcholine, dopamine and norepinephrine

  • Helps create and repair brain cell membranes and DNA.

  • Protects brain cells from the damaging effects of free radicals and aging

Nootropic Effects

  • Energizes brain cells

  • Enhances memory and recall

  • Promotes focus and attention

  • Supports overall cognitive function

We will cover some of the research backing these beneficial CDP choline effects a little later in this article. We'll also discuss its potential in another central nervous system pathway: the eyes. Beyond the brain, citicoline is suggested as a vision enhancer.

How Citicoline Might Work

Next let's take a look at some citicoline bioactivities believed to account for its various benefits.

Brain Energy

Citicoline has been suggested to help the brain generate electrical impulses by supporting proper function of mitochondria: the powerhouses that generate cell energy. 

Healthy mitochondrial function results in higher levels of ATP energy in brain cells, which in turn powers not only mental energy, but also the demanding tasks of higher-order cognition and brain regeneration. One human research study found that Cognizin® Citicoline increased frontal lobe brain energy levels by 13.6%.

Brain Regeneration

In addition to supporting the energy that fuels brain regeneration, Citicoline promotes formation and healthy function of brain cell membranes as a cholinergic compound that raises brain levels of phosphatidylcholine.

Phosphatidylcholine is one of the phospholipid building block compounds that makes up about 30% of all brain tissue. Due to its ability to affect brain phospholipid composition, Citicoline may help with brain renewal, support efficient formation of new brain cells and promote brain cell membrane integrity.(5)

Neurotransmitters (Brain Chemicals)

Citicoline helps to form acetylcholine, which is the brain's most important executive neurotransmitter.(6) Acetylcholine is largely responsible for the function of working memory, learning and information processing, as well as muscle contraction and speech.

Since acetylcholine levels decline with age, and low acetylcholine is linked to brain degeneration, researchers have suggested that Citicoline (as Cognizin) may be a useful potential therapy for age-related cognitive decline.(7)

Citicoline may also support brain chemical dopamine and norepinephrine production, which are associated with more immediate benefits for mood and performance-driven cognition. Its far-reaching impact on brain chemicals position citicoline as one of the best nootropics for neurotransmitters.

Brain Circulation

Citicoline in supplement form has been suggested to promote healthy cerebral circulation. In one study of patients with brain degeneration and memory problems, researchers reported that left temporal cerebral blood flow appeared to normalize after supplementation with citicoline.(8) This may suggest potential to help with cerebrovascular disorders in general.

Brain Protection

Other brain-protective nootropic supplements supply antioxidant activity that helps to neutralize the brain cell-damaging effects of toxic free radicals. Citicoline adds another level of neuroprotective activity that may be even more important: Citicoline protects hippocampal neurons in the brain via phosphatidylcholine synthesis, helping to strengthen brain cell membranes and enhance neural repair.(9)

Citicoline Supplement Research Summaries

So what about the research behind citicoline? There have been a few human clinical trials on this brain nutrient, along with several animal research and "petri dish" style studies. Let's take a look at a few that focus on citicoline's potential roles in brain performance.

Citicoline may help brain energy and brain cell regeneration

In a randomized controlled trial, 16 healthy men and women with an average age of 47 took either 500 mg or 2,000 mg Cognizin® Citicoline every day for 6 weeks and were then evaluated for changes to their brains’ structure and function.

Researchers reported the Cognizin® Citicoline was associated with a 14% increase in brain ATP (“cellular currency” for brain energy) and 35% increase in brain cell membrane turnover (repair, rejuvenation & replacement). Researchers suggested these benefits may help counter brain degeneration related to aging and low brain energy levels.(10)

Citicoline improves verbal memory and may help rejuvenate brain cells

In this randomized placebo controlled trial, subjects were given 500 mg of Citicoline daily for six weeks, and then continued with either more Citicoline or placebo for another six weeks.

Researchers reported Citicoline was associated with a 7.3% increase in brain photodiesters, and that subjects’ performance in verbal learning improved as photodiesters increased. Researchers have suggested that that chronic citicoline increases phosphodiesters, sparks the synthesis and rejuvenation of brain cell membrane phospholipids, and therefore may help with age-related changes in the brain.(11)

While not mentioned in this specific placebo controlled study, these changes may also suggest help for age-related cognitive impairment and other chronic cerebral disorders.

Citicoline may help with attentional performance

In this randomized controlled clinical trial, 60 women age 40 to 60 took 250 mg Cognizin® Citicoline, 500 mg Cognizin® Citicoline, or placebo every day for 28 days, and were then administered cognitive performance testing.

Researchers reported that the testing results of this placebo controlled clinical trial showed both doses of Cognizin® were linked to higher test scores, with the 500 mg serving showing the greatest benefit. Researchers concluded that Citicoline may enhance cognitive function and attentional performance in middle-aged women.(12)

Citicoline may help memory in elderly subjects

Elderly study subjects supplemented with Cognizin® Citicoline CDP Choline (500 mg or 1000 mg), placebo, or a drug daily for a span of four weeks prior to mental performance testing.

Researchers reported that, when compared to placebo, Citicoline improved memory, word recall, immediate recall, and delayed recall. Researchers attributed these benefits to Citicoline’s neuroregenerative and cerebral circulation-boosting properties, and suggested it may be helpful for memory loss in geriatric populations.(13)

Healthy adolescents may improve attention with Citicoline supplements

75 healthy adolescent males received 250 mg Cognizin® Citicoline, 500 mg Cognizin® Citicoline, or placebo daily for 28 days. Study subjects completed cognitive performance tests at the study’s starting point and end point.

Researchers reported that the study subjects who took Citicoline showed improvements in attention and psychomotor speed (versus placebo). The larger dosage of Citicoline was more strongly associated with mental performance benefits, including increased accuracy of attention, improved detection ability during attention tasks, and decreased cognitive and behavioural disturbances.(14)

**Those under age 18 should only take dietary supplements under the direction of a doctor. 

Is Citicoline a drug?

This question is a little complicated to answer. In the United States, citicoline is sold as a supplement. As such, its claims relate to supporting healthy brain function, enhancing some aspects of cognition, fighting cognitive decline and assisting with mild cognitive impairment.

In other parts of the world, oral citicoline is considered for more serious health concerns and cognitive deficits. For example, in Europe and Japan, citicoline treatment is used for acute stroke, traumatic brain injury, chronic cerebrovascular diseases and other CNS disorders (central nervous system), along with age-related cognitive dysfunctions. Its use for these concerns reflects citicoline's extensive pharmacological and clinical review.

Let's take a look at some of citicoline's other uses around the world, where it is sometimes administered more like a pharmaceutical drug than a supplement.

Acute ischaemic stroke

In an acute ischaemic stroke, blood flow to the brain is abruptly cut off. Parts of the brain that do not receive blood flow become damaged, as brain cells die. This is known as an ischemic brain injury.

As we mentioned earlier, citicoline breaks down into choline and cytidine. These two compounds are required for the synthesis of phosphatidylcholine, which is a key raw material that is used to repair and create healthy cell membranes, including brain cells. Due in part to these bioactivities:

Oral citicoline treatment has been approved in Japan and some parts of Europe for assisting people with acute ischemic stroke.

Brain cell membrane repair and regeneration -- which citicoline is suggested to support -- play a significant role in recovery from acute ischemic stroke.

Researchers have cited data from multiple clinical trials that support the potential of chronic citicoline intake as a safe way to support recovery from issues related to acute stroke.(15)

Vascular dementia

Mild vascular cognitive impairment refers to mental performance issues brought on by insufficient blood flow to the brain. Vascular cognitive impairment deficits that follow this cerebral disorder include issues with memory (including verbal memory), attention and executive functions.

In a similar vein and related to acute ischemic stroke is vascular dementia: a chronic cerebrovascular disease where these symptoms worsen. Vascular dementia is the second most common form of dementia, caused by poor blood flow to the brain for any reason, including strokes and mini-strokes (transient cerebral ischemia).

CDP-Choline has been researched for its potential to help with vascular dementia and other cerebrovascular disorders.

In one review, researchers reported that CDP-choline appeared to assist with memory function and behavior in individuals with memory problems, including subjects with mild-to-moderate vascular cognitive impairment, vascular dementia or senile dementia. Researchers concluded some evidence backs CDP-choline's beneficial effects and called for more study, especially in the clinical aspects of vascular dementia and vascular mild cognitive impairment.(16)

Citicoline combination therapy

Combination therapy refers to when multiple drugs are use together to target a single health concern. One example is a research study that found citicoline and the drug citalopram to be an effective combination therapy for helping with depression. Researchers noted citicoline's influence on mood-related brain chemicals may contribute to its beneficial mood effects.(17)

Other Citicoline Uses

Citicoline for vision

Research suggests citicoline helps protect neurons. But neurons are not limited to the brain. They include retinal cells required for sharp vision and overall eye health. In one review, researchers have proposed Glaucoma patients may benefit from citicoline supplementation, suggesting that the compound's neuroprotective activity may represent a safe, effective way to support vision.(18) Researchers have also suggested citicoline eyedrops reduce progression of glaucoma.(19)

Citicoline FAQ

Now let's take a look at some common questions related to this powerful brain nutrient.

Citicoline Dosage: How much should you take?

How much Citicoline should you take per day?

The dose of Citicoline that you use ultimately depends on what you are looking to get out of the nootropic.

For serious cases of cognitive dysfunction, brain injury, or other concerns, the usual daily therapeutic dosage of citicoline in humans is 500–2,000 mg. In other words, 7–28 mg/kg of oral CDP choline per day for a person of average bodyweight (70 kg).

But for day-to-day cognitive enhancement, you don't need to use anywhere near this much Citicoline. The clinical evidence suggests that as little as 150mg of Citicoline per day is sufficient to support focus, learning, and information processing speeds.

There is a dose-dependent relationship up to around 250mg per day. Beyond that point, larger doses of Citicoline do not seem to confer any extra benefits to otherwise healthy people.

Can you take Citicoline every day?

Is it safe to take Citicoline every day? Not only is it safe to take CDP choline every day, but you should take it on a daily basis. Citicoline (cytidine 5 diphosphocholine) has multiple different mechanisms of action. One of these is increased brain cell maintenance and development via the donation of cytidine. Long-term, daily CDP choline use has been found to have significant benefits over using it on an infrequent basis due to overall better brain cell development and health.

What is a common side effect of citicoline?

Citicoline is naturally occurring within the body. Therefore, it is regarded as having low toxicity and little concern for side effects. Most clinical research studies on it report that no side effects were experienced by subjects. However, as with any supplements, individual sensitivities vary. Rarely reported side effects associated with citicoline supplementation may include digestive distress, nausea, sleep problems and blood pressure imbalance.

Can citicoline help with anxiety?

In one early study, researchers reported that citicoline appeared to have the potential to help ease symptoms of anxiety and major depressive disorder in post-stroke patients.(20) Researchers noted that more clinical study was needed for this therapy, however. Citicoline may indeed have potential to help with anxiety, but other nootropics are backed by stronger and more extensive research. To learn more, read our article on the best nootropics for anxiety.

Does citicoline reduce brain inflammation?

Some early animal research suggests that citicoline may play a role in regulating brain inflammation.(21) Researchers believe it may regulate enzymes that are involved in the breakdown of cell membranes. While this bioactivity may suggest potential, as with citicoline for anxiety, there are other nutrients with far more research for modulating inflammatory responses, including but not limited to the Omega-3 fatty acid DHA (docosahexaenoic acid), which also happens to be one of the best nootropics for adults overall.

Does citicoline help ADHD?

Above we have referenced one research study using Cognizin® that suggested citicoline may benefit adolescent males by improving attention and reducing impulsivity. While the research is early, it does suggest that the Cognizin® form, at least, may assist with attention on some level. This is not necessarily help for attention deficit hyperactivity disorder (ADHD), however. To learn more about some nootropics and brain supplements for ADHD specifically, read our article on the topic here.

Citicoline vs. Choline: What's the difference?

Citicoline and choline are not the same. Choline is one component of Citicoline. But citicoline is distinct from choline because it also supplies cytidine. For more information on this topic, check out our article here.

Is Citicoline the same thing as CDP choline?

There is actually a distinction between Citicoline and CDP-Choline (cytidine diphosphate choline). When physicians adminster the compound as a therapy (e.g. to help with brain injury recovery), it is called Citicoline. When produced naturally in the brain, it is CDP-Choline. But ultimately, citicoline and CDP choline are structurally the same; one and the same thing.

Best Brain Supplement with Citicoline: Mind Lab Pro®

Mind Lab Pro® Universal Nootropic™

Mind Lab Pro®'s Citicoline optimizes brainpower at a cellular level while nourishing the brain with building block neuronutrients – uniquely supporting the healthy brain metabolism, repair, maintenance and regeneration that are crucial for sharp overall cognition.

With additional support for neurotransmitters, brain circulation and brain defenses, Citicoline is the driving-force ingredient of Mind Lab Pro®'s 100% Brainpower™ effects: A single nootropic that boosts multiple pathways to optimize mental performance and whole-brain health.

Mind Lab Pro® includes 11 brain nutrients:

  1. Citicoline, 250 mg

  2. Phosphatidylserine (PS): Best overall memory-boosting nootropic.

  3. Bacopa, 150 mg. Bacopa monnieri as full-spectrum extract, 24% bacosides with 9 bioactives)

  4. Lion’s Mane, 500 mg: Organic lion's mane mushroom (fruit and mycelium)

  5. Maritime Pine Bark Extract, 75 mg: Standardized to 95% proanthocyanidins

  6. N-Acetyl L-Tyrosine, 175 mg

  7. L-Theanine, 100 mg

  8. Rhodiola rosea: Standardized to 3% rosavins and 1% salidrosides

  9. Vitamin B6, 2.5 mg, from NutriGenesis®

  10. Vitamin B9, 100 mcg, from NutriGenesis®

  11. Vitamin B12, 7.5 mcg, from NutriGenesis®

Stacked together in Mind Lab Pro®, these nootropics support every aspect of peak cognitive performance. It is designed to help with:

  • Mental clarity and fast processing speed

  • Concentration, attention and focus

  • Multitasking and performing under pressure

  • All forms of memory, including new learning

  • Mood, stress resistance and motivation

Mind Lab Pro® is also designed to nourish the brain for long range health, helping with age-related cognitive concerns and strengthening antioxidant defenses for healthy brain aging.

Mind Lab Pro® is Backed By Research.

Mind Lab Pro® is one of the only nootropic supplements on the market that has been the subject of rigorous clinical human trials.

In this research, it demonstrated clinical efficacy by improving brain performance across several key cognitive markers.

  1. In one study, researchers reported that subjects taking Mind Lab Pro for 30 days experienced significant improvements (when compared to those taking placebo) in performing information processing tasks involving simple reaction time (SRT), choice reaction time (CRT) and anticipation.(1)

  2. A second study found that subjects taking Mind Lab Pro demonstrated significant improvements across all memory functions that were tested, including auditory, visual, visual working, immediate and delayed recall memory.(2)

Why Mind Lab Pro® includes Citicoline

 

 

Best Brain Supplement with Cognizin® Citicoline: Performance Lab® Mind

In this article, we have referenced citicoline as a generic nutrient along with a patented form called Cognizin® citicoline. This particular form of citicoline has been researched more extensively than any other.

Mind Lab Pro® uses a quality generic citicoline as part of its 11-ingredient nootropic stack.

Performance Lab® Mind, on the other hand, is a more streamlined 4-ingredient nootropic stack that uses patented Cognizin® citicoline. It supplies:

  • Cognizin® Citicoline, 250 mg

  • Sharp-PS® Green (Phosphatidylserine), 100 mg

  • Ajipure® L-Tyrosine, 250 mg

  • Maritime Pine Bark Extract (95% proanthocyanidins), 75 mg

Where Mind Lab Pro is universal, Performance Lab® Mind is a little more focused as a brain supplement. It promotes mental performance and mental recovery at once, in a brain-healthy formula for the long haul.

Conclusion

Whether you call it cytidine diphosphate choline, CDP Choline, diphosphocholine CDP choline, or simply citicoline, this naturally occurring compound remains one of the best nootropics you can take.

Mind Lab Pro and Performance Lab Mind are two top supplements that supply this powerful brain-booster. Both are high-quality formulations that are sure to deliver citicoline's best benefits for mental performance, brain health and more.

     

    References

    1. Liu L, Qiao S, Zhuang L, Xu S, Chen L, Lai Q, Wang W. Choline Intake Correlates with Cognitive Performance among Elder Adults in the United States. Behav Neurol. 2021 Oct 29;2021:2962245. doi: 10.1155/2021/2962245. PMID: 34745383; PMCID: PMC8570899.

    2. Dobolyi A, Juhász G, Kovács Z, Kardos J. Uridine function in the central nervous system. Curr Top Med Chem. 2011;11(8):1058-67. doi: 10.2174/156802611795347618. PMID: 21401495.

    3. Utley A, Gonzalez Y, Imboden CA. The Efficacy of A Nootropic Supplement on Information Processing in Adults: A Double Blind, Placebo Controlled Study. Biomed J Sci & Tech Res 49(1)-2023.
      BJSTR. MS.ID.007746

    4. Abbott-Imboden C., Gonzalez Y., Utley A. (2023). Efficacy of the nootropic supplement Mind Lab Pro on memory in adults: Double blind, placebo-controlled study. Human Psychopharmacology: Clinical and Experimental, e2872. https://doi.org/10.1002/hup.2872

    5. Martynov MY, Gusev EI. Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke. J Exp Pharmacol. 2015 Oct 1;7:17-28. doi: 10.2147/JEP.S63544. PMID: 27186142; PMCID: PMC4863531.

    6. Synoradzki K, Grieb P. Citicoline: A Superior Form of Choline? Nutrients. 2019 Jul 12;11(7):1569. doi: 10.3390/nu11071569. PMID: 31336819; PMCID: PMC6683073.

    7. Fioravanti M, Buckley AE. Citicoline (Cognizin) in the treatment of cognitive impairment. Clin Interv Aging. 2006;1(3):247-51. doi: 10.2147/ciia.2006.1.3.247. PMID: 18046877; PMCID: PMC2695184.

    8. León-Carrión J, et al.  The role of citicholine in neuropsychological training after traumatic brain injury. NeuroRehabilitation. 2000; 14(1):33-40.

    9. Alvarez-Sabín J, Román GC. Citicoline in vascular cognitive impairment and vascular dementia after stroke. Stroke. 2011 Jan;42(1 Suppl):S40-3.

    10. Silveri, 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 California

    11. Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, Yurgelun-Todd DA, Renshaw PF. Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacology (Berl). 2002 May;161(3):248-54. doi: 10.1007/s00213-002-1045-y. Epub 2002 Mar 22. PMID: 12021827.

    12. E. McGlade, A. Locatelli, J. Hardy, T. Kamiya, M. Morita, K. Morishita, Y. Sugimura and D. Yurgelun-Todd, "Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women," Food and Nutrition Sciences, Vol. 3 No. 6, 2012, pp. 769-773. doi: 10.4236/fns.2012.36103.

    13. Alvarez XA, et al. Citicoline improves memory performance in elderly subjects.Methods Find Exp Clin Pharmacol. 1997 Apr;19(3):201-10.

    14. McGlade E, Agoston AM, DiMuzio J, Kizaki M, Nakazaki E, Kamiya T, Yurgelun-Todd D. The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males. J Atten Disord. 2019 Jan;23(2):121-134. doi: 10.1177/1087054715593633. Epub 2015 Jul 15. PMID: 26179181.

    15. Alvarez-Sabín J, Román GC. The role of citicoline in neuroprotection and neurorepair in ischemic stroke. Brain Sci. 2013 Sep 23;3(3):1395-414. doi: 10.3390/brainsci3031395. PMID: 24961534; PMCID: PMC4061873.

    16. Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD000269. doi: 10.1002/14651858.CD000269.pub3. PMID: 15846601.

    17. Roohi-Azizi M, Arabzadeh S, Amidfar M, Salimi S, Zarindast MR, Talaei A, Akhondzadeh S. Citicoline Combination Therapy for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin Neuropharmacol. 2017 Jan/Feb;40(1):1-5. doi: 10.1097/WNF.0000000000000185. PMID: 28085707.

    18. Iulia C, Ruxandra T, Costin LB, Liliana-Mary V. Citicoline - a neuroprotector with proven effects on glaucomatous disease. Rom J Ophthalmol. 2017 Jul-Sep;61(3):152-158. doi: 10.22336/rjo.2017.29. PMID: 29450391; PMCID: PMC5710031.

    19. Rossetti L, Iester M, Tranchina L, Ottobelli L, Coco G, Calcatelli E, Ancona C, Cirafici P, Manni G. Can Treatment With Citicoline Eyedrops Reduce Progression in Glaucoma? The Results of a Randomized Placebo-controlled Clinical Trial. J Glaucoma. 2020 Jul;29(7):513-520. doi: 10.1097/IJG.0000000000001565. PMID: 32541370; PMCID: PMC7337116.

    20. Arcadi FA, Corallo F, Torrisi M, Scarfì C, Lo Buono V, Formica C, Bramanti P, Marino S, Bonanno L, De Cola MC. Role of citicoline and choline in the treatment of post-stroke depression: an exploratory study. J Int Med Res. 2021 Nov;49(11):3000605211055036. doi: 10.1177/03000605211055036. PMID: 34727752; PMCID: PMC8573512.

    21. Adibhatla RM, Hatcher JF. Citicoline decreases phospholipase A2 stimulation and hydroxyl radical generation in transient cerebral ischemia. J Neurosci Res. 2003 Aug 1;73(3):308-15. doi: 10.1002/jnr.10672. PMID: 12868064.

    These statements have not been approved by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

    This article is an opinion and explanation of current research given by the author. It is not an expression of a medical diagnosis or treatment and should not be relied on as such.

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