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5 Citicoline (CDP-Choline) Benefits + Dosage & Side Effects

Written by Aleksa Ristic, MS (Pharmacy) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Aleksa Ristic, MS (Pharmacy) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Citicholine

Citicoline is praised for cognition-enhancing properties among the young and elderly alike. Clinical studies confirmed some of its promoted benefits, revealed other unexpected perks, but also pointed to significant limitations. Read on for an ultimate breakdown of citicoline benefits, dosage, and safety profile.

What is Citicoline?

Citicoline (cytidine-5-diphosphocholine, CDP-choline) is crucial for the production of phospholipids such as phosphatidylcholine. These molecules build cell membranes and protective nerve coatings in the body [1].

Citicoline is a more complex molecule than regular choline, or even alpha-GPC, but it’s identical to what your brain naturally makes. To avoid confusion, scientists decided to call it “citicoline” when given as a therapy and “CDP-choline” when it’s produced in the body [2].

Once ingested, it releases two compounds: cytidine and choline. After they pass the blood-brain barrier, neurons in the brain use them to make citicoline and other phospholipids [3].

Choline boosts acetylcholine and other neurotransmitters that keep the nervous system running smoothly. The body transforms citicoline into a number of other beneficial compounds. For this reason, citicoline may have more benefits and a better side-effects profile than regular choline [4, 5, 3].

Snapshot

Proponents:

  • Boosts cognition
  • Prevents brain damage
  • May help with depression and drug addiction
  • Supports stroke recovery
  • Improves eyesight

Skeptics:

  • Most benefits lack stronger clinical evidence
  • Long-term use may put a strain on the kidneys
  • Not suitable for children and pregnant women

How It Works

Citicoline increases the production of neurotransmitters and cellular building blocks. Besides acetylcholine, it also boosts norepinephrine and dopamine in the brain [4, 6].

It can enhance brain blood flow and stimulate mitochondria to produce more energy [4, 5, 2].

Sufficient levels of CDP-choline preserve phosphatidylcholine and sphingomyelin, which build the protective nerve sheet called myelin. Citicoline also inhibits the inflammatory enzyme phospholipase A2 and boosts the master antioxidant glutathione [7, 8].

All in all, citicoline works by balancing neurotransmitters and protecting the nervous system from oxidative and age-related damage [9, 10, 1].

Dietary Sources

The body makes citicoline from cytidine and choline. The best way to increase the levels of citicoline through food is to consume enough food sources that provide both.

Choline-rich foods include [11, 12]:

  • Organ meats (liver)
  • Eggs
  • Chicken
  • Fish
  • Whole grains
  • Beans

Cytidine, an RNA nucleoside, is most concentrated in meat (especially organ meats); it’s also found in colostrum [13, 14].

Citicoline supplements (Cognizin, Somazina) are another potential sources of additional choline, along with:

  • Choline
  • alpha-GPC
  • Phosphatidylcholine
  • Lecithin

CDP-Choline vs. Alpha-GPC

Although both CDP-choline and alpha-GPC provide choline and share many health benefits, the body breaks down and uses them differently.

CDP-choline releases choline, cytidine, and other metabolites. It can also be transformed into phosphatidylcholine, which the brain uses to make acetylcholine or to build cell membranes. Alpha-GPC more directly supplies choline for the production of acetylcholine [15].

In turn, CDP-choline has a broader range of potential benefits, but alpha-GPC may have an edge in boosting physical and mental performance [16, 17].

Citicoline Health Benefits

Possibly Effective:

1) Cognitive Enhancement

Age-Related Cognitive Decline

Cognition tends to decline with aging, due to reduced brain blood flow or other causes. A review of 14 clinical trials concluded that CDP-choline could improve memory and behavior in people with mild to moderate cognitive impairment, including those with poor brain circulation [9].

According to the data from over 2,800 older patients, memory problems disappeared in 21% and improved in 45% of the cases upon receiving citicoline. This study lacked a placebo control so we should take the results with a grain of salt [18].

Citicoline (1,000 mg for 9 months) had beneficial effects on 350 older patients with mild cognitive impairment as it [19]:

  • Strengthened the nerve membranes
  • Boosted the levels of noradrenaline and dopamine
  • Prevented oxidative damage

In three studies of 210 patients with dementia and poor brain circulation, CDP-choline improved memory, reaction speed, and behavior. Higher citicoline dosage (2,000 mg) yielded better results [20, 21, 22].

Nootropic Effects

Many use citicoline to sharpen their mind, enhance memory, and prevent cognitive decline. Let’s see what the science says about its nootropic effects…

In two clinical trials on 135 healthy adults, citicoline (250-500 mg) improved focus and mental clarity [23, 24].

A beverage with caffeine and CDP-choline (250 mg) enhanced cognition and reduced reaction times in 60 volunteers. Caffeine is a known stimulant and it likely contributed to the results [25].

In 24 healthy adults, higher citicoline doses (500 or 1000mg) improved a variety of cognitive markers – processing speed, working and verbal memory, executive function – but only in low cognitive performers [26].

In the same study, supplementation had no effects in medium performers and even slightly impaired cognition in high performers [26]

Marijuana abuse can impair cognition. In one study of 19 chronic marijuana smokers, citicoline (2000 mg daily for 8 weeks) reduced impulsive reactions and improved cognition. All included participants wanted to stop smoking, and the researchers thought that citicoline’s effects might help steer them in that direction [27, 28].

According to preliminary research, citicoline may enhance focus and mental clarity, especially in low cognitive performers.

2) Stroke Recovery

Cut blood supply to a specific brain region can kill the neurons and inflict massive brain damage. Citicoline may help by strengthening nerve membranes and blocking free radical production [29, 30].

According to a meta-analysis of 4 clinical trials (1,300+ patients), citicoline at 2,000 mg within the first 24 h after a stroke increases the chance of complete recovery by 38% [10].

The data from over 4,000 stroke survivors reveal that citicoline improves the outcomes and aids in recovery; higher doses (2,000 – 4,000 mg) were more effective. The lack of placebo control in this study doesn’t allow for definite conclusions [31].

Two studies of over 3,000 patients found no significant benefits of CDP-choline for acute stroke [32, 33].

Drugs that dissolve blood clots remain the first choice for acute stroke. Two comprehensive reviews concluded that citicoline could provide additional benefits or help the patients who can’t receive the first-choice treatment [34, 35].

Prompt citicoline administration may improve stroke recovery, but the research is limited. Drugs that dissolve blood clots remain the first choice for acute stroke.

3) Vision Problems

Just like it shields the nerves in the brain and spinal cord, citicoline may have the same beneficial effects on the optic nerve. It may reverse the damage of neurons in your retina and help with eye disorders such as [1]:

  • Optic neuropathy
  • Glaucoma
  • “Lazy eye”

Glaucoma

Increased eye pressure and other factors can damage the optic nerve and cause glaucoma, sometimes even leading to total blindness [36].

In two clinical trials with 80 glaucoma patients, long-term treatment with oral citicoline repaired nerve damage, improved eyesight, and slowed down disease progression [37, 38].

Eye drops with citicoline showed the same results in another two clinical trials (68 patients) [39, 40].

Amblyopia

Amblyopia or “lazy eye” occurs when the eye and brain don’t communicate well. It results in blurry vision in one eye [41].

Oral citicoline improved standard lazy eye treatment (eye patching) in three clinical trials with 190 children [42, 43, 44].

Injections with CDP-choline (1,000 mg daily) healed the optic nerve and improved vision in 10 adults with amblyopia. This study had a tiny sample and lacked a placebo control, making the results questionable [45].

Optic Neuropathy

Optic neuropathy is another form of optic nerve damage that may hinder your eyesight. In 26 patients with optic neuropathy, citicoline (1,600 mg/day for 2 months) sharpened vision by repairing nerve damage [46].

Insufficient Evidence:

No valid clinical evidence supports the use of citicoline for any of the conditions in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.

4) Brain Damage

Oxidative stress, autoimmune response, and environmental toxins can inflict severe brain cell damage. Citicoline protects the brain and spinal cord against these stressors by preserving the cells’ myelin sheath and boosting vital neurotransmitters.

Alzheimer’s Disease

In three clinical trials, citicoline (1,000 mg daily for 1 – 3 months) improved the symptoms of Alzheimer’s disease by [47, 48, 49]:

  • Enhancing mental performance
  • Stimulating blood flow in the brain
  • Cutting the levels of inflammatory molecules (histamine and IL1B)

However, two studies lacked placebo controls, making the results questionable.

In the third study, patients with a genetic predisposition for Alzheimer’s disease – APOE-e4 carriers – experienced greater benefits. This is an important finding as APOE-e4 carriers respond differently (often worse) to various interventions [48, 50].

Citicoline boosted the effects of Alzheimer’s disease drug treatment, slowing progression in two observational trials (over 600 patients) [51, 52].

In rats with Alzheimer’s disease, citicoline protected the nerves against protein mutations and reduced blood flow. As a result, the rats suffered less cognitive impairment, and their memory improved [53].

Citicoline might help with Alzheimer’s disease and improve standard treatment, but the available clinical evidence is weak.

Parkinson’s Disease

The destruction of dopamine neurons in Parkinson’s disease causes muscle stiffness, trembling, and other symptoms.

In rats with Parkinson’s disease, citicoline relieved muscle stiffness by raising the levels of dopamine in the brain. It also boosted the effects of standard treatment [54, 55].

Multiple Sclerosis

Inflammatory destruction of outer nerve sheet, myelin, can trigger multiple sclerosis with severe physical and cognitive impairments. In animals with multiple sclerosis, scientists observed the potential of citicoline to enhance myelin recovery and movement coordination [56, 57].

5) Mental Disorders and Drug Addiction

Depression

The addition of citicoline to an antidepressant drug (citalopram) improved depression symptoms and recovery in a study with 50 patients [58].

In rats, CDP-choline raised noradrenaline, dopamine, and serotonin levels in the brain centers for memory, emotions, and movement [59, 60].

Meth and Cocaine Addiction

Citicoline reduced depression in 60 methamphetamine (meth) addicts but didn’t impact drug use (2,000 mg/day for 3 months). In another study of 31 meth addicts, citicoline protected the brain and reduced drug use [61, 62].

In over 130 cocaine addicts with bipolar disorder, citicoline (500 – 2,000 mg for 3 months) reduced drug use but didn’t impact mood. However, it produced no effects in a trial of 20 heavy cocaine users [63, 64, 65].

A review of nine trials concluded that citicoline may provide mild benefits for substance addiction, especially cocaine, but underlined the need for stronger clinical evidence [66].

Schizophrenia

Citicoline boosted the effects of standard treatment in 66 patients with schizophrenia. It improved the so-called “negative” symptoms, such as blunted emotions, poor communication, and stiffness. These are especially hard to treat with conventional drugs [67].

In 24 healthy adults, CDP-choline enhanced cognition by stimulating nicotinic acetylcholine receptors, which are often underactive in schizophrenia [26].

The preliminary research is promising, but there’s not enough evidence to support the use of citicoline for mental disorders and drug addiction.

Side Effects & Safety

This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.

Many clinical trials with citicoline have confirmed its safety. In rare cases, it may cause mild digestive and nerve issues [18, 31, 25, 47, 61, 10, 37].

In a safety study on rats, citicoline caused no significant side effects even in much higher doses than usual (2,000 mg/kg). Long term use of high doses raised creatinine levels and kidney mineralization, likely due to its phosphorus content [68].

In another study on rats, citicoline increased the blood levels of ACTH, which stimulates the production of the stress hormone, cortisol. However the researchers injected citicoline directly into brain fluid, and it’s not clear whether oral consumption would have this effect [69].

Sensitive Groups

Children, pregnant women, and breastfeeding women should avoid citicoline until we know more about its safety in these sensitive groups.

If you’ve had an allergic reaction to any choline-containing supplement (choline, lecithin, alpha-GPC), you may want to avoid citicoline.

Citicoline Dosage & Supplements

The below doses may not apply to you personally. If your doctor suggests using citicoline, work with them to find the optimal dosage according to your health condition and other factors.

The following citicoline dosage produced some beneficial effects in clinical trials:

  • Boosting cognition and memory: 250 – 1,000 mg/day [25, 23, 26]
  • Age-related cognitive decline: 1 000 – 2,000 mg/day, 4+ weeks [19, 20, 70]
  • Alzheimer’s disease: 1,000 mg/day, 1 – 3 months [47, 48, 49]

Higher doses of 2,000 – 2,500 mg daily for 6+ weeks were efficient for [61, 64, 71, 31, 34]:

  • Depression
  • Drug addiction
  • Stroke recovery

Most eye diseases responded to 800-1,600 mg of citicoline and the treatments lasted for 2-4 months. For glaucoma, 3 eye drops daily for 4 months were also efficient [37, 46, 42, 39, 40].

Supplements

Citicoline supplements have not been approved by the FDA for medical use. In general, regulatory bodies aren’t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.

Most products on the market contain pills with 250 – 500 mg of citicoline (CDP-choline). Their potency may be the critical factor since many conditions require a daily citicoline dosage of 2,000 mg or more.

Vegan-friendly citicoline supplements are also available.

User Reviews

The opinions expressed in this section are solely from the users who may or may not have a medical background. SelfHacked does not endorse any specific product, service, or treatment. Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice because of something you have read on SelfHacked.

Most users have reported positive experiences with citicoline supplements for cognitive support and brain fog. Some have even managed to relieve the symptoms of depression and Parkinson’s disease.

A smaller part of users reaped no benefits from citicoline. The most common side effects include diarrhea, headache, and insomnia.

Takeaway

Citicoline (CDP-choline) shields the nerves by strengthening their membranes and raising the levels of vital neurotransmitters. It may have nootropic effects in healthy people, prevent the elderly from cognitive decline, and support stroke recovery.

Oral supplements or drops may also help with eye diseases such as glaucoma, while there’s not enough evidence for mental health and drug addiction benefits.

You can get its building blocks through food, especially by eating more organ meats. However, the doses used in clinical trials (1000-2000 mg/day) may only be reached with supplements.

Citicoline is safe and well-tolerated. Mild side effects, such as digestive issues and headaches, are possible. Children, pregnant women, and people allergic to choline-containing supplements should avoid it, while others should consult with their doctor first.

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About the Author

Aleksa Ristic

Aleksa Ristic

MS (Pharmacy)
Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets. 
Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

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