Looking for a natural brain booster? Look no further! Citicoline will enhance your cognition and mental clarity, shield your brain against damage, and prevent mental disorders. Read on for an ultimate breakdown of citicoline pros and cons.

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 your body [1].

Citicoline is a more complex molecule than regular choline (or even than 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].

Your body knows how to “recycle” citicoline. Once you take citicoline as a supplement, it releases two compounds: cytidine and choline. Once they pass the blood-brain barrier, neurons in the brain use them to make citicoline again [3].

Choline and cytidine offer some benefits on their own. Choline boosts acetylcholine and other neurotransmitters that keep the nervous system running smoothly and efficiently [4, 5, 3].

There’s more: the body transforms citicoline into a number of other beneficial compounds. For this reason, citicoline has more powerful benefits and a better side-effects profile than regular choline [3].

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 your 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].

Snapshot

PROs

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

CONs

  • May raise the risk of heart disease and prostate cancer
  • Long-term use may put a strain on the kidneys
  • Not suitable for children and pregnant women

Dietary Sources

Your body makes citicoline from cytidine and choline. The best way to increase your 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, being an RNA nucleoside, is most concentrated in meat (especially organ meats). It’s also found in colostrum [13, 14].

Citicoline supplements (Cognizin, Somazina) are a major source of additional choline, along with pure choline, alpha-GPC, and 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, 15].

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

Citicoline Health Benefits

1) Boosts Cognition

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 [18, 19].

A beverage with caffeine and CDP-choline (250 mg) enhanced cognition and reduced reaction times in 60 volunteers [20].

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 [21].

In the same study, supplementation had no effects in medium performers. And here’s the curious part: it even slightly impaired cognition in high performers. It could be that people with exceptional cognitive abilities already have enough CDP-choline and that adding more could be “too much of a good thing.”  [21]

Heavy, chronic marijuana use impairs cognition. In one study of 19 chronic marijuana smokers, citicoline (2000 mg daily for 8 weeks) reduced impulsive reactions, improved cognition, and altered patterns of brain activity. All included participants wanted to stop smoking and researchers considered that citicoline’s effects might help steer them in that direction [22, 23].

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 disappear in 21% and improve in 45% of the cases upon receiving citicoline [24].

This study lacked a placebo control so we should take the results with a grain of salt.

Citicoline (1,000 mg for 9 months) had beneficial effects on 350 older patients with mild cognitive impairment as it [25]:

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

In studies on 120 patients with memory loss, CDP-choline increased memory and reaction speed. Higher citicoline dosage (2,000 mg) yielded better results [26, 27].

Citicoline reversed cognitive decline in another study on 237 older patients, but this one lacked a placebo control [28].

3) Protects the Brain

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 3 clinical trials, citicoline (1,000 mg daily for 1 – 3 months) relieved the symptoms of Alzheimer’s disease by [29, 30, 31]:

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

Patients with a genetic predisposition for Alzheimer’s disease – APOE-e4 carriers – experienced greater benefits. Despite being a small trial (30 people), this is an extremely important finding. APOE-e4 carriers respond differently (often worse) to various interventions [30, 32].

Citicoline boosted the effects of Alzheimer’s disease drug treatment, slowing progression in 2 observational trials (over 600 patients). The trial used acetylcholinesterase inhibitors, which prevent acetylcholine breakdown [33, 34].

Many natural nootropic substances have a similar mechanism of action, and citicoline might synergize with them.

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 [35].

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 [36, 37].

Side Effects of Antipsychotic Drugs

Long-term antipsychotic treatment can cause a movement disorder that looks similar to Parkinson’s disease (tardive dyskinesia). Antipsychotics can block dopamine, bring other neurotransmitters out of balance, and cause choline deficiency. This explains why citicoline might help [38].  

CDP-choline improved this disorder in a study from the ’80s with 10 patients (500 – 1,200 mg daily, 1 month). However, it had no effect on 5 patients with the same disorder [39, 40].

We can’t draw reliable conclusions from the above case reports.

Multiple Sclerosis

Inflammatory destruction of outer nerve sheet, myelin, can trigger multiple sclerosis with severe physical and cognitive impairments. In animals with multiple sclerosis, citicoline enhanced myelin recovery and movement coordination [41, 42].

4) Helps With Mental Disorders and Drug Addiction

Depression

Addition of citicoline to an antidepressant drug (citalopram) improved depression symptoms and recovery in a study with 50 patients [43].

In rats, CDP-choline raised noradrenaline, dopamine, and serotonin levels in the brain centers for memory, emotions, and movement. Optimal levels of these neurotransmitters may keep depression and other mental disorders at bay [44, 45].

Meth and Cocaine Addiction

Citicoline relieved depression in 60 methamphetamine (meth) addicts but didn’t impact drug use (2,000 mg/day for 3 months). In another study on 31 meth addicts, citicoline protected the brain and reduced drug use [46, 47].

In over 130 cocaine addicts with bipolar disorder, citicoline (500 – 2,000 mg for 3 months) reduced drug use but didn’t impact mood [48, 49].

However, citicoline produced no effects in a trial with 20 heavy cocaine users [50].

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 social and cognitive problems. These are especially hard to treat with conventional drugs [51].

In 24 healthy adults, CDP-choline enhanced cognition by stimulating certain (nicotinic) acetylcholine receptors that are often underactive in schizophrenia [21].

5) Aids in Stroke Recovery

Cut blood supply to a specific brain region can kill the neurons and inflict massive brain damage. Citicoline may prevent stroke or improve recovery by strengthening nerve membranes and blocking free radical production [52, 53].

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 4K 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 [54].

However, 2 studies on over 3K patients found no significant benefits of CDP-choline for acute stroke [55, 56].

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 [57, 58].

Citicoline may also reverse brain damage caused by the chronic lack of blood supply or poor circulation. In over 2,800 older patients with this issue, citicoline improved dizziness, fatigue, insomnia, and sleep issues. This was another data analysis without a placebo control [24].

6) Improves Eyesight

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

  • Optic neuropathy
  • Glaucoma
  • Diabetic retinopathy
  • “Lazy eye”
  • Short-sightedness

Glaucoma

Increased eye pressure and other factors can damage the optic nerve and cause glaucoma, sometimes even leading to total blindness [59].

In 2 clinical trials with 80 glaucoma patients, long-term treatment with citicoline repaired nerve damage, improved eyesight, and slowed down disease progression [60, 61].

Eye drops with citicoline showed the same results in another 2 clinical trials (68 patients) [62, 63].

Amblyopia

Amblyopia or “lazy eye” occurs when the eye and brain don’t communicate well. It results in blurry vision in one eye [64].

Citicoline improved standard lazy eye treatment (eye patching) in 3 clinical trials with 190 children [65, 66, 67].

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 [68].

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 [69].

Myopia

Myopia (short-sightedness, near-sightedness) is the world’s top cause of vision loss. If distant objects appear blurry, you’re probably dealing with myopia [70].

In guinea pigs, citicoline reversed myopia by boosting the levels of dopamine in the retina [71].

Diabetic Retinopathy

High glucose and oxidative stress in diabetes can damage the retinal nerves and blood vessels and cause vision loss [72].

In mice with the condition, citicoline reduced two inflammatory pathways: NF-κB and TNF-a. As a result, it prevented the death of retinal nerves and improved eyesight [73].

A combination of citicoline and homotaurine protected the retina against toxic levels of glutamate and sugar in test tubes [74].

7) May Decrease Appetite

Higher doses of CDP-choline (2000 mg/day) reduced cravings for high-calorie foods and decreased appetite in 16 healthy volunteers  [75].

We need more research on this subject before proclaiming citicoline safe and effective for appetite and weight control.

Side Effects & Safety

Many clinical trials with citicoline have confirmed its excellent safety. In rare cases, it may cause mild digestive and nerve issues [24, 54, 20, 29, 46, 10, 60].

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 [76].

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 [77].

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.

Dosage & Supplements

The following citicoline dosage produced beneficial effects in clinical trials:

  • Boosting cognition and memory: 250 – 1,000 mg/day [20, 18, 21]
  • Age-related cognitive decline: 1 000 – 2,000 mg/day, 4+ weeks [25, 26, 28]
  • Alzheimer’s disease: 1,000 mg/day, 1 – 3 months [29, 30, 31]

Higher doses of 2,000 – 2,500 mg daily for 6+ weeks were efficient for [46, 46, 49, 78, 54, 57]:

  • Depression
  • Drug addiction
  • Schizophrenia
  • Stroke recovery

Appetite reduction required a dosage of 2,000 mg/day for 6 weeks [75].

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 [60, 69, 65, 62, 63].

Supplements

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.

Reviews

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.

Other users reaped no benefits from citicoline. The most common side effects include diarrhea, headache, and insomnia.

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Takeaway

Citicoline (CDP-choline) shields your nerves by strengthening their membranes and raising the levels of vital neurotransmitters. It’s a powerful booster of cognition, focus, and memory. Citicoline may also combat mental disorders and eye diseases such as glaucoma.

You can get its building blocks through food, especially by eating more organ meats. However, you’ll need to consider supplements to reach the doses used in clinical trials (1000-2000 mg/day).

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 citicoline.

About the Author

Aleksa Ristic, MSc (Pharmacy)

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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