The Cognitive Benefits of Citicoline
A neuroprotective drug and supplement.
Medically reviewed by Suzanne Fisher, RD
Citicoline, also known as cytidine-5’-diphosphocholine or CDP-choline, is a fat molecule that is an important part of the cell membrane.
Researchers have studied citicoline in the setting of neurological (brain and nerve) diseases, such as dementia. It is commonly used to enhance cognitive function.
This article discusses citicoline's potential benefits and safety.
Citicoline Supplement Facts
Active Ingredient(s): Citicoline
Alternate Name(s): Cytidine-5’-diphosphocholine (CDP-choline)
Legal Status: Over-the-counter (OTC) dietary supplement (United States); prescription drug (Japan and Europe)
Suggested Dose: The therapeutic dose of citicoline ranges from 500 to 2,000 milligrams (mg) per day. Citicoline can be given intravenously (IV, within a vein), intramuscularly (within a muscle), and orally (by mouth).
Safety Considerations: Caution should be taken if you are pregnant or breastfeeding because the safety of citicoline is unknown in these populations.
What Is Citicoline?
Citicoline has been studied to treat the following conditions:
Brain stroke
Dementia prevention and treatment
Traumatic brain injury
Nerve pain and injury (animal models)
Citicoline has improved cognition in people with neurological conditions. And it has also improved memory and cognitive function in healthy people.
Citicoline works to protect the brain by:
Increasing dopamine, norepinephrine, and serotonin levels
Serving as a precursor to acetylcholine, a type of chemical messenger that helps brain and body functions
Lowering levels of glutamate, a brain chemical that causes damage to the brain under low oxygen conditions
Blocking phospholipase A2, a type of enzyme that then reduces inflammation
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Older adult solving a crossword puzzleUses
Explainer
Supplement use should be individualized and vetted by a healthcare professional, such as a registered dietitian (RD) or registered dietitian nutritionist (RDN), pharmacist, or healthcare provider. No supplement is intended to treat, cure, or prevent disease.
Age-Related Cognitive Decline
Citicoline supplementation improved memory in older adults with age-associated memory impairment compared to a placebo (no treatment) group. However, the study is not generalizable to young adults or people with cognitive diseases like dementia and Alzheimer’s disease (AD).
A review of a collection of studies showed a positive effect of citicoline on cognitive function in people with mild vascular cognitive impairment, vascular dementia, or AD. Because citicoline was used with the standard treatment (acetylcholinesterase inhibitor) for AD, the effect of citicoline alone on AD is unclear.
Cognitive Enhancement
In a study, a citicoline-caffeine-based drink improved attention, mental alertness, and memory. Since citicoline was combined with caffeine, it is unclear what the effect of citicoline alone is on attention and memory.
Based on a study in young, healthy males, citicoline improved motor function and attention after four weeks of supplementation. However, study results might not apply to populations other than young, healthy males.
Eye Surgery Recovery
Using citicoline eye drops three times a day for one month after eye surgery aided the recovery of corneal sensitivity after LASIK (laser-assisted in situ keratomileusis).
Stroke Treatment
A systematic review of studies found citicoline alone benefited acute ischemic stroke (blood clots in the brain). However, citicoline offers limited benefits on top of standard stroke treatment with rtPA or recombinant tissue plasminogen activator (clot-busting drug).
Furthermore, one study in people with a first ischemic stroke showed that after the stroke, people who received citicoline over two years had reduced cognitive impairment.
Neuroprotection
Citicoline has been studied for the following neuroprotective (protecting the nerves and brain) effects:
Add-on therapy in Parkinson's disease (PD): Citicoline improved motor functions, delayed cognitive impairment, and reduced slowed movement, rigidity, and tremor in people with PD. Moreover, it was an effective add-on therapy for treating PD intravenously, intramuscularly, and orally. The add-on use of citicoline allowed for a smaller dose of levodopa therapy, which reduced levodopa-associated side effects.
Add-on therapy in major depressive disorder (MDD): Citicoline with Celexa (citalopram) in people with medium to severe MDD effectively treated MDD compared to placebo (add-on treatment with no citicoline). The effects of citicoline alone are unclear.
Add-on therapy in schizophrenia: Citicoline added to standard therapy (risperidone) in people with chronic stable schizophrenia improved negative symptoms in people with schizophrenia.
Alcohol use disorder: The therapeutic use of citicoline for alcohol use disorder is unclear due to inconsistent results among the clinical studies.
Bipolar I disorder and cocaine dependence: A study in people with bipolar I disorder and cocaine dependence found citicoline reduced cocaine use in the short term. Further studies are warranted.
Glaucoma: The intake of citicoline oral solution over three months has been shown to improve the quality of life in adults with open-angle glaucoma (increased eye pressure due to blockage in the drainage system).
Hypoxic-ischemic encephalopathy (HIE): HIE is a type of brain damage caused by decreased oxygen or blood flow to the brain. In a clinical trial of neonates with moderate to severe HIE, intravenous citicoline for four weeks reduced the number and duration of seizures. The study suggested that citicoline could potentially be a neuroprotector drug in neonates with HIE.
Nonproliferative diabetic retinopathy (NPDR): Citicoline and vitamin B12 eye drops improved NPDR in people with type 1 diabetes. Because citicoline was combined with vitamin B12, it is unclear if it alone has any therapeutic benefit for NPDR.
Methamphetamine dependence: A study in adults dependent on methamphetamine suggested citicoline increased gray matter in the brain and reduced craving for and use of methamphetamine.
Traumatic brain injury (head injury): In an analysis of studies, treatment with citicoline improved independence in people with acute head injury.
While citicoline may benefit various cognitive conditions, further research is needed to confirm these results.
Food Sources
Besides supplementation, another way to increase citicoline levels is by consuming cytidine- and choline-rich foods. Citicoline is composed of cytidine and choline. Cytidine is found in meat, especially organ meats.
Foods rich in choline include the following:
Beef liver, pan-fried, 3 ounces (356 mg per serving)
Egg, hard-boiled, 1 large egg (147 mg per serving)
Beef top round, separable lean only, braised, 3 ounces (117 mg per serving)
Chicken breast, roasted, 3 ounces (72 mg per serving)
Beef, ground, 93% lean meat, broiled, 3 ounces (72 mg per serving)
Fish, cod, Atlantic, cooked, dry heat, 3 ounces (71 mg per serving)
Beans, kidney, canned, one-half cup (45 mg per serving)
Quinoa, cooked, 1 cup (43 mg per serving)
Brussels sprouts, boiled, one-half cup (32 mg per serving)
Broccoli, chopped, boiled, drained, one-half cup (31 mg per serving)
Dosage
The usual therapeutic dose for humans used in clinical trials is 500 to 2,000 mg daily.
Listed below are the citicoline dosing for various conditions used in clinical trials.
Add-on therapy in PD: Usual treatment with levodopa/carbidopa for five weeks plus citicoline 1,000 mg intravenously daily from weeks three to five.
Add-on therapy in MDD: Citicoline 100 mg by mouth every 12 hours plus Celexa 20 mg per day (for the first week) and 40 mg daily by mouth for the following five weeks.
Add-on therapy in schizophrenia: 1,000 milligrams (mg) by mouth per day for three days, 2,000 mg per day (in two divided doses) on day four for four days, and 2,500 mg per day (in two divided doses) starting week two; used with up to 6 mg of risperidone daily in the study.
Age-related cognitive decline: Two 250 mg capsules of citicoline (500 mg/day) by mouth with breakfast for 12 weeks.
Cocaine dependence in bipolar I disorder: 500 mg by mouth per day for one week, then 1,000 mg per day at week two, 1500 mg per day at week four, and 2,000 mg per day at week six, for 12 weeks total.
Cognitive enhancement: Beverage consisting of 250 mg of citicoline and caffeine (amount unclear). For motor function and attention in adolescent males, 250 or 500 mg capsule by mouth per day for 28 days.
Glaucoma: Citicoline oral solution of 50 mg per milliliter (mL) (mg/mL) used for a daily dose of 10 mL or 500 mg of citicoline by mouth in the morning.
Head injury: For moderate to severe head injury, 2 g by mouth for 60 days; for severe head injury, 3 g intravenously (IV) for 21 days.
Stroke treatment: 250 to 2,000 mg from 10 days to six weeks. In the clinical trials, citicoline was given intravenously, orally, or both intravenously and orally; for cognitive impairment in people poststroke, 1 gram (g) daily by mouth for two years.
Methamphetamine dependence: 1 gram (g) of CDP-choline capsule by mouth twice daily for eight weeks.
Neuroprotection: In neonates (newborns) with HIE, 10 milligrams (mg) per kilogram (kg) per 12 hours (h) intravenously for four weeks plus other supportive measures.
Nonproliferative diabetic retinopathy: One drop of citicoline and vitamin B12 eye drops containing citicoline 2%, hyaluronic acid 0.2%, and cyanocobalamin (vitamin B12) 0.05% into one eye three times daily for 36 months.
Safety
Citicoline is naturally present in the human body and is a nontoxic substance. Citicoline taken by mouth at amounts of up to 1 g per day has been shown to be safe and well-tolerated.
Overall, citicoline is well-tolerated and has no adverse systemic cholinergic side effects (e.g., increased saliva and tear production, urination and defecation, and decreased heart rate).
Avoid citicoline if you're allergic to it or its components (parts). Seek immediate medical attention if you have a severe allergic reaction (itching, hives, shortness of breath).
Side Effects
Although no serious side effects were noted in some studies, mild side effects include the following:
Increased appetite
Increased flatulence (passing gas)
Increased burping
Common side effects include the following:
Interactions
While there are few studies on drug interactions with citicoline, citicoline theoretically can increase the effect of levodopa by increasing dopamine levels.
Moreover, citicoline with levodopa allowed for a lower dose of levodopa in studies.
Precautions
Many clinical trials exclude people who are pregnant or breastfeeding. Therefore, the safety of citicoline in people who are pregnant or breastfeeding is unknown.
Although citicoline is well-tolerated, it is essential not to take more than instructed.
Please consult with your healthcare provider before starting citicoline.
Explainer
Dietary supplements are not regulated like prescription medications in the United States. Therefore, some may be safer than others. When choosing a supplement, consider factors such as third-party testing, potential drug interactions, and other safety concerns. Talk to a healthcare provider or a registered dietitian nutritionist (RD or RDN) about supplement quality and safety.
Similar Supplements
Other supplements that have cognitive-enhancing properties include the following:
Antioxidant polyphenols: Polyphenols, such as resveratrol, improved cognitive function in people with mild cognitive impairment and Alzheimer’s disease in clinical study.
B vitamins: B vitamins have decreased cognitive decline, and a higher dietary folate intake has been shown to lower dementia risk.
Medium-chain triglycerides (MCT): Consuming MCT jelly by mouth three times daily for a daily MCT dose of 17.3 g for 30 days improved cognition in people aged between 57 and 87 years with mild to moderate Alzheimer’s disease.
Omega-3 fatty acids: An analysis of a collection of studies revealed that omega-3 supplementation affects cognitive function in adults of advanced age in a positive way.
Selenium: Supplementation with selenium has been shown to improve cognitive function in people with mild cognitive impairment and Alzheimer’s disease.
Vitamin D: A clinical trial conducted in China found that daily vitamin D supplementation of 800 international units (IU) by mouth daily for 12 months improved cognitive function by reducing oxidative stress in participants aged 65 and older with mild cognitive impairment.
Similar to citicoline, the supplements above are believed to improve cognitive function. However, whereas citicoline is naturally found in the human body as CDP-choline, the above supplements are not produced by the human body.
Summary
Not only does citicoline protect the brain, but it also has an excellent safety profile.
Several clinical studies indicate citicoline's therapeutic potential in various neurological conditions, including age-related cognitive decline and stroke treatment and recovery.
Frequently Asked Questions
How does citicoline work to improve cognitive function?
Citicoline works to improve cognitive function by increasing brain choline and promoting the production of acetylcholine, a neurotransmitter essential for memory. Additionally, citicoline increases levels of dopamine, norepinephrine, and serotonin.
How is citicoline administered?
Citicoline is administered via the following routes: oral (by mouth), intravenous (within a vein), or intramuscular (within a muscle).
What is the difference between citicoline and choline?
Once citicoline is ingested, it is broken down into two molecules: cytidine and choline.
After these two molecules cross the blood-brain barrier separately and reach the brain cells, they combine to form CDP-choline (citicoline) again.
Citicoline serves as a source for making phosphatidylcholine, one of the parts of cell membranes.
Choline, one of the breakdown products of citicoline, serves as one of the building blocks for the production of acetylcholine, a neurotransmitter (chemical messenger) involved in memory and muscle movement.
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