Citicoline (CDP-Choline): Benefits, Dosage, Side Effects And Research

ByJustin Updated on

Citicoline, also called CDP-choline (cytidine diphosphate-choline), is a compound your body already makes on the way to building cell membranes. As a supplement, citicoline breaks down into choline and cytidine, and small randomized trials suggest it may modestly support attention in healthy adults and memory in older adults at 250 to 500 mg a day. Most of those trials were funded by Kyowa Hakko, the maker of Cognizin, the best-known branded form.

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Key Takeaways

  • Citicoline is broken down into choline and cytidine; cytidine is then largely converted to uridine in the blood.
  • Randomized trials in healthy women, adolescent boys and older adults reported small improvements in attention or memory at 250 to 500 mg/day, but samples were small and the trials were industry-funded.
  • Cognizin is a branded citicoline made by Kyowa Hakko; it is the form used in most of the healthy-adult research.
  • Citicoline is about 21% choline by weight, so it supplies less choline per milligram than alpha-GPC.
  • It has been well tolerated in trials. Reported side effects were mild and included headache, digestive symptoms and increased appetite.

What Is CDP-Choline And How Does Citicoline Work?

When you swallow citicoline, it breaks down into cytidine and choline. Blood cytidine is quickly and almost completely converted to uridine.[5] Both pieces are building blocks the brain can use to make new phospholipids for cell membranes.

The choline half matters because choline is needed to produce acetylcholine, a neurotransmitter for memory, mood and muscle control, and to build phosphatidylcholine and sphingomyelin, two major membrane phospholipids.[9] The uridine half is what sets citicoline apart from most other choline supplements. You can read more about it on our uridine page.

In the U.S., citicoline is sold as a dietary supplement. It has also been tested at much higher doses, including intravenously, in clinical trials for stroke (covered below).[6]

What Is Cognizin?

Cognizin is the trade name for citicoline produced by Kyowa Hakko Bio, a subsidiary of Japan’s Kirin Group. It is the form used in the healthy-adult trials covered below,[1][3] which is useful to know when you compare products. Kyowa has self-affirmed GRAS status for Cognizin in the U.S. at intakes up to 1,505 mg of citicoline per day across foods, according to the company’s own regulatory filing.[8]

Citicoline Benefits: What The Research Shows

Attention In Healthy Adults (Evidence: Limited)

The McGlade 2012 trial is the study most supplement marketing cites. Sixty healthy women aged 40 to 60 took 250 mg or 500 mg of Cognizin or placebo daily for 28 days. On a computerized sustained-attention test, the 250 mg group made fewer omission and commission errors than placebo, and the 500 mg group made fewer commission errors.[1]

Context matters here. Each group had just 20 people, all p-values were one-tailed, and two authors were Kyowa Hakko employees.[1] The results are encouraging, not definitive.

A follow-up trial in 75 healthy adolescent males found that 28 days of 250 mg or 500 mg Cognizin improved attention and motor speed and reduced impulsivity compared with placebo, and that higher weight-adjusted doses predicted better attention scores.[2] This trial was also funded by Kyowa Hakko.[2]

Memory In Older Adults (Evidence: Limited To Moderate)

The Nakazaki 2021 trial randomized 100 adults aged 50 to 85 with age-associated memory impairment to 500 mg/day of Cognizin or placebo for 12 weeks. Citicoline improved episodic memory and an overall memory composite score more than placebo.[3] The absolute changes were small; for example, the composite memory score rose from 75.6 to 79.1 on citicoline versus 74.8 to 75.5 on placebo.[3] Kyowa Hakko Bio sponsored the trial.

In people with existing brain disorders, a Cochrane review of 14 trials found some evidence that citicoline had a positive effect on memory and behavior in older adults with chronic cerebral disorders, at least in the short to medium term. It found no evidence of benefit on attention in this group, and most trials lasted only 20 to 30 days.[4] A 2023 review also concluded that citicoline may support memory in aging but called for more research.[5]

Stroke Recovery (Evidence: Did Not Hold Up)

Citicoline was once seen as promising after stroke, but the large ICTUS trial changed that. It randomized 2,298 people with moderate to severe acute ischemic stroke to citicoline (1,000 mg every 12 hours for 6 weeks, intravenously for the first 3 days and then by mouth) or placebo. It was stopped early for futility, with recovery rates nearly identical between groups, and the authors concluded citicoline was not effective in that setting.[6] This is a good reminder that small positive studies do not always survive large trials.

CDP Choline And Dopamine

You will see claims that citicoline “boosts dopamine.” The adolescent trial authors proposed a dopamine mechanism to explain their results, but dopamine was not measured, so that explanation is speculative.[2] Treat dopamine claims for citicoline in humans as unproven.

Citicoline Dosage And Cognizin Dosage

The healthy-adult trials used 250 mg or 500 mg a day.[1][3] The European Union allows up to 500 mg/day in food supplements,[8] and Australia’s regulator advised that there was sufficient data to establish safe use at up to 500 mg daily in adults.[7]

Purpose Dose Duration Study
Attention, healthy women 40–60 250 or 500 mg/day (Cognizin) 28 days McGlade 2012[1]
Attention and motor speed, adolescent males 250 or 500 mg/day (Cognizin) 28 days McGlade 2015[2]
Memory, adults 50–85 with age-associated memory impairment 500 mg/day (2 x 250 mg Cognizin) 12 weeks Nakazaki 2021[3]
Acute ischemic stroke (no benefit) 2,000 mg/day 6 weeks ICTUS[6]

A practical CDP choline dose for a healthy adult is 250 to 500 mg once daily. There is no evidence that higher doses work better for healthy people. Most people take it in the morning because it is used for focus, though timing has not been studied.

CDP Choline Vs Choline Bitartrate And Other Choline Sources

At 500 mg/day, citicoline provides about 107 mg of choline and about 250 mg of cytidine,[7] so it is roughly 21% choline by weight. That is well below the adult Adequate Intake of 425 to 550 mg of choline a day.[9] In other words, people take citicoline for its specific research, not as a cheap way to meet choline needs.

  • Choline bitartrate is the cheapest way to add choline, but it has no comparable cognitive trials in healthy adults. NIH notes that no studies have compared choline bioavailability across supplement forms.[9]
  • Alpha-GPC is about 40% choline by weight[10] and has more sports research, but no uridine component. See our alpha-GPC vs citicoline comparison for the full breakdown.
  • Phosphatidylcholine is the main choline form in food and makes up about half of the choline Americans eat.[9]

Forms And What To Look For

  • Branded vs generic: Cognizin is the form used in most healthy-adult trials. Generic citicoline is chemically the same compound; the brand mainly tells you the source and manufacturing.
  • Citicoline sodium: many supplements use the sodium salt. Check whether the label lists milligrams of citicoline or of citicoline sodium.
  • Capsules vs powder: CDP choline powder is cheaper per gram but harder to dose accurately without a milligram scale.
  • Testing: choose brands that publish third-party lab results.

Citicoline Side Effects And Cognizin Side Effects

Citicoline has a good tolerability record. The Cochrane review reported that it was well tolerated with no noticeable side effects across its trials.[4] In the 12-week Nakazaki trial, there were six adverse events in the citicoline group and two on placebo, all described as mild and transient: increased appetite, weight gain, flatulence, headache and burping.[3] In the large ICTUS stroke trial, at 2,000 mg/day, there were no significant differences in safety or adverse events compared with placebo.[6]

Some users report headaches or feeling overstimulated. Those reports are anecdotal, but if it happens, a lower dose is the obvious fix.

Very high choline intakes from all sources can cause fishy body odor, sweating, vomiting and low blood pressure, which is why the adult upper limit for choline is 3,500 mg/day.[9] Normal citicoline doses supply far less choline than that.

Drug Interactions And Who Should Avoid It

  • Pregnant women and children: Australia’s regulator concluded that safety has not been established in these groups and that use is not recommended.[7]
  • People taking medications that affect acetylcholine or dopamine, including drugs for Parkinson’s disease or dementia, should ask their prescriber first. Interaction data for supplement doses are limited.
  • Anyone recovering from stroke or with diagnosed cognitive impairment should use citicoline only under medical supervision and not in place of standard care.

How Citicoline Stacks With Other Nootropics

Citicoline is a common “choline base” in stacks. It is often paired with phosphatidylserine and bacopa monnieri for memory, or with L-tyrosine and L-theanine and caffeine for focus. These combinations have not been tested as stacks, so add one ingredient at a time. Most people do not need both citicoline and alpha-GPC. Our best supplements for focus guide covers other options.

Where To Buy Citicoline

For a standalone citicoline product, Nootropics Depot sells third-party-tested citicoline through its authorized Amazon store. Make sure the listing says “Sold by Nootropics Depot.”

Check Nootropics Depot Citicoline On Amazon

Cognizin Citicoline In Mind Lab Pro

Mind Lab Pro contains 250 mg of Cognizin citicoline per two-capsule serving. That matches the lower dose used in the McGlade attention trials,[1] though it is half the 500 mg/day used in the Nakazaki memory trial.[3] It is combined with 100 mg of sunflower phosphatidylserine, bacopa, lion’s mane, L-theanine and other ingredients, some of which are below their study doses. We view it as a broad, well-tolerated daily stack. See our full Mind Lab Pro review.

Check Mind Lab Pro Price

Citicoline FAQs

What Is CDP Choline?

CDP choline (citicoline) is cytidine diphosphate-choline, a natural intermediate in making phosphatidylcholine for cell membranes. As a supplement, it breaks down into choline and cytidine.[5]

Is Cognizin The Same As Citicoline?

Yes. Cognizin is Kyowa Hakko’s branded citicoline. It is the same compound as generic citicoline, and it is the form used in the main healthy-adult trials.[1][3]

What Is The Best Cognizin Dosage?

Studies used 250 mg or 500 mg a day.[1][3] Start at 250 mg and move to 500 mg if you tolerate it well.

What Are The Side Effects Of Cognizin?

In trials, side effects were uncommon and mild, including headache, digestive symptoms and increased appetite.[3]

Should I Take CDP Choline Or Alpha-GPC?

Citicoline has more research on attention and memory in healthy adults; alpha-GPC delivers more choline per milligram and has more sports research. Our alpha-GPC vs citicoline guide compares them in detail.

How Long Does Citicoline Take To Work?

The attention trials measured effects after 28 days, and the memory trial after 12 weeks.[1][3] Plan on several weeks of daily use before judging it.

Medical disclaimer: This article is for educational purposes only and is not medical advice. Dietary supplements are not evaluated by the FDA to diagnose, treat, cure or prevent any disease. Talk with your doctor or pharmacist before starting a supplement, especially if you are pregnant, nursing, take prescription medication or have a medical condition. Read our full medical disclaimer.

References

  1. McGlade E, et al. Improved attentional performance following citicoline administration in healthy adult women. Food and Nutrition Sciences. 2012;3(6). DOI
  2. McGlade E, et al. The effect of citicoline supplementation on motor speed and attention in adolescent males. Journal of Attention Disorders. Published online 2015. DOI
  3. Nakazaki E, et al. Citicoline and memory function in healthy older adults: a randomized, double-blind, placebo-controlled clinical trial. The Journal of Nutrition. 2021. DOI
  4. Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database of Systematic Reviews. 2005;(2):CD000269. Cochrane
  5. Świątkiewicz M, Grieb P. Citicoline for supporting memory in aging humans. Aging and Disease. 2023;14(4):1184-1195. PubMed
  6. Citicoline in the treatment of acute ischemic stroke: an international, randomized, multicentre, placebo-controlled study (ICTUS trial). American College of Cardiology Journal Scan, 2012. ACC; trial registration NCT00331890
  7. Therapeutic Goods Administration (Australia). Advisory Committee on Complementary Medicines, ratified minutes of the 15th meeting, December 2013 (item 5.4, citicoline). TGA
  8. Kyowa Hakko Bio Co., Ltd. Application to Food Standards Australia New Zealand: citicoline as a nutritive substance in formulated caffeinated beverages, executive summary. December 2023. FSANZ
  9. National Institutes of Health, Office of Dietary Supplements. Choline: Fact Sheet for Health Professionals. NIH ODS
  10. Health Canada. Summary of Health Canada’s safety assessment of L-alpha-glycerylphosphorylcholine for use as a supplemental ingredient. 2023. Health Canada

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