Ingredient Reference
Citicoline (CDP-Choline): Chemistry, Forms, Studied Amounts and Safety
A reference page on what citicoline is, how it is made, how much choline it carries, how to read a label, what amounts human studies used, and who should check with a clinician first.
See Brain Energy CapsulesCiticoline on the Label
The planned amounts in Brain Energy Capsules, per serving.
Status: Planned formula. Pre-order to join the launch list. No payment is taken now. How to use it: follow the label directions once it launches. The formula has no caffeine or other stimulants. How this compares with research amounts: 500 mg a day is the amount in the 12-week memory trial and the higher arm of a 28-day attention study. It supplies roughly 106 mg of choline.
Citicoline at a Glance
| Item | Details |
|---|---|
| Names | Citicoline; CDP-choline; cytidine 5'-diphosphocholine; choline cytidine 5'-pyrophosphate. |
| Formula | C14H26N4O11P2, molecular weight 488.32 g/mol, CAS 987-78-0. |
| Choline content | About 106 mg per 500 mg, roughly 21% by weight. |
| Amounts in human studies | 250 to 2,000 mg a day for 4 to 12 weeks; single doses up to 4,000 mg. |
| Main cautions | Levodopa, meclofenoxate, pregnancy and breastfeeding, children, total choline intake. |
| US status | Sold as a dietary supplement. FDA does not approve supplements before sale. |
Here for benefits or timing? What citicoline does, timing and reported side effects in plain terms are in Citicoline Benefits: What It Does, Dosage, Side Effects and When to Take It. For a head-to-head choice, see Citicoline vs Alpha GPC: Which Choline Supplement Is Better?
What Citicoline Is: Structure and Metabolism
Citicoline is a nucleotide-linked form of choline built from four parts: the base cytosine, the sugar ribose, a pyrophosphate bridge and choline. Cells make it themselves as a natural precursor of phospholipids, chiefly phosphatidylcholine, a major component of cell membranes. It also serves as a source of choline for making acetylcholine.
What happens after you swallow it
Citicoline is split into choline and cytidine during digestion. In people, cytidine is readily converted to uridine, which is the main circulating pyrimidine in humans, while in rats it is cytidine. In one human study, less than 1% of a 300 mg dose appeared in feces over five days. About 16% of the dose was excreted over that time, mostly as exhaled carbon dioxide and in urine, which points to good absorption.
How supplement citicoline is made
The citicoline that the European Food Safety Authority (EFSA) assessed was made by an enzymatic reaction of orotic acid and choline chloride. The enzymes came from cultures of Corynebacterium ammoniagenes and genetically modified E. coli. The product was then filtered, purified on resin, decolorized and crystallized with methanol. EFSA found no residual enzymes or recombinant DNA in three batches.
Forms, Choline Math and Labels
| Choline source | Choline by weight | Carried with the choline |
|---|---|---|
| Citicoline | About 21% (106 mg in 500 mg) | Cytidine, which becomes uridine |
| Alpha GPC (choline alfoscerate) | About 41% | Glycerophosphate |
Counting choline across products
For adults, the adequate intake of choline is 425 mg daily for women and 550 mg for men (450 mg in pregnancy and 550 mg during lactation). Adults have a tolerable upper intake level of 3,500 mg a day, counting food and supplements together, set from the amounts linked with low blood pressure and fishy body odor. A 500 mg serving of citicoline adds about 106 mg, so it sits well below that limit on its own, but stacks with alpha GPC, choline bitartrate or other choline products should be added up.
What to check on a label
- Citicoline in mg per serving, and whether a salt form such as citicoline sodium is named, since the figure may refer to the salt.
- Purity: the EU specification calls for at least 98% citicoline on a dry basis, heavy metals no more than 10 ppm and arsenic no more than 2 ppm.
- Branded ingredient: several trials below used a branded citicoline supplied by its maker, Kyowa Hakko, which also funded them.
- Other choline sources in the same formula.
- Stimulants: whether caffeine or similar ingredients are added. Brain Energy Capsules have none.
Citicoline in Human Studies
Studies in healthy adults, from blood levels to brain scans to cognitive tests.
| Study | Who | Amount a day | Length | Measured | Result |
|---|---|---|---|---|---|
| Dinsdale 1983, summarized by EFSA | 12 volunteers | 600 or 1,000 mg | 5 days | Tolerability | Passing headaches in 4 and 5 of 12, against 1 of 12 on placebo |
| Wurtman 2000, Biochem Pharmacol | 12 healthy adults | One dose each of 500 mg, 2 g and 4 g, plus placebo | One day per dose | Plasma choline and uridine | Choline rose with dose and stayed raised for 5 to 10 hours; uridine climbed after 500 mg |
| Silveri 2008, NMR Biomed | 16 healthy adults, average age 47 | 500 or 2,000 mg | 6 weeks | Frontal brain energy and membrane compounds by phosphorus MR spectroscopy | Phosphocreatine up about 7% and beta-NTP, an ATP marker, up about 14%; changes tended to be larger at 500 mg |
| McGlade 2012, Food Nutr Sci | 60 healthy women aged 40 to 60 | 250 or 500 mg, or placebo | 28 days | Continuous Performance Test II (sustained attention) | Fewer errors than placebo at both doses; at 500 mg, the omission error result was a trend |
| Nakazaki 2021, J Nutr | 100 healthy adults, ages 50 to 85, reporting age-associated memory complaints | 500 mg, or placebo | 12 weeks | Computerized memory tests | Paired associate and composite memory scores improved more than placebo; 99 of 100 finished |
Studied Amounts and Limits
Amounts from research and regulators, not directions. Follow your product's label.
| Setting | Amount |
|---|---|
| Attention study, healthy women | 250 or 500 mg a day for 28 days |
| Brain scan study | 6 weeks at 500 or 2,000 mg daily |
| Memory trial, adults 50 to 85 | 500 mg a day for 12 weeks |
| Single-dose blood study | 500, 2,000 and 4,000 mg |
| EU limit, food supplements | 500 mg a day |
| EU limit, foods for special medical purposes | 250 mg per serving, 1,000 mg a day |
| Choline upper limit, adults, all sources | 3,500 mg a day |
Safety, Side Effects and Interactions
In the 12-week trial at 500 mg, six adverse events occurred with citicoline and two with placebo, including increased appetite, weight gain, flatulence, headache and burping, all described as mild and transient. Across other studies reviewed by EFSA, reported effects included headache, insomnia, stomach upset and restlessness. WebMD lists anxiety or restlessness and upset stomach, and notes that allergic reactions, which can be serious, may occur. Very high choline intakes are linked with fishy body odor, vomiting, heavy sweating and drooling, low blood pressure and liver toxicity.
| Medicine or situation | What is reported |
|---|---|
| Levodopa | Citicoline may enhance its effects; a medicine label advises against combining them without medical advice (EFSA). WebMD also flags this pairing. |
| Meclofenoxate | Should not be given with citicoline (EFSA). |
| Other choline supplements | Add up total choline and stay within 3,500 mg a day. |
| Children | EU rules state foods with citicoline are not intended for children. |
| Pregnancy and breastfeeding | Effects on pregnancy and passage into breast milk are not known (WebMD). |
Ask a clinician first if you take levodopa or any prescription medicine, are pregnant or breastfeeding, or are under 18. Stop and get help right away if you notice hives, facial or throat swelling, or trouble breathing.
Regulatory Status in the US
In the US, citicoline is sold in dietary supplements under the Dietary Supplement Health and Education Act of 1994 (DSHEA). FDA does not approve supplements before they are marketed; the maker or seller is responsible for safety and labeling, and structure and function statements must carry the FDA disclaimer shown at the bottom of this page.
For comparison, the EU authorized citicoline as a novel food in 2014 (Decision 2014/423/EU) after EFSA concluded in 2013 that it is safe under the proposed uses: up to 500 mg a day in food supplements, with labels naming it "citicoline" and stating that it is not intended for children. EFSA also noted that citicoline may interact with certain medicines.
Citicoline FAQ
Is supplement citicoline the same molecule the body makes?
Yes. Cells make citicoline as a step toward phosphatidylcholine. Supplement citicoline is produced by an enzymatic process and purified to the same structure.
How much choline does 500 mg of citicoline provide?
About 106 mg, or roughly 21% of its weight. Alpha GPC carries about 41% choline by weight.
What does citicoline break down into?
Choline and cytidine. In people, cytidine is readily converted to uridine.
What is the molecular formula of citicoline?
C14H26N4O11P2, with a molecular weight of 488.32 g/mol and CAS number 987-78-0.
What is the EU limit for citicoline in food supplements?
500 mg a day, under Decision 2014/423/EU, and labels must state that it is not intended for children.
Which medicines should I ask about before taking citicoline?
Levodopa and meclofenoxate are the ones named in regulatory and reference sources. Ask your clinician about any prescription medicine.
How much citicoline is in Brain Energy Capsules?
500 mg per serving, with 20 mg of PQQ and 25 mg of L-ergothioneine, and no caffeine or other stimulants. It is a planned formula; pre-ordering takes no payment now.
More on Citicoline
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Related ingredient pages
Sources
- Wurtman RJ, et al. Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochemical Pharmacology, 2000. PubMed 10974208
- Silveri MM, et al. Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy. NMR in Biomedicine, 2008. PubMed 18816480
- McGlade E, et al. Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women. Food and Nutrition Sciences, 2012. DOI 10.4236/fns.2012.36103
- 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. PubMed 33978188
- EFSA Panel on Dietetic Products, Nutrition and Allergies. Scientific Opinion on the safety of citicoline as a Novel Food ingredient (includes the Dinsdale 1983 data). EFSA Journal, 2013. DOI 10.2903/j.efsa.2013.3421
- Commission Implementing Decision 2014/423/EU authorising citicoline as a novel food ingredient. legislation.gov.uk
- Kansakar U, et al. Choline supplements: An update. Frontiers in Endocrinology, 2023. DOI 10.3389/fendo.2023.1148166
- NIH Office of Dietary Supplements. Choline: Fact Sheet for Health Professionals. ods.od.nih.gov
- WebMD. Citicoline. Vitamins and Supplements. webmd.com
- US Food and Drug Administration. Questions and Answers on Dietary Supplements. fda.gov
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. If you are pregnant, nursing, under 18, taking levodopa or other medication, or managing a health condition, consult a qualified healthcare professional before use.