Cognizin® Citicoline

1. ADDF Cognitive Vitality (2017). Citicoline (CDP-choline) – For Researchers. (Source for: CDP-choline is a naturally occurring compound produced by the body and a precursor in phosphatidylcholine synthesis).

2. Synoradzki, K.; Grieb, P. (2019). Citicoline: A Superior Form of Choline? (Source for: notes citicoline (cytidine-5′-diphosphocholine) has been used as a prescription nootropic since the 1970s and recently as a food ingredient, with no nutrition or health claim authorized in the EU).

3. Grieb, P. et al. (2014). Neuroprotective Properties of Citicoline: Facts, Doubts and Unresolved Issues. (Source for: orally administered citicoline is quickly hydrolyzed to choline and cytidine, which cross into the brain and are used to resynthesize CDP-choline in neurons).

4. Natural Medicine Journal (2016). Citicoline – A Novel Therapeutic Agent… – Technical introduction. (Source for: Describes citicoline as a mononucleotide composed of ribose, cytosine, diphosphate, and choline, highlighting its role as an intermediate in phosphatidylcholine synthesis).

5. Kyowa Hakko Bio (2016). Cognizin® Citicoline – Fact Sheet for Health Professionals. (Source for: States that citicoline is present only in very low amounts in foods (highest in liver and brain, which are not commonly consumed)).

6. New Drug Approvals blog (2021). Citicoline. (Source for: Provides chemical and industrial insights. Confirms the IUPAC name… and notes an industry-standard two-step fermentation process, with newer one-step fermentation in development).

7. Google Patents (2013). WO2013128393A1 – Process for preparing pure citicoline. (Source for: Describes a synthetic route reacting cytidine-5′-monophosphate with phosphorylcholine (calcium salt) using DCC, yielding highly pure citicoline (≥99% HPLC purity) after removing impurities with dicarboxylic acid).

8. Kyowa Holdings (2021). The History of Kyowa Hakko Bio and Citicoline (Investor report) – Highlights Kyowa’s fermentation technology. (Source for: Indicates use of nucleic acid–producing and citicoline biosynthesis–enhancing bacteria, inexpensive substrates (orotic acid, choline chloride), and a simple fermentation process to produce citicoline, with two microorganisms controlled simultaneously).

9. EFSA Panel on Nutrition (2024). Scientific Opinion on “Citicoline” and memory (Article 13(5) health claim). EFSA Journal 18(7): 8861. (Source for: Concludes that a cause-and-effect relationship has not been established between citicoline intake and improvement of memory in aging adults).

10. ADDF Cognitive Vitality (2017). Citicoline (CDP-choline) – For Researchers. (Source for: Summarizes that citicoline is well-tolerated with few or no adverse effects and widely used in cognition studies. Also notes that in most clinical studies, citicoline doses ranged from 250 mg to 1,000 mg per day over up to 12 weeks with a good safety profile. Minor GI side effects were the only notable issues in a small percentage of subjects).

11. Cognizin® Citicoline Novel Food Approval – Kyowa Hakko Europe News (2014). (Source for: Confirms EU Commission Decision 2014/423 authorizing citicoline as a novel food ingredient at max 500 mg/day in supplements (1000 mg/day in special medical foods), and notes Cognizin’s GRAS status in the US (self-affirmed in 2009)).

12. Synoradzki & Grieb (2019) – Additional data. (Source for: Reports that citicoline’s toxicity is substantially lower than choline’s: on a molar basis, >20-fold higher LD50 for citicoline vs choline, suggesting a very wide safety margin for citicoline supplementation).

13. New Drug Approvals blog (2021) – Pharmacokinetic excerpt. (Source for: Notes that after oral ingestion of citicoline, the majority is excreted as CO2 (via respiration), and the remaining fraction is excreted in urine within about 24 hours, indicating effective absorption and complete metabolism of the dose).