Citicoline (CDP-Choline)

Citicoline (also known as CDP‑choline or cytidine‑5′‑diphosphocholine) is a naturally occurring nucleotide that serves as an intermediate in the biosynthesis of phosphatidylcholine, a major phospholipid of cell membranes. When taken as a dietary supplement, its primary purpose is to support neuronal membrane integrity and support the synthesis of the neurotransmitter acetylcholine, thereby influencing cognitive and neuro‑protective functions.

• Citicoline is chemically known as cytidine 5′‑diphosphate choline (IUPAC: (2‑R‑hydroxy‑3‑(phosphonooxy)propyl) 5‑(2‑deoxy‑β‑D‑ribofuranosyl)‑1‑phosphoryl‑4‑hydroxy‑5‑(phosphonooxy)‑diphosphate).
• Molecular formula: C₁₄H₃₅N₃O₁₄P₂, molecular weight ≈ 489.98 g/mol.
• Structure: The molecule consists of a cytidine nucleoside linked via a diphosphate bridge to a choline moiety.
• Properties:
  • Highly water‑soluble.
  • Stable at neutral pH.
  • Exists as a sodium or calcium salt in most commercial preparations.
  • The phosphodiester bond (phosphoryl‑choline) is the key functional group enabling its conversion into phosphatidylcholine and CTP.
  • The compound is a zwitterion at physiological pH, conferring high bioavailability (≈ 90 % oral absorption) and rapid plasma clearance (half‑life ~ 6–8 h).

• Production: Commercial citicoline is produced primarily by synthetic chemical routes: condensation of cytidine monophosphate (CMP) with choline chloride under controlled pH, followed by purification and conversion to the sodium or calcium salt.
• Cytidine Source: Some manufacturers obtain cytidine from biotechnological fermentation of Saccharomyces or E. coli cultures, then chemically couple the choline component.
• Natural Sources: Natural dietary sources contain only trace amounts (e.g., liver, egg yolk, fish) and are not practical for supplementation.
• Quality Considerations:
  • GMP‑certified manufacturing.
  • Verification of > 95 % purity by HPLC.
  • Absence of heavy metals and residual solvents.
  • Third‑party testing (e.g., USP, NSF).
  • Consistent particle size and stable salt form (Na or Ca) ensure reproducible bioavailability.