{ "id": "epkksaz2c5", "slug": "glycerophosphocholine", "title": "Glycerophosphocholine", "updated": "2026-10-15", "topic_path": [ { "id": "physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/topics/physical" }, { "id": "physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry" }, { "id": "physical.chemistry.organic", "label": "Organic substances", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.organic" }, { "id": "physical.chemistry.organic.carbonyl_and_carboxyl_chemistry", "label": "Carbonyl and carboxyl chemistry", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.organic.carbonyl_and_carboxyl_chemistry" } ], "geo": [ { "id": "geo.nongeo.nodate.physical.chemistry.organic.carbonyl_and_carboxyl_chemistry", "label": "Non-geographic · Not dated: Carbonyl and carboxyl chemistry", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.physical.chemistry.organic.carbonyl_and_carboxyl_chemistry", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.nodate", "label": "Non-geographic · Not dated", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate" }, { "id": "geo.nongeo.nodate.physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.physical" }, { "id": "geo.nongeo.nodate.physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.physical.chemistry" }, { "id": "geo.nongeo.nodate.physical.chemistry.organic", "label": "Organic substances", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.physical.chemistry.organic" }, { "id": "geo.nongeo.nodate.physical.chemistry.organic.carbonyl_and_carboxyl_chemistry", "label": "Carbonyl and carboxyl chemistry", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.physical.chemistry.organic.carbonyl_and_carboxyl_chemistry" } ] } ], "excerpt": "Glycerophosphocholine (GPC), also called alpha-GPC or, as a drug and supplement, choline alfoscerate, is a water-soluble breakdown product of phosphatidylcholine that serves as a choline donor and kidney osmolyte.", "snippet": "Glycerophosphocholine (GPC), also called alpha-GPC or, as a drug and supplement, choline alfoscerate, is a water-soluble breakdown product of phosphatidylcholine that serves as a choline donor and kidney osmolyte.", "node": "physical.chemistry.organic.carbonyl_and_carboxyl_chemistry", "markdown": "# Glycerophosphocholine\n\n**Glycerophosphocholine** (GPC; also called sn-glycero-3-phosphocholine, L-alpha-glycerylphosphorylcholine, alpha-GPC, or, as the drug and supplement form, choline alfoscerate) is a small, water-soluble phosphodiester consisting of a glycerol molecule linked through a phosphate group to choline. It has the molecular formula C₈H₂₀NO₆P and a molecular weight of 257.22 g/mol.[1](https://pubchem.ncbi.nlm.nih.gov/compound/glycerophosphocholine) In biology it is the deacylated breakdown product of phosphatidylcholine, the most common membrane phospholipid; in medicine and nutrition the same molecule is used as a choline donor and cholinergic precursor.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC8235064/)\n\n| Key fact | Detail |\n|---|---|\n| Identity | Glycerophosphocholine, IUPAC name 2,3-dihydroxypropyl 2-(trimethylazaniumyl)ethyl phosphate; CAS 563-24-6; PubChem CID 11234[1](https://pubchem.ncbi.nlm.nih.gov/compound/glycerophosphocholine) |\n| Formula / mass | C₈H₂₀NO₆P, 257.22 g/mol[1](https://pubchem.ncbi.nlm.nih.gov/compound/glycerophosphocholine) |\n| Metabolic origin | Deacylated catabolic product of phosphatidylcholine; further hydrolyzed to free choline and glycerol-3-phosphate by the glycerophosphodiesterase (GDE/Gpcpd) family[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC8235064/) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC13209640/) |\n| Osmolyte role | Accumulates in renal medullary cells, protecting them from high interstitial NaCl and urea during operation of the renal concentrating mechanism[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC2943332/) |\n| Occurrence | Metabolite found in or produced by *Escherichia coli* (strain K12, MG1655) and *Saccharomyces cerevisiae*[1](https://pubchem.ncbi.nlm.nih.gov/compound/glycerophosphocholine) |\n| Drug and supplement use | Choline alfoscerate, used for cognitive impairment; typical trial doses 600 to 1200 mg/day[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC11412009/) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC8235064/) |\n| Safety signal | In a Korean cohort of about 12 million adults, α-GPC use was associated with higher 10-year stroke risk (total stroke aHR 1.46, 95% CI 1.43–1.48)[6](https://pubmed.ncbi.nlm.nih.gov/34817582/) |\n\n## Chemistry\n\nGlycerophosphocholine is a glycerophosphocholine-class compound in which the sn-3 hydroxyl of glycerol carries a phosphate esterified to choline, leaving the sn-1 and sn-2 hydroxyls free.[1](https://pubchem.ncbi.nlm.nih.gov/compound/glycerophosphocholine) • [7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4207189/) The molecule is zwitterionic, carrying a quaternary ammonium group and a phosphate charge in an inner salt, and it is water soluble, unlike its acylated parent phosphatidylcholine.[1](https://pubchem.ncbi.nlm.nih.gov/compound/glycerophosphocholine) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC8235064/) The stereospecific form is sn-glycero-3-phosphocholine, and the name choline alfoscerate refers to the same structure when marketed as a drug or supplement.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4207189/)\n\n## Metabolism\n\nGPC sits at a central point in phosphatidylcholine (PC) turnover. When PC is deacylated, by removal of its two fatty-acid chains, the resulting GPC is further hydrolyzed to free choline and glycerol-3-phosphate by the glycerophosphodiesterase (GDE/Gpcpd) family of enzymes.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC13209640/) In the digestive tract, dietary phosphatidylcholine is partly hydrolyzed by pancreatic phospholipase A2 and brush-border phospholipase B, with a portion re-esterified into chylomicrons and the remainder broken down through glycerophosphocholine to glycerophosphate and free choline.[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC7468900/) The same pathway operates in cultured cells: studies in murine neuroblastoma, C6 glioma, rat brain glia, and human fibroblasts showed catabolism of phosphatidylcholine proceeding via glycerophosphocholine.[9](https://www.sciencedirect.com/science/article/pii/0005276088901142) GPC also accumulates during physiological processes involving phospholipid remodeling, and in higher plant cells a dedicated glyceryl-phosphodiester phosphodiesterase splits it into sn-glycerol-3-phosphate and free choline.[10](https://pmc.ncbi.nlm.nih.gov/articles/PMC166557/)\n\n## Osmotic regulation in the kidney\n\n**A compatible osmolyte.** Cells of the renal medulla normally face high interstitial concentrations of NaCl and urea generated by the urinary concentrating mechanism. These cells accumulate large amounts of GPC, which acts as a compatible and counteracting osmolyte protecting them from osmotic stress; renal epithelial MDCK cells in culture show the same accumulation when exposed to high NaCl and urea.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC2943332/) • [11](https://pmc.ncbi.nlm.nih.gov/articles/PMC52395/?page=2) GPC abundance is osmotically regulated: it is built up under hypertonic stress and degraded by GPC:choline phosphodiesterase (GPC-PDE) activity, hydrolyzing it to glycerol-3-phosphate and choline.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC2943332/)\n\n## Choline supplementation and metabolism\n\nAs alpha-GPC, the compound is marketed as a choline source. A randomized cross-over study in six healthy adult men compared single doses of 550 mg choline equivalent given as choline chloride, choline bitartrate, alpha-glycerophosphocholine, and egg phosphatidylcholine. All four supplements raised plasma choline and betaine to a similar extent, with egg-PC peaking latest at about 3 hours; the water-soluble supplements, including GPC, rapidly increased the gut-microbe-derived metabolite trimethylamine oxide (TMAO), whereas egg-PC did not.[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC8783899/) An ex vivo fermentation study of human stool found that choline, phosphatidylcholine, and GPC were all converted to trimethylamine, and that the prebiotic fiber GOS significantly reduced this conversion.[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC12370400/)\n\nOn the regulatory side, a US GRAS notice (GRN 419) described alpha-GPC as a hydrolysis product of lecithin and reported that after oral administration it is converted to phosphorylcholine, which can cross the blood-brain barrier and serve for acetylcholine and phosphatidylcholine biosynthesis in the brain; after an intramuscular dose in volunteers, plasma choline peaked between 0.25 and 0.5 hours and returned to near baseline by 6 hours.[14](https://www.fda.gov/media/187804/download) A later notice (GRN 1141) sought use of alpha-GPC at up to 600 mg per serving in soft drinks, sports and [energy drinks](https://www.edgepedia.org/energy-drink), beverage mixes, coffee and tea, gummy candy, nutritional beverages, protein powders, and cereal and nutrition bars; the FDA ceased evaluation of that notice at the notifier's request in April 2024.[15](https://www.fda.gov/media/186764/download?attachment=)\n\n## Clinical research\n\n**Cognitive indications.** Choline alfoscerate is a choline-containing phospholipid used to treat cognitive function impairments in specific neurological conditions.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC11412009/) A 2023 systematic review of Alzheimer's disease studies included seven randomized controlled trials and one prospective cohort study and found significant effects of alpha-GPC in combination with donepezil on cognition (mean difference 1.72, 95% CI 0.20 to 3.25, across 4 RCTs), functional outcomes, and behavioral outcomes.[16](https://pubblicazioni.unicam.it/bitstream/11581/480884/2/J%20Alzheimers%20Dis.%202023%20vol.%2092%281%29%20pp.%2059%E2%80%9370.pdf) A 12-week multicenter randomized double-blind trial tested 600 mg alpha-GPC daily against placebo in 100 subjects with amnestic mild cognitive impairment.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC11412009/) Previous clinical studies cited in the motivation trial reported no serious side effects or toxicities when subjects took 1200 mg/day orally for 6 months.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC8235064/)\n\n**Stroke signal.** A population-based retrospective cohort study using South Korean National Health Insurance data compared 108,877 alpha-GPC users with 11,900,100 nonusers over 10 years. Users had a higher risk of total stroke (adjusted hazard ratio 1.46, 95% CI 1.43–1.48), ischemic stroke (aHR 1.36, 95% CI 1.33–1.39), and hemorrhagic stroke (aHR 1.36, 95% CI 1.28–1.44), in a dose-response manner after adjustment for traditional cerebrovascular risk factors.[6](https://pubmed.ncbi.nlm.nih.gov/34817582/) This association, together with the TMAO findings above, is the main caution raised against widespread supplemental use.[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC8783899/)\n\n## Industrial use\n\nGPC is also a manufacturing intermediate. Synthetic phospholipids with the natural stereochemical configuration are preferably synthesized from glycerophosphocholine obtained by hydrolyzing purified natural phosphatidylcholine to remove the fatty acids; acylation of GPC with activated acyl derivatives yields diacyl phosphatidylcholines in the same sn-glycero-3 configuration as natural lipids, and mixed-chain PCs can be made by organic or enzymatic routes from this starting material.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4207189/)\n\n## References\n\n1. [Glycerophosphocholine, CID 11234, PubChem](https://pubchem.ncbi.nlm.nih.gov/compound/glycerophosphocholine)\n2. [Alpha-Glycerylphosphorylcholine Increases Motivation in Healthy Volunteers, PMC8235064](https://pmc.ncbi.nlm.nih.gov/articles/PMC8235064/)\n3. [A Friend or Foe: Physiological Significance, Therapeutic Uses, and Potential Risks of Glycerophosphocholine, PMC13209640](https://pmc.ncbi.nlm.nih.gov/articles/PMC13209640/)\n4. [What's New About Osmotic Regulation of Glycerophosphocholine, PMC2943332](https://pmc.ncbi.nlm.nih.gov/articles/PMC2943332/)\n5. [Efficacy and safety of choline alphoscerate for amnestic mild cognitive impairment, PMC11412009](https://pmc.ncbi.nlm.nih.gov/articles/PMC11412009/)\n6. [Association of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 Years, JAMA Network Open](https://pubmed.ncbi.nlm.nih.gov/34817582/)\n7. [The use of natural and synthetic phospholipids as pharmaceutical excipients, PMC4207189](https://pmc.ncbi.nlm.nih.gov/articles/PMC4207189/)\n8. [Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men, PMC7468900](https://pmc.ncbi.nlm.nih.gov/articles/PMC7468900/)\n9. [Phosphatidylcholine metabolism in cultured cells: catabolism via glycerophosphocholine, Biochimica et Biophysica Acta](https://www.sciencedirect.com/science/article/pii/0005276088901142)\n10. [Glycerophosphocholine Metabolism in Higher Plant Cells, PMC166557](https://pmc.ncbi.nlm.nih.gov/articles/PMC166557/)\n11. [Accumulation of glycerophosphocholine (GPC) by renal cells, PMC52395](https://pmc.ncbi.nlm.nih.gov/articles/PMC52395/?page=2)\n12. [Differential metabolism of choline supplements in adult volunteers, PMC8783899](https://pmc.ncbi.nlm.nih.gov/articles/PMC8783899/)\n13. [Ex vivo study on prebiotic and choline combination to modulate gut bacteria and reduce TMA production, PMC12370400](https://pmc.ncbi.nlm.nih.gov/articles/PMC12370400/)\n14. [GRAS Notice 419, Part 6, Narrative and Safety Information, US FDA](https://www.fda.gov/media/187804/download)\n15. [GRAS Notice (GRN) 1141 Agency Response Letter, US FDA](https://www.fda.gov/media/186764/download?attachment=)\n16. [Choline alfoscerate in Alzheimer's disease: systematic review, Journal of Alzheimer's Disease 92 (2023) 59–70](https://pubblicazioni.unicam.it/bitstream/11581/480884/2/J%20Alzheimers%20Dis.%202023%20vol.%2092%281%29%20pp.%2059%E2%80%9370.pdf)\n\n---\n*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Organic substances › Carbonyl and carboxyl chemistry*\n\n*Initially written Oct 15, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/glycerophosphocholine", "markdown_url": "https://www.edgepedia.org/glycerophosphocholine.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"Glycerophosphocholine\", Edgepedia (EdgeChat), https://www.edgepedia.org/glycerophosphocholine. Edgepedia Community License 1.0.", "credit_md": "\"[Glycerophosphocholine](https://www.edgepedia.org/glycerophosphocholine)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/glycerophosphocholine](https://www.edgepedia.org/glycerophosphocholine). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"Glycerophosphocholine\", Edgepedia (EdgeChat), https://www.edgepedia.org/glycerophosphocholine. Edgepedia Community License 1.0.", "speakable": "Glycerophosphocholine, also called alpha-GPC or, as a drug and supplement, choline alfoscerate, is a water-soluble breakdown product of phosphatidylcholine that serves as a choline donor and kidney osmolyte." }