Alpha-GPC

Last Updated: August 17 2022

Alpha-glycerophosphocholine (alpha-GPC or α-GPC) is a cholinergic compound that is used for cognitive-enhancement, and to increase power output in athletes. It appears to also support cellular membranes, and may help prevent cognitive decline.

Alpha-GPC is most often used for

What is alpha-GPC?

Alpha-GPC (alpha-glycerophosphocholine or choline alphoscerate) is a choline-containing phospholipid. When ingested, alpha-GPC is metabolized into choline and glycerol-1-phosphate. Choline is a precursor of acetylcholine, a neurotransmitter involved in memory, attention, and skeletal muscle contraction. Glycerol-1-phosphate is used to support cellular membranes.[1]

Alpha-GPC appears to easily cross the blood-brain barrier and is rapidly absorbed. It is currently the best cholinergic for increasing plasma and brain choline levels.[2]

What are alpha-GPC’s main benefits?

Oral supplementation of alpha-GPC is primarily of interest for nootropic or cognitive-enhancement purposes. There are a number of rodent studies that support this effect, but it has yet to be shown in otherwise healthy humans. In older adults with mild to moderate dementia — which involves disrupted cholinergic neurotransmission — alpha-GPC improves cognitive symptoms (e.g., memory and attention impairment).[3][1] Alpha-GPC may also improve the effectiveness of acetylcholinesterase inhibitors (i.e., drugs that increase acetylcholine availability by slowing down its breakdown), which are used for treating Alzheimer’s disease.[3]

Athletes are another population that may benefit from alpha-GPC supplementation. Preliminary evidence suggests that alpha-GPC increases vertical jump power.[4][5] Additionally, a pilot study reported that alpha-GPC increased peak bench press force, but not peak power or rate of force development.[6] Whether alpha-GPC increases isometric strength is currently unclear.[5][7]

What are alpha-GPC’s main drawbacks?

Alpha-GPC is generally well tolerated. Serious side effects have not been reported in human trials at a dosage of 1,200 mg per day for six months.[8] The No Observed Adverse Effect Level is 150 mg per kg of body weight per day.

Recently, concerns have been raised about the potential of alpha-GPC to increase the risk of cardiovascular disease (CVD) because it serves as a substrate for the synthesis of trimethylamine-N-oxide (TMAO) in the gut, and TMAO is associated with adverse cardiovascular outcomes in people with CVD and in mechanistic studies.[9]

A 2021 cohort study of more than 12 million participants (at least 50 years old), including 108,877 alpha-GPC users, reported that alpha-GPC use for at least 12 months was associated with an increased risk of stroke over 10 years.[10] Moreover, a 2021 mouse study found that alpha-GPC supplementation promoted atherosclerosis.[11]

However, the currently available evidence is preliminary in nature, so randomized controlled trials and large cohort studies are needed to confirm these findings.

How does alpha-GPC work?

Mechanistic evidence suggests that alpha-GPC exerts its effects by increasing the synthesis and release of acetylcholine in the brain, where it is involved in memory, motivation, arousal, and attention.[12][13][14][15]

Acetylcholine is also responsible for the action potential that stimulates muscles to contract. Therefore, it’s theorized that increased acetylcholine levels lead to a stronger signal for muscle contraction and, consequently, increased force production.

What else is Alpha-GPC known as?
Note that Alpha-GPC is also known as:
  • Alpha-glycerylphosphorylcholine
  • L-alpha-glycerophosphocholin
  • glycerophosphocholine
  • L-alpha-glyceryl-phosphorylcholine
  • Choline Alphoscerate
Alpha-GPC should not be confused with:
Dosage information

For attenuating symptoms of cognitive decline, almost all studies used a dosage of 1,200 mg per day, divided into three doses of 400 mg.

For boosting power output, studies have used a dosage of 300–600 mg, supplemented 30–60 minutes prior to exercise.

Examine Database
References
5.^Lena Marcus, Jason Soileau, Lawrence W Judge, David BellarEvaluation of the effects of two doses of alpha glycerylphosphorylcholine on physical and psychomotor performanceJ Int Soc Sports Nutr.(2017 Oct 5)
6.^Ziegenfuss T, Landis J, Hofheins JJ Int Soc Sports Nutr.()
7.^David Bellar, Nina R LeBlanc, Brian CampbellThe effect of 6 days of alpha glycerylphosphorylcholine on isometric strengthJ Int Soc Sports Nutr.(2015 Nov 17)
8.^Amy M Brownawell, Edward L Carmines, Federica MontesanoSafety assessment of AGPC as a food ingredientFood Chem Toxicol.(2011 Jun)
10.^Gyeongsil Lee, Seulggie Choi, Jooyoung Chang, Daein Choi, Joung Sik Son, Kyuwoong Kim, Sung Min Kim, Seogsong Jeong, Sang Min ParkAssociation of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 YearsJAMA Netw Open.(2021 Nov 1)
11.^Zeneng Wang, Jennie Hazen, Xun Jia, Elin Org, Yongzhong Zhao, Lucas J Osborn, Nisreen Nimer, Jennifer Buffa, Miranda K Culley, Daniel Krajcik, Bert-Jan H van den Born, Koos Zwinderman, Bruce S Levison, Max Nieuwdorp, Aldons J Lusis, Joseph A DiDonato, Stanley L HazenThe Nutritional Supplement L-Alpha Glycerylphosphorylcholine Promotes AtherosclerosisInt J Mol Sci.(2021 Dec 15)
12.^Seyed Khosrow Tayebati, Daniele Tomassoni, Antonio Di Stefano, Piera Sozio, Laura Serafina Cerasa, Francesco AmentaEffect of choline-containing phospholipids on brain cholinergic transporters in the ratJ Neurol Sci.(2011 Mar 15)
13.^Francesco Amenta, Seyed Khosrow Tayebati, Daniela Vitali, Maria Antonietta Di TullioAssociation with the cholinergic precursor choline alphoscerate and the cholinesterase inhibitor rivastigmine: an approach for enhancing cholinergic neurotransmissionMech Ageing Dev.(2006 Feb)
15.^C M Lopez, S Govoni, F Battaini, S Bergamaschi, A Longoni, C Giaroni, M TrabucchiEffect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholinePharmacol Biochem Behav.(1991 Aug)
16.^Tayebati SK, Tomassoni D, Nwankwo IE, Di Stefano A, Sozio P, Cerasa LS, Amenta FModulation of monoaminergic transporters by choline-containing phospholipids in rat brainCNS Neurol Disord Drug Targets.(2013 Feb 1)
19.^Zhang K, Wang X, Huang J, Liu YPurification of L-alpha glycerylphosphorylcholine by column chromatographyJ Chromatogr A.(2012 Jan 13)
20.^Armah CN, Sharp P, Mellon FA, Pariagh S, Lund EK, Dainty JR, Teucher B, Fairweather-Tait SJL-alpha-glycerophosphocholine contributes to meat's enhancement of nonheme iron absorptionJ Nutr.(2008 May)
22.^Brockerhoff H, Yurkowski MSimplified preparation of L-alpha-glyceryl phosphoryl cholineCan J Biochem.(1965 Oct)
23.^Brownawell AM, Carmines EL, Montesano FSafety assessment of AGPC as a food ingredientFood Chem Toxicol.(2011 Jun)
25.^Gatti G, Barzaghi N, Acuto G, Abbiati G, Fossati T, Perucca EA comparative study of free plasma choline levels following intramuscular administration of L-alpha-glycerylphosphorylcholine and citicoline in normal volunteersInt J Clin Pharmacol Ther Toxicol.(1992 Sep)
31.^Subbaiah PV, Ganguly JStudies on the phospholipases of rat intestinal mucosaBiochem J.(1970 Jun)
34.^Parthasarathy S, Subbaiah PV, Ganguly JThe mechanism of intestinal absorption of phosphatidylcholine in ratsBiochem J.(1974 Jun)
37.^Le Kim D, Betzing HIntestinal absorption of polyunsaturated phosphatidylcholine in the ratHoppe Seylers Z Physiol Chem.(1976 Sep)
38.^Subbaiah PV, Ganguly JTransesterification of lysolecithin in the intestinal mucosa of ratsIndian J Biochem.(1971 Dec)
39.^Kawamura T, Okubo T, Sato K, Fujita S, Goto K, Hamaoka T, Iemitsu MGlycerophosphocholine enhances growth hormone secretion and fat oxidation in young adultsNutrition.(2012 Nov-Dec)
40.^Tayebati SK, Amenta FCholine-containing phospholipids: relevance to brain functional pathwaysClin Chem Lab Med.(2013 Mar 1)
43.^Abbiati G, Fossati T, Lachmann G, Bergamaschi M, Castiglioni CAbsorption, tissue distribution and excretion of radiolabelled compounds in rats after administration of {14C}-L-alpha-glycerylphosphorylcholineEur J Drug Metab Pharmacokinet.(1993 Apr-Jun)
45.^Sigala S, Imperato A, Rizzonelli P, Casolini P, Missale C, Spano PL-alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the ratEur J Pharmacol.(1992 Feb 18)
46.^Aleppo G, Nicoletti F, Sortino MA, Casabona G, Scapagnini U, Canonico PLChronic L-alpha-glyceryl-phosphoryl-choline increases inositol phosphate formation in brain slices and neuronal culturesPharmacol Toxicol.(1994 Feb)
47.^Schettini G, Ventra C, Florio T, Grimaldi M, Meucci O, Scorziello A, Postiglione A, Marino AMolecular mechanisms mediating the effects of L-alpha-glycerylphosphorylcholine, a new cognition-enhancing drug, on behavioral and biochemical parameters in young and aged ratsPharmacol Biochem Behav.(1992 Sep)
48.^Lopez CM, Govoni S, Battaini F, Bergamaschi S, Longoni A, Giaroni C, Trabucchi MEffect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholinePharmacol Biochem Behav.(1991 Aug)
49.^Tayebati SK, Tomassoni D, Di Stefano A, Sozio P, Cerasa LS, Amenta FEffect of choline-containing phospholipids on brain cholinergic transporters in the ratJ Neurol Sci.(2011 Mar 15)
50.^Tomassoni D, Catalani A, Cinque C, Di Tullio MA, Tayebati SK, Cadoni A, Nwankwo IE, Traini E, Amenta FEffects of cholinergic enhancing drugs on cholinergic transporters in the brain and peripheral blood lymphocytes of spontaneously hypertensive ratsCurr Alzheimer Res.(2012 Jan)
51.^Canal N, Franceschi M, Alberoni M, Castiglioni C, De Moliner P, Longoni AEffect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamineInt J Clin Pharmacol Ther Toxicol.(1991 Mar)
52.^Ferraro L, Tanganelli S, Marani L, Bianchi C, Beani L, Siniscalchi AEvidence for an in vivo and in vitro modulation of endogenous cortical GABA release by alpha-glycerylphosphorylcholineNeurochem Res.(1996 May)
55.^Hoffman JR, Ratamess NA, Gonzalez A, Beller NA, Hoffman MW, Olson M, Purpura M, Jäger RThe effects of acute and prolonged CRAM supplementation on reaction time and subjective measures of focus and alertness in healthy college studentsJ Int Soc Sports Nutr.(2010 Dec 15)
56.^Nelson TJ, Sun MK, Hongpaisan J, Alkon DLInsulin, PKC signaling pathways and synaptic remodeling during memory storage and neuronal repairEur J Pharmacol.(2008 May 6)
57.^Glanzman DLPKM and the maintenance of memoryF1000 Biol Rep.(2013)
58.^Ren SQ, Yan JZ, Zhang XY, Bu YF, Pan WW, Yao W, Tian T, Lu WPKCλ is critical in AMPA receptor phosphorylation and synaptic incorporation during LTPEMBO J.(2013 May 15)
61.^Wang QJPKD at the crossroads of DAG and PKC signalingTrends Pharmacol Sci.(2006 Jun)
63.^Nitsch R, Pittas A, Blusztajn JK, Slack BE, Growdon JH, Wurtman RJAlterations of phospholipid metabolites in postmortem brain from patients with Alzheimer's diseaseAnn N Y Acad Sci.(1991)
66.^Walter A, Korth U, Hilgert M, Hartmann J, Weichel O, Hilgert M, Fassbender K, Schmitt A, Klein JGlycerophosphocholine is elevated in cerebrospinal fluid of Alzheimer patientsNeurobiol Aging.(2004 Nov-Dec)
68.^Gentile MT, Reccia MG, Sorrentino PP, Vitale E, Sorrentino G, Puca AA, Colucci-D'Amato LRole of cytosolic calcium-dependent phospholipase A2 in Alzheimer's disease pathogenesisMol Neurobiol.(2012 Jun)
69.^Milanesi L, Sheynis T, Xue WF, Orlova EV, Hellewell AL, Jelinek R, Hewitt EW, Radford SE, Saibil HRDirect three-dimensional visualization of membrane disruption by amyloid fibrilsProc Natl Acad Sci U S A.(2012 Dec 11)
73.^Parnetti L, Abate G, Bartorelli L, Cucinotta D, Cuzzupoli M, Maggioni M, Villardita C, Senin UMulticentre study of l-alpha-glyceryl-phosphorylcholine vs ST200 among patients with probable senile dementia of Alzheimer's typeDrugs Aging.(1993 Mar-Apr)
74.^Barbagallo Sangiorgi G, Barbagallo M, Giordano M, Meli M, Panzarasa Ralpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trialAnn N Y Acad Sci.(1994 Jun 30)
76.^Ceda GP, Ceresini G, Denti L, Marzani G, Piovani E, Banchini A, Tarditi E, Valenti Galpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjectsHorm Metab Res.(1992 Mar)
78.^Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, Yurgelun-Todd DA, Renshaw PFChronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy studyPsychopharmacology (Berl).(2002 May)
79.^Silveri MM, Dikan J, Ross AJ, Jensen JE, Kamiya T, Kawada Y, Renshaw PF, Yurgelun-Todd DACiticoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopyNMR Biomed.(2008 Nov)
80.^Hurrell RF, Reddy MB, Juillerat M, Cook JDMeat protein fractions enhance nonheme iron absorption in humansJ Nutr.(2006 Nov)
81.^Conrad ME, Umbreit JN, Moore EGIron absorption and transportAm J Med Sci.(1999 Oct)