Alpha-GPC
•Last Updated: September 28 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
Last Updated: September 28 2022
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.[2]
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]
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.
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.
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:
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.
Research FeedRead all studies
1.^Enea Traini, Vincenzo Bramanti, Francesco AmentaCholine alphoscerate (alpha-glyceryl-phosphoryl-choline) an old choline- containing phospholipid with a still interesting profile as cognition enhancing agentCurr Alzheimer Res.(2013 Dec)
2.^G Gatti, N Barzaghi, G Acuto, G Abbiati, T Fossati, E PeruccaA 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)
3.^De Jesus Moreno Moreno MCognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trialClin Ther.(2003 Jan)
4.^Parker A, Byars A, Purpura M, Jager RThe effects of alpha-glycerylphosphorylcholine, caffeine or placebo on markers of mood, cognitive function, power, speed, and agilityJ Int Soc Sports Nutr.(2015 Sep)
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)
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)
9.^Yongzhong Zhao, Zeneng WangImpact of trimethylamine N-oxide (TMAO) metaorganismal pathway on cardiovascular diseaseJ Lab Precis Med.(2020 Apr)
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)
14.^M Trabucchi, S Govoni, F BattainiChanges in the interaction between CNS cholinergic and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a cholinomimetic drugFarmaco Sci.(1986 Apr)
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)
18.^Scapicchio PLRevisiting choline alphoscerate profile: a new, perspective, role in dementiaInt J Neurosci.(2013 Feb 19)
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)
21.^SCHMIDT G, HERSHMAN B, THANNHAUSER SJThe isolation of alpha-glycerylphosphorylcholine from incubated beef pancreas; its significance for the intermediary metabolism of lecithinJ Biol Chem.(1945 Dec)
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)
26.^Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta FCholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluationJ Neurol Sci.(2007 Jun 15)
27.^Di Perri R, Coppola G, Ambrosio LA, Grasso A, Puca FM, Rizzo MA multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementiaJ Int Med Res.(1991 Jul-Aug)
28.^Amenta F, Tayebati SK, Vitali D, Di Tullio MAAssociation with the cholinergic precursor choline alphoscerate and the cholinesterase inhibitor rivastigmine: an approach for enhancing cholinergic neurotransmissionMech Ageing Dev.(2006 Feb)
29.^Tayebati SK, Di Tullio MA, Tomassoni D, Amenta FNeuroprotective effect of treatment with galantamine and choline alphoscerate on brain microanatomy in spontaneously hypertensive ratsJ Neurol Sci.(2009 Aug 15)
30.^Amenta F, Carotenuto A, Fasanaro AM, Rea R, Traini EThe ASCOMALVA trial: association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in Alzheimer's disease with cerebrovascular injury: interim resultsJ Neurol Sci.(2012 Nov 15)
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)
41.^Klein J, Gonzalez R, Köppen A, Löffelholz KFree choline and choline metabolites in rat brain and body fluids: sensitive determination and implications for choline supply to the brainNeurochem Int.(1993 Mar)
42.^Klein JMembrane breakdown in acute and chronic neurodegeneration: focus on choline-containing phospholipidsJ Neural Transm.(2000)
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)
44.^Trabucchi M, Govoni S, Battaini FChanges in the interaction between CNS cholinergic and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a cholinomimetic drugFarmaco Sci.(1986 Apr)
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)
53.^Noradrenergic modulation of cortical acetylcholine release is both direct and gamma-aminobutyric acid-mediated
54.^Beani L, Bianchi C, Tanganelli S, Antonelli T, Simonato M, Rando SInversion of the alpha-2 and alpha-1 noradrenergic control of the cortical release of acetylcholine and gamma-aminobutyric acid in morphine-tolerant guinea pigsJ Pharmacol Exp Ther.(1988 Oct)
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)
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)
59.^Govoni S, Battaini F, Lucchi L, Pascale A, Trabucchi MPKC translocation in rat brain cortex is promoted in vivo and in vitro by alpha-glycerylphosphorylcholine, a cognition-enhancing drugAnn N Y Acad Sci.(1993 Sep 24)
60.^Lucchi L, Pascale A, Battaini F, Govoni S, Trabucchi MCognition stimulating drugs modulate protein kinase C activity in cerebral cortex and hippocampus of adult ratsLife Sci.(1993)
62.^Govoni S, Lucchi L, Battaini F, Trabucchi MProtein kinase C increase in rat brain cortical membranes may be promoted by cognition enhancing drugsLife Sci.(1992)
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)
64.^Wurtman RJCholine metabolism as a basis for the selective vulnerability of cholinergic neuronsTrends Neurosci.(1992 Apr)
65.^Wurtman RJ, Blusztajn JK, Maire JC"Autocannibalism" of choline-containing membrane phospholipids in the pathogenesis of Alzheimer's disease-A hypothesisNeurochem Int.(1985)
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)
67.^Yang X, Sheng W, He Y, Cui J, Haidekker MA, Sun GY, Lee JCSecretory phospholipase A2 type III enhances alpha-secretase-dependent amyloid precursor protein processing through alterations in membrane fluidityJ Lipid Res.(2010 May)
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)
70.^De Jesus Moreno Moreno MCognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trialClin Ther.(2003 Jan)
71.^A neurotropic approach to the treatment of multi-infarct dementia using L-α-glycerylphosphorylcholine
72.^Parnetti L, Amenta F, Gallai VCholine alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical dataMech Ageing Dev.(2001 Nov)
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)
77.^Agarwal N, Sung YH, Jensen JE, daCunha G, Harper D, Olson D, Renshaw PFShort-term administration of uridine increases brain membrane phospholipid precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4TBipolar Disord.(2010 Dec)
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)
82.^Troesch B, Egli I, Zeder C, Hurrell RF, de Pee S, Zimmermann MBOptimization of a phytase-containing micronutrient powder with low amounts of highly bioavailable iron for in-home fortification of complementary foodsAm J Clin Nutr.(2009 Feb)
83.^Amenta F, Carotenuto A, Fasanaro AM, Rea R, Traini EThe ASCOMALVA trial: association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in Alzheimer's disease with cerebrovascular injury: interim resultsJ Neurol Sci.(2012 Nov 15)