What is alpha-GPC?
Alpha-GPC (alpha-glycerophosphocholine or choline alphoscerate) is a choline-containing phospholipid. When ingested, alpha-GPC is rapidly absorbed and easily crosses the blood-brain barrier. It 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]
What are alpha-GPC’s main benefits?
Oral supplementation of alpha-GPC is primarily of interest for nootropic or cognitive-enhancement purposes. While there are certain cases in which alpha-GPC seems to be beneficial, there isn’t any research in healthy humans that suggests it provides some general “cognitive enhancement”. There are a number of rodent studies that show an improvement in learning and memory in supplemented animals, but these effects have yet to be demonstrated in 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).[2][1] Alpha-GPC may also help those with glioblastoma, a type of brain cancer that is very difficult to treat. A 2022 study found that the overall survival rate of people with glioblastoma improved when alpha-GPC was added to surgical and chemotherapeutic treatments.[3] Alpha-GPC may also improve the effectiveness of acetylcholinesterase inhibitors (drugs that increase acetylcholine’s availability by slowing down its breakdown), which are used for treating Alzheimer’s disease.[2][4] When Alpha-GPC is added to this standard Alzheimer’s treatment, it may improve behavioral symptoms, functional outcomes, and cognitive symptoms.[5]
Athletes are another population that may benefit from alpha-GPC supplementation. Preliminary evidence suggests that alpha-GPC increases vertical jump power. In one study, both caffeine and alpha-GPC improved vertical jump power, with the greatest improvement in participants who took a 200 mg dose of alpha-GPC.[6][7] Additionally, a pilot study reported that alpha-GPC increased peak bench press force, but not peak power or rate of force development.[8] In one study done in trained cyclists, alpha-GPC improved peak power and time to fatigue when used with L-citrulline.[9] Whether alpha-GPC increases isometric strength is currently unclear.[7][10]
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.[11] The no-observed-adverse-effect level (NOAEL) 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. While an association may exist here, the causative link between TMAO and CVD isn’t particularly strong. In healthy people this may not be something to worry about, but in people with a high risk of CVD it may be prudent to consider the added risk.[12][13]
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.[14] Moreover, a 2021 mouse study found that alpha-GPC supplementation promoted atherosclerosis.[15]
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.[16][17][18][19]
Acetylcholine is also responsible for the action potentials that stimulate muscles to contract. Therefore, it’s theorized that increased acetylcholine levels lead to a stronger signal for muscle contraction and, consequently, to increased force production.
What are other names for Alpha-GPC
- Alpha-glycerylphosphorylcholine
- L-alpha-glycerophosphocholin
- glycerophosphocholine
- L-alpha-glyceryl-phosphorylcholine
- Choline Alphoscerate
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.
Frequently asked questions
Alpha-GPC (alpha-glycerophosphocholine or choline alphoscerate) is a choline-containing phospholipid. When ingested, alpha-GPC is rapidly absorbed and easily crosses the blood-brain barrier. It 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]
Oral supplementation of alpha-GPC is primarily of interest for nootropic or cognitive-enhancement purposes. While there are certain cases in which alpha-GPC seems to be beneficial, there isn’t any research in healthy humans that suggests it provides some general “cognitive enhancement”. There are a number of rodent studies that show an improvement in learning and memory in supplemented animals, but these effects have yet to be demonstrated in 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).[2][1] Alpha-GPC may also help those with glioblastoma, a type of brain cancer that is very difficult to treat. A 2022 study found that the overall survival rate of people with glioblastoma improved when alpha-GPC was added to surgical and chemotherapeutic treatments.[3] Alpha-GPC may also improve the effectiveness of acetylcholinesterase inhibitors (drugs that increase acetylcholine’s availability by slowing down its breakdown), which are used for treating Alzheimer’s disease.[2][4] When Alpha-GPC is added to this standard Alzheimer’s treatment, it may improve behavioral symptoms, functional outcomes, and cognitive symptoms.[5]
Athletes are another population that may benefit from alpha-GPC supplementation. Preliminary evidence suggests that alpha-GPC increases vertical jump power. In one study, both caffeine and alpha-GPC improved vertical jump power, with the greatest improvement in participants who took a 200 mg dose of alpha-GPC.[6][7] Additionally, a pilot study reported that alpha-GPC increased peak bench press force, but not peak power or rate of force development.[8] In one study done in trained cyclists, alpha-GPC improved peak power and time to fatigue when used with L-citrulline.[9] Whether alpha-GPC increases isometric strength is currently unclear.[7][10]
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.[11] The no-observed-adverse-effect level (NOAEL) 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. While an association may exist here, the causative link between TMAO and CVD isn’t particularly strong. In healthy people this may not be something to worry about, but in people with a high risk of CVD it may be prudent to consider the added risk.[12][13]
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.[14] Moreover, a 2021 mouse study found that alpha-GPC supplementation promoted atherosclerosis.[15]
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.[16][17][18][19]
Acetylcholine is also responsible for the action potentials that stimulate muscles to contract. Therefore, it’s theorized that increased acetylcholine levels lead to a stronger signal for muscle contraction and, consequently, to increased force production.
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References
- ^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)
- ^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)
- ^Kim YJ, Lee TK, Noh MG, Jung TY, Kim IY, Jung S, Lee KH, Moon KSEffect of Choline Alphoscerate on the Survival of Glioblastoma Patients: A Retrospective, Single-Center Study.J Clin Med.(2022-Oct-13)
- ^Kansakar U, Trimarco V, Mone P, Varzideh F, Lombardi A, Santulli GCholine supplements: An update.Front Endocrinol (Lausanne).(2023)
- ^Sagaro GG, Traini E, Amenta FActivity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis.J Alzheimers Dis.(2023)
- ^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)
- ^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)
- ^Ziegenfuss T, Landis J, Hofheins JAcute supplementation with alpha-glycerylphosphorylcholine augments growth hormone response to, and peak force production during, resistance exerciseJ Int Soc Sports Nutr.(2008 Sep)
- ^Harrington RNEffects of branched chain amino acids, l-citrulline, and alpha-glycerylphosphorylcholine supplementation on exercise performance in trained cyclists: a randomized crossover trial.J Int Soc Sports Nutr.(2023-Dec)
- ^David Bellar, Nina R LeBlanc, Brian CampbellThe effect of 6 days of alpha glycerylphosphorylcholine on isometric strengthJ Int Soc Sports Nutr.(2015 Nov 17)
- ^Amy M Brownawell, Edward L Carmines, Federica MontesanoSafety assessment of AGPC as a food ingredientFood Chem Toxicol.(2011 Jun)
- ^Yongzhong Zhao, Zeneng WangImpact of trimethylamine N-oxide (TMAO) metaorganismal pathway on cardiovascular diseaseJ Lab Precis Med.(2020 Apr)
- ^Yang S, Li X, Yang F, Zhao R, Pan X, Liang J, Tian L, Li X, Liu L, Xing Y, Wu MGut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target.Front Pharmacol.(2019)
- ^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)
- ^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)
- ^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)
- ^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)
- ^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)
- ^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)
