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
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. Alpha-GPC appears to easily cross the blood-brain barrier and is rapidly absorbed.
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). 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.
Athletes are another population that may benefit from alpha-GPC supplementation. Preliminary evidence suggests that alpha-GPC increases vertical jump power. Additionally, a pilot study reported that alpha-GPC increased peak bench press force, but not peak power or rate of force development. Whether alpha-GPC increases isometric strength is currently unclear.
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. 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.
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. Moreover, a 2021 mouse study found that alpha-GPC supplementation promoted atherosclerosis.
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.
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.
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.
- ^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)
- ^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)
- ^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)
- ^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)
- ^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)
- ^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)
- Alzheimer's Disease Symptoms - 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)
- Growth Hormone - Tim Ziegenfuss, Jamie Landis and Jennifer HofheinsAcute supplementation with alpha-glycerylphosphorylcholine augments growth hormone response to, and peak force production during, resistance exerciseJISSN.()
- Growth Hormone - 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 Jun 5)
- Iron Absorption - 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)
- Iron Absorption - Charlotte N Armah, Paul Sharp, Fred A Mellon, Sandra Pariagh, Elizabeth K Lund, Jack R Dainty, Birgit Teucher, Susan J Fairweather-TaitL-alpha-glycerophosphocholine contributes to meat's enhancement of nonheme iron absorptionJ Nutr.(2008 May)