α-GPC (L-Alpha glycerylphosphorylcholine)

L-Alpha glycerylphosphorylcholine (α-GPC, choline alfoscerate) is a natural choline compound. It is parasympathomimetic, meaning it activates the "rest and digest" branch of the nervous system.

α-GPC rapidly delivers choline to the brain across the blood–brain barrier and is a biosynthetic precursor of the neurotransmitter acetylcholine.

α-GPC is readily hydrolyzed and absorbed through oral intake to form free choline. It is able to increase both dopamine and serotonin concentrations in the frontal cortex and cerebellum of rats following ingestion.

Effects on Cognition

Attention

A study on 19 healthy college students showed that a nootropic blend consisting of α-GPC in addition to other compounds (choline bitartrate, phosphatidylserine, vitamins B3, B6, and B12, folic acid, L-tyrosine, anhydrous caffeine, acetyl-L-carnitine, and naringin), resulted in increased reaction time and alertness, as measured by both a self-report questionnaire and reaction time measured by a Makoto testing device.1

Memory

A study in 26 individuals showed that daily ingestion of a nootropic blend containing α-GPC was effective in improving memory (recall, recognition, and short-term memory) at both 2 weeks and 10 weeks into the treatment period.2

Structure & Synthesis

Choline can be supplemented from several different sources. Popular sources include α-GPC, choline bitartate and CDP-choline. By weight, choline represents 40% of α-GPC, 18% of CDP-choline, and 40% of choline bitartate. Choline bitartate is inexpensive, but is not as bioavailable as α-GPC or CDP-choline and cannot cross the brain-blood barrier. CDP-choline is a less efficient delivery mechanism of choline; one needs to take more than twice as much CDP-choline than α-GPC to get the same amount of choline.

α-GPC naturally occurs in the brain. When the brain is low on free choline for acetylcholine, the brain breaks down cell membranes to cannabalize choline. α-GPC is that catabolic byproduct, and thus is reliably able to cross the blood brain barrier intact.

The best natural source of α-GPC is in red meat.3Its natural availability is otherwise scarce.

α-GPC can be synthesized synthetically via phosphorylation and reduction steps with (R)-glycidol as a starting material.4

Mechanisms of Action

Choline (various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation) is a chemical precursor or "building block" needed to produce acetylcholine.5

This is clinically important because there is a large body of research suggesting that learning, memory, intelligence, and mood are mediated at least in part by acetylcholine metabolism in the brain.6This is commonly referred to as the "cholinergic effect".

Role of cholinergic receptors in memory

Increased binding to cholinergic receptors has been implicated in memory.

The role of cholinergic receptors in memory has been studied extensively in animal models by administering cholinergic antagonists and measuring resulting changes in memory. Injection of cholinergic antagonists in the perirhinal cortex has resulted in impaired encoding of information for stimuli recognition.7Scopolamine injection into the hippocampus impairs spatial encoding8, and infusions into the medial septum impair spatial learning and reduce acetylcholine release in the hippocampus.9

Infusions of carbachol (a cholinergic agonist) were able to reverse memory impairment caused by a certain dosage of scopolamine. However, impairment caused by a higher dosage was not reversible.9Meanwhile, infusions of scopolamine into the CA3 region of the hippocampus have been shown to cause impairments in memory encoding in rats as tested with the Hebb-Williams maze.10

How to take

Alpha-GPC is ~40% choline by weight, therfore 1,000 mg alpha-GPC = ~400 mg of choline. A standard dosage of alpha-GPC is 300-600 mg.

Safety and side effects

Yes, α-GPC is approved as a dietary supplement component under provisions of the Dietary Supplement Health and Education Act of 1994. It is classified as generally recognized as safe (GRAS).

There are no reported major side effects of α-GPC. Minor side effects include headache and heartburn, but these are rare if α-GPC is taken in safe quantities.5,11,12,13Most individuals should be able to safely tolerate up to 1.2 g of α-GPC per day.11,14

  1. Hoffman, J. R., Ratamess, N. A., Gonzalez, A., Beller, N. A., Hoffman, M. W., Olson, M., ... & Jager, R. (2010). The effects of acute and prolonged CRAM supplementation on reaction time and subjective measures of focus and alertness in healthy college students. Journal of the International Society of Sports Nutrition, 7(1), 1-8.

  2. Richter, Y., Herzog, Y., Eyal, I., & Cohen, T. (2011). Cognitex supplementation in elderly adults with memory complaints: an uncontrolled open label trial. Journal of dietary supplements, 8(2), 158-168.

  3. Armah, C. N., Sharp, P., Mellon, F. A., Pariagh, S., Lund, E. K., Dainty, J. R., ... & Fairweather-Tait, S. J. (2008). L-alpha--glycerophosphocholine contributes to meat's enhancement of nonheme iron absorption. The Journal of nutrition, 138(5), 873-877.

  4. Park, J. M., De Castro, K. A., Ahn, H., & Rhee, H. (2010). Facile syntheses of L-alpha-glycerophosphorylcholine. Bull. Korean Chem. Soc, 31, 2689-2691

  5. Parnetti, L., Mignini, F., Tomassoni, D., Traini, E., & Amenta, F. (2007). Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation?. Journal of the neurological sciences, 257(1), 264-269.

  6. Hasselmo, M. E. (2006). The role of acetylcholine in learning and memory. Current opinion in neurobiology, 16(6), 710-715.

  7. Tang, Y., Mishkin, M., & Aigner, T. G. (1997). Effects of muscarinic blockade in perirhinal cortex during visual recognition. Proceedings of the National Academy of Sciences, 94(23), 12667-12669.

  8. Blokland, A., Honig, W., & Raaijmakers, W. G. (1992). Effects of intra-hippocampal scopolamine injections in a repeated spatial acquisition task in the rat. Psychopharmacology, 109(3), 373-376.

  9. Elvander, E., Schott, P. A., Sandin, J., Bjelke, B., Kehr, J., Yoshitake, T., & Ogren, S. O. (2004). Intraseptal muscarinic ligands and galanin: influence on hippocampal acetylcholine and cognition. Neuroscience, 126(3), 541-557.

  10. Rogers, J. L., & Kesner, R. P. (2003). Cholinergic modulation of the hippocampus during encoding and retrieval. Neurobiology of learning and memory, 80(3), 332-342.

  11. Scapicchio, P. L. (2013). Revisiting choline alphoscerate profile: a new, perspective, role in dementia?. International Journal of Neuroscience, 123(7), 444-449.

  12. Parnetti, L., Amenta, F., & Gallai, V. (2001). Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mechanisms of ageing and development, 122(16), 2041-2055

  13. Moreno, M. D. J. M. (2003). Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial. Clinical therapeutics, 25(1), 178-193.

  14. Brownawell, A. M., Carmines, E. L., & Montesano, F. (2011). Safety assessment of AGPC as a food ingredient. Food and Chemical Toxicology, 49(6), 1303-1315.

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