Acronyms:
- GPC = l-alpha-glycerylphosphorylcholine
- LTP = Long Term Potentiation
- NGF & BDNF = "Nerve Growth Factor" & "Brain Derived Neurotrophic Factor"
- MOA = Mechanism of Action
- TMA & TMAO = "trimethylamine" & "trimethylamine N-oxide" respectively
- BBB = Blood Brain Barrier
Synonyms: l-alpha-glycerylphosphorylcholine (αGPC), Choline alfoscerate, L-alpha-Lecithin, glycerophosphocholine**
αGPC basic specifications
PubChem: pubchem.ncbi.nlm.nih.gov/compound/Choline-Alfoscerate
Chemical name / classification: l-alpha-glycerylphosphorylcholine
Molecular formula: C8H20NO6P
Visual: White crystalline, takes on water from the air extremely quickly to begin clumping to liquid. Can look almost like cake icing.
Molar mass: 257.22 g/mol
Smell: ND
Taste: Sweet not distinctive flavour profile
Primary Use of αGPC:
GPC is primarily used in the cognitive health and sports supplementation community, with some cross use in common foods as a constituent of soy lecithin.
GPC is a choline donor, with approximate 40% choline yield by weight. This contributes as a precursor to multiple pathways, most notably the acetylcholine neurotransmitter which has:
- functions in neuroprotection, notable evidence in preventing cognitive decline with age;
- cognitive performance with particular emphasis on states of focus, memory and motivation - this is expected due to the elevated dopamine and norepinephrine that accompanies increased acetylcholine; note that the initiation of this adrenergic cascade will also result in increased GABA release >> this MAY account for the drowsiness effect associated with alpha-GPC overdosing, commonly in the above 1g range.
- influence on synaptic plasticity and LTP pathways, elevating NGF and BDNF;
- improved muscle contraction and therefore force output, due to the role acetylcholine plays in muscle contraction signalling;
- anecdotally improved reaction time, with Olympic sprinters supplementing high doses to improve “off-the-line” response.
GPC has a key advantage compared to free choline, choline bitartrate or choline citrate in the fact that it lacks the two fatty acid bonds that commonly decreases water solubility. Hence GPC has good water solubility and can easily cross the blood brain barrier with what is expected passive transport, which can be seen in rat studies where brain GPC levels quickly follow serum GPC levels to equalise.
This said, much of GPC is still metabolised in the liver and gut before crossing the blood brain barrier, where it still plays a valuable role in the peripheral nervous system and as a substrate in the liver to support healthy function - 7mg/kg/day being a cited number as minimum rdi to prevent liver damage and fatty liver disease.
Choline in both brain and body also plays a role as a precursor to betaine production, which is then converted to SAMe >> the result of which helping to support methylation balance and prevent excesses of homocysteine which can hamper neurotransmitter activity, and is strongly associated with mood disorders.
Common αGPC Dosing Protocols
GPC is commonly dosed in preworkout and nootropic supplements in the range between 300mg and 600mg, as a result of clinical literature supporting this dose range for acute benefit. However do note dosing in clinical literature goes as high as 1.2g daily for further benefit.
As a precursor ingredient to the essential neurotransmitter acetylcholine, its best used regularly to support total brain choline stores and prevent deficiency. This is also best as there is conflicting evidence as to whether the brain acetylcholine will in fact increase concentration in response to increased available choline, with most solid evidence showing that acetylcholine is manufactured on demand (when supply is low).
Best dosing is approximately 60 - 120minutes before desired acute performance peak to allow for crossing of the BBB.
For standalone doses, commonly 300 - 500mg is a good range, with higher doses anecdotally causing drowsiness. If paired alongside stimulants, dosing higher 400 - 800mg can be considered. This provides a complimentary smoothing focus, clarity and motivation effect with the likes of a coffee to make the classic nootropic combination of stimulants + cholinergics. This also helps ensure additional acetylcholine release due to stimulant intake does not lead to acetylcholine deficits, which are associated with brain fog and fatigue.
Total daily dosing of up to 1200mg is well supported as safe for long-term use over a period of multiple months.
Atherosclerosis and αGPC
First, what is atherosclerosis and why care?
Atherosclerosis is the buildup of plaques made from cholesterol, fats and other compounds in and on artery walls. This causes a loss in flexibility (hardening) and narrowing, and can even sometimes cause a blockage leading to a blood clot and stroke.
Second, what is the relationship between Alpha GPC and atherosclerosis?
Brace for things getting a bit technical in this section, however regardless of background I'm sure you'll get the gist of it.
As a source of choline GPC does contain and hence break down to, both directly and indriectly via choline, into trimethylamine (TMA). This occurs by cleaving actions by the “choline TMA lyse” enzyme “cut C/D”, which is produced by gut bacteria.
The TMA is then oxidised by hepatic flavin monooxygenases (FMOs) into trimethylamine N-oxide (TMAO). TMAO has been shown to modulate multiple proatherogenic effectors, including NF-κB, MAPK signaling, NLRP3 inflammasome activation, and increases pro-inflammatory monocyte abundance in circulating blood.
This said, also consider that choline is an essential nutrient for protecting against liver disease as well as neuronal decline, so a balance must be struck to ensure an adequate tradeoff per individual. Similar cases are made with betaine and carnitine which also promote TMAO production, albeit to lesser extents.
Dose response is also a significant consideration, and do note that 1,200mg daily dosed GPC has been studied in humans for a period of several months with no indications for serious toxicity concern, hence at that dose it may be expected to contribute to a minor level, that which is of more concern to individuals pre-disposed to atherosclerosis, or living lifestyles that add compounding factors.
Sourcing Quality
GPC is an expensive ingredient, however is widely available and manufacturable, so it is not a common ingredient to have quality issues. That said, under-dosing is widespread, especially in the preworkout category.
Additionally, the industry standard for manufacturers is to use 50% GPC by yield powder, combined with 50% calcium phosphate in order to combat the highly hygroscopic nature and allow it to maintain a fluid texture running through mixing and pouring equipment. This is not often declared, and many uninformed supplement companies are unaware of this fact and that it is manufacturing standard. Hence any supplement label that does not state GPC purity is likely only a 50% purity, which leads to an under-dose both compared to the label claim and also why most preworkouts and nootropics are under-dosed by true GPC yield compared to clinical research their GPC content.
Example: label claiming 300mg alpha-GPC with no purity stated, but because it’s a 50% yield, in fact there is only 150mg alpha-GPC.
At NSC we have used a 98% purity GPC in the past, however directly as a result of the manufacturing challenges later bent to the industry standard of 50% with calcium phosphate. The currently available GPC formulation is a bottle of 60 capsules, each yielding 300mg of GPC. For more information on that, see the product page here.
Further reading
Re: cognitive performance
Re: athersclerosis and stroke risk
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LATEST REVISION: 12th February 2023