Alpha-GPC: Nootropic use, common dosing, and quality sourcing

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**

Alpha-GPC 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.

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.

However GPC has the additional benefit compared to free choline, choline bitartrate or choline citrate in the fact that it lacks 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 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. 

HOWEVER, if you have risks heart health do note there is some speculative evidence and plausible mechanisms by which it can contribute to stroke risk and other issues with consistent use. This should be considered in your pros and cons analysis and perhaps investigating other mechanisms to support acetylcholine would be prudent. Simple MOA is via increasing TMA from more choline available, which can then convert to TMAO which is notably implicated in heart health factors and stroke risk. More choline is good for many things but has some downsides, reminder that nothing it a perfect system, this pathway also applies for other choline precursors, Betaine and Carnitine. Also has some mechanisms increasing pro-inflammatory cytokines that contributes to atherosclerosis also.

GPC is sometimes used before sleep to provide an acute support to REM sleep activities, theoretically a good application, limited research performed.

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 hydroscopic 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.

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