Alpha-GPC (Alpha-glycerophosphocholine or sometimes just glycerophosphocholine) is a Choline-containing supplement that, although found in a variety of food products that are also rich in choline, appears to be pharmacologically active at higher doses.
Alpha-GPC is mostly marketed due to it conferring dietary choline to the body following oral ingestion, and being the most efficient choline prodrug at doing so (able to influence both systemic and brain concentrations of choline). Due to the provision of the other half of the alpha-GPC molecule (glycerophosphate), alpha-GPC also appears to support the structure of cellular membranes, which is not a common mechanism attributed to choline prodrugs (only CDP-choline is associated with lipid membranes in this sense).
Oral supplementation of alpha-GPC is of interest for nootropic purposes, as it appears to have cognitive-enhancing properties (no human evidence exists to support this in otherwise-healthy youth, but it does have support in rodents) and attenuate the rate of cognitive decline in the elderly. In regards to reducing the rate of cognitive decline, alpha-GPC at high doses (1,200 mg) does appear to be somewhat effective in mild to moderate Alzheimer's disease and works nicely with the standard therapy (acetylcholinesterase inhibitors).
Athletes are at times interested in alpha-GPC due to its ability to enhance growth hormone production (of which only acute spikes have been reported so far, so it may fall to the same problems that Arginine has on growth hormone) and to enhance power output, which has a lone pilot study in support of 600 mg alpha-GPC prior to exercise. Although ergogenic properties of alpha-GPC cannot be ruled out and look promising, it requires more evidence.
Alpha-glycerylphosphorylcholine, L-alpha-glycerophosphocholin, glycerophosphocholine, L-alpha-glyceryl-phosphorylcholine, Choline Alphoscerate
Alpha-GPC is approximately 40% choline by weight, and as such 1,000 mg alpha-GPC confers about 400 mg of dietary choline.
A standard dosage of alpha-GPC is 300-600 mg, according to the most common label doses. This dose is in accordance with the study using alpha-GPC to enhance power output (600 mg) and the two studies noting an increase in growth hormone secretion, and is likely a good dose to take for athletes.
For the usage of alpha-GPC in attenuating symptoms of cognitive decline, almost all studies use a dosage of 1,200 mg daily, divided into three doses of 400 mg. It is unsure how lower doses would benefit cognition, but the 1,200 mg appears to be consistently associated with benefit.
Rat studies suggest that the effects of alpha-GPC oral ingestion peak at 300-600 mg/kg, which is an estimated human dose of 48-96 mg/kg (and for a 150lb human, 3,272-6,545 mg daily).
For those of you who want to look more in depth at the anti-Alzheimer's aspect, look to the " Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data" review article. There is a lot of literature that is not published in english that cannot be cited on this page (due to a language and access barrier) that is covered in that review.
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects alpha-gpc has on your body, and how strong these effects are.
|Grade||Level of Evidence|
|A||Robust research conducted with repeated double-blind clinical trials|
|B||Multiple studies where at least two are double-blind and placebo controlled|
|C||Single double-blind study or multiple cohort studies|
|D||Uncontrolled or observational studies only|
Level of Evidence
||Magnitude of Effect Size
The rate of cognitive decline of either degenerative or vascular origin appears to be significantly reduced with Alpha-GPC supplementation
The lone pilot study noted a 14% increase in power output as assessed by bench throws, requires replication but seems stronger than caffeine based on this study.
|C||Symptoms of Alzheimers||
At least among nutraceuticals, Alpha-GPC appears to significantly improve cognition in persons with Alzheimer's disease at the dose of 1,200mg when taken as a daily supplement ... show
Some biomarkers of hepatic fat oxidation increased at rest, no indication as to the potency of this relative to reference drugs.
See 2 studies
Has noted an increase in circulating growth hormone, but measurements were acute (whole-day measurements of growth hormone are more reliable due to hourly fluctuations)
See 2 studies
It is possible that Alpha-GPC increases iron absorption from non-meat sources (nonheme iron), but the evidence is currently mixed and a very low dose of 46mg may be required ... show
L-alpha-glycerylphosphorylcholine (shortened to Alpha-GPC usually, also known as choline alphoscerate or glycerophosphocholine) is a choline containing phospholipid and an intermediate of lecithin metabolism or simply a lecithin molecule with two less fatty acids. It is a choline pro-drug, and is known to be a precursor to acetylcholine and Phosphatidylcholine in the body following ingestion.
Alpha-GPC is found as a naturally occurring constituent of red meat products and organ tissue but for the most part is scarce in appreciable amounts in naturally occurring sources. Most supplements containing Alpha-GPC are made synthetically, where it can be enzymatically created from egg or Soy lecithin. Due to this synthesis and the source, it is sometimes referred to as a semisynthetic derivative of lecithin.
Alpha-GPC is a choline containing phospholipid, and is used as a precursor for both acetylcholine synthesis and phospholipid synthesis in the brain. It is essentially a prodrug for both choline and glycerophosphate
Some food sources and their contents include:
Although the concentrations in food are well below that which is achieved with supplementation, Alpha-GPC appears to be fairly widespread in food sources with the only appreciable food sources being dairy and meat products (with an emphasis on organ meats) and wheat germ
Structurally speaking, Alpha-GPC is a choline molecule bound to a glycerol molecule via a phosphate group. It is Phosphatidylcholine (a lecithin molecule) without its two fatty acids.
The molar mass of Alpha-GPC is 257.221g, and is 40% choline by weight (ie. 1,000mg Alpha-GPC confers 400mg free choline).
Alpha-GPC is a lecithin molecule (phosphatidylcholine in particular) without the two additional fatty acids
When controlling for the amount of Choline in each supplement, Alpha-GPC requires 46% the dose of CDP-choline and due to being relatively higher in choline on a weight basis, administration of the same doses of either agent result in the group given Alpha-GPC experiencing a greater serum increase in choline. Alpha-GPC is considered to be a more effective (assessed by potency on a weight basis) cholinergic than both choline and CDP-choline when looking at serum values or benefit from clinical interventions.
Alpha-GPC has also been found to potentiate the effects of the acetylcholinesterase inhibitor rivastigmine in a dose-dependent manner whereas choline per se was ineffective, and this interaction has resulted in synergistic neuroprotection elsewhere in rats and interim results so far support the idea of pairing Alpha-GPC with an acetylcholinesterase inhibitor for the treatment of Alzheimer's.
Alpha-GPC appears to be the best currently known cholinergic in increasing plasma and brain choline levels, as it has better transportation into the brain than does choline (somewhat similar to CDP-choline) but since it is a greater percentage choline by weight (relative to CDP-choline) taking X dose of either drug gives more choline when using Alpha-GPC
Lecithin is metabolized when lysolecithin (from metabolism of lecithin by pancreatic phospholipase) is subject to phospholipase B to form glycerophosphorylcholine (synonymous with Alpha-GPC), which is then readily hydrolyzed by intestinal mucosal cells to form free Choline and glycerophosphate (via glycerylphosphorylcholine diesterase); this step can potentially be circumvented when lecithin is subject to Phospholipase D in the brain, which directly converts lecithin into glycerophosphate and choline (KM of 0.83).
Alpha-GPC can also be formed as a byprodut when two molecules of lysolecithin reconfigure into a molecule of lecithin (via an acetylation that is active when high concentrations of lysolecithin are present, with a KM of 3.6mM).
Alpha-GPC is an intermediate in lecithin metabolism, and thus uses some of the same enzymes for its metabolism and absorption
Oral ingestion of Alpha-GPC does appear to increase plasma choline concentrations, with one study reporting an increase in plasma choline with 1,000mg Alpha-GPC in otherwise healthy young men from 8.1+/-1.4μmol/L up to 12.1+/-1.9μmol/L (49% at 60 minutes) and 11.4+/-1.7μmol/L (41% at 120 minutes).
Phosphocholine (200-300nmol/g) and glycerophosphocholine (500-600nmol/g) concentrations in neural tissue are relatively higher than that of free choline or acetylcholine itself (less than 30nmol/g collectively),
Free choline and acetylcholine are relatively low in neural tissue, whereas concentrations of storage forms of choline (phosphocholine and Alpha-GPC) are relatively higher
It has been noted that the concentrations of glycerophosphocholine found in the brain is comparable or slightly lesser than that found in the blood, suggesting fairly easy passage via the blood brain barrier.
Alpha-GPC has been noted to be incorporated into brain phospholipids within 24 hours of ingestion in rats, and brain concentrations are increased by either oral ingestion or intravenous injections.
However, at least one study has noted that (using radiolabelled choline from Alpha-GPC) that the ability of excised neuronal tissue to release acetylcholine in response to stimulation peaked when the tissue was excised 1-3 hours after oral ingestion, and was not different than control at 8 hours. When measured after 24 hours, there was still some radiolabelled choline being synthesized into acetylcholine.
Can be taken up into the brain when orally ingested, and while a single large dose appears to consistently influence the brain over the course of 24 hours it may have a relative spike 1-3 hours post ingestion
One study has noted that repeated, but not single, injections of Alpha-GPC has resulted in a greater neuronal accumulation of inositol phosphate. This was not blocked by atropine (antagonist of muscarinic cholinergic receptors), and was hypothesized to be due to an increase in phospholipid synthesis. Along these lines, Alpha-GPC has been found to potentiate potassium-invoked calcium release in the hippocampus and receptor-mediated production of inositol phosphate, which is a similar phenomena as seen with Uridine (which is thought to act via support phospholipids).
Possible improvement in phospholipid biosynthesis associated with Alpha-GPC, and events which are seen with Alpha-GPC but are not readily replicated with choline are thought to be due to interactions with phospholipid metabolism
It has been noted that Alpha-GPC (150mg/kg) is able to increase dopamine concentrations in the frontal cortex and cerebellum of rats following ingestion which was not seen with an equal dose of choline from CDP-choline and the dopamine metabolite DOPAC has been noted to be increased in the striatum. Alpha-GPC has also been noted to enhance potassium-invoked dopamine release from neurons, which is thought to be due to interactions at the cellular membrane.
Both Alpha-GPC (150mg/kg and CDP-Choline are able to increase the dopamine transporter in these brain regions.
Limited evidence suggests that oral ingestion of Alpha-GPC can be dopaminergic, by both increasing dopamine release during neuronal action potentials and possibly by stimulating the expression of receptors
The serotonin transporter (SERT) does not appear to have its expression altered with oral Alpha-GPC.
Has at least once been implicated in increasing brain serotonin concentrations following oral administration
Oral ingestion of 300-600mg/kg Alpha-GPC to rats has been found to not inherently modify brain acetylcholine concentrations (relative to control), although the reduction of acetylcholine concentrations seen with scopolamine are partially reversed. Another study has found an increase in acetylcholine concentrations only in the frontal cortex, with no significant influence on the cerebellum and striatum.
In the striatum and cortex the protein content of the vesicular acetylcholine transporter appears to be increased and while this applied to both CDP-choline and Alpha-GPC, the increase in the transporter with Alpha-GPC appeared to apply to all tested brain regions. This implicates the glycerophosphate moiety, as the dosages (325mg/kg CDP-choline and 100mg/kg Alpha-GPC) were matched for choline content.
Can possibly increase brain acetylcholine levels, although this may be localized to the frontal cortex. It is more reliable in preserving acetylcholine concentrations during stressors (such as anticholinergics) and Alpha-GPC is also implicated in increasing expression of the vesicular acetylcholine transporter
Alpha-GPC has been shown to not enhance high-affinity choline uptake into the hippocampus.
Administration of Alpha-GPC prior to scopolamine (cholinergic toxin) administration is able to attenuate the performence impairment from scopolamine when taken three hours prior to the test (single dose, scopolamine given 30 minutes before testing) with maximal benefit seen at either 600mg/kg or 300mg/kg. This has been confirmed in a pilot study in otherwise healthy humans where the amnesiac effects of scopolamine were ablated, and appeared to be due to the cholinergic properties as amnesia via benzodiazepines was not affected. Comparatively speaking, this anti-amnesiac effect is more potent than both idebenone (synthetic analogue of CoQ10) and Aniracetam (mentioned via this review, primary study not available online).
Appears to be protective against cholinergic toxins
It has been noted that due to the ability of Alpha-GPC to increase cholinergic activity in the brain, that activation of nicotinic acetylcholine receptors (and subsequent activation of PI3K) could confer protection against glutamate-induced neurotoxicity.
No evidence directly assessing the interactions of Alpha-GPC and glutaminergic neurotransmission, but theoretically it can be neuroprotective (a trait common to choline containing compounds)
Alpha-GPC has been implicated in GABA release via the noradrenergic system. 30-300mg/kg intraperitoneal injections has been noted to increase GABA release with peak efficacy after 150 minutes (130% of baseline) and potentiated by atropine but not mecamylamine (reaching nearly 160% in half the time) while it was abolished by the alpha-1 adrenergic receptor antagonist prazosin and slightly hindered by physostigmine. The Alpha-1 adrenergic receptor is known to facilitate GABA release.
In vitro, 1.2mM but not 0.12mM was effective in increasing spontaneous GABA release from neurons and was again inhibited by prazosin.
Alpha-GPC appears to increase GABA release secondary to acting through Alpha-1 adrenergic receptors. It is not yet clear whether Alpha-GPC is acting as a ligand at these receptors (similar to Agmatine), whether it merely potentiates the signalling of other ligands, or whether this is just due to an increase in noradrenaline release
Protein Kinase C (PKC) is an intracellular intemediate that appears to be associated with memory formation when activated and is involved in long term potentiation as well. This activation of PKC is present at a concentration of 50nM and may be related to the phospholipid component as a related structure, diacylglyceride, is a known PKC activator.
Administration of Alpha-GPC to rats has been noted to promote PKC translocation in the rat cortex at an oral dose of 600mg/kg peaking at one hour after oral administration and either normalizing or dipping below control 5 hours after ingestion. The potency of 600mg/kg Alpha-GPC in activating PKC is similar to 100mg/kg Oxiracetam and 30mg/kg Aniracetam (higher doses being ineffective).
Alpha-GPC does not appear to influence forskolin or noradrenaline-induced adenyl cyclase activity.
Alpha-GPC appears to activate PKC in the hippocampus of rats following the standard supplemental dosages
When given to young rats without cognitive impairment, intraperitoneal injections of 100-200mg/kg daily (but not 25-50mg/kg) for 21 days two hours prior to training was associated with improved learning in both active and passive avoidance learning tasks.
Appears to have some evidence for efficacy in otherwise cognitively healthy young rats
It has been noted that Alzheimer's Disease (postmortem evaluation) is associated with an increased rate of phospholipid degradation which is hypothesized to be due to an increased requirement of choline (and thus, degrading choline containing phospholipids) as it is well established that acetylcholine can be derived from choline-containing phospholipids (Phosphatidylcholine) by a process sometimes referred to as autocannabilism.
In this sense, glycerophosphocholine is a biomarker as despite its enzyme of catabolism (GPC-cholinephosphodiesterase) being unaltered, it itself bioaccumulates indicating a breakdown of the lipid membrane. This is thought to be a part of pathology since the traditional biomarker of Alzheimer's disease, β-amyloid proteins, can activate phospholipase A2 in neurons and accelerate phospholipid degradation due to this.
Choline metabolism is known to be upregulated in Alzheimer's disease, and secondary to this increased requirement for choline there appears to be damage to the cellular membrane consisting of choline-containing phospholipids. Alpha-GPC is implicated here, but its role in treatment of membranes is uncertain
400mg thrice daily (1,200mg daily) over 180 days in persons with mild to moderate Alzheimer's noted that the Alpha-GPC group had a decrease in ADAS-Cog scores (indicating cognitive improvement) despite placebo having mild worsening. Other parameters measured (MMSE, GDS, ADAS-Behav, ADAS-Total, and CGI) had similar results, and while benefits were noted at 90 days there appeared to be further benefits at the end of the 180 day trial.
1,000mg Alpha-GPC has elsewhere been shown (intramuscular injections) to have benefit in vascular dementia over 90 days in regards to behavioural, memory, and verbal symptoms. It generally outperforms the same dosage of CDP-choline.
A review on the topic investigating 17 studies noted that the general usage of Alpha-GPC against cognitive disorders of degenerative or vascular origin (Alzheimer's, dementia, stroke, transitory ischemic attack) noted fairly consistent improvements on MMSE scores in the range of 10-26% (degenerative disorder origin) and 8-30% (vascular origin). While Alpha-GPC at the therapeutic dosage (1200mg daily) was more effective in the one trial where it was compared against ALCAR (a variant of L-Carnitine), it seems to be either more potent or equally effective to Oxiracetam.
When using the standard therapeutic dosage of 1,200mg Alpha-GPC taken in three divided dosages (400mg thrice a day), there appears to be improvement on cognitive and affective symptoms in persons with cognitive decline and Alzheimer's over prolonged periods
A review (no meta-analysis conducted) looking at three uncontrolled trials of 2484 patients with either transitory ischemic attack or stroke noted that one month of intramuscular administration (1,000mg) followed up by five months of oral therapy (1,200mg) noted consistent improvement in function as assessed by CGRS (19-21% improvement), MMSE (12-15% improvement), and GDS (20% improvement) relative to control. Of these trials, the largest can be located online.
When given immediately following a stroke or ischemia attack, appears to be neuroprotective. Due to the human trials starting treatment with intramuscular injections and then following up with oral maintenance, it is not sure how doing solely oral therapy works
Supplemental of Alpha-GPC given 600mg Alpha-GPC prior to a power test (bench throws) reported a 14% power output improvement relative to placebo when taken 45 minutes prior to activity; this was a pilot study.
Preliminary evidence that Alpha-GPC can enhance power output
One study using Alpha-GPC at 1,000mg has reported that, in otherwise healthy men, an increase in plasma biomarker of lipolysis (the ketone bodies acetoacetate and 3-hydroxyacetate, as well as free fatty acids) was reported to occur 120 minutes after supplement ingestion; the study did not measure time points beyond 120 minutes.
Growth hormone secretion in response to stimulation (via GHRH) is amplified with administration of Alpha-GPC, and although it is effective in both youth and elderly it seems that elderly persons experience a greater relative increase (due to having less output initially). This was attributed to the cholinergic properties of Alpha-GPC and can occur without exogenous stimulation by GHRH. One trial in otherwise healthy adults given 1,000mg Alpha-GPC noted that plasma choline increased 30-120 minutes postingestion (returning to baseline at 4 hours) and the spike in growth hormone was only reported at 60 minutes (from 1.4+/-1.6 to 4.5+/-2.7ng/mL; 221% increase) which normalized at 120 minutes.
One other study has reported that 600mg Alpha-GPC taken 45 minutes prior to physical exercise is able to augment the exercise-induced growth hormone spike from 5.0+/-4.8ng/mL in placebo to 8.4+/-2.1 ng/mL with supplementation. The increase appeared to be significantly more than placebo when measured immediately and up to 15 minutes after exercise cessation, normalizing at 60 minutes.
Appears to increase growth hormone secretion following oral ingestion, but due to a rapid normalization of growth hormone concentrations within 2 hours it may not lead to practical benefits (see the Arginine page and its growth hormone subsection for more info on this topic)
Uridine is a nucleotide which is used supplementally to increase brain phospholipid synthesis, and some other supplements (Triacetyluridine or CDP-choline) are uridine prodrugs in the sense that they confer uridine to the body following their ingestion.
Supplementation of uridine (via either uridine itself or prodrugs) has been noted to increase concentrations of some brain phospholipids and namely phosphoethanolamine, but the increase in glycerophosphocholine has not always been detected (a failure with 500mg uridine in youth for a week but a 5.1% increase over 6 weeks in older adults given 500mg CDP-choline although 500mg has elsewhere failed to significantly influence GPC levels).
Supplemental Uridine and/or uridine prodrugs may increase brain glycerophosphocholine concentrations, but it seems quite unreliable
Alpha-GPC appears to be able to enhance the absorption of nonheme iron from food products similar to how Vitamin C does when it is in a 2:1 ratio with iron, and due to this Alpha-GPC is thought to be or at least contribute to the phenomena where meat products can enhance the absorption of nonheme iron. This study used 46mg Alpha-GPC and it was of comparable potency to vitamin C, but elsewhere there has been a failure reported with a doubling of this ratio (4:1) or 70mg Alpha-GPC. Both studies used a mixed meal to deliver Alpha-GPC and nonheme iron, and it is unsure why the difference in results occurs.
There is mixed evidence for how Alpha-GPC can influence iron absorption, and it is not sure if it requires a lower dose or if it is only effective in experimental settings. More research is required on this topic
The LD50 of orally ingested Alpha-GPC appears to be greater than 10,000mg/kg in rats and mice, and subchronic toxicity studies with 1,000mg/kg in rats leads to slight weight loss and reductions in food consumption. It was said that the No Observed Adverse Effect Level (NOAEL) was 150mg/kg over 26 weeks in rats, which is approximately 24mg/kg in humans (for a 150lb person, 1,636mg).
Alpha-GPC does not appear to possess mutagenic activity.