Alpha-GPC

Alpha-glycerophosphocholine (Alpha-GPC or α-GPC) is a cholinergic compound that is used for its cognitive-promoting properties, and to enhance power output in athletes. It appears to also support cellular membranes, and may aid in preventing cognitive decline.

This page features 68 unique references to scientific papers.


Confused about what actually Works?
MUST GET: Supplement Stack Guides - Saving You Money & Time

   

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.

Follow this Page for updates

Confused about Supplements?
Get the Stack Guides

Also Known As

Alpha-glycerylphosphorylcholine, L-alpha-glycerophosphocholin, glycerophosphocholine, L-alpha-glyceryl-phosphorylcholine, Choline Alphoscerate


Do Not Confuse With

Choline, DMAE, CDP-choline


Things to Note

  • Although traditionally known as being nonstimulatory, some persons do report cognitive stimulation with supplemental alpha-GPC.
  • It may be prudent to take alpha-GPC alongside dietary fatty acids for absorption (due to it being a phospholipid), although this does not appear to be an absolute requirement.

Is a Form of


Goes Well With

  • Acetylcholinesterase inhibitors (for any choline-related property, such as attenuating symptoms of Alzheimer's)

Does Not Go Well With

  • Anticholinergics

Caution Notice

Examine.com Medical Disclaimer
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.


Kurtis Frank

The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Alpha-GPC has in your body, and how strong these effects are.
GradeLevel of Evidence
ARobust research conducted with repeated double blind clinical trials
BMultiple studies where at least two are double-blind and placebo controlled
CSingle double blind study or multiple cohort studies
DUncontrolled or observational studies only
Level of Evidence
EffectChange
Magnitude of Effect Size
Scientific ConsensusComments
CGrowth Hormone

Minor

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)

CFat Oxidation

Minor

Some biomarkers of hepatic fat oxidation increased at rest, no indication as to the potency of this relative to reference drugs.

CCognitive Decline

Notable

The rate of cognitive decline of either degenerative or vascular origin appears to be significantly reduced with Alpha-GPC supplementation

CSymptoms of Alzheimers

Notable

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

CPower Output

Minor

The lone pilot study noted a 14% increase in power output as assessed by bench throws, requires replication

DIron Absorption

Minor

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


Studies Excluded from Consideration


Disagree? Join the Alpha-GPC Discussion

Table of Contents:


Edit1. Sources and Structure

1.1. Sources

L-alpha-glycerylphosphorylcholine (shortened to Alpha-GPC usually, also known as choline alphoscerate or glycerophosphocholine) is a choline containing phospholipid[5] and an intermediate of lecithin metabolism or simply a lecithin molecule with two less fatty acids.[6] It is a choline pro-drug, and is known to be a precursor to acetylcholine and Phosphatidylcholine in the body following ingestion.[7][8]

Alpha-GPC is found as a naturally occurring constituent of red meat products[9] and organ tissue[10] but for the most part is scarce in appreciable amounts in naturally occurring sources.[8] Most supplements containing Alpha-GPC are made synthetically, where it can be enzymatically created from egg[11] or Soy lecithin.[8] Due to this synthesis and the source, it is sometimes referred to as a semisynthetic derivative of lecithin.[12]

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:

  • Toasted wheat germ (33.78mg/100g), wheat crackers (10.94mg/100g), and wheat bread (4.93mg/100g)[13]
  • Oat bran (33.25mg/100g)[13]
  • 2% Milk (9.98mg/100g) and skim milk (9.70mg/100g)[13]
  • Cheese (2.30mg/100g), Cottage cheese (8.39mg/100g), Cream cheese (9.26mg/100g)[13]
  • Yogurt (7.79-9.10mg/100g)[13]
  • Eggs (0.60mg/100g)[13]
  • Chicken breast (1.12-1.20mg/100g) and liver (8.80mg/100g)[13]
  • Pork sausage (7.41mg/100g), cooked pork loin (22.51mg/100g)[13]
  • Beef liver (77.93mg/100g)[13]
  • Atlantic cod (30.04mg/100g), Salmon (5.89mg/100g)[13]
  • Bananas (5.60mg/100g), blueberries (0.61mg/100g), avocado (0.73mg/100g), grapefruit (1.16mg/100g), cantelope (0.71mg/100g), oranges (1.10mg/100g), and strawberries (0.86mg/100g)[13]
  • Broccoli (1.32mg/100g), cabbage (3.47mg/100g), cucumber (0.48mg/100g), spinach (0.21mg/100g), onions (0.57mg/100g), sauerkraut (0.94mg/100g), sweet potatoes (1.97mg/100g), brussel sprouts (3.18mg/100g), and raw mushrooms (5.11mg/100g)[13]
  • Beer (light at 2.98mg/100g, regular at 5.06mg/100g) and Coffee (0.67mg/100g)
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

1.2. Structure and Properties

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

1.3. Comparisons to other choline sources

When controlling for the amount of Choline in each supplement, Alpha-GPC requires 46% the dose of CDP-choline[5] 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.[14] 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.[15][2]

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,[16] and this interaction has resulted in synergistic neuroprotection elsewhere in rats[17] and interim results so far support the idea of pairing Alpha-GPC with an acetylcholinesterase inhibitor for the treatment of Alzheimer's.[4]

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


Edit2. Pharmacology

2.1. Absorption

Lecithin is metabolized when lysolecithin (from metabolism of lecithin by pancreatic phospholipase[6][18]) is subject to phospholipase B to form glycerophosphorylcholine (synonymous with Alpha-GPC),[19][20][21] which is then readily hydrolyzed by intestinal mucosal cells to form free Choline and glycerophosphate (via glycerylphosphorylcholine diesterase[22][6]); 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).[23][6]

Alpha-GPC can also be formed as a byprodut when two molecules of lysolecithin reconfigure into a molecule of lecithin[6][24] (via an acetylation that is active when high concentrations of lysolecithin are present, with a KM of 3.6mM[25]).

Alpha-GPC is an intermediate in lecithin metabolism, and thus uses some of the same enzymes for its metabolism and absorption

2.2. Serum

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).[26]

2.3. Neurological Kinetics

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),[27][28][29]

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.[30]

Alpha-GPC has been noted to be incorporated into brain phospholipids within 24 hours of ingestion in rats,[30] and brain concentrations are increased by either oral ingestion or intravenous injections.[31]

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.[32] When measured after 24 hours, there was still some radiolabelled choline being synthesized into acetylcholine.[32]

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


Edit3. Neurology

3.1. Mechanisms

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.[33] Along these lines, Alpha-GPC has been found to potentiate potassium-invoked calcium release in the hippocampus and receptor-mediated production of inositol phosphate,[34] 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

3.2. Dopaminergic Neurotransmission

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[5] and the dopamine metabolite DOPAC has been noted to be increased in the striatum.[31] Alpha-GPC has also been noted to enhance potassium-invoked dopamine release from neurons,[31] 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.[5]

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

3.3. Serotonergic Neurotransmission

It has been noted that Alpha-GPC (150mg/kg) is able to increase serotonin concentrations in the frontal cortex and cerebellum of rats following ingestion, which was not seen with CDP-choline.[5]

The serotonin transporter (SERT) does not appear to have its expression altered with oral Alpha-GPC.[5]

Has at least once been implicated in increasing brain serotonin concentrations following oral administration

3.4. Cholinergic Neurotransmission

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.[35][32] Another study has found an increase in acetylcholine concentrations only in the frontal cortex, with no significant influence on the cerebellum and striatum.[36]

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.[36][37] This implicates the glycerophosphate moiety, as the dosages (325mg/kg CDP-choline and 100mg/kg Alpha-GPC) were matched for choline content.[36]

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.[32]

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)[35][32] with maximal benefit seen at either 600mg/kg[35] or 300mg/kg.[32] 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.[38] Comparatively speaking, this anti-amnesiac effect is more potent than both idebenone (synthetic analogue of CoQ10) and Aniracetam (mentioned via this review,[7] primary study not available online).

Appears to be protective against cholinergic toxins

3.5. Glutaminergic Neurotransmission

It has been noted[7] 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)

3.6. GABAergic Neurotransmission

Alpha-GPC has been implicated in GABA release via the noradrenergic system.[39] 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.[39] The Alpha-1 adrenergic receptor is known to facilitate GABA release.[40][41]

In vitro, 1.2mM but not 0.12mM was effective in increasing spontaneous GABA release from neurons and was again inhibited by prazosin.[39]

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

3.7. Attention

One study using Alpha-GPC alongside both Caffeine and Phosphatidylserine has found increased attention and reaction time in persons undergoing acute stress.[1]

3.8. Memory and Cognition

Protein Kinase C (PKC) is an intracellular intemediate that appears to be associated with memory formation when activated[42][43] and is involved in long term potentiation as well.[44] This activation of PKC is present at a concentration of 50nM[45][46] and may be related to the phospholipid component as a related structure, diacylglyceride, is a known PKC activator.[47]

Administration of Alpha-GPC to rats has been noted to promote PKC translocation in the rat cortex at an oral dose of 600mg/kg[45] peaking at one hour after oral administration[46][48] and either normalizing or dipping below control 5 hours after ingestion.[48] The potency of 600mg/kg Alpha-GPC in activating PKC is similar to 100mg/kg Oxiracetam and 30mg/kg Aniracetam (higher doses being ineffective).[46]

Alpha-GPC does not appear to influence forskolin or noradrenaline-induced adenyl cyclase activity.[34]

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.[34]

Appears to have some evidence for efficacy in otherwise cognitively healthy young rats

3.9. Alzheimer's Disease

It has been noted that Alzheimer's Disease (postmortem evaluation) is associated with an increased rate of phospholipid degradation[49] which is hypothesized to be due to an increased requirement of choline (and thus, degrading choline containing phospholipids)[27] as it is well established that acetylcholine can be derived from choline-containing phospholipids (Phosphatidylcholine) by a process sometimes referred to as autocannabilism.[50][51]

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.[49][52] 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[53] and accelerate phospholipid degradation due to this.[54][55]

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.[56]

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.[3][2]

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).[57] 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),[58] it seems to be either more potent or equally effective to Oxiracetam.[57]

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

3.10. Ischemia and Stroke

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.[57] Of these trials, the largest can be located online.[59]

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


Edit4. Physical Performance and Skeletal Muscle

4.1. Power Output

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.[60]

Preliminary evidence that Alpha-GPC can enhance power output


Edit5. Fat Mass and Obesity

5.1. Interventions

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.[26]


Edit6. Interactions with Hormones

6.1. Growth Hormone

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).[61] This was attributed to the cholinergic properties of Alpha-GPC[61] and can occur without exogenous stimulation by GHRH.[26] 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.[26]

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.[60] The increase appeared to be significantly more than placebo when measured immediately and up to 15 minutes after exercise cessation, normalizing at 60 minutes.[60]

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)


Edit7. Nutrient-Nutrient Interactions

7.1. Uridine (and Uridine prodrugs)

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,[62][63] but the increase in glycerophosphocholine has not always been detected (a failure with 500mg uridine in youth for a week[62] but a 5.1% increase over 6 weeks in older adults given 500mg CDP-choline[63] although 500mg has elsewhere failed to significantly influence GPC levels[64]).

Supplemental Uridine and/or uridine prodrugs may increase brain glycerophosphocholine concentrations, but it seems quite unreliable

7.2. Iron

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,[9] 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.[65][66] This study used 46mg Alpha-GPC and it was of comparable potency to vitamin C,[9] but elsewhere there has been a failure reported with a doubling of this ratio (4:1) or 70mg Alpha-GPC.[67] 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


Edit8. Safety and Toxicology

8.1. General

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.[12] 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).[12]

Alpha-GPC does not appear to possess mutagenic activity.[12]

References

  1. Hoffman JR, et al. The effects of acute and prolonged CRAM supplementation on reaction time and subjective measures of focus and alertness in healthy college students. J Int Soc Sports Nutr. (2010)
  2. Di Perri R, et al. A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia. J Int Med Res. (1991)
  3. A neurotropic approach to the treatment of multi-infarct dementia using L-α-glycerylphosphorylcholine
  4. Amenta F, et al. The ASCOMALVA trial: association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in Alzheimer's disease with cerebrovascular injury: interim results. J Neurol Sci. (2012)
  5. Tayebati SK, et al. Modulation of monoaminergic transporters by choline-containing phospholipids in rat brain. CNS Neurol Disord Drug Targets. (2013)
  6. Zeisel SH. Dietary choline: biochemistry, physiology, and pharmacology. Annu Rev Nutr. (1981)
  7. Scapicchio PL. Revisiting choline alphoscerate profile: a new, perspective, role in dementia. Int J Neurosci. (2013)
  8. Zhang K, et al. Purification of L-alpha glycerylphosphorylcholine by column chromatography. J Chromatogr A. (2012)
  9. Armah CN, et al. L-alpha-glycerophosphocholine contributes to meat's enhancement of nonheme iron absorption. J Nutr. (2008)
  10. SCHMIDT G, HERSHMAN B, THANNHAUSER SJ. The isolation of alpha-glycerylphosphorylcholine from incubated beef pancreas; its significance for the intermediary metabolism of lecithin. J Biol Chem. (1945)
  11. Brockerhoff H, Yurkowski M. Simplified preparation of L-alpha-glyceryl phosphoryl choline. Can J Biochem. (1965)
  12. Brownawell AM, Carmines EL, Montesano F. Safety assessment of AGPC as a food ingredient. Food Chem Toxicol. (2011)
  13. Concentrations of Choline-Containing Compounds and Betaine in Common Foods
  14. Gatti G, et al. A comparative study of free plasma choline levels following intramuscular administration of L-alpha-glycerylphosphorylcholine and citicoline in normal volunteers. Int J Clin Pharmacol Ther Toxicol. (1992)
  15. Parnetti L, et al. Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation. J Neurol Sci. (2007)
  16. Amenta F, et al. Association with the cholinergic precursor choline alphoscerate and the cholinesterase inhibitor rivastigmine: an approach for enhancing cholinergic neurotransmission. Mech Ageing Dev. (2006)
  17. Tayebati SK, et al. Neuroprotective effect of treatment with galantamine and choline alphoscerate on brain microanatomy in spontaneously hypertensive rats. J Neurol Sci. (2009)
  18. Subbaiah PV, Ganguly J. Studies on the phospholipases of rat intestinal mucosa. Biochem J. (1970)
  19. Lecithinase and lysolecithinase of intestinal mucosa
  20. Absorption of lipids
  21. Parthasarathy S, Subbaiah PV, Ganguly J. The mechanism of intestinal absorption of phosphatidylcholine in rats. Biochem J. (1974)
  22. ENZYME: 3.1.4.2
  23. The transphosphatidylation activity of phospholipase D
  24. Le Kim D, Betzing H. Intestinal absorption of polyunsaturated phosphatidylcholine in the rat. Hoppe Seylers Z Physiol Chem. (1976)
  25. Subbaiah PV, Ganguly J. Transesterification of lysolecithin in the intestinal mucosa of rats. Indian J Biochem. (1971)
  26. Kawamura T, et al. Glycerophosphocholine enhances growth hormone secretion and fat oxidation in young adults. Nutrition. (2012)
  27. Tayebati SK, Amenta F. Choline-containing phospholipids: relevance to brain functional pathways. Clin Chem Lab Med. (2013)
  28. Klein J, et al. Free choline and choline metabolites in rat brain and body fluids: sensitive determination and implications for choline supply to the brain. Neurochem Int. (1993)
  29. Klein J. Membrane breakdown in acute and chronic neurodegeneration: focus on choline-containing phospholipids. J Neural Transm. (2000)
  30. Abbiati G, et al. Absorption, tissue distribution and excretion of radiolabelled compounds in rats after administration of {14C}-L-alpha-glycerylphosphorylcholine. Eur J Drug Metab Pharmacokinet. (1993)
  31. Trabucchi M, Govoni S, Battaini F. Changes in the interaction between CNS cholinergic and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a cholinomimetic drug. Farmaco Sci. (1986)
  32. Sigala S, et al. L-alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the rat. Eur J Pharmacol. (1992)
  33. Aleppo G, et al. Chronic L-alpha-glyceryl-phosphoryl-choline increases inositol phosphate formation in brain slices and neuronal cultures. Pharmacol Toxicol. (1994)
  34. Schettini G, et al. Molecular mechanisms mediating the effects of L-alpha-glycerylphosphorylcholine, a new cognition-enhancing drug, on behavioral and biochemical parameters in young and aged rats. Pharmacol Biochem Behav. (1992)
  35. Lopez CM, et al. Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine. Pharmacol Biochem Behav. (1991)
  36. Tayebati SK, et al. Effect of choline-containing phospholipids on brain cholinergic transporters in the rat. J Neurol Sci. (2011)
  37. Tomassoni D, et al. Effects of cholinergic enhancing drugs on cholinergic transporters in the brain and peripheral blood lymphocytes of spontaneously hypertensive rats. Curr Alzheimer Res. (2012)
  38. Canal N, et al. Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine. Int J Clin Pharmacol Ther Toxicol. (1991)
  39. Ferraro L, et al. Evidence for an in vivo and in vitro modulation of endogenous cortical GABA release by alpha-glycerylphosphorylcholine. Neurochem Res. (1996)
  40. Noradrenergic modulation of cortical acetylcholine release is both direct and gamma-aminobutyric acid-mediated
  41. Beani L, et al. Inversion of the alpha-2 and alpha-1 noradrenergic control of the cortical release of acetylcholine and gamma-aminobutyric acid in morphine-tolerant guinea pigs. J Pharmacol Exp Ther. (1988)
  42. Nelson TJ, et al. Insulin, PKC signaling pathways and synaptic remodeling during memory storage and neuronal repair. Eur J Pharmacol. (2008)
  43. Glanzman DL. PKM and the maintenance of memory. F1000 Biol Rep. (2013)
  44. Ren SQ, et al. PKCλ is critical in AMPA receptor phosphorylation and synaptic incorporation during LTP. EMBO J. (2013)
  45. Govoni S, et al. PKC translocation in rat brain cortex is promoted in vivo and in vitro by alpha-glycerylphosphorylcholine, a cognition-enhancing drug. Ann N Y Acad Sci. (1993)
  46. Lucchi L, et al. Cognition stimulating drugs modulate protein kinase C activity in cerebral cortex and hippocampus of adult rats. Life Sci. (1993)
  47. Wang QJ. PKD at the crossroads of DAG and PKC signaling. Trends Pharmacol Sci. (2006)
  48. Govoni S, et al. Protein kinase C increase in rat brain cortical membranes may be promoted by cognition enhancing drugs. Life Sci. (1992)
  49. Nitsch R, et al. Alterations of phospholipid metabolites in postmortem brain from patients with Alzheimer's disease. Ann N Y Acad Sci. (1991)
  50. Wurtman RJ. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurosci. (1992)
  51. Wurtman RJ, Blusztajn JK, Maire JC. "Autocannibalism" of choline-containing membrane phospholipids in the pathogenesis of Alzheimer's disease-A hypothesis. Neurochem Int. (1985)
  52. Walter A, et al. Glycerophosphocholine is elevated in cerebrospinal fluid of Alzheimer patients. Neurobiol Aging. (2004)
  53. Yang X, et al. Secretory phospholipase A2 type III enhances alpha-secretase-dependent amyloid precursor protein processing through alterations in membrane fluidity. J Lipid Res. (2010)
  54. Gentile MT, et al. Role of cytosolic calcium-dependent phospholipase A2 in Alzheimer's disease pathogenesis. Mol Neurobiol. (2012)
  55. Milanesi L, et al. Direct three-dimensional visualization of membrane disruption by amyloid fibrils. Proc Natl Acad Sci U S A. (2012)
  56. De Jesus Moreno Moreno M. 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. Clin Ther. (2003)
  57. Parnetti L, Amenta F, Gallai V. Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mech Ageing Dev. (2001)
  58. Parnetti L, et al. Multicentre study of l-alpha-glyceryl-phosphorylcholine vs ST200 among patients with probable senile dementia of Alzheimer's type. Drugs Aging. (1993)
  59. Barbagallo Sangiorgi G, et al. alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Ann N Y Acad Sci. (1994)
  60. Alpha-GPC and power output; growth hormone
  61. Ceda GP, et al. alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects. Horm Metab Res. (1992)
  62. Agarwal N, et al. Short-term administration of uridine increases brain membrane phospholipid precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4T. Bipolar Disord. (2010)
  63. Babb SM, et al. Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacology (Berl). (2002)
  64. Silveri MM, et al. Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy. NMR Biomed. (2008)
  65. Hurrell RF, et al. Meat protein fractions enhance nonheme iron absorption in humans. J Nutr. (2006)
  66. Conrad ME, Umbreit JN, Moore EG. Iron absorption and transport. Am J Med Sci. (1999)
  67. Troesch B, et al. Optimization of a phytase-containing micronutrient powder with low amounts of highly bioavailable iron for in-home fortification of complementary foods. Am J Clin Nutr. (2009)

(Common phrases used by users for this page include what is alpha GPC 50%, how to take alpha gcp, clinical trials on alpha gpc and HGH release, Benifits of Alpha GPC, Alpha-Glyceryl Phosphoryl Choline, Alpha GPC headaches)

(Users who contributed to this page include , magnusson, , , cheminutra)