Alpha GPC Nootropic Research, Effects & Safety Overview

Alpha GPC is a cholinergic supplement that increases the availability of the nutrient choline in the brain.

This leads to increased synthesis of the neurotransmitter acetylcholine which is implicated in memory, focus, reasoning and learning.

It has received Generally Recognized As Safe (GRAS) status from the FDA and is available without a prescription in most countries.

As an effective choline pro-drug, it increases systemic and brain concentrations of this nutrient. It rapidly crosses the blood-brain barrier following oral administration to deliver choline to neural tissues and increasing levels of the neurotransmitter acetylcholine.

Alpha GPC has been shown to reduce cognitive decline in elderly humans, to enhance cognitive performance in rats and to increase human growth hormone production and power output in athletes.

• Boosts memory, learning and cognition.
• Increases Dopamine and Serotonin levels.
• Improves attention, focus, energy and reaction time.
• Increases growth hormone, strength, and fat oxidation [Link]

Product Name: Alpha GPC (Alpha L-Glycerylphosphorylcholine, Choline Alfoscerate)
Chemical Name: [(2S)-2,3-Dihydroxypropyl] 2-trimethylazaniumylethyl phosphate
Formula: C8H20NO6P
Molecular Weight: 257.221 g/mol
CAS Number: 28319-77-9

Alpha GPC

Cholinergic Supplement

Memory

Attention

Neuro- protective

How It Works:

• Choline source to support memory function
• Increases attention, focus & energy
• Neuroprotective for brain cell health

Dosage:

Between 300mg to 1,200mg per day

Safety:

Generally Regarded as Safe

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Alpha GPC Nootropic Research

Alpha GPC or Alpha L-glycerophosphocholine is an endogenous cholinomimetic dietary supplement and acetylcholine precursor.

It is a natural phospholipid that contains choline and is a precursor to phosphatidylcholine synthesis in the brain. [8]

It occurs naturally in the body as an intermediate of lecithin metabolism.

It is also found in small amounts in yogurt, eggs, chicken breast, beef liver, milk, cheese, toasted wheat germ and certain fruits and vegetables. Biosynthetic supplement sources are typically derived from soy lecithin products. [3]

Alpha GPC Chemical Structure

The molecular structure of Alpha GPC features a choline molecule bound by a phosphate group to a glycerol molecule.

It has also been described as a phosphatidylcholine lecithin molecule with two of the fatty acids missing. [8]

This makes it both a phospholipid and a source of 40% free choline by weight. A typical 1,200 mg per day dosage of Alpha GPC therefore yields 480 mg of choline.

It is most commonly compared to Citicoline (CDP Choline) which is another nootropic bio-available source of choline for the brain.

Citicoline provides 21% choline by weight which means that the effective dosage for this supplement is almost twice that of Alpha GPC.

Ingesting the same dosages of both of these compounds results in a greater serum increase of choline for those individuals given Alpha GPC. [8, 6]

In clinical interventions, Alpha GPC is shown to be more effective and more potent than both choline and CDP Choline. [11, 12]

Alpha GPC Pharmacology

Alpha GPC is an intermediary in the conversion of lecithin into free form Choline in the brain.

Lecithin is first metabolized into lysolecithin from pancreatic phospholipase. The lysolecithin then is transformed by phospholipase B into alpha-glyceryphosphorylcholine or Alpha GPC choline which is then hydrolyzed to form choline.

Alternatively, Alpha GPC can be produced from lecithin by Phospholipase D directly in neural tissue. [2]

When ingesting oral Alpha GPC or administering intramuscularly, the supplement increases plasma choline levels and is readily incorporated into brain tissue. [7]

1000mg of oral Alpha GPC increases serum choline levels in young, healthy male volunteers from 8.1+/-1.4?mol/L up to 12.1+/-1.9?mol/L at 60 minutes and 1.4+/-1.7?mol/L at 120 minutes. [56]

One study found that Alpha GPC was incorporated into brain phospholipids in rats 24 hours following ingestion. [3]

Another study found that release of acetylcholine from stimulated neurons was highest 1-3 hours following ingestion. [4]

Brain concentrations of glycerophosphocholine are comparable to blood concentrations which demonstrates a high degree of penetration of the blood-brain barrier. [5]

Alpha GPC Mechanism of Action

The primary mechanism of action for Alpha GPC is an increase in cholinergic neurotransmission.

150 mg/kg/day administered to rats significantly increased acetylcholine neurotransmitter concentrations in the frontal cortex, but not the striatum or cerebellum.

Alpha GPC also stimulated increased vesicular acetylcholine transporter (VAChT) expression and choline transporter (CHT) expression in all brain areas examined.

These presynaptic cholinergic transporters are responsible for sustaining ACh synthesis and release from neurons. [13]

Dopamine and Serotonin

Alpha GPC is observed to increase dopamine and serotonin concentrations in the cerebellum and frontal cortex of rats following administration of a 150mg/kg oral dosage.

This increase is not reported when administering an equal dosage of choline from Citicoline (CDP Choline).

Alpha GPC also increases expression of the dopamine transporter but not the serotonin transporter. [8]

In another study, Alpha GPC was observed to increase potassium (K+) stimulated dopamine release in the brain. [7]

Memory and Learning

Alpha GPC was shown to reduce scopolamine-induced amnesia in young and aged rats while improving performance in active avoidance tests.

These passive and active avoidance behavioral tasks are used to assess memory and cognition.

Subchronic treatment (21 days) by intraperitoneal injections of 100-200mg/kg Alpha GPC two hours before training led to improved performance in unimpaired rates in the active avoidance learning task.

The same result was observed in the passive avoidance test on rats that had been administered Alpha GPC alongside the amnesia-inducing compound scopolamine two hours prior to the testing event. [21]

Alpha GPC has been shown to activate Protein Kinase C (PKC) in the rat hippocampus when administered at 600mg/kg orally.

PKC is an enzyme thought to be responsible for long-term potentiation which is the process by which memories are stored in the brain. When activated, it may improve memory formation. [14]

Alpha GPC increase PKC activity for 1 hour following administration and was observed to induce translocation at concentration as low as 50nM in cortical slices. [17]

Alpha GPC and Alzheimer’s Disease

Patients diagnosed with Alzheimer’s disease exhibit impaired presynaptic cholinergic function.

Treatment with cholinesterase inhibitors is observed to reduce memory impairments by increasing acetylcholine concentrations. [22]

Alzheimer’s patients also experience increased choline metabolism and degradation of phospholipid membranes containing choline through autocannibalism. [24]

Evidence for this is found in the increased levels of glycerophosphocholine (GPCh), phosphocholine (PCh), and choline in the cerebrospinal fluid of patients. [25]

It is theorized that by supplying the brain with supplemental phospholipid-containing choline in the form of Alpha GPC, additional degeneration of neuronal membranes may be reduced by increasing cholinergic neuron viability. [24]

1200mg of oral Alpha GPC per day split over three equal administrations in patients with moderate Alzheimer’s found improvements in cognitive function over 180 days.

Patients given a placebo saw a degredation in cognitive function as measured by higher ADAS-Cog scores over the same period. [26]

In another 90 day study, 1000mg of intramuscular Alpha GPC resulted in benefits for vascular dementia as measured by memory, verbal and behavioral performance. [11]

Focus and Alertness

CRAM supplementation is the name given to the supplement stack containing alpha-glycerophosphocholine, choline bitartrate, phosphatidylserine, vitamins B3, B6, and B12, folic acid, L-tyrosine, anhydrous caffeine, acetyl-L-carnitine, and naringin.

In one study on healthy college students, this Alpha GPC stack was found to decrease reaction time and increase subjective feelings of focus and alertness.

Participants who were given the CRAM supplement regimen reported greater energy and less fatigue following exhaustive exercise than those given a placebo. [9]

Neuroprotective

Alpha GPC exhibits a neuroprotective effect in humans who have suffered a cerebral stroke or ischemic attack caused by acute cerebrovascular disease.

One review study looked at 2484 patients who were given 1000mg of Alpha GPC a day via intramuscular injection for one month followed by five months of 1200 per day oral dosages.

The study found improvements in Mini Mental State Evaluation (MMSE) tests of 12-15%, Clinicians’ Global Rating Scale (CGRS) of 19-21% improvement and Global Deterioration Scale (GDS) of 20%. [10]

Human Growth Hormone

Taking Alpha GPC increases secretions of Human Growth Hormone in young and old human volunteers.

Alpha GPC was administered with GH-release hormone (GHRH) and found to increase GH levels more than when administering GHRH on its own.

The effect was most pronounced in elderly individuals who often experience decreased GH secretions as they age.

Ceda et al propose that the increased cholinergic tone provided by Alpha GPC supplements causes the enhanced GH release. [57]

Kawamura et al further showed that it can increase GH secretion without concurrent administration of GHRH.[56]

This effect is more pronounced when ingesting Alpha GPC prior to physical exercise.

Taking 600mg of Alpha GPC 45 minutes before activity resulted in an increase in the exercise-induced growth hormone spike from a level of 5.0+/-4.8ng/mL with a placebo to 8.4+/-2.1 ng/mL. [58]

In another study, a 221% increase in growth hormone secretion occurred 60 minutes following ingestion. Levels were normalized within 120 minutes of oral ingestion. [56]

Muscle Strength

Evidence suggests that Alpha GPC may be an effective pre-workout supplement for bodybuilders and competitive weight lifters.

Administering 600mg of Alpha GPC 45 minutes before exercise resulted in a 14% increase in power output in a test of bench throws strength compared to a placebo. [58]

Weight Loss

Alpha GPC increases hepatic fat oxidation in healthy, young adults. 120 minutes following ingestion of 1000mg Alpha GPC Choline, an increase in serum acetoacetate and 3-hydroxybutyrate levels was observed by Kawamura et al.

These are ketone bodies that are biomarkers of fat metabolism and suggest significant weight loss potential of this supplement. [56]

This is consistent with studies on Choline which demonstrate rapid reduction of body mass with no negative side effects on static strength or biochemical levels. [59]

Safety and Side Effects

Alpha GPC is on the GRAS supplement list provided by the FDA and has few reported side effects when used within an appropriate dosage range.

The oral No Observed Adverse Effect Level (NOAEL) is 150mg/kg over 26 weeks in rats. This is approximately equivalent to a 24mg/kg dosage in humans (1300 mg for a 120 lb individual to 2100mg for a 200 lb individual). [1]

Brownawell et al found the oral LD50 of Alpha-GPC to be equal to or greater than 10,000mg/kg in rats and mice. Subchronic toxicity studies with 1,000mg/kg in rats leads to reductions in food consumption and minor weight gain. [1]

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