Alpha GPC Medline

L-Alpha Glycerylphosphorylcholine

Summary

Phospholipids are fat soluble molecules that contain a phosphoric acid residue; there are two major categories of phospholipids, one which contains a glycerol backbone (phosphoglycerides) and another which contains a sphingosine backbone (sphingomyelin). While phosphoglycerides are the predominant lipids in biological membranes, sphingolipids are also important components of some cellular membranes, the myelin sheath and of lipoproteins in plasma. The lysophospholipids are an important subclass of phospholipids that account for one to two percent of the total phospholipids in animal cells. There are more than 100 different types of phospholipids; the major ones being phosphatidic acid, phosphatidylcholine (lecithin), phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol and diphosphatidylglycerol. Phosphatidylcholine (PC) is the most abundant phospholipid in animal tissue. In addition to its primary role in membrane structure, phosphatidylcholine (PC) is an important structural component of the plasma lipoproteins and bile.
L-Alpha Glycerylphosphorylcholine (Alpha-GPC) is a naturally occurring phospholipid precurser and metabolite derived from soy lecithin. Alpha-GPC has been shown to potentiate the effects of growth hormone releasing hormone (GHRH) and increase human growth hormone (hGH) secretion in young and elderly individuals plus patients with Senile Dementia of the Alzheimer’s Type (SDAT). Alpha-GPC also affects numerous biochemical and neurotrasmitter systems that have been implicated in the development of age-related memory dysfunction (ARMD).
Administration of Alpha-GPC has been shown to improve neuropsychological parameters in patients with SDAT and ARMD. Alpha-GPC also improves memory and cognitive performance in patients with dementia, and benefits those recovering from cerebral ischemic attacks. Alpha-GPC has been shown to reduce the recovery time in comatose patients suffering from head injury and antagonize the effects of scopolamine to improve memory, attention, and performance in healthy individuals. Alpha-GPC’s cognitive and growth hormone (GH) enhancing effects appear to be primarily the result of stimulation of the cholinergic neurotransmitter system; however, other biochemically-related modulations and neurotransmitter systems have been implicated.
Alpha-G.P.C. has been documented extensively by published studies in both animals and humans to contribute to at least five (5) significant human health functions. These relevant ‘mind-body’ activities include, but may not be limited to the following:

1. increases in endogenous human Growth Hormone (hGH) secretion by the anterior pituitary in conjunction with Growth Hormone Releasing Hormone (GHRH); that is, both Alpha-G.P.C. and GHRH act concertedly to stimulate the release of hGH, naturally;

2. stimulation of the enzymatic synthesis of phosphatidylcholine (PC) in nerves, muscle cells and all cell membranes, counteracting the age-related decrease in phospholipid (PC) biosynthesis; thus, Alpha-GPC contributes directly to improved mental focus and stimulation of cognitive function;

3. acts as a precursor of acetylcholine (ACh); thus, Alpha-GPC activates cholinergic transmission which permits the development of more strength from work-outs and training programs, plus reducing levels of somatostatin in the hypothalamic-pituitary axis;

4. elevations in blood and tissue levels of the essential nutrient, choline, which supports improved lipotrophic functions (methyl group transferases) in the liver, and acts synergistically with S-adenosyl-L-methionine (SAM or SAMe) and folic acid, vitamin B12 and vitamin B6 to facilitate methyl group transfers in the brain and liver;

5. produces improved balanced and coordination when combined with ‘skill set’ practice and training as a result of normalized nerve transmission in the brain, and in cardiac, skeletal and smooth muscles.

Ageing, chronic or severe disease states, and prolonged stress – including athletic endeavors like marathons or ‘ironman/ironwoman’ events are associated with decreased hormone production, especially reduced secretion of human Growth Hormone (hGH) from the anterior pituitary. These life events are also associated with lower levels of free choline in the blood and tissues. Concommitantly, both quality of life and lifespan decrease, sexual desire and potency diminish, resistence to disease is reduced, muscles loose both protein (mass) and tone, and body fat levels increase.
In clinical situations, significantly reduced secretion of hGH is associated with short stature, generalized muscle wasting, Andropause, anxiety, undesireable mood and affect changes which are often associated with depression, abnormal sleep patterns, loss of energy and stamina, and decreased cellular and humoral (antibody) immune functions leading to increased susceptibility to disease. Since 1984, the Food and Drug Administration (F.D.A.) has approved the use of recombinant human Growth Hormone (hGH) for the treatment of dwarfism due to hGH deficiency, Adult Onset Growth Hormone Deficiency (Somatopause), Turner’s syndrome, ans wasting associated with AIDS/HIV. Alpha-GPC can be used in anti-ageing programs, as a less expensive altenative to injecting recombinant hGH, and to treat or reduce the symptoms of the Somatopause.
Fate and distribution studies demonstrate that orally administered Alpha-G.P.C. is absorbed quickly from the gastrointestinal tract and is transported in the blood to all cells and tissues, especially the brain. Alpha-G.P.C. crosses the ‘blood-brain’ barrier and acts as a central nervous system (CNS) cholinergic stimulant while it simultaneously increases the GHRH-stimulated secretion of hGH by the somatotrophe cells in the anterior pituitary. The current understanding of Alpha-G.P.C.’s actions in the brain is that it increases hGH secretion in the pituitary by two (2) separate but interacting neuro-endocrine mechanisms; these are:

1. modulatory – increasing cholinergic tone lending to decreased levels of
somatostatin (produced by the hypothalamus), as a result of the
administration of Alpha-G.P.C.;
2. regulatory – stimulation of hGH synthesis resulting from ‘up regulation’ of Growth Hormone Releasing Hormone/Factor (GHRH/GHRF) in conjunction with receptor-linked stimulation of the adenylate cyclase (cAMP)-Protein kinase C (PKC)-inositol triphosphate (IP3) intracellular control mechanisms regulating hGH synthesis at the genomic level and its subsequent secretion by the anterior pituitary.

Alpha-GPC has been administered to over three thousand (3,000) patients and volunteers in clinical trials and studies that have been published in the peer-reviewed literature. Minor, transient side effects have been reported to occur at a one percent (1%) frequency; these side effects, for orally administered Alpha-GPC, included diarrhea, dizziness, gastralgis, heartburn, insomnia, restlessness and skin rashes, which resolved when the amount of Alpha-GPC administered was either decreased or eliminated.
As a multifunctional, natural compound, Alpha-GPC can be used as a ‘stand alone’ ingredient or as a ‘lead’ ingredient in multi-ingredient product formulations designed for buccal (sublingual) or oral administration. Alpha-GPC can be marketed as a natural human Growth Hormone secretagogue for anti-ageing applications, used in performance enhancement products, and as a Nutraceutical adjuvant to injections of recombinant hGH in clinical practices, such as Gerontology and Preventive Medicine.

alpha-Glycerophosphocholine in the mental recovery ofcerebral ischemic attacks. An Italian multicenter clinical trial.

Barbagallo Sangiorgi G, Barbagallo M, Giordano M, Meli M, Panzarasa R

Institute of Internal Medicine and Geriatrics, University of Palermo, Italy.

The clinical efficacy and the tolerability of alpha-glycerophosphocholine (alpha-GPC), a drug able to provide high levels of choline for the nervous cells of the brain and to protect their cell walls, have been tested in a clinical open multicenter trial on 2044 patients suffering from recent stroke or transient ischemic attacks. alpha-GPC was administered after the attack at the daily dose of 1000 mg im for 28 days and orally at the dose of 400 mg tid during the following 5 months after the first phase. The evaluation of the efficacy on the psychic recovery was done by the Mathew Scale (MS) during the period of im drug administration, and using the Mini Mental State Test (MMST), the Crichton Rating Scale (CRS), and the Global Deterioration Scale (GDS) during the following period of oral administration. The MS mean increased 15.9 points in 28 days in a statistically significant way (p < 0.001) from 58.7 to 74.6. At the end of the 5 month oral administration, the CRS mean significantly decreased 4.3 points, from 20.2 to 15.9 (p < 0.001); the MMST mean significantly increased (p < 0.001) from 21 to 24.3 at the end of the trial, reaching the "normality" score at the 3rd month assessment. The GDS score at the end of the trial corresponded to "no cognitive decline" or "forgetfulness" in 71% of the patients. Adverse events were complained of by 44 patients (2.14%); in 14 (0.7%) the investigator preferred to discontinue therapy. The most frequent complaints were heartburn (0.7%), nausea-vomit (0.5%), insomnia-excitation (0.4%), and headache (0.2%). The trial confirms the therapeutic role of alpha-GPC on the cognitive recovery of patients with acute stroke or TIA, and the low percentage of adverse events confirms its excellent tolerability.

Publication Types:

Clinical trial

Multicenter study

PMID: 8030842, UI: 94303894

Drugs Aging 1993 Mar-Apr;3(2):159-64

Multicentre study of l-alpha-glyceryl-phosphorylcholine vs ST200 among patients with probable senile dementia of Alzheimer's type.

Parnetti L, Abate G, Bartorelli L, Cucinotta D, Cuzzupoli M, Maggioni M, Villardita C, Senin U

Institute of Gerontology and Geriatrics, University of Perugia, Italy.

A multicentre, randomised, controlled study compared the efficacy of l-alpha-glyceryl-phosphorylcholine (alpha GPC) and ST200 (acetyl-l-carnitine) among 126 patients with probable senile dementia of Alzheimer's type (SDAT) of mild to moderate degree. Efficacy was evaluated by means of behavioural scales and psychometric tests. The results showed significant improvements in most neuropsychological parameters in the alpha GPC recipients. Improvements also occurred in the ST200 recipients but to a lesser extent. Tolerability was good in both groups. These positive findings require replication in larger, double-blind, longitudinal studies coupling clinical and biological determinations.

Publication Types:

Clinical trial

Multicenter study

Randomized controlled trial

PMID: 8477148, UI: 93237692

Pharmacol Toxicol 1994 Feb;74(2):95-100

Chronic L-alpha-glyceryl-phosphoryl-choline increases inositol phosphate formation in brain slices and neuronal cultures.

Aleppo G, Nicoletti F, Sortino MA, Casabona G, Scapagnini U, Canonico PL

Institute of Pharmacology, University of Catania School of Medicine, Italy.

Repeated, but not single injections of L-alpha-glyceryl-phosphorylcholine (alpha GPC) significantly increased basal [3H]inositol monophosphate (InsP) formation in hippocampal, cortical, and striatal slices of male rats. The effect was dose-dependent and was accompanied by an increased incorporation of [3H]inositol into the phospholipid fraction. Incubation of brain slices with different neurotransmitter antagonists, such as atropine, prazosin, or L-2-amino-4-phosphonobutanoate (L-AP4) did not modify the increase in [3H]InsP formation produced by alpha GPC, suggesting that the effect is not mediated by an increased availability of a specific neurotransmitter. Similar results were obtained in cerebellar and cortico-striatal neurones in primary culture exposed to daily addition of alpha GPC since the second day of maturation in vitro. We suggest that alpha GPC treatment may result in an increased rate of phospholipid synthesis, including the phosphoinositides available for signal transduction at central nervous system level.

PMID: 8190709, UI: 94248120

Absorption, tissue distribution and excretion of radiolabelledcompounds in rats after administration of[14C]-L-alpha-glycerylphosphorylcholine.

Abbiati G, Fossati T, Lachmann G, Bergamaschi M, Castiglioni C

LPB Research Institute, Cinisello B., Milan, Italy.

The kinetics and metabolism of L-alpha-glycerylphosphoryl-choline (alpha-GPC) were investigated in male and female rats after i.v. (10 mg/kg) and oral doses (100-300 mg/kg). alpha-GPC was labelled with [14C]-glycerol ([14G]-GPC) or [14C]-choline ([14C]-GPC). Different kinetic and metabolic profiles were observed after i.v. and oral administration. It is assumed that alpha-GPC is hydrolyzed by phosphodiesterases in the gut mucosa. The different labeled metabolites have different kinetic properties of absorption, distribution and clearance, leading to different blood concentration-time curves of total radioactivity. Both labeled compounds gave a wide distribution of radioactivity, particularly concentrated in the liver, kidney, lung and spleen compared to blood. Brain concentrations of [14C]-GPC were comparable to ([14G]-GPC) or lower than ([14C]-GPC) total blood radioactivity. The metabolite profile in the perfused brain showed a small amount of choline and two unknown metabolites, probably the same as in blood. In addition, choline was incorporated into brain phospholipids in increasing amounts within 24 h of dosing. In all cases renal and fecal excretion of radioactivity was low and comparable for [14G]-GPC and [14C]-GPC. Mostly the administered radioactivity was exhaled as 14CO2, this degradation being faster and more pronounced for the glycerol-labelled metabolites than for the choline-labelled metabolites for both routes of administration. In all cases the results were the same for male and female rats.

PMID: 8243501, UI: 94062871

Pharmacol Biochem Behav 1992 Feb;41(2):445-8

Behavioral effects of L-alpha-glycerylphosphorylcholine: influence on cognitive mechanisms in the rat.

Drago F, Mauceri F, Nardo L, Valerio C, Lauria N, Rampello L, Guidi G

Institute of Pharmacology, University of Catania Medical School, Italy.

The phosphorylcholine precursor, L-alpha-glycerylphosphorylcholine (alpha-GPC), was injected at the dose of 100 mg/kg/day for 20 days to aged male rats of the Sprague-Dawley strain, 24 months old, showing a deficit of learning and memory capacity. The drug was also administered to rats with amnesia induced pharmacologically with bilateral injections of kainic acid into the nucleus basalis magnocellularis (NBM). Learning and memory capacity of the animals, studied with tests of active and passive avoidance behavior, was improved after treatment with alpha-GPC in all experimental groups. These results indicate that this drug affects cognitive mechanisms in the rat through an involvement of central neurotransmission.

PMID: 1574535, UI: 92244949

Ann N Y Acad Sci 1994 Jun 30;717:253-69

Pharmacol Biochem Behav 1991 Aug;39(4):835-40

Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine.

Lopez CM, Govoni S, Battaini F, Bergamaschi S, Longoni A, Giaroni C, Trabucchi M

Institute of Pharmacological Sciences, University of Milan, Italy.

The present study investigates the effect of the administration of alpha-glycerylphosphorylcholine (alpha-GPC) on scopolamine-induced amnesia and on brain acetylcholine (ACh) levels and release in rats. The results indicate that alpha-GPC, when administered orally, reverses the amnesia caused by scopolamine in passive avoidance. The peak effect is observed using 600 mg/kg IG, 5 h before training. The effect of the drug is long lasting (up 30 h) in accordance with its pharmacokinetic characteristics. Since, alpha-GPC administered IG is cleaved within the gut mucosal cells to glycerophosphate and free choline, it is tempting to speculate that this drug acts by increasing the ACh precursor pool. This view is supported also by the observation that alpha-GPC partially counteracts the decrease of brain ACh levels elicited by scopolamine administration. The effect is observed in the hippocampus and cortex, but not in the striatum. Moreover, in ex vivo experiments, alpha-GPC is able to increase the amount of ACh released by rat hippocampus slices following potassium stimulation.

PMID: 1662399, UI: 92108116

Life Sci 1993;53(24):1821-32

Cognition stimulating drugs modulate protein kinase C

activity in cerebral cortex and hippocampus of adult rats.

Lucchi L, Pascale A, Battaini F, Govoni S, Trabucchi M Inst. Pharmacological Sciences, Univ. of Milan, Italy.

The in vivo and in vitro effect of oxiracetam, aniracetam and alpha-glycerylphosphorylcholine (alpha GPC) on protein kinase C (PKC) activity was studied in rat brain cortex and hippocampus. Administration of oxiracetam and alpha GPC in vivo elicited an early increase of particulate histone-directed PKC activity accompanied by a decrease of soluble activity and followed a few hours later by a down regulation of the enzyme. The effect was also observed in vitro when either oxiracetam or alpha GPC were administered at nanomolar concentrations to rat brain cortex slices. Aniracetam had no effect in the cortex but promoted PKC translocation both in vivo and in vitro in the hippocampus. In cortex slices the effect of oxiracetam was antagonized by the addition of AP-5, an NMDA receptor blocker, but not by CNQX and L-AP3, antagonists of AMPA and metabotropic glutamate receptors, respectively. Scopolamine also prevented the increase of particulate PKC elicited by oxiracetam in vitro. In the hippocampus the increase of particulate PKC activity was antagonized by AP-5, CNQX and L-AP3, indicating participation by both ionotropic and metabotropic glutamate receptors in the action of aniracetam. The data support the hypothesis that PKC activation may be a common mechanism amongst cognition stimulating drugs from different chemical classes.

PMID: 8246681, UI: 94066690

Int J Clin Pharmacol Ther Toxicol 1992 Sep;30(9):331-5

A comparative study of free plasma choline levels following intramuscular administration of L-alpha-glycerylphosphorylcholine and citicoline in normal volunteers.

Gatti G, Barzaghi N, Acuto G, Abbiati G, Fossati T, Perucca E

Department of Internal Medicine and Therapeutics, University of Pavia, Italy.

L-alpha-glycerylphosphorylcholine (alpha-GPC) is a recently developed cognitive enhancer whose mode of action is considered to involve the release of free choline, which is then utilized for acetylcholine and phosphatidylcholine biosynthesis in the brain. The purpose of this study was to evaluate the profile of free plasma choline levels following a single i.m. dose of alpha-GPC in 12 normal volunteers. Citicoline (CTC), which also acts as a choline precursor, was included for comparison purposes. Each subject was studied on three randomized occasions, (i) in a control day in the absence of drug administration (to evaluate the plasma level profile of endogenous choline), (ii) after i.m. alpha-GPC (1,000 mg) and (iii) after i.m. CTC (1,000 mg) respectively, with a wash-out period of at least 1-week between sessions. Blood samples for plasma choline HPLC determinations were collected at regular intervals over a 6 h period. In the control session, plasma choline levels remained stable during the sampling period. The administration of alpha-GPC was associated with a rapid rise in plasma choline, peak levels being usually observed at the first (0.25 h) or second (0.5 h) sampling time after the injection. Thereafter, the concentration of choline declined gradually and returned to near baseline values at the end of the observation period. After the administration of CTC, plasma choline levels showed a similar time course but were considerably lower than those observed after the administration of alpha-GPC.

Publication Types:

Clinical trial

Randomized controlled trial

PMID: 1428296, UI: 93052943

Pharmacol Biochem Behav 1992 Sep;43(1):139-51

Molecular mechanisms mediating the effects of L-alpha-glycerylphosphorylcholine, a new cognition-enhancing drug, on behavioral and biochemical parameters in young and aged rats.

Schettini G, Ventra C, Florio T, Grimaldi M, Meucci O, Scorziello A, Postiglione A, Marino A

Department of Human Communicative Science, II School of Medicine, Naples, Italy.

The behavioral effects of the acute and subchronic administration of L-alpha-glycerylphosphorylcholine (alpha-GPC) on passive and active avoidance behavioral tasks were investigated. When administered IP after training together with scopolamine 2 h before retest, alpha-GPC reverses the scopolamine-induced amnesia in the passive avoidance conditioning in young and old rats. Furthermore, the subchronic treatment with alpha-GPC positively and significantly influences the performance of both young and old animals in the active avoidance test. Moreover, in in vitro/ex vivo experiments alpha-GPC potentiates receptor-stimulated phosphatidylinositol hydrolysis in cortical synaptoneurosomes derived from young and old animals. In young but not old animals, alpha-GPC significantly potentiates potassium (40 mM)-stimulated intrasynaptosomal calcium oscillations in purified synaptosomes derived from the hippocampus. These results show that alpha-GPC improves the performance of animals in both active and passive conditioning tasks. Furthermore, subchronic treatment with the compound enhances in young and restores in aged animals the transduction of the signal, namely, the receptor-mediated production of inositol phosphate and the potassium-induced calcium mobilization. These modifications may represent at least part of the molecular mechanism of action of the compound.

PMID: 1409797, UI: 93028672

Pharmacol Biochem Behav 1992 Feb;41(2):445-8

Behavioral effects of L-alpha-glycerylphosphorylcholine: influence on cognitive mechanisms in the rat.

Drago F, Mauceri F, Nardo L, Valerio C, Lauria N, Rampello L, Guidi G

Institute of Pharmacology, University of Catania Medical School, Italy.

PMID: 1574535, UI: 92244949