Alpha-GPC was initially discovered by Adolph Strecker, a German chemist in 1864. Within two years after he had discovered it, numerous laboratories in Europe had already begun its synthesis. Some of the initial studies indicated that choline had a crucial role in cognitive ability and physical health although information on its mechanism of action lacked at the time. In 1998, the U.S. Institute of Medicine named choline as a vital nutrient. Despite the human body being able to produce Alpha-GPC from choline-rich food sources like soy, beef, eggs, liver, and milk, these secreted amounts are small, and these foods also happen to lack the necessary quantities of this nutrient. As a result, most people have deficits in their choline levels. Considering that choline is essential for normal growth and development, people began searching for choline supplements. Currently, Alpha-GPC is mostly prescribed as treatment for Alzheimer's and a variety of other degenerative neurological conditions. Within Europe, doctors prescribe Alpha-GPC supplements as medication but in the U.S., it is still classified as a dietary supplement for brain health.
Several scientific studies have shown that GPC efficiently slows down the rate of structural changes that take place within the brain as a result of aging leading to loss of neuronal function. Researchers found that prolonged treatment of rats using GPC dissolved in their drinking water positively influenced/countered the loss of brain cells and neuro-connecting fibers as a result of aging. Mice treated with GPC were observed to have significantly higher neuro-connecting fibers in terms of the area they covered and their density when compared to age-matched controls. It was also noted that the quantity of granule neurons in the hippocampus had increased significantly in the GPC treated rodents compared to the control group of 24 month old rats. The researchers suggested that GPC treatment neutralizes some anatomical alterations of the hippocampus that take place during old age. In another similar research, researchers investigated the density of nerve cells within the hippocampus and the cerebellar cortex of adult (12 months of age) rats and old (24 months of age) mice. The study results indicated that GPC therapy administered for six months was able to reverse the age-dependent reduction in nerve cells.
In other studies, it has been established that GPC has the potential to assist restore muscarinic M1 receptors when administered in old rats. M1 receptors are a category of acetylcholine receptors whose quantity of sites falls with age. Researchers in Italy examined the effects of aging on rats' hippocampus and then made similar observations after the same rats were administered with GPC. Old rats that had been treated with GPC were observed to have had partial restoration of acetylcholinesterase reactivity and choline acetyltransferase immunoreactivity within their hippocampus. The GPC therapy was also observed to partly counter the age-related decrease in M1 receptors in old rats.
These researchers followed up with another study in which they evaluated the effects of a 6-month GPC therapy on the density and pattern of M1 chorlinergic receptors inside the brains of old rats. The results were similar as GPC therapy partly countered the decline in levels of muscarinic M1 receptor sites. The researchers linked the fall in M1 muscarinic sites observed in aged rats to loss of terminals or nerve cells in hippocampal and also concluded that GPC boosts the expression of muscarinic M1 cholinergic receptors. In other studies, it has also been concluded that chronic GPC treatment in aged rats restored the levels of M1 receptors to levels observed in hippocampus and striatum of young rats and partly reversed the stiffness of membrane in both regions. Researchers have also investigated the therapeutic properties of GPC in the treatment of dementia and Alzheimer's disease. In these trials, to evaluate the ability to correct the cholinergic function in Alzheimer's patients, the researchers used acetylcholinesterase inhibitors, M1 muscarinic agonists, cholinesterase inhibitors, and acetylcholine precursors. Some small studies and clinical trials have revealed that GPC enhances the availability of acetylcholine, its production and also enhances cognitive dysfunction although just slightly. A larger, multi-center, placebo-controlled, randomized study also gave similar results. In this particular study, researchers contrasted the efficiency of GPC and ALCAR (acetyl-l-carnitine) in 126 patients who had been diagnosed with mild to moderate senile dementia of the Alzheimer's type. The observations showed significant enhancements in a majority of the neuropsychological parameters in GPC treated patients that were superior to that of the ALCAR treated group.
As a result of several studies, scientists have established that GPC has potential therapeutic properties in the treatment of cognitive deficits that are closely linked to stroke (cerebrovascular events). Stroke disrupts the flow of blood and this leads to a series of events that involve glutamate flooding the NMDA receptors (excitotoxicity) and this then causes the death of neurons within the affected regions of the brain. In a multi-center trial conducted in Italy, 2,044 patients who had recently suffered transient ischemia attacks or stroke, the effects of GPC were examined. During phase 1 of the study, GPC was administered intramuscularly at a dose of 1gm/day for a period of 28 days. In phase 2, it was orally administered at a dose of 400mg/day for the following of 5 months. Researchers noted a positive linkage among all the parameters after using successive standard measuring scales. When deterioration was measured using the Global Deterioration Scale, the researchers did not observe any cognitive decline or forgetfulness in 71% of the patients involved in the study. In three uncontrolled clinical trials, researchers observed that administration of GPC to patients who had acute cerebrovascular stroke or transient ischemic attack indicated that it had potential to assist in the functional recovery of cerebral stroke patients although more trials were necessary. In a meta-analysis that reviewed 13 clinical trials with a total of 4,054 patients, the scientists sought to evaluate the therapeutic significance of GPC in the treatment of different forms of dementia conditions like senile dementia of the Alzheimer's type or vascular dementia as well as in acute cerebrovascular conditions like stroke and transitory ischemic attack (TIA). In 10 controlled clinical trials that compared GPC to another drug or a placebo, it was noted that the clinical results for GPC treated groups were superior or identical to those noted in the control groups that were under treatment and superior to results obtained from the placebo groups.
Researchers have also investigated the therapeutic significance of GPC in the treatment of memory loss caused by trauma, disease, or infection. Amnesia (partial memory loss) is closely linked to blocked or reduced acetylcholine and as such, a number of studies have been performed to examine the potential of GPC to assist in reversing memory loss. In one animal-based study, GPC was administered to aged male rats (24 months old) that had learning and memory impairments. GPC was also administered to rats that had scopolamine (this drug blocks the acetylcholine receptors) induced amnesia. In both groups, researchers observed improvements in learning and memory capacity.
Other studies established that GPC reverses pharmacologically induced amnesia in rats and partly offsets the decline in the levels of acetylcholine within the brain that are brought about by the administration of scopolamine. In other experiments whereby the hippocampus slices from rats were examined, researchers established that GPC administration leads to rising in a the amount of acetylcholine released. In one study, researchers observed that oral administration of GPC averted learning impairment and reversed amnesia that had been induced by scopolamine. The researchers observed that GPC lead to enhanced acetylcholine release and brought about acetylcholine formation. The researchers concluded that GPC's mechanism of action may be linked to its ability to boost the synthesis of hippocampal acetylcholine and its release.
Researchers have also shown that GPC enhances the release of Gamma-Aminobutyric Acid (GABA) which is an amino acid with inhibitory neurotransmitter properties within the central nervous system. The decline in levels of GABA leads to mood disorders, dementia, and psychoses linked to Huntington's and Alzheimer's disease.