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Researchers have found that GPC can be useful in the treatment of cognitive deficits that often arise from cerebrovascular (stroke) events. When blood flow is disrupted by a stroke, the result is a cascade of events involving glutamate flooding NMDA receptors (excitotoxicity), which then leads to neuron death in the affected region of the brain.
An Italian multicenter trial looked at GPC in 2,044 patients suffering from recent stroke or transient ischemic attacks. GPC was administered, in phase 1, after the attack at the daily dose of 1 gram intramuscularly for 28 days and, in phase 2, orally at the dose of 400 mg during the next five months. Using a series of different standard measuring scales, a positive association was found in all parameters. According to one scale that measured deterioration (Global Deterioration Scale), "no cognitive decline" or "forgetfulness" was reported for 71% of the patients.
A review of 13 published clinical trials comprising 4,054 patients in all, set out to weigh the benefits of GPC treatment for various forms of dementia disorders, including senile dementia of the Alzheimer's type or vascular dementia, and in acute cerebrovascular diseases, such as transitory ischemic attack (TIA) and stroke. Results from 10 controlled trials comparing GPC to a reference drug or placebo showed that GPC's clinical results were better or equal to those observed in control groups under active treatment and superior to the results observed in placebo groups. Meanwhile, three uncontrolled trials examining the use of GPC in acute cerebrovascular stroke and transient ischemic attack ("mini stroke") demonstrated promise that it could help with the functional recovery of patients with cerebral stroke, but would require further investigation.
Another area of research has focused on the loss of memory function that occurs due to any number of causes, including disease, trauma or infection. Since amnesia (partial memory loss) has been related to decreased or blocked acetylcholine, researchers have set out to examine reversing this damage using GPC.
In one study, GPC was injected for 20 days into aged male rats (24 months old) with learning and memory capacity deficits. It was also administered to rats with amnesia, which was experimentally induced by scopolamine, a drug that works by blocking acetycholine receptors. Results indicated that learning and memory capacity improved in both groups.
Other researchers found that oral GPC reverses pharmacologically induced amnesia and partially counteracts the decrease of brain acetylcholine levels elicited by scopolamine administration. Additionally, in experiments that involved analyzing hippocampus slices from rats, scientists found that GPC was able to increase the amount of acetylcholine released. Another study showed that administering oral GPC to rats prevented the learning impairment and reversed amnesia induced by scopolamine. This study showed that GPC increased acetylcholine release and resulted in acetylcholine formation. The authors concluded that the behavioral effects of GPC's ability may relate to its ability to increase hippocampal acetylcholine synthesis and release.
Explaining the effects
Scientists have homed in on a number of means by which GPC may elicit its various brain fortifying effects. It is believed that GPC's mode of action may involve the release of free choline, which then aids in the synthesis of acetylcholine and phosphatidylcholine. A study involving 12 volunteers compared GPC to CDP-choline and showed that plasma choline was higher after GPC. Some researchers have suggested that GPC "may result in an increased rate of phospholipid synthesis, including the phosphoinositides available for signal transduction at central nervous system level."
In other research, investigators demonstrated how GPC increased gamma-aminobutyric acid (GABA) release. This amino acid acts as an inhibitory neurotransmitter in the central nervous system. Decreased amounts of GABA have been shown to contribute to the dementia, mood disorders and psychoses related to Huntington's and Alzheimer's disease.
GPC has also been called a growth hormone sensitizer, which basically means that it has the ability to potentiate the effects of growth hormone releasing hormone (GHRH) and increase human growth hormone (hGH) secretion, as one study showed. Researchers wanted to assess what effect GPC would have on growth hormone secretion, so they administered growth hormone-releasing hormone (GHRH) to young and old human volunteers, either in combination with GPC or exclusively. Results revealed a greater growth hormone response to the GHRH plus GPC than to GHRH alone, and the effect was more pronounced in elderly subjects.
Moreover, other researchers have been able to show that GPC treatment may increase the expression of nerve growth factor receptors in the rat cerebellar cortex. Nerve growth factor is important for regulating the growth and maturation process of cholinergic neurons in the central nervous system, as well as their repair, survival and regeneration. Unfortunately, the receptors for these vital proteins fall prey to the ravages of age, making them less effective over time at performing their neurprotective work. However, findings from one study suggest that GPC can undo these age-related effects, after the daily administration of GPC to rats for six months.
Other researchers have demonstrated that GPC increases protein kinase C activity after just one hour following oral administration. And in vitro, GPC promoted protein kinase C translocation in cortical slices from rats at concentrations.
GPC also increases the release of the neurotransmitter dopamine, a chemical messenger in the brain that regulates emotions, sensation of pain and pleasure and physical movement. This may be useful in the treatment of Parkinson's disease, which has been found to involve an imbalance between dopaminergic and cholinergic transmission. In Parkinson's disease, dopamine-transmitting neurons die. That's why patients are given L-DOPA, a drug that produces dopamine in the brain as a replacement for endogenous dopamine. If GPC can perform a similar task, it may become another way to ameliorate Parkinson's.
At a glance, GPC seems to have much to offer the aging brain by increasing the bioavailability of choline, restoring the number of acetylcholine receptors and decreasing progressive cell membrane stiffness that occurs with cognitive aging. But as anyone knows, the most effective drug therapy in the world won't work if patients do not, or cannot, take it.
GPC has been shown in numerous human studies to have high tolerability and safety. In one study, side effects, such as heartburn, nausea-vomiting, insomnia-excitation and headache were reported by just 2% (44) of patients, and only four patients dropped out of the study due to unwanted effects. The authors conclude that, "The trial confirms the therapeutic role of GPC on the cognitive recovery of patients with acute stroke or TIA, and the low percentage of adverse events confirms its excellent tolerability."
An open clinical trial was carried out to compare the efficacy and the tolerability of 1 gram/day GPC with 1 gram/day CDP-choline, both given intramuscularly for 90 days in 120 patients with mild to moderate vascular dementia. Besides reporting good symptomatic relief and tolerability with both treatments, results suggested GPC tested more highly on both accounts, according to clinical measurements and patients reports, compared with CDP-choline. Other studies have echoed the same kind of positive reports.
Given the growing evidence that suggests glycerylphosphorylcholine's (GPC) usefulness in preventing and treating many conditions that tax our mental faculties, coupled with a vote for its safety and tolerability, it would not be surprising to see this neuroceutical gaining more ground in neuropsychiatry circles and popularity among people who want to preserve their brain power for as long as possible.
1. Parnetti L, et al. Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mech Ageing Dev 2001 Nov;122(16):2041-55.