Life Extension Magazine July 2003
Preserving Brain Function with GPC
Promising new research
New results from a multi-center clinical trial further bolster the case for GPC supplementation.1 Researchers in Mexico concluded that GPC improves cognitive function significantly among patients with mild to moderate cognitive impairment. The impairment was attributed to probable early Alzheimer's disease. With an enrollment of only 261 patients, the study was fairly small. But the results are nevertheless encouraging. They echo positive findings from previous studies that have examined the efficacy and safety of GPC in humans.3
In the Mexico study, participants received 1200 mg GPC per day, for six months. Subjects ranged in age from 60 to 80 years. All had suffered documented declines in cognitive function before entering the study. Patients were randomly assigned to receive either GPC or dummy placebo pills. Baseline psychometric tests, administered to both patient groups before the double-blind trial began, showed no statistically significant differences. In essence, all subjects entered the study at a more or less comparable level of early cognitive decline.
On a variety of scales designed to assess the progression of Alzheimer's disease, GPC patients scored more favorably than patients from the control group, all of whom received placebo. A favorable score on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) was considered the primary objective indicator of the oral supplement's effectiveness.
At the end of the six-month trial, GPC patients' average scores had decreased by 3.2 points, while placebo patients' scores increased by 2.9 points in the same period. A lower score on the ADAS-Cog is highly favorable, indicating less cognitive impairment. In other words, the mental status of patients on GPC therapy improved, while those receiving no therapy (placebo) worsened. These findings are comparable to the results obtained with the use of the prescription drugs Aricept™(donepezil HCl) Exelon™ (rivastigmine tartrate) and Reminyl™ (galantamine hydrochloride) in the treatment of AD patients, and with fewer side effects.
Other efficacy indicators were similarly favorable (see Figure 1, below). GPC patients' scores on all parameters of the Alzheimer's Disease Assessment Scale (ADAS-Total), Mini-Mental State Examination (MMSE), Global Deterioration Scale (GDS), and Clinical Global Impression (CGI) scale consistently improved versus baseline scores after three and six months of therapy, while placebo-group patients' scores either remained unchanged or worsened. After six months, improvement among GPC patients was also documented using the Alzheimer's Disease Assessment Scale-Behavioral Subscale (ADAS-Behav), and the Global Improvement Scale (GIS).
These results are heartening, given that the trial was tightly controlled. To rule out any interference due to expectations, researchers and participants alike were "blinded"; no one involved knew whether a given patient was receiving GPC or placebo, until after all data had been gathered. To further rule out confounding factors, potential participants were assessed for depression, alcoholism, anemia, systemic diseases (such as AIDS or cancer), stroke in the previous six months, neurological disorders (other than mild to moderate Alzheimer's disease) or certain vitamin deficiencies. Patients suffering from any of these additional conditions were excluded from participation.
Tolerability data were similarly encouraging. In most patients, drug-related adverse events were mild; no patients were withdrawn due to adverse events. The most common complaints among GPC patients included constipation and nervousness. In all, only 11 out of 132 patients complained of adverse events. In the placebo group, three out of 129 patients registered mild complaints, including nausea, dizziness, hostility and headache.
No one has suggested that brain aging is a perfectly elucidated, simple process. On the contrary, it's likely that numerous complex interrelated processes contribute to mental decline as we age. For example, researchers at the University of Utah School of Medicine recently made headlines when they released data indicating that declining levels of another neurotransmitter, gamma-aminobutyric acid (GABA), may also play a role in eroding brain function. They found, in essence, that boosting GABA in elderly test animals increased their ability to focus dramatically.
Interestingly, past research has shown that GPC stimulates release of GABA, raising the amount available to the brain.24 Some of the dementias, mood disorders and psychoses of both Huntington's and Alzheimer's diseases have been linked to depleted GABA.25
Besides playing a crucial role in memory, attention and general cognition, acetylcholine is also vital to the maintenance of normal sleep patterns. Insomnia is a troubling and all too common symptom of advancing age. Once-sound sleepers find themselves transformed into light sleepers by the encroaching years. This inability to screen out extraneous stimuli is a direct result of acetylcholine depletion. Acetylcholine drives the so-called stimulus barrier, a faculty of the brain that allows us to screen out distractions while concentrating on a task or problem, and to ignore intrusive sounds when sleeping. Insomnia often becomes severe in advanced Alzheimer's disease. Although clinical trials have largely ignored this quality-of-life parameter, it stands to reason that restoring acetylcholine to normal, youthful levels will also restore healthy sleep.
Other intriguing research has shown that when GPC is co-administered with growth hormone releasing hormone (GHRH) higher levels of human growth hormone (hGH) are released than is the case when GHRH is given alone. GPC evidently acts to potentiate the effects of GHRH.26 Although the effect was demonstrated in young and old alike, the increase was more dramatic in elderly subjects.
Yet another study alludes to further potential benefits of GPC supplementation. Rats that received GPC for six months experienced increased expression of nerve growth factor receptors in the cerebellar cortex. Nerve growth factor is crucial to the regulation of acetylcholine receptor function. It influences receptor growth and maturation and is involved in receptor repair, maintenance and regeneration. Like other components of the body, nerve growth factor receptors are incapacitated with advancing age. GPC - in the rat model, at least - appears to further reverse the effects of aging by reversing this deterioration.27
One thing is clear. GPC therapy is already proven beneficial in humans, and it's available for approximately one third the cost of some popular prescription drugs that are currently used for the treatment of Alzheimer's symptoms, such as the acetylcholinesterase inhibitors Aricept™(donepezil HCl) and Exelon™ (rivastigmine tartrate).
If researchers such as Dr. Lucilla Parnetti are right, and early intervention is our greatest hope for nipping cognitive decline in the bud, GPC may well prove to be a valuable new weapon in the age-fighting arsenal.
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