European Therapy Helps Prevent Brain Aging and Restore Neurologic FunctionSeptember 2002
Glycerylphosphorylcholine is a drug prescribed in Europe to treat neurological disease. It is sold in the United States as a dietary supplement to protect against age-related brain deterioration and memory loss.
In the November 2001 issue of Mechanisms of Ageing and Development, an extensive review was published about the muliple effects of glycerylphosphorylcholine (GPC).1 The analysis covered thirteen published clinical trials examining a total of 4,054 patients with various forms of brain disorders including adult-onset cognitive dysfunction, Alzheimer's disease, stroke and transient ischemic attack. The overall consistent finding was that "administration of GPC significantly improved patient clinical condition."
The researchers stated that the effects of glyceryl-phosphorylcholine (GPC) were superior to the results observed in the placebo groups, especially with regard to cognitive disorders relating to memory loss and attention deficit. They noted that the therapeutic benefits of GPC were superior to those of acetylcholine precursors used in the past, such as choline and lecithin. What most impressed the researchers was data indicating that GPC helps faciliate the functional recovery of patients who have suffered a stroke.
Brain aging is characterized by cerebral circulatory deficit and neurotransmitter deficiency, along with structural deterioration to neurons and their connective transmission lines (axons and dentrites). A significant body of research indicates that glyceryl-phosphorylcholine (GPC) may be of benefit in helping to prevent every one of these pathological events. It may thus be possible to both protect against underlying causes of brain aging while partially restoring cognitive function.
This article describes the scientific studies that substantiate the benefits of glycerylphosphorylcholine.
Mechanisms of Ageing and Development is the official journal of the British Society for Research on Ageing.* This non-profit organization was the first scientific body to be concerned specifically with gerontology as a scientific discipline.
The aim of the Society is to foster an experimental approach to the problems of biological aging and to promote research to understand the causes of aging. Many of the now accepted molecular and medical concepts of aging were first introduced in the journal Mechanisms of Ageing and Development.
*Note that "ageing" is the British spelling for aging. The British Society for Research on Ageing grew out of the "Club for Ageing" founded in the 1940's by Vladimir Korenchevsky.
Choline-fuelled signalling molecules are at the seat of learning, memory and behavior. As a result, there has been a lot of buzz around manipulating cholinergic neuronal transmission in order to slow or undo the neurologic effects of aging.
The tricky part is not how much choline can be pumped into the brain, but how efficiently this critical raw material can be transported to various regions of the brain. Otherwise, it's like gassing up a car that has a clunked out engine.
A large problem in aging and diseased brains is the slowing of cholinergic transport, while cholinergic neurons drop in number. In Alzheimer's disease, cholinergic cells shrivel up and die at a fast-forward pace. Scientists believe that even in healthy aging people, malfunctioning and decreased numbers of choline-powered neurons are somewhat to blame for short-term memory loss and cognitive decline.
The reason why choline has to get where it's going in the brain is that it has a big to-do list. In addition to being the precursor for the neurotransmitter acetylcholine, choline also synthesizes phosphatidylcholine. Brain cell membrane integrity is dependent on phosphatidylcholine. When choline levels are low, phosphatidylcholine can function to produce more acetylcholine. The problem with low choline is that it compromises the integrity of brain cell membranes, since boosting the production of acetylcholine diverts phosphatidylcholine away from its critical job of maintaininig cell membranes. This all explains why the brain has such a voracious appetite for choline.
Help on the way
Enter L-alpha glycerylphosphoryl-choline (GPC), a byproduct of phosphatidylcholine, and a precursor that's useful in stoking the cholinergic neurotransmitter system. More specifically, it aids in the synthesis of several brain phospholipids, which increases the availability of acetylcholine in various brain tissues. The GPC form of choline has been shown in studies to reverse the cognitive and behavioral glitches seen in aging, Alzheimer's disease (AD), stroke and memory loss.
the synthesis of several brain
phospholipids, which increases
the availability of acetylcholine
in various brain tissues. The
GPC form of choline has been
shown in studies to reverse the
cognitive and behavioura
glitches seen in aging.
Studies suggest that glyceryl-phoshorylcholine is effective in slowing the expression of structural changes that occur in the brain as a result of age. These changes result in the loss of neuronal function, as well as a decline in the number of neurons and their receptors. One study found that long-term treatment of rats with GPC in their drinking water was effective in countering the loss of neuro-connecting fibers and brain cells that are consistent with aging. In GPC-treated rats, both the area occupied by neuro-connecting fibers and their density were significantly higher than in age-matched controls. Moreover, the number of granule neurons of the hippocampus (nerve cells that transmit information to the cerebellum) was higher in GPC-treated animals than in control 24-month-old rats. The authors stated that is appears that "glycerylphosphorylcholine treatment counteracts some anatomical changes of the rat hippocampus occurring in old age."2
Other research shows similar findings. Scientists looked at the density of nerve cells in the hippocampus and in the cerebellar cortex in adult (12-month-old) and old (24-month-old) rats. Results showed that a six-month treatment with GPC countered the age-dependent reduction of nerve cells.3
A number of studies have also demonstrated the ability of GPC to help restore muscarinic M1 receptors in old rats. These are a type of acetylcholine receptor whose number of sites tend to decrease with age. Italian researchers assessed the effects of aging and of GPC treatment on the hippocampus of experimental rats. Treatment with GPC restored, in part, choline acetyltransferase immunoreactivity and acetylcholinesterase reactivity in the hippocampus of aged rats. The treatment also countered, in part, the age-related loss of M1 receptors in old rats.4
In a later study, this scientific team examined specifically how six-month treatment with GPC would affect the density and pattern of M1 cholinergic receptors in rat brains. And again, they found that GPC treatment countered, in part, the loss of muscarinic M1 receptor sites in old rats. The authors suggest that the reduction in muscarinic M1 sites noticeable in aging rats may reflect a loss of nerve cells and/or terminals in these hippocampal fields, and that GPC increased the expression of muscarinic M1 cholinergic receptors.5 Likewise, other researchers concluded that chronic treatment of aged rats with GPC restored the number of M1 receptors to levels found in the striatum and hippocampus from young animals, and partially reversed membrane stiffness in both regions.6
The idea that cholinergic treatments might help dementia of the Alzheimer's kind goes back to what's known as the "cholinergic hypothesis" set forth about 20 years ago.7 That's when a U.S. researcher found and reported that the number of cholinergic neurons in the basal forebrain was substantially lower in Alzheimer's disease patients than in healthy individuals, and that the loss of cholinergic innervation from this area of the brain might be the basis of disease-related cognitive changes. Since then, research has characterized the Alzheimer's brain as having substantive degenerative loss of cholinergic receptors and a deficiency of acetycholine, which could explain the breakdown in cholinergic transmission that leads to dementia, learning and memory impairment.
While certainly not an exclusive theory on the underpinnings of Alzheimer's disease and how to treat it, the theory has given rise to a number of cholinergic-based therapies aimed at bettering cholinergic transmission. Primarily, therapies have included the use of acetylcholine precursors, M1 muscarinic agonists, and acetylcholinesterase or cholinesterase inhibitors in order to restore cholinergic function in the Alzheimer's disease brain. Inhibiting the natural breakdown of acetylcholine through esterase inhibitors and stimulating acetylcholine release with cholinergic precursors, such as choline and phosphatidylcholine (lecithin), have been the focus of many clinical trials.
A limited amount of research and small clinical trials have demonstrated that GPC boosts acetylcholine availability, its release, and even slightly improves cognitive dysfunction.8 Moreover, a larger, multicenter, randomized, controlled study echoed the results of smaller studies. Researchers compared the efficacy of GPC and acetyl-l-carnitine among 126 patients with probable senile dementia of Alzheimer's type of mild to moderate degree. Results showed significant improvements in most neuropsychological parameters in the GPC recipients that was greater than improvements in the acetyl-l-carnitine group.9