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LE Magazine September
2002
European
Therapy Helps Prevent Brain Aging and Restore Neurologic
Function
Page 1 of 2
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.
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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.
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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.
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]
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| More specifically, GPC 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 behavioural glitches
seen in aging. |
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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]
Dementia
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.
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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]
Continued on Page 2
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