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by Parris M. Kidd, PhD
GPC or GlyceroPhosphoCholine (pronounced
gli-sero-fos-fo-ko-lean) is a small molecule with
a large place in the biochemical scheme of life.
It is used throughout the body to facilitate
basic life processes and as a foundation substance
for homeostasis (maintenance of basic
life processes), growth, renewal and revitalization.
As a dietary supplement GPC has excellent
safety and tolerability while offering
unique benefits for the brain and other organs.
It qualifies for an elite category of health giving
substance: ortho-nutraceutical.
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| Above: Molecular layouts
of PC (Phosphatidyl Choline)
and GPC (Glycero Phospho Choline). |
GPC Is an Ortho-Nutraceutical Crucial to Life
Technically, GPC is not a vitamin. Human cells
do have the capacity to produce it, but its
marked benefits as a supplement suggest the
body sometimes requires more GPC than it can
make. Rather, GPC is one of those limited
number of substances our cells make on
demand to feed their metabolic machinery;
without these life would come to an abrupt end.
These substances were christened orthomolecules
(molecules orthodox to the body) by
the late Professor Linus Pauling. Vitamin C is an orthomolecule. So also is GPC. But GPC is
more than the average orthomolecule.
GPC is also more beneficial, safer and more
biochemically versatile than the typical
nutraceutical, probably due to being orthomolecular.
This justifies a new descriptor for
GPC: Ortho-nutraceutical.
Clinical Trials With GPC: Impressive Brain Benefits
A minimum 24 clinical trials have been done
with GPC. Thirteen of the trials were conducted
randomized and controlled, and seven
were double-blind. All these trials resulted in
positive findings: GPC benefits attention,
mental focus, recall and other higher mental
functions (cognition). GPC offers superior
benefit for individuals with severe memory
decline, especially where circulation has been
compromised. It has proven especially valuable
for brain recovery following stroke or other circulatory
injury. The vast majority of the subjects
who received GPC experienced clinically
meaningful benefit, including healthy youth,
the middle-aged and the elderly.
Mental Performance in Healthy Youth
Two double-blind trials were conducted with
GPC given by mouth, to male and female volunteers
aged 19–38 years. Both used the scopolamine
amnesia model. The drug scopolamine
depletes the key chemical transmitter acetylcholine
from the brain, thereby inducing a
temporary amnesia: lowering of attentiveness,
recall capacity, overall mental performance. In
the first double-blind trial, subjects preloaded
with GPC for seven to 10 days tested significantly
better than placebo on word recall (also
called immediate learning) as well as on tests of
attention.
An important finding from this first
double-blind trial was that GPC improved the
baseline recall capacities; this suggests GPC can
improve mental performance in young healthy
people. GPC also improves the EEG (electroencephalograph)
patterns of young healthy brains.
The second double-blind GPC-scopolamine
trial used healthy men and women
ages 22-33. GPC taken by mouth was compared
with two drugs, idebenone and aniracetam.
GPC protected recall learning against loss
due to scopolamine, along with “working
memory” (a combination of reasoning and
attention). GPC worked better than did the
two drugs.
Mental Performance (Middle age)
In controlled trials with middle-aged subjects,
GPC improved a number of mental performance
measures, including reaction time, which
is related to acetylcholine nerve pathways, and
visual cortex performance which also represents
broader brain functions.
Superior Benefits Against Vascular Dementia
In a number of controlled trials GPC consistently
improved mental deterioration related
to poor circulation (“vascular dementia”).
Memory, other cognitive processing and mood
were significantly improved. In three separate
controlled comparison trials using subjects
with vascular dementia, GPC outperformed
citicoline (CDP-choline), another watersoluble
PC precursor.
Promising Findings About Alzheimer’s Dementia
In a controlled comparison trial against
advanced Alzheimer’s dementia, GPC performed
roughly twice as well as did the orthomolecule
acetylcarnitine. In two direct comparison trials
against severe memory loss, GPC also surpassed
the pharmaceutical oxiracetam.
A recently published double-blind trial
documented substantial benefits from GPC
against mild to moderate Alzheimer’s. The
investigators noted the degree of benefit
equaled or surpassed the benefits from the
pharmaceuticals officially approved for this
insidious disease.
Trauma Recovery (Stroke, Surgery)
GPC has produced impressive benefits for
brain trauma recovery. More than 3,000 stroke
patients have been tested. One huge study involved 176 hospital centers within Italy.
Starting with 2,044 hospitalized patients, a
total 2,004 completed six months of close
observation and functional testing while on
GPC. At the end of the study the investigators
judged that GPC had helped more than 95 percent
of the patients significantly. There were
no life-threatening adverse effects, nor did
blood analyses and other laboratory monitoring
reveal any abnormal effects. The investigators
concluded that GPC had excellent
tolerability. Two other large stroke trials produced
similar positive results.
GPC has improved mental functioning in
subjects impaired from heart surgery. Cases of
head trauma and coma also reportedly benefited.
In a small trial with acute ischemia
patients, GPC also improved patient outcome.
Thus for stroke, trauma and other neuroprotective
applications, GPC ostensibly is without
equal, even when compared to the available
pharmaceuticals.
The Many Biochemical Faces of GPC
GPC supports human health through a variety of mechanisms:
Bioavailable Choline Resource
Choline is a vitamin-like essential nutrient.
GPC serves as an “active choline” reservoir and
buffer, able to raise blood choline levels
quickly and efficiently, including within the
brain. GPC is readily processed to choline by
enzymes, at minimal energy cost to the body.
Choline is used (a) as a methyl group
source for metabolic regulation, (b) as a
starting molecule for the chemical transmitter
acetylcholine and (c) for incorporation into
choline phospholipids. Free choline is poorly
bioavailable, unstable and potentially toxic—very little of the body’s choline is present as the
free form. GPC seemingly is the body’s main
choline reservoir.
Reservoir for AcetylCholine, Chemical Transmitter
GPC is a major choline reservoir for the biosynthesis
of acetylcholine. This chemical transmitter
is involved in brain circuit maturation,
expansion, renewal and repair, as well as in the
“plasticity” adjustments of the circuitry that
occur during adult life. Acetylcholine is also
used to regulate the internal organs via the
autonomic nervous system and for nerve stimulation
of the skeletal muscles. Acetylcholine
insufficiency is linked to impairment of the
higher mental functions and problems with
other organs.
Source of PhosphatidylCholine (PC) for Membranes
Membranes are the centers for energetics and
metabolism in all cells. The proteins that are the
catalysts for most life processes are housed on or
within cell membranes. Membranes are dynamic
molecular assemblies built on a support matrix
of phospholipids, of which phosphatidylcholine
(PC) is the most abundant. The body’s trillions of
cells make membrane mass at a fast pace, as they
grow by adding on surface area and later split in
half to produce more cells. Adding membrane
creates demand for phosphatidylcholine, and
this is most efficiently created from GPC.
GPC is a “de-acylated” PC—the PC molecule
without its usual fatty acid tails (see illustration).
Though it is found in the watery cell
cytoplasm, GPC is an energy-effective starter
substrate for making membrane-phase PC.
GPC builds up to high levels in the cytoplasm
without doing damage, then is drawn upon to
make PC for building new membrane as this
becomes necessary.
Starter for Omega-3 PhosphatidylCholine
Enzymes are readily available that efficiently
splice fatty acids onto the “tail-less” GPC molecule
to convert it into PC. In certain tissues,
such enzymes specifically splice the omega-3
DHA (docosahexaenoic acid) onto GPC to generate
a PC-DHA. This highly polyunsaturated
molecule has a potent fluidizing effect on the
membrane matrix, with awesome functional
consequences.
The vast majority of the energetic and
molecular transformations that make up life
occur on or in membranes, and the more fluid
the membrane system, the more efficiently it
can perform. Membrane efficiency distinguishes
higher animals from lower. Nowhere is
this more important than in the excitable tissues,
including the retinal light sensing cells,
the nerve cells and muscle fibers. All these
membrane systems are enriched in omega-3
PC, enabling their proteins to “flip” or “spin”
faster in the membrane environment.
Osmotic Protectant for the Organs
Our cells’ tolerance for high concentrations of
GPC makes possible its protective osmotic
buffer role. Basic life processes (homeostasis)
call for keeping the total number of molecules
stable inside our cells. Excessive molecular
build up increases osmotic pressure and draws
water into the cell. GPC is a foremost osmotic
pressure regulator in the brain, liver, kidney,
muscle and other organs. As an osmoprotectant
GPC can reach concentrations hardly
exceeded by any other orthomolecule.
Other Organ Systems
Supported by GPC
The Muscular System. For our muscles to
spring into action they must be stimulated by
acetylcholine released from a nerve ending.
GPC is the most readily available source of
choline to make this important nerve-muscle
transmitter. But GPC probably plays another
valuable and different role in muscle contractility.
The outermost membrane of the muscle
fiber must be extremely fluid in order to coordinate
the contraction process. High quantities
of PC-DHA are used to ensure adequate
membrane fluidity. Duchenne Muscular
Dystrophy, the most common muscular dystrophy
in humans, is a muscle contractile dysfunction
that destroys the capacity to walk.
Duchenne is known to be membrane-based
and features a relative deficiency of GPC in the
affected muscle fibers. Duchenne may be a
human example of a GPC deficiency disease.
Sperm Maturation and Fertility. For reasons
similar to other tissues, fluidity is also important
for spermatozoal function. The epididymal
cells that nurture the sperm cells also
draw on GPC to make PC-DHA, which
becomes incorporated in the outer sperm cell
membrane.
Mature spermatozoa, once activated, must
swim vigorously in order to fulfill their destiny.
This intense movement is initiated within the
outer membrane system, which is highly fluid
due to a generous endowment of PC-DHA.
Many studies have linked low sperm levels of
GPC to poor sperm performance and compromised
male fertility. GPC is also found in the
female reproductive tract and its role in female
reproduction remains to be clarified.
The Kidneys. The very functions of these
organs make osmotic protection imperative.
The nephron cells must concentrate urea and
other by-products of metabolism to very high
concentrations. As these substances accumulate,
they threaten to drive up the osmotic
pressure and so cause swelling (edema) leading
to damage from osmotic shock. GPC is built
up to very high concentrations in the kidneys,
in parallel with the increasing urea concentrations.
As urea becomes progressively more
concentrated moving from the kidney cortex
to the papilla, GPC correspondingly builds in
concentration.
Endocrine Support: Growth Hormone
GPC may be valuable for brain revitalization
through hormonal restoration also. Several
studies were done, using both old and young individuals, to assess whether it could achieve
restoration of growth hormone (GH) production
by the pituitary gland.
The pituitary is the body’s “master”
hormone-producing gland. Through cyclic
release of growth hormone and other hormones
it coordinates maintenance and
renewal activities throughout the body. As
humans reach middle age, their growth hormone
production drops, and in some older
individuals growth hormone can be totally
absent from the blood. But GPC was found to
improve growth hormone release when coinjected
into older individuals with growth
hormone releasing hormone (GHRH).
The use of GPC markedly improved growth
hormone release, over and above the GHRH
effect. GPC boosted GH release in your
volunteers but more so in the older volunteers.
Other research indicates GPC may boost
another very important hormone—thyroidstimulating
hormone—and probably others.
This research is still preliminary but hints at
further utility of GPC for brain revitalization
and healthy aging.
Substantial animal research supports GPC’s
brain revitalization benefits. In rats it facilitates
learning and memory acquisition, as it raises
acetylcholine in the key hippocampus zone. In
aging rats GPC stimulated the hypothalamuspituitary
axis that produces growth hormone;
protected against the depletion of hippocampal
and cortical nerve cells, slowed the
loss of neurotransmitter receptors with aging,
conserved the membrane receptors for nerve
growth factor, and had other impressive brainrestorative
effects.
Dosing, Safety, Tolerability
The oral intake level of GPC used in the clinical
trials was usually 1,200 milligrams (mg)
per day. Half that intake—600 mg GPC per
day—approximately doubles brain choline
levels. A reasonable dosing strategy for dietary
supplementation with GPC would be 1200
mg/day between meals for one month, then
600 mg/day for maintenance. Those clinically
symptomatic may stay on 1200 mg/day indefinitely or until improvement is noted. Some of
the stroke trials gave GPC intramuscularly
(1,000 mg) for a month for faster effect, then
switched to the 1,200 mg oral intake.
GPC works in natural biochemical concert
with the vitamins, the dietarily essential minerals
and other orthomolecular supplements.
Of the more than 4,000 patients who have so
far received GPC in clinical trials, not one has
experienced a serious adverse effect. Further,
during the large stroke trials involving elderly
patients taking many pharmaceuticals, no
drug-GPC interactions were noted.
A Dietary Supplement for All Ages.
Among nutrients or drugs, GPC is unique for
improving mental performance in the healthy
young as well as in the middle-aged and the
elderly. It is a key ortho-nutraceutical for protection,
renewal and repair at all ages. Its benefits
surpassed pharmaceuticals (oxiracetam,
aniracetam, idebenone) and nutraceuticals
(acetylcarnitine, CDP-choline) in direct, controlled
comparison trials.
The ideal of healthy living suggests having
as many as possible of our organ systems functioning
at full capacity. Healthy aging suggests
experiencing the aging process free of crippling
degenerative disease. GPC’s stellar clinical
record makes it indispensable to healthy living
and healthy aging.
References available upon request, send a
SASE to totalhealth.
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