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Nutritional Protocols to Protect and
Extend Mental Function
Ward Dean, MD and Jim English
Across the globe, millions of people start the
New Year by heading to the local gym. Some aim to lose those sagging
excess pounds that seem to reappear after the holidays. Others hope
to revitalize lagging energy levels, stave off the effects of advancing
age, and reduce their risk of developing degenerative diseases.
Unfortunately, despite all the known benefits
physical exertion confers (including increased life span and improved
quality of life), no amount of exercise can address the greatest
challenge facing contemporary aging adults: the prospect of having
one's body out-last one's brain.
The human brain controls all life systems, and
as the body ages, so does the brain. Traditional health care has
promoted the concept that it is entirely normal and acceptable to
experience declines in mental performance with advancing age.
This concept is slowly being discarded as health-care
professionals begin to cope with the alarming increase in the number
of patients suffering from age-related cognitive dysfunction, dementia
and memory impairment. This problem is further exacerbated by an
alarming increase in the incidence of Alzheimer's disease, Parkinson's
disease and age-related mental decline. For example, Alzheimer's,
a progressive degenerative disease that commonly appears after the
age of 50, is the most common cause of dementia and one of the most
feared threats to mental health and cognitive performance.
Alzheimer's currently afflicts one person in ten
over the age of 65, and nearly half of all individuals over the
age of 85. It is estimated that over four million people in the
US, and an estimated 12 million people worldwide, now have Alzheimer's.
These numbers are expected to almost double in the coming decades,
further draining already strained health care resources, leaving
almost no family untouched. (1)
Researchers and pharmaceutical companies are pouring vast resources
into developing new diagnostic methods and treatments for Alzheimer's
and other degenerative brain conditions. Research in the field of
human memory has shown that there are a number of drugs and nutritional
compounds that can support healthy brain function and help us maintain
and prolong our capacity to think and reason.
Double-blind controlled trials conducted in Europe
and the US support the role of several nutritional supplements and
drugs in slowing down the age-related loss of higher-level cognitive
functions. These changes can appear in healthy individuals as young
as 50 years of age.
This article reviews some of the most promising
and potent anti-aging therapies for protecting our 10 billion brain
cells. Combined with lifestyle habits known to influence mental
health, such as eating a healthy diet, exercising regularly, and
reducing stress and exposure to environmental pollutants, these
strategies can help preserve brain function and contribute to an
improved quality of life.
Fig.
1. Comparison of healthy brain
(left) with age-matched brain damaged from Alzheimer's reveals
damage and loss of
tissue. |
Huperzine is a unique nutritional supplement
that offers hope to those suffering from Alzheimer's disease and
other age-related mental conditions. Alzheimer's is characterized
by the destruction of nerve cells in several key areas of the brain
devoted to mental functions, including a substantial loss of presynaptic
cholinergic neurons in brains of patients. (2)
This results in a dramatic decrease in the neurotransmitter
acetylcholine, a vital neurotransmitter with a fundamental role
in memory and intracellular communication between nerve cells. Research
has shown that levels of acetylcholine are deficient in the brains
of patients with Alzheimer's disease. What little acetylcholine
is still produced in the patient's brain is quickly broken down
by the brain enzyme, acetylcholinesterase (AChE), leading to a shortage
of the neurotransmitter, contributing to the patient's loss of memory
and other cognitive functions.
Huperzine is derived from the ancient Chinese
herb Huperzia serrata, traditionally used to treat fever, inflammation
and irregular menstruation. In the late 1980s, researchers discovered
that Huperzine-A, an alkaloid extracted from the raw plant, readily
crosses the blood-brain barrier to prevent acetylcholinesterase
(AChE) from destroying acetylcholine.
Researchers found that Huperzine works in a manner
similar to the AChE inhibitors (such as tacrine and donepezil) to
impair the ability of AChE to degrade acetylcholine. (3) By inhibiting
the actions of AChE and increasing acetylcholine concentrations
in the brain, Huperzine-A has been shown to be effective in alleviating
some of the symptoms associated with acetylcholine deficiencies.
"Hup-A appears to bind more tightly and specifically
to acetylcholinesterase than the other AChE inhibitors," crystallographer
Prof. Joel Sussman, one of the authors of the study said. "It
is as if this natural substance were ingeniously designed to fit
into the exact spot in AChE where it will do the most good."
Researchers have demonstrated that patients suffering
from Alzheimer's and various other memory disorders gain significant
benefit from huperzine, both in terms of memory and life quality.
In one placebo-controlled, double-blinded study, researchers found
that 58% of Alzheimer's patients experience significant improvement
in both cognitive and memory function when given 200 mcg of Huperzine
per day. (4)
Other significant effects have been noted in patients,
both in terms of their life quality and their ability to retrieve
past memories. Huperzine's memory-enhancing properties suggest that
it may be an effective agent for improving memory and learning in
healthy humans as well. These findings suggest that Huperzine not
only protects from the effects of Alzheimer's and senile memory
deficits, but also provides a unique and exciting supplement for
supporting memory in the healthy aging human as well.
Acetyl-L-Carnitine (ALC) is a cognitive enhancer and neuroprotective
agent that protects against a wide range of age-related degenerative
changes in the brain and nervous system. ALC is an ester of carnitine
that modulates cellular concentrations of free coenzyme A and acetyl-coenzyme
A, two compounds integrally involved in numerous cellular functions,
including the transfer of fatty acids across mitochondrial membranes
for energy production.
ALC is found in various concentrations in the
brain and its levels are significantly reduced with aging. (7) ALC
also significantly reduces damaged fats, such as lipofuscin, in
the brains of aged rats. In addition to accumulating in the aging
brain, lipofuscin also accumulates in the skin as 'aging spots,'
those brownish pigmented blemishes that accumulate in the backs
of hands of many people over fifty. (5) The reduction of these deposits
following consumption of ALC may be evidence of a slowing in the
aging process in the brain.
ALC also has the ability to cross into the brain
where it acts as a powerful antioxidant, preventing the deterioration
of brain cells that normally occurs with age. Because of this protective
effect, ALC may be beneficial in the prevention and treatment of
free-radical mediated diseases, such as Alzheimer's and Parkinson's
disease. (6)
:
As mentioned earlier, Alzheimer's disease primarily effects cholinergic
function. ALC has been shown to promote both the release (8) and
synthesis (9) of acetylcholine. Additionally, ALC promotes high
affinity uptake of choline, which declines significantly with age.
(10)
:
In addition to ALC's cholinergic-enhancing properties, researchers
have shown that ALC has numerous beneficial effects on dopaminergic
neurons. (11) The decline of the dopaminergic neurotransmission
system is most evident in Parkinson's disease patients.
ALC has been shown to improve age-related changes
of dopamine receptors, including improved release and binding of
dopamine. Research has shown that ALC can prevent dopaminergic neuron
death caused by MPTP, a neurotoxin that mimics neurological symptoms
similar to Parkinson's disease by selectively killing dopaminergic
neurons. (12)
:
The NMDA (N-Methyl-D-Aspartic acid) receptor system is one of the
most important receptor systems involved with cognitive function
and memory. NMDA receptors are widely distributed in the brain,
and their effects are mediated by excitatory amino acids like glutamate.
It has been shown that the density of NMDA receptors declines with
age. Damage to the NMDA receptors is also the most severe adverse
effect of the street drug, Ecstasy (MDMA). Treatment with
ALC restores NMDA receptor numbers to a significant degree. (13)
In fact, even a single dose of ALC can significantly increase the
number of available NMDA receptors.
: One of the most important, and often overlooked, receptor
systems is that of glucocorticoids. The hypothalamus in the brain
is the site of negative feedback between the pituitary and adrenal
gland. This is the center that regulates the production of glucocorticoids
(principally, cortisol) by the adrenals. The number of glucocorticoid
receptors in the hypothalamus declines significantly with age, (14)
and this results in an imbalance in the hypothalamus-pituitary-adrenal
(HPA) axis.
ALC treatment has been shown to prevent this age-related
decline in receptor number. (15) Because these receptors are central
to neuroendocrine aging, their decrease is considered a consistent
marker for aging. It appears that ALC may have substantial potential
for helping to slow the degradation of this principle marker of
neuroendocrine aging.
: One of the most exciting areas of brain
research has been the functions of Nerve Growth Factor (NGF). NGF
mediates many of its effects through a receptor system (NGF receptor
system). Unfortunately, aging is associated with a significant drop
in the number of NGF receptors in certain brain regions, as well
as a decrease in the amount of NGF produced. Because NGF is important
for the growth and continued maintenance of neurons, the age-related
decline in NGF function is thought to be directly involved in brain
aging.
ALC has the ability to partially reverse both
of these changes, and has even been shown to positively effect both
neuronal survival and growth. (16) ALC's ability to enhance NGF
effects suggests a tremendous potential for this natural compound
in many diseases and conditions affecting the brain and nervous
system.
:
A group of Italian scientists (Paradies, et al, 1994) evaluated
the effect of dietary ALC on the mitochondrial membranes of young
and old rats. They found that the activity of the enzyme, cytochrome
c oxidase, declined about 30% in the old rats, compared to the young.
This may explain the reduction in ATP formation (and reduced energy)
with age. The scientists found that dietary ALC restored cytochrome
c oxidase activity in old rats to that of the younger animals (Fig.
2).
Fig.
2. Acetyl-L-carnitine benefit for the "younger-old"
over the "older-old" in Alzhheimer's disease, as
elucidated by tri-linear analysis. The lind trending downward
indicates deterioration, while the line upward indicates
improvement.
(from Brooks et al). |
Furthermore, in a follow-up study, they found that the activity
of another enzyme, the ADP carrier protein adenine nucleotidase
(ANT) also decreases with age. Decreased ANT can also result in
reduced production of ATP. The scientists again found that ALC restored
ANT activity to more youthful levels.
Finally, the same scientists found that mitochondrial
levels of cardiolipin, a key lipid subfraction, were also much improved
(Fig.3). In fact, they hypothesized that this dramatic improvement
in cardiolipin fraction was the key element in its other demonstrated
benefits.
The authors concluded that restoration of these
functions to youthful levels should allow more efficient oxidative
phosphorylation, thereby improving performance in aged animals.
Phosphatidylserine (PS) is a naturally-occurring phospholipid nutrient
that has been shown to improve cognitive functions and enhance mental
ability. PS is essential to the healthy functioning of the human
brain where it affects an assortment of nerve cell functions, including:
conduction of nerve impulses; accumulation, storage and release
of neurotransmitters; the activity and number of receptors involved
in synaptic discharge; and the biological maintenance of cellular
'housekeeping' functions.
Supplementation of the diet with PS has been proven
to slow, halt, or in many cases, even reverse cognitive degeneration
due to Age-Related Cognitive Decline (ARCD), (18,19,24) and dementing
illnesses like Alzheimer's disease. (17,20-23,25) PS has been scientifically
established to be among the most effective substances to consistently
result in dramatic cognitive improvements and enhancements of other
higher brain functions.
PS is extremely bioavailable and crosses the blood-brain
barrier with ease. Once in the brain, the PS molecule as a unit
merges smoothly into the nerve cell membrane where it is available
to facilitate cell-level energy and homeostasis, as well as enhance
neurotransmitter production, release, and action. PS also serves
as a precursor reservoir for the related phospholipids, phosphatidylethanolamine
and phosphatidylcholine.
Findings from many controlled clinical trials
indicate that PS consistently ameliorates memory loss and other
cognitive decline related to aging. (33) In 14 double-blind clinical
trials, conducted with subjects aged 50 and older, PS benefited
all degrees of cognitive impairment. (17-20,21-26,28-30) In one
US trial by Crook, et al (1991) on subjects with age-related cognitive
decline (ARCD), (19) PS reversed the decline of name-face acquisition
skills by a statistical 12 years; i.e., from average scores attained
by 64-year-old subjects to average scores attained by 52-year-olds.
As the investigators noted, it's as if they had 'rolled back the
clock' measuring 'cognitive biological age' by roughly 12 years,
in terms of overall cognitive status.
In double-blind trials conducted with more severely
afflicted subjects, PS brought about statistically and clinically
significant improvements in measures of recall, learning, concentration,
adaptability, mood and sociability. In other double-blind trials,
PS improved neuro-physiological measures such as EEG (electroencephalogram)
and reflexes (as judged by flicker-fusion response time). (31)
In another human trial conducted with young male
volunteers, PS significantly improved EEG alpha rhythm (which often
declines with aging and memory loss). (31) In older subjects with
severe cognitive impairment, PS dramatically enhanced brain glucose
consumption (assessed via positron emission tomographic [PET] imaging)
and partially restored the 24-hour rhythm of TSH (thyroid-stimulating
hormone) secretion in aged men. (32) Also, in elderly subjects,
PS enhanced the hypothalamic-pituitary-adrenal (HPA) stress-coping
axis, as assessed by the dexamethasone suppression test. (27)
Vinpocetine is a powerful memory-enhancer that facilitates cerebral
metabolism by improving cerebral microcirculation, stepping up brain
cell ATP production, and increasing utilization of glucose and oxygen.
Vinpocetine has the unique ability to selectively increase blood
flow to the brain, particularly improving blood flow to the impaired
area, without lowering blood flow to other parts of the body.
Because of its selective effects on improving cerebral circulation,
vinpocetine is often used for the treatment of cerebral circulatory
disorders such as memory problems, acute stroke, aphasia (loss of
the power of expression), apraxia (inability to coordinate movements),
motor disorders, dizziness and other cerebro-vestibular (inner-ear)
problems, and headache.
In a series of studies involving 882 patients
with neurological disorders ranging from stroke to cerebral insufficiency,
vinpocetine was found to confer significant improvements in 62%
of the patients. In one of the studies, cerebral insufficiency patients
were asked to memorize a list of 10 words. Without vinpocetine the
subjects were able to memorize an average of six words. After a
month of treatment the average went up to 10 words. (34)
Reactive oxygen species (ROS) are believed to
play a crucial role in the neuronal damage occurring in ischemic
injury (stroke) and neurodegenerative disorders. Researchers at
the Center for Neurosciences in Portugal performed animal studies
to examine the antioxidant effects of vinpocetine to prevent the
formation of ROS and lipid peroxidation in brain synaptosomes. They
found that vinpocetine significantly decreased oxidative stress
and inhibited ROS formation up to 83%. The researchers concluded
that the antioxidant effects of vinpocetine contributed to reducing
neuronal damage in pathological situations. (35)
Baby boomers and other aging adults face a loss of cognitive powers
and impaired mental functions. Even otherwise healthy aging adults
may expect to experience noticeable declines in mental abilities.
Research supports the role of a number of potent anti-aging therapies
that pay multiple dividends in helping us maintain our identity,
while acting to slow brain aging and preserve cognitive function.
Rather than waiting for signs of an irreversible
decline in mental abilities or other, more serious cognitive problems,
it would be prudent to take steps to support the brain's ability
to heal and self-repair. In short, we can take steps now to slow
age-dependent brain cell changes, preserve vital functions, and
maintain good health and vigor. To paraphrase, the mind is a terrible
thing to waste.
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