
Brain Survival &
Enhancement Strategies
Nutritional Protocols to Protect and
Extend Mental Function
by 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 ones
body out-last ones 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
Alzheimers disease, Parkinsons disease and age-related mental
decline. For example, Alzheimers, 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.
Alzheimers 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 Alzheimers.
These numbers are expected to almost double in the coming
decades, further draining already strained health care
resources, leaving almost no family untouched. (1)
Hope for Aging Brains
Researchers and pharmaceutical companies are pouring vast
resources into developing new diagnostic methods and treatments
for Alzheimers 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.
Huperzine
Huperzine is a unique nutritional supplement that offers hope to
those suffering from Alzheimers disease and other age-related
mental conditions. Alzheimers 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 Alzheimers disease. What little
acetylcholine is still produced in the patients brain is quickly
broken down by the brain enzyme, acetylcholinesterase (AChE),
leading to a shortage of the neurotransmitter, contributing to
the patients 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
Alzheimers 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 Alzheimers 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. Huperzines
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 Alzheimers 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
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 www.ed diseases, such as Alzheimers and Parkinsons
disease. (6)
- Alzheimers Disease: As mentioned earlier, Alzheimers
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)
- Parkinsons Disease: In addition to ALCs
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 Parkinsons
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
Parkinsons disease by selectively killing dopaminergic
neurons. (12)
- Restoring NMDA Receptors: 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 www.ed 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.
- Reversing Neuroendocrine Aging: 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.
- Restoring Nerve Growth Factor Function:
One of the most exciting areas of brain research has been
the functions of Nerve Growth Factor (NGF). NGF www.es 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) ALCs ability to
enhance NGF effects suggests a tremendous potential for this
natural compound in many diseases and conditions affecting
the brain and nervous system.
- Restoring Mitochondrial Enzyme Activity
and Cardiolipin to more Youthful Levels: 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). 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)
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 Alzheimers 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, its
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
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)
Conclusion
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 brains 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.
Highly recommended
source of nutrients and supplements.
How did we
qualify VRP?
References:
1. Alzheimers Association, General Statistics and Demographics,
www.alz.org/hc/overview/stats.htm.
2. Watkins PB, Zimmerman HJ, Knapp MJ. Hepatotoxic effects of
tacrine administration in patients with Alzheimers disease. JAMA
1994 Apr 6; 271:992-8
3. Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman
JL. Structure of acetylcholinesterase complexed with the
nootropic alkaloid, (-)-huperzine A. Nat Struct Biol 1997
Jan;4(1):57-63.)
4. Xu SS; Gao ZX; Weng Z; Du ZM; Xu WA; Yang JS; Zhang ML; Tong
ZH; Fang YS; Chai XS; et al, Efficacy of tablet huperzine-A on
memory, cognition, and behavior in Alzheimers disease. Chung Kuo
Yao Li, Hsueh Pao16:391-5, 1995.)
5. Ramacci MT, De Rossi M, Lucreziotti MR, Mione MC, Amenta F.
Effect of long-term treatment with acetyl-L-carnitine on
structural changes of aging rat brain. Drugs Exp Clin Res
1988;14(9):593-601.)
6. Puca FM, Genco S, Specchio LM, et al. Clinical
pharmacodynamics of acetyl-L-carnitine in patients with
Parkinsons disease. Int J Clin Pharmacol Res
1990;10(1-2):139-43.)
7. F. Maccari, A. Arseni, P. Chiodi, et al, Exp Geront 1990; 25:
127-134.) In numerous animal studies ALC has been shown to have
the remarkable ability of improving not only cognitive changes,
but also morphological (structural) and neurochemical changes.
ALC has varied effects on cholinergic activity.
8. A. Imperato, M.T. Ramacci, L. Angelucci, et al, Neurosci Lett
1989; 107: 251-255.)
9. V. Dolezal and S. Tucek, J Neurochem 1981; 36: 1323-1330.
10. D. Curti, F. Dagani, M.R. Galmozzi, et al, Mech Ageing Dev
1989; 47: 39-45.
11. H. Sershen, L.G. Harsing, M. Banay-Schwartz, et al, J
Neurosci Res 1991; 30: 555-559.
12. Bodis-Wollner, E. Chung, M.F. Ghilardi, et al, J Neural
Transm Park Dis Diment Sci 1991; 3: 63-72.
13. L. Fiore and L. Rampello, Acta Neurol 1989; 11: 346-350.
14. R.M. Sapolsky, L.C. Krey, and B.S. McEwen, J Neurosci 1985;
5: 1222-1227.
15. F.R. Patacchioli, F. Amenta, M.T. Ramacci, et al, J Neurosci
Res 1989; 23: 462-466.
16. G. Taglialetela, L. Angelucci, M.T. Ramacci, et al, Brain
Res Dev Brain Res 1991; 59: 221-230
17. Amaducci, L and the SMID Group. Phosphatidylserine in the
treatment of Alzheimers disease: results of a multicenter study.
Psychopharmacol. Bulletin, 1988, 24: 130-4.
18. Cenacchi, B, Bertoldin T, Farina C, Fiori M.G., Crepaldi G.
Cognitive decline in the elderly: a double-blind,
placebo-controlled multicenter study on efficacy of
phosphatidylserine administration. Aging (Clin. Exp. Res.),
1993, 5: 123-33.
19. Crook, T.H., Tinklenburg, J, Yesavage J, Petrie W, Nunzie
M.G., and Massari, D.C. Effects of phosphatidylserine in
age-associated memory impairment. Neurol, 1991. 41: 644-9.
20. Crook, T.H., Petrie W, Wells C, Massari, D.C. Effects of
phosphatidylserine in Alzheimers disease. Psychopharmacol.
Bulletin,, 1992. 28: 61-6.
21. Delwaide, P.J., Gyselynk-Mambourg A.M., Hurlet A. and Ylieff
M. Double-blind randomized controlled study of
phosphatidylserine in demented patients. Acta Neurol. Scand,
1986. 73:136-40.
22. Engel, R.R., Satzger W, Gunther W, Kathmann N, Bove D,
Gerkes, Munch U and Hippius H. Double-blind cross-over study of
phosphatidylserine vs. placebo in subjects with early cognitive
deterioration of the Alzheimer type. Eur. Neuropsychopharmacol,
1992. 2: 149-55.
23. Funfgeld, E.W., Baggen, M, Nedwidek, P, et al. Double-blind
study with phosphatidylserine (PS) in Parkinsonian patients with
senile dementia of Alzheimers type (SDAT). Progr. Clin. Biol.
Res, 1989. 317: 1235-46.
24. Gindin, J, et al., 1995. The Effect of Plant
Phosphatidylserine on Age-Associated Memory Impairment and Mood
in the Functioning Elderly. Rehovot, Israel: Geriatric Institute
for Education and Research, and Department of Geriatrics, Kaplan
Hospital.
25. Hershowitz M, et al. Long-term treatment of dementia
Alzheimer type with phosphatidylserine: effect on cognitive
functioning and performance in daily life. In, Bazan NG, et al
(eds.) Phospholipids in the Nervous System: Biochemical and
Molecular Pathology, 1989. Padua, Italy: Liviana Press.
26. Maggioni, M, Picotti, G.B., Bondiolotti ,G.P., Panerai, A.
Cenacchi, T. Nobil, P. and Brambilla, F. Effects of
phosphatidylserine therapy in geriatric patients with depressive
disorders. Acta Psychiatr. Scand. 1990. 81: 265-70.
27. Monteleone, P, Maj, M, Beinat, L, Natale, M, and Kemali, D.
Blunting by chronic phosphatidylserine administration of the
stress-induced activation of the hypothalamos-pituitary-adrenal
axis in healthy men. Eur. J. Clin. Pharmacol ,1992. 41: 385-8.
28. Nerozzi, D., et al. Phosphatidylserine and impaired memory
in the elderly. La Clinica Terapeutica, 1989. 120: 399-404.
[Translated from the Italian]
29. 15 Palmieri, G, Palmieri, R, Inzoli, M.R., et al.
Double-blind controlled trial of phosphatidylserine in patients
with senile mental deterioration. Clin. Trials J., 1987. 24:
73-83.
30. Ransmayr, G, Plorer, S, Gerstenbrand, F, and Bauer, G.
Double-blind placebo-controlled trial of phosphatidylserine in
elderly patients with arteriosclerotic encephalopathy. Clin.
Trials J., 1987. 24: 62-72.
31. Rosadini, G, Sannita ,W.G., Nobili, F, and Cenacchi, T.
Phosphatidylserine: quantitative EEG effects in healthy
volunteers. Neuropsychobiol, 1991. 24: 42-8.
32. Kidd, P., 1995. Phosphatidylserine (PS), A Remarkable Brain
Cell Nutrient. Lucas Meyer, Inc, Decator, Il.
33. Dean, W., Morgenthaler, J. Fowkes, S. 1993
Phosphatidylserine Smart Drugs II, The Next Generation, Health
Freedom Publications. Menlo Park, CA. pp. 75-80.
34. Gedeon Richter product literature, Cavinton.
35. Santos MS, Duarte AI, Moreira PI, Oliveira CR Synaptosomal
response to oxidative stress: effect of vinpocetine. Free Radic
Res 2000 Jan;32(1):57-66
|