LIFE EXTENSION WEEKLY UPDATE, NOVEMBER 9 2001
IN THIS ISSUE, NOVEMBER 9, 2001:
LIFE EXTENSION WEEKLY UPDATE EXCLUSIVE: New mechanism found for NSAIDs
against Alzheimer's disease
PROTOCOL: Alzheimer's disease
FEATURED PRODUCTS OF THE WEEK: Phosphatidylserine, Vinpocetine
LIFE EXTENSION MAGAZINE; OVERSTOCK SALE FOR MEMBERS ONLY!
LIFE EXTENSION WEEKLY UPDATE EXCLUSIVE
New mechanism found for NSAIDs against Alzheimer's disease
In a study partly funded by the National Institutes of Health published in
the November 8 2001 issue of the journal Nature http://www.nature.com ,
researchers at the University of California San Diego School of Medicine and
the Mayo Clinic in Jacksonville, Florida discovered that the nonsteroidal
anti-inflammatory drugs ibuprofen, indomethacin and sulindac sulphide
inhibit the formation of the most harmful plaque-producing protein that
occurs in Alzheimer's disease, independently of their anti-inflammatory
effect. Although it is known that the use of nonsteroidal antinflammatory
drugs, or NSAIDS, is associated with a lower incidence of Alzheimer's
disease, control of inflammatory processes in the brain through
cyclooxygenase inhibition appeared to be their most obvious mechanism of
action.
Alzheimer's disease involves the abnormal production and deposit of
amyloid-beta peptides which form plaques in the brains of its sufferers.
The harmful protein inhibited by the drugs is the 42-residue isoform of the
amyloid-beta peptide, or AB42, which is the type of amyloid-beta initially
deposited in the brains of Alzheimer's patients, and believed to be the main
culprit in the disease.
The researchers treated cell cultures with increasing concentrations of the
different NSAIDs and analyzed levels of AB40 and AB42. The AB42 peptide was
found to have been lowered up to 80% by ibuprofen, indomethacin and
sulindac. Other NSAIDs: aspirin, Naproxen and celecoxib, failed to lower
AB42. When the researchers gave ibuprofen to mice bred to produce amyloid
precursor protein, they had lower brain levels of AB42. The researchers
then treated cells genetically engineered to lack the cyclooxygenase, or
COX, enzymes with sulindac and found that AB42 levels were lowered as well.
This proved that an anti-inflammatory response, dependent on COX inhibition,
was not involved in the drug's action. It is the anti-inflammatory action
of NSAIDs that is the cause of their adverse gastrointestinal and
kidney-related effects. Currently, the drugs are not recommended for
Alzheimer's disease because the high doses needed could lead to these
unwanted effects. Senior author Edward Koo, of UC San Diego's Department of
Neurosciences explained, "The dose required to inhibit production of AB42 is
far too high. This is a secondary effect of the NSAIDs. For example, a
patient would need to take the equivalent of more than 16 tablets of Advil a
day. Our findings suggest a new mechanism through which NSAIDs might confer
protection from Alzheimer's disease - a mechanism independent of direct
anti-inflammatory properties of NSAIDs."
This new discovery will aid in the development of anti-Alzheimer's therapies
with fewer side effects.
PROTOCOL
Alzheimer's disease
Alzheimer's disease is the most common cause of dementia. However, it is a
diagnosis of exclusion. The diagnosis is only 85% to 90% accurate and the
diagnosis is only absolutely confirmed by brain biopsy after death. Brain
biopsy is usually unacceptable prior to death, and other causes of dementia
must be considered and eliminated before the diagnosis of Alzheimer's is
made.
Alzheimer's-like symptoms can be manifested by a variety of different
diseases including:
Space-occupying lesions in the brain, such as brain cancer and subdural
hematoma.
Neurological damage, such as occurs after a stroke or with multiple
infarctions.
Other neurological disorders, such as Parkinson's disease (a deficiency of
dopamine), Huntington's disease, and multiple sclerosis.
Infectious diseases such as meningitis, late-stage syphilis, and AIDS.
Endocrine disorders, such as hypothyroidism and hypoglycemia.
Cardiovascular disorders, such as congestive heart failure and vascular
disease.
Liver or kidney dysfunction.
Nutritional deficiencies of vitamin E, magnesium, and B vitamins (B12, folic
acid, niacin and thiamin) can also produce symptoms which might be mistaken
for dementia.
Standard lab tests for Alzheimer's disease include:
CBC
Thyroid panel: T3, T4, TSH
Liver function tests
STD testing: VRDL for syphilis, HIV if young
EKG to assess heart function
EEG to differentiate focal vs. diffuse brain dysfunction
Vitamin B12 and folate levels
A CT or MRI of the head is usually ordered to determine if the symptoms are
caused by multi-infarct dementia or a subdural hematoma.
Several alternative lab tests may be helpful in evaluating patients with
Alzheimer's disease to guide treatments. These include:
A comprehensive hormone panel, including estrogen (E1, E2 and E3),
progesterone, testosterone, and melatonin
Adrenal function test, including cortisol and DHEA
Oxidative stress levels
Essential Fatty Acid Panel
Homocysteine, B6, B12, and folate levels
Markers of inflammation, including C-Reactive Protein (CRP)
Hair mineral analysis to assess heavy metal toxicity
A comprehensive vitamin panel (including vitamins A, C, E, and K and
beta-carotene) should be considered.
http://www.lef.org/cgi-local/welcome.cgi/id=151067357/sgroup_id=699/welcome.
html
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FEATURED PRODUCTS OF THE WEEK
Phosphatidylserine
In 1988, the Foundation published an article about studies in Europe showing
phosphatidylserine could slow and reverse the rate of brain cell aging in
laboratory animals. Phosphatidylserine restored mental function in older
animals to levels exceeding those found in some younger animals. Although
studies in humans with Alzheimer's disease were less dramatic, they still
produced significant improvements in cognitive function. In patients with
mild dementia, significant cognitive and behavioral enhancing effects were
observed. In one study with mildly demented elderly patients, the
improvement in neural function continued 30 days after discontinuing
phosphatidylserine (PS) therapy. This suggests that relatively low doses or
cyclical dosing of PS therapy over an extended period of time in healthy
people may produce sustained antiaging results.
Brain tissues are especially rich in PS, but aging causes a decline in the
PS content of cells throughout the body. Research has shown that in addition
to improving neural function, PS enhances energy metabolism in all cells. In
the brain, PS helps maintain cell membrane integrity and youthful synaptic
plasticity, protecting brain cells against the functional deterioration that
occurs as a result of aging.
http://www.lef.org/cgi-local/welcome.cgi/id=151067358/sgroup_id=699/welcome.
html
Vinpocetine
Vinpocetine is derived from vincamine, the major indole alkaloid of the
periwinkle plant. Vinpocetine has been used for many years in Europe to
enhance memory and mental function by increasing neuronal firing rate. No
toxic effects have been seen from vinpocetine use at levels far above
therapeutic dosages.
When taken orally, vinpocetine can:
Improve blood supply to the brain
Increase oxygen and glucose use by the brain
Improve brain tolerance to hypoxic excitoxicity
Increase vasodilation response to hypoxia
Increase ATP levels in the brain
Reduce abnormal coagulation of blood
Raise brain levels of the neurotransmitter serotonin
http://www.lef.org/cgi-local/welcome.cgi/id=151067359/sgroup_id=699/welcome.
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LIFE EXTENSION MAGAZINE, October 2001
How Coenzyme Q10 protects the brain
Conclusion of a 3-Part Series on Cellular Bioenergetics and CoQ10
Alzheimer's disease is the most common adult-onset dementia. In recent years
researchers have discovered many of the mechanisms involved in the disease,
but we cannot yet clearly separate causes from effects in this complex
pathology. The theories we discuss are necessarily quite speculative.
The main effects of Alzheimer's disease on brain tissue are extensive neuron
loss and insoluble fibrous deposits called senile plaques and
neurofibrillary tangles. The core of the plaques is a toxic protein,
amyloid-beta, that assails cells on several fronts. Amyloid-beta generates
oxidative stress, damages mitochondrial DNA, impairs cellular bioenergetics,
and alters proteins so as to form neurofibrillary tangles.
A number of recent studies have found that the degree of disability in
Alzheimer's disease patients correlates with impairment of energy metabolism
in the brain. In fact, a new study suggests that cellular energy production
may be a better indicator than senile plaques of Alzheimer's disease
severity. This study of Alzheimer's patients in a nursing home found that
their degree of clinical disability correlated with a mitochondrial
abnormality involved in cellular respiration, but did not correlate with the
density of senile plaques.
Together with amyloid-beta, a potent free radical called peroxynitrite
oxidizes lipids in neuronal membranes. This generates the highly toxic
byproduct HNE that is found in excess in multiple regions of the Alzheimer's
disease brain. HNE kills brain cells directly, and also indirectly by making
them more vulnerable to excitotoxicity. As we have seen, the coantioxidants
coQ10 and vitamin E protect cell membranes from lipid peroxidation, and
coQ10 has been found to reduce peroxynitrite damage and HNE formation in the
bloodstream.
We do not know whether Alzheimer's disease arises from a single underlying
cause. An interesting multiple-factor theory was published in the journal
Gerontology (Ying W, 1997). According to this theory, Alzheimer's disease
develops from four causes: imbalances in APP (amyloid precursor protein) and
calcium, oxidative damage and bioenergetic deficit. The author cites studies
showing that each of the factors reinforces and is reinforced by each of the
other factors. This "deleterious network," as the author calls it,
potentially fits the therapeutic profile of coQ10. However, CoQ10 has never
been included in a clinical trial for Alzheimer's disease. The reasons for
this may not be scientific ones, as discussed at the end of this article.
http://www.lef.org/cgi-local/welcome.cgi/id=151067360/sgroup_id=699/welcome.
html
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