www.perpetualcommotion.com
"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children
of Hurin
Notes
What this page is for:
The
information in these
Web pages is for the time
when the
medical community throws its hands in the air and says, “There’s
nothing we can
do for you, go home and die.” This
alternative medicine stuff might all be hooey, but given the choice
between
trying it and going home to wait around for the grim reaper, why not
give it a
try? “It ain’t
over, ‘til it’s over.”
As I've said before, I'm all for whatever works, whether that's Enbrel,
supplements, methylene blue, or licking the butts of South American
tree toads (I made that last one up).
Thanks to all of the people who have provided the information I have
gleaned from the various message boards. These are clues and leads, and
yes, it is OUR responsibility to research them further.
Again I must say that I really appreciate the, "we're gonna take
matters into our own hands and do something" attitude of some of the
people I have run into, especially on the Alz.org
"Medications/Treatments
for
Alzheimer's
and
Other
Related
Dementias" forum, instead of a
bunch of people just holding hands and commiserating about how horrible
these diseases are, and how the doctors don't have any answers. OK,
commiserating can help ease the anxiety and depression, but doing
something-- trying some of these things mentioned here and elsewhere--
doing IS helping.
********************************************************************************************
Mainstream
Medicine
I’m not against
mainstream, traditional medicine. It has a lot of offer.
The
experience, training, and knowledge of
these professionals should not be discounted.
If they have a drug or therapy that makes sense and has solid
research
and testing behind it, go for it!
Mainstream physicians denounce
"alternative
medicine" as quackery [from the German word for
mercury, quacksalber, once used to treat disease???]. They say
that alternative medicine providers are just exploiting people's
desperate attempts to find a cure. But I can assure you that
after spending thousands of dollars on tests, neurologists, physicians,
and hospitals, just to be told, "sorry, there's nothing we can
do for you, just go home and die", mainstream medicine is more than
happy to take all your money without even offering hope. If
mainstream medicine can't even offer hope, then pursuing alternatives
is more than justified. AD is a terminal
illness.
What difference does it make to the AD suffer if he spends all of his
savings on a possible cure that doesn't work? It's his money to
do with as he pleases. Traditional medicine is just as happy to
take every penny of your money as alternative medicine is.
Traditional medicine is every bit as bad when it comes to diseases they
are ineffective in dealing with as "quack medicine" is.
Both will take your money with a smile, or with a lawyer and collection
agency if necessary.
********************************************************************************************
A Rut:
A good example of how
physicians can get stuck in a rut and refuse to accept change
is stomach ulcers. For many decades
they insisted that if you had a stomach ulcer, you had too much acid,
probably
because you worried too much or were under too much stress.
However, as time went on, in the 1980’s
researchers
found that stomach ulcers were caused by a bacteria!
But now comes the sticky part.
What if this bacteria could have been eliminated by eating
dandylions
instead of an patentable drug? (This is
just an absurd example to illustrate a point.)
What would have been the financial incentive to push the medical
community into using dandylions instead of expensive drugs to reduce
stomach
acid? Why would the mental health
industry want to give up “treating” these obviously overstressed
individuals? There would be no incentive. Physicians, drug
companies, and researchers
seeking grant money would have scoffed at the very idea of using a mere
common
lawn weed to cure a nasty illness. But
fortunately for ulcer suffers, dandylions weren’t the cure, an
expensive drug
was.
********************************************************************************************
Profit
Motive:
There is nothing wrong
making a profit for
providing a
product or service. It is the best
incentive to get people to do what they are the best at doing when they
don’t
feel like doing it. But it is
wrong to block competition through the use of artificial government
regulations
or trade guilds that control a profession (with government
endorsement).
It is also wrong to push high cost drugs or
therapies that have little or no benefit over other drugs, or even
herbs, that
have about the same benefit, just because more profit can be made from
the high
cost products. For us as consumers of
medical care, it is a matter of discerning motive.
Full disclosure of alternatives and benefits would be the ideal,
but it is not going to happen while human nature rules human
nature.
The cure for this ailment is
self-education.
********************************************************************************************
Physicians
Vs.
Doctors:
Most physicians and
surgeons are not true
“doctors”, in that
they do not hold a Ph.D. They ‘practice’
medicine, they don’t create it, study it, or research it.
Few physicians have the time or incentive to
truly study the latest research. If you
are lucky, you will be dealing with one that has found the time, or had
just
been to a conference, or happen to have picked up the right medical
journal and
read the right article. Otherwise, they
are pretty much in the dark as they race from examining room to
examining room
to give each patient their full five minutes worth of attention.
So it is left to you, the concerned relative
or the patient to educate yourself as much as you can so that you can
ask the
right questions. If you don’t get the
right answers, then either your information is wrong and you need to do
some
more digging, or you need to find another physician.
Few physicians will be willing to even acknowledge your
self-education,
and if your sources are not mainstream, instant contempt for the source
will block
out any consideration of the information.
When you have to confront the physician (since many drugs and
therapies
can only be had by way of a physician or his prescriptions), make sure
you only
quote or provide mainstream publications, studies, journal articles,
etc.
********************************************************************************************
Who is
the
customer?:
When you are dealing with
physicians, hospitals
and
pharmaceutical companies, remember who the customer is:
Insurance companies and/or the government
(Medicare). The healthcare industry
serves the purse holder not you!
Somewhere along the line, these mega organizations have to keep
the
masses pacified, but if your condition lies outside of the norm, you
are out of
luck. They will probably not want to
deal with your problem because dealing with you will take too much of
their
time or their resources. Since you are
not the customer, they only have to take care of enough cases to keep
the purse
holder happy. The next time you are in
a hospital and you are dismayed by the way you are being treated,
remember: You are not the customer,
your insurance company is.
********************************************************************************************
The
real
challenge...
The real challenge may be...
Even if you find something in these pages you think might work, and the
doctors agree with it, the real challenge might be getting the patient
to change their lifestyle. Habbits and behavior will probably be
your greatest obstacle. This is like watching your grandfather
smoke himself to death with cigarettes. You know they are bad for
him, and that his is smoking way way to much. But what can you
do? You just can't stop him, and so you must just stand there and
watch him pound nails in his own coffin. A person who is starting
to show the signs of dementia, either from Alzheimer's or from Vascular
Dementia, may not even be able to help themselves. They may not
have an appetite to eat better food. They may not be able to
swallow or feed themselves. Their primary caregiver may not
believe that mere lifestyle and eating habbits and herbs and medicine
or anything can help. Fatalism or a state of denial can doom the
dementia sufferer to an inevitable decline. The only way pills
can help you, if they can, is if you have enough faith to swallow them.
This may be your greatest challenge. This, more than anything
else may be something you will not be able to overcome.
The person you used to know is
there, but
she isn't. It's like a book with missing pages; a hard drive with
sectors randomly wiped out.
********************************************************************************************
Possible
causes of dementia: [Find
out more about these and elaborate]
-Tauopathies (Alzheimer's disease, corticobasal degeneration, FTD, PSP,
etc.)
-Multiple "mini strokes", a.k.a. TIA (Transient Ischemic Attacks [check
this!!!!!!!!!!]
-Brain tumors
-Chemical imbalances
-Spinal fluid pressure
********************************************************************************************
The
Irony of Iron
Let's put these piece of the
puzzle
together.
J. S.
Richardson, Department of Pharmacology, College of Medicine,
University of Saskatchewan, Saskatoon, Can "...feels the major cause of
Alzheimer's Disease is excess brain iron levels. So as liver iron
builds up, brain iron levels build up. Dr. McLachlan at the University
of
Toronto Dementia Clinic showed that aluminum was the cause of
Alzheimer's
Disease (D.R.C. McLachlan et al. Desferroxamine. Lancet, June 1991). He
is
using an iron chelator called deferoxamine to treat Alzheimer's Disease
and
his results are probably better than any other treatment program for
Alzheimer's. He stated that the drug arrests the disease. Dr.
Richardson and Dr. McLachlan have been arguing, "Is it the iron, or is
it the aluminum?" The same medication lowered both." If the
presence of
excess iron has more impact on the progression of AD, then the
administration
of an iron chelator is indicated.
http://www.annalsnyas.org/cgi/content/abstract/695/1/73Now let's fast forward to November
of 2005.
From the Dec 12, 2005 online
issue of Drug Topics
"Deferasirox
(Exjade,
Novartis)
was
approved
in
November
and
touts
itself
as
the
first
and
only
once-daily
oral
iron
chelator.
The
drug
is
approved
for
the
treatment
of
chronic
iron
overload
due
to
blood
transfusions
in
adults
and
children
age
two
and
older.
According
to
Novartis,
deferasirox
tablets
should
be
dispersed
into
orange
juice,
apple
juice,
or
water,
and
administered
as
a
drink. Previously available iron chelator therapy
[intramuscular injections desferal, or desferioxamine or
desferrioxamine] often required a subcutaneous infusion lasting eight
to 12 hours per night.
"Clinical trials for
deferasirox included more than 1,000 adults and
children and showed that doses of 20-30 mg/kg/day led to reductions in
liver iron concentration, an indication for body iron content in
patients receiving blood transfusions. The new drug will cost about 20%
more
than desferrioxamine (Desferal, Novartis). The list price is $89.49/gm,
which at an average dosage, comes to more than $32,000 annually for
treatments other than sickle cell disease. Costs for sickle cell
treatment are
about a third lower."
http://www.drugtopics.com/drugtopics/article/articleDetail.jsp?id=256787
At $89.49/gm, or $32,000 annually,
and if this drug is as effective at
arresting the progression of AD as DR. McLachlan's desferroxamine
trial, then Novartis would have plenty of financial incentive to
saturate all
media outlets with the news, "Exjade stops Alzheimer's disease".
Interestingly, the clinical trials of EXJADE did not include enough
subjects of the age most likely to suffer from Alzheimer's.
Geriatric
Use
EXJADE did not include
sufficient numbers of subjects aged 65 and over
to determine whether they respond differently from younger subjects.
Thirty patients ≥65 years of
age were included in clinical trials of EXJADE. The majority of these
patients had myelodysplastic syndrome (MDS, n=27; other anemias, n=3).
In general, caution should be used in elderly patients
due to the greater frequency of decreased hepatic, renal, or cardiac
function, and of concomitant
disease or other drug therapy.
http://www.fda.gov/cder/foi/label/2005/021882lbl.pdf
Another very interesting paper is "Iron
metabolism
in
Parkinsonian
syndromes"
Mov Disord. 2006
Sep;21(9):1299-310. In this paper, it is pointed out that iron
metabolism seems to be involved in a host of nasty neuro-degenerative
diseases that have Parkinsonism as a primary symptom. See Parkinsonian Syndromes for
more on this topic.
Supplements
that
might be used to treat iron overload are IP6
and curcumin.
Dr. Paolo Zamboni, a professor of
medicine at the University of Ferrara in Italy appears to have found a
connection between iron accumulation and multiple sclerosis (MS).
This accumulation of iron in the brain is due to a reduced flow of
blood in the vessels that drain blood from the brain. He
hypothesized that iron damages the blood vessels and allows
the metal, along with other unwelcome cells, to cross the brain-blood
barrier. Combine this with the "Iron metabolism in Parkinsonian
syndromes" article above, and we have the intriguing idea that perhaps Parkinsonian syndromes are also
caused by blood circulation problem. (See more at CCSVI)
One has to wonder what other
diseases CCSVI could cause?
********************************************************************************************
Chelation
Therapy
Those few physicians who practice
intravenous chelation
therapy to treat heart disease (specifically arterial sclerosis)
claim to have noticed that after about 100
treatments
[cite source for this], those patients with AD reported a regression of
their symptoms. Unfortunately, there hasn't been a study to back
up these claims that the mainstream medical community will
accept. The common excuse given by chelation therapy
practitioners as to why this procedure is not accepted is: There
isn't enough money in it. But surely, we all run the risk of
developing these terrible conditions, even doctors and the CEO's of
pharmaceutical companies. Who knows, maybe they secretly use
chelation therapy themselves to stave off diseases like AD.
(Isn't it interesting how old former presidents
have been getting of late? Now there's a conspiracy
theory for you to chew on!) The chelation therapist themselves
don't know for sure why it works.
Their only claim is that they have observed that it does. But
intravenous chelation therapy is expensive since it must be
administered by a physician. There is an alternative to this
alternative: Oral chelation therapy. IV chelation
practitioners denounce oral chelation therapy, because, well, if people
can get the same effect by something they take by mouth, without the
assistance of a highly paid physician, then the physician's income
might be affected. I hardly think so, in the long run:
There are plenty of other illnesses to go around, and if you manage to
beat AD, something else will surly go wrong. Physicians and
pharmaceutical companies really have nothing to worry about.
Perhaps plain old ignorance and reluctance to accept
new
ideas
[link to section on stomach ulcers] is what is impeding chelation
therapy as an accepted treatment for AD and other diseases.
Chelating agents such as Phytic
Acid and EDTA may only be a temporary measure to delay
further damage until some treatement that treats the cause of the
amyloid-beta plaque formation is found.
********************************************************************************************
Phytic
Acid
(myo-inositol hexakisphosphate, IP6, InsP6)
(phytic
acid)
A Dr.
McLachlan published a paper in the June 1991 issue of the Lancet
describing research where AD patients where given the iron/aluminum
chelator desferrioxamine. It was originally theorized that
aluminum played a part in AD, and the study was meant to confirm
this. However, later a J.S. Richardson published a paper
disputing the aluminum theory and suggesting rather that excess iron
was the real culprit. The interesting thing is that AD in the
patients administered desferrioxamine in the McLachlan tests, did not
advance. In fact, some reviewers of this report state that
desferrioxamine effectively arrested Alzheimer's disease.
Put the McLachlan study together
with the
following...
This quote from Inhibition of
iron-catalysed
hydroxyl radical formation by inositol polyphosphates: a possible
physiological function for myo-inositol
hexakisphosphate by Phillip T. HAWKINS (and others) Biochem..
J. (U.K) 1993 tells most of the story...
"Some idea of
the relative
affinity of
InsP6
for Fe3+ was deduced by competition experiments measuring the
decolorization of FeCl3/catechol complexes (see the Materials and
methods section). Any compound that is able to compete with
catechol for Fe3+ in the same
concentration range as the Fe'+-catechol complex (0.25 mM in this case)
must have an affinity for Fe3+ that is of a similar order to, or
greater than, that of catechol (the
K1 for which is approx. 10-20; Martell and Smith, 1982). The data
(Figure 2) show that InsP6, EDTA and Desferral all fall into this
category; the greater potency of InsP6 compared with the other two
chelators is presumably because InsP6 has multiple phosphates which
are capable of chelating Fe3+ with high affinity (i.e. more than one
Fe3+ can be bound per InsP6; Graf et al., 1987)."
If IP6 has a greater affinity for
iron than
desferrioxamine (desferral), then it seems highly likely that IP6
supplements would have a similar effect on AD.
IP6 is sold in
healthfood stores as a "immune system enhancement" for those afflicted
with cancer. Some brands also contain pure myo-inositol (without
the phosphates). This compound, pure myo-inositol, even though it
is an isomer of
scyllo-inositol, has not shown a positive
effect on AD symptoms.
********************************************************************************************
Scyllitol
(scyllo-inositol, cocositol, quercinitol)
Scyllitol
(scyllo-inositol) is one of the six naturally occuring isomers of cyclohexanehexol.
According to a paper published in
the
journal Nature Medicine on June 11, 2006, mice genetically engineered
to have Alzheimer's disease
when fed scyllitol either did not
develop the disease, or recovered most mental function and life
expectancy of normal mice.
Upon some research on the web, it
turns out
that scyllitol is a naturally occuring sugar found in many plants and
in soil, (presumably synthesized by bacteria). Interestingly, the
most abundant source I've found so far is coconut palm leaves, and
coconut milk. However, at something like 5 parts per million, you
would probably have to consume enormous quantities of coconut milk to
get a dose of scyllitol to have an effect. But the real
significance of this is that scyllitol is a naturally occuring
substance found in food, and therefore, could not be patented.
Supplement makers should be able to extract it from food sources.
Perhaps the bacteria responsible for the presence of scyllitol in soil
could be identified, and then used in sort of a fermentation process.
But since the chemical can not be
patented,
I envision that it will be denounced as "quack medicine", "dangerous",
or whatever; in order to discourage it's manufacture and use. In
my opinion, this is a major breakthrough, and no delay should be
allowed in bringing it to mass availability. Since it's already
present in our food, at most, it won't do anything.
It is interesting that US Patent #
4847082
was filed by Robert Sabin on January 21, 1987 for a "Method of
treatment of Alzheimer's disease using phytic acid". That was
over 19 years ago. The patent sould have expired by now.
********************************************************************************************
COGNIShunt
An interesting question would be,
what
happens to the amyloid beta if scyllitol dissolves it? Imagine a
jar full of paint thinner. Dip your paintbrush into the jar, and
the paint comes off the brush, but it's now dissolved in the paint
thinner. If the paint thinner evaporates, the once dissolved
paint coats the bottom of the jar. Perhaps if scyllitol dissolves
amyloid beta plaques, then a device such as the COGNIshunt would be
needed to clear out the contaminated fluid.
However, the company that was
developing
the COGNIShunt, Eunoe, Inc. "ceased operations" in 2005. I guess
this means they went out of business. A company called Integra
LifeSciences bought the "intellectual property" of Eunoe, Inc.
But in Integra's December 31, 2006 Annual Report they seem to claim the
cost of this aquisition as a loss:
"In
September
2005,
we
acquired
the
intellectual
property
estate
of
Eunoe,
Inc.
for
$0.5
million
in
cash.
Prior
to
ceasing
operations,
Eunoe,
Inc.
was
engaged
in
the
development
of
its
innovative
COGNIShunt®
system
for
the
treatment
of
Alzheimer’s
disease
patients.
The
acquired
intellectual
property
has
not
been
developed
into
a
product
that
has
been
approved
or
cleared
by
the
FDA and has no future
alternative use other
than in clinical applications involving the regulation of cerebrospinal
fluid. Accordingly, we recorded the entire acquisition price as an
in-process research and development charge in 2005."
Hmmm. Too bad. Seemed
like a
promising idea. Was there any real science behind this? Or
was this some sort of bad joke on us all in order to perpetuate some
sort of investment scam? I hope not.
********************************************************************************************
Clioquinol
- An old drug with new possibilities
[I wonder if clioquinol is
effective against Helicobacter pylori?]
********************************************************************************************
Research
&
Drugs Under Development
[search Google
for AF267B 3/2/06]
********************************************************************************************
Aluminosilicates
If
aluminosilicates are in themselves toxic to nerve cells, then the
elimination of amyloid beta plaques may not be enough. It may
slow down the progression of AD, but not arrest it. The body may
in fact
form Amyloid beta as
a way of protecting the brain from the toxic affects of
aluminosilicates.
But the band aid itself may eventually becomes a problem when
iron (or other
metal ions) attach to the AB. Where do the so called
"globulomers"
come into play? How are they formed? Could the presence of
the aluminosilicates cause the formation of the golbulomers? Or, could
it be a chemical reaction that occurs on the surface of the AB with
iron attached acting as a catalyst that not only forms toxic OH, but
also
toxic globulomers? Also, what role does scyllo-inositol play, and
how
might ethanol consumption botch things up? It would be
informative to know if there
is a relationship between ethanol consumption and AD, either promoting
or inhibitting. Apparently, there have been studies
that show that red wine consumption is protective against AD. It
has been
suggested that
it is the red pigments or tannins. But could it be the ethanol
itself promoting the production of scyllitol in the brain? In
mice,
adding scyllitol
to their diet has been shown to dissolve (or cause the dissolution of)
amyloid
beta plaques. But in humans, the body is capable of synthesizing
scyllitol. Ethanol
consumption has been shown to cause high levels of scyllitol to
accumulate in the
CIS. Either ethanol disrupts the normal metabolic processes that
scyllitol participates in, or it spurs the CIS to produce more
scyllitol than
normal. If the latter is true, then moderate ethanol consumption
should
lead to the elimination of amyloid beta plaques.
Other interesting things to note:
- Desferrioxamine, the iron (and aluminum) chelator has been
proven to arrest the progression of Alzheimer's disease symptoms.
Do iron
or other metal ions bound to beta amyloid plaques play an essential
role in AD? Would deferasirox (Exjade) or myo-inositol hexakisphosphate
(IP6 or
InsP6)be as effective?
- Clioquinol, a antiobiotic and weak metal chelator, has been shown to
halt AD progression and cause the eventual dissolution of AB plaues.
How does this drug afftect globulomers, which appear to be separate
entities from
the plaques? (Perhaps it reduces the Helicobacter pylori bacterial
infection?)
- Could AD be prevented in asymptomatic people by preventing the
formation of aluminosilicates in the brain? This could easily be
accomplished by food supplements and/or dietary changes. [What
foods and/or supplements?]
- If aluminosilicate formation is the beginning of the AD process, is
there a way to directly attack aluminosilicate? Such substances
as hydrochloric acid will disolve it, but in-vivo use of hydrochloric
acid
is impossible. There may be other ways of attacking it.
Perhaps more complex compounds that are able to cross the
blood-brain barrier are
able to disolve aluminosilicates without causing the surrounding tissue
damage.
Another far-out thought is the use of modulated x-rays or microwave
r.f. to impart enough energy to the aluminosilicate that it will
disassociate, and the constituent parts will bind harmlessly with other
materials
(which would have to be made available before applying the energy).
Aluminosilicates are essentially rocks that can not be removed from the
brain by usual methods.
- Could a mechanical pump
(e.g. COGNIShunt®) be used to
remove CIS fluids, and thereby provide a way to remove aluminosilicate
precipitates from the CIS?]
********************************************************************************************
Aluminum:
I found this paper on the effects
of aluminum and tau formation in a rat study.
Do aluminium and/or glutamate induce
Alz-50 reactivity?
"...These
results
suggest:
(1)
aluminium
enters
neurons
and
(2)
aluminium
alone
induces
possible
conformational
changes
in
tau
as
detected
by
the
Alz-50
antibody,
while
aluminium
combined
with
glutamate,
or
glutamate
alone,
do
not."
PMID: 9530999 [PubMed] and,
http://www.springerlink.com/content/m756l301187u1j84/
I wonder if it possible to have
"aluminum poisoning"? I mean, if you
somehow ingest too much aluminum, does it stick around like lead and
mercury? I wonder if there is a way to flush it out. Also, I wonder if
the presence of some other metal, such as mercury or lead or copper,
could interfere with normal aluminum elimination processes, leading to
excess aluminum, and therefore tau problems.
********************************************************************************************
Type
III Diabetes
See
also Coconut Oil, Cinnamon, Methylene
Blue
[Need more info-- research in
Canada-- Certain diabetes drugs help? --
Basic idea is that brain cells don't metabolize sugar well, leading to
build-up of AB plaques. Also find info on recent research
indicating that pancreatic diabetes (types I & II) can be caused by
malfunctioning nerve cells in the pancrease. I wonder if these
two are related?]
Getting
Diabetes
Before 65 More Than Doubles Risk For Alzheimer's Disease
ScienceDaily (Jan. 28, 2009)
"Diabetics have a significantly greater risk of dementia, both
Alzheimer's disease — the most common form of dementia — and other
dementia, reveals important new data from an ongoing study of twins.
The risk of dementia is especially strong if the onset of diabetes
occurs in middle age, according to the study..."
http://www.sciencedaily.com/releases/2009/01/090127152835.htm
Related article appearing February
3, 2009 on ScienceDaily.com about AD as a "type 3 diabetes".
So, the question is, does cinnamon help with sugar metabolism, or with
preventing and reversing tau protein corruption? Or both? Is there
enough of the tau-buster chemical in the typical quantity of cinnamon
people have been taking (about 1/2 tsp) to be effective?
When the news about this "water-soluble component of common cinnamon"
first appeared last year, this was pretty much our only option to fight
tau. Since then, we've learned about methylene blue and niacinamide.
For improving sugar metabolism, we now know about MCT oil and coconut
oil.
Here's the article:
Insulin Is A Possible New Treatment For
Alzheimer's
ScienceDaily (Feb. 3, 2009)
"A Northwestern University-led research team reports that insulin, by
shielding memory-forming synapses from harm, may slow or prevent the
damage and memory loss caused by toxic proteins in Alzheimer's disease.
The findings, which provide additional new evidence that Alzheimer's
could be due to a novel third form of diabetes, will be published
online the week of Feb. 2 by the Proceedings of the National Academy of
Sciences (PNAS)..."
http://www.sciencedaily.com/releases/2009/02/090202174818.htm
********************************************************************************************
Curcumin (Turmeric)
See
also Curcumin
[Need more info-- Read in Reader's
Digest-- villages in India where
there is a low incidence of AD. Could be a genetic thing, like
the villages in Italy where heart disease is rare.]
A report in
the Journal of Biological Chemistry, February 18, 2005 uses the phrase
"disaggregated" amyloid-β fibrils. Does this mean it disolved
amyloid-β?
From Wikipedia: Little
curcumin is
absorbed.
Co-supplementation with 20mg peperine
(extract of black pepper) increased absorption by 2000%. However,
peperine can interfere with the metabolism of other drugs, and should
be taken with caution, if at all. I'm leaning toward not using
peperine.
Curcumin is also a potent iron and
copper chelator.
There are anectdotal reports that
500mg of curcumin twice per day will "normalize" high blood
pressure. Those who are on blood pressure medications for high
blood pressure should be aware of the possibility of overmedication
should this effect of curcumin develop.
********************************************************************************************
Alternative
Alzheimer's
Disease
Treatment
See
also Patricia's Protocol
Nutritional
Alteratives
The following is speculation.
- MCTs
-
to
provide
an
alternative
energy
source
due
to
neuronal
glucose
hypometabolism
- Phytic Acid
- (a.k.a. IP6) to
chelate free metal ions involved with nerve cell damage
- Curcumin
- to dissolve amyloid-β
proteins which might cause neuronal damage
- Lithium
- to prevent tau protein
corruption, induce neurogenesis
- Cinnamon
- to prevent tau proten correuption,
aggregation and undo aggregations
already
formed
- Niacinamide
-
to prevent tau proten
correuption, aggregation and undo aggregations
already
formed
- Methylene
Blue - To prevent tau protein corruption, aggregation, undo
aggregations
already formed, and prevent neuronal senescence.
********************************************************************************************
NPH
(Normal Pressure Hydrocephalus)
Fluid in the ventricals (cavities) of the brain is not removed as it
should causing the cavities to expand and press on the surrounding
brain tissue. This causes a host of mental problems that can be
confused with AD or vascular dementia. However, NPH is treatable
with a shunt to carry away the fluid and restore normal pressure.
Unfortunately, most physicians don't look for this since it only
affects about 5% of dementia suffers, and may not realize that this is
the problem until too much damage has occured. I must thank my
mother in law for showing me an article about this disease that she cut
out of the June 1, 2007 issue of Womans Day magazine. If not for
her, I would never have known about it. Interestingly, a couple
of weeks ago I had a chance to ask a woman who lives a few houses down
the street from me about the condition of her mother. We had
found her wandering the streets a couple of time a few years ago, and
were told that she had AD. It turns out that a observant
radiologist noticed that she in fact had NPH! All those
years she had been treated for AD. But, much damage had been done
by the time they put in the shunt. Even though her symptoms did
improve, she subsequently had a bad fall that cause serious head
trauma, and she isn't doing so well.
Recently, I read an article that said that researchers had determined
that injury to brain tissue could lead to AD. The damaged and
dying cells cause amyloid beta plaques to form. The amyloid beta
plaques are toxic to the healthy surrounding brain cells, and cause
them to expire. This domino effect, if left unchecked, can lead
to full blown AD. An interesting thought is, for people who have
had a brain injury due to either stroke or head trauma, if a substance
was administered that prevented the accumulation of amyloid beta, or
even dissolved it, or at least made it non-toxic, would that be enough
to halt the progression of injury related AD? Hmmm. Perhaps
it would be a good idea to give brain injury patients 300 to 500 mg of curcumin on an empty stomach every day just to be
on the safe side. Since curcumin has no known side effects, is
derived from the curry spice turmeric, and is not expensive; if there
is a chance it works as well on humans as it does on mice, then it
certainly would be a prudent thing to do.
In many countries with socialized medicine (such as Germany), there is
an emphasis on diagnostics to determine who would be likely candidates
for a ventriculoperitoneal shunt (i.e. a tube from the cavity in the
brain to the gut). There is no limit to the demand for
healthcare, so there must some way to ration it. In the U.S., it
is rationed by who can pay for it. In socialist countries, it is
rationed by how valuable the recipient is to the state. So, there
is a lot of literature about how to diagnose NPH based on if the
patient's symptoms improve during testing. Not much, if anything,
about how to halt the progressive decline of someone already suffering
from the condition.
It is interesting to note that there is some disagreement about the
root cause of the disease. Most articles you will read mention
the "reabsorption of the CSF by the subarachnoid villi", yet research
shows that it is in fact the capillaries that do the absorbing.
Perhaps idiopathic (without a known cause) is actually a manifestation
of high blood pressure, and could be treated in a similar manner???
********************************************************************************************
Infrared:
There has been some recent reports that near-infrared light at a
wavelength of 1072nm has proven to have beneficial therapeutic
effects. http://www.sciencebasedmedicine.org/?p=32
http://www.sciencedaily.com/releases/2008/01/080124104917.htm
That
something
this
simple
could
actually
stimulate
the
restoration
of
neurons
definitely
stretches
one's
credulity,
but
given
the
simplicity
of
the
technique,
it
certainly
seems
worth
exploring
further.
The researchers created an helmet with several infrared light emitting
diodes (LEDs) with light output centered at 1072nm on the inside.
It is claimed that a mere 10 minute per day treatment would be all that
is required. The research was first performed, as is usual, on
mice. "Emotional
responses
and
memory
performance
of
middle-aged
CD1
mice
in
a
3D
maze:
Effects
of
low
infrared
light" by S. Michalikovaa, A. Ennaceura,
Author, R. van Rensburgb and P.L. Chazot
Seems simple enough for someone handy with electronics and making
things to create such a device. But a quick search of the
Internet for 1072nm LEDs will result in a problem. 1072nm LEDs
can't be found. 1070nm LEDs are manufactured, but the cost is
prohibitive. Add to this that it is not clear how much light
power, and therefore, how many LEDs are required.
I noticed on Restorelite's web page about
the device
they sell
to treat cold sores
with 1072nm near infrared (NIR) light, that they claim that water is
opaque
to most of the IR spectrum, EXCEPT for a "window at 1072nm". So, I
thought, could an ordinary infrared heating lamp be used as a
broad-spectrum source
with an interposed zip lock
bag full of water as a filter to block the heating IR while
allowing the only the 1072nm light to pass? I found sources
for industrial
IR
lamps that target the NIR spectrum too. However, one can buy a
250W IR heating lamp
of the type used in bathrooms or to keep food warm in restaurants for
about $3. Since the treatment time per day is short, about 10
minutes, such a lamp connected to a timer switch and a bag full of
distilled water might be a very inexpensive source for this light.
Yes, 250W is a
lot of power, most of which is not useful for this purpose. It
reminds me of that old Star Trek episode where these light sensitive
parasitic creatures (which reminded me of flying fried eggs!) make
people go crazy. One gets Spock in the back and to cure him, they
expose him to the full spectrum and intensity of the sun at a close
distance. Of course, this blinds poor old Mr. Spock. Then,
Dr. McCoy figures out that only one wavelength was
needed to destroy the parasite.
I have not been able to confirm that water is transparent to IR light
at 1072nm. All I've been able to find is the following from
Restorelite http://www.restorelite.co.uk/science.php
"Looking at the graph we can see how water
transmits virtually all of
the light within the ultraviolet and visual spectrum wavelengths.
Within most of the infrared wavelengths water acts as a barrier to
light apart from a peak transparency at 1072nm and a smaller optical
window at 1280nm. If we compare this transmission spectrum with the
known and recognised wavelengths at which photobiological reactions
occur we can see quite clearly that living cells have adapted by
evolution to light transmitted by water."
So, according to Restorelite, water is opaque to most of the IR
spectrum, and transparent at 1072nm.
My thoughts were that if water is transparent at 1072nm, then a layer
of water would act as a filter. Only 1072nm (and 1280nm) should
pass through, all other IR light should be blocked. An
incandescent heat lamp will produce
a wide spectrum of light, from visible to far infrared (heating).
Somewhere in there should be 1072. A layer of water in a plastic
bag would filter out the heating IR. Of course, a timer switch as
is commonly found connected to the heat lamps used in showers
and bathrooms would be crucial in order to limit the time that the
light was on, prevent burning someone and prevent
catching something on fire. These bulbs get HOT!
In order to test this, it will be necessary to measure the spectrum and
intensity of the 1072nm infrared light that passes through such a water
filter. Perhaps this could be accomplished using a standard
prism, a light sensor, a protractor, and Snell's law. Based on
where a certain color of visible light appears when passed through the
prism, one could predict using Snell's law what angle 1072nm
(invisible) light would be at,
and measure it's presence. If water is transparent at
1072nm, then this method should work. It will also be important
to know what the
IR transmission spectrum of zip lock plastic bags is. Using LEDs
would be preferable, but until these can be easily obtained, this may
be the only option.
Perhaps there is a ionized gas light source, like neon
lights, that instead of emitting visible light, would emit NIR light
********************************************************************************************
RF (Radio Frequency)
Finally, evidence that cellphone radiation may be
GOOD for you
LA Times January 6, 2010 3:01 pm
Poor cellphones. They get blamed for causing brain
tumors, reducing bone density, prompting headaches and dizziness, and
more. Though most rigorous research has exonerated the phones (not to
mention the laws of physics), many people remain unconvinced.
Now comes a study from the University of South
Florida that links cellphones to Alzheimer’s disease. But there’s a
twist: The researchers found that radiation from the phones protected
mice from the disease, and might even reverse the symptoms...
http://latimesblogs.latimes.com/booster_shots/2010/01/cell-phone-radiation-alzheimers-disease.html
Cell Phone Exposure May Protect Against
and Reverse Alzheimer's Disease
ScienceDaily (Jan. 7, 2010)
..."It surprised us to find that cell phone
exposure, begun in early adulthood, protects the memory of mice
otherwise destined to develop Alzheimer's symptoms," said lead author
Gary Arendash, PhD, USF Research Professor at the Florida ADRC. "It was
even more astonishing that the electromagnetic waves generated by cell
phones actually reversed memory impairment in old Alzheimer's
mice."...The researchers showed that exposing old Alzheimer's mice to
electromagnetic waves generated by cell phones erased brain deposits of
the harmful protein beta-amyloid, in addition to preventing the
protein's build-up in younger Alzheimer's mice... The highly-controlled
study allowed researchers to isolate the effects of cell phone exposure
on memory from other lifestyle factors such as diet and exercise. It
involved 96 mice, most of which were genetically altered to develop
beta-amyloid plaques and memory problems mimicking Alzheimer's disease
as they aged. Some mice were non-demented, without any genetic
predisposition for Alzheimer's, so researchers could test the effects
of electromagnetic waves on normal memory as well.
Both the Alzheimer's and normal mice were exposed
to the electromagnetic field generated by standard cell phone use for
two 1-hour periods each day for seven to nine months. The mice didn't
wear tiny headsets or have scientists holding cell phones up to their
ears; instead, their cages were arranged around a centrally-located
antenna generating the cell phone signal. Each animal was housed the
same distance from the antenna and exposed to electromagnetic waves
typically emitted by a cell phone pressed up against a human head.
If cell phone exposure was started when the
genetically-programmed mice were young adults -- before signs of memory
impairment were apparent -- their cognitive ability was protected...
http://www.sciencedaily.com/releases/2010/01/100106193217.htm
Could Your Cell Phone Help Shield You
From Alzheimer's?
WEDNESDAY, Jan. 6 (HealthDay News via Yahoo! news)
Cell phone addicts of the world, listen up: Electromagnetic waves
emanating from these ubiquitous gadgets may prevent or even reverse
Alzheimer's disease, researchers say.
Normal mice who had long-term exposure to such electromagnetic waves
avoided developing Alzheimer's, while mice who were already sick
started getting better, scientists report in the Jan. 6 issue of the
Journal of Alzheimer's Disease...
http://news.yahoo.com/s/hsn/20100108/hl_hsn/couldyourcellphonehelpshieldyoufromalzheimers
This is very interesting. In a microwave oven, the
RF energy basically causes the water and fat molecules to shake
mechanically in order to cause heat. It doesn't break chemical bonds.
It's often referred to as "non-ionizing radiation".
However, I would be hesitant to expose my head to
this sort of radiation on purpose. If something has the ability to be
helpful, it also has the ability to be harmful, or vice-versa.
I should explain the connection to microwave ovens.
It is thought that the frequency and power levels in the radio
frequency (RF) transmitting devices being discussed only causes heating
of materials. Microwave ovens are a good example of this effect. The RF
energy is converted into heat in the food, and that is all. When the
oven shuts off, no "radiation" remains. Just heat. We may jokingly say
things like we're going to "nuke the popcorn", but that's just a phrase.
Also, microwave ovens are pretty good at confining
the RF energy inside the oven. Unless the door is damaged. To be safe,
I don't stand too close to the door when heating things. No need to
inadvertently cook some body part.
It is assumed that for the heating effect, there is
nothing special about the frequency being used, other than
considerations for interference with other radio communication
services, and the costs involved with the equipment.
The energy levels of hand-held communications
devices is much much less than microwave ovens, radar transmitters,
radio and TV broadcast transmitters, or even cell phone towers.
At the beginning of the 20th century, there was a
fight between Thomas Edison and the Westinghouse company over the power
generation and distribution technology. Edison's empire was built
around the use of "direct current" (DC) electricity. Westinghouse was
promoting Nikola Tesla's "alternating current" system. Radio frequency
radiation is the same idea, but at a much much higher frequency. Edison
produced a lot of propaganda trying to scare people away from using the
Westinghouse system. I think that echos of that propaganda can still be
heard today, even though few realize where it started.
Accidental discoveries are often the most important
ones. I mean, these guys were trying to prove that cell phone use was
unhealthy. Instead, they found something completely different.
Here I'm going to deviate from my normal position
of "what do you have to lose", and advise caution on this one. BUT...
the equipment to do this is readily available, not too expensive, and
well... probably no more harmful than having a cell phone plastered to
the side of your face for two 1hr periods every day. Of course, if you
consider the size of a mouse to that of a man, well, maybe the field
strengths (which translate into power levels required by the
transmitter at whatever distance from the antenna you are) have to be a
bit more. Still, this is easily in reach. For those interested in
pursuing this further, you could look to amateur radio (ham radio)
dealers for transmitting equipment.
Now, as to why it might work. If the only
effect that non-ionizing RF radiation like this has on tissue is to
create heat by shaking water and fat molecules, perhaps the biochemical
process that leads to amyloid beta plaque formation is very heat
sensitive. Perhaps even the slight heating cause by the exposure
to this RF is enough to prevent the plaque formation.
An interesting connection may also be to
"hyperphosphorylation of the tau protein. As I understand it,
these mice they use for these AD experiments do not form the tau tangle
characteristic of human Alzheimer's disease. I could be
wrong. But it was found that anesthesia-induced
hypothermia can cause tau hyperphosphylation. Maybe the
heating of the RF prevents this. It will be interesting to find
out.
********************************************************************************************
Enbrel
(Etanercept):
See also Helicobacter pylori
Drug
'can
reverse
Alzheimer's
symptoms
in
minutes' The Evening Standard
(UK)
"A drug used for arthritis can reverse the symptoms of Alzheimer's "in
minutes". It appears to tackle one of the main features of the disease
- inflammation in the brain."
Lead author of the study Edward Tobinick, of the University of
California and Director of the Institute for Neurological Research
Published in the Journal of Neuroinflammation, 5.2 (Jan 9, 2008): p2
http://www.enbrel.com/
http://en.wikipedia.org/wiki/Etanercept
********************************************************************************************
Polyphenols:
See also cinnamon,
grape seed extract, tannins, tau busters
"Inhibition of Amyloid Fibril Formation by Polyphenols: Structural
Similarity and Aromatic Interactions as a Common Inhibition Mechanism"
http://www.tau.ac.il/lifesci/departments/biotech/members/gazit/documents/52.pdf
I know this is mostly about amyloid-beta (Alzheimer's, or AD), but it
also mentions tau (a form of which is also involved in AD). Tannic acid
and curcumin are also discussed.
While tau, not amyloid-beta (A-beta), is the mechanism which causes
CBD, often people have more than one type of neurodegenerative disease.
There may be an AD component to the symptoms of some CBD sufferers. So,
medications or supplements that will affect A-beta might be beneficial.
["Polyphenols" may be the "cinnamon
proanthocyanidins", "grape seed
extract", and "tannins".]
********************************************************************************************
Tannins and Tannic Acid:
See also cinnamon, grape seed extract, polyphenols, tau busters
I found this interesting chart of some study of the properties of some
compounds to inhibit tau oligomer formation. As I understand it, CBD
(corticobasal degeneration) is thought to be the result of tau protein
accumulations?
http://www.oligomerix.com/Neuroscience2006Poster.pdf
"• Compounds inhibiting aggregation of beta amyloid may inhibit tau
oligomer formation (morin), may have no effect (curcumin) or facilitate
tau oligomer formation (Congo red, ThS)
• Genistein, a neuroprotective antioxidant, may also function as an
inhibitor of aggregation
• A novel compound inhibiting tau oligomer formation was found using
this assay (4-amino 1,1'-azobenzene - 3,4-disulfonic acid)"
Tannic acid is also mentioned as a tau oligomer inhibitor. I know what
tannic acid is. I found that morin is a plant flavonoid like silymarin,
but I don't know much about it.
I wonder what plants are high in morin? I wonder if it crosses the
blood/brain barrier? I wonder if tannic acid does?
If tannic acid is a tau oligomer inhibitor, and if it crosses into the
brain, I wonder if consuming foods or supplements high in tannins would
be helpful.
Wikipedia lists
these foods as high in tannins:
+ tea
+ wine (especially red wine)
+ pomegranates
+ persimmons
+ berries (cranberries
+ beer (some, from hops)
+ legumes (red beans, black beans)
From Wikipedia: "The term [tannin] is widely applied to any large
polyphenolic compound containing sufficient hydroxyls and other
suitable groups (such as carboxyls) to form strong complexes with
proteins and other macromolecules." So, not all tannins are
"tannic acid", and I haven't found which type of tannin would inhibit
tau oligomer formation.
NOTE: "proanthocyanidins" are related to tannins. See Wikipedia.
See also Cinnamon
********************************************************************************************
Anesthetics:
Can inhaled anesthetics initiate a biochemical cascade or domino effect
leading to degenerative neurological diseases? So many people have
noticed a big change in their LO's mental abilities after surgery that
I think there are too many clouds to believe they don't carry the rain.
Symptoms appearing after surgery seems to be a common thread in these
tales. In my mother's case, the surgery was in mid 1999. We started
noticing symptoms in mid 2000. Since we know that CBD progresses
slowly, I think the 1 year between surgery (with inhaled anesthetic)
and the development of symptoms is not out of character. It is also
interesting that the first case of
CBD was identified in 1968, and it was over 10
years later that other cases were reported. Is it possible that the
disease, as we see it now, did not exist before this,
and is being caused by exposure to a chemical? The inhaled anesthetic,
halothane was introduced in 1956, and used through the 1980s. It was
replaced in the 1980s by enflurane and isoflurane. [from Wikipedia]. Prior to
1956, volatile anaesthetics such as diethyl ether and cyclopropane were
used.
The Inhalation Anesthetic Isoflurane
Induces a Vicious Cycle of
Apoptosis and Amyloid ß-Protein Accumulation
The Journal of Neuroscience, February 7, 2007, 27(6):1247-1254;
doi:10.1523/JNEUROSCI.5320-06.2007
http://www.jneurosci.org/cgi/content/abstract/27/6/1247
"... Collectively, these findings suggest that isoflurane can induce
apoptosis, which, in turn, increases BACE and {gamma}-secretase levels
and Aß secretion. Isoflurane also promotes Aß aggregation.
Accumulation of aggregated Aß in the media can then promote
apoptosis. The result is a vicious cycle of isoflurane-induced
apoptosis, Aß generation and aggregation, and additional rounds
of apoptosis, leading to cell death."
Molecular mechanism behind
aggregation of amyloid beta peptide due to
anesthetics
Medical Research News Published: Sunday, 28-Jan-2007
http://www.news-medical.net/?id=21529
"Previous studies by the Pittsburgh researchers found that the inhaled
anesthetics halothane and isoflurane and the intravenous anesthetic
propofol encouraged the growth and clumping of Abeta in a test tube
experiment."
Anesthesia Leads to Tau
Hyperphosphorylation through Inhibition of
Phosphatase Activity by Hypothermia
The Journal of Neuroscience, March 21, 2007, 27(12):3090-3097;
doi:10.1523/JNEUROSCI.4854-06.2007
http://www.jneurosci.org/cgi/content/abstract/27/12/3090
"...We found that, regardless of the anesthetic used, anesthesia
induced rapid and massive hyperphosphorylation of tau, rapid and
prolonged hypothermia, inhibition of Ser/Thr PP2A (protein phosphatase
2A), but no changes in APP metabolism or Aß (ß-amyloid
peptide) accumulation. Reestablishing normothermia during anesthesia
completely rescued tau phosphorylation to normal levels. Our results
indicate that changes in tau phosphorylation were not a result of
anesthesia per se, but a consequence of anesthesia-induced hypothermia,
which led to inhibition of phosphatase activity and subsequent
hyperphosphorylation of tau..."
Hmmm.
Role Of Anesthetics In Alzheimer's
Disease: Molecular Details Revealed
ScienceDaily (Jan. 25, 2007) — Inhaled anesthetics commonly used in
surgery are more likely to cause the aggregation of Alzheimer's
disease-related plaques in the brain than intravenous anesthetics say
University of Pittsburgh School of Medicine researchers in a journal
article published in the Jan. 23 issue of Biochemistry. This is the
first report using state-of-the-art nuclear magnetic resonance (NMR)
spectroscopic technique to explain the detailed molecular mechanism
behind the aggregation of amyloid β (Aβ) peptide due to various
anesthetics...
http://www.sciencedaily.com/releases/2007/01/070125110605.htm
Common Anesthetic May Induce Cell
Death, Generation Of Alzheimer's-Associated Protein
ScienceDaily (Feb. 7, 2007) — A new study has found how one of the most
commonly used anesthetics may produce Alzheimer's-like changes in the
brain. Previous studies have shown that applying the anesthetic
isoflurane to cultured neural cells can lead to generation of
amyloid-beta protein -- the key component of senile plaques seen in the
brains of Alzheimer's patients -- and to the cell-death process known
as apoptosis. In the Feb. 7 Journal of Neuroscience, researchers from
Massachusetts General Hospital (MGH) and colleagues describe how
isoflurane may set off a process in which A-beta generation and
apoptosis interact with and magnify each other. Since this work was
done in cell cultures, it is unknown whether the findings reflect a
possible effect of the anesthetic on human brains...
http://www.sciencedaily.com/releases/2007/02/070207091556.htm
Common Anesthetic Induces
Alzheimer's-Associated Changes In Mouse Brains
ScienceDaily (Nov. 14, 2008) — For the first time researchers have
shown that a commonly used anesthetic can produce changes associated
with Alzheimer's disease in the brains of living mammals, confirming
previous laboratory studies...
http://www.sciencedaily.com/releases/2008/11/081112124410.htm
Inhaled Anesthetics Accelerate
Appearance Of Brain Plaque In Animals
ScienceDaily (Mar. 10, 2007) — Researchers at the University of
Pennsylvania's School of Medicine have discovered that common inhaled
anesthetics increase the number of amyloid plaques in the brains of
animals, which might accelerate the onset of neurodegenerative diseases
like Alzheimer's...
http://www.sciencedaily.com/releases/2007/03/070309141127.htm
Anesthesia And Alzheimer's Disease
ScienceDaily (Apr. 25, 2008) — In studies of human brain cells, the
widely-used anesthetic desflurane does not contribute to increased
production of amyloid-beta protein; however, when combined with low
oxygen conditions, it can produce more of this Alzheimer's associated
protein...
http://www.sciencedaily.com/releases/2008/04/080425123402.htm
Surgery Not Linked to Memory Problems
in Older Patients
ScienceDaily (Nov. 19, 2009) — For years, it has been widely assumed
that older adults may experience memory loss and other cognitive
problems following surgery. But a new study from researchers at
Washington University School of Medicine in St. Louis questions those
assumptions. In fact, the researchers were not able to detect any
long-term cognitive declines attributable to surgery in a group of 575
patients they studied... We were able to use patients as their own
controls before and after surgery and to compare groups of patients
over time, and we did not detect any evidence of a long-term cognitive
decline," Evers says. "Our findings suggest that if older people
physically recover from surgery, they should expect that within six
months or a year, they will return to their previous level of cognitive
ability, too."...
http://www.sciencedaily.com/releases/2009/11/091119111339.htm
Anesthesia Increases Risk of
Developing Alzheimer's Disease in Patients With Genetic Predisposition,
Study Suggests
ScienceDaily (Mar. 25, 2010) — A new study confirms that anesthesia is
safe for normal mice but potentially harmful for mice with genetic risk
factors for Alzheimer's disease (AD). Over several months,
investigations have focused on analyzing the effects of the anesthesia
in normal mice and in mice with mutations that produce AD. The use of
repetitive anesthesia with isoflurane (one of the most common
anesthetics by inhalation) increases the risk of developing changes
similar to those observed in AD brains in mice with mutations of the
amyloid precursor protein (APP)...
http://www.sciencedaily.com/releases/2010/03/100324155359.htm
Alzheimer's: Bigger Molecular-Sized
Anesthetics Do Not Promote Amyloid Beta Peptide Micro-Aggregation
ScienceDaily (Apr. 20, 2010) — Alzheimer's disease (AD) is a
neurodegenerative disorder affecting millions of people worldwide and
has become a major global concern. Uncontrolled oligomerization
(aggregation) of Aβ peptide is the hallmark of AD and it is believed to
be causally related to AD pathomechanism. Intensive research
(biophysical, animal model and clinical) is underway to investigate the
cause of this unexplained aggregation of Aβ peptide, which is probably
triggered by some agent or process in predisposed individuals, and
subsequently to trace the molecular pathways involved in the
phenomenon. In the April issue (Vol 20, 1, pages 127-134, 2010)
of the Journal of Alzheimer's Disease, a laboratory observation based
on state-of-the-art nuclear magnetic resonance spectroscopy, suggests a
molecular pathway for a possible link between anesthesia and Aβ peptide
aggregation. It was observed that the larger sized intravenous
anesthetic diazepam (both at clinical and at very high concentration),
when incubated in isolation with amyloid beta-peptide, does not promote
aggregation in laboratory results monitored serially, even sixty-three
days after the onset of incubation. However, if diazepam is
co-incubated with halothane (a general inhaled anesthetic with small
molecular size, and often used as an add-on in the clinical setting),
profound amyloid beta-peptide oligomerization is observed, and the
presence of the larger molecular-sized diazepam is rendered ineffective
in preventing Aβ oligomerization...
http://www.sciencedaily.com/releases/2010/04/100421102528.htm
********************************************************************************************
Copper:
********************************************************************************************
Lithium:
See also Tau Busters
Lithium at 50: have the
neuroprotective effects of this unique cation
been overlooked?
Biological Psychiatry. 1999 Oct
1;46(7):929-40. PMID: 10509176 [PubMed]
Manji HK, Moore GJ, Chen G.
Department of Psychiatry and
Behavioral Neurosciences,
Wayne State University School
of Medicine, Detroit, Michigan 48201, USA.
"Recent advances in cellular
and molecular biology have resulted in the
identification of two novel, hitherto completely unexpected targets of
lithium's actions, discoveries that may have a major impact on the
future use of this unique cation in biology and medicine. Chronic
lithium treatment has been demonstrated to markedly increase the levels
of the major neuroprotective protein, bcl-2 in rat frontal cortex,
hippocampus, and striatum. Similar lithium-induced increases in bcl-2
are also observed in cells of human neuronal origin, and are observed
in rat frontal cortex at lithium levels as low as approximately 0.3
mmol/L. Bcl-2 is widely regarded as a major neuroprotective protein,
and genetic strategies that increase bcl-2 levels have demonstrated not
only robust protection of neurons against diverse insults, but have
also demonstrated an increase the regeneration of mammalian CNS axons.
Lithium has also been demonstrated to inhibit glycogen synthase kinase
3 beta (GSK-3 beta), an enzyme known to regulate the levels of
phosphorylated tau and beta-catenin (both of which may play a role in
the neurodegeneration observed in Alzheimer's disease). Consistent with
the increases in bcl-2 levels and inhibition of GSK-3 beta, lithium has
been demonstrated to exert robust protective effects against diverse
insults both in vitro and in vivo. These findings suggest that lithium
may exert some of its long term beneficial effects in the treatment of
mood disorders via underappreciated neuroprotective effects. To date,
lithium remains the only medication demonstrated to markedly increase
bcl-2 levels in several brain areas; in the absence of other adequate
treatments, the potential efficacy of lithium in the long term
treatment of certain neurodegenerative disorders may be warranted."
Inhibition of glycogen synthase
kinase-3 by lithium correlates with
reduced tauopathy and degeneration in vivo
Proceedings of the National
Academy of Sciences of the United States
of America
PNAS | May 10, 2005 | vol. 102
| no. 19 | 6990-6995
"Neurofibrillary tangles
composed of hyperphosphorylated, aggregated
tau are a common pathological feature of tauopathies, including
Alzheimer's disease. Abnormal phosphorylation of tau by kinases or
phosphatases has been proposed as a pathogenic mechanism in tangle
formation. To investigate whether kinase inhibition can reduce
tauopathy and the degeneration associated with it in vivo, transgenic
mice overexpressing mutant human tau were treated with the glycogen
synthase kinase-3 (GSK-3) inhibitor lithium chloride. Treatment
resulted in significant inhibition of GSK-3 activity. Lithium
administration also resulted in significantly lower levels of
phosphorylation at several epitopes of tau known to be
hyperphosphorylated in Alzheimer's disease and significantly reduced
levels of aggregated, insoluble tau. Administration of a second GSK-3
inhibitor also correlated with reduced insoluble tau levels, supporting
the idea that lithium exerts its effect through GSK-3 inhibition.
Levels of aggregated tau correlated strongly with degree of axonal
degeneration, and lithium-chloride-treated mice showed less
degeneration if administration was started during early stages of
tangle development. These results support the idea that kinases are
involved in tauopathy progression and that kinase inhibitors may be
effective therapeutically."
http://www.pnas.org/cgi/content/abstract/102/19/6990?ck=nck
Lithium delays progression of
amyotrophic lateral sclerosis.
"ALS is a devastating
neurodegenerative disorder with no effective
treatment. In the present study, we found that daily doses of lithium,
leading to plasma levels ranging from 0.4 to 0.8 mEq/liter, delay
disease progression in human patients affected by ALS. None of the
patients treated with lithium died during the 15 months of the
follow-up, and disease progression was markedly attenuated when
compared with age-, disease duration-, and sex-matched control patients
treated with riluzole for the same amount of time. In a parallel study
on a genetic ALS animal model, the G93A mouse, we found a marked
neuroprotection by lithium, which delayed disease onset and duration
and augmented the life span. These effects were concomitant with
activation of autophagy and an increase in the number of the
mitochondria in motor neurons and suppressed reactive astrogliosis.
Again, lithium reduced the slow necrosis characterized by mitochondrial
vacuolization and increased the number of neurons counted in lamina VII
that were severely affected in saline-treated G93A mice. After lithium
administration in G93A mice, the number of these neurons was higher
even when compared with saline-treated WT. All these mechanisms may
contribute to the effects of lithium, and these results offer a
promising perspective for the treatment of human
patients affected by ALS."
http://www.pnas.org/cgi/reprint/105/6/2052
Here is another take on the use of lithium:
[From "The Misunderstood Mineral Part 1" By Jonathan V. Wright, M.D.]
http://www.tahoma-clinic.com/lithium1.shtml
I suggest reading the whole article, but here is an excerpt...
Taking (grey) matters into your own hands
"Hercule
Poirot,
Agatha
Christie's
famous
fictional
detective,
had
an
amusing
quirk
in
his
incessant
concern
for
his
"little
grey
cells."
I
thought
of
Hercule
several
years
ago
when
I
saw
the
following
headline
in
an
issue
of
the
Lancet:
"Lithium-induced
increase
in
human
brain
grey
matter."
"That may not sound like an
earth-shattering piece of news, but it
actually was quite a major discovery. To that point, medical experts
believed that once our brains matured, it was all downhill from then
on. Decades of autopsies, x-rays, and, more recently, brain scans have
repeatedly shown that brains shrink measurably with aging. But
according to their report in the Lancet, Wayne State University
(Detroit) researchers found that lithium has the ability to both
protect and renew brain cells.1 Eight of 10 individuals who took
lithium showed an average 3 percent increase in brain grey matter in
just four weeks.
"Lithium may help to generate
entirely new cells too: Another group of
researchers recently reported that lithium also enhances nerve cell DNA
replication.2 DNA replication is a first step in the formation of a new
cell of any type.
"The Wayne State study used
high-dose lithium, but I'm certainly not
using that amount myself, nor do I recommend it. Prescription
quantities of lithium just aren't necessary for "everyday" brain cell
protection and re-growth. Studies done years ago have shown that very
low amounts of lithium can also measurably influence brain function for
the better."
[From "The Misunderstood Mineral Part 2" By Jonathan V. Wright, M.D.]
Lithium fights crime and some of your
most nagging health concerns
"Turns out it's not only the
strict use of the death penalty lowering
crime rates in some areas of Texas. And while I'm sure "Dubya" would be
quick to take credit, it's not stricter laws or changes in sentencing
guidelines either. Using 10 years of data accumulated from 27 Texas
counties, researchers found that the incidence of homicide, rape,
burglary, and suicide, as well as other crimes and drug use, were
significantly lower in counties whose drinking water supplies contained
70-170 micrograms of lithium per liter than those with little or no
lithium in their water.
"The researchers wrote: "These
results suggest that lithium at low
dosage levels has a generally beneficial effect on human
behavior...increasing the human lithium intakes by supplementation, or
the lithiation [adding lithium] of drinking water is suggested as a
possible means of crime, suicide, and drug-dependency reduction at the
individual and community level."
"And that's not to mention all
of the lithium health benefits we went
over in Part 1: It may be useful in treating Alzheimer's disease,
senile dementia, and possibly Parkinson's disease. Lithium not only
protects brain cells against normal wear and tear, but also offers
additional protection against a whole variety of toxic molecules,
including patent medications. It can also promote brain cell
regeneration and increase brain cell mass. In essence, the research
suggests that lithium is a brain anti-aging nutrient.
"All of these results are every
bit as good as (if not better than) the
data that led to dumping toxic waste (fluoride) into so many public
water supplies. So why haven't public health and safety "authorities"
been pushing for further intensive research on water-borne lithium and
criminal behavior?"
http://www.tahoma-clinic.com/lithium2.shtml
Some more on using lithium:
Rescuing Fruit Flies from Alzheimer's
Disease
ScienceDaily (July 16, 2010) — Investigators have found that fruit fly
(Drosophila melanogaster) males -- in which the activity of an
Alzheimer's disease protein is reduced by 50 percent -- show
impairments in learning and memory as they age. What's more, the
researchers were able to prevent the age-related deficits by treating
the flies with drugs such as lithium, or by genetic manipulations that
reduced nerve-cell signaling. The research team -- Thomas A. Jongens,
Ph.D., associate professor of Genetics at the University of
Pennsylvania School of Medicine; Sean M. J. McBride M.D, Ph.D. and
Thomas McDonald M.D., at the Albert Einstein College of Medicine; and
Catherine Choi M.D., Ph.D. at Drexel University College of Medicine --
worked with the familial form of Alzheimer's disease (FAD), an
aggressive form of the disease that is caused by mutations in one of
the two copies of the presenilin (PS) or amyloid precursor protein
(APP) genes. Studies in animal models have previously shown that the
FAD-linked PS mutations lead to less presenilin (psn) protein activity.
Their findings are published in the Journal of Neuroscience. "The
results from our study suggest a new route to explore for the treatment
of familial Alzheimer's disease and possibly the more common sporadic
forms of Alzheimer's disease," notes Jongens. "They also reveal that
proper presenilin activity levels are required to maintain normal
cognitive capabilities during aging."...
http://www.sciencedaily.com/releases/2010/07/100715172014.htm
********************************************************************************************
Cinnamon:
See also Tau Busters
I ran across this rather tantalizing statement in a Web
page: "cinnamon
extract inhibits the aggregation of tau and disassembles fibers that
have already formed"
The title is "CINNAMON EXTRACT USEFUL FOR INHIBITING THE AGGREGATION
OF TAU AND TREATING ALZHEIMER'S DISEASE" by a researcher at the
University of California, Santa Barbara by the name of Donald Graves
Published on 2/22/2008???
http://www.ibridgenetwork.org/UCSB/cinnamon-extract-useful-for-inhibiting-the-aggregation-of-tau
Here is the first piece of information I found about this:
Cinnamon
extract
inhibits
the
aggregation
of
tau
and
disassembles
fibers
that
have
already
formed
"Researchers at the University
of California, Santa Barbara have
discovered an extract of common cinnamon that contains a class of small
organic molecules that inhibit several key processes in Alzheimer's
disease. The cinnamon extract inhibits the aggregation of tau and
disassembles fibers that have already formed, suggesting that
neurofibrillary tangles can possibly be reversed by these compounds.
The extract exhibits potent inhibitory activity, is orally available,
water-soluble, non-toxic, and the bioactive molecules are likely brain
permeable. The extract is readily produced in large quantities and can
be encapsulated in powder form for oral administration. These
properties make the cinnamon extract a highly favorable substance for
development into an effective therapeutic to slow or prevent
Alzheimer's disease."
http://www.ibridgenetwork.org/innovations/download_tech_brief/3417
I'm amazed that in the whole wide universe of the Internet, there is
little mention of this.
What I have found out is that there are several types of "cinnamon",
depending on what plant they come from. Look it up on Wikipedia: http://en.wikipedia.org/wiki/Cinnamon
There is no indication of which species of cinnamon plant was used in
the research. Since Chinese cinnamon (cassia, or Cinnamomum aromaticum)
is the most common species found in the United States, and the research
was done at the University of California in Santa Barbara; it is
reasonable to assume that they used cassia cinnamon.
There is some debate about a toxic components of cassia cinnamon,
especially coumarin (which
apparently isn't present in significant proportions in Ceylon
cinnamon). The toxins seem to be
present in the lipid (fat) soluble components, but not the water
soluble parts. Now, in his previous research publications, Graves was
looking at "water soluble" components of cinnamon for controlling sugar
metabolism. Perhaps a connections between some recent speculation that
Alzheimer's disease is, in some cases, a product of sugar metabolism,
in essence a "type III" diabetes; and the possible use of a cinnamon
extract to treat AD, may have lead them to examine the effects on tau.
This would then be one of those surprise discoveries. So, they
were looking at water
soluble cinnamon extracts. I take it from reading
other web pages on using cinnamon to control diabetes (http://www.mendosa.com/newsletter_april.htm)
that
the
water
soluble
extracts
are
relatively
easy
to
separate
by
"boiling
cinnamon
in
water
and
pouring
off
the
soluble
portion
and
discarding
the
solid
cinnamon."
(See Patricia's Protcol for more
on making a "cinnamon tea"-- extracting
the water soluble components of
cinnamon.)
Just how much coumarin is in cassia cinnamon? According to the
German government, from "between approximately 2100 and approximately
4400 mg/kg cinnamon powder". I've found several references on
various web sites stating that cassia has a 5% courmarin content.
I think these folks must be mathematically challenged. There are
1000 grams in a kilogram. There are 1000 milligrams in a
gram. So, if there are 4400 mg per kg, that is 4400mg per
1000x1000mg or 4400/1,000,000 or 0.44%. Maximum. So, if you take
1 gram of cassia cinnamon, you get 4.4mg of coumarin. The recommended Tolerable Daily Intake (TDI)
established by the European Food Safety Authority is 0.1 milligram per
kilogram (kg) of body weight. There are 2.2 pounds per
kilogram. So, a 120 lb woman would weight about 55 kg. She
would have to eat 1250mg of cassia cinnamon. If
this is a problem, use the "aqueous extract".
The following is from a German government publication, "High daily
intakes of cinnamon: Health risk cannot be ruled out" BfR Health
Assessment No. 044/2006, 18 August 2006:
When
it
comes
to
individual
ingredients
the
coumarin
concentration
in
cassia
cinnamon
is particularly
problematic.
The
values
measured
in
cinnamon
capsules
(CVUA
Stuttgart)
confirm the
high coumarin levels in
cassia cinnamon (between approximately 2100 and approximately 4400 mg/kg cinnamon powder) as
had also been previously measured by CVUA (Münster, BfR 2006). By
contrast, coumarin can only be found in traces or below the measurement
limit in Ceylon cinnamon.
Depending on the dose recommendation the taking of capsules with
cinnamon powder can lead to an exceeding
of the tolerable daily intake of 0.1 milligram coumarin per kilogram
body weight that can be ingested daily over a lifetime without posing a
risk to health (Tolerable Daily Intake, TDI) established by the
European Food Safety Authority (EFSA).
The consumption of capsules
containing cassia cinnamon powder is also likely to lead to an exceeding of the
above-mentioned TDI for coumarin. Solely regarding this coumarin
exposure, there are
theoretically two
steps which could be taken to reduce it:
¤ the replacement of
cassia cinnamon by Ceylon cinnamon (so far we do not know whether it has a similar effect
on the blood sugar level of diabetics to that of cassia cinnamon; the recommendation of
replacement is subject to the assumption that the effects of cassia cinnamon are
confirmed by reliable studies),
¤ the use of aqueous
extracts of cassia cinnamon which, according to the CVUA analyses
in Stuttgart, leads to far
lower coumarin exposure (exhaustion of the TDI only in the single-digit percentage
range). These extracts probably also have a far lower proportion
of essential oils (in
particular cinnamaldehyde).
http://www.bfr.bund.de/cm/245/high_daily_intakes_of_cinnamon_health_risk_cannot_be_ruled_out.pdf
[I am highly suspicious of EU regulation and certification, and of that
from any individual EU country. There is a high degree of
industrial protectionism in them. They create artificial barriers
to competitors entering a market. The governments protect their
businesses, not only from foreign competitors, but from domestic
entrepreneurs. The "old boys network". People are expected to not
disrupt the order of things, and definitely not aspire to attain wealth
beyond their class.]
I haven't been able to find much more about this, but as you can
imagine, I'm extremely interested. I don't know what the "extract" is,
exactly, and if regular old cinnamon has enough of this stuff to do the
job. You would think that, if real, this would be a MAJOR news
story. Yet I found it difficult to even find mention of it.
I want to make it clear that I'm not saying that this WILL work. There
haven't been any formal studies done yet. At least, I haven't
been able to find any. All I've found are reports from people
giving it to someone afflicted with AD. I believe that it MIGHT
work; that it is cheap, easy enough and safe enough to try. You
don't have to get government funding, insurance coverage, or a
physician to administer it. If it doesn't work, you are out a
small amount of money, time, and someone ate a lot of cinnamon for two
months. But if it does work... Instead of watching your loved one
slip away from you a little each day, here you have the chance to DO
something more than just watch in frustration.
In the bigger picture are the millions of other people suffering with
these tauopathies, and their families who have no idea that there is a
spice in their own cupboards that might help. If this works-- if
this water-soluble cinnamon extract actually is able to interrupt the
tau protein step of the disease process-- millions of people might find
relief from these horrible afflictions. But they will need to
know about it, and they will need to believe in it enough to try it.
On the down side, the price of cinnamon is likely to skyrocket. I
wonder if it is possible to buy "cinnamon futures"? ;)
Another point. These tauopathies eventually lead to the loss of
brain tissue. Interrupting the disease process will not restore
this. Other compounds or therapies will be needed to do that job,
if it is possible. The information and memories lost with when
neurons expire obviously can not be recovered. The conditions and
processes that produced the corrupted tau in the first place will not
be affected and will continue to exist. The best you can hope for
is some slight recovery while neurons that are still viable but just
inactive come back on line, followed by a period of
stabilization. I would be happy with this.
Update Feb. 25, 2009
I have found more information! A patent appliation on the World
Intellectual Property Organization web site, proves that this idea is
real. It was published on October 9, 2008. I still wonder if there is
enough of this stuff in raw, ground cinnamon, of whatever species, to
help. For now, I can still hope.
For those who doubted...
Title:
PROANTHOCYANIDINS
FROM
CINNAMON
AND
ITS
WATER
SOLUBLE
EXTRACT
INHIBIT
TAU
AGGREGATION
Abstract: Compositions
comprising proanthocyanidin compositions (e.g.
those extracted from cinnamomum species) that are observed to bind tau
and inhibit its aggregation as well as methods for making and
using such compositions are
disclosed. In certain embodiments of the
invention, the proanthocyanidins can be used as a probe to identify
and/or characterize tau isoforms in a variety of contexts. In other
embodiments of the invention, these compositions are used in methods
designed to treat neurological disorders associated with tau
aggregation (e.g. Alzheimer's disease).
Pub. No.: WO/2008/121412
International Application No.:
PCT/US2008/004236
Publication Date: 09.10.2008
International Filing Date: 31.03.2008
IPC: A61K 36/54 (2006.01)
Applicants: THE REGENTS OF THE
UNIVERSITY OF CALIFORNIA [US/US]; 1111
Franklin Street, 12th Floor,
Oakland, CA 94607 (US) (All Except US).
LEW, John [CA/US]; (US) (US
Only).
GRAVES, Donald, J. [US/US];
(US) (US Only).
Inventors: LEW, John; (US).
GRAVES, Donald, J.; (US).
http://www.wipo.int/pctdb/en/wo.jsp?WO=2008121412
http://www.wipo.int/pctdb/en/wo.jsp?WO=2008121412&IA=US2008004236&DISPLAY=DESC
Update November 5, 2009
Cinnamon Extract Inhibits Tau
Aggregation Associated with Alzheimer's Disease In Vitro
Journal Journal of Alzheimer's Disease
Publisher IOS Press
ISSN 1387-2877 (Print)
1875-8908 (Online)
Issue Volume 17, Number 3 / 2009
DOI 10.3233/JAD-2009-1083
Pages 585-597
Subject Group Neurosciences
Authors
Dylan W. Peterson1,
Roshni C. George1, Francesca
Scaramozzino1, Nichole E. LaPointe1, Richard A.
Anderson2, Donald J. Graves1, John Lew1
1Department of
Molecular, Cellular, and Developmental
Biology, University of California, Santa Barbara, CA, USA
2Beltsville Human
Nutrition Center, Beltsville, MD, USA
Abstract
An aqueous extract of Ceylon
cinnamon (C. zeylanicum) is found to
inhibit tau aggregation and filament formation, hallmarks of
Alzheimer's disease (AD). The extract can also promote complete
disassembly of recombinant tau filaments and cause substantial
alteration of the morphology of paired-helical filaments isolated from
AD brain. Cinnamon extract (CE) was not deleterious to the normal
cellular function of tau, namely the assembly of free tubulin into
microtubules. An A-linked proanthocyanidin trimer molecule was purified
from the extract and shown to contain a significant proportion of the
inhibitory activity. Treatment with polyvinylpyrolidone effectively
depleted all proanthocyanidins from the extract solution and removed
the majority, but not all, of the inhibitory activity. The remainder
inhibitory activity could be attributed to cinnamaldehyde. This work
shows that compounds endogenous to cinnamon may be beneficial to AD
themselves or may guide the discovery of other potential therapeutics
if their mechanisms of action can be discerned.
http://iospress.metapress.com/content/06h5g61751404678/
http://www.ncbi.nlm.nih.gov/pubmed/19433898?dopt=Abstract
http://www.diabetesaction.org/site/DocServer/Tau_J_Alzheimers_09.pdf?docID=781
Here is some information on Dr.
Richard Anderson:
http://www.sparc.ars.usda.gov/pandp/people/people.htm?personid=144
There is also a commercial water-soluble product available called
Cinnulin for those who want to avoid the inconvenience of making the cinnamon tea. It appears to be made
using the process detailed in the above patent application. This
is just for your information and should not be construed as an
endorsement of the product.
Cinnamon may also inhibit the
effects of TNF-alpha
(See Immune System effects and Enbrel for
more info.)
Research Project: CHROMIUM AND POLYPHENOLS FROM CINNAMON IN THE
PREVENTION AND ALLEVIATION OF GLUCOSE INTOLERANCE
Research
Project:
CHROMIUM
AND
POLYPHENOLS
FROM
CINNAMON
IN
THE PREVENTION
AND ALLEVIATION OF GLUCOSE INTOLERANCE
Location: Diet, Genomics and
Immunology Lab
Title: Tumor Necrosis
Factor-alpha Stimulates the Overproduction of Intestinal Apolipoprotein
B48-containing Very Low Density Lipoproproteins
Authors
item Qin,
Bolin - ARS RESEARCH ASSOCIATE
item
Khosrowl, Adeli - UNIV OF TORONTO, ONTARIO
item
Anderson, Richard
Research conducted
cooperatively with:
item
Integrity Nutraceuticals International
Submitted to: Diabetes
Publication Type: Abstract
Publication Acceptance Date:
March 12, 2008
Publication Date: June 10, 2008
Citation: Qin, B., Khosrowl,
A., Anderson, R.A. 2008. Tumor Necrosis Factor-alpha Stimulates the
Overproduction of Intestinal Apolipoprotein B48-containing Very Low
Density Lipoproproteins. Diabetes. 888:102.
Technical Abstract: Tumor
necrosis factor-alpha(a)(TNFa), a proinflammatory cytokine, is involved
in obesity-associated pathologies including type 2 diabetes and
atherosclerosis. TNFa enhanced postprandial apoB48-VLDL1 overproduction
by about 89% compared with the control after 90 min olive oil loading;
TNFa did not significantly affect apoB-48 VLDL2 expression. In
addition, acute oral treatment of Cinnulin PF (a water soluble cinnamon
extract, 50 mg per kg BW), which has insulin-like metabolic actions,
inhibits TNFa-induced postprandial overproduction of apoB48-containing
lipoproteins. Fresh isolated primary enterocytes of hamsters were
stimulated with TNFa (10 ng per mL for 4hs), to investigate the
expression of insulin signaling pathway genes, insulin receptor (IR),
IRS1, IRS2, Akt1, and phosphatidylinositol3-kinase (PI3K), and the key
regulators of lipid metabolism, microsomal triglyceride transfer
protein(MTP), sterol regulatory element-binding protein (SREBP)1c, and
phosphatase and tensin homology (PTEN), as well as the inflammatory
factor genes, ILa, ILBeta, IL6, and TNFa. Quantitative real-time PCR
assays showed that TNFa decreased IR, IRS1, IRS2, PI3K and Akt1 mRNA
levels of enterocytes by 45, 59, 60, 59, and 38%, respectively, of
controls. In summary, TNFa stimulates the postprandial apoB-48 VLDL1
overproduction via regulation of mRNA levels of proteins in the
intestinal insulin signaling pathway, and perturbs the expression of
MTP, PTEN, and SREBP1c, as well as enhances the expression of
inflammation factors. Taken together with previous studies, the
improvement of insulin sensitivity will inhibit the overproduction of
apoB48-containing lipoproteins induced by factors and diets that
increase TNFa levels.
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=222820
And also...
Location:
Diet,
Genomics
and
Immunology
Lab
(United
States
Department
of
Agriculture
Agricultural Research Service)
Project Number:
1235-51520-037-00
Project Type: Appropriated
Start Date: Nov 18, 2004
End Date: Jan 22, 2009
Objective:
Overall objective of the
proposed research is to help control the incidence of impaired glucose
metabolism and decrease the conversion of glucose intolerance to
diabetes. Specific objectives include the following. 1)Elucidate the
role of Cr in the onset of impaired glucose metabolism using a
stress-induced rat model for Cr deficiency. 2)Determine methods to
assess Cr status and elucidate its functions in human nutrition.
3)Define the role and mechanistic effects of insulin potentiating
polyphenols from cinnamon on intracellular signals that regulate
insulin-induced glucose uptake and oxidative stress.
Approach:
Compounds that enhance insulin
activity lead to a more sensitive response to insulin and improve
glucose tolerance. Increased levels of stress lead to loss of nutrients
including chromium (Cr), a nutrient that is involved in glucose and
insulin metabolism. We propose to elucidate the role of Cr in a
stress-induced diabetes rat model. Steroid-induced diabetes in people
taking steroids such as prednisone has been shown to be reversed by
increased intake of chromium. This project is designed to elucidate the
role of the chronic stress of low level administration of the steroid,
dexamethasone, in the augmentation of deficiency of chromium. These
studies will facilitate our collaborative human study to elucidate the
roles of Cr in human nutrition and also methods to assess Cr status.
There are currently no reliable methods to assess Cr status. This study
will combine reliable analytical measures of chromium status with
studies to elucidate the function of chromium in human nutrition. We
also propose to define the role and mechanistic effects of insulin
potentiating polyphenols from cinnamon on intracellular signals that
regulate insulin-induced glucose uptake, oxidative stress and NF-'B
activation. These studies should lead to a greater understanding of the
roles of chromium and polyphenols from cinnamon in the prevention and
alleviation of glucose intolerance and type 2 diabetes.
http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=408448
Update
July
30,
2010
There has been some reports on
the Alz.org
message
board that whole cinnamon has been more effective than the
water-soluble extract. Most people have been opting to use Ceylon
cinnamon rather than the cheaper and more readily available cassia
(Chinese) cinnamon because Ceylon cinnamon contains less of the
blood-thinning chemical coumarin. This allows people to take more
of it-- say 1 tsp three times per day-- without being concerned with
the buildup of coumarin.
********************************************************************************************
Infection
and Immune System Response:
See also Helicobacter pylori
"A number of
chronic diseases are in fact caused by one or more
infectious agents. For example, stomach ulcers are caused by
Helicobacter pylori, chronic lung disease in newborns and chronic
asthma in adults are both caused by Mycoplasmas and Chlamydia
pneumonia, while some other pathogens have been associated with
atherosclerosis. The realization that pathogens can produce slowly
progressive chronic diseases has opened new lines of research into
Alzheimer's disease."
Here are some excerpts from an article found on ScienceDaily.com:
Cold
Sore
Virus
Linked
To
Alzheimer's
Disease:
New
Treatment,
Or
Even
Vaccine
Possible
ScienceDaily
(Dec. 7, 2008)
"Professor
Itzhaki explains: "We suggest that HSV1 enters the brain in
the elderly as their immune systems decline and then establishes a
dormant infection from which it is repeatedly activated by events such
as stress, immunosuppression, and various infections."
"The ensuing
active HSV1 infection causes severe damage in brain cells,
most of which die and then disintegrate, thereby releasing amyloid
aggregates which develop into amyloid plaques after other components of
dying cells are deposited on them."
"Her
colleague Dr Matthew Wozniak adds: "Antiviral agents would inhibit
the harmful consequences of HSV1 action; in other words, inhibit a
likely major cause of the disease irrespective of the actual damaging
processes involved, whereas current treatments at best merely inhibit
some of the symptoms of the disease..."
"They believe
the herpes simplex virus is a significant factor in
developing the debilitating disease and could be treated by antiviral
agents such as acyclovir, which is already used to treat cold sores and
other diseases caused by the herpes virus."
http://www.sciencedaily.com/releases/2008/12/081207134109.htm
Another earlier article:
New Evidence Found Linking Herpes And
Alzheimer’s
ScienceDaily
(May 12, 2000)
"Could Lead
to New Treatments Targeting the Herpes Virus"
"Researchers
have long suspected a connection between the herpes virus
and Alzheimer’s disease. A new study provides a potential explanation
that could lead to development of a vaccine to prevent the disease or
new drugs to treat it, according to the researchers. The study appears
in the May 16 issue of Biochemistry, a peer-reviewed publication of the
American Chemical Society, the world’s largest scientific society."
"Researchers
at the University of California, Irvine, demonstrated that
a synthetic protein that resembles the herpes simplex 1 virus (HSV-1)
mimics the structure and function of a protein called beta-amyloid, a
toxic agent that accumulates in the brains of Alzheimer’s patients."
"Genetic
sequencing revealed that two-thirds of a portion of the viral
protein is identical to the beta-amyloid protein. The researchers
showed that, like beta-amyloid, it could kill brain neurons, a key
feature in the development of Alzheimer’s. Moreover, in laboratory
experiments, the viral protein formed abnormal twisted fibers like
those found in the brains of Alzheimer’s patients — the definitive
hallmark of the disease..."
http://www.sciencedaily.com/releases/2000/05/000512083302.htm
And, another...
Cold Sore Virus Might Play Role In
Alzheimer's
ScienceDaily
(Jan. 3, 2007)
"A gene known
to be a major risk factor for Alzheimer's disease puts
out the welcome mat for the virus that causes cold sores, allowing the
virus to be more active in the brain compared to other forms of the
gene..."
http://www.sciencedaily.com/releases/2007/01/070103110103.htm
From these articles (I suggest reading the full articles and others you
can find), it seems to be a reasonable theory that this HSV1 virus
invades the brain as one's immune system weakens with age, stress or
truma. Infected cells then expire, leaving behind amyloid beta (AB).
Some people's central nervous system (NS) are probably better than
other people's at removing this amyloid beta. So, most people develop
the classic characteristics of AD, which are loss of brain mass, clumps
of AB, and intracellular tau tangles. Others, whose CNS clears out the
AB still suffer the loss of brain mass as the disease ravages the
brain, and other proteins accumulate, such as just the tau tangles or
clumps of tau. Could this be behind CBD?
What this theory says to me is that there is a chance that many of what
today seem like separate neurodegenerative diseases may actually be
manifestations of the same root cause: A virus. But it also says that
most of the things we have been trying will ultimately fail. Enbrel
addresses inflammatory responses. Methylene blue and cinnamon attack
tau and maybe help neurons live longer. MCT's (coconut oil) and
cinnamon address sugar metabolism. Lithium fights tau corruption.
Curcumin is used in the hopes of reducing the AB load. Likewise with
all of the other the pharmaceuticals and supplements we have discussed
and had such hopes for.
But, none of these attack what might be the root cause, HSV1; and if
they don't, then their positive effects are all doomed to eventually be
overwhelmed by the virus' insatiable hunger for brain cells. It is
every bit as horrific as the plot from some "B" science fiction movie.
Does anyone have experience with this drug they mention in the first
article, acyclovir? What is the likelihood that a physician would
prescribe this drug to someone suspected of having AD just to see if it
helps?
[NOTE: Jan. 17, 2009: Recently, some people have mentioned in
posts to some discussion forums that curcumin, resveratrol and lauric
acid (coconut oil!) may
fight the HSV-1 virus. Need to find more info and links to sources.]
I've read before about urinary tract infections causing a sudden
worsening of AD symptoms. The question that came to my mind was, why
does this happen?
I think I have a possible answer. And with this answer comes the
opportunity to do something for someone suffering from AD.
There was a small two-year study done in Greece that was recently
published. 50 subjects with AD symptoms were tested for the presence of
a Helicobacter pylori (Hp) infection (the bacteria that is said to
cause most stomach ulcers). It turned out that nearly 90% of the
subjects had H.pylori. So the researchers treated the infection.
Eradication of the bacteria was successful in about 85% of the cases.
The amazing thing was that in ALL of the 85% where the eradication of
the H.pylori was successful, their AD symtoms did not progress over the
2 years of the study, and in fact, their mental abilities improved
somewhat. Even though this was a very small study with only 50
participants, to me the results say that there might be something to
this that we can use.
How can an H.pylori infection of the stomach affect the brain? The
researchers speculated that the body produces substances in its fight
against the bacteria that might have deleterious side effects when the
blood carries them to the brain. One of these substances is called
"tumor necrosis factor alpha", (TNF-alpha).
Last year, there was some excitement over a drug being researched
called "Rember". It was theorized that this drug acted directly on the
tau protein of the neurons to prevent them from becoming corrupted, or
to even dissolve clumps and tangles of currupted tau that had already
formed. The researchers were disappointed to discover that the highest
dose pill they used was not effective because, unlike its smaller dose
cousins, the 100mg pill dissolved in the intestines rather than the
stomach. What is "Rember"? Well, it is essentially methylene blue. And
methylene blue happens to be an antibiotic known to kill off H.pylori.
Let's go to the other side of the Earth for another piece of the
puzzle. In California there is this controversial physician, Dr.
Tobinick, who discovered by accident that when he injected the
arthritis drug Enbrel into the spines of his patients suffering from
spinal arthritis, sometimes their AD symptoms would suddenly improve in
a matter of minutes. How could this happen? Well, Enbrel blocks the
effects of TNF!
What does this have to do with urinary tract infections? Could a UTI
cause the body to produce TNF? A quick search of the Internet with
Google using the two phrases "tumor necrosis factor" "urinary tract
infection" makes me think that, yes indeed, we may have the connection.
The body produces TNF in its fight against the UTI bacteria, which is
then circulated by the blood to the brain.
What can you do with this? Find out if your loved one with AD symptoms
has a chronic infection. Look for H.pylori, a UTI, maybe even pockets
of infection in the jaw left over from a tooth problem. Another
possibility is the presence of Lyme disease. If they have one of these
infections, get it treated.
********************************************************************************************
Helicobacter
pylori
(the
stomach
ulcer
bacteria):
See also Infection and Immune System Response
Broccoli Sprouts
Cinnamon
Enbrel
Methylene
blue
Rember
Can a Helicobacter pylori bacterial infection be the root cause of many
(75%) cases of Alzheimer's disease cases? Genetic or other
factors would then comprise the root cause of the other 25%.
"Eradication of
Helicobacter pylori may be beneficial in the management
of Alzheimer’s disease"
Abstract:
Infectious agents have been proposed as potential causes of
Alzheimer’s disease (AD). Recently, we documented a high prevalence of
Helicobacter pylori (Hp) infection in patients with AD. We aim to
access the effect of Hp eradication on the AD cognitive (MMSE: Mini
Mental State Examination and CAMCOG: Cambridge Cognitive Examination
for the Elderly) and functional (FRSSD: Functional Rating Scale for
Symptoms of Dementia) status parameters. In the first part of the
study, a total of 50 consecutive patients with AD and 30 age-matched
anaemic controls underwent an upper gastrointestinal endoscopy, and
gastric mucosal biopsies were obtained to detect the presence of Hp
infection by histologic analysis and rapid urease test. Serum
anti-Hp-specific IgG level was analysed by enzyme-linked immunosorbent
assay. In the second part, Hp-positive AD patients received a triple
eradication regimen (omeprazole, clarithromycin and amoxicillin), and
all patients were followed up for 2 years, while under the same
treatment with cholinesterase inhibitors. Hp was detected in 88% of AD
patients and in 46.7% of controls (P < 0.001). Hp eradication was
successful in 84.8% of treated patients. At the 2-year clinical
endpoint, cognitive and functional status parameters improved in the
subgroup of patients where Hp eradication was successful (P < 0.001
and P = 0.049 for MMSE and CAMCOG, respectively; P < 0.001 for
FRSSD), but not in the other patients. Hp eradication may positively
influence AD manifestations, suggesting a possible common link between
Hp and AD.
http://www.springerlink.com/content/83147756538x7031/?p=4d07d65b60894df3bab4620921dcd1e6&pi=2
What caught my attention is this statement: "At the 2-year clinical
endpoint, cognitive and functional status parameters improved in the
subgroup of patients where Hp eradication was successful ..., but not
in the other patients. Hp eradication may positively influence AD
manifestations, suggesting a possible common link between Hp and AD."
I have to connect the links here to AD here.
We've recently read that corrupted tau proteins can have
characteristics similar to the prions of "mad cow disease", scrapie,
chronic wasting disease of deer, and CJD of humans:
Rogue
protein
'spreads
in
brain'
BBC Sunday, 7
June 2009
Scientists
have shown a rogue protein thought to cause Alzheimer's can
spread through the brain, turning healthy tissue bad. They believe the
tau protein may share characteristics with the prion proteins which
cause vCJD. When injected into the brains of healthy mice it triggered
formation of protein tangles linked to Alzheimer's. However, experts
stressed the Nature Cell Biology study did not mean tau could be passed
from person to person. Tau is a protein present in all nerve cells,
where it plays a key role in keeping them functioning properly. But a
rogue form of the protein can trigger the formation of protein clumps
within nerve cells known as neurofibrillary tangles. It is thought that
these tangles are likely to be a major cause of Alzheimer's disease...
Tau is a protein present in all nerve cells, where it plays a key role
in keeping them functioning properly. But a rogue form of the protein
can trigger the formation of protein clumps within nerve cells known as
neurofibrillary tangles. It is thought that these tangles are likely to
be a major cause of Alzheimer's disease.
http://news.bbc.co.uk/2/hi/health/8084787.stm
It is interesting to note that the degeneration tends to follow the
path of neural networks:
Neuronal
subpopulations
and
genetic
background
in
tauopathies:
a
catch
22
story?
L.
Bue´e*, A. Delacourte
Neurobiology
of Aging 22 (2001) 115–118
"...these
vulnerable neurons degenerate following precise pathways.
Regarding encephalopathy such as PEP, it is clear that a virus follows
neural networks for its propagation. It is now well established that
there is also a sequential degeneration of vulnerable networks of
neurons in AD and PSP. In AD, both biochemical and neuropathological
studies show that NFT formation starts in the hippocampal formation
(from transentorhinal to entorhinal and then hippocampus), progresses
sequentially as follows anterior, inferior and medium temporal cortex,
and then spreads into polymodal association areas, unimodal areas and
primary and/or sensory areas..."
http://www.alzheimer-adna.com/pdf/2001/2001Bueecatch22.pdf
[Note:
here
seems
to
be
a
similar
progression
in
Parkinson's
disease:
How The Pathology Of Parkinson's Disease
Spreads
ScienceDaily
(July 29, 2009) — Accumulation of the synaptic protein
alpha-synuclein, resulting in the formation of aggregates called Lewy
bodies in the brain, is a hallmark of Parkinson's and other related
neurodegenerative diseases. This pathology appears to spread throughout
the brain as the disease progresses. Now, researchers at the University
of California, San Diego School of Medicine and Konkuk University in
Seoul, South Korea, have described how this mechanism works... "The
discovery of cell-to-cell transmission of this protein may explain how
alpha-synuclein aggregates can pass to new, healthy cells," said first
author Paula Desplats, project scientist in UC San Diego's Department
of Neurosciences. "We demonstrated how alpha-synuclein is taken up by
neighboring cells, including grafted neuronal precursor cells, a
mechanism that may cause Lewy bodies to spread to different brain
structures."... In these studies, autopsies of deceased Parkinson's
patients who had received implants of therapeutic fetal neurons 11 to
16 years prior revealed that alpha-synuclein had propagated to the
transplanted neurons...
http://www.sciencedaily.com/releases/2009/07/090727191914.htm]
Can toxins produced by bacteria initiate the process?
Can a Hp infection explain the success some people have been
experiencing with the "perispinal Enbrel injections"? Enbrel is thought
to work by inhibiting the effects of "tumor necrosis factor alpha",
(TNF-alpha). And guess what
substance a Helicobactor pylori infection in the stomach causes the
body to produce? Yep, TNF-alpha. In the full text of the Heliobacter
article, it says on page 8, "However, Hp, an extracellular
bacterium,
could affect the brain and other target organs, such as the heart,
indirectly, through the release of numerous cytokines, including
TNF-[alpha] acting at a distance."
To me, this gives a reason for why the perispinal injection of Enbrel should work, why reports of its success are
not merely wishful thinking. It's the link to a cause that validates
the idea. I think that the success of Enbrel
also supports the theory
for the mechanism by which Hp in the stomach affects the brain.
For those experiencing improvements from Enbrel
treatments, I think
this says, check to
see if there is also an H-pylori infection present. If so, treating the
H.pylori infection may increase the time needed between treatments, or
may even eliminate the need for Enbrel treatments entirely.
(There may be other
bacteria or viruses that could cause the body to produce TNF-alpha,
such as Herpes simplex virus type 1
(HSV1) and Chlamydophila (Chlamydia) pneumoniae.)
Here is the link to the full text of the paper. Even for those like me,
still in the process of learning language of biochemistry, it is
understandable enough for one to grasp the ideas. (It is rarely
necessary to know the intimate details of how a computer works in order
to be effective in using a computer.):
http://www.springerlink.com/content/83147756538x7031/fulltext.pdf
Wild speculation time:
If an Hp infection turns out to be the initiating factor in many cases of AD, then for
those currently suffering with the disease, I would
first stop the progression, then eradicate the infection(s). We appear
to have at least two ways to stop the progression at this time: Enbrel
or the MCT oil
regimen. They don't seem to conflict, targetting different steps of the
disease process, so it would probably be wise to use both. There
may also be some benefit to suing the tau
busters, as this may attack even another step in the disease
process.
Obviously, if eliminating a chronic bacterial infection reduces the
body's production of TNF-alpha to normal levels, there would be no need
for TNF-alpha blocking drugs such as Enbrel. This news will not be
greeted with enthusiasm by the pro-Tobinick faction. Nor will it
make the "there's
nothing we can do, we're powerless, everyone should just die now and
get it over with" crowd happy.
In the Greek study, Hp was detected in 88% of AD patients. Hp
eradication was successful in
84.8% of treated patients, which is about normal for all cases of Hp
infection. If you multiply 88% by 84.8%, you get ~75%... which,
coincidently, seems to be about
the percentage of people that are helped by MCT/coconut
oil.
I'm sure people are thinking, my loved one never had a stomach ulcer,
yet now she has AD. Well, one does not need to have an ulcer to
have an Hp infection. I don' t know where they got this statistic, but
I found...
90% of the
people with an Helicobacter pylori (Hp) infection do not have
stomach
trouble or ulcers. Or, to put it another way, only 10% of people with
an Hp infection have
stomach trouble.
"H.
pylori gastritis produces no symptoms in 90 percent of infected
persons. The prevalence of H. pylori infection varies geographically
and has been demonstrated to be as high as 52 percent in the United
States. Factors associated with higher infection rates are increasing
age, African-American or Hispanic race, lower levels of education, and
birth in a developing country."
http://www.aafp.org/afp/20020401/1327.html
I'm sure that not everyone with an Hp infection will
develop AD. However, one of the greatest risk factors for developing AD
is age. Perhaps the cumulative effects of a chronic H.pylori
infection explains this.
I
looked up
the statistics for Aricept. It is only effective for 50% of the people
who take it, and then, it is only effective for about 6 to 12 months.
If
the statistics of the Greek study holds true, then one could expect the
eradication of an Hp infection to be effective for about 75% of those
treated, and that the effect should last at least 2 years (which was
the
limit of how long they tracked the test participants).
If I were in charge of an insurance company, I think I would consider
the cost of treating an Hp infection followed by the stabilization of
the patient as a discount when compared to six months worth of Aricept,
followed by the cost of a nursing home.
There
are some interesting charts in the full text .pdf file of the paper:
http://www.springerlink.com/content/83147756538x7031/fulltext.pdf
The original article was from researchers in Greece, so the statistics
given for the prevalence of Hp infection may be different in your
country.
Another thought I had was that the treatment for Hp is a two or three
week course of multiple antibiotics. This probably knocks out a whole
bunch of other bacteria in all parts of the body. What if the culprit
is NOT Hp, but gets killed off by the Hp antibiotics?
Whatever the case, I think there are some simple tests such as a blood
test for Hp antibodies, or this "breath test" that could be done
relatively easily. I think it's worth asking the phsyicians about.
From what I've read, this bug is particularly hard to treat. They seem
to be using a cocktail of three drugs for something like 14 days. The
antibiotics can have side effects, making the treatment unpleasant.
I
started
thinking, what substances, other than prescription antibiotics, inhibit
or eliminate Hp bacteria? I've heard that Pepto-Bismol will (the
bismuth in it). And then I remembered that in Chinese medicine, cinnamon
had long been used to treat stomach problems. A quick search of the
Internet found that yes, indeed, cinnamon has been and is being
investigated for its anti-Hp potential. But, which component of
cinnamon is it? I don't know. This may mean that using whole ground
cinnamon may be more effective than using extracts.
Some
foods or
spices may also reduce the Hp infection, but I haven't found anything
yet, other than prescription antibiotics, that will eliminate it.
Broccoli sprouts,
dill, and cinnamon may be good candidates.
"Probiotics", or "good bacteria" may help by crowding out the
H-pylori. Others will have to be explored.
For broccoli sprouts,
it's the sulforaphane in them that seems to help.
Of
course, if you can get a physician to test for Hp, and then prescribe
antibiotics, go for it!
There
are
probably several conditions that eventually lead to AD. This particular
one would not address genetic causes or exposure to a toxin.
I doubt that this is the end of the story. Never the less, I think that
the idea of Helicobacter pylori being involved should be aggresively
researched. If eliminating a
Helicobacter pylori infection worked for 3 out of 4 cases, that would
be a good start! How much needless suffering could be avoided if
people only knew this?
I started thinking about other antibiotics. I read that methylene blue
is used as an antibiotic to treat urinary tract infections, malaria,
and even bacteria "infections" in fish aquariums. Does it also
eliminate Hp? Could that be why it has helped people with AD (Rember
study)? Well, maybe. I found this article, but I don't have the whole
text. It is intriguing.
"Evaluation of
methylene blue and triple therapy for eradication of
Helicobacter pylori infection in the nude mouse model"
KARITA M. (1)
; TADA M. (1) ; OKITA K. (1) ; TSUDA M. ; NAKAZAWA T.
International
symposium on Helicobacter pylori and its diseases No5,
Tokyo , JAPON (04/04/1992)
1993, vol. 5,
SUP1 (6 ref.), pp. S79-S83
European
journal of gastroenterology & hepatology
Abstract:
"Objective: To determine how far Helicobacter pylori
infection can be eradicated with methylene blue and triple therapy
(amoxicillin, metronidazole, bismuth subnitrate), using a nude mouse
model. Methods: Four weeks after inoculation of H. pylori into the
stomach, two groups of nude mice were administered methylene blue or
triple therapy via the stomach for 1 week. A control group of nude mice
was given culture fluid alone after the inoculation. The number of H.
pylori and histological changes in the stomach were determined weekly
for 5 weeks, starting from the completion of drug administration.
Results: In the methylene blue treatment group, the concentration of H.
pylori was significantly reduced for 1-3 weeks after treatment compared
with the control group..."
http://cat.inist.fr/?aModele=afficheN&cpsidt=4893514
It is interesting to
note in this article about the experimental drug Rember,
ICAD: Tau-Targeted
Therapy Slows Alzheimer's Progression for 19 Months it says,
"In
the
trial
reported
here,
321
patients
were
randomized
to
30
mg,
50
mg,
100
mg
or
placebo.
The
drug,
Dr.
Wischik
said,
was
effective
when
it
dissolved
in
the
stomach,
but
was
not
effective
when
the
drug
was
absorbed
through
the
intestines.
This
was
an
issue
for
the
100-mg
dose,
which
had
'absolutely
no
activity
because
it
didn't
dissolve
in the stomach.'"
http://www.medpagetoday.com/MeetingCoverage/ICAD/10320
As I wrote above, the
Helicobacter pylori bacteria finds methylene
blue to be rather toxic. This tends to support the idea that the
dominant effect of Rember may not have been as a "Tau aggregation
inhibitor
(TAI)", but rather as an antibiotic. This would explain why the 100mg
dose was not effective when it dissolved in the intestines, whereas the
30 and 60mg doses, which disolved in the stomach, were effective. The
antibiotic effect of the rember (which is
basically methylene blue)
reduced the H.pylori infection, thereby reducing the TNF levels. It
seems to me that anyone getting Enbrel
injections to reduce TNF levels
should take a hard look at this.
A final thought on this topic, this concept may also apply to the other
rare neurodegenerative diseases such as PSP, CBD, the FTD, etc.
********************************************************************************************
eSadists,
Kevorkians, Ghosts, and the Company of Misery
Over the course of the last two years, I have run across a curious
breed of people who seem to get off on the pain and suffering of
others. In general, they're called "sadists". That's not really
something new, but these people I'm talking about inhabit Internet
discussion groups, often obtaining a measure of control by becoming
"moderators", or
cozying up to the moderators. They maintain a facade of
compassion and seem very knowledgeable about the disease. I call these
people "eSaists". They seem
to feed off the fear, despair and desperation of people watching
helplessly as their loved-ones slowly slip away. They are like some
creature from an old episode of Star Trek or the "horla" of 19th
century French literature.
An eSadist enjoys the suffering of others, and often infests discussion
groups where hopelessly incurable diseases are discussed. They talk
incessantly about things like hospice, durable powers of attorney, and
brain donations. They taunt desperate people with "possible cures" and
new developments that are years and years away. "They're working on it
now, but it won't be available to help your loved one."
The real test is when a possible treatment is brought up that those
interested could start pursuing TODAY. The eSadist will balk at the
idea. They will openly attack not only the idea, but the person who
dares to introduce the subject. If they have the power to squelch the
idea and the person, they will use it.
Another key characteristic of
an eSadist is that since a possible treatment available immediately
might rob them of sad and desperate souls to taunt and feed off of,
they will never pass along their knowledge of a ray of hope for an
effective treatment. They will keep it to themselves, and only dispense
their knowledge when their credibility and motives are challenged.
Kevorkians behave in a similar manner, but they have given up. To
them, death is the only answer. They are tired, and want to be
free from the burden of caring and worrying about their loved
one. They don't want there to be an effective therapy. They
don't want to preserve a life that they have judged to be not worth
living any longer. Their excuse is that that don't want their
loved one to suffer any longer. But the real reason is
selfishness, and that they can not admit.
Those in the Company of Misery are like ghosts haunting an old wishing
well. They have already lost a loved one to some
incurable disease. Like the Kevorkians and the eSadists, they
really don't want to see any drug, supplement or therapy work,
especially if such could have
been available to help their departed loved one, if only they had known
in time. They just can't move on with their lives. They want
others to join in. Misery loves company.
It is wise to identify personalty types like these, and avoid them.
********************************************************************************************
Rember
See also Methylene blue
Helicobacter
pylori
Hsp70
Tau
Busters
Rember: "The drug
works by dissolving the tangle of tau fibres
which releases waste products that kill nerve cells, and by preventing
the fibres from becoming tangled."
http://www.dailymail.co.uk/health/article-1039677/Daily-pill-halts-Alzheimers-hailed-biggest-breakthrough-disease-100-years.html
http://www.msnbc.msn.com/id/25918231
http://www.telegraph.co.uk/news/uknews/2471076/Alzheimerandrsquos-sufferers-given-hope-by-new-generation-of-drugs.html
Cost/Availability: Unobtainable for the next couple of
years. Except,
Rember is said to be a close cousin of methylene blue!
It is interesting to note that in this article about Rember,
ICAD: Tau-Targeted
Therapy Slows Alzheimer's Progression for 19 Months it says,
"In
the
trial
reported
here,
321
patients
were
randomized
to
30
mg,
50
mg,
100
mg
or
placebo.
The
drug,
Dr.
Wischik
said,
was
effective
when
it
dissolved
in
the
stomach,
but
was
not
effective
when
the
drug
was
absorbed
through
the
intestines.
This
was
an
issue
for
the
100-mg
dose,
which
had
'absolutely
no
activity
because
it
didn't
dissolve in the stomach.'"
http://www.medpagetoday.com/MeetingCoverage/ICAD/10320
As I wrote elsewhere, the Helicobacter pylori bacteria finds methylene
blue to be rather toxic. This tends to support the idea that the
dominant effect may not have been as a "Tau aggregation inhibitor
(TAI)", but rather as an antibiotic. This would explain why the 100mg
dose was not effective when it dissolved in the intestines, whereas the
30 and 60mg doses, which disolved in the stomach, were effective. The
antibiotic effect of the rember (which is basically methylene blue)
reduced the H.pylori infection, thereby reducing the TNF levels. It
seems to me that anyone getting Enbrel injections to reduce TNF levels
should take a hard look at this.
********************************************************************************************
Methylene Blue
See also Rember
Helicobacter
pylori
Hsp70
Tau Busters
Potential
Alzheimer's, Parkinson's
Cure Found In Century-old Drug
ScienceDaily
(Aug. 18, 2008)
"A new study
conducted by researchers at Children's Hospital &
Research Center Oakland shows that a century-old drug, methylene blue,
may be able to slow or even cure Alzheimer's and Parkinson's disease.
Used at a very low concentration – about the equivalent of a few
raindrops in four Olympic-sized swimming pools of water – the drug
slows cellular aging and enhances mitochondrial function, potentially
allowing those with the diseases to live longer, healthier lives."
"Methylene
blue, first discovered in 1891, is now used to treat
methemoglobinemia, a blood disorder. But because high concentrations of
methylene blue were known to damage the brain, no one thought to
experiment with low concentrations. Also, drugs such as methylene blue
do not easily reach the brain."
http://www.sciencedaily.com/releases/2008/08/080818101335.htm
No mention in the full article of its possible effect on tau, which,
given the close connection between Rember and methylene blue, is
interesting.
Given this new piece of information, and the other article about
Rember, I checked into the availability of methylene blue.
"Methylene blue has been around forever, used for
urinary tract
infections, malaria, and all sorts of things, up to treating protozoal
infections in fish tanks. (For that matter, it's turned up over the
years as a surreptitious additive to blueberry pies and the like,
turning the unsuspecting consumer's urine greenish/blue, generally to
their great alarm: a storied med school prank from the old days)."
http://pipeline.corante.com/archives/2008/07/31/rember_for_alzheimers_methylene_blues_comeback.php
Sure enough, methylene blue is available from pet supply stores. Here
is an example:
http://www.petsolutions.com/default.aspx?ItemId=64000052&EID=SZ64000052&SID=SHZIL
I don't know if I would try this pet store MB or not. I offer it only
for your
information. It doesn't seem to hurt fish. But according to that
other article from Science Daily on August 18, it is "used at a very
low concentration – about the equivalent of a few raindrops in four
Olympic-sized swimming pools of water". Seems kind of dilute to
me.
********************************************************************************************
The circular
logic of "Standard of Care"
(Don't expect any help from your physician)
You: "Hi, doctor. Thanks for calling me back. As you
know, my mother has this incurable and ultimately fatal disease.
I read that methylene blue was found to halt it's progression.
Can we try giving it to my mother for a month and see how she does?"
Physician: "Well, no one in our area is using it for that, so I
can't. It wouldn't be the current standard of care."
You: "So no physician will use it until some other physician uses it?"
Physician: "That's right. You will have to find a clinical study
somewhere."
You: "Is this 'standard of care' a legal restriction?"
Physician: "No. But if a procedure isn't the current
'standard of care', I can't prescribe it."
You: "If it's not a legal restriction, who says you can't?"
Physician: "Well, if I were to use a treatment that was not the
current 'standard of care', and the patient has a bad reaction, then
there would be legal problems."
You: "So this is to avoid law suits?"
Physician: [crickets]
You: "She's got a terminal illness, what can it hurt?"
Physician: "You will have to find a research hospital studying
this."
You: "What if I can't? What if all the physicians say they can't
try it because no one else has tried it yet?"
Physician: "I can't help you."
You: "You can help, but you won't. You know what's going to
happen if something isn't done."
Physician: "I can't help you."
You: "I can get methylene blue from other sources, but I would
rather have the prescription drug and medical supervision."
Physician: "You mean you are going to try to treat her yourself?"
You: "If I have to. You won't. No physician will because no
other physician will. You leave me no choice."
Physician: "You can't do that."
You: "Why not?"
Physician: "You might hurt her."
You: "Hurt her? She's dying!
I
have
to
try
something."
Physician: "You can't try something no one else has tried. How do
you know that it will work?"
You: "I don't know. But I do know what happens to someone with
this disease if the current 'standard of care' is all they get."
The medical establishment derrides "alternative medicine" as quackery,
but it is too timid to try anything without a massive clinical trial
with double-blind studies and millions of dollars spent of physican
salaries to oversee it. Who will pay for such an expensive thing
if there is no money to be made on the drug being tested? And
even if some government or charity ponies up the cash, how long will it
take for the study to be completed? You can count on it taking
way to long. Your loved one will be past the point of help, and
the outcome for them will be the same as if you tried an experimental
drug and it failed.
Make good friends of Ms. Google and Mr. Yahoo. Search. Keep searching,
and never ever give up. Motivation sometimes finds answers that
education misses.
********************************************************************************************
Coconut Oil
See also Coconut Oil
Recipes
Doctor says an
oil lessened
Alzheimer's effects on her husband
By Eve
Hosley-Moore, Times Correspondent
In print:
Wednesday, October 29, 2008
" In Alzheimer's disease, certain brain cells may
have difficulty
metabolizing glucose, the brain's principal source of energy. Without
fuel, these precious neurons may begin to die. But researchers have
identified an alternative energy source for brain cells — fats known as
ketone bodies, explained Dr. Theodore VanItallie, a medical doctor and
professor emeritus at the College of Physicians and Surgeons at
Columbia University in New York City. He has been researching ketones
for more than 35 years.
"Ketones are
a high-energy fuel that nourish the brain," VanItallie
said, explaining that when you are starving, the body produces ketones
naturally. When digested, the liver converts MCT oil into ketones. In
the first few weeks of life, ketones provide about 25 percent of the
energy newborn babies need to survive.
"As Dr.
Newport continued to read about MCT oil and the new medication,
she discovered something surprising: Non-hydrogenated coconut oil is
more than 60 percent MCT oil, and this medication derived its MCT oil
from this readily available tropical tree."
http://www.tampabay.com/news/aging/article879333.ece
See also Scyllitol
Impaired Energy
Metabolism Linked
With Initiation Of Plaques In Alzheimer's Brain
ScienceDaily
(Jan. 3, 2009)
"Here, for
the first time we provide evidence linking impaired energy
metabolism, an AD-relevant stress, with BACE1 translation mediated by
eIF2α phosphorylation," says Dr. Vassar. "Our findings implicate
phosphorylated eIF2α in both the initiation and progression of sporadic
AD. Future experiments will determine whether inhibition of eIF2α
phosphorylation could be an efficacious therapeutic approach for the
prevention and treatment of AD..."
http://www.sciencedaily.com/releases/2008/12/081224215536.htm
Brain Starvation
As We Age Appears To
Trigger Alzheimer's: Improving Blood Flow
To Brain Is Preventive Strategy
ScienceDaily
(Dec. 28, 2008)
"A slow,
chronic starvation of the brain as we age appears to be one of
the major triggers of a biochemical process that causes some forms of
Alzheimer's disease..."
http://www.sciencedaily.com/releases/2008/12/081224215704.htm
Blood Sugar
Linked To Normal
Cognitive Aging
ScienceDaily
(Dec. 31, 2008)
"Maintaining
blood sugar levels, even in the absence of disease, may be
an important strategy for preserving cognitive health, suggests a study
published by researchers at Columbia University Medical Center
(CUMC)..."
http://www.sciencedaily.com/releases/2008/12/081230072238.htm
As far as I
can determine, the test "FDG-PET" ([(18)F]-fluoro-deoxyglucose
positron
emission
tomography) detects areas
of the brain experiencing glucose
hypometabolism.
Typical cerebral metabolic patterns
in neurodegenerative brain diseases.
Mov Disord. 2010 Jul 28. [Epub ahead of print]
Teune LK, Bartels AL, de Jong BM, Willemsen AT, Eshuis SA, de Vries JJ,
van Oostrom JC, Leenders KL.
Department of Neurology, University Medical Center Groningen,
Groningen, The Netherlands.
Abstract
The differential diagnosis of neurodegenerative brain diseases on
clinical grounds is difficult, especially at an early disease stage.
Several studies have found specific regional differences of brain
metabolism applying [(18)F]-fluoro-deoxyglucose positron emission
tomography (FDG-PET), suggesting that this method can assist in early
differential diagnosis of neurodegenerative brain diseases.We have
studied patients who had an FDG-PET scan on clinical grounds at an
early disease stage and included those with a retrospectively confirmed
diagnosis according to strictly defined clinical research criteria.
Ninety-six patients could be included of which 20 patients with
Parkinson's disease (PD), 21 multiple system atrophy (MSA), 17
progressive supranuclear palsy (PSP), 10 corticobasal degeneration
(CBD), 6 dementia with Lewy bodies (DLB), 15 Alzheimer's disease (AD),
and 7 frontotemporal dementia (FTD). FDG PET images of each patient
group were analyzed and compared to18 healthy controls using
Statistical Parametric Mapping (SPM5).Disease-specific patterns of
relatively decreased metabolic activity were found in PD (contralateral
parietooccipital and frontal regions), MSA (bilateral putamen and
cerebellar hemispheres), PSP (prefrontal cortex and caudate nucleus,
thalamus, and mesencephalon), CBD (contralateral cortical regions), DLB
(occipital and parietotemporal regions), AD (parietotemporal regions),
and FTD (frontotemporal regions).The integrated method addressing a
spectrum of various neurodegenerative brain diseases provided means to
discriminate patient groups also at early disease stages. Clinical
follow-up enabled appropriate patient inclusion. This implies that an
early diagnosis in individual patients can be made by comparing each
subject's metabolic findings with a complete database of specific
disease related patterns. (c) 2010 Movement Disorder Society.
PMID: 20669302
http://www.ncbi.nlm.nih.gov/pubmed/20669302
Fluorodeoxyglucose-Positron Emission
Tomography in the differential diagnosis of early-onset dementia: a
prospective, community-based study
Peter K Panegyres, Jeffrey M Rogers, Michael
McCarthy, Andrew Campbell and Jing Shan Wu
1 Neurodegenerative Disorders Research, 185 York St, Subiaco WA,
Australia
2 Neurosciences Unit, Health Department of Western Australia,
Perth WA, Australia
3 Department of Nuclear Medicine, Royal Perth Hospital, Perth WA,
Australia
4 WA PET/Cyclotron Service, Sir Charles Gairdner Hospital, Perth
WA, Australia
BMC Neurology 2009, 9:41doi:10.1186/1471-2377-9-41
Background
The aim of this study was to evaluate the diagnostic accuracy of
positron emission tomography (PET) using F18 fluorodeoxyglucose (FDG)
in the differential diagnosis of early-onset Alzheimer's disease (AD)
and other dementias in a community-dwelling population.
Methods
A prospective sample of 102 individuals presenting consecutively to a
primary care centre for examination of suspected early-onset dementing
diseases. The mean age of symptom onset of dementia in our patients was
60.06 ± 4.28 years (mean ± 1SD, 95% lower confidence
intervals (CI) 54.75, upper 63.37). Patients were evaluated using
standard clinical criteria for the diagnosis of dementia. Functional
neuroimaging data was obtained and nuclear medicine physicians blind to
the clinical diagnosis generated FDG-PET diagnoses. Final clinical
diagnoses based on all available data were then established and
compared against PET diagnoses.
Results
Forty-nine patients received a final clinical diagnosis of early-stage
AD (MMSE score 20.97 ± 5.10). There were 29 non-AD demented
patients, 11 depressed patients and a miscellaneous group of 13
patients. Among patients with AD, the sensitivity and specificity of
FDG-PET was 78% (95% CI: 66–90%) and 81% (95% CI: 68–86%),
respectively. The positive likelihood ratio (PLR) for a FDG-PET scan
positive for the diagnosis of AD was 4.11 (95% CI: 2.29–7.32) and
negative likelihood ratio (NLR) for a negative FDG-PET scan in the
absence of AD was 0.27 (95% CI: 0.16–0.46). The pre-test probability
was 48% and post-test probability was 79.02%. The specificity of
FDG-PET in the differential diagnosis of other dementias, including
frontotemporal dementia, was greater than 95%.
Recruitment methods in this study provide a sample that may be more
representative of patients in the general population and indicate that
FDG-PET imaging can contribute to the diagnosis of AD in younger adults
with major increases in the positive likelihood rates and post-test
probability.
Conclusion
The high specificity of FDG-PET suggests this technique might help in
the diagnosis of frontotemporal dementia and other forms of early-onset
dementia...
http://www.biomedcentral.com/1471-2377/9/41
Posts and articles from Dr. Mary Newport about MCT oil and coconut oil:
Doctor says an
oil lessened
Alzheimer's effects on her husband
Eve
Hosley-Moore, Times Correspondent
St.
Petersburg Times
In Print:
Wednesday, October 29, 2008
"After two
weeks of taking coconut oil, Steve Newport's results in an
early onset Alzheimer's test gradually improved says his wife, Dr. Mary
Newport. Before treatment, Steve could barely remember how to draw a
clock. Two weeks after adding coconut oil to his diet, his drawing
improved. After 37 days, Steve's drawing gained even more clarity. The
oil seemed to "lift the fog," his wife says..."
http://www.tampabay.com/news/aging/article879333.ece
More posts by Dr. Newport
Dr. Newport's web site: http://www.coconutketones.com
Dr. Newport's blog: http://coconutketones.blogspot.com
Dr. Newport's April 2009 "update"
(.pdf version)
Dr. Newport's September
2009 "Diet guidelines" (.pdf version)
Update 11/15/2009:
I thought I should bring Dr. Newport's Thursday, October 29, 2009 blog
entry to your attention. There are some very intriguing ideas here.
And, they involve supplements that could easily be obtained by the
average person who would like to pursue these ideas further.Here is an
excerpt:
I hear from some people who are very discouraged
because they do not see improvement in their loved one with
Alzheimer's. About half of the people in the MCT oil studies declined
minimally rather than improving, but declined less than the people who
took the placebo. So this strategy may be worthwhile continuing even if
results are not obvious in the beginning. Also, some people improve
rather slowly but over two to three months, the changes may become more
apparent, or perhaps you will see that things are not worse.
If you are
considering giving up on this, you might consider the possibility that
this strategy could at least stabilize or slow down the process for
your loved one. Hopefully we will be able to learn why some people
improve and others don't. After attending the American College of
Nutrition Conference at the beginning of October, I have some ideas
about why this happens. It could be that the cells are so depleted of
the various substances they need to make energy inside the cell that
the cells don't recover simply by providing ketone. I learned more
about other disease processes where there is also a problem with energy
production in mitochondria, the organelles inside of the cells that
manufacture ATP, the very basic energy that drives the whole function
of the cell. Each cell has hundreds to thousands of mitochondria.
Dr. Stephen
Sinatra discussed several dietary supplements that help people with
severe congestive heart failure by providing certain subtances involved
in manufacturing ATP in the mitochondria in the cells. In the case of
congestive heart failure, the cardiac cells have become depleted of
these substances and are not making enough ATP to keep the cell going.
Three of the supplements we have been giving Steve for quite some time,
CoQ10, L-carnitine and magnesium, but the fourth I did not know about,
D-ribose. D-ribose is a simple sugar normally made inside the cell from
glucose, and is one of the building blocks for ATP. It makes sense that
if glucose cannot even get into the cell that the cell will not be able
to make D-ribose, which is critical to making ATP. It is not stored
elsewhere in the body and it is not present in any quantity in foods,
but is used by body builders and available as a supplement. For people
with cardiac diseases, Dr. Sinatra recommends taking about 5 - 7 grams
of D-ribose per day. It comes in a powder (disappears without much
taste in coffee or any drink) or chewable tablet (not so good to my
tastebuds.) I have many questions about it, such as does it cross the
blood brain barrrier and how does it enter the cell, and of course, it
is safe? I have not been able to find out much about it. If there is a
chemist or other scientist out there with more information about
D-ribose, I would appreciate hearing from you. When I learn more I will
post something about it.
Dr. Sinatra
has a book called, "The Sinatra Solution: Metabolic Cardiology" that
discusses these supplements in detail, but is very technical. I believe
that this strategy could help people with AD since the mitochondria
work the same as far as producing enery in all of the cells. After
reading up about this, part of the problem in AD may be that the cells
become depleted of these substances, such as CoQ10, from some of the
medications our people with AD are often on (anti-depressants,
statins.) Also the whole process of making energy in the mitochondria
depends on being able to get glucose (or ketone bodies as an
alternative) into the cells in the first place and this is not
happening...
********************************************************************************************
Dr. Sinatra (The
Sinatra Solution)
See also,
Coconut Oil / MCT Oil
D-Ribose
Acetyl-L Carnitine
Magnesium
CoQ10
[Adaptation of The Sinatra Solution to treat brain glucose
hypometabolism]
Heart Health Center
http://www.drsinatra.com/MainSite/HealthCenter.aspx?Healthcenter=JRCA_HC
Heart
Health
Memory Health Center
http://www.drsinatra.com/MainSite/HealthCenter.aspx?Healthcenter=JRCA_HC
Memory
[EDIT NOTE: Get the list of the four recommended supplements
(carnitine, D-ribose, magnesium, CoQ10) from this
site, and add to Nutritional Alternatives page]
********************************************************************************************
D-Ribose
D-Ribosylated Tau
forms globular
aggregates with high cytotoxicity.
Chen L, Wei
Y, Wang X, He R.
State
Key Laboratory of Brain and Cognitive Sciences, Institute of
Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang
District, 100101 Beijing, China.
Cell
Mol Life Sci. 2009 Aug;66(15):2559-71. Epub 2009 Jun 11.
Although
the
glycation
of
Tau
that
is
involved
in
paired
helical
filament
formation
in
Alzheimer's
disease
has
been
widely
studied,
little
attention
has
been
paid
to
the
role
of
D-ribose
in
the
glycation
of
Tau.
Here,
we show that Tau is rapidly glycated in the presence of
D-ribose, resulting in oligomerization and polymerization. Glycated
derivatives appeared after 24 h incubation. Western blotting indicated
the formation of advanced glycation end-products (AGEs) during initial
stages of glycation. Thioflavin T-positive (ThT-positive) aggregations
that appeared from day 4 indicated the globular-like features. Atomic
force microscopy revealed that the surface morphology of ribosylated
Tau40 was globular-like. Kinetic studies suggested that D-ribosylated
Tau is slowly oligomerized and rapidly polymerized with ThT-positive
features. Moreover, D-ribosylated Tau aggregates were highly toxic to
SHSY5Y cells and resulted in both apoptosis and necrosis. This work has
demonstrated that D-ribose reacted with Tau protein rapidly, producing
ThT-positive aggregations which had high cytotoxicity.
PMID:
19517062
http://www.ncbi.nlm.nih.gov/pubmed/19517062?ordinalpos=1&itool=PPMCLayout.PPMCAppController.PPMCArticlePage.PPMCPubmedRA&linkpos=1
I was able to get the full text of the article from my school's library
(it helps that the university has a medical school). No, I don't
understand most of it. But I keep trying to educate myself on the terms
I don't understand. Wikipedia is a great help. Even if it sometimes has
errors, it provides a good starting point.
An important term in this discussion is "glycation":
"(sometimes called non-enzymatic glycosylation)
is the result of a sugar molecule, such as fructose or glucose, bonding
to a protein or lipid molecule without the controlling action of an
enzyme. All blood sugars are reducing molecules. Glycation may occur
either inside the body (endogenous glycation) or outside the body
(exogenous glycation). Enzyme-controlled addition of sugars to protein
or lipid molecules is termed glycosylation; glycation is a haphazard
process that impairs the functioning of biomolecules, whereas
glycosylation occurs at defined sites on the target molecule and is
required in order for the molecule to function. Much of the early
laboratory research work on fructose glycations used inaccurate assay
techniques that led to drastic underestimation of the importance of
fructose in glycation."
The paper says that D-ribose is produced both internal to cells and
externally, so cells are continuously exposed to this simple sugar. It
may be that while D-ribose is an important chemical in intracellular
processes, dietary D-ribose may have no effect since apparently the
body produces the stuff anyway.
The type of tau protein corruption described in the paper caused by
"ribosylation" is "clumping". In AD, tau aggregations are always
described as twisted helical pairs, not clumps. However, other
neurodegenerative diseases such as the FTD corticobasal degeneration
(CBD) DO have this characteristic. What I still want to find out is,
are the clumped tau proteins of CBD the same as those described in the
D-ribose paper? If so, perhaps the problem is that D-ribose *is* being
produced, but not used. It just hangs around. Eventually, it runs into
a tau protein, binds with it in some random fashion, and clumps form.
Some confusing thoughts and questions come to mind. I'm just thinking
in writing here...
Say for this case there are mitochondria in a neuron that are still
functioning and converting glucose to D-ribose, which if I understand
the process correctly, is used to create ATP
(adenosine triphosphate). I understand that ATP is used and recycled
over and over again as the currency of energy for cellular processes,
but does it need to be replaced every so often? Do ketones allow
malfunctioning cells to use the D-ribose instead of letting it just
float around until it causes mischief? But then, if you can live on
medium chain triglycerides as a back-up energy source, and D-ribose is
needed to create ATP, do cells eventually need glucose to replace lost
ATP?
For the case of CBD (corticobasal degeneration)
or PSP (progressive supranuclear palsy), perhaps D-ribose is not a good
thing to add to the diet, or at best it has no effect; whereas for
congestive heart failure it is. For CBD and PSP, there may be an excess
of D-ribose. But maybe the other supplements mentioned in the "Sinatra solution" of magnesium,
L-carnitine (acetyl-L carnitine for the
brain?), and CoQ10, along with MCTs, would help use up the excess D-ribose
before it caused problems.
********************************************************************************************
Magnesium
********************************************************************************************
Acetyl-L
Carnitine
********************************************************************************************
Resveratrol
********************************************************************************************
Coenzyme Q10
(CoQ10)
********************************************************************************************
Fish Oil
(EPA/DHA)
DHA,Part
of
the
Gerbil Food
Cocktail for memory enhancement.
********************************************************************************************
Lecithin
(choline)
Part
of the Gerbil Food
Cocktail for memory enhancement.
From the Now Foods website:
Lecithin: A
Forgotten Giant?
"Lecithin is
composed of a group of phosphorus containing fats or phospholipids the
most important being phosphatidylcholine, phosphatidylinositol, and
phosphatidylethanolamine. Lecithin can be found in a variety of foods
including egg yolks, milk, meats, fish, and legumes... Commercially
lecithin is derived from soybeans."
http://www.nowfoods.com/HealthLibrary/HealthArticles/HealthNotes/M013934.htm
********************************************************************************************
Uridine
Part of the Gerbil Food
Cocktail for memory enhancement.
Found in breast milk??? Metabolized from orotates?
********************************************************************************************
Niacinamide
/ nicotinamide
See also Tau Busters
Here is a thread about niacinamide on
the Alz.org forum. It is from early
November of 2008:
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/3931050033
Apparently, nicotinamide combats the tau protein problem common to so
many of these neurodegenerative diseases. Also known as "niacinamide",
it appears to be readily available from health food stores. The dosing
given to the mice was 200 mg/kg/day in their drinking water. I don't
know if this number is for the mass of the water, or the body weight of
the mice. "The mice received the equivalence of about 2 g of
nicotinamide for humans." Several supplement suppliers make 500mg
capsules or tablets. This would mean one would have to take 4 of these
per day. Not so bad.
Here are the article cited in the thread:
First, a Google search:
http://news.google.com/news?hl=en&tab=in&ned=us&q=vitamin+b3&btnG=Search+News
The abstract for the niacinamide study:
Nicotinamide
Restores Cognition in Alzheimer's Disease Transgenic Mice
via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of
Thr231-Phosphotau
Kim N.
Green,1 Joan S. Steffan,2 Hilda Martinez-Coria,1 Xuemin Sun,3
Steven S. Schreiber,3,5 Leslie Michels Thompson,1,2,4 and Frank M.
LaFerla1
Departments
of 1Neurobiology and Behavior, 2Psychiatry and Human
Behavior, 3Neurology, 4Biological Chemistry, and 5Anatomy and
Neurobiology, University of California, Irvine, Irvine, California
92697-4545
"Memory loss
is the signature feature of Alzheimer's disease, and
therapies that prevent or delay its onset are urgently needed.
Effective preventive strategies likely offer the greatest and most
widespread benefits. Histone deacetylase (HDAC) inhibitors increase
histone acetylation and enhance memory and synaptic plasticity. We
evaluated the efficacy of nicotinamide, a competitive inhibitor of the
sirtuins or class III NAD+-dependent HDACs in 3xTg-AD mice, and found
that it restored cognitive deficits associated with pathology.
Nicotinamide selectively reduces a specific phospho-species of tau
(Thr231) that is associated with microtubule depolymerization, in a
manner similar to inhibition of SirT1. Nicotinamide also dramatically
increased acetylated {alpha}-tubulin, a primary substrate of SirT2, and
MAP2c, both of which are linked to increased microtubule stability.
Reduced phosphoThr231-tau was related to a reduction of
monoubiquitin-conjugated tau, suggesting that this posttranslationally
modified form of tau may be rapidly degraded. Overexpression of a
Thr231-phospho-mimic tau in vitro increased clearance and decreased
accumulation of tau compared with wild-type tau. These preclinical
findings suggest that oral nicotinamide may represent a safe treatment
for AD and other tauopathies, and that phosphorylation of tau at Thr231
may regulate tau stability.
http://www.jneurosci.org/cgi/content/abstract/28/45/11500
Nicotinamide
Restores Cognition in Alzheimer's Disease Reduces
Alzheimer's tau lesions and memory loss in mice
By Will
Block Life Enhancement
"At the end
of the trial, the AD mice performed as well in memory
testing as healthy mice, a remarkable result strongly suggesting that
nicotinamide had protected their brains from memory loss, and restored
memory that would have been lost. “Cognitively, they were cured,” first
author of the study, Dr. Kim Green said. “They performed as if they’d
never developed the disease.”3 “The vitamin completely prevented
cognitive decline associated with the disease, bringing them back to
the level they’d be at if they didn’t have the pathology,” said Dr.
Green. “It actually improved behavior in non-demented animals too.”4
Meaning that healthy mice fed nicotinamide outperformed mice on a
normal diet. “This suggests that not only is it good for Alzheimer’s
disease, but if normal people take it, some aspects of their memory
might improve,” said Dr. Frank LaFerla, the lead author of the study..."
"Nicotinamide
is
a
water
soluble
member
of
the
B
vitamin
group.
Also
known
as
niacinamide,
nicotinamide
is
the
amide
of
nicotinic
acid
(vitamin
B3),
also
known
as
niacin.
In
vivo,
niacin
is
converted
to
nicotinamide
and
although
the
two
are
identical
in
their
vitamin
functions,
nicotinamide
does
not
have
the
same
pharmacologic
effects
of
niacin,
which
may
affect
the
liver negatively in some individuals.
Unlike niacin, nicotinamide does not reduce cholesterol or cause
flushing. In cells, niacin forms the coenzymes nicotinamide adenine
dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate
(NADP). Although the pathways for nicotinamide and nicotinic acid are
very similar. NAD+ and NADP+ are coenzymes in a wide variety of
enzymatic oxidation-reduction reactions..."
"In their
search for just what was going on, nicotinamide did not
affect levels of the protein beta amyloid, which clumps in the brain to
form plaques, the second type of Alzheimer’s lesion. Given this lack of
effect on beta amyloid levels, the researchers figured the compound
must be improving cognition through some other mechanism. Upon
analyzing protein extracts from whole brain samples of treated and
control AD mice, they found a 20 percent reduction in levels of tau in
the nicotinamide-treated animals. They saw no differences at several
tau sites typically phosphorylated in AD mice at the end of eight
months, but a whopping 60 percent reduction in Thr231-phospho-tau—a
particular species of tau that has been reported to interfere with
microtubule polymerization and is a commonly used biomarker for AD—in
the nicotinamide group compared with vehicle. “It’s incredibly
dramatic,” Green told the Alzheimer’s Research Forum. “This thing [a
biomarker for AD] is just wiped from the brain very specifically...”5
References
1. Wang SS. When Alzheimer’s hits at 40. New York Times,
Nov. 14, 2008.
2. Green KN, Steffan JS, Martinez-Coria H, Sun X,
Schreiber SS, Thompson LM,LaFerla FM. Nicotinamide restores cognition
in Alzheimer’s disease transgenic mice via a mechanism involving
sirtuin inhibition and selective reduction of Thr231-phosphotau. J
Neurosci 2008 Nov 5;28(45):11500-10.
3. Dotinga R. Vitamin holds promise for Alzheimer’s
disease. Healthday Nov. 5, 2008.
4. Sample I. Vitamin pill that may slow Alzheimer’s goes
on trial. The Guardian, Nov. 05 2008.
5. Anon. Alzheimer’s Research Forum. Nov. 8, 2008.
http://www.life-enhancement.com/article_template.asp?ID=2049
Understanding neurofibrillary tangles (image)
http://www.life-enhancement.com/images/LEM0901tangles_large.jpg
********************************************************************************************
Apple Juice
Apple Juice Can
Delay Onset Of
Alzheimer's Disease, Study Suggests
ScienceDaily
(Jan. 24, 2009)
"In the most
recent study Shea and his team demonstrated that mice
receiving the human equivalent of 2 glasses of apple juice per day for
1 month produced less of a small protein fragment, called
"beta-amyloid" that is responsible for forming the "senile plaques"
that are commonly found in brains of individuals suffering from
Alzheimer's disease..."
http://www.sciencedaily.com/releases/2009/01/090122100826.htm
Amy
Chan and Thomas B. Shea. Dietary Supplementation with Apple Juice
Decreases Endogenous Amyloid-%u03B2 Levels in Murine Brain. Journal of
Alzheimer's Disease, 16:1 (January 2009)
********************************************************************************************
Tau Busters
See also Cinnamon
Methylene
Blue
Niacinamide
Grape seed extract
Davunitide
Nypta
There
are six substances we have heard about since late 2007
that might be tau-busters. The six "tau buster" candidates known to me at
this time are: Cinnamon proanthocyanidins, methylene blue (Rember), niacinamide (nicotinamide), grape seed extract, davunetide and the newest
member of the club, Nypta. The wording
describing the action of these is almost identical:
"capable of inhibiting tau peptide aggregations, as well as
dissociating preformed tau peptide aggregates".
GSK-3 inhibitor drugs lithium and "NP-12"
(Noscira,
Spain),
may
also
prevent
tau
protein
corruption.
Lithium
has
side
effects
that
make
it
difficult
to
use.
Clinical
trials
of
NP-12
are
ongoing
(as
of
3/6/2010).
In
the
clinical
trials,
the
drug
is
referred
to
as
"NP031112"
NP-12 is the commonly
used name for NP031112. The drug is also known as Nypta®. The
active ingredient is
4-benzyl-2-naphtalen-1-yl-1,2,4-thiadiazolidine-3,5-dione.
********************************************************************************************
Grape
Seed Extract
See also Tau Busters
A
message was posted on the Yahoo "PSPinformatin" discussion group in
late
June of 2009:
--- In pspinformation@yahoogroups.com, Connie
Arizzo
<conniearz@...> wrote:
>
> Aletta,
My nephew, a research doctor attended a seminar about psp.
He had heard of the disease, but took more interest in it when my
husband was diagnosed with it. He said that grape seed extract given to
mice and rats in the laboratory reversed the symtoms in psp. It did not
cure it, but the lab animals were able to function again with less
help. However, the extract has not been tested in humans. He suggested
to me that my husband take six pills a day, 2 each morning, noon and
night. He said the pills would not hurt him as they are just grape seed
extract, and it would take months to see a difference, if any. Since we
are both home bound I put him on the extract so now, its a wait and see
situation. The extract can be purchased at Sam's club, costco, bj's
etc. very cheaply. Time will tell.
http://health.groups.yahoo.com/group/pspinformation/message/10381
I did a quick search with Google. This is all I came up with, but I
probably
missed something:
Grape Seed
Polyphenolic Extract as a
Potential Novel Therapeutic Agent in Tauopathies
Journal
Journal of Alzheimer's Disease
Publisher
IOS Press
ISSN
1387-2877 (Print) 1875-8908 (Online)
Issue Volume
16, Number 2 / 2009
Pages 433-439
Abstract:
"Abnormal misfoldings of the microtubule-associated protein
tau, leading to the aggregation of tau into paired helical filaments
that are ultimately deposited as neurofibrillary tangles, is a key
neuropathologic feature of a number of neurodegenerative disorders
collectively referred to as tauopathies. We recently observed that a
particular grape seed polyphenolic extract (GSPE), namely,
Meganatural-Az® may attenuate the generation and stability of
misfolded proteins. We hypothesized that Meganatural-Az® GSPE might
also attenuate tau protein misfolding that leads to the generation of
tau filamentary aggregates that are critical for the initiation and
progression of neurodegeneration and/or cognitive dysfunctions in
tauopathies. In this study, we used in vitro aggregations of synthetic
Ac-^{306}VQIVYK^{311} tau peptide as a model system to explore whether
Meganatural-Az® GSPE might modulate aggregations of tau protein. We
demonstrate that this GSPE is capable of inhibiting tau peptide
aggregations, as well as dissociating preformed tau peptide aggregates.
Results from this study suggest that this GSPE might provide beneficial
disease-modifying bioactivities in tau-associated neurodegenerative
disorders by modulating tau-mediated neuropathologic mechanisms. Our
observation, in conjunction with the emonstrated bioavailability, as
well as safety and tolerability, of this GSPE, supports the development
of Meganatural-Az® GSPE for the prevention and/or treatment of
tau-associated
neurodegenerative
disorders."
http://iospress.metapress.com/content/fq65p9545646548m/
Some more on grape seed extract....
Development of a
grape seed polyphenolic extract with anti-oligomeric
activity as a novel treatment in progressive supranuclear palsy and
other tauopathies.
J Neurochem. 2010
Jun 20. [Epub ahead of print]
Pasinetti
GM, Ksiezak-Reding H, Santa-Maria I, Wang J, Ho L.
Center of
Excellence for Novel Approaches to Neurodiagnostics and
Neurotherapeutics, Brain Institute, Center of Excellence for Research
in Complementary and Alternative Medicine in Alzheimer's Disease,
Department of Neurology, Mount Sinai School of Medicine, 1 Gustave L.
Levy Place, Box 1137, New York, NY 10029, USA.
Abstract
A diverse
group of neurodegenerative diseases - including progressive
supranuclear palsy (PSP), corticobasal degeneration (CBD) and
Alzheimer's disease (AD) among others, collectively referred to as
tauopathies - are characterized by progressive, age-dependent
intracellular formations of misfolded protein aggregates that play key
roles in the initiation and progression of neuropathogenesis. Recent
studies from our laboratory reveal that grape seed-derived polyphenolic
extracts (GSPE) potently prevent tau fibrillization into neurotoxic
aggregates and therapeutically promote the dissociation of preformed
tau aggregates (Ho et al., 2009). Based on our extensive
bioavailability, bioactivity and functional pre-clinical studies,
combined with the safety of GSPE in laboratory animals and in humans,
we initiated a series of studies exploring the role of GSPE
(Meganatural-Az((R)) GSPE) as a potential novel botanical drug for the
treatment of certain forms of tauopathies including PSP, a
neurodegenerative disorder involving the accumulation and deposition of
misfolded tau proteins in the brain characterized, in part, by abnormal
intracellular tau inclusions in specific anatomical areas involving
astrocytes, oligodendrocytes and neurons (Takahashi et al., 2002). In
this mini-review article, we discuss the biochemical characterization
of GSPE in our laboratory and its potential preventative and
therapeutic role in model systems of abnormal tau processing pertinent
to PSP and related tauopathies.
PMID:
20569300 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/20569300
********************************************************************************************
Davunetide
See also Tau Busters
A message was posted on another message board I frequent about a drug
called davunetide. It is a press release from a company called Allon
Therapeutics Inc. about another potential tau-buster drug they call
"davunetide intranasal" (AL-108). They are conducting a clinical trial
for a tauopathy FTD called PSP (progressive supranuclear palsy).
http://allontherapeutics.com/ir_news_25Jun_2009.html
If the reason that Rember appeared to be effective was because of its
effect on the Helicobacter pylori (and the resulting reduction in TNF),
not on its ability to "prevent tau aggregation and disaggregate
aggregations already formed", then I expect the results of the AL-108
clinical trial will be disappointing.
However, if it does pan out, then this will support the rationale for
attacking the tau problem.
So, now we have 5 potential tau-busters: cinnamon
proanthocyanidins, methylene blue, niacinamide, grape
seed
extract, and
davunetide. Anyone who holds the opinion that davunetide has the
potential to be effective because of its effect on the tau protein
problem of tauopathies should also be encouraged to know that the other
potential tau-busters are MUCH easier to obtain than davunetide.
********************************************************************************************
Statins
Perhaps physicians have been too enthusiastic about the use of statins,
prescribed them too often, instead of telling people, "exercise more,
lose weight and change what you eat."
Statins Show Dramatic Drug And Cell
Dependent Effects In The Brain
ScienceDaily (Oct. 28, 2009) — Besides their tremendous value in
treating high cholesterol and lowering the risk of heart disease,
statins have also been reported to potentially lower the risks of other
diseases, such as dementia. However, a study in the October Journal of
Lipid Research finds that similar statin drugs can have profoundly
different effects on brain cells -both beneficial and detrimental.
These findings reinforce the idea that great care should be taken when
deciding on the dosage and type of statin given to individuals,
particularly the elderly...
http://www.sciencedaily.com/releases/2009/10/091028114017.htmPerhaps
different
statin
drugs
have
different
effects.
I found this article recently on ScienceDaily.com. It is about the
effects of Simvastatin (Zocor?) on Parkinson's disease in a "mouse
model". I did a quick search on Google for the protein mentioned in the
article, "p21Ras". It seems that it is involved with several diseases.
Widely Used
Cholesterol-lowering Drug
May Prevent Progression Of Parkinson's Disease
ScienceDaily
(Nov. 9, 2009)
Simvastatin,
a commonly used, cholesterol-lowering drug, may prevent
Parkinson's disease from progressing further. Neurological researchers
at Rush University Medical Center conducted a study examining the use
of the FDA-approved medication in mice with Parkinson's disease and
found that the drug successfully reverses the biochemical, cellular and
anatomical changes caused by the disease. Pahan and colleagues from
Rush, along with researchers at the University of Nebraska Medical
Center in Omaha published these findings in the October 28 issue of the
Journal of Neurosciences. The authors have shown that the activity of
one protein called p21Ras is increased very early in the midbrain of
mice with Parkinson's pathology. Simvastatin enters into the brain and
blocks the activity of the p21Ras protein and other associated toxic
molecules, and goes on to protect the neurons, normalize
neurotransmitter levels, and improves the motor functions in the mice
with Parkinson's...
http://www.sciencedaily.com/releases/2009/10/091029211647.htm
Here's a
link to another article about the same paper which was
published in the Oct. 28 issue of the Journal of Neuroscience:
http://www.medpagetoday.com/Neurology/ParkinsonsDisease/16754?userid=116512&impressionId=1257229214086&utm_source=mSpoke&utm_medium=email&utm_campaign=DailyHeadlines&utm_content=Group1
********************************************************************************************
Nypta
See also Tau Busters
GSK-3 inhibitor drugs lithium and "NP-12"
(Noscira,
Spain),
may
also
prevent
tau
protein
corruption.
Lithium
has
side
effects
that
make
it
difficult
to
use.
Clinical
trials
of
NP-12
are
ongoing
(as
of
3/6/2010).
In
the
clinical
trials,
the
drug
is
referred
to
as
"NP031112"
NP-12 is the commonly
used name for NP031112. The drug is also known as Nypta®. The
active ingredient is
4-benzyl-2-naphtalen-1-yl-1,2,4-thiadiazolidine-3,5-dione.
More about Nypta:
From
ClinicalTrials.gov
"Safety,
Tolerability,
and
Efficacy
of
Two
Different
Oral
Doses
of
NP031112
Versus
Placebo
in
the
Treatment
of
Patients
With
Mild-to-Moderate
Progressive
Supranuclear
Palsy
(Tauros)"
http://www.clinicaltrial.gov/ct2/show/NCT01049399
********************************************************************************************
Anti-oxidant
trio
therapy
See also Alpha
lipoic acid (ALA)
Alpha
tocopherol
(vitamin
E)
N-acetylcysteine
(NAC)
Single drug to arrest Alzheimer's
Arnab Ganguly, Times of India, Feb 5, 2009, 01.08am IST
A team of researchers at SSKM Hospital's bio-chemistry department is
working on a medicine that will be, at one and the same time, a
preventive cure for Alzheimer's and age-related diseases.
The medicine will be derived from three known anti-oxidants alpha lipoic acid, alpha
tocopherol and n-acetylcysteine which are used
for treating chronic obstructive pulmonary diseases, diabetes and a
number of other diseases...
http://timesofindia.indiatimes.com/city/kolkata-/Single-drug-to-arrest-Alzheimers-age-woes/articleshow/4078149.cms
http://findarticles.com/p/articles/mi_8012/is_20090205/ai_n39536073/?tag=content;col1
Unfortunately, at this time (April 29, 2101), I don't know how much of
each supplement to use. For the time being, I will use the
manufacturer's recommended dosage found on the bottles.
********************************************************************************************
Alpha-lipoic Acid
(ALA)
See also Anti-oxidant trio therapy
Alpha-lipoic acid
as a new treatment
option for Alzheimer's disease--a 48 months follow-up analysis.
Hager K,
Kenklies M, McAfoose J, Engel J, Münch G.
Department
of Medical Rehabilitation and Geriatrics,
Henriettenstiftung, Hannover, Germany.
J
Neural Transm Suppl. 2007;(72):189-93.
Oxidative
stress
and
neuronal
energy
depletion
are
characteristic
biochemical
hallmarks
of
Alzheimer's
disease
(AD). It is therefore conceivable that
pro-energetic and antioxidant drugs such as alpha-lipoic acid might
delay the onset or slow down the progression of the disease. In a
previous study, 600mg alpha-lipoic acid was given daily to nine
patients with AD (receiving a standard treatment with choline-esterase
inhibitors) in an open-label study over an observation period of 12
months. The treatment led to a stabilization of cognitive functions in
the study group, demonstrated by constant scores in two
neuropsychological
tests
(the
mini
mental
state
exam,
MMSE
and
the
Alzheimer's
diseaseassessment
score
cognitive
subscale, ADAScog). In
this report, we have extended the analysis to 43 patients over an
observation period of up to 48 months. In patients with mild dementia
(ADAScog < 15), the disease progressed extremely slowly (ADAScog:
+1.2 points/year, MMSE: -0.6 points/year), in patients with moderate
dementia at approximately twice the rate. However, the progression
appears dramatically lower than data reported for untreated patients or
patients on choline-esterase inhibitors in the second year of long-term
studies. Despite the fact that this study was not double-blinded,
placebo-controlled and randomized, our data suggest that treatment with
alpha-lipoic acid might be a successful 'neuroprotective' therapy
option for AD. However, a state-of-the-art phase II trial is needed
urgently.
PMID:
17982894 [PubMed - in process]
Some message board threads about alpha lipoic acid:
"Alpha-lipoic acid as a new treatment option for Alzheimer's disease"
Alz.org message board Nov. 7, 2007
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/375102261/m/8591018062
"Alpha Lipoic Acid"
Alz.org message board March 26, 2010
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/903303553
Ray
Sahelian: http://www.raysahelian.com/lipoic.html
WebMD:
http://www.webmd.com/vitamins-supplements/ingredientmono-767-Alpha+Lipoic+Acid+ALPHA-LIPOIC+ACID.aspx?activeIngredientId=767&activeIngredientName=Alpha+Lipoic+Acid+(ALPHA-LIPOIC+ACID)&source=2
********************************************************************************************
Alpha
tocopherol (Vitamin E)
See also Anti-oxidant trio therapy
Ray
Sahelian: http://www.raysahelian.com/vitamine.html
WebMD:
http://www.webmd.com/vitamins-supplements/ingredientmono-954-VITAMIN+E.aspx?activeIngredientId=954&activeIngredientName=VITAMIN+E&source=3
********************************************************************************************
N-acetylcysteine
(NAC)
See also Anti-oxidant trio therapy
Ray Sahelian: http://www.raysahelian.com/acetylcysteine.html
WebMD: http://www.webmd.com/vitamins-supplements/ingredientmono-1018-N-ACETYL+CYSTEINE.aspx?activeIngredientId=1018&activeIngredientName=N-ACETYL+CYSTEINE&source=3
********************************************************************************************
Amyloid
Beta and Alzheimer's Disease
There has
been some discussion that perhaps amyloid beta proteins are not a step
in the process of Alzheimer's disease, but rather a symptom. This
would explain the rather disappointing results from drug trials for
medications that target amyloid beta plaques.
Alzheimer's
Memory Problems Originate With Protein Clumps Floating in
the Brain, Not Amyloid Plaques
ScienceDaily
(Apr. 28, 2010) — Using a new mouse model of Alzheimer's
disease, researchers at Mount Sinai School of Medicine have found that
Alzheimer's pathology originates in amyloid-beta (Abeta) oligomers in
the brain, rather than the amyloid plaques previously thought by many
researchers to cause the disease...
http://www.sciencedaily.com/releases/2010/04/100427111257.htm
********************************************************************************************
Multiple Sclerosis
(MS)
Here are some news articles about MS from Science Daily I ran across.
Multiple
Sclerosis Successfully Reversed In Mice: New
Immune-Suppressing Treatment Forces The Disease Into Remission
ScienceDaily
(Aug. 12, 2009) — A new experimental treatment for
multiple sclerosis (MS) completely reverses the devastating autoimmune
disorder in mice, and might work exactly the same way in humans, say
researchers at the Jewish General Hospital Lady Davis Institute for
Medical Research and McGill University in Montreal...
http://www.sciencedaily.com/releases/2009/08/090811143725.htm
New Pill To Treat
Multiple Sclerosis
ScienceDaily
(Apr. 30, 2009) — A new drug for multiple sclerosis can
dramatically reduce the chances of a relapse or a deterioration of the
condition, according to a new study from researchers at Queen Mary,
University of London...
http://www.sciencedaily.com/releases/2009/04/090429205613.htm
Little Pill Means
Big News in the Treatment of Multiple Sclerosis
ScienceDaily
(Jan. 26, 2010) — A new drug for multiple sclerosis
promises to change the lives of the 100,000 people in the UK who have
the condition, say researchers at Queen Mary, University of London. A
major trial of the oral drug Cladribine -- results of which are
published in the New England Journal of Medicine on 20 January 2010 --
has shown that it significantly reduces relapse and deterioration of
the disease, and goes a long way to eliminating the unpleasant side
effects associated with existing therapies. Cladribine promises to be
the first ever treatment in tablet form for MS, and only needs be taken
for between 8 to 10 days a year, eliminating the need for regular
injections and intravenous infusions otherwise endured by sufferers.
The ease with which Cladribine tablets can be administered, combined
with its relatively few side effects, make it a hugely exciting
development in the world of MS...
http://www.sciencedaily.com/releases/2010/01/100120211016.htm
Inexpensive
Hypertension Drug Could Be Multiple Sclerosis Treatment,
Study Suggests
ScienceDaily
(Aug. 19, 2009) — Turning serendipity into science,
researchers at the Stanford University School of Medicine have found a
link, in mice and in human brain tissue, between high blood pressure
and multiple sclerosis. Their findings suggest that a safe, inexpensive
drug already in wide use for high blood pressure may have therapeutic
value in multiple sclerosis, as well... Next, the investigators turned
to an equally well-established animal model: a laboratory-bred strain
of mouse that, after being immunized with a particular chemical,
develops brain lesions very similar to those observed in multiple
sclerosis. When, before immunization with the disease-triggering
chemical, mice got lisinopril dosages equivalent to those prescribed
for humans with high blood pressure, they didn't develop the paralysis
characteristic of disease progression. Strikingly, if it was given
after the mice developed full-blown symptoms, lisinopril reversed their
paralysis...
http://www.sciencedaily.com/releases/2009/08/090817184437.htm
Note: lisinopril is available NOW. Even though it is a blood pressure
drug, if it is safe to try, a physician can prescribe it "off label".
Promising Therapy
for Relapsing Multiple Sclerosis
ScienceDaily
(Feb. 18, 2010) — An international team of researchers has
found that adding a humanized monoclonal antibody called daclizumab to
standard treatment reduces the number of new or enlarged brain lesions
in patients with relapsing multiple sclerosis. This new study was
published online Feb. 16, 2010, and in the March edition of the Lancet
Neurology...
http://www.sciencedaily.com/releases/2010/02/100216140307.htm
Note: Daclizumab had been available in Europe. It was used to prevent
rejection of transplanted organs, such as a kidney. Due to low sales
volumes, the manufacturer no longer sells it. Perhaps this will change
if it is effective against MS.
CCSVI
Dr. Paolo Zamboni, a professor of
medicine at the University of Ferrara in Italy appears to have found a
connection between iron accumulation and multiple sclerosis (MS).
This accumulation of iron in the brain is due to a reduced flow of
blood in the vessels that drain blood from the brain. He
hypothesized that iron damages the blood vessels and allows
the metal, along with other unwelcome cells, to cross the brain-blood
barrier. Combine this with the "Iron metabolism in Parkinsonian
syndromes" article above, and we have the intriguing idea that perhaps Parkinsonian syndromes are also
caused by blood circulation problem.
Researcher's labour of love leads to MS
breakthrough
André Picard and Avis Favaro
From Saturday's Globe and Mail Published on Friday, Nov. 20, 2009
9:07PM EST Last updated on Tuesday, Dec. 15, 2009 9:20PM EST
Elena Ravalli was a seemingly healthy 37-year-old when she began to
experience strange attacks of vertigo, numbness, temporary vision loss
and crushing fatigue. They were classic signs of multiple sclerosis, a
potentially debilitating neurological disease.
It was 1995 and her husband, Paolo Zamboni, a professor of medicine at
the University of Ferrara in Italy, set out to help. He was determined
to solve the mystery of MS – an illness that strikes people in the
prime of their lives but whose causes are unknown and whose effective
treatments are few.
What he learned in his medical detective work, scouring dusty old books
and using ultra-modern imaging techniques, could well turn what we know
about MS on its head: Dr. Zamboni's research suggests that MS is not,
as widely believed, an autoimmune condition, but a vascular disease.
Fighting for
his wife's health, Dr. Zamboni looked for answers in the medical
literature. He found repeated references, dating back a century, to
excess iron as a possible cause of MS. The heavy metal can cause
inflammation and cell death, hallmarks of the disease. The vascular
surgeon was intrigued – coincidentally, he had been researching how
iron buildup damages blood vessels in the legs, and wondered if there
could be a similar problem in the blood vessels of the brain.
Using ultrasound to examine the vessels leading in and out of the
brain, Dr. Zamboni made a startling find: In more than 90 per cent of
people with multiple sclerosis, including his spouse, the veins
draining blood from the brain were malformed or blocked. In people
without MS, they were not.
He hypothesized that iron was damaging the blood vessels and allowing
the heavy metal, along with other unwelcome cells, to cross the crucial
brain-blood barrier. (The barrier keeps blood and cerebrospinal fluid
separate. In MS, immune cells cross the blood-brain barrier, where they
destroy myelin, a crucial sheathing on nerves.)
More striking still was that, when Dr. Zamboni performed a simple
operation to unclog veins and get blood flowing normally again, many of
the symptoms of MS disappeared. The procedure is similar to
angioplasty, in which a catheter is threaded into the groin and up into
the arteries, where a balloon is inflated to clear the blockages. His
wife, who had the surgery three years ago, has not had an attack since.
The researcher's theory is simple: that the underlying cause of MS is a
condition he has dubbed “chronic cerebrospinal venous insufficiency.”
If you tackle CCSVI by repairing the drainage problems from the brain,
you can successfully treat, or better still prevent, the disease...
http://www.theglobeandmail.com/news/national/researchers-labour-of-love-leads-to-ms-breakthrough/article1372414/
First Blinded Study of Venous
Insufficiency Prevalence in Multiple Sclerosis Shows Promising Results
ScienceDaily (Feb. 14, 2010) — More than 55 percent of multiple
sclerosis patients participating in the initial phase of the first
randomized clinical study to determine if persons with MS exhibit
narrowing of the extracranial veins, causing restriction of normal
outflow of blood from the brain, were found to have the abnormality...
These preliminary results are based on the first 500 participants in
the Combined Transcranial and Extracranial Venous Doppler Evaluation
(CTEVD) study, which began at UB in April 2009. Investigators are
planning to examine 500 additional subjects, who will be assessed in
the second phase of the study with more advanced diagnostic tools.
Complete data on the first 500 will be presented at the American
Academy of Neurology meeting in April. Robert Zivadinov, MD, PhD, UB
associate professor of neurology and principal investigator on the
study, says he is "cautiously optimistic and excited" about the
preliminary data. Zivadinov directs the Buffalo Neuroimaging Analysis
Center (BNAC), located in Kaleida Health's Buffalo General Hospital,
where the study is being conducted... The investigation is the first
step in determining if a condition called chronic cerebrospinal venous
insufficiency (CCSVI) is a major risk factor for MS. CCSVI is a complex
vascular condition discovered and described by Paolo Zamboni, MD, from
Italy's University of Ferrara. Zamboni's original investigation in a
group of 65 patients and 235 controls showed CCSVI to be associated
strongly with MS, increasing the risk of having MS by 43 fold. Zamboni
and Zivadinov hypothesize that this narrowing restricts the normal
outflow of blood from the brain, resulting in alterations in the blood
flow patterns within the brain that eventually cause injury to brain
tissue and degeneration of neurons.
http://www.sciencedaily.com/releases/2010/02/100210110744.htm
One has to wonder what other
diseases CCSVI could cause? (See more at Irony
of
Iron)
Lion's Mane Mushroom (a.k.a Bearded
Tooth Mushroom, Hedgehog Mushroom, Bearded Hedgehog Mushroom, pom pom
mushroom, or Bearded Tooth Fungus)
From the Alz.org messag board
thread "Anyone
on
Lion's
Mane
Mushroom?"
The Anti-Dementia effect of Lion's Mane
mushroom and its clinical application - Hericium erinaceum - Lion's Mane
Townsend Letter for Doctors and Patients, April, 2004 by Hirokazu
Kawagishi, Cun Zhuang, Ellen Shnidman
Our research on
components of Lion's Mane mushroom (Hericium erinaceum) and their
biological activities in cell culture is a case where positive
antidementia results in the laboratory have been confirmed by analogous
results in human use. In this article, we will introduce both the
results from the laboratory and their clinical application... One of
the major new approaches to the study of treatments for Alzheimer's
disease concerns the search for agents that stimulate Nerve Growth
Factor (NGF) production in the brain. NGF is part of a family of
proteins that play a role in the maintenance, survival and regeneration
of neurons during adult life... We have been engaged in a study to
search for NGF synthesis-promoting agents in medicinal mushrooms since
1991. We discovered a class of benzyl alcohol and chroman derivatives
in the fruit body of Lion's Mane mushroom called the hericenones C-H
that stimulate NGF production from mouse astroglial cells in culture...
http://findarticles.com/p/articles/mi_m0ISW/is_249/ai_114820665/
Here's a study
about another mushroom with a very similar scientific name. Lion's Mane
is Hericium erinaceum. Yamabushitake is Hericium erinaceus. Hmm...
PHYTOTHERAPY RESEARCH
Phytother. Res. 23, 367–372 (2009)
Published online 10 October 2008 in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/ptr.2634
Improving Effects of the Mushroom Yamabushitake (Hericium erinaceus) on
Mild Cognitive Impairment: A Double-blind Placebo-controlled Clinical
Trial
Koichiro Mori1*, Satoshi Inatomi1, Kenzi Ouchi1, Yoshihito Azumi1 and
Takashi Tuchida2
1Mushroom Laboratory, Hokuto Corporation, 800-8, Shimokomazawa, Nagano,
381-0008, Japan
2Isogo Central and Neurosurgical Hospital, 1-16-26, Mori, Isogoku,
Yokohama, 235-0023, Japan
A double-blind, parallel-group, placebo-controlled trial was performed
on 50- to 80-year-old Japanese men and women diagnosed with mild
cognitive impairment in order to examine the efficacy of oral
administration of Yamabushitake (Hericium erinaceus), an edible
mushroom, for improving cognitive impairment, using a cognitive
function scale based on the Revised Hasegawa Dementia Scale (HDS-R).
After 2 weeks of preliminary examination, 30 subjects were randomized
into two 15-person groups, one of which was given Yamabushitake and the
other given a placebo. The subjects of the Yamabushitake group took
four 250 mg tablets containing 96% of Yamabushitake dry powder three
times a day for 16 weeks. After termination of the intake, the subjects
were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial,
the Yamabushitake group showed significantly increased scores on the
cognitive function scale compared with the placebo group. The
Yamabushitake group’s scores increased with the duration of intake, but
at week 4 after the termination of the 16 weeks intake, the scores
decreased significantly. Laboratory tests showed no adverse effect of
Yamabushitake.
The results obtained in this study suggest that Yamabushitake is
effective in improving mild cognitive impairment.
http://www.saferemedies.com/downloads/Hericeum_Erinaceus_Clinical_Trial.pdf
Neurotrophic
factors are essential to maintain and organize neurons functionally;
thereby neurotrophic factor-like substances or their inducers are
expected to be applied to the treatment of neurodegenerative diseases
such as Alzheimer's disease. In the present study, we firstly examined
the effects of ethanol extracts of four edible mushrooms, Hericium
erinaceus (Yamabushitake), Pleurotus eryngii (Eringi), Grifola frondosa
(Maitake), and Agaricus blazei (Himematsutake), on nerve growth factor
(NGF) gene expression in 1321N1 human astrocytoma cells. Among the four
mushroom extracts, only H. erinaceus extract promoted NGF mRNA
expression in a concentration-dependent manner. In addition, secretion
of NGF protein from 1321N1 cells was enhanced by H. erinaceus extracts,
and the conditioned medium of 1321N1 cells incubated with H. erinaceus
extract enhanced the neurite outgrowth of PC12 cells. However,
hericenones C, D and E, constituents of H. erinaceus, failed to promote
NGF gene expression in 1321N1 cells. The enhancement of NGF gene
expression by H. erinaceus extracts was inhibited by the c-jun
N-terminal kinase (JNK) inhibitor SP600125. In addition, H. erinaceus
extracts induced phosphorylation of JNK and its downstream substrate
c-Jun, and increased c-fos expression, suggesting that H. erinaceus
promotes NGF gene expression via JNK signaling. Furthermore we examined
the efficacy of H. erinaceus in vivo. ddY mice given feed containing 5%
H. erinaceus dry powder for 7 d showed an increase in the level of NGF
mRNA expression in the hippocampus. In conclusion, H. erinaceus
contains active compounds that stimulate NGF synthesis via activation
of the JNK pathway; these compounds are not hericenones.
http://www.ncbi.nlm.nih.gov/pubmed/18758067
It was found that an exo-biopolymer (M.W. 1,000,000, molar ratio of
1.5:1.7:1.2:0.6:0.9, glucose:galactose:xylose:mannose:fructose, purity
99%) purified from the liquid culture broth of Hericium erinaceus
mycelium enhanced the growth of rat adrenal nerve cells. The polymer
also improved the extension of the neurites of PC12 cell. Its efficacy
was found to be higher than those from known nerve growth factors such
as Nerve Growth Factor (NGF) and Brain-Derived Nerve Factor (BDNF). The
effect of two standards has not been observed above 0.1 (mg l(-1)) of
supplementation; however, the polymer did show the effect of cell
growth and neurite extension at up to 1.0 (mg l(-1)) of addition. While
the polymer improved both cell growth and neurite extension, NGF and
BDNF did only outgrowth of the neurites. Maximum cell density and
length of the neurites were observed as 1.5x10(5) (viable cells ml(-1))
and 230 mum, respectively in adding 0.8 (mg l(-1)) of the biopolymer
for 8 days cultivation. The control growth was observed only as
1.2x10(5) (viable cell ml(-1)) of maximum cell density and 140 mum of
maximum length, respectively. It was also confirmed that the polymer
reacted with the nerve cells within 30 min after adding the sample,
compared to 80 min in adding two other growth factors. Number of
neurite-bearing cells remained relatively steady in adding the polymer
even when the cell growth started to be decreased. It was interesting
that the polymer effectively delayed apoptosis of PC12 cells by
dramatically reducing the ratio of apoptotic cells to 20% from 50% of
the control.
http://www.ncbi.nlm.nih.gov/pubmed/19003308
Here's a couple of links to
websites that sell the mushroom either in powdered or extract form.
This is information only, no endorsement should be inferred. I
don't know enough yet about which is better. The clinical trials
mentioned above used 5 grams of the whole dried mushroom once a day, in
a soup for the patients so I imagine either way is good. The real
erinacine extract isn't available yet and with that patent lock on it,
may never be as an over the counter drug.
http://www.cordycepsreishiextracts.com/lions_mane_mushroom_extract.htm
http://www.sunfood.com/buy/1/8/433/Lion-s-Mane--Mushroom-Science--90-veg-caps--300-mg--All-Natural/1297.aspx
http://www.swansonvitamins.com/SW1096/ItemDetail
http://www.alohamedicinals.ca/hericium.htm
http://www.mushroomharvest.com/catalog/product_info.php?cPath=36_39&products_id=102
http://www.mushroomharvest.com/catalog/product_info.php?cPath=36_40&products_id=222
Here's a website that explains the
difference in water vs alcohol extract.
http://www.cordycepsreishiextracts.com/quality_difference.htm
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