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:
I'm
creating and maintaining these pages for my own use to keep track and
try to make sense of all of this information. I then make it all
available to the entire world in case someone might be helped by
it. 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
- Exposure to toxins
Occurrence of beta-methylamino-l-alanine
(BMAA) in ALS/PDC patients from Guam.
Acta Neurol Scand. 2004 Oct ;110 (4):267-9 15355492 Cit:30
S J Murch, P A Cox, S A Banack, J C Steele, O W Sacks
Institute for Ethnobotany, National Tropical Botanical Garden, Kalaheo,
HI 96741, USA.
We tested the brain tissues of the Chamorro people of Guam who died of
amyotrophic lateral sclerosis/Parkinsonism dimentia complex (ALS/PDC)
for the neurotoxin beta-methylamino-l-alanine (BMAA). We used validated
high-pressure liquid chromatography and liquid chromatography-mass
spectrometry analyses to test well-characterized archival tissues of
the superior frontal gyrus from eight Chamorros from Guam and a
comparison group of 15 Canadians. BMAA was found as a free amino acid
in 83% of Chamorro ALS/PDC patients (3-10 microg/g) as a
protein-associated amino acid in 100% of the Chamorro individuals
(149-1190 microg/g). Both forms of BMAA were also found at comparable
levels in two Canadians who died of progressive neurodegenerative
disease. BMAA, which is produced by cyanobacteria, may be associated
with some cases of neurodegenerative disease.
********************************************************************************************
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
Iron Accumulation in Parkinsonian
Syndromes:
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.
More info: Human Metabolome
Database
Description:
Scyllitol
is
an
isomer
of
cyclohexanehexol
or
inositol.
It was first
isolated from the kidneys of fish in 1858 by Staedeler and Freierchs.
Scyllitol is a naturally occurring plant sugar alcohol found most
abundantly in the coconut palm. It appears to accumulate in a number of
human tissues and biofluids through dietary consumption. It has
traditionally been considered to be a B vitamin although it has an
uncertain status as a vitamin and a deficiency syndrome has not been
identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed,
p1379). Results reported by Viola et al (PMID: 15340856) suggest that
high CSF concentrations of scyllo-inositol can be induced by chronic
alcoholism. scyllo-Inositol (also called "scyllitol") when fed to
transgenic mice that exhibit a memory disease very similar to human
Alzheimer's disease, can block the accumulation of soluble amyloid-beta
(Aβ) plaques in the brain. Scyllitol was found to reverse memory
deficits in the mice, reduce the amount of Aβ plaque in the brains of
the mice, and reversed other symptoms associated with the presence of
Aβ in the brain (PMID: 16767098).
http://www.hmdb.ca/metabolites/HMDB06088
********************************************************************************************
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 extract)
See
also Curcumin, Copper,
Vitamin D
[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.]
Some observations on the spectrum of
dementia
Neurology India, Year: 2004 Volume: 52 Issue: 2 Page:
213-214
Sanjeev Jha, R Patel
Department of Neurology, SGPGIMS, Lucknow, India
A study was
designed to generate epidemiological and clinical data on dementia, in
a teaching hospital in India. It was conducted on 124 (94 male and 30
female) elderly patients (aged more than 60 years) presenting with
clinical syndrome of dementia (DSM-3). Their age range was 64-78 (mean
65.7 4.1) years. Detailed clinical, biochemical, radiological and
electrophysiological evaluation was done to establish etiology.
Patients with psychiatric ailments, cranial trauma and tumors were
excluded. The study period was 4.2 years. Multi-infarct dementia (MID)
was observed to be commonest cause of dementia and was present in 59
(47.6%) cases. There were 10 (8%) patients each of tuberculosis (TB)
and neurocysticercosis (NCC). Alcohol-related dementia was present in
13 (10.5%), while malnutrition (Vitamin B12 deficiency) was present in
9 (7.2%). Alzheimer's Disease (AD) was present (NINCDS-ADRDA criteria)
in 6 patients (4.8%). There were 3 (2.4%) cases 1 each of Huntington's
disease, Parkinson's and Normal Pressure Hydrocephalus and 2 each of
diabetes, hypothyroidism, hyperthyroidism and Creutzfeldt' Jakob
Disease. We conclude that AD, which is irreversible and common in the
west, is relatively uncommon in India as compared to MID, infections
and malnutrition, which are potentially treatable.
http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2004;volume=52;issue=2;spage=213;epage=214;aulast=Jha
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 piperine
(extract of black pepper, a.k.a. Bioperine) 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.
In a study using mice, low-dose
curcumin was found to enhance adult
hippocampal neurogenesis.
See, Curcumin stimulates
proliferation of embryonic neural progenitor cells and neurogenesis in
the adult hippocampus. High dose levels were found to be
"cytotoxic": "Curcumin exerted biphasic effects on cultured NPC - low
concentrations stimulated cell proliferation, whereas high
concentrations were cytotoxic."
http://www.ncbi.nlm.nih.gov/pubmed/18362141?dopt=Abstract
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.
Effect on TNF-Alpha:
I know that curcumin is used as an
anti-inflammatory agent, so I searched Google on curcumin and TNF. I
found research papers saying that curcumin inhibited TNF, and some that
said that it "sensitized" cancer cells to TNF (which I guess is a good
thing). Here's and example:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T4P-3YVDRW0-6P&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=7a734d2000776a9f4ca641b1bd4aae02
Scientists ID possible biomarker to gauge
Alzheimer's prognosis, effect of therapies
University of California - Los Angeles
17-Mar-2011
...They incubated the immune cells overnight with amyloid beta to test
the cells' ability to "turn on" MGAT3. They also added a synthetic form
of curcumin to some of the cells to gauge the effect it had on MGAT3
expression and the absorption of amyloid beta.
Based on the results, the researchers identified three groups of
Alzheimer's patients.
Type 0 patients: This group had very low expression of MGAT3 and very
low absorption rates of amyloid beta.
Type I patients: This group also had low expression of MGAT3 and low
amyloid beta absorption rates, but the strength of the MGAT3 message
and the absorption of amyloid beta increased when researchers
stimulated the macrophages with synthetic curcumin.
Type II patients: This group initially had high amyloid beta absorption
rates, but when scientists added synthetic curcumin, MGAT3 expression
lessened and absorption was reduced.
In addition, researchers found that for Type I and Type II patients,
the clearing of amyloid beta was dependent on vitamin D3, a type of
vitamin D that occurs naturally in these cells. When they blocked
vitamin D3 use by the macrophages in the laboratory, they found that
absorption of amyloid beta suffered.
"These findings demonstrate three very different levels of immunity and
possible reactions to natural therapies of vitamin D3 and curcumin,"
Fiala said. "These differences could point to a new way to track the
progression of Alzheimer's disease and the effectiveness of these
natural therapies based on an individual patient's immunity."
Fourteen of the 20 Alzheimer's disease patients have been followed for
two years, and researchers noted that those who were Type 0 had a worse
two-year prognosis regarding the loss of their ability to live
independently than the other two types of patients... During the study,
researchers also noted that one Type II patient who underwent hip
surgery experienced temporary cognitive dysfunction related to the
general surgery anesthesia, which is a phenomenon that can occur.
Researchers checked the patient's MGAT3 immunity and found that the
patient's ability to clear amyloid beta had declined after surgery but
improved in later months, along with cognitive function, possibly due
to the vitamin D3 supplementation the patient had undertaken...
http://www.eurekalert.org/pub_releases/2011-03/uoc--sip031711.php
Common Yellow Lab Dye Profoundly Extends
Lifespan in Healthy Nematodes, and Slows Alzheimer's Disease-Like
Pathology in Worms
ScienceDaily (Mar. 30, 2011) — Basic Yellow 1, a dye used in
neuroscience laboratories around the world to detect damaged protein in
Alzheimer's disease, is a wonder drug for nematode worms. In a study
appearing in Nature, the dye, also known as Thioflavin T (ThT)...
Alavez said curcumin, the
active ingredient in the popular Indian spice turmeric, also had a
significant positive impact on both healthy worms and those bred to
express a gene associated with Alzheimer's. "People have been making
claims about the health benefits of curcumin for many years. Maybe
slowing aging is part of its mechanism of action,"...
http://www.sciencedaily.com/releases/2011/03/110330131258.htm
Reference:
Silvestre Alavez, Maithili C. Vantipalli, David J. S. Zucker, Ida M.
Klang, Gordon J. Lithgow. Amyloid-binding
compounds
maintain protein homeostasis during ageing and extend
lifespan. Nature, 2011
********************************************************************************************
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)
See also CCSVI,
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.
More articles:
http://www.liebertonline.com/doi/pdf/10.1089/pho.2010.2814
Dementia patient makes 'amazing' progress after using infra-red helmet
15th July 2008
http://www.dailymail.co.uk/health/article-1034936/Dementia-patient-makes-amazing-progress-using-infrared-helmet.html
Terry Pratchett Battles Alzheimer’s With Retro-Futurist Headgear
Jan 20, 2009
http://gizmodo.com/#!5135176/terry-pratchett-battles-alzheimers-with-retro+futurist-headgear?comment=10162103:10162363
Emotional responses and memory performance of middle-aged CD1 mice in a
3D maze: Effects of low infrared light
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WNM-4PMYXT7-1&_user=10&_coverDate=05%2F31%2F2008&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_searchStrId=1695274432&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5445b8ba4a927eddda939641b43bccd7&searchtype=a
Infra Red Helmet For Reversing Early Alzheimer's To Be Tested
http://www.medicalnewstoday.com/articles/95334.php
Clinical Trials
Go to clinicaltrials.gov and search for - infrared alzheimer's - and
you'll see this:
1 Active, not recruiting - Far Infrared Treatment for Alzheimer's
Disease Condition: Alzheimer Disease
2 Recruiting - Efficacy of 1072nm Infrared Stimulation on Executive
Functioning in Dementia
3 Active, not recruiting - Far Infrared Radiation Treatment of Dementia
and Other Mental Illness
For more info on the actively recruiting clinical trial, see:
http://clinicaltrials.gov/ct2/show/NCT01059877?term=infrared+alzheimer%27s&rank=2
http://tp//www.quietmindfdn.org/NF_media_files/MID_study_promo_piece.pdf
Cold Sore Cure Gives Ray of Light for Alzheimer's
http://www.virulite.com/alzheimer_cure_personal_care_magazine_%20jan_2008.pdf
********************************************************************************************
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
Cellphone Radiation May Thwart
Alzheimer's
TechNewsWorld
01/07/10 2:02 PM PT
After years of controversy over whether cellphone radiation might cause
cancer, scientists have reached the startling conclusion that it might
actually cure Alzheimer's disease. Young mice exposed to long-term
radiation equivalent to human cellphone use of a couple of hours a day
were protected from Alzheimer's, and memory function was restored in
old mice already afflicted.
http://www.technewsworld.com/edpick/69052.html
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, Inflammation,
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
Reversal Of
Alzheimer's Symptoms Within Minutes In Human Study
ScienceDaily
(Jan. 9, 2008)
An
extraordinary new scientific study, which for the first time documents
marked improvement in Alzheimer’s disease within minutes of
administration of a therapeutic molecule, has just been published in
the Journal of Neuroinflammation. This new study highlights the
importance of certain soluble proteins, called cytokines, in
Alzheimer’s disease. The study focuses on one of these cytokines, tumor
necrosis factor-alpha(TNF), a critical component of the brain’s immune
system. Normally, TNF finely regulates the transmission of neural
impulses in the brain. The authors hypothesized that elevated levels of
TNF in Alzheimer’s disease interfere with this regulation. To reduce
elevated TNF, the authors gave patients an injection of an anti-TNF
therapeutic called etanercept. Excess TNF-alpha has been documented in
the cerebrospinal fluid of patients with Alzheimer’s. The new study
documents a dramatic and unprecedented therapeutic effect in an
Alzheimer’s patient: improvement within minutes following delivery of
perispinal etanercept, which is etanercept given by injection in the
spine. Etanercept (trade name Enbrel) binds and inactivates excess TNF.
Etanercept is FDA approved to treat a number of immune-mediated
disorders and is used off label in the study...
http://www.sciencedaily.com/releases/2008/01/080109091102.htm
Arthritis drugs
could help prevent memory loss after surgery, study suggests
Imperial College London
News and Events
November 1, 2010
Anti-inflammatory
drugs
currently
used
to
treat
diseases
such
as
rheumatoid
arthritis
may
also
help
prevent
cognitive
problems
after
surgery,
according
to
a
new
study
by
researchers
at
Imperial
College
London
and
University
of
California,
San
Francisco
(UCSF).
The research
also reveals for the first time that a specific inflammatory response
in the brain may explain why many patients experience memory loss or
other forms of cognitive dysfunction after surgery or critical
illness... Previous studies have linked post-operative cognitive
decline with the rise in blood levels of a cytokine called
interleukin-1 beta (IL-1β), which is involved in inflammation. For this
study, Maze and his colleagues studied another cytokine called tumour
necrosis factor (TNF-α), which is known to regulate the immune system's
inflammatory response before interleukin-1 is produced...
http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_2-11-2010-9-27-7
Anti-TNF Therapies for Rheumatoid
Arthritis Could Reduce Alzheimer’s Risk
American College
of Rheumatology (ACR)
11/1/2010
8:00 AM EDT
Newswise -
Anti-TNF therapies commonly used to treat rheumatoid arthritis have
been found to potentially reduce the risk of developing Alzheimer's
dementia among people with rheumatoid arthritis, according to research
presented this week at the American College of Rheumatology Annual
Scientific Meeting in Atlanta...
http://www.newswise.com/articles/view/570196/?sc=rsmn
TNF-alpha modulation for treatment of
Alzheimer's disease: a 6-month pilot study
Abstract
Context
Current
pharmacologic treatments for Alzheimer's disease (AD) do not prevent
long-term clinical deterioration. Tumor necrosis factor (TNF)-alpha, a
proinflammatory cytokine, has been implicated in the pathogenesis of AD.
Objective
To
investigate the use of a biologic TNF-alpha inhibitor, etanercept was
given by perispinal extrathecal administration for the treatment of AD.
Methods
This was a
prospective, single-center, open-label, pilot (proof-of-concept) study,
in which 15 patients with mild-to-severe AD were treated for 6 months.
We administered etanercept, 25-50 mg, once weekly by perispinal
administration. Main outcome measures included the Mini-Mental State
Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive
subscale (ADAS-Cog), and the Severe Impairment Battery (SIB).
Results
The average
age of our patient population was 76.7. The mean baseline MMSE was 18.2
(n = 15); the mean baseline ADAS-Cog was 20.8 (n = 11); and the mean
baseline SIB was 62.5 (n = 5). There was significant improvement with
treatment, as measured by all of the primary efficacy variables,
through 6 months: MMSE increased by 2.13 ± 2.23, ADAS-Cog
improved (decreased) by 5.48 ± 5.08, and SIB increased by 16.6
± 14.52.
Conclusion
An
increasing amount of basic science and clinical evidence implicates
inflammatory processes and resulting glial activation in the
pathogenesis of AD. This small, open-label pilot study suggests that
inhibition of the inflammatory cytokine TNF-alpha may hold promise as a
potential approach to AD treatment. Further study in randomized,
placebo-controlled clinical trials is merited.
http://www.ncbi.nlm.nih.gov/pubmed/16926764
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1785182/
Arthritis Drugs Linked to Lower Odds
of Alzheimer's
TNF Blockers Associated With 55% Reduced Risk of Dementia
By Charlene Laino
WebMD Health News
Nov. 9, 2010 (Atlanta) -- People who take drugs called TNF blockers for
rheumatoid arthritis may potentially reduce their odds of developing
Alzheimer's disease, preliminary research suggests.
The use of TNF blockers was associated with a 55% lower risk of
Alzheimer's disease in people with rheumatoid arthritis... TNF blockers
neutralize a protein, called tumor necrosis factor alpha (TNF), that is
overproduced in inflammatory diseases like rheumatoid arthritis [...and
chronic infections like H.pylori, etc. -ed].
"Studies have shown that TNF is also elevated in the cerebrospinal
fluid of Alzheimer's patients and that higher levels correlate with the
progression of the disease," Chou tells WebMD.
To further explore the possible association between rheumatoid
arthritis, Alzheimer's, and TNF blockers, Chou and colleagues combed
through a medical and pharmacy claims database that included
information on 8.5 million U.S. adults.
Chou presented his findings here at the annual meeting of the American
College of Rheumatology... When they further analyzed the risk
according to the three TNF blockers studied, the researchers found that
Enbrel was associated with a nearly 70% reduced risk of Alzheimer's...
"Theoretically, it may cross the blood-brain earlier more easily,"...
http://www.webmd.com/alzheimers/news/20101108/arthritis-drugs-linked-lower-odds-alzheimers?src=RSS_PUBLIC
Rapid cognitive improvement in
Alzheimer's disease following perispinal etanercept administration.
J
Neuroinflammation. 2008 Jan 9;5:2.
http://www.ncbi.nlm.nih.gov/pubmed/18184433
TNF-alpha modulation for treatment of
Alzheimer's disease: a 6-month pilot study.
MedGenMed.
2006
Apr
26;8(2):25.
http://www.ncbi.nlm.nih.gov/pubmed/16926764
Regulation of peripheral inflammation
by spinal p38 MAP kinase in rats.
PLoS Med. 2006 Sep;3(9):e338.
http://www.ncbi.nlm.nih.gov/pubmed/16953659
Intrathecal inflammation precedes
development of Alzheimer's disease.
http://www.ncbi.nlm.nih.gov/pubmed/12933918
Anti-TNF therapy in the injured
spinal cord.
Esposito E, Cuzzocrea S.
Trends Pharmacol Sci. 2011 Feb;32(2):107-15.
At
the time
of approval of etanercept by the FDA, the role of TNF in neurological
disorders was incompletely understood. Novel methods of drug delivery
were needed because of the high molecular weight of etanercept and the
problems faced by large molecules in traversing the blood–brain
barrier(BBB). Perispinal methods were designed for selective delivery
of etanercept. Perispinal administration results in rapid local
delivery of etanercept to the vertebral venous system and the
cerebrospinalfluid(CSF), with rapid local delivery to sites of TNF
excess[52]. Rapid response suggests immediate neutralization of excess
TNF, resulting in normalization of synaptic mechanisms.
PubMed 21185611
http://www.ncbi.nlm.nih.gov/pubmed/21185611
********************************************************************************************
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:
See also Enbrel
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.
"... 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."
"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."
"...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:
See also Curcumin
Unraveling Alzheimer's: Simple Small
Molecules Could Untangle Complex Disease
ScienceDaily (Dec. 10, 2010) —
New molecular tools developed at the University of Michigan show
promise for "cleansing" the brain of amyloid plaques, implicated in
Alzheimer's disease... In earlier work, Lim and her team developed
dual-purpose molecular tools that both grab metal ions and interact
with amyloid-beta. The researchers went on to show that in solutions
with or without living cells, the molecules were able to regulate
copper-induced amyloid-beta aggregation, not only disrupting the
formation of clumps, but also breaking up clumps that already had
formed...
http://www.sciencedaily.com/releases/2010/12/101209130959.htm
********************************************************************************************
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
Fountain of Youth from the Tap?
Environmental Lithium Uptake Promotes Longevity, Scientists Demonstrate
in Worms
ScienceDaily (Feb. 18, 2011) — A regular uptake of the trace element
lithium can considerably promote longevity. This is the result of a new
study by scientists of Friedrich Schiller University Jena...
http://www.sciencedaily.com/releases/2011/02/110218111709.htm
********************************************************************************************
Cinnamon:
See also Tau Busters, Inflammation,
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
HSV
Inflammation
"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. Periodontal
(gum) disease may increase the risk of cognitive dysfunction associated
with Alzheimer's disease in healthy individuals as well as in those who
already are cognitively impaired. Another
possibility is the presence of Lyme disease. If they have one of these
infections, get it treated.
Lyme Disease:
Chitosan Oligosaccharide has found a nich use
in treatment of Lyme disease symptoms.
http://www.lyme-disease-research-database.com/alan-macdonald-transcription.html
Borrelia:
Borrelia and
Alzheimer disease
Posted 21
August 2005 [to www.alzforum.org]
By Liz
Shepherd
Here in South
Carolina, several patients diagnosed with Alzheimer disease actually
had DNA PCR positive Borrelia cultures grown from their brains. The
symptoms for these illnesses do in fact overlap. Many psychiatrists now
say that all brain disease is infectious. Have you actually LOOKED for
a common denominator? Have all Alzheimer brains been checked for
Borrelia? My guess is you may be very surprised to find out what is
causing Alzheimer's.
http://www.alzforum.org/res/adh/hyp/default.asp#borrelia
The Pathogen Hypothesis (Live
Discussion on www.alzforum.org)
Moderator’s
summary: Pathogens as a cause of
Alzheimer’s disease
By June
Kinoshita
The notion
that microbes such as herpes simplex virus 1 (HSV1) and Chlamydophila
pneumoniae (Cp) could be a causal factor in Alzheimer’s diseases would
probably be viewed by the main stream of AD researchers as being beyond
the pale. Although a small body of recent findings has reported
strikingly strong associations between these pathogens and AD [1,7],
subsequent attempts to replicate the findings have met with mixed
results (discussed in [10]). At this juncture, it might be convenient
to dismiss the hypothesis, but as both sides of this debate session
agreed, there are plausible reasons for these discrepancies that
deserve to be resolved through further research. While opinions
diverged on the strength of evidence for and against the hypothesis,
there was a consensus that the possibility of common infectious agents
causing such a widespread scourge of old age is one that is too
important to ignore.
http://www.alzforum.org/res/for/journal/balin/default.asp
Among Older Patients, Severe Sepsis
Associated With Development of Cognitive and Functional Disability
ScienceDaily (Oct.
27, 2010)
Older adults who survived severe sepsis were more likely to develop
substantial cognitive impairment and functional disability, according
to a study in the October 27 issue of JAMA... The researchers found
that the prevalence of moderate to severe cognitive impairment
increased 10.6 percentage points among patients who survived severe
sepsis, and their odds of acquiring moderate to severe cognitive
impairment were 3.3 times higher. Also, a high rate of new functional
limitations was seen following sepsis, with an additional average
increase of 1.5 new functional limitations per person among those with
no or mild to moderate pre-existing functional limitations.
Nonsepsis
general hospitalizations were associated with no change in moderate to
severe cognitive impairment and with the development of fewer new
limitations.
"Cognitive
and functional declines of the magnitude seen after severe sepsis are
associated with significant increases in caregiver time, nursing home
admission, depression, and mortality. These data argue that the burden
of sepsis survivorship is a substantial, underrecognized public health
problem with major implications for patients, families, and the health
care system."...
http://www.sciencedaily.com/releases/2010/10/101026161241.htm
Tooth Loss May Be Linked to Memory
Loss
Gum infection may cause inflammation that affects the brain, researcher
suggests
TUESDAY, Jan. 4 (HealthDay News)
http://www.businessweek.com/lifestyle/content/healthday/648432.html
********************************************************************************************
TNF-Alpha
See also Enbrel
Chitosan
Cat's
Claw
Cinnamon
Curcumin
Inflammation
NT-020 references in AFA
Supplements that might block TNF-Alpha
Note: The body uses TNF-alpha to fight infections. Blocking
tumor necrosis factor-alpha (an inflammation-causing cytokine), raises
the risk of activating a latent infection such as tuberculosis due
to the importance of this cytokine in the immune defense against them.
From
the Alz.org message board "Medications/Treatments for Alzheimer's and
Other Related Dementias"
Posted August 05, 2008
12:11 PM
...I would love to see that replicated by a supplement that is
relatively free of side-effects such as Chitosan oligosaccharide, cats,
claw, or whatever. So I'm looking at these and others to see if there
is yet more than one road that leads to Rome so to speak. I've always
heard there are many. I bet there is. Right now I'm kind of excited
about cats claw (cc) as it passes through the BBB in 2 minutes. There
appears to be very limited experience with it on AD patients so we
don't really know what sort of response it might elicit from an AD
patient, yet it has good data showing it works by TNF-alpha
suppression...and it has been reported to be as safe as coffee.
Nevertheless some side-effects have been reported that might involve
kidney function...so maybe not as safe as coffee. Also very rapid
response of cc has been reported in other inflammatory diseases that it
has been used for in human patients...
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/4081064272?r=3891056613#3891056613
Some more
references to earlier research:
Elevated circulating tumor necrosis factor
levels in Alzheimer's disease.
Fillit H, Ding WH, Buee L, Kalman J, Altstiel L, Lawlor B, Wolf-Klein G.
Neurosci Lett. 1991 Aug
19;129(2):318-20.
Cellular
localization of human immunodeficiency virus infection within the
brains of acquired immune deficiency syndrome patients.
Wiley
CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MB.
PNAS 1986;83(18): 7089-7093
Role of human immunodeficiency virus
and cytomegalovirus in AIDS encephalitis.
Wiley
CA, Nelson JA. Am J Pathol.
1988 October; 133(1): 73–81.
Tumor necrosis factor identified in
multiple sclerosis brain.
Hofman
FM, Hinton DR, Johnson K, Merrill JE. J
Exp Med. 1989 August 1; 170(2): 607–612.
http://www.pnas.org/cgi/doi/10.1073/pnas.1014557107
See Haark 2004, Medeiros 2007, Riazi 2008, McAfoose and Baume 2008, and
Leisz 2009.
Breakthrough or False Hope?
Etanercept Case Report Draws Scrutiny
http://www.alzforum.org/new/detail.asp?id=1738
Targeting TNF-Alpha to Elucidate and
Ameliorate Neuroinflammation in Neurodegenerative Diseases.
CNS
Neurol Disord Drug Targets. 2011 Feb 2. [Epub ahead of print]
Frankola
KA,
Greig
NH,
Luo
W,
Tweedie
D.
PMID: 21288189
Systemic inflammation is associated
with MCI and its subtypes: the Sydney Memory and Aging Study.
Dement
Geriatr Cogn Disord. 2010;30(6):569-78. Epub 2011 Jan 20.
PMID: 21252552
Tumor necrosis factor-alpha mediated
signaling in neuronal homeostasis and dysfunction.
Cell
Signal. 2010 Jul;22(7):977-83. Epub 2010 Jan 21.
Park
KM, Bowers WJ.
Department of Pharmacology and Physiology, University of Rochester
Medical Center, Rochester, NY 14642, USA.
Abstract
Tumor necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory
molecule, which upon engagement with its cognate receptors on target
cells, triggers downstream signaling cascades that control a number of
cellular processes related to cell viability, gene expression, ion
homeostasis, and synaptic integrity. In the central nervous system
(CNS), TNF-alpha is produced by brain-resident astrocytes, microglia,
and neurons in response to numerous intrinsic and extrinsic stimuli.
This review will summarize the key events that lead to TNF-alpha
elaboration in the CNS, and the effects that these inflammatory signals
impart on neuronal signaling in the context of homeostasis and
neuropathology.
PMID: 20096353
********************************************************************************************
Chitosan
(Water-soluble Chitosan, chitosan oligosaccharide)
Here is a Pubmed citation:
It says that that WSC (water-soluble chitosan) inhibited "TNF-alpha". I
assume there is a "TNF-beta", etc. What brand of TNF does etanercept
inhibit?
Interestingly, they used desferrioxamine (desferral) to create the
elevated levels of TNF. But, other researchers in Canada have used
desferral to arrest the progression of AD. So, *there's* a puzzle...
Desferral is used primarily as a powerful iron chelator, on the same
order as phytic acid (IP6).
This research was done in Japan. I wonder if WSC is available in the US?
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0G-451DD9T-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ee4019d7850933a86133b8fc20be802d
From the Alz.org message board "Medications/Treatments for Alzheimer's
and Other Related Dementias":
Posted July 23,
2008 01:43 PM
After very
extensive review of nearly everything out there for treatment of AD, I
have come to the conclusion that water-soluble chitosan (WSC) is the
only non-drug "supplement" out there that targets TNF. Let me say that
again...WSC targets TNF in the brain. Because it appears to be safe,
has never been linked to shell-fish allergies (a topic addressed in the
chitosan literature) is marketed in edible form, and is used as a
general energy and anti-aging tonic, mostly in China, and has animal
model AD research showing that it targets TNF in a manner similar to
Enbrel, I think it is worthy of trying...
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/4081064272?r=2661005413#2661005413
Sources???: http://en.haidebei.com/newEbiz1/EbizPortalFG/portal/html/ProductInfoExhibit.html?ProductInfoExhibit_ProductID=c373e911f56523978f6e9d2e0a9b4fa4&ProductInfoExhibit_isRefreshParent=false
http://www.outletnutrition.com/713947559905.html
http://heavenshealth.com/benefits.htm
This is
a US supplier of water soluble chitosan.
http://www.alibaba.com/countrysearch/US-suppliers/Water_Soluble_Chitosan.html
********************************************************************************************
Cat's Claw
(Uncaria tomentosa,
Una de Gato)
The content of this topic was moved to
Notes_II
********************************************************************************************
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
Vulnerable Brain Region May Be
Central to Progression of Alzheimer's
Disease
ScienceDaily (Nov. 7, 2010)
New research is helping to unravel the events that underlie the
"spread" of Alzheimer's disease (AD) throughout the brain. The
research, published by Cell Press in the November 4th issue of the
journal Neuron, follows disease progression from a vulnerable brain
region that is affected early in the disease to interconnected brain
regions that are affected in later stages... "Our findings directly
support the hypothesis that AD-related dysfunction is propagated
through networks of neurons, with the EC as an important hub region of
early vulnerability,"...
http://www.sciencedaily.com/releases/2010/11/101103135239.htm
[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
How Disordered Proteins Spread from Cell
to Cell, Potentially Spreading Disease
ScienceDaily (Feb. 18, 2011) — ...Kopito
found that the mutant protein associated with Huntington's disease can
leave one cell and enter another one, stirring up trouble in each new
cell as it progresses down the line. The spread of the misfolded
protein may explain how Huntington's progresses through the brain.
This disease, like Parkinson's and Alzheimer's, starts in one area of
the brain and spreads to the rest of it. This is also similar to the
spread of prions, the self-replicating proteins implicated in mad cow
disease and, in humans, Creutzfeldt-Jakob disease. As the misfolded
protein reaches more parts of the brain, it could be responsible for
the progressive worsening of these diseases...
http://www.sciencedaily.com/releases/2011/02/110218165254.htm]
Apparently, the amyloid beta plaques have prion-like properties too:
Alzheimer's has 'infectious' mechanism
Cosmos Online
Monday, 25 October 2010
by Gareth Barton
These misfolded proteins have properties similar to prions, the
researchers concluded. Prions are tiny, infectious protein particles
can cause disease, such as mad cow disease which passes from infected
cattle to humans through their meat.
In the study,
the researchers removed brain tissue from mice with Alzheimer's-like
symptoms, and injected into it into the stomach cavity of healthy mice.
Four months later, the previously healthy mice showed symptoms similar
to those of Alzheimer's disease and their brains had similarly disease
brain tissue.
http://www.cosmosmagazine.com/news/3824/alzheimers-disease-has-infectious-element
Peripheral Induction of Alzheimer's-Like
Brain Pathology in Mice
ScienceDaily
(Oct. 25, 2010)
Pathological
protein deposits linked to Alzheimer's disease and cerebral amyloid
angiopathy can be triggered not only by the administration of
pathogenic misfolded protein fragments directly into the brain but also
by peripheral administration outside the brain...
http://www.sciencedaily.com/releases/2010/10/101021141453.htm
Peripherally
Applied
Aβ-Containing
Inoculates
Induce
Cerebral
β-Amyloidosis
Yvonne S.
Eisele
Science DOI:
10.1126/science.1194516
Published
Online October 21, 2010
The
intracerebral injection of β-amyloid–containing brain extracts can
induce cerebral β-amyloidosis and associated pathologies in susceptible
hosts. Here, we found that intraperitoneal inoculation with
β-amyloid–rich extracts induced β-amyloidosis in the brains of
β-amyloid precursor protein transgenic mice after prolonged incubation
times
http://www.sciencemag.org/cgi/content/abstract/science.1194516
Could A-beta plaques from animal tissue in our food be a problem?
I'm not a vegetarian, but (pardon the pun) it is food for thought.
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.
Other things to research: Lauric acid in coconut oil kills
H.pylori?
********************************************************************************************
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.
Your body is a machine. It drags you, the soul, along whether you
want to go or not, first to life, then to death.
Ecclesiastes 8:8 "No man has power to retain the
spirit, or authority over the day of death..."
You do not
have
have an internal on/off switch that you can switch off at will.
The idea that you do is a New Agey style concept that subtly attempts
to dismiss Christ's supernatural act of giving up his spirit as his
final miracle performed in his human body, ending the torment of his
crucifixion. It was a supernatural act, get it? We do not
have that ability. All we can do is inflict violence on ourselves
to kill the machine. That is suicide. Our bodies do not
tidy things up like a shopkeeper at the end of the day to shut down in
an organized manner. Our bodies want to keep going no matter what
our minds may want to do, and they fight to survive. But, they do
at some point lose the battle. There is a common sequence of
events to this defeat that many incorrectly describe as "their body
shutting down". That phrase implies that the person's mind or
body wills it. But the mind can't will it, and the body has no
will of its own. Again, it is a machine. At any point in
the failure sequence, if the cause of the failure is identified and
corrected, the body rebounds, and continues on. Physicians say this
when in fact, they just don't know what else to do. They lack the
skills, knowlege, medicine or equipment. Saying "their body is
shutting down" is a way of shifting the blame for their inadequacies
from themselves to the patient. If the patient or their body or
both have decided to "give up the ghost", then, well heck, the
physicians are not to blame, and can justify not trying anything else.
I'm trying to figure out what is driving force behind hospice. I
mean, it sounds like a kind an compasionate thing to do, to help
suffering and dying people in their final days by giving them palative
care and pain-killing drugs. Most people rave about how much help
they are. But if you look deeper, you find problems. First
is, who pays for it and why? It's not cheap to hire all of these
people and someone has to pay. Obviously, there is a limit since
if you don't expire quick enough, hospice disappears. Hmmm.
So, are insurance companies behind hospice to save money by keeping
people out of hospitals and from seeking extraordinary
medications? Is it Medicare?
Is there something more nefarious going on?
When the noted French atheist Voltaire expired, it is said that he was
screaming as he saw the gates of Hell opening up for him:
History tells the story of the renowned atheist,
Voltaire, one of the most aggressive antagonists of Christianity. He
wrote many things to undermine the church, and once said of Jesus
Christ, "Curse the wretch. In 20 years, Christianity will be no more.
My single hand will destroy the edifice it took 12 apostles to rear."
Needless to
say, Voltaire was less than successful. And on his deathbed, a nurse
who attended him was reported to have said, "For all the wealth in
Europe, I would not see another atheist die."
The
physician, waiting up with Voltaire at his death, said that he cried
out with utter desperation, "I am abandoned by God and man. I will give
you half of what I am worth if you will give me six months of life.
Then I shall go to hell and you will go with me, oh, Christ, oh, Jesus
Christ!"
http://www.wnd.com/index.php?pageId=44827
Rather inconvenient for those who, like Voltaire seek to "destroy the
edifice it took 12 apostles to rear". What better way of
preventing people from witnessing the final moments of a non-believer's
agony than to drug them up with morphine, or what have you? So,
is the purpose of hospice to prevent the Voltaire effect and therefore
thwart the inadvertent conversion of any who happen to be in the
vicinity?
If the purpose of hospice is to prevent suffering, I'm all for
it. But it just doesn't seem that all those providing the
services are doing so out of the goodness of their hearts.
********************************************************************************************
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
Mitochondrial Dysfunction
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 (Medium Chain
Triglycerides, MCT)
See also Coconut Oil
Recipes
More posts by Dr. Newport
Mitochondrial
Dysfunction
Dr. Sinatra
Note:
1. MCT oil may decrease the frequency and
severity of myoclonus in patients with certain neurodegenerative
diseases such as Alzheimer's disease, corticobasal syndrome (CBS, CBD,
CBGD), and frontotemporal dementia (FTD).
2. MCT oils added to the diet may also reduce the frequency and
severity of cold sores (herpes simplex virus-1) and other related
herpes viruses such as herpes zoster (chicken pox/shingles).
Coconut oil:
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
Glucose Hypometabolism:
Note: ALA may also positively affect glucose
metabolism.
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
Brain fuel metabolism, aging, and
Alzheimer's disease.
Nutrition.
2011
Jan;27(1):3-20.
Epub
2010
Oct
29.
Cunnane S,
Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S, Castellano
A, Pifferi F, Bocti C, Paquet N, Begdouri H, Bentourkia M, Turcotte E,
Allard M, Barberger-Gateau P, Fulop T, Rapoport SI.
Abstract
Lower brain glucose metabolism is present before the onset of
clinically measurable cognitive decline in two groups of people at risk
of Alzheimer's disease--carriers of apolipoprotein E4, and in those
with a maternal family history of AD. Supported by emerging evidence
from in vitro and animal studies, these reports suggest that brain
hypometabolism may precede and therefore contribute to the
neuropathologic cascade leading to cognitive decline in AD. The reason
brain hypometabolism develops is unclear but may include defects in
brain glucose transport, disrupted glycolysis, and/or impaired
mitochondrial function. Methodologic issues presently preclude knowing
with certainty whether or not aging in the absence of cognitive
impairment is necessarily associated with lower brain glucose
metabolism. Nevertheless, aging appears to increase the risk of
deteriorating systemic control of glucose utilization, which, in turn,
may increase the risk of declining brain glucose uptake, at least in
some brain regions. A contributing role of deteriorating glucose
availability to or metabolism by the brain in AD does not exclude the
opposite effect, i.e., that neurodegenerative processes in AD further
decrease brain glucose metabolism because of reduced synaptic
functionality and hence reduced energy needs, thereby completing a
vicious cycle. Strategies to reduce the risk of AD by breaking this
cycle should aim to (1) improve insulin sensitivity by improving
systemic glucose utilization, or (2) bypass deteriorating brain glucose
metabolism using approaches that safely induce mild, sustainable
ketonemia.
PMID: 21035308 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21035308
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
Ketone bodies are
selectively used by individual brain regions.
Science.
1979 Jul 20;205(4403):325-7.
Hawkins RA,
Biebuyck JF.
Abstract
Close study
of 3-hydroxybutyrate uptake by brain suggests that its metabolism is
limited by permeability. Furthermore, the permeability characteristics
vary from region to region; areas known to have no blood-brain barrier
show the highest rate of utilization. The results imply that rather
than substitute fuels, ketone bodies should be considered supplements
which partially supply specific areas but are incapable of supporting
the entire energy requirement of all brain regions.
PMID: 451608
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/451608?dopt=AbstractPlus
It is interesting that the idea of using ketone bodies as a "subsitute
fuel" was around in 1979. I haven't read the whole paper, so I
don't know the context. It probably was not in regards to
combating glucose hypometabolism. So, what fuels the brains of
people when they are starving? Is it the conversion of muscle
protein to glucose? I have to wonder if more modern imaging
technology agrees with this paper from 1979.
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...
********************************************************************************************
Mitochondrial
Dysfunction
See also,
Dr. Sinatra
More posts by Dr. Newport
Multifunctional
Cocktail
Anti-oxidant
trio
therapy [?]
Methylene Blue
ALA
Cognisure
Parkinson's
Disease
"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 (adenosine
triphosphate), the very basic energy that drives the whole function
of the cell. Each cell has hundreds to thousands of mitochondria."
The article below talks about research into the role of amyloid-beta
proteins in creating nitric oxide, which then damages the "powerhouse"
of the cell, the mitochondria. Could this be why neurons then have a
problem with glucose metabolism, and why MCTs help?
I remember reading another article about how LOW concentrations of
methylene blue may help preserve mitochondrial function: "the drug
slows cellular aging and enhances mitochondrial function". The
concentration is reported to be ridiculously low (meaning, more
research into the original paper is warranted.) But, if it is true that
very dilute methylene blue solutions are beneficial, then I have an
"act of desperation" option: Kordon's 2.3% Methylene Blue solution...
for fish! If a "very low concentration -- about the equivalent of a few
raindrops in four Olympic-sized swimming pools of water" would be
effective, then what about a drop of fish aquarium methylene blue in a
gallon or five of drinking water?
But even if you were to decide on going with laboratory-grade MB, which
is a bit pricey, at this level of concentration, a small quantity of MB
would last years.
Here are the articles:
Alzheimer's Disease Linked To Mitochondrial Damage
ScienceDaily
(Apr. 2, 2009)
Investigators
at
Burnham
Institute
for
Medical
Research
(Burnham)
have
demonstrated
that
attacks
on
the
mitochondrial
protein
Drp1
by
the
free
radical
nitric
oxide—which
causes
a
chemical
reaction
called
S-nitrosylation—mediates
neurodegeneration
associated
with
Alzheimer's
disease.
Prior
to
this
study,
the
mechanism
by
which
beta-amyloid
protein
caused
synaptic
damage
to
neurons
in
Alzheimer's
disease
was
unknown...
These
findings
suggest
that
preventing
S-nitrosylation
of
Drp1
may
reduce
or
even
prevent
neurodegeneration
in
Alzheimer's
patients.
The
paper
was
published
in
the
April
3
issue
of
the
journal
Science...
The
team
of
scientists,
led
by
neuroscientist
and
clinical
neurologist
Stuart
A.
Lipton,
M.D.,
Ph.D.,
director
of
the
Del
E.
Webb
Center
for
Neuroscience,
Aging
and
Stem
Cell
Research,
showed
that
S-nitrosylated
Drp1
(SNO-Drp1)
facilitates
mitochondrial
fragmentation,
damaging
regions
of
nerve
cell
communication
called
synapses.
Mitochondria
are
the
energy storehouses of the cell, and
their compromise by excessive fragmentation causes synaptic injury and
eventual nerve cell death. Synapses are critical for learning and
memory and their impairment leads to the dementia seen in Alzheimer's
patients...
http://www.sciencedaily.com/releases/2009/04/090402143453.htm
Interesting research suggests that maybe "free radicals" may not be as
big of a problem...
Free Radicals
Good for You? Banned Herbicide Makes Worms Live Longer
ScienceDaily
(Dec. 20, 2010) — It sounds like science fiction – Dr. Siegfried Hekimi
and his student Dr Wen Yang, researchers at McGill’s Department of
Biology, tested the current “free radical theory of aging” by creating
mutant worms that had increased production of free radicals, predicting
they would be short-lived. But they lived even longer than regular
worms! Moreover, their enhanced longevity was abolished when they were
treated with antioxidants such as vitamin C...
http://www.sciencedaily.com/releases/2010/12/101220084442.htm
Methylene blue...
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
This also begs the question, as I've stated before, that if such an
unimaginably small concentration of MB can be beneficial, can
comparatively dilute solutions of other chemicals in our water, food,
or environment be harmful?
Another point I would like to make is that there are steps to the
disease process. All of these things we have discussed appear to
interrupt different stages. So even if low-concentration MB is
effective, other steps of the disease process, once set in motion, may
still progress. I'm thinking of this in relation to why attacking the
amyloid beta plaque problem doesn't seem too effective. Perhaps it
really is, in the long term, or if the therapy was started early enough
before symptoms appeared. But once symptoms appear, there is a whole
freight train of other ones in motion. So, snipping off the locomotive
without activating the breaks on the box cars means that the train will
keep rolling on and on for a long, long time.
Early Role of
Mitochondria in Alzheimer's Disease May Help Explain Limitations to
Current Beta Amyloid Hypothesis
ScienceDaily
(Oct. 13, 2010) — Before Alzheimer's patients experience memory loss,
the brain's neurons have already suffered harm for years... A new study
in mouse models by researchers at Columbia University Medical Center
has found that the brain's mitochondria -- the powerhouses of the cell
-- are one of the earliest casualties of the disease. The study, which
appeared in the online Early Edition of PNAS, also found that impaired
mitochondria then injure the neurons' synapses, which are necessary for
normal brain function.
"The damage
to synapses is one of the earliest events in Alzheimer's disease, but
we haven't been able to work out the events that lead to the damage.
Our new findings, along with previous research, suggest that
mitochondrial changes harm the synapses, and that we may be able to
slow down Alzheimer's at a very early stage by improving mitochondrial
function."
Drugs that
restore mitochondria function may be able to treat Alzheimer's disease
in its earliest stages. One potential drug, cyclosporin, is already used in
organ transplant and autoimmune patients. Cyclosporin suppresses the
immune system, but it also blocks
amyloid beta (Aβ) peptides-induced mitochondrial injury, Dr. Yan
has found in previous studies (Du et al. Nature Medicine, 2008).
Cyclosporin,
however, has too many toxic side effects for long term use in other
patients...
Most
Alzheimer's researchers initially believed that Aβ peptides caused the
disease after aggregating together in large, extracellular plaques, a
defining feature of Alzheimer's-affected brains. But Dr.Yan's findings,
along with those of many other scientists, now point to an earlier role
for Aβ peptides inside the brain's neurons.
The
mitochondria are damaged, the researchers found, when (Aβ) peptides
breach the mitochondria's walls and accumulate on the inside. Even low
concentrations of Aβ peptides, equivalent to the levels found in cells
years before symptoms appear, impair the mitochondria, particularly
mitochondria that supply power to the neuron's synapses.
When filled
with Aβ peptides, these synaptic mitochondria were unable to travel
down the neurons' long axons to reach, and fuel, the synapse. And the
mitochondria that did make the journey failed to provide adequate
energy to operate the synapses. Without operating synapses, neurons are
unable to function.
"Since
cyclosporin is already FDA approved for use in organ transplant and
autoimmune patients, this research has the potential to lead to more
rapid clinical trials and progress quickly," said Dr. Yan...
http://www.sciencedaily.com/releases/2010/10/101013122557.htm
In Parkinson's
Disease, Brain Cells Abandon Mitochondria
ScienceDaily
(Oct. 8, 2010) — In a study that sheds new light on the causes of
Parkinson's disease, researchers report that brain cells in Parkinson's
patients abandon their energy-producing machinery, the mitochondria. A
shutdown in fuel can have devastating effects on brain cells, which
consume roughly 20 percent of the body's energy despite making up only
2 percent of body weight... researchers, now show that a root cause of
Parkinson's disease may lie in 10 gene sets related to energy
production that spur neurons in the brain to "divorce" their
mitochondria and related energy-producing pathways..."The most exciting
result from our study for me is the discovery of PGC-1alpha as a new
therapeutic target for early intervention in Parkinson's disease.
PGC-1alpha is a master switch that activates hundreds of mitochondrial
genes, including many of those needed to maintain and repair the power
plants in the mitochondria,"... FDA-approved medications [Actos, CoQ10]
that activate that PGC-1alpha are already available for widespread
diseases like diabetes. These medications may jumpstart the development
of new Parkinson's drugs; instead of having to start from scratch,
pharmaceutical companies may be able to dust off their drug libraries
and find look-alike drugs capable of targeting PGC-1alpha in the brain.
"As we wrap up our first year of publishing the journal, the new study
from Zheng et al. exemplifies the goal of Science Translational
Medicine, applying knowledge and technology from different fields-such
as neuroscience, genomics and bioinformatics-to achieve new
discoveries,"...
http://www.sciencedaily.com/releases/2010/10/101006151557.htm
Brain Might Be Key to Leptin's
Actions Against Type 1 Diabetes, Researchers Find
ScienceDaily (Nov. 14, 2010)
New findings by UT Southwestern Medical Center researchers suggest a
novel role for the brain in mediating beneficial actions of the hormone
leptin in type 1 diabetes... They found that infusing leptin into the
lateral ventricle of the animals' brains reversed the lethal
consequences of type 1 diabetes. The results establish the brain as a
potentially critical site for mediating the metabolism-improving
actions of leptin,...
http://www.sciencedaily.com/releases/2010/10/101019171711.htm
As mentioned
earlier, one inherits their mitochondria from their mothers...
Alzheimer's Disease Inherited Through
Maternal Line, Study Finds
ScienceDaily (Nov. 15, 2010)
"Our data indicate that adult children of mothers with Alzheimer's may
be at increased risk for developing the disease. It is therefore
extremely important to understand the genetic mechanisms involved in
maternal transmission of Alzheimer's disease, which are currently
unknown. Identifying a genetic predictor for the disease might lead to
preventive treatments years before the onset of clinical symptoms."
http://www.sciencedaily.com/releases/2010/11/101115111007.htm
********************************************************************************************
Dr. Sinatra (The
Sinatra Solution)
See also,
Coconut Oil / MCT Oil
D-Ribose
Acetyl-L Carnitine
Magnesium
CoQ10
Mitochondrial
Dysfunction
More posts by Dr. Newport
[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
http://www.drsinatra.com/sinatra-health-center-heart-health-dr-sinatras-healthy-heart-program
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.
Some other aticles:
1. Chen L, Wei Y, Wang X, He R. D-Ribosylated Tau forms globular
aggregates with high cytotoxicity Cell Mol Life Sci. 2009, 66(15),
2559-2571.
2. Lan Chen, Yan Wei, Xueqing Wang, Rongqiao He (2010) Ribosylation
rapidly induces a-synuclein protein into advanced glycation end
products in molten globules with high cytotoxicity. PLoS ONE 5(2):
e9052.
********************************************************************************************
Magnesium
********************************************************************************************
Acetyl-L
Carnitine
Dr. Stephen Sinatra - Statins, CoQ10,
and Carnitine
Statins, CoQ10, and Carnitine - What
Doctors Don't Tell Patients
...Carnitine's role is to exclusively ferry fatty acids to be oxidized
to make ATP. So the body needs a lot of it to be optimally
energized. A normal heart muscle derives 60-70 percent of its
fuel from fat... Equally important, carnitine transports waste material
out of the mitochondria, such as toxic metabolites that could otherwise
disturb the burning of fats and cause disruption inside of cells...
http://www.spacedoc.net/stephen_sinatra_3
********************************************************************************************
Resveratrol
See also Metformin
Extending Life
and Fighting Disease with Resveratrol
Life
Extension magazine article(8pgs)
August 2009
by Julius
Goepp, MD.
Scientists
are dicovering significant additional benefits that resveratrol confers
in fighting aging and degenerative disease.
While much
of this research was initiated by a prolific group at Harvard
University and in the biotech industry, scientists around the globe are
now making unprecedented discoveries that define resveratrol's multiple
preventive and therapeutic potentials.
Most
exciting are findings showing how resveratrol may help protect against
devastating age-related diseases including cancer, diabetes,
atherosclerosis and Alzheimer's...."
...We've
long known that resveratrol has potent antioxidant and
anti-inflammatory effects, making it a key item in our armamentarium of
supplements that can prevent age-associated chronic illnesses. The real
news is that resveratrol continues to be linked to the life-extending
effects of the powerful sirtuin molecules that control the fundamental
processes associated with aging itself. By potently activating
sirtuins, resveratrol stabilizes DNA to prevent cancerous changes,
switches on antioxidant and anti-inflammatory defense mechanisms native
to cells, and even instructs certain cells to commit organized suicide
by apoptosis. The end result is an almost incredible array of health
benefits, from reduction in cardiovascular risk factors to protection
against neurodegenerative disease to cancer prevention. Indeed,
resveratrol is being actively explored now by big pharmaceutical
companies eager to cash in on its potency by creating new drugs derived
from the natural molecule....
[NEED LINK!]
Compound Found in
Red Wine Neutralizes Toxicity of Proteins Related to Alzheimer's
ScienceDaily
(June 22, 2010)
... research
led by Rensselaer Professor Peter M. Tessier. The findings, published
in the May 28 edition of the Journal of Biological Chemistry... "We've
shown how resveratrol has very interesting selectivity to target and
neutralize a select set of toxic peptide isoforms. Because resveratrol
picks out the clumps of peptides that are bad and leaves alone the ones
that are benign, it helps us to think about the structural differences
between the peptide isoforms." Isoforms are different packing
arrangements of a particular peptide. Deformations of a particular
peptide -- the Aβ1-42 peptide -- have been linked to Alzheimer's
disease. Improperly folded peptides have been shown to collect in
accumulations called "plaques" within the brain. Those plaques are
often found near areas of cell death in diseased brains...
http://www.sciencedaily.com/releases/2010/06/100622112556.htm
********************************************************************************************
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
A supplement
called "Red Yeast Rice" (RYR) is said to have the same effects as
statin drugs. Here is a good case where just because something is
"natural" doesn't mean it is without deleterious effects.
********************************************************************************************
Coenzyme Q10
(CoQ10)
Note: CoQ10 may be useful in combating the negative effects of
certain statin drugs.
********************************************************************************************
Fish Oil
(EPA/DHA, docosahexaenoic acid)
DHA,Part
of
the
Gerbil Food
Cocktail for memory enhancement.
Liver Defect
Likely Cause of DHA Deficiency in Alzheimer's Patients, UCI Study Finds
ScienceDaily
(Sep. 9, 2010
UC Irvine
researchers have discovered that markedly depleted amounts of an
omega-3 fatty acid in brain tissue samples from Alzheimer's patients
may be due to the liver's inability
to produce the complex fat, also
contained in fish-oil supplements. In postmortem liver tissue from
Alzheimer's patients, the UCI team found a defect in the organ's
ability to make DHA from shorter molecules present in leafy plants and
other foods. Previous studies have shown that most brain DHA is
manufactured in the liver. Non-Alzheimer's livers did not have this
defect...
http://www.sciencedaily.com/releases/2010/09/100908171122.htm
DHA 'Fish Oil' Supplements Do Not
Seem to Slow Cognitive, Functional Decline in Alzheimer's Disease
ScienceDaily (Nov. 3, 2010)
Patients with mild to moderate Alzheimer's disease (AD) who received
supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA),
believed to possibly reduce the risk of AD, did not experience a
reduction in the rate of cognitive and functional decline, compared to
patients who received placebo, according to a study in the November 3
issue of JAMA, a theme issue on aging...
http://www.sciencedaily.com/releases/2010/11/101102101623.htm
DHA Improves Memory and Cognitive
Function in Older Adults, Study Suggests
ScienceDaily (Nov. 9, 2010)
A study published in the November edition of Alzheimer's &
Dementia: The Journal of the Alzheimer's Association suggests that
taking docosahexaenoic acid (DHA) may improve memory and learning in
older adults with mild cognitive impairments. This is promising news
for many aging Americans who are searching for options to maintain
memory and support overall cognitive health...
http://www.sciencedaily.com/releases/2010/11/101108151346.htm
Cognitive findings of an exploratory
trial of docosahexaenoic acid and lutein supplementation in older women.
Nutr
Neurosci. 2008 Apr;11(2):75-83.
Johnson EJ,
McDonald K, Caldarella SM, Chung HY, Troen AM, Snodderly DM.
Jean Mayer US Department of Agriculture Human Nutrition Research Center
on Aging at Tufts University, Boston, Massachusetts 02111, USA.
elizabeth.johnson@tufts.edu
Abstract
INTRODUCTION: Low dietary intake of docosahexaenoic acid (DHA) and/or
foods rich in lutein may be associated with increased risk of cognitive
decline in the elderly.
SUBJECTS AND METHODS: The cognitive benefit of DHA and lutein in
unimpaired elder women was explored in the context of a 4-month,
double-blind, intervention trial of DHA and lutein supplementation for
eye health. Forty-nine women (aged 60-80 years) were randomized to
receive DHA (800 mg/day; n = 14), lutein (12 mg/day; n = 11), a
combination of DHA and lutein (n = 14) or placebo (n = 10). Subjects
underwent cognitive tests measuring verbal fluency, memory, processing
speed and accuracy, and self-reports of mood at randomization and upon
completion of the trial.
RESULTS: Following supplementation, verbal fluency scores improved
significantly in the DHA, lutein, and combined treatment groups (P <
0.03). Memory scores and rate of learning improved significantly in the
combined treatment group (P < 0.03), who also displayed a trend
toward more efficient learning (P = 0.07). Measures of mental
processing speed, accuracy and mood were not affected by
supplementation.
CONCLUSIONS: These exploratory findings suggest that DHA and lutein
supplementation may have cognitive benefit for older adults.
PMID: 18510807 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/18510807
Algal DHA Omega-3 Improved Memory and
Learning in Healthy Adults 55 and Older
"... MIDAS found that healthy people with memory complaints who took
900 mg algal DHA capsules for six months had almost double the
reduction in errors on a test that measures learning and memory
performance versus those who took a placebo, a benefit roughly
equivalent to having the learning and memory skills of someone three
years younger. The DHA was well-tolerated and subjects taking the DHA
also experienced a lower heart rate, providing a significant
cardiovascular benefit...
http://www.alzheimersreadingroom.com/2010/05/algal-dha-omega-3-improved-memory-and.html
Algal DHA improves memory function in
healthy aging adults
http://www.news-medical.net/news/20100504/Algal-DHA-improves-memory-function-in-healthy-aging-adults-MIDAS.aspx
Good Diets Fight Bad Alzheimer's
Genes: Diets High in Fish Oil Have a Beneficial Effect in Patients at
Risk, Researcher Says
ScienceDaily (Feb. 15, 2011)... In preliminary results, the researchers
are exhilarated to find that a diet high in Omega 3 oils and low in
cholesterol appears to significantly reduce the negative effects of the
APOE4 gene in mouse models... "The main take-away message here is that
good diets can alleviate the effects of bad genes..."
http://www.sciencedaily.com/releases/2011/02/110215102848.htm
Supplementing
with
DHA
(fish
oil)
increases
BDNF? If you find a good source for
uridine (UMP), please let me know!
Chronic
Administration of DHA and UMP Improves the Impaired Memory of
Environmentally Impoverished Rats
Sarah
Holguin, Yi Huang, Jenny Liu, and Richard Wurtman
UMP and DHA
may protect the brains of IC reared animals by restoring neuronal
function to levels normally observed in brains of control or EC rats.
Rats exposed to IC conditions [43] or made DHA-deficient [44] have
decreased brain weight and size, while DHA administration increases
brain weight and size [44]. Brains of IC reared rats also exhibit
decreased neurogenesis [45] and synaptogenesis [46], DHA has
been shown
to promote neurite outgrowth in hippocampal neurons [47] and uridine
promotes neurite outgrowth from PC12 cells [24]. DHA supplementation
increased brain-derived neurotrophic factor (BDNF) levels in rats [48]
while consuming a diet deficient in DHA decreased these levels [49];
BDNF induces neurogenesis in the hippocampal dentate gyrus [50]..
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2478743/?tool=pubmed
********************************************************************************************
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.
Wikipedia entries:
Uridine:
Uridine is a molecule (known as a nucleoside) that
is formed when uracil is attached to a ribose ring (also known as a
ribofuranose) via a β-N1-glycosidic bond.
If uracil is
attached to a deoxyribose ring, it is known as a deoxyuridine.
[edit]
Dietary sources of uridine
Uridine is
one of the four basic components of ribonucleic acid (RNA); the other
three are adenosine, guanosine, and cytidine. Upon digestion of foods
containing RNA, uridine is released from RNA and is absorbed intact in
the gut. Some common food sources of uridine are:
*
Sugarcane
extract
*
Tomatoes
(0.5
to
1.0
g
uridine
per
kilogram
dry
weight)
*
Brewer’s
yeast
(3%
uridine
by
dry
weight)
*
Beer
*
Broccoli
*
Organ
meats
(liver,
pancreas,
etc.)
Consumption
of RNA-rich foods may lead to high levels of purines (adenosine and
guanosine) in blood. High levels of purines are known to increase uric
acid production and may aggravate or lead to conditions such as gout.
Moderate consumption of yeast, about 5 grams per day, should provide
adequate uridine for improved health with minimal side
effects.[citation needed]
Note: It has
been suggested that the RNA content of yeast products should be
chemically reduced if these products are to be consumed in high amounts
(50 grams or more per day) as a source of protein. However, such
processing is expensive and, as of 2008, commonly available brewer's
yeast products were not RNA-reduced.[citation needed]
Harvard
researchers report that supplementation in rats with a combination of
uridine and EPA/DHA omega-3 fatty acids has antidepressant activity
equivalent to that of commonly prescribed antidepressant medications,
such as Prozac and other SSRIs.[5]
http://en.wikipedia.org/wiki/Uridine
Uridine
monophosphate:
Uridine monophosphate, also known as 5'-uridylic
acid and abbreviated UMP, is a nucleotide that is found in RNA. It is
an ester of phosphoric acid with the nucleoside uridine. UMP consists
of the phosphate group, the pentose sugar ribose, and the nucleobase
uracil; hence, it is a ribonucleoside monophosphate. Another common
shorthand for the molecule is uridylate - the deprotonated form of the
molecule, which is predominant in aqueous solution. As a substituent it
takes the form of the prefix uridylyl-...
Uridine Monophosphate in Foods
In brain research studies such as those mentioned in this article,
uridine monophosphate is used as a convenient delivery compound for
uridine. Uridine is the active ingredient of the compound. A common
misconception is that uridine and its compounds are not available in
significant quantities from foods and must be obtained from expensive
supplements or prescription drugs. This is not so. Uridine
monophosphate is a major component of RNA. Any food rich in RNA, such
as Brewer's yeast or some organ meats, will provide significant
quantities of it. For more information, consult the article on uridine.
http://en.wikipedia.org/wiki/Uridine_monophosphate
Another name for orotic acid is uracil-6-carboxylic acid. Uracil is one
ribose sugar away from uridine.
Found in breast milk. Metabolized from orotates. I'm not sure it
can be obtained in the diet. The articles I've read about the
Gerbil Food Cocktail say that it is synthesized by the liver and
kidneys.
Brewer's yeast is a good source of uridine (from the RNA). Many
brewer's yeasts are byproducts of brewing beer, and are therefore quite
bitter and beer-like. You can find brewer's yeast that is grown
on sugar beets or molasses, and has a much better taste.
I found this interesting statement in a post to a message board.
I don't know the source.
Effect of oral CDP-choline on plasma choline and
uridine levels in humans.
Wurtman RJ,
Regan M, Ulus I, Yu L.
Department
of Brain & Cognitive Sciences, Massachusetts Institute of
Technology, Cambridge, MA 02139, USA.
Biochem
Pharmacol. 2000 Oct 1;60(7):989-92.
Twelve
mildly hypertensive but otherwise normal fasting subjects received each
of four treatments in random order: CDP-choline (citicoline; 500, 2000,
and 4000 mg) or a placebo orally at 8:00 a.m. on four different
treatment days. Eleven plasma samples from each subject, obtained just
prior to treatment (8:00 a.m.) and 1-12 hr thereafter, were assayed for
choline, cytidine, and uridine. Fasting terminated at noon with
consumption of a light lunch that contained about 100 mg choline.
Plasma choline exhibited dose-related increases in peak values and
areas under the curves (AUCs), remaining significantly elevated, after
each of the three doses, for 5, 8, and 10 hr, respectively. Plasma
uridine was elevated significantly for 5-6 hr after all three doses,
increasing by as much as 70-90% after the 500 mg dose, and by 100-120%
after the 2000 mg dose. No further increase was noted when the dose was
raised from 2000 to 4000 mg. Plasma cytidine was not reliably
detectable, since it was less than twice blank, or less than 100 nM, at
all of the doses. Uridine is known to enter the brain and to be
converted to UTP; moreover, we found that uridine was converted
directly to CTP in neuron-derived PC-12 cells. Hence, it seems likely
that the circulating substrates through which oral citicoline increases
membrane phosphatide synthesis in the brains of humans involve uridine
and choline, and not cytidine and choline as in rats.
PMID:
10974208 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/10974208
So, it sounds like 500 mg to 1000 mg citicholine taking along with fish
oil might be worth a shot at duplicating those test results??
Dietary
uridine-5'-monophosphate supplementation increases potassium-evoked
dopamine release and promotes neurite outgrowth in aged rats.
Wang L,
Pooler AM, Albrecht MA, Wurtman RJ.
Department
of Brain and Cognitive Sciences, Massachusetts Institute of Technology,
Cambridge, MA 02142, USA.
J Mol
Neurosci. 2005;27(1):137-45.
Abstract
Membrane
phospholipids like phosphatidylcholine (PC) are required for cellular
growth and repair, and specifically for synaptic function. PC synthesis
is controlled by cellular levels of its precursor,
cytidine-5'-diphosphate choline (CDP-choline), which is produced from
cytidine triphosphate (CTP) and phosphocholine. In rat PC12 cells
exogenous uridine was shown to elevate intracellular CDP-choline
levels, by promoting the synthesis of uridine triphosphate (UTP), which
was partly converted to CTP. In such cells uridine also enhanced the
neurite outgrowth produced by nerve growth factor (NGF). The present
study assessed the effect of dietary supplementation with uridine-5'-monophosphate disodium
(UMP-2Na+, an additive in infant milk formulas) on striatal
dopamine (DA) release in aged rats. Male Fischer 344 rats consumed
either a control diet or one fortified with 2.5% UMP for 6 wk, ad
libitum. In vivo microdialysis was then used to measure spontaneous and
potassium (K+)-evoked DA release in the right striatum. Potassium
(K+)-evoked DA release was significantly greater among UMP-treated
rats, i.e., 341+/-21% of basal levels vs. 283+/-9% of basal levels in
control rats (p<0.05); basal DA release was unchanged. In general,
each animal's K+-evoked DA release correlated with its striatal DA
content, measured postmortem. The levels of neurofilament-70 and
neurofilament-M proteins, biomarkers of neurite outgrowth, increased to
182+/-25% (p<0.05) and 221+/-34% (p<0.01) of control values,
respectively, with UMP consumption. Hence, UMP treatment not only
enhances membrane phosphatide production but also can modulate two
membrane-dependent processes, neurotransmitter release and neurite
outgrowth, in vivo.
PMID:
16055952 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/16055952
The opinion that uridine can not be obtained from the diet seems to
have come from an interview by Anne Trafton of
the MIT News Office for an April 27, 2006 article about
Richard Wurtman's research, which was published in the November issue
of Brain Research. A
similar statement was in a November 26, 2007 article.
MIT research
offers new hope for Alzheimer's patients
Anne
Trafton, News Office
April 27,
2006
Choline can
be found in meats, nuts and eggs, and omega-3 fatty acids are found in
a variety of sources, including fish, eggs, flaxseed and meat from
grass-fed animals. Uridine, which is
found in RNA and produced by the liver and kidney, is not obtained from
the diet. However, uridine is found in human breast milk, which
is a good indication that supplementary uridine is safe for humans to
consume, Wurtman said.
http://web.mit.edu/newsoffice/2006/alzheimers.html
'Cocktail' of
compounds improves brain function in rodents
Treatment
undergoing a clinical study in Alzheimer's patients
Anne
Trafton, News Office
November 26,
2007
...Omega-3
fatty acids are not produced in the body but are found in a variety of
sources, including fish, eggs, flaxseed and meat from grass-fed
animals. Choline can be synthesized in the body and obtained through
the diet; it is found in meats, nuts and eggs. Uridine cannot be obtained from food sources,
but
is
a
component
of
human
breast
milk
and
can
be
produced
in
the
body.
http://web.mit.edu/newsoffice/2007/alzheimers-1126.html
This may be
the paper mentioned in Trafton's 2006 article:
Oral uridine-5'-monophosphate (UMP)
increases brain CDP-choline levels
in gerbils.
Cansev M,
Watkins CJ, van der Beek EM, Wurtman RJ.
Department
of Brain and Cognitive Sciences, Massachusetts Institute of Technology,
E25-604, MIT, Cambridge, MA 02139, USA.
Brain Res.
2005 Oct 5;1058(1-2):101-8. Epub 2005 Aug 29.
Abstract
We examined
the biochemical pathways whereby oral uridine-5'-monophosphate (UMP)
increases membrane phosphatide synthesis in brains of gerbils. We
previously showed that supplementing PC12 cells with uridine caused
concentration-related increases in CDP-choline levels, and that this
effect was mediated by elevations in intracellular uridine triphosphate
(UTP) and cytidine triphosphate (CTP). In the present study, adult
gerbils received UMP (1 mmol/kg), a constituent of human breast milk
and infant formulas, by gavage, and plasma samples and brains were
collected for assay between 5 min and 8 h thereafter. Thirty minutes
after gavage, plasma uridine levels were increased from 6.6 +/- 0.58 to
32.7 +/- 1.85 microM (P < 0.001), and brain uridine from 22.6 +/-
2.9 to 89.1 +/- 8.82 pmol/mg tissue (P < 0.001). UMP also
significantly increased plasma and brain cytidine levels; however, both
basally and following UMP, these levels were much lower than those of
uridine. Brain UTP, CTP, and CDP-choline were all elevated 15 min after
UMP (from 254 +/- 31.9 to 417 +/- 50.2, [P < 0.05]; 56.8 +/- 1.8 to
71.7 +/- 1.8, [P < 0.001]; and 11.3 +/- 0.5 to 16.4 +/- 1, [P <
0.001] pmol/mg tissue, respectively), returning to basal levels after
20 and 30 min. The smallest UMP dose that significantly increased brain
CDP-choline was 0.05 mmol/kg. These results show that oral UMP, a
uridine source, enhances the synthesis of CDP-choline, the immediate
precursor of PC, in gerbil brain.
PMID:
16126180 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/16126180
The following research was done on rats. I have not found similar
research on humans. Please send me a note if you find some.
The effect of RNA
supplementation of rat diets on the composition of body fluids.
Heaf DJ,
Davies JI.
Br J Nutr.
1976 Nov;36(3):381-402.
Abstract
1. In a
number of separate experiments, yeast RNA, mixtures of its constituent
nucleosides, its constituent bases and ribose were administered orally
to rats. In each instance, the resultant changes in the composition of
body fluids were monitored using sensitive methods. 2. Ingestion of RNA
(100 g/kg diet) caused detectable increases in intestinal ribose,
inorganic phosphate, uridine, pseudouridine, uracil, inosine, uric acid
and probably other purine bases. Their accumulation did not detectably
affect the rate of passage of food along the digestive tract, even
though some nucleosides are known to affect gut motility. 3. Although
plasma levels of uric acid and uridine were higher when RNA was
administered in the diet, these changes were very slight compared with
those in plasma uracil, which in some experiments were increased more
than 20-fold compared with control levels (300 mumol/l). Analysis of
erythrocytes indicated that the internal environment of at least some
cells of the body are similarly altered. 4. Analyses indicated that all
dietary RNA-phosphate passed into the urine from the gut but most of
the RNA-ribose was probably metabolized. Uracil and uric acid levels in
the urine reflected plasma composition. 5. The effect of orally
administered mixed nucleosides on blood and urine composition was
similar to that of RNA, but the response to an equivalent mixture of
free bases differed in several respects; cytosine, adenine and
hypoxanthine appeared in urine only under these circumstances.
PMID: 795459
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/795459
This is perhaps the most useful article. Beer consumption raised
blood plasma uridine levels by a factor of 1.8 (180%) compared to
overnight fasting levels.
Effect of beer on
the plasma concentrations of uridine and purine bases.
Yamamoto T,
Moriwaki Y, Takahashi S, Tsutsumi Z, Ka T, Fukuchi M, Hada T.
Division of
Endocrinology and Metabolism, Department of Internal Medicine, Hyogo
College of Medicine, Hyogo, Japan.
Metabolism.
2002 Oct;51(10):1317-23.
Abstract
We conducted
the present study to determine whether beer, both with and without
ethanol content, increases the plasma concentration and urinary
excretion of purine bases and uridine. Because 10 mL of regular beer
(with ethanol) was found to contain 0.34 g of freeze-dried beer
(without ethanol) and 0.5 mg of uridine, 5 healthy males were given
regular beer (10 mL/kg of body weight) and freeze-dried beer (0.34 g/kg
of body weight) or uridine (0.5 mg/kg of body weight). The plasma
concentrations of hypoxanthine, xanthine, and uridine increased by
3.5-fold (P <.05), 4.7-fold (P <.05), and 1.8-fold (P <.05),
respectively, 30 minutes after regular beer ingestion, and the urinary
excretion of hypoxanthine, xanthine, and uridine increased by 4.0-fold
(P <.05), 4.5-fold (P <.01), and 1.7-fold (P <.05),
respectively, when measured 1 hour after ingestion. The plasma
concentrations of uric acid and total purine bases increased by 6.5% (P
<.05) and 7.6% (P <.05), respectively, 30 minutes after regular
beer ingestion, whereas the urinary excretion of uric acid did not
increase, while that of total purine bases increased by 1.3-fold (P
<.05) when measured 1 hour after ingestion. As for freeze-dried
beer, the plasma concentrations of uric acid total purine bases
increased by 4.4% (P <.05) and 4.6% (P <.05), respectively, and
that of uridine by 1.5-fold (P <.01) 30 minutes after ingestion,
while the urinary excretion of uridine increased by 1.4-fold (P
<.01) 1 hour after ingestion. However, the plasma concentrations and
urinary excretion of hypoxanthine and xanthine and the urinary
excretion of uric acid and total purine bases did not change
significantly. As for uridine ingestion, the plasma concentration of
uridine increased by 1.37-fold (P <.01) 30 minutes after ingestion,
and the urinary excretion of uridine increased by 1.3-fold (P <.01)
1 hour after ingestion. However, the plasma concentrations and urinary
excretion of hypoxanthine, xanthine, uric acid, and total purine bases
did not change significantly. These results suggest that the purines in
beer played a major role in the increase in the plasma concentration of
uric acid, while both uridine and ethanol in beer had a significant
effect on the increase in plasma concentration of uridine.
PMID:
12370853 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/12370853
This article is only useful in that it provides the amount of RNA in
baking yeast, which is the same species as brewer's yeast. 66.2g of RNA
per kg of dry yeast. Table 1 on p. 239
Safety
considerations of DNA in food.
Jonas DA,
Elmadfa I, Engel KH, Heller KJ, Kozianowski G, König A,
Müller D, Narbonne JF, Wackernagel W, Kleiner J.
Institute of
Nutritional Sciences, University of Vienna, Vienna, Austria.
Ann Nutr
Metab. 2001;45(6):235-54.
PMID:
11786646 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/11786646
Effect of oral
CDP-choline on plasma choline and uridine levels in humans.
Wurtman RJ,
Regan M, Ulus I, Yu L.
Department
of Brain & Cognitive Sciences, Massachusetts Institute of
Technology, Cambridge, MA 02139, USA.
Biochem
Pharmacol. 2000 Oct 1;60(7):989-92.
Abstract
Twelve
mildly hypertensive but otherwise normal fasting subjects received each
of four treatments in random order: CDP-choline (citicoline; 500, 2000,
and 4000 mg) or a placebo orally at 8:00 a.m. on four different
treatment days. Eleven plasma samples from each subject, obtained just
prior to treatment (8:00 a.m.) and 1-12 hr thereafter, were assayed for
choline, cytidine, and uridine. Fasting terminated at noon with
consumption of a light lunch that contained about 100 mg choline.
Plasma choline exhibited dose-related increases in peak values and
areas under the curves (AUCs), remaining significantly elevated, after
each of the three doses, for 5, 8, and 10 hr, respectively. Plasma uridine was elevated significantly
for 5-6 hr after all three doses, increasing by as much as 70-90% after
the 500 mg dose, and by 100-120% after the 2000 mg dose. No further
increase was noted when the dose was raised from 2000 to 4000 mg.
Plasma cytidine was not reliably detectable, since it was less than
twice blank, or less than 100 nM, at all of the doses. Uridine is known
to enter the brain and to be converted to UTP; moreover, we found that
uridine was converted directly to CTP in neuron-derived PC-12 cells.
Hence, it seems likely that the circulating substrates through which
oral citicoline increases membrane phosphatide synthesis in the brains
of humans involve uridine and choline, and not cytidine and choline as
in rats.
PMID:
10974208 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/10974208
********************************************************************************************
B-complex
Vitamins
See also B6
B9
B12
Niacinamide
Recommended dosages gleaned from the articles cited below:
B-Vitamin Trio:
vitamin B6 (pyridoxine HCl) - 20mg
vitamin B9
(folate or folic acid) - 0.8mg (= 800 mcg.)
vitamin B12 (cyanocobalamin) - 0.5mg (= 500
mcg.)
Here in the U.S., I found "Tri-B" from Carlson. It has 25mg B-6,
800mcg B9, 400mcg B-12. Close enough for me!
B vitamins found to halve brain shrinkage in old
Wed Sep 8,
2010 5:01pm EDT
LONDON
(Reuters) - Daily tablets of large doses of B vitamins can halve the
rate of brain shrinkage in elderly people with memory problems and may
slow their progression toward dementia... The pills, called "TrioBe
Plus" contained around 300 times the recommended daily intake of B12,
four times daily advised folate levels and 15 times the recommended
amount of B6...
http://www.reuters.com/article/idUSTRE6875CL20100908
B-Complex Vitamins May Help Slow Progression of
Dementia
ScienceDaily
(Oct. 27, 2010)
Large doses of B-complex vitamins could reduce the rate of brain
shrinkage by half in elderly people with memory problems and slow the
progression of dementia.
http://www.sciencedaily.com/releases/2010/10/101027155126.htm
Vitamin B
treatment could delay onset of Alzheimer's - study
Published
Date: 08 September 2010
The
research, published in the online journal Public Library of Science
ONE, is controversial because it defies current scientific dogma about
the way to tackle Alzheimer's...
http://www.yorkshireeveningpost.co.uk/news/Vitamin-B-treatment-could-delay.6520596.jp
10p pill to beat Alzheimer's disease:
Vitamin B halts memory loss in breakthrough British trial
By Fiona Macrae
Last updated at 12:12 PM on 9th September 2010
The breakthrough centres on a compound called homocysteine which is
naturally made in the body and, at high levels, has been linked to
memory loss and Alzheimer's... Vitamin B is known to break down
homocysteine, so the researchers decided to look at whether giving
patients the vitamin would be good for memory... High dose vitamins may
trigger cancer and are known to fuel existing cancers. They may also
react with medicines including arthritis and psoriasis drugs. Despite
this, Professor Smith says he ‘would not hesitate’ to take the cocktail
of 20mg of vitamin B6, 0.8mg of vitamin B9, or folate, and 0.5mg of
vitamin B12, himself, if he were diagnosed with MCI.
http://www.dailymail.co.uk/health/article-1310330/Vitamin-B-halts-memory-loss-10p-pill-beat-Alzheimers-disease.html
Read more:
http://www.dailymail.co.uk/health/article-1310330/Vitamin-B-halts-memory-loss-10p-pill-beat-Alzheimers-disease.html#ixzz0zOqfSHaZ
Homocysteine-Lowering
by
B
Vitamins
Slows
the
Rate
of
Accelerated
Brain
Atrophy
in
Mild
Cognitive
Impairment:
A
Randomized
Controlled
Trial
A. David
Smith1, Stephen M. Smith, Celeste A. de Jager, Philippa Whitbread,
Carole Johnston, Grzegorz Agacinski, Abderrahim Oulhaj, Kevin M.
Bradley, Robin Jacoby, Helga Refsum
Results
A total of
168 participants (85 in active treatment group; 83 receiving placebo)
completed the MRI section of the trial. The mean rate of brain atrophy
per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group
and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment
response was related to baseline homocysteine levels: the rate of
atrophy in participants with homocysteine >13 µmol/L was 53%
lower in the active treatment group (P = 0.001). A greater rate of
atrophy was associated with a lower final cognitive test scores. There
was no difference in serious adverse events according to treatment
category...
The treatment group received oral TrioBe Plus® (Meda AB/Recip AB,
Box 906, Pipers väg 2A, SE-170 09 Solna, Sweden) containing 0.8 mg
folic acid, 0.5 mg cyanocobalamin and 20 mg pyridoxine HCl, or a
placebo.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012244
B Vitamins Slow
Brain Atrophy in People With Memory Problems
ScienceDaily
(Sep. 12, 2010) — Daily tablets of certain B vitamins can halve the
rate of brain shrinkage in elderly people who suffer from mild memory
problems, an Oxford University study has shown... The team found that
on average the brains of those taking the folic acid, vitamin B6 and
B12 treatment shrank at a rate of 0.76% a year, while those in the
placebo group had a mean brain shrinkage rate of 1.08%. People with the
highest levels of homocysteine benefited most, showing atrophy rates on
treatment that were half of those on placebo...
http://www.sciencedaily.com/releases/2010/09/100912213050.htm
According to the Wikipedia entry for B12, cyanocobalamin is converted
to methylcobalamin.
********************************************************************************************
Vitamin B6
(Pyridoxine)
Seven forms of this vitamin are known:
* Pyridoxine (PN), the form that is given as vitamin
B6 supplement
* Pyridoxine 5'-phosphate (PNP)
* Pyridoxal (PL)
* Pyridoxal 5'-phosphate (PLP), the metabolically
active form
* Pyridoxamine (PM)
* Pyridoxamine 5'-phosphate (PMP)
* 4-Pyridoxic acid (PA), the catabolite which is
excreted in the urine
All forms except PA can be interconverted.
********************************************************************************************
Vitamin B9
(folate, folic acid)
********************************************************************************************
Vitamin B12 (cobalamin,
cyanocobalamin, methylcobalamin)
Wikipedia entry:
Vitamin B12, vitamin B12 or vitamin B-12, also
called cobalamin, is a water soluble vitamin with a key role in the
normal functioning of the brain and nervous system, and for the
formation of blood. It is one of the eight B vitamins. It is normally
involved in the metabolism of every cell of the human body, especially
affecting DNA synthesis and regulation, but also fatty acid synthesis
and energy production. As the largest and most structurally complicated
vitamin, it can be produced industrially only through bacterial
fermentation-synthesis.
Vitamin B12
consists of a class of chemically-related compounds (vitamers), all of
which have vitamin activity. It contains the biochemically rare element
cobalt. Biosynthesis of the basic structure of the vitamin in nature is
only accomplished by simple organisms such as some bacteria and algae,
but conversion between different forms of the vitamin can be
accomplished in the human body. A common synthetic form of the vitamin,
cyanocobalamin, does not occur in nature, but is used in many
pharmaceuticals and supplements, and as a food additive, because of its
stability and lower cost. In the body
it is converted to the physiological forms, methylcobalamin and
adenosylcobalamin, leaving behind the cyanide, albeit in minimal
concentration. More recently, hydroxocobalamin (a form produced by
bacteria), methylcobalamin, and adenosylcobalamin can also be found in
more expensive pharmacological products and food supplements. The
utility of these is presently debated...
http://en.wikipedia.org/wiki/Vitamin_b12
Vitamin B12 May
Reduce Risk of Alzheimer's Disease
ScienceDaily
(Oct. 18, 2010) — A new study shows that vitamin B12 may protect
against Alzheimer's disease, adding more evidence to the scientific
debate about whether the vitamin is effective in reducing the risk of
memory loss... The study found that for each micromolar increase in the
concentration of homocysteine, the risk of Alzheimer's disease
increased by 16 percent, whereas each picomolar increase in
concentration of the active form of vitamin B12 reduced risk by two
percent. The results stayed the same after taking into account other
factors, such as age, gender, education, smoking status, blood pressure
and body mass index. The addition of folate did not appear to raise or
lower the risk of Alzheimer's disease...
http://www.sciencedaily.com/releases/2010/10/101018162922.htm
Another resource is the book
Here is one reader review from Amazon.com:
I am an MD, a nutritional physician, and a
psychiatrist (Canadian-board-certified) who has been studying vitamin
B12 extensively since 1976, and applying that knowledge in my private
nutritional, metabolic and psychiatric practice in Tucson AZ since 1994
(and Portsmouth VA before that).
This book is
an outstanding compilation of anecdotes, references and experiences on
the "underground devastator" of our society. The reason why this is not
common knowledge in the medical profession in the US is because the
laboratory "normal range" is way too low. In Japan the range is 2.5
times higher at its low end - and Japan has very little "Alzheimer's
Dementia", and less depression and bipolar disorders, than we do in the
US.
In the 26
years that I have been investigating B12, memory disorders and
depressive/ bipolar illnesses, NO patient who came to me with a memory
problem (early Alzheimer's) has gone on to Alzheimer's dementia, and I
have a near-perfect track record in helping people overcome depression
and bipolar disorders. These outcomes are largely due to my permanent
optimization of every patient's serum B12 level.
Congratulations
to
Ms
Sally
Pacholok
RN
on
an
outstanding
recording
of
most
of
the
important
facts
and
treatments
for
this
serious
condition.
I
believe
it
to
be
the
best
book
out
there
for
a
combination
of
both
medical
and
lay
readers
on
this
condition.
[To anyone
reading this review: Please do not simply go and buy B12 tablets or
lozenges and start taking them, before getting an accurate serum level
measured.]
John V
Dommisse MD, MBChB, FRCP(C)
Tucson, AZ,
USA
--------------------------------------------------------------------------------
Protective
effects of a vitamin B12
analogue, methylcobalamin, against glutamate cytotoxicity in cultured
cortical neurons
Akaike A
Tamura Y Sato Y Yokota T,
Eur J
Pharmacol (1993 Sep 7) 241(1):1-6
The effects
of methylcobalamin, a vitamin B12 analogue, on
glutamate-induced neurotoxicity were examined using cultured rat
cortical neurons. Cell viability was markedly reduced by a brief
exposure to glutamate followed by incubation with glutamate-free medium
for 1 h. Glutamate cytotoxicity was prevented when the cultures were
maintained in methylcobalamin-containing medium. Glutamate cytotoxicity
was also prevented by chronic exposure to S-adenosylmethionine, which
is formed in the metabolic pathway of
methylcobalamin. Chronic exposure to methylcobalamin and S-
adenosylmethionine also inhibited the cytotoxicity induced by
methyl-D-aspartate or sodium
nitroprusside that releases nitric oxide. In cultures maintained in a
standard medium, glutamate cytotoxicity was not affected by adding
methylcobalamin to the glutamate-containing medium. In contrast, acute
exposure to
MK-801, a NMDA receptor antagonist, prevented glutamate cytotoxicity.
These
results indicate that chronic exposure to methylcobalamin protects
cortical neurons against NMDA receptor-mediated glutamate
cytotoxicity.
--------------------------------------------------------------------------------
Methylcobalamin
and
Diabetic
Neuropathy
Clinical usefulness of intrathecal
injection of methylcobalamin in patients with diabetic neuropathy
Ide H Fujiya
S Asanuma Y Tsuji M Sakai H
Agishi Y, Clin Ther (1987) 9(2):183-92
Seven men
and four women with
symptomatic diabetic neuropathy were treated with methylcobalamin
(2,500 micrograms
in 10 ml of saline) injected intrathecally. Treatment was begun when
patients had good metabolic control, as determined by measurements
of plasma glucose and hemoglobin, and was repeated several times with a
one-month interval between injections. Three patients were
re-treated one year after the last intrathecal injection. Symptoms in
the
legs, such as paresthesia, burning pains, and heaviness, dramatically
improved. The effect appeared within a few hours to one week and lasted
from
several months to four years. The mean peroneal motor-nerve conduction
velocity did not change significantly. The mean (+/- SD)
concentration of methylcobalamin in spinal fluid was 114 +/- 32 pg/ml
before
intrathecal injection (n = 5) and 4,752 +/- 2,504 pg/ml one month after
intrathecal methylcobalamin treatment (n = 11). Methylcobalamin
caused no side effects with respect to subjective symptoms or
characteristics
of spinal fluid. These findings suggest that a high concentration of
methylcobalamin in spinal fluid is highly effective and safe for
treating
the symptoms of diabetic neuropathy.
--------------------------------------------------------------------------------
Nerve
Regeneration with Methylcobalamin
Ultra-high dose methylcobalamin promotes
nerve regeneration in experimental acrylamide neuropathy.
Watanabe T
Kaji R Oka N Bara W Kimura J,
J Neurol Sci (1994 Apr) 122(2):140-3
Despite
intensive searches for
therapeutic agents, few substances have been convincingly shown to
enhance nerve
regeneration in patients with peripheral neuropathies. Recent
biochemical evidence suggests that an ultra-high dose of
methylcobalamin
(methyl-B12) may up-regulate gene transcription and thereby protein
synthesis. We examined the effects of ultra-high dose of methyl-B12 on
the
rate of nerve regeneration in rats with acrylamide neuropathy, using
the
amplitudes of compound muscle action potentials (CMAPs) after tibial
nerve
stimulation as an index of the number of regenerating motor fibers.
After intoxication with acrylamide, all the rats showed equally
decreased
CMAP amplitudes. The animals were then divided into 3 groups; rats
treated
with ultra-high (500 micrograms/kg body weight,
intraperitoneally) and low (50 micrograms/kg) doses of methyl- B12, and
saline-treated
control rats. Those treated with ultra-high dose showed significantly
faster CMAP recovery than saline-treated control rats, whereas the
low-dose group showed no difference from the control.
Morphometric analysis revealed a similar difference in fiber density
between
these groups. Ultra-high doses of methyl-B12 may be of clinical use for
patients with peripheral neuropathies.
--------------------------------------------------------------------------------
Methylcobalamin,
Bell's
Palsy
Methylcobalamin treatment of Bell's Palsy
Jalaludin
MA, Methods Find Exp Clin
Pharmacol (1995 Oct) 17(8):539-44
Bell's palsy
patients were assigned into
three treatment groups: steroid (group 1), methylcobalamin (group 2)
and
methylcobalamin + steroid (group 3). Comparison between the three
groups
was based on the number of days needed to attain full recovery, facial
nerve scores, and improvement of concomitant symptoms. The time
required
for complete recovery of facial nerve function was significantly
shorter
in the methylcobalamin and methylcobalamin plus steroid groups than
in the steroid group. The facial nerve score after 1-3 weeks of
treatment
was significantly more severe (p < 0.001) in the steroid group
compared to the methylcobalamin and methylcobalamin plus steroid
groups. The
improvement of concomitant symptoms was better in the
methylcobalamin treated groups than the group treated with steroid
alone.
--------------------------------------------------------------------------------
Nerve
Terminal Regeneration
Methylcobalamin (methyl-B12) promotes
regeneration of motor nerve terminals degenerating in anterior
gracile muscle of gracile axonal dystrophy (GAD) mutant mouse.
Yamazaki K
Oda K Endo C Kikuchi T
Wakabayashi T, Neurosci Lett (1994 Mar 28) 170(1):195-7
We examined
the effects of
methylcobalamin (methyl-B12, mecobalamin) on degeneration of motor
nerve terminals in
the anterior gracile muscle of gracile axonal dystrophy (GAD) mutant
mice. GAD mice received orally methyl-B12 (1 mg/kg body wt/day) from
the 40th day after birth for 25 days. In the distal endplate zone of
the
muscle, although most terminals were degenerated in both the untreated
and methyl-B12-treated GAD mice, sprouts were more frequently observed
in
the latter. In the proximal endplate zone, where few degenerated
terminals were seen in both groups of the mice, the perimeter of the
terminals
was increased and the area of the terminals was decreased significantly
in
the methyl-B12-treated GAD mice. These findings indicate that
methyl-B12
promotes regeneration of degenerating nerve terminals in GAD
mice.
--------------------------------------------------------------------------------
Fighting
Neurotoxicity
Protective effects of methylcobalamin, a
vitamin B12 analogue, against glutamate-induced neurotoxicity in
retinal cell culture.
Kikuchi M
Kashii S Honda Y Tamura Y
Kaneda K Akaike, Invest Ophthalmol Vis
Sci (1997
Apr) 38(5):848-54
Purpose: To
examine the effects of
methylcobalamin on glutamate- induced neurotoxicity in the cultured
retinal
neurons. Methods: Primary cultures obtained from the fetal rat retina
(gestation days 16 to 19) were used for the experiment. The
neurotoxicity was
assessed quantitatively using the trypan blue exclusion method.
Results:
Glutamate neurotoxicity was prevented by chronic exposure to
methylcobalamin and S-adenosylmethionine (SAMe), which is formed in the
metabolic
pathway of methylcobalamin. Chronic exposure to methylcobalamin and
SAMe also inhibited the neurotoxicity induced by sodium
nitroprusside that release nitric oxide. By contrast, acute exposure to
methylcobalamin did not protect retinal neurons against glutamate
neurotoxicity.
Conclusions: Chronic administration of methylcobalamin
protects cultured retinal neurons against N-methyl-D-
aspartate-receptor-mediated glutamate neurotoxicity, probably by
altering the membrane
properties through SAMe-mediated methylation.
--------------------------------------------------------------------------------
Methyl Donor
Effects
Effect of cobalamin derivatives on in
vitro enzymatic DNA methylation: methylcobalamin can act as a methyl
donor.
Leszkowicz A
Keith G Dirheimer G,
Biochemistry (1991 Aug 13) 30(32):8045-51
Methylcytosine
synthesis
in
DNA
involves
the
transfer
of
methyl
groups
from
S-adenosylmethionine
to
the
5'-position
of
cytosine
through
the
action
of
DNA
(cytosine-5)-methyltransferase.
The
rate
of
this
reaction
has
been
found
to
be
enhanced
by
cobalt
ions.
We
therefore
analyzed
the
influence
of
vitamin
B12
and
related
compounds
containing
cobalt
on
DNA
methylation.
Vitamin
B12,
methylcobalamin,
and
coenzyme
B12
(methylcobalamin)
were
found
to
enhance
significantly
the
de
novo
DNA
methylation
in
the
presence
of
S-adenosylmethionine
for
concentrations
up
to
1
microM,
but
at
higher
concentrations
these
compounds
were
found
to
inhibit DNA methylation.
Methylcobalamin
behaves as a competitive inhibitor of the enzymatic methylation
reaction (Ki = 15 microM), the Km for S-adenosylmethionine being 8
microM.
In addition, the use of radioactive methylcobalamin shows that
it can be used as a methyl donor in the de novo and maintenance DNA
methylation reactions. Thus, two DNA methylation pathways could exist:
one
involving methylation from S-adenosylmethionine and a second one
involving methylation from methylcobalamin.
********************************************************************************************
Niacinamide
/ nicotinamide
See also Tau Busters
B-complex
Vitamins
Wikipedia entry:
Nicotinamide, also known as niacinamide and
nicotinic acid amide, is the amide of nicotinic acid (vitamin B3 /
niacin). Nicotinamide is a water-soluble vitamin and is part of the
vitamin B group. Nicotinic acid, also known as niacin, is converted to
nicotinamide in vivo, and, though the two are identical in their
vitamin functions, nicotinamide does not have the same pharmacologic
and toxic effects of niacin, which occur incidental to niacin's
conversion. Thus nicotinamide does not reduce cholesterol or cause
flushing,[1] although nicotinamide may be toxic to the liver at doses
exceeding 3 g/day for adults. In cells, niacin is incorporated into
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...
http://en.wikipedia.org/wiki/Niacinamide
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
Vitamin B3
Reduces Alzheimer's Symptoms, Lesions: Clinical Trial On
Nicotinamide Effect In Alzheimer's Patients
ScienceDaily
(Nov. 5, 2008) — An over-the-counter vitamin in high doses
prevented memory loss in mice with Alzheimer's disease, and UC Irvine
scientists now are conducting a clinical trial to determine its effect
in humans. Nicotinamide, a form of vitamin B3, lowered levels of a
protein called phosphorylated tau that leads to the development of
tangles, one of two brain lesions associated with Alzheimer's disease.
The vitamin also strengthened scaffolding along which information
travels in brain cells, helping to keep neurons alive and further
preventing symptoms in mice genetically wired to develop Alzheimer's.
"Nicotinamide has a very robust effect on neurons," said Kim Green, UCI
scientist and lead author of the study. "Nicotinamide prevents loss of
cognition in mice with Alzheimer's disease, and the beauty of it is we
already are moving forward with a clinical trial."...
http://www.sciencedaily.com/releases/2008/11/081104180926.htm
********************************************************************************************
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
Dietary
supplementation with apple juice decreases endogenous amyloid-beta
levels in murine brain.
Amy
Chan and Thomas B. Shea.
Journal of
Alzheimer's Disease, 16:1 (January 2009)
http://www.ncbi.nlm.nih.gov/pubmed/19158432
Apple juice may also increased the
amount of acetylcholine:
An Apple a Day
for AD? Antioxidants in Apples May Help Memory and Fight Alzheimer's
Disease
By Jennifer
Warner
WebMD Health
News
Aug. 4, 2006
-- "An apple (or two) a day may help keep Alzheimer's away -- and fight
the effects of aging on the brain. A new study shows drinking apple
juice may improve memory by preventing the decline of an essential
neurotransmitter known as acetylcholine..."
http://www.webmd.com/alzheimers/news/20060804/alzheimers-apple
WARNING: Juices can interact with prescription meds either negating or
enhancing their effect. So, you have to do your homework. For example,
if you take the beta blocker atenenol, you shouldn't take it with
orange juice. The OJ will will block the drug's effect.
********************************************************************************************
Tau Busters
See also Cinnamon
Methylene
Blue
Niacinamide
Grape seed extract
Davunitide
Nypta
Valproic
Acid
Tau
Metformin
Epothilone D
Discovery Of Molecular Cause Of
Alzheimer's Disease Could Bring Early Diagnosis, Treatment Closer
25 May 2009
... The crucial protein, called a tau protein, is a normal part of the
brain and central nervous system. But in Alzheimer's patients, tau
proteins go out of control and form tangles that, along with senile
plaques, are the primary cause of the degenerative disease.
Several years ago, it was discovered that tau proteins in normal brains
contain only three to four attached phosphates, while abnormal tau in
Alzheimer's patients have anywhere from 21 to 25 additional
phosphates...
http://www.medicalnewstoday.com/articles/151234.php
There
are several substances we have heard about since late 2007
that might be 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.
Phenothiazine-mediated rescue of cognition
in tau transgenic mice requires neuroprotection and reduced soluble tau
burden
It has traditionally been thought that the pathological accumulation of
tau in Alzheimer's disease and other tauopathies facilitates
neurodegeneration, which in turn leads to cognitive impairment.
However, recent evidence suggests that tau tangles are not the entity
responsible for memory loss, rather it is an intermediate tau species
that disrupts neuronal function.
Thus, efforts to discover
therapeutics for tauopathies emphasize soluble tau reductions as well
as neuroprotection.
Results: Here, we found that neuroprotection alone
caused by methylene blue (MB), the parent compound of the anti-tau
phenothiaziazine drug, RemberTM, was insufficient to rescue cognition
in a mouse model of the human tauopathy, progressive supranuclear palsy
(PSP) and fronto-temporal dementia with parkinsonism linked to
chromosome 17 (FTDP17): Only when levels of soluble tau protein were
concomitantly reduced by a very high concentration of MB, was cognitive
improvement observed. Thus, neurodegeneration can be decoupled from tau
accumulation, but phenotypic improvement is only possible when soluble
tau levels are also reduced.
Conclusions: Neuroprotection
alone is not sufficient to rescue tau-induced memory loss in a
transgenic mouse model.
Development of neuroprotective
agents is an area of intense investigation in the tauopathy drug
discovery field. This may ultimately be an unsuccessful approach if
soluble toxic tau intermediates are not also reduced.
Thus, MB and related compounds,
despite their pleiotropic nature, may be the proverbial "magic
bullet"because they not only are neuroprotective, but are also able to
facilitate soluble tau clearance. Moreover, this shows that
neuroprotection is possible without reducing tau levels.
This indicates that there is a
definitive molecular link between tau and cell death cascades that can
be disrupted.
Author: John O'LearyQingyou
LiPaul MarinecLaura BlairErin CongdonAmelia JohnsonUmesh JinwalJohn
KorenJeffrey JonesClara KraftMelinda PetersJose AbisambraKaren
DuffEdwin WeeberJason GestwickiChad Dickey
Credits/Source: Molecular
Neurodegeneration 2010
http://7thspace.com/headlines/362179/phenothiazine_mediated_rescue_of_cognition_in_tau_transgenic_mice_requires_neuroprotection_and_reduced_soluble_tau_burden_.html
Full text of the article:
On page 11
of the article, it says "A treatment of 650mg/day in a 70kg (154lb)
human equates to 9.3mg/kg/day." So, 650mg spread through the day.
However, on Page 2 it says that FDA guidelines are 10mg/kg (of body
mass) for a mouse is equivalent to ~1mg/kg for a human. This seems to
be a contradiction. I'm not sure where they got that 650mg number from. In the article
it mentions that they were using 5 times the recommended dose. I don't
know where they got the "recommended dose" from. It might be that they
are using this 10:1 mouse to man ratio. It probably should have been
65mg/day dose for a 70kg human is about 1mg/kg. Then multiply by 10.
The equivalent for a mouse would be about 10mg/day for a mouse. But a
short cut to get that number would be to multiply the human dose by 10
and then divide by the weight of 70kg. If this is so,
65mg isn't so bad. If I remember correctly, the clinical trials of
Rember (a variation on the methylene blue theme) used something like
60mg 3 times per day. There is a post about it on the group's Yahoo web
site about 2 years ago.
********************************************************************************************
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.
Pilot Clinical Trial Meets Primary
Endpoint With Allon's Davunetide
Medical News Today
Article Date: 11 Oct 2010 - 3:00 PDT
Allon Therapeutics Inc. (TSX: NPC) announced that a pilot clinical
trial successfully met its primary endpoint of safety and tolerability,
with the Company's lead neuroprotective drug candidate davunetide, in
patients with progressive supranuclear palsy (PSP) and other types of
frontotemporal dementia (FTD) like corticobasal syndrome, and
progressive non-fluent aphasia. FTD is a group of rapidly progressive
and fatal degenerative brain diseases, often misdiagnosed as
Parkinson's or Alzheimer's disease... Allon's laboratory and animal
studies have shown that davunetide improves cognition in a number of
disease models through a mechanism believed to involve effects on
microtubules, structures in the brain critical to communication between
cells...
http://www.medicalnewstoday.com/articles/204182.php
********************************************************************************************
Valproic
Acid (Depakote)
See also Tau Busters
Valproic acid (VPA) is a chemical compound that has
found clinical use as an anticonvulsant and mood-stabilizing drug,
primarily in the treatment of epilepsy, bipolar disorder, and less
commonly major depression. It is also used to treat migraine headaches
and schizophrenia. It is marketed under the brand names Depakote,
Depakote ER, Depakene, Depacon, Depakine, Stavzor.
Related
drugs include the sodium salts sodium valproate, used as an
anticonvulsant, and a combined formulation, valproate semisodium, used
as a mood stabilizer and additionally in the U.S. also as an
anticonvulsant.
VPA is a
histone deacetylase inhibitor and is under investigation for treatment
of HIV and various cancers...
http://en.wikipedia.org/wiki/Valproic_acid
Phase II
trial: Active (NCT00385710
on clinicaltrials.gov)
"Progressive Supranuclear Palsy (PSP) is a relentlessly progressive
neurodegenerative disorder, clinically characterized by parkinsonism
with prominent axial involvement and postural instability, bulbar
symptoms, supranuclear ophthalmoplegia, and executive dysfunction.
Abnormal neuronal and glial tau aggregations affecting the basal
ganglia and selective brainstem structures result in dysfunction of the
five frontosubcortical circuits and brainstem functions. There is no
effective treatment for PSP. One of the key feature in the aggregation
of tau is its phosphorylation by kinases such as glycogen synthase
kinase 3b (GSK3b). Recent reports have shown that valproic acid was
able to inhibit the activity of GSK3b and could exert a neuroprotective
effect through this inhibition. The investigators thus decided to
conduct this controlled study to assess the putative neuroprotective
effects in patients with PSP."
********************************************************************************************
Nypta
See also Tau Busters, Inflammation,
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
NP031112, a thiadiazolidinone
compound, prevents inflammation and neurodegeneration under excitotoxic
conditions: potential therapeutic role in brain disorders.
Luna-Medina R, Cortes-Canteli M, Sanchez-Galiano S, Morales-Garcia JA,
Martinez A, Santos A, Perez-Castillo A.
Instituto de Investigaciones Biomédicas, Consejo Superior de
Investigaciones Científicas, Universidad Autónoma de
Madrid, 28029
Madrid, Spain.
Abstract
Inflammation and neurodegeneration coexist in many acute damage and
chronic CNS disorders (e.g., stroke, Alzheimer's disease, Parkinson's
disease). A well characterized animal model of brain damage involves
administration of kainic acid, which causes limbic seizure activity and
subsequent neuronal death, especially in the CA1 and CA3 pyramidal
cells and interneurons in the hilus of the hippocampus. Our previous
work demonstrated a potent anti-inflammatory and neuroprotective effect
of two thiadiazolidinones compounds, NP00111
(2,4-dibenzyl-[1,2,4]thiadiazolidine-3,5-dione) and NP01138
(2-ethyl-4-phenyl-[1,2,4]thiadiazolidine-3,5-dione), in primary
cultures of cortical neurons, astrocytes, and microglia. Here, we show
that injection of NP031112, a more potent thiadiazolidinone derivative,
into the rat hippocampus dramatically reduces kainic acid-induced
inflammation, as measured by edema formation using T2-weighted magnetic
resonance imaging and glial activation and has a neuroprotective effect
in the damaged areas of the hippocampus. Last, NP031112-induced
neuroprotection, both in vitro and in vivo, was substantially
attenuated by cotreatment with GW9662 (2-chloro-5-nitrobenzanilide), a
known antagonist of the nuclear receptor peroxisome
proliferator-activated receptor gamma, suggesting that the effects of
NP031112 can be mediated through activation of this receptor. As such,
these findings identify NP031112 as a potential therapeutic agent for
the treatment of neurodegenerative disorders.
J Neurosci. 2007 May
23;27(21):5766-76.
PMID: 17522320 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/17522320
Free article: Journal of Neuroscience http://www.jneurosci.org/cgi/content/full/27/21/5766
********************************************************************************************
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.
This might be the paper referred to in the Times of India article cited
in my earlier post:
Neurosci Lett. 2010 Oct 11;483(2):123-6. Epub 2010
Aug 5.
Sinha M,
Saha A, Basu S, Pal K, Chakrabarti S.
Department
of Biochemistry, Institute of Postgraduate Medical Education and
Research (IPGMER), Kolkata, West Bengal, India.
Abstract
The study
has shown that in aged (22-24 months) rat brains an elevation of
homocysteine level (42%) and a decrease in dehydroepiandrosterone
sulphate (DHEA-S) content (32%) occur compared to those in the brains
of young rats (4-6 months). Such changes in the brain levels of
homocysteine and DHEA-S in aged rats are prevented, when the diet daily
of the rats is supplemented with a combination of antioxidants
(N-acetyl cysteine 50 mg, alpha-lipoic acid 3 mg and alpha-tocopherol
1.5 mg - each per 100 g of body weight) starting from 18 months until
these are sacrificed between 22 and 24 months. The brain content of
reduced glutathione is also decreased in aged rats as compared to that
in young ones and the phenomenon can again be prevented completely by
the same regimen of antioxidant supplementation. The changes in the
levels of homocysteine and DHEA-S in aged rat brain have been related
to associated glutathione depletion and oxidative stress and the
implications of the results highlighted in the pathogenesis of
Alzheimer's disease.
PMID:
20691758 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/20691758
Let's see how these quantities would translate to a person weighing
100lbs. There are 2.2lbs per kilogram (kg). There are 1000g
per kg. For a 100lb woman, 45.5kg
N-acetyl cysteine (NAC) 50 mg/100g (of body
weight) 500mg/kg 22727mg
23.0g (WOW!)
alpha-lipoic
acid
(ALA) 3 mg/100g
30mg/kg
1363mg 1.4g
alpha-tocopherol (Vit. E) 1.5 mg/100g
15mg/kg
682mg
0.7g
Methinks something is rotten in the state of West Bengal.
[Does this target mitochondrial dysfunction?????]
********************************************************************************************
Alpha-lipoic Acid
(ALA)
See also Anti-oxidant trio therapy
ALA
is available only by prescription in Europe. It is available over
the counter in the U.S.
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]
Laboratory studies have also indicated that lipoic acid reverses the
age-associated decline in the proper functioning of mitochondria.
[From http://www.raysahelian.com/lipoic.html Need citation! It
could be in mprovement of insulin sensitivity in patients with type 2
diabetes mellitus after oral administration of alpha-lipoic acid.
Kamenova P. Hormones (Athens). 2006 Oct-Dec;5(4):251-8. Department of
Diabetology, University Hospital of Endocrinology, Medical University,
Sofia, Bulgaria. ]
From the Linus Pauling Institute at Oregon State
University:
Supplements
...Since taking LA with a meal decreases its bioavailability, it is
generally recommended that LA be taken on an empty stomach (one hour
before or two hours after eating)...
Glucose Utilization
There is limited evidence that high doses of LA can improve glucose
utilization in individuals with type 2 DM [diabetes mellitus]...
Cognitive Decline and Dementia
LA alone or
in combination with other antioxidants or L-carnitine has been found to
improve measures of memory in animal models of age-associated cognitive
decline, including rats (62, 63), mice (64) and dogs (65). However, it
is not clear whether oral LA supplementation can slow cognitive decline
related to aging or other pathology in humans. An uncontrolled,
open-label trial in 9 patients with Alzheimer’s disease and related
dementias, who were also taking acetylcholinesterase inhibitors,
reported that oral supplementation with 600 mg/day of racemic
LA appeared to stabilize cognitive function over a one-year period
(66). However, the significance of these findings is difficult to
assess without a control group for comparison. A randomized controlled
trial found that oral supplementation with 1200 mg/day of racemic LA
for 10 weeks was of no benefit in treating HIV-associated cognitive
impairment (67). Although studies in animals suggest that LA may be
helpful in slowing age-related cognitive decline, randomized controlled
trials are needed to determine whether LA supplementation is effective
in preventing or slowing cognitive decline associated with age or
neurodegenerative disease.
http://lpi.oregonstate.edu/infocenter/othernuts/la/
I think I also read somewhere that ALA is not a strong antioxidant, so
it might be broken down disadvantageously if combined with other
antioxidants.
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
Dr. Sahelian recommends 10-50mg per day or every other day. There
have been reports that higher doses of ALA can cause tachycardia or
heart arrhythmias (in susceptible people).
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
(r)-, but not
(s)-alpha lipoic acid stimulates deficient brain pyruvate dehydrogenase
complex in vascular dementia, but not in Alzheimer dementia.
J Neural
Transm. 2004 Mar;111(3):295-310. Epub 2003 Oct 24.
Frölich
L, Götz ME, Weinmüller M, Youdim MB, Barth N, Dirr A, Gsell
W, Jellinger K, Beckmann H, Riederer P.
In dementia
of Alzheimer type (DAT), cerebral glucose metabolism is reduced in
vivo, and enzymes involved in glucose breakdown are impaired in
post-mortem brain tissue. Pyruvate dehydrogenase complex activity
(PDHc) is one of the enzymes known to be reduced, while succinate
dehydrogenase activity (SDH), another enzyme of oxidative glucose
metabolism is unchanged. In dementia of vascular type (DVT), variable
changes in glucose metabolism have been demonstrated in vivo, while
changes of enzyme activities in post-mortem brain tissue are unknown.
Here, PDHc and SDH activity were stimulated with each of the two
stereoisomers of alpha lipoic acid in post-mortem parietal brain cortex
of patients with DAT, DVT, and one case of Pick's disease and compared
to stimulation effects in a control group, matched for age, sex,
post-mortem delay, and storage time of brain tissue. PDHc in DAT and
DVT, but not in Pick's disease was reduced. PDHc activity could be
slightly stimulated by 10 micro M of the physiological stereoisomer
(r)-alpha-lipoic acid, in controls and DVT (possibly also in Pick's
disease), but not in DAT. In all groups investigated SDH was activated
by 100 micro M and 1 mM of both isomers of alpha-lipoic acid, whereas
10 mM of both stereoisomers of alpha-lipoic acid caused an inhibition
of both, PDHc and SDH activity. The loss of basal and of
(r)-alpha-lipoic acid stimulated PDHc activity indicate that a
functional or structural impairment of PDHc may exist in DAT and DVT
which is not merely attributable to loss of mitochondria since basal
and stimulated SDH activities are similar in controls, DVT and DAT,
thus indicating selective vulnerability of PDHc.
http://www.ncbi.nlm.nih.gov/pubmed/14991456?dopt=Abstract
Lipoic acid: a
novel therapeutic approach for multiple sclerosis and other chronic
inflammatory diseases of the CNS.
Salinthone
S, Yadav V, Bourdette DN, Carr DW.
Abstract
The
naturally occurring antioxidant lipoic acid (LA) was first described as
an essential cofactor for the conversion of pyruvate to Acetyl-CoA, a
critical step in respiration. LA is now recognized as a compound that
has many biological functions. Along with its reduced form
dihydrolipoic acid (DHLA), LA reduces and recycles cellular
antioxidants such as glutathione, and chelates zinc, copper and other
transition metal ions in addition to heavy metals. LA can also act as a
scavenger of reactive oxygen and nitrogen species. By acting as an
insulin mimetic agent, LA stimulates glucose uptake in many different
cell types and can also modulate insulin signaling. The p38 and ERK MAP
kinase pathways, AKT and NFkappaB are all regulated by LA. In addition,
LA activates the prostaglandin EP2 and EP4 receptors to stimulate the
production of the small molecule cyclic adenosine 5' monophosphate
(cAMP). These diverse actions suggest that LA may be therapeutically
effective in treating oxidative stress associated diseases. This review
discusses the known biochemical properties of LA, its antioxidant
properties, its ability to modulate signal transduction pathways, and
the recent progress made in the utilization of LA as a therapeutic
alternative for multiple sclerosis, Alzheimer's disease and diabetic
neuropathy.
PMID:
18537699 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/18537699
Lipoic acid as an anti-inflammatory
and neuroprotective treatment for Alzheimer's disease.
Maczurek
A,
Hager
K,
Kenklies
M,
Sharman
M,
Martins
R,
Engel
J,
Carlson
DA,
Münch
G.
Department of Pharmacology, School of Medicine, University of Western
Sydney, Australia.
Adv
Drug Deliv Rev. 2008 Oct-Nov;60(13-14):1463-70. Epub 2008 Jul 4.
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder
that destroys patient memory and cognition, communication ability with
the social environment and the ability to carry out daily activities.
Despite extensive research into the pathogenesis of AD, a
neuroprotective treatment - particularly for the early stages of
disease - remains unavailable for clinical use. In this review, we
advance the suggestion that lipoic acid (LA) may fulfil this
therapeutic need. A naturally occurring cofactor for the mitochondrial enzymes pyruvate dehydrogenase and alpha-ketoglutarate
dehydrogenase, LA has been shown to have a variety of properties which
can interfere with the pathogenesis or progression of AD. For example,
LA increases acetylcholine (ACh) production by activation of choline
acetyltransferase and increases glucose uptake, thus supplying more
acetyl-CoA for the production of ACh. LA chelates redox-active
transition metals, thus inhibiting the formation of hydroxyl radicals
and also scavenges reactive oxygen species (ROS), thereby increasing
the levels of reduced glutathione. In addition, LA down-regulates the
expression of redox-sensitive pro-inflammatory proteins including TNF and inducible nitric oxide synthase.
Furthermore, LA can scavenge lipid peroxidation products such as
hydroxynonenal and acrolein. In human plasma, LA exists in an
equilibrium of free and plasma protein bound form. Up to 150 muM, it is
bound completely, most likely binding to high affinity fatty acid sites
on human serum albumin, suggesting
that one large dose rather than continuous low doses (as provided by
"slow release" LA) will be beneficial for delivery of LA to the brain.
Evidence for a clinical benefit for LA in dementia is yet limited.
There are only two published studies, in which 600 mg LA was given
daily to 43 patients with AD (receiving a standard treatment with
choline-esterase inhibitors) in an open-label study over an observation
period of up to 48 months. Whereas the improvement in patients with
moderate dementia was not significant, the disease progressed extremely
slowly (change in ADAScog: 1.2 points=year, MMSE: -0.6 points=year) in
patients with mild dementia (ADAScog<15). Data from cell culture and
animal models suggest that LA could be combined with nutraceuticals
such as curcumin, (-)-epigallocatechin gallate
(from green tea) and docosahexaenoic acid
(from fish oil) to synergistically decrease
oxidative stress, inflammation, Abeta levels and Abeta plaque load and
thus provide a combined benefit in the treatment of AD.
PMID: 18655815 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/18655815
********************************************************************************************
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
Phytonutrients and Metabolic Stimulants as
protection Against Neurodegeneration and Excitotoxicity
The Journal of the American
Nutraceutical Association
January 2000 Vol. 2, No. 3 Pg. 33
In a subsequent study reported in the Annals of Neurology in 1992,
Stanley Fahn found that supplementing early stage Parkinson’s patients
with 3,200 iu/day of vitamin E (the form was not disclosed), and 3000mg
/day of vitamin C could delay the onset of a need for levodopa by 2 to
3 years.69 This was a pilot study and not controlled.
http://www.ana-jana.org/Journal/journals/JANAVol23.pdf
********************************************************************************************
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
["Cerefolin with NAC (http://www.cerefolin.com/)
contains
Vitamin
B12,
methylfolate,
NAC?]
********************************************************************************************
Amyloid
Beta and Alzheimer's Disease
See also Curcumin
Infection
Copper
Apple
Juice
EGCG
(Green Tea Extract)
Oligomers
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
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
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
The Alzheimer's
Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide
Soscia,
Kirby, Washicosky, Tucker, Ingelsson, Hyman, Burton, Goldstein, Duong,
Tanzi, Moir
March 3, 2010
Abstract
Background
The amyloid
β-protein (Aβ) is believed to be the key mediator of Alzheimer's
disease (AD) pathology. Aβ is most often characterized as an incidental
catabolic byproduct that lacks a normal physiological role. However, Aβ
has been shown to be a specific ligand for a number of different
receptors and other molecules, transported by complex trafficking
pathways, modulated in response to a variety of environmental
stressors, and able to induce pro-inflammatory activities.
Methodology/Principal
Findings
Here, we
provide data supporting an in vivo function for Aβ as an antimicrobial
peptide (AMP). Experiments used established in vitro assays to compare
antimicrobial activities of Aβ and LL-37, an archetypical human AMP.
Findings reveal that Aβ exerts antimicrobial activity against eight
common and clinically relevant microorganisms with a potency equivalent
to, and in some cases greater than, LL-37. Furthermore, we show that AD
whole brain homogenates have significantly higher antimicrobial
activity than aged matched non-AD samples and that AMP action
correlates with tissue Aβ levels. Consistent with Aβ-mediated activity,
the increased antimicrobial action was ablated by immunodepletion of AD
brain homogenates with anti-Aβ antibodies.
Conclusions/Significance
Our findings
suggest Aβ is a hitherto unrecognized AMP that may normally function in
the innate immune system. This finding stands in stark contrast to
current models of Aβ-mediated pathology and has important implications
for ongoing and future AD treatment strategies.
Soscia "The
Alzheimer’s Disease-Associated Amyloid b-Protein Is an Antimicrobial
Peptide" PLOS March 2010,Volume 5, Issue 3, e9505: www.plosone.org
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009505
The Amyloid
Question
Chemical
& Engineering News Volume 88, Number 14 pp. 12 - 17
April 5, 2010
Lisa M.
Jarvis
...The worry
among some experts is that the development of amyloid-β-targeting
compounds by Pfizer, Elan Pharmaceuticals, Eli Lilly & Co.,
Bristol-Myers Squibb, and others began long before the underlying
biology of the peptide was well understood. New research suggests that
amyloid-β may also play a beneficial role in the brain, whereas other
studies claim the peptide is overproduced only after another neurotoxin
does its dirty work. With nearly every drug in the pipeline targeting
some aspect of the amyloid-β pathway, some Alzheimer’s researchers are
concerned that industry has placed all its eggs in one fragile
basket... Currently, patients’ only treatment options are drugs that
dampen the symptoms of the disease. Pfizer’s Aricept keeps
acetylcholinesterase from breaking down the neurotransmitter
acetylcholine, maximizing the amount available to carry messages, and
Forest Laboratories’ Namenda blocks a glutamate receptor thought to
play a role in learning and memory...
http://pubs.acs.org/cen/email/html/8814cover.html
Researchers
Discover Weak Link in Alzheimer’s Drug Candidates
Nanotech-Now.com
April 2nd, 2010
...Some
current therapies being investigated for Alzheimer's disease may cause
further neural degeneration and cell death, according to a breakthrough
discovery by UC San Diego researchers. By combining three dimensional
computer simulations with high resolution atomic force microscopy
membrane protein and cell imaging, electrical recording and various
cellular assays, UCSD nano-biophysicist Ratnesh Lal and his colleagues
investigated the structure and function of truncated peptides, known as
nonamyloidgenic peptides, formed by some Alzheimer's drug candidates...
http://www.nanotech-now.com/news.cgi?story_id=37558
The research paper:
Truncated
β-amyloid peptide channels provide an alternative mechanism for
Alzheimer’s Disease and Down syndrome
PNAS
February 16,
2010
...The
toxicity of nonamyloidogenic peptides via an ion channel mechanism
necessitates a reevaluation of the current therapeutic approaches
targeting the nonamyloidogenic pathway as avenue for AD treatment...
http://www.pnas.org/content/107/14/6538.long
Alzheimer's drugs cause brain damage and
actually worsen memory loss
NaturalNews
April 21,
2010
...Big
Pharma drugs that are being used on humans right now and promoted as
potential treatments for Alzheimer's disease (AD) could cause the very
brain damage and memory loss they are supposed to treat. That's the
conclusion of University of California at San Diego (UCSD) scientists
who just published their groundbreaking findings in the Proceedings of
the National Academy of Sciences...
http://www.naturalnews.com/028622_Alzheimers_brain_damage.html
The medical device CogniShunt was conceived
as a way to drain CFS (cerebral-spinal fluid) in the hopes that this
would lower the amyloid beta protein levels in the brain.
Alzheimer's Plaques Lead to Loss of Nitric Oxide in
Brain
ScienceDaily
(Jan. 17, 2011)... Levels of nitric oxide (NO) -- a signaling molecule
that helps regulate blood flow, immune and neurological processes --
are known to be low in the brains of people who have Alzheimer's
disease, but the reason for that hasn't been clear, said study
co-author Jeffrey S. Isenberg, M.D., M.P.H., associate professor,
Division of Pulmonary, Allergy, and Critical Care Medicine, Pitt School
of Medicine.
"Our
research sheds light on how that loss of NO might happen, and reveals
biochemical pathways that drug discoverers might be able to exploit to
find new medicines for Alzheimer's. There is evidence that suggests
enhancing NO levels can protect neurons from degenerating and dying."...
http://www.sciencedaily.com/releases/2011/01/110110103832.htm
An Alzheimer's Vaccine in a Nasal
Spray?
ScienceDaily (Feb. 28, 2011)
...researchers led by Dr. Dan Frenkel of Tel Aviv University's
Department of Neurobiology at the George S. Wise Faculty of Life
Sciences are working on a nasally-delivered 2-in-1 vaccine that
promises to protect against both Alzheimer's and stroke. The new
vaccine repairs vascular damage in the brain by rounding up "troops"
from the body's own immune system...
http://www.sciencedaily.com/releases/2011/02/110228104310.htm
Alzheimer's-Like Brain Changes Found in Cognitively Normal Elders With
Amyloid Plaques
ScienceDaily (Mar. 30, 2011) — Researchers using two brain-imaging
technologies have found that apparently normal older individuals with
brain deposits of amyloid beta -- the primary constituent of the
plaques found in the brains of Alzheimer's disease patients -- also had
changes in brain structure similar to those seen in Alzheimer's
patients...
http://www.sciencedaily.com/releases/2011/03/110330111353.htm
Reference: J. Alex Becker, Trey Hedden, Jeremy Carmasin, Jacqueline
Maye, Dorene M. Rentz, Deepti Putcha, Bruce Fischl, Douglas N. Greve,
Gad A. Marshall, Stephen Salloway, Donald Marks, Randy L. Buckner,
Reisa A. Sperling, Keith A. Johnson. Amyloid-β
associated
cortical thinning in clinically normal elderly.
Annals of Neurology, 2011
********************************************************************************************
Multiple Sclerosis
(MS)
See also CCSVI
ALA
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.
Lipoic acid: a
novel therapeutic approach for multiple sclerosis and other chronic
inflammatory diseases of the CNS.
Salinthone
S, Yadav V, Bourdette DN, Carr DW.
Abstract
The
naturally occurring antioxidant lipoic acid (LA) was first described as
an essential cofactor for the conversion of pyruvate to Acetyl-CoA, a
critical step in respiration. LA is now recognized as a compound that
has many biological functions. Along with its reduced form
dihydrolipoic acid (DHLA), LA reduces and recycles cellular
antioxidants such as glutathione, and chelates zinc, copper and other
transition metal ions in addition to heavy metals. LA can also act as a
scavenger of reactive oxygen and nitrogen species. By acting as an
insulin mimetic agent, LA stimulates glucose uptake in many different
cell types and can also modulate insulin signaling. The p38 and ERK MAP
kinase pathways, AKT and NFkappaB are all regulated by LA. In addition,
LA activates the prostaglandin EP2 and EP4 receptors to stimulate the
production of the small molecule cyclic adenosine 5' monophosphate
(cAMP). These diverse actions suggest that LA may be therapeutically
effective in treating oxidative stress associated diseases. This review
discusses the known biochemical properties of LA, its antioxidant
properties, its ability to modulate signal transduction pathways, and
the recent progress made in the utilization of LA as a therapeutic
alternative for multiple sclerosis, Alzheimer's disease and diabetic
neuropathy.
PMID:
18537699 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/18537699
The
discovery detailed in the next article may be related to CCSVI.
Multiple Sclerosis Blocked in Mouse
Model: Barring Immune Cells from Brain Prevents Symptoms
ScienceDaily (Mar. 7, 2011) — Scientists have blocked harmful immune
cells from entering the brain in mice with a condition similar to
multiple sclerosis (MS)...
http://www.sciencedaily.com/releases/2011/03/110307103652.htm
********************************************************************************************
CCSVI
See
also Multiple Sclerosis (MS), Inflammation, NPH,
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)
Alzheimer's Disease
...The role venous drainage issues play in the brain in causing
neurodegenerative diseases is not new, however. I have been writing
about it since 1987. If you do a Google search for "stenosis
Alzheimer's" or "NPH Alzheimer's" you will find an article I published
in 1990 calling for epidemiological research into the role of venous
drainage issues in the brain in Alzheimer's disease.
When I first started looking for a
possible cause of normal pressure hydrocephalus I found an old
neurology textbook by Adams and Victor. In the section on NPH it
stated that, "A matter of considerable interest is the role of blockage
of the dural sinuses (the large main veins of the brain) in tension
hydrocephalus. The problem is that blockages are rarely found."... http://www.upright-health.com/alzheimers.html
********************************************************************************************
Lion's Mane Mushroom (a.k.a Bearded
Tooth Mushroom, Hedgehog Mushroom, Bearded Hedgehog Mushroom, pom pom
mushroom, or Bearded Tooth Fungus)
See
also BDNF, Neurogenesis,
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
********************************************************************************************
Multifunctional
Cocktail
See also Pyruvate,
creatine, niacinamide
Anti-oxidant
trio
therapy
Mitochondrial Dysfunction
Phase I trial: Active (NCT00605930
on clinicaltrials.gov)
(as of September 11, 2010).
[From PubMed ID#: 20472654]
See:
Rational therapeutic approaches to
progressive supranuclear palsy
Brain 2010: 133; 1578–1590
http://brain.oxfordjournals.org/content/133/6/1578.full.pdf+html
Table 1 of the above article lists "puruvate". This must be a
typo. In the text, it refers to "pyruvate".
"Pyruvate is a free radical
scavenger..."
Fernandez-Gomez
FJ,
Pastor
MD,
Garcia-Martinez
EM,
Melero-
Fernandez de Mera R,
Gou-Fabregas M, Gomez-Lazaro M, et al.
Pyruvate
protects cerebellar granular cells from 6-hydroxydopamineinduced
cytotoxicity by activating the
Akt signaling pathway and increasing glutathione
peroxidase expression. Neurobiol Dis 2006;
24: 296–307.
Wang X, Perez E, Liu R, Yan LJ, Mallet RT, Yang SH. Pyruvate protects
mitochondria from oxidative stress in human neuroblastoma SK-N-SH
cells. Brain Res 2007; 1132: 1–9.
********************************************************************************************
Pyruvate
Also see ALA
Wikipedia entries:
Pyruvic acid (CH3COCOOH) is an organic acid. It is also a ketone, as
well as being the simplest alpha-keto acid. The carboxylate (COOH) ion
(anion) of pyruvic acid, CH3COCOO-, is known as pyruvate, and is a key
intersection in several metabolic pathways. It can be made from glucose
through glycolysis, supplies energy to living cells in the citric acid
cycle (also known as the Krebs cycle), and can also be converted to
carbohydrates via gluconeogenesis, to fatty acids or energy through
acetyl-CoA, to the amino acid alanine and to ethanol...
http://en.wikipedia.org/wiki/Pyruvic_acid
Pyruvate kinase (EC: 2.7.1.40) is an enzyme involved in glycolysis. It
catalyzes the transfer of a phosphate group from phosphoenolpyruvate
(PEP) to ADP, yielding one molecule of pyruvate and one molecule of
ATP...
http://en.wikipedia.org/wiki/Pyruvate_kinase
Here are some other links...
Our bodies make pyruvate naturally every day during the metabolism or
digestion of sugars and starches. Pyruvate is the compound to start the
Krebs cycle.
The Krebs cycle is an energy cycle in the body of enzymes and chemical
actions that yield direct precursors to ATP or ATP itself.
Pyruvate is actually derived from pyruvic acid. Although pyruvic acid
alone is chemically unstable and can cause gastrointestinal discomfort
and nausea, when combined with a salt (such as sodium or calcium), it
becomes stabilized pyruvate. As well as being a naturally formed
product of digestive processes, pyruvate also exists in many different
foods. Red apples, cheese, dark beer, and red wine are just a few.
Dietary supplements of pyruvate are also available. Bodybuilding.com's
carries the highest quality pyruvate supplements... It works by
increasing amount of ATP available to the energy engines of cells,
mitochondria, as well as inhibiting fat production...
http://www.bodybuilding.com/store/pyruvate.html
PYRUVATE: A COMPREHENSIVE REVIEW
http://www.williamsukala.com/articles/pyr_comp_review_1997.htm
Pyruvate Dehydrogenase & Krebs
Cycle
Glycolysis enzymes are located in the cytosol of cells.
Pyruvate enters the mitochondrion to be metabolized further.
(r)-, but not (s)-alpha lipoic acid
stimulates deficient brain pyruvate dehydrogenase complex in vascular
dementia, but not in Alzheimer dementia.
http://www.ncbi.nlm.nih.gov/pubmed/14991456?dopt=Abstract
Mitochondrial compartments:
The mitochondrial matrix contains Pyruvate Dehydrogenase and enzymes of
Krebs Cycle, plus other pathways such as fatty acid oxidation...
http://rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/krebs.htm
********************************************************************************************
Creatine
Creatine supplementation and cognitive
performance in elderly individuals.
Neuropsychol Dev Cogn B Aging
Neuropsychol Cogn. 2007 Sep; McMorris T, Mielcarz G, Harris RC, Swain
JP, Howard A. School of Sport, Exercise and Health Sciences, University
of Chichester, College Lane, Chichester, West Sussex PO19 6PE, UK.
The purpose of this study was
to examine the effect of creatine supplementation on the cognitive
performance of elderly people. Participants were divided into two
groups, which were tested on random number generation, forward and
backward number and spatial recall, and long-term memory tasks to
establish a baseline level. Group 1 were given 5 g four times a day of
placebo for 1 week, followed by the same dosage for the second week.
Group 2 were given placebo both weeks. Participants were retested at
the end of each week. Results showed a significant effect of creatine
supplementation on all tasks except backward number recall. It was
concluded that creatine supplementation aids cognition in the elderly...
From Dr. Ray Sahelian's web site:
[Advise
for
bodybuilders
using
creatine]
A
cautious
approach
would
be
to
limit
intake
to
3
to
5
grams
almost
every
day
for
two
weeks
followed
by
3
grams
two
to
four
times
a
week.
It
would
be
wise
to
take
a
few
days
off
each
month.
It
would
also
be
safer
to
take
two
full
weeks
off
every
3
to
4
months.
http://www.raysahelian.com/creatine.html
********************************************************************************************
Head/Brain Injury
See also Tau Busters
Lou Gehrig may not have had Lou Gehrig's disease?
Sports Brain Trauma May Cause Disease
Mimicking ALS, Researchers Find
ScienceDaily (Aug. 17, 2010) —
New research by the Center for the Study of Traumatic Encephalopathy
(CSTE) at Boston University School of Medicine (BUSM) and the
Department of Veterans Affairs (VA) provides the first pathological
evidence that repetitive head trauma experienced in collision sports is
associated with motor neuron disease, a neurological condition that
affects voluntary muscle movements. The most common form of motor
neuron disease is amyotrophic lateral sclerosis (ALS) or Lou Gehrig's
disease. The findings will be published in the September issue of the
Journal of Neuropathology and Experimental Neurology... In this study,
funded in part by an unrestricted gift from the National Football
League (NFL) to the CSTE, McKee found that when they died, all 12
athletes showed neuropathological evidence of chronic traumatic
encephalopathy (CTE), a progressive degenerative brain disease
characterized by deposits of an abnormal form of tau protein and
believed to be caused by repetitive head trauma. In the three athletes
with motor neuron disease, abnormal tau protein deposits were not only
found throughout the brain, but also in the spinal cord...
http://www.sciencedaily.com/releases/2010/08/100817134304.htm
There have been some discussion about head injury, stroke, or other
brain injury being the [spark] that begins the downward spiral of
several neurodegenerative diseases, especially, Alzheimer's disease.
Phytonutrients and Metabolic Stimulants as
protection Against Neurodegeneration and Excitotoxicity
The Journal of the American
Nutraceutical Association
January 2000 Vol. 2, No. 3 Pg.
30
With severe injuries to the
brain the amount of glutamate in the extracellular space may reach
levels 100X that normally seen.7,8 This can overwhelm the glutamate
transporter system, resulting in prolonged activation of the glutamate
receptor with a resultant excess calcium entry into the neuron.
Normally, intracellular calcium is carefully regulated within the cell,
either by extrusion from the cell or by trapping by the mitochondria or
endoplasmic reticulum. In cases of cellular dysfunction, as seen with
ischemia/hypoxia, hypoglycemia and neurodegenerative disorders, these
homeostatic mechanism malfunctions lead to calcium accumulation
intracellularly. Elevated levels of calcium can trigger activation of
protein kinase C with subsequent expression of membrane bound
phospholipase A2 triggering the release of arachidonic acid from the
cell membrane. Arachidonic acid is then acted on by lipoxygenase and
cyclooxygenase I and II, leading to the generation of leukotrienes and
prostaglandins ( PGE2, PGD2 ). These eicosanoids are responsible for a
cascade of inflammatory reactions that include the generation of
reactive oxygen species and inflammatory cytokines ( IL-1ß,IL-6, TNF-alpha).11-12 These reactive oxygen species
damage cellular proteins ( protein carbonyl products), DNA and lipids (
lipid peroxidation). Intracellular calcium also induces and activates
nitric oxide synthease ( NOS) which, when overactive, can lead to the
formation of the powerful nitrogen radical peroxynitrite formed from a
reaction of nitric oxide with the superoxide radical.13 Peroxynitrite
can enter the mitochondria and damage the electron transport enzymes,
especially complex I and IV, leading to impaired energy production by
the mitochondria, making the neuron infinitely more susceptible to
excitotoxicity The generation of increased levels of free radicals
within the cell, if intense enough, can activate the p53 tumor
suppressor gene triggering apoptosis.14 Excess glutamate can also kill
neurons by necrosis as well.
http://www.ana-jana.org/Journal/journals/JANAVol23.pdf
Can head injury cause motor neuron
disease?
Neurology Now:
November/December 2010 - Volume 6 - Issue 6 - p 11–13
doi: 10.1097/01.NNN.0000392627.15551.f6
Departments: The Waiting Room
http://journals.lww.com/neurologynow/Fulltext/2010/06060/Can_head_injury_cause_motor_neuron_disease_.4.aspx
********************************************************************************************
Stem Cell
Therapy
See also BDNF
GCFS
Lion's Mane Mushroom
Aphanizomenon
flos-aquae (AFA)
There has been a lot of excitement over the use of stem cell therapy in
treating neurodegenerative diseases. If the progression can be
stopped, do things like stem cell therapy or neurogenesis
become
realistic options? That's what I keep wondering.
Some people are going to China and Germany for stem cell therapy. Maybe
with GCSF, this will not be necessary.
Alzheimer's
Symptoms Reversed: Blood Stem Cell Growth Factor Reverses Memory
Decline In Mice
ScienceDaily
(July 2, 2009)
"The
granulocyte-colony stimulating factor (GCSF) significantly reduced
levels of the brain-clogging protein beta amyloid deposited in excess
in the brains of the Alzheimer's mice, increased the production of new
neurons and promoted nerve cell connections."
"The
researchers showed that injections under the skin of filgrastim
(Neupogen®) -- one of three commercially available GCSF compounds
-- mobilized blood stem cells in the bone marrow and neural stem cells
within the brain and both of these actions led to improved memory and
learning behavior in the Alzheimer's mice. "The beauty in this less
invasive approach is that it obviates the need for neurosurgery to
transplant stem cells into the brain,"
"GCSF is a
blood stem cell growth factor or hormone routinely administered to
cancer patients whose blood stem cells and white blood cells have been
depleted following chemotherapy or radiation. GCSF stimulates the bone
marrow to produce more white blood cells needed to fight infection. It
is also used to boost the numbers of stem cells circulating in the
blood of donors before the cells are harvested for bone marrow
transplants..."
"GCSF has
been used and studied clinically for a long time, but we're the first
group to apply it to Alzheimer's disease..."
http://www.sciencedaily.com/releases/2009/07/090701160557.htm
But, I'm not so enthusiastic...
Watching Stem
Cells Repair The Human Brain
ScienceDaily
(Aug. 19, 2009)
There is no known cure for neurodegenerative diseases such as
Huntington's, Alzheimer's and Parkinson's. But new hope, in the form of stem
cells created from the patient's own bone marrow, can be found —
and
literally seen — in laboratories at Tel Aviv University.
This study
is based on differentiated mesenchymal cells (MSC), which were discovered at Tel
Aviv University. Bone marrow cells are transformed into NTFs-secreting
stem cells, which can then be used to treat neurodegenerative diseases. This
advance circumvents the ethical debate caused by the use of stem
cells
obtained from embryos.
Although
there is a drawback to using this particular type of stem cell — the
higher
degree of difficulty involved in rendering them "neuron-like" — the
benefits are
numerous. "Bone marrow-derived MSCs bypass ethical and production
complications,"
says
Dr.
Cohen,
"and
in
the
long
run,
the
cells
are
less
likely to be rejected
because they come from the patients themselves. This means you don't need
immunosuppressant therapy."
http://www.sciencedaily.com/releases/2009/08/090819153931.htm
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.
Their
findings – the first to show neuron-to-neuron transmission of
alpha-synuclein – will appear in the Proceedings of the National
Academy of Sciences (PNAS) on July 29.
"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."
"Our
findings indicate that the stem cells used to replace lost or damaged
cells in the brains of Parkinson's disease patients are also
susceptible to degeneration,"
In a large
proportion of Parkinson's disease cases, the aggregation of
alpha-synuclein progresses in a predictable pattern – from the
lower brainstem, into the limbic system and eventually to the
neocortex, the part of the brain responsible for higher level cognitive
functions. The hypothesis of disease progression by neuron-to-neuron
transmission of alpha-synuclein that encouraged this study was
supported by findings of two separate reports in 2008. 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.
Next, the
team tested to determine if alpha-synuclein could be transmitted
directly from host to grafted cells in a mouse model of Parkinson's
disease. Brains of the mouse model were grafted with fresh, healthy
stem cells. Within four weeks, cells containing Lewy body-like masses
were quite common, supporting the cell-to cell transmission mechanism.
http://www.sciencedaily.com/releases/2009/07/090727191914.htm
There are substances that are touted as being able to "release more
adult stem cells" from the bone marrow into the body. See Aphanizomenon flos-aquae (AFA)
********************************************************************************************
Brain-Derived
Neurotrophic Factor (BDNF)
See also Lion's Mane Mushroom
Alzheimer's
Prevented And Reversed With Natural Protein In Animal Models
ScienceDaily
(Feb. 9, 2009)
"Memory
loss, cognitive impairment, brain cell degeneration and cell death were
prevented or reversed in several animal models after treatment with a
naturally occurring protein called brain-derived neurotrophic factor
(BDNF). The study by a University of California, San Diego-led team
– published in the February 8, 2009 issue of Nature Medicine
– shows that BDNF treatment can potentially provide long-lasting
protection by slowing, or even stopping the progression of Alzheimer's
disease in animal models... For these experiments, the researchers
injected the BDNF gene or protein in a series of cell culture and
animal models, including transgenic mouse models of Alzheimer's
disease; aged rats; rats with induced damage to the entorhinal cortex;
aged rhesus monkeys, and monkeys with entorhinal cortex damage...."
http://www.sciencedaily.com/releases/2009/02/090208133135.htm
Axons Necessary
For Voluntary Movement Regenerated
ScienceDaily
(Apr. 9, 2009)
"For the
first time, researchers have clearly shown regeneration of a critical
type of
nerve fiber that travels between the brain and the spinal cord and which
is required
for voluntary movement... "This finding establishes a method for
regenerating
a system of nerve fibers called corticospinal motor axons. Restoring these
axons is an essential step in one day enabling patients to regain voluntary
movement after spinal cord injury,"... This work builds on another study
from Tuszynski's laboratory, published in the February 8, 2009 issue of Nature
Medicine, which reported that BDNF also exhibits potential as a therapy for
reducing brain cell loss in Alzheimer's disease..."
http://www.sciencedaily.com/releases/2009/04/090406192229.htm
On January 07, 2009 11:02 AM Dr Mary Newport posted the following to
the "New Study: Brain starvation appears to trigger AD" topic on the Alz.org Medications and Treatments
forum:
On February 15, 2009 01:30 PM RArmant
post the following to the "Ultimate Alzheimer's Cocktail" topic:
"Fish oil can help keep the arteries from blocking
up. DHA and EPA both drive down blood
triglyceride level about equally. However DHA appears to be important
for the
brain. It can help increase Brain-derived neurotrophic factor(bdnf).
Bdnf might
help with brain repair... My suggestion for Alzheimer's is to go with
fish oil
that has a high DHA to EPA ratio such as Carlson's Super-DHA that
contains 500
mgs of DHA and 100 mg of EPA per capsule."
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/1891020913?r=4371031443#4371031443
There is also mention of BDNF in a post by vend95 on May 05, 2008 in the
"Promising Drug PRX-03140" topic:
"PRX-03140
is a novel, oral investigational drug candidate for Alzheimer's
disease. It is selective for the 5-HT4 receptor in the brain and is
believed to stimulate both acetylcholine production and release - which
enables symptomatic improvement in Alzheimer's patients - and the
alpha-secretase pathway - which may slow Alzheimer's disease
progression. Recent Phase 2a results indicated that patients receiving
daily oral 150 mg doses of PRX-03140 as monotherapy for two weeks
achieved a mean 3.6 point improvement on the Alzheimer's Disease
Assessment Scale cognitive subscale (ADAS-cog) versus a 0.9 point
worsening in patients on placebo (p= 0.021). In three Phase 1 trials
and the Phase 2a trial, with more than 180 patients and healthy
subjects, PRX-03140 has been well-tolerated. In a 14-day Phase 1b
clinical trial, treatment with PRX-03140 resulted in changes in brain
wave activity in Alzheimer's patients that are consistent with those
seen in clinical trials with currently approved drugs for Alzheimer's
disease. In preclinical studies, PRX-03140 has shown to improve
cognitive function through increasing levels of acetylcholine, and has
led to increased levels of soluble amyloid precursor protein (sAPP) and
brain-derived neurotrophic factor (BDNF) in regions of the brain known
to be important for memory."
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/3231069892?r=4751085103#4751085103
Post by neuroprof on May 04,
2009 01:04 PM:
Post by neuroprof on July
31, 2009 10:41 AM
Post by lucho on August 01,
2009 07:12 PM
Neural Stem Cells
May Rescue Memory In Advanced Alzheimer's, Mouse Study Suggests
ScienceDaily
(July 22, 2009)
UC Irvine
scientists have shown for the first time that neural stem cells can
rescue memory in mice with advanced Alzheimer's disease, raising hopes
of a potential treatment for the leading cause of elderly dementia that
afflicts 5.3 million people in the U.S... The stem cells didn't improve
cognition by becoming new neurons, nor did they act by reducing the
number of plaques and tangles. Rather, the stem cells were found to
have secreted a protein called brain-derived neurotrophic factor, or
BDNF. This caused existing tissue to sprout new neurites, strengthening
and increasing the number of connections between neurons. When the team
selectively reduced BDNF from the stem cells, the benefit was lost,
providing strong evidence that BDNF is critical to the effect of stem
cells on memory and neuronal function... Diseased mice injected
directly with BDNF also improved cognitively but not as much as with
the neural stem cells, which provided a more long-term and consistent
supply of the protein...
http://www.sciencedaily.com/releases/2009/07/090720190726.htm
You can also do a search on ScienceDaily.com for BDNF
http://www.sciencedaily.com/search/?type=news&keyword=BDNF§ion=all&filename=&period=1825&sort=relevance
Supplementing with DHA (fish oil) increases BDNF?
Chronic
Administration of DHA and UMP Improves the Impaired Memory of
Environmentally Impoverished Rats
Sarah
Holguin, Yi Huang, Jenny Liu, and Richard Wurtman
UMP and DHA
may protect the brains of IC reared animals by restoring neuronal
function to levels normally observed in brains of control or EC rats.
Rats exposed to IC conditions [43] or made DHA-deficient [44] have
decreased brain weight and size, while DHA administration increases
brain weight and size [44]. Brains of IC reared rats also exhibit
decreased neurogenesis [45] and
synaptogenesis [46], DHA has been shown
to promote neurite outgrowth in hippocampal neurons [47] and uridine
promotes neurite outgrowth from PC12 cells [24]. DHA supplementation
increased brain-derived neurotrophic factor (BDNF) levels in rats [48]
while consuming a diet deficient in DHA decreased these levels [49];
BDNF induces neurogenesis in the hippocampal dentate gyrus [50]..
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2478743/?tool=pubmed
********************************************************************************************
Granulocyte-colony Stimulating Factor(GCSF)
This drug is apparently available and in use for other diseases. Good
luck
convincing a physician to use this "off label".
Alzheimer's
Symptoms Reversed: Blood Stem Cell Growth Factor Reverses Memory Decline In Mice
ScienceDaily
(July 2, 2009)
The
granulocyte-colony stimulating factor (GCSF) significantly reduced
levels of the brain-clogging protein beta amyloid deposited in excess
in the brains of the Alzheimer's mice, increased the production of new
neurons and promoted nerve cell connections.
The
researchers showed that injections under the skin of filgrastim
(Neupogen®) -- one of three commercially available GCSF compounds
-- mobilized blood stem cells in the bone marrow and neural stem cells
within the brain and both of these actions led to improved memory and
learning behavior in the Alzheimer's mice. "The beauty in this less
invasive approach is that it obviates the need for neurosurgery to
transplant stem cells into the brain,
GCSF is a
blood stem cell growth factor or hormone routinely administered to
cancer patients whose blood stem cells and white blood cells have been
depleted following chemotherapy or radiation. GCSF stimulates the bone
marrow to produce more white blood cells needed to fight infection. It
is also used to boost the numbers of stem cells circulating in the
blood of donors before the cells are harvested for bone marrow
transplants...
GCSF has
been used and studied clinically for a long time, but we're the first
group to apply it to Alzheimer's disease...
http://www.sciencedaily.com/releases/2009/07/090701160557.htm
********************************************************************************************
Green Tea (EGCG, epigallocatechin
gallate)
See also Oligomers,
Green Tea Has
Rejuvenating Effect on Damaged Brain Cells
Researchers
at the Technion Institute of Science in Haifa have shown that feeding
green tea extract to mice with Parkinson's and Alzheimer's disease
protects brain cells from dying, and helps 'rescue' already damaged
neurons in the brain...
http://alzheimersweekly.com/content/green-tea-has-rejuvenating-effect-damaged-brain-cells
EGCG remodels mature alpha-synuclein and
amyloid-beta fibrils and reduces cellular toxicity. Bieschke J, Russ
J, Friedrich RP, Ehrnhoefer DE, Wobst H, Neugebauer K, Wanker EE.
Proc Natl
Acad Sci U S A. 2010 Apr 27;107(17):7710-5.
Abstract
Protein
misfolding and formation of beta-sheet-rich amyloid fibrils or
aggregates is related to cellular toxicity and decay in various human
disorders including Alzheimer's and Parkinson's disease. Recently, we
demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG)
inhibits alpha-synuclein and
amyloid-beta fibrillogenesis. It
associates with natively unfolded polypeptides and promotes the
self-assembly of unstructured oligomers of a new type. Whether EGCG
disassembles preformed amyloid fibrils, however, remained unclear.
Here, we show that EGCG has the ability to convert large, mature
alpha-synuclein and amyloid-beta fibrils into smaller, amorphous
protein aggregates that are nontoxic to mammalian cells. Mechanistic
studies revealed that the compound directly binds to beta-sheet-rich
aggregates and mediates the conformational change without their
disassembly into monomers or small diffusible oligomers. These findings
suggest that EGCG is a potent remodeling agent of mature amyloid
fibrils.
http://www.ncbi.nlm.nih.gov/pubmed/20385841?dopt=Abstract
Alzheimer
Research Forum Comment by: Jun Tan, Terrence Town
Submitted
27
April
2010
Posted
27
April
2010
...Erich
Wanker and colleagues show that EGCG, the main polyphenolic constituent
of green tea, reduces cellular toxicity by inhibiting β amyloid and
α-synuclein fibrillogenesis...
http://www.alzforum.org/pap/annotation.asp?powID=101554
Green tea consumption and cognitive
function: a cross-sectional study from the Tsurugaya Project 1.
Am J
Clin Nutr. 2006 Feb;83(2):355-61.
Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata
S, Nagatomi R, Arai H, Tsuji I.
Division of Epidemiology, Department of Public Health and Forensic
Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Abstract
BACKGROUND: Although considerable experimental and animal evidence
shows that green tea may possess potent activities of neuroprotection,
neurorescue, and amyloid precursor protein processing that may lead to
cognitive enhancement, no human data are available.
OBJECTIVE: The objective was to examine the association between green
tea consumption and cognitive function in humans.
DESIGN: We analyzed cross-sectional data from a community-based
Comprehensive Geriatric Assessment (CGA) conducted in 2002. The
subjects were 1003 Japanese subjects aged > or =70 y. They completed
a self-administered questionnaire that included questions about the
frequency of green tea consumption. We evaluated cognitive function by
using the Mini-Mental State Examination with cutoffs of <28, <26,
and <24 and calculated multivariate-adjusted odds ratios (ORs) of
cognitive impairment.
RESULTS: Higher consumption of green tea was associated with a lower
prevalence of cognitive impairment. At the <26 cutoff, after
adjustment for potential confounders, the ORs for the cognitive
impairment associated with different frequencies of green tea
consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI:
0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72)
for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were
1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55,
1.38) (P for trend = 0.33) for black or oolong tea and 1.00
(reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80)
(P for trend = 0.70) for coffee. The results were essentially the same
at cutoffs of <28 and <24.
CONCLUSION: A higher consumption of green tea is associated with a
lower prevalence of cognitive impairment in humans.
PMID: 16469995 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/16469995
Free article: American Journal of Clinical Nutrition, Vol. 83, No. 2,
355-361, February 2006
http://www.ajcn.org/content/83/2/355.long
********************************************************************************************
Prozac
Prozac (Fluoxetine)
Prozac - The University Of Maryland School Of Medicine treated Down
syndrome mice with prozac for 24 days (2006). It increased
neurogenesis (the formation of new
nerves) to a normal level (View
details). This is like increasing the hardware on your computer. It
allows you to run more complicated software. In fetuses with Down
syndrome, neurons fail to show normal dendritic development, yielding a
"tree in winter" appearance. This developmental failure is thought to
result in mental retardation
http://www.changingmindsfoundation.com/education.html
********************************************************************************************
Neurogenesis
See also ALA,
Anatabine, Blueberries, BDNF, Curcumin, GCSF, Lion's Mane Mushroom, Lithium,
Prozac, Stem Cell Therapy,
The Reinvention
of the Self
Brain &
Behavior / by Jonah Lehrer / February 23, 2006
Elizabeth
Gould overturned one of the central tenets of neuroscience. Now she’s
building on her discovery to show that poverty and stress may not just
be symptoms of society, but bound to our anatomy.
http://seedmagazine.com/content/article/the_reinvention_of_the_self/P1/
********************************************************************************************
Blueberries
See also AFA, Inflammation,
This article has some eye catching claims from studies with mice and
blueberry extract. Among all the claims, the performance of blueberry
extract fed mice with amyloid plaque along with blueberries' potential
for neurogenesis and diminishing
inflammation are particularly
noteworthy. I remember reading years ago that Dr. J. Joseph was so
impressed with some findings with blueberries that he added them to his
diet daily.
Food for the Aging Mind
United
States Department of Agriculture Agricultural Research Service
...Examination
of
the
brain
tissue
of
those
blueberry-fed
rats
showed
much
higher
levels
of
dopamine
than
were
found
in
the
other
groups.
Dopamine
has
many
functions
within
the
brain.
In
particular,
it
can
affect
the
way
the
brain
controls
movements.
“We
suspected that the combined antioxidant potency of compounds in
blueberry extract may have reduced inflammatory compounds in the brains
of these older animals,” says Joseph. “Inflammation ordinarily
contributes to neuronal and behavioral shortfalls during aging.”
Tests have
since shown that blueberry compounds cross the blood-brain barrier and
localize in rodent brain tissue...
http://www.ars.usda.gov/is/AR/archive/aug07/aging0807.htm
Milk Destroys
Antioxidant Benefits in Blueberries
Tuesday, February 03, 2009 by: Barbara L. Minton, citizen journalist
(NaturalNews) Not much is better than a bowl of fresh blueberries.
Bursting with flavor and sweetness, low in calories, and packed with
nutrients and antioxidants, these tiny fruits are anti-aging
superstars. There is however one word of caution. Blueberries lose
their power when eaten with milk.
...A
study reported in the August, 2008 journal Nutrition and Neuroscience
looked at cognitive impairment in age-related neurodegenerative
diseases such as Alzheimer's as being due to long-term exposure and
increased susceptibility to inflammatory insults. They investigated
whether polyphenols in blueberries could reduce the deleterious effects
of induced inflammation.
Rats were
fed a diet that included a non-steroidal anti-inflammatory drug
(NSAID), or a 2 percent blueberry diet. After two weeks and behavioral
evaluation, the rats were examined and total RNA from the hippocampus
was extracted to analyze the expression of inflammation-related genes.
The researchers found the blueberry diet was able to improve cognitive
performance to a much greater degree than was the NSAID diet. Blueberry
eaters showed a reduction in several factors influencing the
inflammatory response. They concluded that blueberry polyphenols can
lessen learning impairments resulting from neurotoxic insult and exert
anti-inflammatory actions, perhaps by alteration of gene expression.
Other
studies have found that diets rich in blueberries significantly
improved both the learning capacity and motor skills of aging animals,
making them mentally equivalent to animals much younger.
http://www.naturalnews.com/025516.html
That's
the
not
so
good
news
from
a
study
presented
in
this
article
if
it
makes
it
inconvenient
to
prepare
a
serving/dose.
It's
been
reported
that
milk/protein
will
have
harmful
effects
on
green
tea also. The better
part of the article tells of a study with rats looking at blueberries
in relation to inflammation and cognitive performance.
I'm
certainly pleased to find out all of these good tasting things like
blueberries, cinnamon, coconut,
and
even
tea are good for you. It would be a
bummer if it were things like cloves and radishes.
When they say, "Blueberry eaters showed a reduction in several factors
influencing the inflammatory response", I wonder what those "factors"
are? I'm going to have to look into it. What I'm wondering about is if TNF-alpha is affected. This would then tie into
chronic infection and Enbrel.
More articles about blueberry extract:
Blueberry
Extracts Boost Brain Function
By Rosalie
Marion Bliss
August 8,
2007
A single
dietary change has allowed laboratory animals with a genetic tendency
toward Alzheimer's disease to perform as well as healthy peers in maze
tests. Agricultural Research Service (ARS) scientists noted the
diet-induced behavioral differences in the Alzheimer's-prone animals
after feeding them blueberry extracts from the equivalent of their
early adulthood to early middle age...
http://www.ars.usda.gov/is/pr/2007/070808.htm
Blueberry Juice
Improves Memory in Older Adults
ScienceDaily
(Jan. 21, 2010)
Scientists
are reporting the first evidence from human research that blueberries
-- one of the richest sources of healthful antioxidants and other
so-called phytochemicals -- improve memory. They said the study
establishes a basis for comprehensive human clinical trials to
determine whether blueberries really deserve their growing reputation
as a memory enhancer... In the study, one group of volunteers in their
70s with early memory decline drank the equivalent of 2-2 l/2 cups of a
commercially available blueberry juice every day for two months. A
control group drank a beverage without blueberry juice. The blueberry
juice group showed significant improvement on learning and memory
tests, the scientists say...
http://www.sciencedaily.com/releases/2010/01/100120121552.htm
********************************************************************************************
Vitamin D3
See also Curcumin
Recommendation from The
Vitamin D Council
Here is a new study out that claims to clear Beta
Amyloid plaques by combining vitamin D3 and a bio-available, possibly
synthetic, curcumin.
Vitamin D, Curcumin May Help Clear Amyloid
Plaques Found In Alzheimer's Disease
ScienceDaily
(July 16, 2009) — UCLA scientists and colleagues from UC Riverside and
the Human BioMolecular Research Institute have found that a form of
vitamin D, together with a chemical found in turmeric spice called
curcumin, may help stimulate the immune system to clear the brain of
amyloid beta, which forms the plaques considered the hallmark of
Alzheimer's disease...
http://www.sciencedaily.com/releases/2009/07/090715131558.htm
Vitamin D,
curcumin may help clear amyloid plaques found in Alzheimer's
UCLA Newsroom
Early
research findings may lead to new treatments for the disease
By Rachel
Champeau July 15, 2009 Category: Health Sciences, Research
UCLA
scientists and colleagues from UC Riverside and the Human BioMolecular
Research Institute have found that a form of vitamin D, together with a
chemical found in turmeric spice called curcumin, may help stimulate
the immune system to clear the brain of amyloid beta, which forms the
plaques considered the hallmark of Alzheimer's disease.
The early
research findings, which appear in the July issue of the Journal of
Alzheimer's Disease, may lead to new approaches in preventing and
treating Alzheimer's by utilizing the property of vitamin D3 — a form
of vitamin D — both alone and together with natural or synthetic
curcumin to boost the immune system in protecting the brain against
amyloid beta...
http://newsroom.ucla.edu/portal/ucla/ucla-study-finds-vitamin-d-may-94903.aspx
Higher vitamin D
linked to better physical functioning in elderly
by Neha
Jindal - April 27, 2010
In a notable
study, researchers claim to have found that higher blood levels of
vitamin D improve physical functioning in the elderly.
Researchers
at Wake Forest University in Winston-Salem, U.S., established that high
levels of vitamin D not only help battle cold, cancer, diabetes and
heart diseases but also perk up physical activity in the aged.
Lead
researcher and assistant professor, internal medicine, Wake Forest
University, Denise Houston, PhD, RD, was quoted by WebMD as saying,
“Those with better vitamin D levels started out better and ended up
better on physical performance tests.”
http://www.themedguru.com/20100427/newsfeature/higher-vitamin-d-linked-better-physical-functioning-elderly-86134554.html
Low Vitamin D Level Tied to Cognitive
Decline
Study Shows
Elderly People With Higher Vitamin D Levels Performed Better on Mental
Tests
By Charlene
Laino
WebMD Health
News
Reviewed by
Louise Chang, MD
April 16,
2010 (Toronto) -- Two new studies add to evidence that older people
with low levels of vitamin D may be more likely to suffer from
cognitive impairment.
The hope is
that vitamin D supplements may be able to slow mental decline -- an
intervention that one research team plans to put to the test this
summer.
Vitamin D is
best known for helping the body absorb calcium, which restores and
strengthens bone, protecting against fracture.
But vitamin
D also seems to have anti-inflammatory effects that may help keep blood
vessels healthy, ensuring nutrient- and oxygen-rich blood flow to brain
cells, says Amie Peterson, MD, of Oregon Health & Science
University in Portland.
In addition,
the presence of vitamin D receptors throughout the brain suggests that
it may directly affect brain tissue, she tells WebMD.
http://www.webmd.com/healthy-aging/news/20100416/low-vitamin-d-level-tied-to-cognitive-decline
Do Vitamin D
Deficiency and Cognitive Decline Go Hand‐in‐Hand?
Neurology
Today
7 January
2010; Volume 10(1); p 10
FALLIK, DAWN
Two
independent research groups showed a connection between vitamin D
deficiency and cognitive decline in cross-sectional studies, while the
third found no statistically significant association in a longitudinal
study.
While
vitamin D has long been known to assist calcium absorption in the body,
investigators have begun to explore, as well, its role in supporting
cognitive function and preventing dementia.
But exactly
what that role is requires further research, according to the lead
investigators of three studies published online Nov. 25 ahead of the
Jan. 5 print edition of Neurology. Two independent research groups
showed a connection between vitamin D deficiency and cognitive decline
in cross-sectional studies, while the third found no statistically
significant association in a longitudinal study.
Although the
findings were inconclusive, the investigators agreed on this point:
Clinicians need to be careful in prescribing supplements, because it is
unclear what dose, if any, is most effective. And they warned patients
not to consider vitamin D a “wonder drug,” because, unlike vitamin C
excess, which the body eliminates, vitamin D is stored in fat, and an
overdose can cause problems...
http://www.aan.com/elibrary/neurologytoday/?event=home.showArticle&id=ovid.com:/bib/ovftdb/00132985-201001070-00007
Originally posted November 19, 2009 12:16 PM to the Alz.org "Curcumin
clinical trial" thread on the Medications/Treatments
for
Alzheimer's
and
Other
Related
Dementias discussion forum:
"...Another study has found that stimulation of
scavenger cells (macrophages) by the vitamin D derivative 1,25
hydroxyvitamin D (which is the hormonally active form of the vitamin),
in combination with compounds called curcuminoids, also have effects on
macrophages which may result in removal of the offending substances and
structures. Vitamin D is known to have beneficial effects on immunity,
and cucurmin (from turmeric) has been shown before to have beneficial
properties..."
Sources:
Masoumi A, et al. J Alzheimers Disease 2009;17:703–17.
http://www.everybody.co.nz/page-8cbc924f-812b-4ba5-8ffa-ad7e42580d64.aspx
It seems rather intriguing. No, I don't understand it completely but it
seems that some form of vitamin D increases the effectiveness of
curcuminoids.
Here is the abstract of the cited paper:
1α,25-dihydroxyvitamin D_{3} Interacts with
Curcuminoids to Stimulate Amyloid-β Clearance by Macrophages of
Alzheimer's Disease Patients
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-2009-1080
Pages 703-717
Authors
Ava
Masoumi1, Ben Goldenson1, Senait Ghirmai2, Hripsime Avagyan1, Justin
Zaghi1, Ken Abel2, Xueying Zheng2, Araceli Espinosa-Jeffrey3, Michelle
Mahanian1, Phillip T. Liu4, Martin Hewison1, Matthew Mizwicki5, John
Cashman2, Milan Fiala1
Abstract
Patients
with Alzheimer's disease (AD) suffer from brain amyloidosis related to
defective clearance of amyloid-β (Aβ) by the innate immune system. To
improve the innate immune system of AD patients, we studied immune
stimulation of macrophages by 1α,25(OH)_{2}-vitamin D_{3}(1,25D3) in
combination with curcuminoids. AD patients' macrophages segregate into
Type I (positively stimulated by curcuminoids regarding MGAT-III
transcription) and Type II (not stimulated). In both Type I and Type II
macrophages, 1,25D3 strongly stimulated Aβ phagocytosis and clearance
while protecting against apoptosis. Certain synthetic curcuminoids in
combination with 1,25D3 had additive effects on phagocytosis in Type I
but not Type II macrophages. In addition, we investigated the
mechanisms of 1,25D3 and curcuminoids in macrophages. The 1,25D3
genomic antagonist analog MK inhibited 1,25D3 but not curcuminoid
effects, suggesting that 1,25D3 acts through the genomic pathway. In
silico, 1,25D3 showed preferential binding to the genomic pocket of the
vitamin D receptor, whereas bisdemethoxycurcumin showed preference for
the non-genomic pocket. 1,25D3 is a promising hormone for AD
immunoprophylaxis because in Type I macrophages combined treatment with
1,25D3 and curcuminoids has additive effects, and in Type II
macrophages 1,25D3 treatment is effective alone. Human macrophages are
a new paradigm for testing immune therapies for AD.
http://iospress.metapress.com/content/k457101686r62685/?p=299e6f877b2848309f40294ee2a89c52&pi=20
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/834108421?r=195102752#195102752
Originally
posted
January
16,
2010
09:17
AM to
the Alz.org
"Curcumin clinical trial" thread on the Medications/Treatments
for
Alzheimer's
and
Other
Related
Dementias discussion forum:
While re-reading the older posts in this tread, I saw a message I
posted back on November 19 about vitamin D that I completely forgot
about.
If I'm reading the articles correctly, it seems that Vitamin D helps
the body use curcumin more effectively to remove the amyloid beta
plaques.
The wording of the abstract makes it sound like they used some exotic
form of Vitamin D, but according to Wikipedia, Vitamin D is converted
to this "1,25 hydroxyvitamin D".
"After vitamin D is produced in the middle layers
of skin or consumed in food, it is converted in the liver and kidney to
form 1,25 dihydroxyvitamin D, (1,25(OH)2D), the physiologically active
form of vitamin D (when "D" is used without a subscript it refers to
either D2 or D3). This physiologically active form of vitamin D is
known as calcitriol. Following this conversion, calcitriol is released
into the circulation, and by binding to a carrier protein in the
plasma, vitamin D binding protein (VDBP), it is transported to various
target organs."
http://en.wikipedia.org/wiki/Vitamin_D
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/834108421?r=512106603#512106603
********************************************************************************************
Caffeine
Caffeine protects
Alzheimer's mice against cognitive impairment and reduces brain
beta-amyloid production.
Arendash GW,
Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR,
Shippy D,
Tan J.
The Byrd
Alzheimer's Center and Research Institute, Tampa, FL 33647, USA.
Neuroscience.
2006
Nov
3;142(4):941-52.
Epub
2006
Aug
28.
A recent
epidemiological study suggested that higher caffeine intake over
decades reduces the risk of Alzheimer's disease (AD). The present study
sought to determine any long-term protective effects of dietary
caffeine intake in a controlled longitudinal study involving AD
transgenic mice. Caffeine (an adenosine receptor antagonist) was added
to the drinking water of amyloid precursor protein, Swedish mutation
(APPsw) transgenic (Tg) mice between 4 and 9 months of age, with
behavioral testing done during the final 6 weeks of treatment. The
average daily intake of caffeine per mouse (1.5 mg) was the human
equivalent of 500 mg caffeine, the amount typically found in five cups
of coffee per day. Across multiple cognitive tasks of spatial
learning/reference memory, working memory, and
recognition/identification, Tg mice given caffeine performed
significantly better than Tg control mice and similar to non-transgenic
controls. In both behaviorally-tested and aged Tg mice, long-term
caffeine administration resulted in lower hippocampal beta-amyloid
(Abeta) levels. Expression of both Presenilin 1 (PS1) and
beta-secretase (BACE) was reduced in caffeine-treated Tg mice,
indicating decreased Abeta production as a likely mechanism of
caffeine's cognitive protection. The ability of caffeine to reduce
Abeta production was confirmed in SweAPP N2a neuronal cultures, wherein
concentration-dependent decreases in both Abeta1-40 and Abeta1-42 were
observed. Although adenosine A(1) or A(2A) receptor densities in cortex
or hippocampus were not affected by caffeine treatment, brain adenosine levels in Tg mice were
restored back to normal by dietary caffeine and could be involved in
the cognitive protection provided by caffeine. Our data demonstrate
that moderate daily intake of caffeine may delay or reduce the risk of
AD.
PMID:
16938404
The complete
paper to the above abstract can be found at --
http://www.byrdinstitute.org/mediaroom/caffeine-study/Caffeine%20Paper.pdf
When they refer to "adenosine", I wonder if they mean ATP. See Mitochondrial Dysfunction for
more on this.
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Updated: December
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