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!!!!!!!!!!]
- Traumatic head injury
- Chronic remote inflammation
- Brain tumors
- Chemical imbalances
- Spinal fluid pressure
- Exposure to toxins
- Aluminosilicate accumulation
- Vitamin B12 deficiency
- CCSVI (chronic cerebrospinal venous
insufficiency)
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.
http://www.ncbi.nlm.nih.gov/pubmed/15355492
********************************************************************************************
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
The content of this section has been moved to Curcumin
********************************************************************************************
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.
Unfortunately, medicines and therapies don't always work for every
person.
For the most part, we don't discuss health food, but rather,
naturally-sourced medicines from plants and animals, and therapies
that are on the fringes of medical research. Most medicines
originate from plants and animals, so discussing and trying those
that may help is appropriate. Every new therapy for treating a
disease starts out as a radical idea on the fringes that the
mainstream is slow to accept.
Some of us want to try some of these unproven things because we
know that the clock is ticking and the conventional "standard of
care" doesn't help much.
The flow usually goes like this. Some observation is made about an
aspect of the disease or the effect of a substance. Then people
scour the available literature to find research to back up the
observation and report what they find. Finally, some take it upon
themselves to try something-- usually based on a research paper
they found-- and report on their success or failure. We've had few
successes. But it is important to know what other people have
tried so that the rest of us can either duplicate a success or
learn from a failure. If we know what was tried, how much, how
often, how long, and what with, trial and error may lead us to a
correct strategy.
It seems likely that there are more than one path that lead to the
same destination. MCT oils (used as a medicine) may work for one a
person on one path, but not for another. Eradication of the
Helicobacter pylori bacteria may halt the progression of
Alzheimer's disease for those individuals who have an H.pylori
infection, but not for those who's AD was initiated by head injury
or genetic predisposition.
So, is it possible that one man's medicine is another man's
poison? Certainly.
********************************************************************************************
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
Lithium Profoundly Prevents
Brain Damage Associated With Parkinson's Disease, Mouse Study
Suggests
ScienceDaily (June 24, 2011) — Lithium profoundly prevents the
aggregation of toxic proteins and cell loss associated with
Parkinson's disease (PD) in a mouse model of the condition.
Preclinical research is now underway at the Buck Institute for
Research on Aging to determine correct dosages for a drug that
continues to be the gold standard for the treatment of bipolar
disorder. The Buck is currently working toward initiating a
Phase IIa clinical studies of lithium in humans in conjunction
with standard PD drug therapy...
http://www.sciencedaily.com/releases/2011/06/110624080329.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.
See Inflammation/Infection
Comparison of bacteriostatic
and bactericidal activity of 13 essential oils against
strains with varying sensitivity to antibiotics
22 AUG 2008
Letters in Applied Microbiology
Volume 47, Issue 3, pages
167–173, September 2008
Abstract
Aims: To compare the
bacteriostatic and bactericidal activity of 13 chemotyped
essential oils (EO) on 65 bacteria with varying
sensitivity to antibiotics.
Methods and Results:
Fifty-five bacterial strains were
tested with two methods used for evaluation of
antimicrobial activity (CLSI recommendations): the agar
dilution method and the time-killing curve method.
EO containing aldehydes
(Cinnamomum verum bark and Cymbopogon citratus), phenols
(Origanum compactum, Trachyspermum ammi, Thymus
satureioides, Eugenia caryophyllus and Cinnamomum verum
leaf) showed the highest antimicrobial activity with
minimum inhibitory concentration (MIC) <2% (v/v)
against all strains except Pseudomonas aeruginosa.
Alcohol-based EO (Melaleuca
alternifolia, Cymbopogon martinii and Lavandula
angustifolia) exhibited varying degrees of activity
depending on Gram status.
EO containing 1·8-cineole
and hydrocarbons (Eucalyptus globulus, Melaleuca cajeputii
and Citrus sinensis) had MIC90% ≥ 10% (v/v). Against P.
aeruginosa, only C. verum bark and O. compactum presented
MIC ≤2% (v/v).
Cinnamomum verum bark, O.
compactum, T. satureioides, C. verum leaf and M.
alternifolia were bactericidal against Staphylococcus
aureus and Escherichia coli at concentrations ranging from
to 0·31% to 10% (v/v) after 1 h of contact.
Cinnamomum verum bark and O. compactum were bactericidal
against P. aeruginosa within 5 min at concentrations
<2% (v/v).
Conclusions: Cinnamomum verum
[Ceylon cinnamon] bark had the highest antimicrobial
activity, particularly against resistant strains.
http://onlinelibrary.wiley.com/doi/10.1111/j.1472-765X.2008.02406.x/full
********************************************************************************************
Infection and Immune System Response:
See also Helicobacter pylori
HSV
Inflammation
The content of this section has been moved to The
Role of Infection and Inflammation in Neurodegenerative Diseases
********************************************************************************************
TNF-Alpha
See also Enbrel
Chitosan
Cat's
Claw
Cinnamon
Curcumin
Inflammation
NT-020 references in AFA
The content of this section has been moved to The Role of Infection and
Inflammation in Neurodegenerative Diseases
********************************************************************************************
Chitosan
(Water-soluble Chitosan, chitosan oligosaccharide)
The
content of this section has been moved to The Role of Infection and Inflammation in
Neurodegenerative Diseases
********************************************************************************************
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.
Bioenergetics breakdown in
Alzheimer's disease: targets for new therapies.
Int
J Physiol Pathophysiol Pharmacol. 2011;3(2):133-9. Epub 2010 Jun
12.
Saxena U.
Source: R and D Strategy, Kareus Therapeutics SA, Switzerland.
Abstract
Alzheimer's disease is rapidly growing worldwide and yet there is
no cure for it. Currently available drugs only provide symptomatic
relief and do not intervene in disease process sufficiently enough
to prevent or cure it. Characteristic features of this disease are
decline in neuronal mass and cognitive functions. The most
dominant hypothesis proposed for pathogenesis of this disease is
called "amyloid hypothesis". It states that excessive production
of amyloid peptides called abeta peptides (Aβ) is the underlying
cause of neuronal death and dysfunction. However, recent drugs
designed based on amyloid hypothesis have failed in clinical
trails, demanding fresh assessment. Early and persistent molecular
events in this disease progression are energy deficiency and high
oxidative stress in the neurons. Our review will put together a
disease model based on known human and animal data with regards to
breakdown in neuronal energy generation. The model will integrate
energy deficits as the cause of neuronal dysfunction and abeta
peptide production culminating in catastrophic loss of cognitive
functions. Finally, based on this model, we will also suggest
enzyme targets in neuronal bioenergetics pathway for design and
development of new disease modifying therapies.
PMID: 21760971 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21760971
PMCID: PMC3134007
Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134007/?report=abstract
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134007/?tool=pubmed
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
The diabetes medication metformin
may interfere with B12 dietary absorption.
B12 and Alzheimer's
Disease
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
B12 and Vascular
Dementia (VD)
B-Vitamin
Deficiency
May Cause Vascular Cognitive Impairment
ScienceDaily
(Sep.
2, 2008) — A deficiency of B-vitamins may cause vascular cognitive impairment,
according to a new study. Researchers at the Jean Mayer USDA
Human Nutrition Research Center on Aging (HNRCA) at Tufts
University used an experimental model to examine the metabolic,
cognitive, and microvascular effects of dietary B-vitamin
deficiency. "Metabolic impairments induced by a diet deficient
in three B-vitamins -folate, B12 and B6- caused cognitive
dysfunction and reductions in brain capillary length and density
in our mouse model," says Aron Troen, PhD, the study's lead
author. "The vascular changes occurred in the absence of
neurotoxic or degenerative changes."...
http://www.sciencedaily.com/releases/2008/09/080902095110.htm
B-vitamin
deficiency
causes hyperhomocysteinemia and vascular cognitive impairment in
mice
Aron M.
Troen*, Melissa Shea-Budgell, Barbara Shukitt-Hale, Donald E.
Smith, Jacob Selhub, and Irwin H. Rosenberg
Jean
Mayer U.S. Department of Agriculture Human Nutrition Research
Center on Aging, Tufts University, 711 Washington Street,
Boston, MA 02111-1524
Communicated
by
Leon E. Rosenberg, Princeton University, Princeton, NJ, June 5,
2008 (received for review July 20, 2007)
Abstract
In
older adults, mildly elevated plasma total homocysteine
(hyperhomocysteinemia) is associated with increased risk of
cognitive impairment, cerebrovascular disease, and Alzheimer's
disease, but it is uncertain whether this is due to underlying
metabolic, neurotoxic, or vascular processes. We report here
that feeding male C57BL6/J mice a B-vitamin-deficient diet for
10 weeks induced hyperhomocysteinemia, significantly impaired
spatial learning and memory, and caused a significant
rarefaction of hippocampal microvasculature without concomitant
gliosis and neurodegeneration. Total hippocampal capillary
length was inversely correlated with Morris water maze escape
latencies (r = −0.757, P < 0.001), and with plasma total
homocysteine (r = −0.631, P = 0.007). Feeding mice a
methionine-rich diet produced similar but less pronounced
effects. Our findings suggest that cerebral microvascular
rarefaction can cause cognitive dysfunction in the absence of or
preceding neurodegeneration. Similar microvascular changes may
mediate the association of hyperhomocysteinemia with human
age-related cognitive decline...
http://www.pnas.org/content/105/34/12474
Other ailments
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.
Vitamin B12 deficiency
What
is
the definition of "deficient"?
Excerpts from from Wikipedia "Vitamin
B12
deficiency"
Serum B12 levels are often low in B12 deficiency, but if other
features of B12 deficiency are present with normal B12 then the
diagnosis must not be discounted. One possible explanation for
normal B12 levels in B12 deficiency is antibody interference in
people with high titres of intrinsic factor antibody.[24] Some
researchers propose that the current standard norms of vitamin
B12 levels are too low.[25] In Japan, the lowest acceptable
level for vitamin B12 in blood has been raised from about 200
pg/ml (145 pM) to 550 pg/ml (400 pM).[26]
There
is confusion in units of B12 deficiency when given by various
labs in various countries. Where units are presented as
pg/liter, or pg/L, they are likely in error.[citation needed]
Where they are presented as pg/mL or pmol/L, they are likely
correct. The ranges for these two units are similar, since the
molecular weight of B12 is approximately 1000, the difference
between mL and L. Thus: 550 pg/mL = 400 pmol/L.
Serum
Homocysteine and Methylmalonic acid levels are considered more
reliable indicators of B12 deficiency than the concentration of
B12 in blood, see for example research at the St. Louis
University.[27] The levels of these substances are high in B12
deficiency and can be helpful if the diagnosis is unclear.
Approximately 10% of patients with vitamin B12 levels between
200–400pg/l will have a vitamin B12 deficiency on the basis of
elevated levels of homocysteine and methylmalonic acid.
Masking effect of Folic acid
The National Institutes of Health has found that "Large amounts
of folic acid can mask the damaging effects of vitamin B12
deficiency by correcting the megaloblastic anemia caused by
vitamin B12 deficiency without correcting the neurological
damage that also occurs", there are also indications that "high
serum folate levels might not only mask vitamin B12 deficiency,
but could also exacerbate the anemia and worsen the cognitive
symptoms associated with vitamin B12 deficiency".[41] Due to the
fact that in the United States legislation has required enriched
flour to contain folic acid to reduce cases of fetal neural-tube
defects, consumers may be ingesting more than they realize.[42]
To counter the masking effect of B12 deficiency the NIH
recommends "folic acid intake from fortified food and
supplements should not exceed 1,000 mcg daily in healthy
adults."[41]
http://en.wikipedia.org/wiki/Vitamin_B12_deficiency
********************************************************************************************
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
Natural
Chemical Found in Grapes May Protect Against Alzheimer's
Disease
ScienceDaily
(July 15, 2011) — Researchers at Mount Sinai School of Medicine
have found that grape seed polyphenols -- a natural antioxidant
-- may help prevent the development or delay the progression of
Alzheimer's disease...
http://www.sciencedaily.com/releases/2011/07/110715135211.htm
Grape
Seed Polyphenolic Extract Specifically Decreases Aβ*56 in the
Brains of Tg2576 Mice.
Liu P,
Kemper LJ, Wang J, Zahs KR, Ashe KH, Pasinetti GM.
J
Alzheimers Dis. 2011 Jul 8. [Epub ahead of print]
N. Bud
Grossman Center for Memory Research and Care, University of
Minnesota Medical School, Minneapolis, MN, USA.
Abstract
Amyloid-β
(Aβ) oligomers, found in the brains of Alzheimer's disease (AD)
patients and transgenic mouse models of AD, cause
synaptotoxicity and memory impairment. Grape seed polyphenolic
extract (GSPE) inhibits Aβ oligomerization in vitro and
attenuates cognitive impairment and AD-related neuropathology in
the brains of transgenic mice. In the current study, GSPE was
administered to Tg2576 mice for a period of five months.
Treatment significantly decreased brain levels of Aβ*56, a
56-kDa Aβ oligomer previously shown to induce memory dysfunction
in rodents, without changing the levels of transgenic amyloid-β
protein precursor, monomeric Aβ, or other Aβ oligomers. These
results thus provide the first demonstration that a safe and
affordable intervention can lower the levels of a
memory-impairing Aβ oligomer in vivo and strongly suggest that
GSPE should be further tested as a potential prevention and/or
therapy for AD.
PMID:21743132[PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21743132
********************************************************************************************
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 (NP-12, Tideglusib,
Zentylor)
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
Efficacy, Safety and
Tolerability of Tideglusib to Treat Mild-to-Moderate
Alzheimer's Disease Patients (ARGO)
Purpose
The main purpose of this study is to evaluate the cognitive
changes after administration of tideglusib versus placebo at two
oral doses and two treatment regimes for 26 weeks in patients
with mild to moderate Alzheimer's disease.
After the 26 week core treatment period, the patients may
continue in the study under blinded conditions for an optional
extension period up to a maximum of 39 additional weeks (total
study duration up to 65 weeks), until the last patient in the
study has completed the 26 week of treatment.
http://clinicaltrials.gov/ct2/show/NCT01350362
FDA Grants Fast Track Status to Tideglusib (Zentylor) for
Progressive Supranuclear Palsy
http://www.drugs.com/news/fda-grants-fast-track-status-tideglusib-zentylor-progressive-supranuclear-palsy-26571.html
********************************************************************************************
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 chronic
cerebrospinal
venous insufficiency
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)
The content of this section has
been moved to The Role of Infection and Inflammation in
Neurodegenerative Diseases.
********************************************************************************************
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
Amyloid-beta
transporter expression at the blood-CSF barrier is
age-dependent.
Pascale
CL, Miller MC, Chiu C, Boylan M, Caralopoulos IN, Gonzalez L,
Johanson CE, Silverberg GD.
Fluids
Barriers CNS. 2011 Jul 8;8(1):21.
Abstract
ABSTRACT:
BACKGROUND: Age is the major risk factor for many
neurodegenerative diseases, including Alzheimer's disease (AD).
There is an accumulation of amyloid-beta peptides (Abeta) in
both the AD brain and the normal aging brain. Clearance of Abeta
from the brain occurs via active transport at the blood-brain
barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB).
With increasing age, the expression of the Abeta efflux
transporters is decreased and the Abeta influx transporter
expression is increased at the BBB, adding to the amyloid burden
in the brain. Expression of the Abeta transporters at the
choroid plexus (CP) epithelium as a function of aging was the
subject of this study. Methods: This project investigated the
changes in expression of the Abeta transporters, the low density
lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein
(P-gp), LRP-2 (megalin) and the receptor for advanced glycation
end-products (RAGE) at the BCSFB in Brown-Norway/Fischer rats at
ages 3, 6, 9, 12, 20, 30 and 36 months, using real time RT-PCR
to measure transporter mRNA expression, and immunohistochemistry
(IHC) to measure transporter protein on isolated rat CP. For
both the RT-PCR and the IHC analyses a single-factor ANOVA
followed by Tukey's pairwise comparisons were used to analyze
the data. Results: There was an increase in the transcription of
the Abeta efflux transporters, LRP-1 and P-gp, no change in RAGE
expression and a decrease in LRP-2, the CP epithelium influx
transporter, at the BCSFB with aging. Decreased Abeta42
concentration in the CP, as measured by quantitative IHC, was
associated with these Abeta transporter alterations.
Conclusions: Age-dependent alterations in the CP Abeta
transporters are associated with a decrease in Abeta42
accumulation in the CP, and are reciprocal to the changes seen
in these transporters at the BBB, suggesting a possible
compensatory role for the BCSFB in Abeta clearance in aging.
PMID:21740544
[PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21740544
Free
Full Text: http://www.fluidsbarrierscns.com/content/8/1/21/abstract
********************************************************************************************
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.
********************************************************************************************
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Home Preface
Brain Failure Notes Notes II References pg. 1 References pg. 2
Nutritional Alternatives
Patricia's Protocol Tauopathy
Discussion Forum
Correspondence Newsletters Poems Memory Enhancement
Click to
join tauopathies
********************************************************************************************
Questions or comments, contact
"perpetualcommotion.com" at gmail.com
Updated:
December 17, 2010
Inception: June 5, 2006