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-- J.R.R. Tolkien The Children of Hurin
- Iron -
General Information:
Names:
Wikipedia entry:
Dr. Ray Shahelien
entry:
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Observations:
See also
IP6
Curcumin
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?
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Known sources:
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Natural sources:
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References:
Myricetin suppresses iron
neurodegeneration
http://forum.lowcarber.org/showthread.php?t=339842
Iron:
Iron metabolism in Parkinsonian syndromes
Mov Disord. 2006 Sep;21(9):1299-310.
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&uid=16817199&cmd=showdetailview
Berg D, Hochstrasser H.
Hertie Institute of Clinical Brain Research and Department of
Medical Genetics, University of Tübingen, Germany.
from the abstract...
"Growing evidence suggests an involvement of iron in the
pathophysiology of neurodegenerative diseases. Several of the
diseases are associated with parkinsonian syndromes, induced by
degeneration of basal ganglia regions that contain the highest
amount of iron within the brain. The group of neurodegenerative
disorders associated with parkinsonian syndromes with increased
brain iron content can be devided into two groups: (1)
parkinsonian syndromes associated with brain iron accumulation,
including Parkinson's disease, diffuse Lewy body disease,
parkinsonian type of multiple system atrophy, progressive
supranuclear palsy, corticobasal ganglionic degeneration, and
Westphal variant of Huntington's disease; and (2) monogenetically
caused disturbances of brain iron metabolism associated with
parkinsonian syndromes, including aceruloplasminemia, hereditary
ferritinopathies affecting the basal ganglia, and panthotenate
kinase associated neurodegeneration type 2. Although it is still a
matter of debate whether iron accumulation is a primary cause or
secondary event in the first group, there is no doubt that
iron-induced oxidative stress contributes to neurodegeneration.
Parallels concerning pathophysiological as well as clinical
aspects can be drawn between disorders of both groups. Results
from animal models and reduction of iron overload combined with at
least partial relief of symptoms by application of iron chelators
in patients of the second group give hope that targeting the iron
overload might be one possibility to slow down the
neurodegenerative cascade also in the first group of inevitably
progressive neurodegenerative disorders."
Live Discussion: Hemochromatosis as a Factor in AD
http://www.alzforum.org/res/for/journal/milward/default.asp
The Integrated Role of Desferrioxamine and Phenserine Targeted
to an Iron-Responsive Element in the APP-mRNA 5'-Untranslated
Region
AMANDA VENTIa, TONY GIORDANOb, PAUL EDERa, ASHLEY I. BUSHa,
DEBOMOY K. LAHIRIc, NIGEL H. GREIGd and JACK T. ROGERSa
http://www.annalsnyas.org/cgi/content/abstract/1035/1/34
Iron: Too Much of a Good Thing
"Recent studies reveal that blood donors exhibit lower rates of
many diseases and experience better than average health.
Additionally, the centuries-old practice of bloodletting is being
revived as a treatment for disorders such as heart disease, cancer
and Alzheimer's.1 Why would blood reduction improve health
parameters? In part, because blood removal helps to control
circulating iron levels."
http://www.chiro.org/nutrition/FULL/Iron_Too_Much_of_a_Good_Thing.html
Is hemochromatosis a risk factor for Alzheimer's disease?
"Excess iron accumulation in the brain is a consistent observation
in Alzheimer's Disease. Iron affects amyloid precursor protein
(AbetaPP) processing and promotes deposition of Abeta. Iron is
also among the most potent biological toxins because of its
ability to react with oxygen to form reactive oxygen species."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12214033&dopt=Abstract
Preliminary evaluation of nanoscale biogenic magnetite in
Alzheimer’s disease brain tissue
"Elevated iron levels are associated with many types of
neurodegenerative disease, such as Alzheimer’s, Parkinson’s and
Huntington’s diseases. However, these elevated iron levels do not
necessarily correlate with elevated levels of the iron storage or
transport proteins, ferritin and transferrin. As such, little is
known about the form of this excess iron. It has recently been
proposed that some of the excess iron in neurodegenerative tissue
may be in the form of the magnetic iron oxide magnetite (Fe3O4).
We demonstrate, for the first time to our knowledge, using highly
sensitive superconducting quantum interference device (SQUID)
magnetometry, that the concentrations of magnetite are found to be
significantly higher in three samples of Alzheimer’s disease
tissue than in three age- and sex-matched controls. These results
have implications, not only for disease progression, but also for
possible early diagnosis."
[The link is to a PDF document]
http://www.pubs.royalsoc.ac.uk/media/biology_letters/dobson.pdf
IRON OVERLOAD - THE MISSED DIAGNOSIS
"Physicians were more interested in anaemias and low iron
deficiency and did not really perform the necessary tests of iron
metabolism to diagnose the opposite end of the spectrum - iron
overload. He described conditions directly related to excess iron
in the body such as arthritis, diabetes, psychiatric illness, and
liver disease."
"Dr. Richardson, Chief of Psychiatry at the University of
Saskatchewan 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. It is my feeling that iron is a far
greater risk in this condition than is aluminum."
http://www.consumerhealth.org/articles/display.cfm?ID=19990303140150
"Although iron deficiency is most commonly linked with anemia,
iron is also a component of many enzymes. The iron associated with
hemoglobin is referred to as heme iron; all other sources are
non-heme. "Heme iron is much better absorbed than non-heme iron,"
notes Hunt. "The absorption of non-heme iron is substantially
influenced by other things that you eat in the same meal. For
instance, ascorbic acid can increase iron absorption by two to
four times." She adds that the phytic acid found in plant sources
"tends to bind the minerals and make them less soluble, so they
pass through the gut instead of being absorbed." She recommends
freeing-up the iron with vitamin C (ascorbic acid) or using a
chelating agent such as EDTA to avoid binding the iron."
[Ooops! Vitamin C increases iron absorption?]
http://www.foodproductdesign.com/current/1105HN.html
Magnetic crystals in brain linked to Alzheimer's
"Tiny magnetic iron crystals in the brain may be linked to the
development of Alzheimer's disease, suggests preliminary
research."
"Dobson says it has been known for 50 years that there is an
association between excess iron and Alzheimer's disease, but that
scientists had been baffled by the form in which this iron
occurs."
http://www.newscientist.com/article.ns?id=dn3611
Scan to reveal brain disease clue
"Scientists say it will help to pin down the role of iron and
other metals in neurological disorders such as Alzheimer's and
Parkinson's disease."
http://news.bbc.co.uk/2/hi/health/4184417.stm
Dr. Cathy W. Levenson
Ph.D., University of Chicago, 1993
Hazel K. Stiebeling Professor of Nutrition, Food and
Exercise Science & Neuroscience
"Apoptosis, or programmed cell death is responsible for neuronal
death after traumatic brain and spinal cord injury, stroke, and
seizures. It also clearly plays a role in many neurodegenerative
diseases including Alzheimer's disease, Parkinson's disease,
amyotrophic lateral sclerosis (ALS) and Huntington’s disease. The
Levenson lab is currently exploring the molecular and cellular
mechanisms responsible for neuronal proliferation, survival, and
apoptosis, with a particular focus on the role of the metals
copper, zinc, and iron."
http://www.neuro.fsu.edu/faculty/levenson/main.html
The book The Iron Time-Bomb by Bill Sardi is available for $7.95
exclusively from Purity Products, one maker of IP-6, a derivative
of rice bran.
http://www.lloydwright.org/2005/Hepatitis-C/articles/Dangers_of_Iron_to_Patients_with_Hepatitis_C.htm
A[beta] Metallobiology and the Development of Novel
Metal-Protein Attenuating
Compounds (MPACs) for Alzheimer's Disease
Cyril C. Curtain1, Kevin J. Barnham1 and Ashley I. Bush
"Abstract: Over a decade of studies have pointed to metal mediated
neural oxidative damage as an attractive target for the treatment
of Alzheimer’s disease. Because of the nature of the blood brain
barrier, systemic depletion of the metals, copper, zinc and
possibly iron, is not a viable approach. However preliminary
studies with CQ, a blood brain barrier penetrating chelating
agent, are showing promise. CQ probably works by combining with
the metal centres, primarily copper and zinc complexes of A[beta],
in the neuropil. This review discusses some of the background that
resulted in CQ becoming a lead compound and how we might advance
our understanding of its action"
http://www.alzforum.org/res/for/journal/allsop/bush.pdf
New Findings Pull Back Curtain
on Relationship Between Iron and Alzheimer's Disease
ScienceDaily (Oct. 7, 2010)
Massachusetts General Hospital researchers say they have
determined how iron contributes to the production of
brain-destroying plaques found in Alzheimer's patients... study
results appear in the Journal of Biological Chemistry... Today it
is clear that, under healthy conditions, iron and APP [amyloid
precursor protein] keep each other in check: If there's too much
iron in a brain cell, more APP is made, and then APP and a partner
molecule escort excess iron out... The researchers also
identified, in the JBC paper, another important player in the
system of checks and balances used to regulate iron in brain
cells. Known as IRP1, which stands for iron-regulating protein 1,
the special molecule attaches to the messenger RNA that holds the
recipe for making APP. When there's less iron in the brain cell,
IRP1 is more likely to hook up with the RNA, which prevents the
production of APP. When there's abundant iron present, IRP1
doesn't hook up with the RNA, and APP production becomes
excessive... "With other research teams, we are investigating
novel therapies that remove excessive iron, and we're looking at
the precise spot on the messenger RNA where IRP1 binds to screen
for drugs that specifically prevent APP production,"...
http://www.sciencedaily.com/releases/2010/10/101006120132.htm
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Updated: July 2, 2012
Inception: July 2, 2012