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- 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/695/1/73

Now 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 TŁbingen, 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 Alzheimerís disease brain tissue
 
"Elevated iron levels are associated with many types of neurodegenerative disease, such as Alzheimerís, Parkinsonís and Huntingtonís 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 Alzheimerís 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 Huntingtonís 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 Alzheimerís 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