Iron metabolism in neurodegenerative diseases
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Swarfmaker
Dec 2, 2010, 8:09:12 AM12/2/10
to Alzheimer's Medicines Supplements and Treatments
If only physicians could help people with CBD. But the neurologist we
saw said there was nothing he could do. So, instead of accepting
"nothing", why not try something? When you buy a lottery ticket, do
you expect to win? No, odds are definitely not in your favor. Yet you
buy one anyway. Why? Well, you know that you have absolutely no chance
of winning at all if you don't at least try. So, here is something to
try when the physicians have nothing to offer...
This article, "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
explores the link between iron and degenerative neurological diseases
such as CBD/CBGD. (In the article, curcumin is mentioned as possibly
being useful in mitigating the damaging effects of iron in the brain.)
Then, this article about IP6 tells me that adding phytic acid to a
CBGD sufferer's diet may be beneficial. IP6/phytic acid is found in
the husks of whole grains. In impoverished parts of the world, where
people eat too much unprocessed whole grains, they tend to be
deficient in minerals.
"Inhibition of iron-catalysed hydroxyl radical formation by inositol
polyphosphates: a possible physiological function for myo-inositol
hexakisphosphate"
Phillip T. HAWKINS, David R. POYNER,* Trevor R. JACKSON, Andrew J.
LETCHER, David A. LANDER and Robin F. IRVINE Department of
Biochemistry, AFRC Institute of Animal Physiology and Genetics
Research, Babraham, Cambridge CB2 4AT, U.K. http://www.biochemj.org/bj/294/0929/2940929.pdf
shows that IP6 (a.k.a. InsP) is an extremely potent iron chelator
(absorbs excess iron floating around, rendering it harmless).
"In 1984, Graf et al. showed that InsP. was a particularly effective
inhibitor of iron-catalysed hydroxyl radical (OH') formation, and
suggested that it might make a useful food additive (Graf et al.,
1984, 1987; Graf and Eaton, 1990)."
"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 InsPJ 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)."
IP6 can be found in health food stores, sold as an immune system
builder. I doubt if this substance alone can slow, halt or reverse
CBD, but maybe this and something else will. There are more CBGD cases
represented here on this list than most neurologists will see in an
entire career. How do they know for sure that nothing will help? Have
they tried IP6? Have they tried curcumin? Have they tried antioxidants
or a combination of these things? Have any of you folks? I could be
mistaken, but I haven't found a research paper on the Internet saying
that the scientific community has. The jury is still out. We don't
know. They don't know. Trying some of these things might lead to a
treatment, just as they have nutritional alternatives for certain
types of glaucoma and type II diabetes.
Recently, this article about iron metabolism appeared on
ScienceDaily.com. I have not found any research on using chelating
agents to mitigate iron metabolism problems. Time to do your own
research. Iron chelating agents that are easily available are IP6,
curcumin, and EDTA.
Iron-moving Malfunction May Underlie Neurodegenerative Diseases, Aging
ScienceDaily (Sep. 26, 2008)
"A glitch in the ability to move iron around in cells may underlie a
disease known as Type IV mucolipidosis (ML4) and the suite of
symptoms---mental retardation, poor vision and diminished motor
abilities---that accompany it, new research at the University of
Michigan shows."
"The same deficit also may be involved in aging and neurodegenerative
diseases such as Alzheimer's and Parkinson's, says lead author Haoxing
Xu, an assistant professor of molecular, cellular and developmental
biology."
"How lipofuscin causes problems in neurons and muscles is not clear,
but it's believed that this is garbage that, in time, compromises the
normal function of the lysosome," Xu said. "And we know the lysosome
is important for all kinds of cell biology, particularly the recycling
of intracellular components, so if it's damaged, the cell is going to
suffer." Indeed, abnormal accumulation of lipofuscin is associated
with a range of disorders including Alzheimer's disease, Parkinson's
disease, and macular degeneration (a degenerative disease of the eye)
and also contributes to the aging process."
Here is an excerpt from page 8 of the the PDF document cited above
"Iron metabolism in Parkinsonian syndromes" about the possible use of
curcumin:
"In an attempt to overcome the problem of brain impermeability of
desferrioxamine, development is under way of brain-permeable iron
chelators, such as VK-28 (5-[4-(2hydroxyl) piperazine-1-ymethyl] -
quinoline-8-ol); bifunctional iron chelators combining iron chelating,
monoamino oxidase A- and B-selective inhibitory and neuroprotective
antiapoptotic properties like HLA-20, M30, and M30A160; and the copper–
iron chelator iodochlorhydroxyquin. Although animal experiments are
promising, the use of these iron chelators must be carefully
controlled to avoid toxic side effects. 176 EGCG ((-)-
epigallocatechin-3-gallate; the major polyphenol of green tea) and
curcurium (a constituent of turmeric) are discussed as nontoxic metal
chelators. Also antioxidant–radical scavengers, such as vitamin
E,lipoic acid, ebselen, melatonin, and glutathione, can be
considered."
"However, it has to be kept in mind that, in comparison with
monogenetically determined causes of brain iron accumulation, iron
overload in PD and atypical parkinsonian syndromes is small. Different
possibly additive neurotoxic mechanisms have to be considered.
Therefore, iron chelation can be only one of several mechanisms to try
to ameliorate neurodegeneration in these disorders."
The text uses the word "curcurium" but I think it is misspelled. The
associated note, #178 reads:
178. Baum L, Ng A. Curcumin interaction with copper and iron suggests
one possible mechanism of action in Alzheimer's disease animal models.
J Alzheimers Dis 2004;6:367–377.
The last paragraph seems reasonable in that excess iron is probably
just one of several necessary targets.
Desferrioxamine, I think, must be injected. There is an oral iron
chelator, Exjade (deferaserox?). Desferrioxamine is also known as
desferal or desferral. In the article "Inhibition of iron-catalysed
hydroxyl radical formation by inositol polyphosphates: a possible
physiological function for myo-inositol hexakisphosphate", (http://
www.biochemj.org/bj/294/0929/2940929.pdf) the authors found that IP6
(a.k.a. InsP6) was a strong chelator of iron, arguably with a stronger
affinity for iron than desferal.
"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 [InsP6 and EDTA] is presumably because InsPJ has
multiple phosphates which are capable of chelating Fe3+ with high
affinity (i.e. more than one Fe3+ can be bound per InsP6"
A good question is, does IP6 cross the blood-brain barrier? I don't
remember, and I can't find anything that says either way. I
searchedfor reference quickly, but didn't come up with anything. I'll
keep searching.
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/
If only physicians could help people with CBD. But the neurologist we
saw said there was nothing he could do. So, instead of accepting
"nothing", why not try something? When you buy a lottery ticket, do
you expect to win? No, odds are definitely not in your favor. Yet you
buy one anyway. Why? Well, you know that you have absolutely no chance
of winning at all if you don't at least try. So, here is something to
try when the physicians have nothing to offer...
This article, "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
explores the link between iron and degenerative neurological diseases
such as CBD/CBGD. (In the article, curcumin is mentioned as possibly
being useful in mitigating the damaging effects of iron in the brain.)
Then, this article about IP6 tells me that adding phytic acid to a
CBGD sufferer's diet may be beneficial. IP6/phytic acid is found in
the husks of whole grains. In impoverished parts of the world, where
people eat too much unprocessed whole grains, they tend to be
deficient in minerals.
"Inhibition of iron-catalysed hydroxyl radical formation by inositol
polyphosphates: a possible physiological function for myo-inositol
hexakisphosphate"
Phillip T. HAWKINS, David R. POYNER,* Trevor R. JACKSON, Andrew J.
LETCHER, David A. LANDER and Robin F. IRVINE Department of
Biochemistry, AFRC Institute of Animal Physiology and Genetics
Research, Babraham, Cambridge CB2 4AT, U.K. http://www.biochemj.org/bj/294/0929/2940929.pdf
shows that IP6 (a.k.a. InsP) is an extremely potent iron chelator
(absorbs excess iron floating around, rendering it harmless).
"In 1984, Graf et al. showed that InsP. was a particularly effective
inhibitor of iron-catalysed hydroxyl radical (OH') formation, and
suggested that it might make a useful food additive (Graf et al.,
1984, 1987; Graf and Eaton, 1990)."
"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 InsPJ 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)."
IP6 can be found in health food stores, sold as an immune system
builder. I doubt if this substance alone can slow, halt or reverse
CBD, but maybe this and something else will. There are more CBGD cases
represented here on this list than most neurologists will see in an
entire career. How do they know for sure that nothing will help? Have
they tried IP6? Have they tried curcumin? Have they tried antioxidants
or a combination of these things? Have any of you folks? I could be
mistaken, but I haven't found a research paper on the Internet saying
that the scientific community has. The jury is still out. We don't
know. They don't know. Trying some of these things might lead to a
treatment, just as they have nutritional alternatives for certain
types of glaucoma and type II diabetes.
Recently, this article about iron metabolism appeared on
ScienceDaily.com. I have not found any research on using chelating
agents to mitigate iron metabolism problems. Time to do your own
research. Iron chelating agents that are easilty available are IP6,
curcumin, and EDTA.
Iron-moving Malfunction May Underlie Neurodegenerative Diseases, Aging
ScienceDaily (Sep. 26, 2008)
"A glitch in the ability to move iron around in cells may underlie a
disease known as Type IV mucolipidosis (ML4) and the suite of
symptoms---mental retardation, poor vision and diminished motor
abilities---that accompany it, new research at the University of
Michigan shows."
"The same deficit also may be involved in aging and neurodegenerative
diseases such as Alzheimer's and Parkinson's, says lead author Haoxing
Xu, an assistant professor of molecular, cellular and developmental
biology."
"How lipofuscin causes problems in neurons and muscles is not clear,
but it's believed that this is garbage that, in time, compromises the
normal function of the lysosome," Xu said. "And we know the lysosome
is important for all kinds of cell biology, particularly the recycling
of intracellular components, so if it's damaged, the cell is going to
suffer." Indeed, abnormal accumulation of lipofuscin is associated
with a range of disorders including Alzheimer's disease, Parkinson's
disease, and macular degeneration (a degenerative disease of the eye)
and also contributes to the aging process."
Here is an excerpt from page 8 of the the PDF document cited above
"Iron metabolism in Parkinsonian syndromes" about the possible use of
curcumin:
"In an attempt to overcome the problem of brain impermeability of
desferrioxamine, development is under way of brain-permeable iron
chelators, such as VK-28 (5-[4-(2hydroxyl) piperazine-1-ymethyl] -
quinoline-8-ol); bifunctional iron chelators combining iron chelating,
monoamino oxidase A- and B-selective inhibitory and neuroprotective
antiapoptotic properties like HLA-20, M30, and M30A160; and the copper–
iron chelator iodochlorhydroxyquin. Although animal experiments are
promising, the use of these iron chelators must be carefully
controlled to avoid toxic side effects. 176 EGCG ((-)-
epigallocatechin-3-gallate; the major polyphenol of green tea) and
curcurium (a constituent of turmeric) are discussed as nontoxic metal
chelators. Also antioxidant–radical scavengers, such as vitamin
E,lipoic acid, ebselen, melatonin, and glutathione, can be
considered."
"However, it has to be kept in mind that, in comparison with
monogenetically determined causes of brain iron accumulation, iron
overload in PD and atypical parkinsonian syndromes is small. Different
possibly additive neurotoxic mechanisms have to be considered.
Therefore, iron chelation can be only one of several mechanisms to try
to ameliorate neurodegeneration in these disorders."
The text uses the word "curcurium" but I think it is misspelled. The
associated note, #178 reads:
178. Baum L, Ng A. Curcumin interaction with copper and iron suggests
one possible mechanism of action in Alzheimer's disease animal models.
J Alzheimers Dis 2004;6:367–377.
The last paragraph seems reasonable in that excess iron is probably
just one of several necessary targets.
Desferrioxamine, I think, must be injected. There is an oral iron
chelator, Exjade (deferaserox?). Desferrioxamine is also known as
desferal or desferral. In the article "Inhibition of iron-catalysed
hydroxyl radical formation by inositol polyphosphates: a possible
physiological function for myo-inositol hexakisphosphate", (http://
www.biochemj.org/bj/294/0929/2940929.pdf) the authors found that IP6
(a.k.a. InsP6) was a strong chelator of iron, arguably with a stronger
affinity for iron than desferal.
"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 [InsP6 and EDTA] is presumably because InsPJ has
multiple phosphates which are capable of chelating Fe3+ with high
affinity (i.e. more than one Fe3+ can be bound per InsP6"
A good question is, does IP6 cross the blood-brain barrier? I
don'tremember, and I can't find anything that says either way. I
searchedfor reference quickly, but didn't come up with anything. I'll
keepsearching.
saw said there was nothing he could do. So, instead of accepting
"nothing", why not try something? When you buy a lottery ticket, do
you expect to win? No, odds are definitely not in your favor. Yet you
buy one anyway. Why? Well, you know that you have absolutely no chance
of winning at all if you don't at least try. So, here is something to
try when the physicians have nothing to offer...
This article, "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
explores the link between iron and degenerative neurological diseases
such as CBD/CBGD. (In the article, curcumin is mentioned as possibly
being useful in mitigating the damaging effects of iron in the brain.)
Then, this article about IP6 tells me that adding phytic acid to a
CBGD sufferer's diet may be beneficial. IP6/phytic acid is found in
the husks of whole grains. In impoverished parts of the world, where
people eat too much unprocessed whole grains, they tend to be
deficient in minerals.
"Inhibition of iron-catalysed hydroxyl radical formation by inositol
polyphosphates: a possible physiological function for myo-inositol
hexakisphosphate"
Phillip T. HAWKINS, David R. POYNER,* Trevor R. JACKSON, Andrew J.
LETCHER, David A. LANDER and Robin F. IRVINE Department of
Biochemistry, AFRC Institute of Animal Physiology and Genetics
Research, Babraham, Cambridge CB2 4AT, U.K. http://www.biochemj.org/bj/294/0929/2940929.pdf
shows that IP6 (a.k.a. InsP) is an extremely potent iron chelator
(absorbs excess iron floating around, rendering it harmless).
"In 1984, Graf et al. showed that InsP. was a particularly effective
inhibitor of iron-catalysed hydroxyl radical (OH') formation, and
suggested that it might make a useful food additive (Graf et al.,
1984, 1987; Graf and Eaton, 1990)."
"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 InsPJ 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)."
IP6 can be found in health food stores, sold as an immune system
builder. I doubt if this substance alone can slow, halt or reverse
CBD, but maybe this and something else will. There are more CBGD cases
represented here on this list than most neurologists will see in an
entire career. How do they know for sure that nothing will help? Have
they tried IP6? Have they tried curcumin? Have they tried antioxidants
or a combination of these things? Have any of you folks? I could be
mistaken, but I haven't found a research paper on the Internet saying
that the scientific community has. The jury is still out. We don't
know. They don't know. Trying some of these things might lead to a
treatment, just as they have nutritional alternatives for certain
types of glaucoma and type II diabetes.
Recently, this article about iron metabolism appeared on
ScienceDaily.com. I have not found any research on using chelating
agents to mitigate iron metabolism problems. Time to do your own
research. Iron chelating agents that are easily available are IP6,
curcumin, and EDTA.
Iron-moving Malfunction May Underlie Neurodegenerative Diseases, Aging
ScienceDaily (Sep. 26, 2008)
"A glitch in the ability to move iron around in cells may underlie a
disease known as Type IV mucolipidosis (ML4) and the suite of
symptoms---mental retardation, poor vision and diminished motor
abilities---that accompany it, new research at the University of
Michigan shows."
"The same deficit also may be involved in aging and neurodegenerative
diseases such as Alzheimer's and Parkinson's, says lead author Haoxing
Xu, an assistant professor of molecular, cellular and developmental
biology."
"How lipofuscin causes problems in neurons and muscles is not clear,
but it's believed that this is garbage that, in time, compromises the
normal function of the lysosome," Xu said. "And we know the lysosome
is important for all kinds of cell biology, particularly the recycling
of intracellular components, so if it's damaged, the cell is going to
suffer." Indeed, abnormal accumulation of lipofuscin is associated
with a range of disorders including Alzheimer's disease, Parkinson's
disease, and macular degeneration (a degenerative disease of the eye)
and also contributes to the aging process."
Here is an excerpt from page 8 of the the PDF document cited above
"Iron metabolism in Parkinsonian syndromes" about the possible use of
curcumin:
"In an attempt to overcome the problem of brain impermeability of
desferrioxamine, development is under way of brain-permeable iron
chelators, such as VK-28 (5-[4-(2hydroxyl) piperazine-1-ymethyl] -
quinoline-8-ol); bifunctional iron chelators combining iron chelating,
monoamino oxidase A- and B-selective inhibitory and neuroprotective
antiapoptotic properties like HLA-20, M30, and M30A160; and the copper–
iron chelator iodochlorhydroxyquin. Although animal experiments are
promising, the use of these iron chelators must be carefully
controlled to avoid toxic side effects. 176 EGCG ((-)-
epigallocatechin-3-gallate; the major polyphenol of green tea) and
curcurium (a constituent of turmeric) are discussed as nontoxic metal
chelators. Also antioxidant–radical scavengers, such as vitamin
E,lipoic acid, ebselen, melatonin, and glutathione, can be
considered."
"However, it has to be kept in mind that, in comparison with
monogenetically determined causes of brain iron accumulation, iron
overload in PD and atypical parkinsonian syndromes is small. Different
possibly additive neurotoxic mechanisms have to be considered.
Therefore, iron chelation can be only one of several mechanisms to try
to ameliorate neurodegeneration in these disorders."
The text uses the word "curcurium" but I think it is misspelled. The
associated note, #178 reads:
178. Baum L, Ng A. Curcumin interaction with copper and iron suggests
one possible mechanism of action in Alzheimer's disease animal models.
J Alzheimers Dis 2004;6:367–377.
The last paragraph seems reasonable in that excess iron is probably
just one of several necessary targets.
Desferrioxamine, I think, must be injected. There is an oral iron
chelator, Exjade (deferaserox?). Desferrioxamine is also known as
desferal or desferral. In the article "Inhibition of iron-catalysed
hydroxyl radical formation by inositol polyphosphates: a possible
physiological function for myo-inositol hexakisphosphate", (http://
www.biochemj.org/bj/294/0929/2940929.pdf) the authors found that IP6
(a.k.a. InsP6) was a strong chelator of iron, arguably with a stronger
affinity for iron than desferal.
"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 [InsP6 and EDTA] is presumably because InsPJ has
multiple phosphates which are capable of chelating Fe3+ with high
affinity (i.e. more than one Fe3+ can be bound per InsP6"
A good question is, does IP6 cross the blood-brain barrier? I don't
remember, and I can't find anything that says either way. I
searchedfor reference quickly, but didn't come up with anything. I'll
keep searching.
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/
If only physicians could help people with CBD. But the neurologist we
saw said there was nothing he could do. So, instead of accepting
"nothing", why not try something? When you buy a lottery ticket, do
you expect to win? No, odds are definitely not in your favor. Yet you
buy one anyway. Why? Well, you know that you have absolutely no chance
of winning at all if you don't at least try. So, here is something to
try when the physicians have nothing to offer...
This article, "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
explores the link between iron and degenerative neurological diseases
such as CBD/CBGD. (In the article, curcumin is mentioned as possibly
being useful in mitigating the damaging effects of iron in the brain.)
Then, this article about IP6 tells me that adding phytic acid to a
CBGD sufferer's diet may be beneficial. IP6/phytic acid is found in
the husks of whole grains. In impoverished parts of the world, where
people eat too much unprocessed whole grains, they tend to be
deficient in minerals.
"Inhibition of iron-catalysed hydroxyl radical formation by inositol
polyphosphates: a possible physiological function for myo-inositol
hexakisphosphate"
Phillip T. HAWKINS, David R. POYNER,* Trevor R. JACKSON, Andrew J.
LETCHER, David A. LANDER and Robin F. IRVINE Department of
Biochemistry, AFRC Institute of Animal Physiology and Genetics
Research, Babraham, Cambridge CB2 4AT, U.K. http://www.biochemj.org/bj/294/0929/2940929.pdf
shows that IP6 (a.k.a. InsP) is an extremely potent iron chelator
(absorbs excess iron floating around, rendering it harmless).
"In 1984, Graf et al. showed that InsP. was a particularly effective
inhibitor of iron-catalysed hydroxyl radical (OH') formation, and
suggested that it might make a useful food additive (Graf et al.,
1984, 1987; Graf and Eaton, 1990)."
"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 InsPJ 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)."
IP6 can be found in health food stores, sold as an immune system
builder. I doubt if this substance alone can slow, halt or reverse
CBD, but maybe this and something else will. There are more CBGD cases
represented here on this list than most neurologists will see in an
entire career. How do they know for sure that nothing will help? Have
they tried IP6? Have they tried curcumin? Have they tried antioxidants
or a combination of these things? Have any of you folks? I could be
mistaken, but I haven't found a research paper on the Internet saying
that the scientific community has. The jury is still out. We don't
know. They don't know. Trying some of these things might lead to a
treatment, just as they have nutritional alternatives for certain
types of glaucoma and type II diabetes.
Recently, this article about iron metabolism appeared on
ScienceDaily.com. I have not found any research on using chelating
agents to mitigate iron metabolism problems. Time to do your own
research. Iron chelating agents that are easilty available are IP6,
curcumin, and EDTA.
Iron-moving Malfunction May Underlie Neurodegenerative Diseases, Aging
ScienceDaily (Sep. 26, 2008)
"A glitch in the ability to move iron around in cells may underlie a
disease known as Type IV mucolipidosis (ML4) and the suite of
symptoms---mental retardation, poor vision and diminished motor
abilities---that accompany it, new research at the University of
Michigan shows."
"The same deficit also may be involved in aging and neurodegenerative
diseases such as Alzheimer's and Parkinson's, says lead author Haoxing
Xu, an assistant professor of molecular, cellular and developmental
biology."
"How lipofuscin causes problems in neurons and muscles is not clear,
but it's believed that this is garbage that, in time, compromises the
normal function of the lysosome," Xu said. "And we know the lysosome
is important for all kinds of cell biology, particularly the recycling
of intracellular components, so if it's damaged, the cell is going to
suffer." Indeed, abnormal accumulation of lipofuscin is associated
with a range of disorders including Alzheimer's disease, Parkinson's
disease, and macular degeneration (a degenerative disease of the eye)
and also contributes to the aging process."
Here is an excerpt from page 8 of the the PDF document cited above
"Iron metabolism in Parkinsonian syndromes" about the possible use of
curcumin:
"In an attempt to overcome the problem of brain impermeability of
desferrioxamine, development is under way of brain-permeable iron
chelators, such as VK-28 (5-[4-(2hydroxyl) piperazine-1-ymethyl] -
quinoline-8-ol); bifunctional iron chelators combining iron chelating,
monoamino oxidase A- and B-selective inhibitory and neuroprotective
antiapoptotic properties like HLA-20, M30, and M30A160; and the copper–
iron chelator iodochlorhydroxyquin. Although animal experiments are
promising, the use of these iron chelators must be carefully
controlled to avoid toxic side effects. 176 EGCG ((-)-
epigallocatechin-3-gallate; the major polyphenol of green tea) and
curcurium (a constituent of turmeric) are discussed as nontoxic metal
chelators. Also antioxidant–radical scavengers, such as vitamin
E,lipoic acid, ebselen, melatonin, and glutathione, can be
considered."
"However, it has to be kept in mind that, in comparison with
monogenetically determined causes of brain iron accumulation, iron
overload in PD and atypical parkinsonian syndromes is small. Different
possibly additive neurotoxic mechanisms have to be considered.
Therefore, iron chelation can be only one of several mechanisms to try
to ameliorate neurodegeneration in these disorders."
The text uses the word "curcurium" but I think it is misspelled. The
associated note, #178 reads:
178. Baum L, Ng A. Curcumin interaction with copper and iron suggests
one possible mechanism of action in Alzheimer's disease animal models.
J Alzheimers Dis 2004;6:367–377.
The last paragraph seems reasonable in that excess iron is probably
just one of several necessary targets.
Desferrioxamine, I think, must be injected. There is an oral iron
chelator, Exjade (deferaserox?). Desferrioxamine is also known as
desferal or desferral. In the article "Inhibition of iron-catalysed
hydroxyl radical formation by inositol polyphosphates: a possible
physiological function for myo-inositol hexakisphosphate", (http://
www.biochemj.org/bj/294/0929/2940929.pdf) the authors found that IP6
(a.k.a. InsP6) was a strong chelator of iron, arguably with a stronger
affinity for iron than desferal.
"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 [InsP6 and EDTA] is presumably because InsPJ has
multiple phosphates which are capable of chelating Fe3+ with high
affinity (i.e. more than one Fe3+ can be bound per InsP6"
A good question is, does IP6 cross the blood-brain barrier? I
don'tremember, and I can't find anything that says either way. I
searchedfor reference quickly, but didn't come up with anything. I'll
keepsearching.
Swarfmaker
Dec 2, 2010, 8:33:26 AM12/2/10
to Alzheimer's Medicines Supplements and Treatments
More on the relationship between iron and a tauopathy:
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
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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