Role of iron in alcoholic liver disease

Discussion in 'Food and nutrition' started by [email protected], Jan 5, 2006.

  1. Role of iron in alcoholic liver disease: introduction and summary of
    the symposium.
    Purohit V, Russo D, Salin M
    Alcohol. 2003 Jun ; 30(2): 93-7

    The National Institute on Alcohol Abuse and Alcoholism and the Office
    of Dietary Supplements, National Institutes of Health, sponsored a
    symposium on the "Role of Iron in Alcoholic Liver Disease" at Bethesda,
    Maryland, USA, October 2002. Alcoholic liver disease is a major cause
    of illness and death in the United States. Oxidative stress plays a key
    role in the pathogenesis of alcoholic liver disease. Iron can induce
    oxidative stress by catalyzing the conversion of superoxide and
    hydrogen peroxide to more potent oxidants such as hydroxyl radicals,
    which can cause tissue injury by initiating lipid peroxidation and
    causing oxidation of proteins and nucleic acids. Increasing evidence
    supports the suggestion that iron plays a significant role in the
    pathogenesis of alcoholic liver disease by exacerbating oxidative
    stress. Understanding the underlying mechanisms by which iron
    participates in the initiation and development of alcoholic liver
    disease may help design strategies for the treatment and prevention of
    the disease. For this symposium, nine speakers were invited to address
    the following issues: (1) iron intake from foods and dietary
    supplements; (2) hepatic iron overload in alcoholic liver disease; (3)
    iron-dependent activation of nuclear factor-kappa B (NF-kappaB) in
    Kupffer cells; (4) iron and cytochrome P450 2E1 (CYP2E1)-dependent
    oxidative stress and liver toxicity; (5) iron-induced oxidative stress
    in alcoholic hepatic fibrogenesis; (6) hemochromatosis and alcoholic
    liver disease; (7) iron as a co-morbid factor in nonhemochromatotic
    liver diseases; (8) iron and liver cancer; and (9) iron chelators and
    iron toxicity. On the basis of these presentations, it is concluded
    that heavy alcohol intake can result in increased accumulation of iron
    in the liver, in both hepatocytes and Kupffer cells. Iron-induced
    oxidative stress may promote the severity of alcoholic liver disease by
    (1) inducing NF-kappaB activation and subsequently increasing
    transcription of proinflammatory cytokines in Kupffer cells; (2)
    exacerbating CYP2E1-induced oxidative stress, especially in
    hepatocytes, through production of more toxic hydroxyl radicals; (3)
    stimulating hepatic stellate cells to produce excess amount of collagen
    and other matrix proteins that can lead to fibrosis; and (4) causing
    DNA damage and mutations that promote the development of liver cancer.
    Dietary iron supplements may further exacerbate the severity of
    alcoholic liver disease by increasing the magnitude of oxidative
    stress. We hope that the studies presented will stimulate further
    research in this exciting area.

    Who loves ya.
    Tom


    Jesus Was A Vegetarian!
    http://jesuswasavegetarian.7h.com


    Man Is A Herbivore!
    http://pages.ivillage.com/ironjustice/manisaherbivore


    DEAD PEOPLE WALKING
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  2. kumar

    kumar Guest

    Can iron overload be related to excess stomach acidity and non-veg
    foods? Excess acidity may improve digestion of iron in foods and
    probably be also related to overriding the intestinal mucus? Alcohol,
    modern stresses and foods, other heavy and citric/acid forming foods
    may increase stomach acidity--so more iron digestion. On the otherhand
    antacids/acid blockers may discourage it.
    [email protected] wrote:
    > Role of iron in alcoholic liver disease: introduction and summary of
    > the symposium.
    > Purohit V, Russo D, Salin M
    > Alcohol. 2003 Jun ; 30(2): 93-7
    >
    > The National Institute on Alcohol Abuse and Alcoholism and the Office
    > of Dietary Supplements, National Institutes of Health, sponsored a
    > symposium on the "Role of Iron in Alcoholic Liver Disease" at Bethesda,
    > Maryland, USA, October 2002. Alcoholic liver disease is a major cause
    > of illness and death in the United States. Oxidative stress plays a key
    > role in the pathogenesis of alcoholic liver disease. Iron can induce
    > oxidative stress by catalyzing the conversion of superoxide and
    > hydrogen peroxide to more potent oxidants such as hydroxyl radicals,
    > which can cause tissue injury by initiating lipid peroxidation and
    > causing oxidation of proteins and nucleic acids. Increasing evidence
    > supports the suggestion that iron plays a significant role in the
    > pathogenesis of alcoholic liver disease by exacerbating oxidative
    > stress. Understanding the underlying mechanisms by which iron
    > participates in the initiation and development of alcoholic liver
    > disease may help design strategies for the treatment and prevention of
    > the disease. For this symposium, nine speakers were invited to address
    > the following issues: (1) iron intake from foods and dietary
    > supplements; (2) hepatic iron overload in alcoholic liver disease; (3)
    > iron-dependent activation of nuclear factor-kappa B (NF-kappaB) in
    > Kupffer cells; (4) iron and cytochrome P450 2E1 (CYP2E1)-dependent
    > oxidative stress and liver toxicity; (5) iron-induced oxidative stress
    > in alcoholic hepatic fibrogenesis; (6) hemochromatosis and alcoholic
    > liver disease; (7) iron as a co-morbid factor in nonhemochromatotic
    > liver diseases; (8) iron and liver cancer; and (9) iron chelators and
    > iron toxicity. On the basis of these presentations, it is concluded
    > that heavy alcohol intake can result in increased accumulation of iron
    > in the liver, in both hepatocytes and Kupffer cells. Iron-induced
    > oxidative stress may promote the severity of alcoholic liver disease by
    > (1) inducing NF-kappaB activation and subsequently increasing
    > transcription of proinflammatory cytokines in Kupffer cells; (2)
    > exacerbating CYP2E1-induced oxidative stress, especially in
    > hepatocytes, through production of more toxic hydroxyl radicals; (3)
    > stimulating hepatic stellate cells to produce excess amount of collagen
    > and other matrix proteins that can lead to fibrosis; and (4) causing
    > DNA damage and mutations that promote the development of liver cancer.
    > Dietary iron supplements may further exacerbate the severity of
    > alcoholic liver disease by increasing the magnitude of oxidative
    > stress. We hope that the studies presented will stimulate further
    > research in this exciting area.
    >
    > Who loves ya.
    > Tom
    >
    >
    > Jesus Was A Vegetarian!
    > http://jesuswasavegetarian.7h.com
    >
    >
    > Man Is A Herbivore!
    > http://pages.ivillage.com/ironjustice/manisaherbivore
    >
    >
    > DEAD PEOPLE WALKING
    > http://pages.ivillage.com/ironjustice/deadpeoplewalking
     
  3. montygram

    montygram Guest

    Not just the iron, but the highly unstable polyunsaturated fatty acids
    that react with the iron, creating very dangerous molecules, do serious
    damage in this context. Don't put the cart before the horse; the PUFAs
    make the excess iron much more dangerous, not the other way around.
     
  4. Comp Biochem Physiol A Mol Integr Physiol. 2006 Jan 19; [Epub ahead of
    print] Links


    The effects of pH and the iron redox state on iron uptake in the
    intestine of a marine teleost fish, gulf toadfish (Opsanus beta).

    Cooper CA, Bury NR, Grosell M.

    Division of Health and Life Sciences, King's College London, 150
    Stamford Street, London, SE1 9NN, UK.

    In the marine teleost intestine the secretion of bicarbonate increases
    pH of the lumen (pH 8.4 -9.0) and importantly reduces Ca(2+) and Mg(2+)
    concentrations by the formation of insoluble divalent ion carbonates.
    The alkaline intestinal environment could potentially also cause
    essential metal carbonate formation reducing bioavailability. Iron
    accumulation was assessed in the Gulf toadfish (Opsanus beta) gut by
    mounting intestine segments in modified Ussing chambers fitted to a
    pH-stat titration system. This system titrates to maintain lumen pH
    constant and in the process prevents bicarbonate accumulation. The
    luminal saline pH was clamped to pH 5.5 or 7.0 to investigate the
    effect of proton concentrations on iron uptake. In addition, redox
    state was altered (gassing with N(2), addition of dithiothreitol (DTT)
    and ascorbate) to evaluate Fe(3+) versus Fe(2+) uptake, enabling us to
    compare a marine teleost intestine model for iron uptake to the
    mammalian system for non-haem bound iron uptake that occurs via a
    ferrous/proton (Fe(2+)/H(+)) symporter called Divalent Metal
    Transporter 1 (DMT1). None of the redox altering strategies affected
    iron (Fe(3+) or Fe(2+)) binding to mucus, but the addition of ascorbate
    resulted in a 4.6-fold increase in epithelium iron accumulation. This
    indicates that mucus iron binding is irrespective of valency and
    suggests that ferrous iron is preferentially transported across the
    apical surface. Altering luminal saline pH from 7.0 to 5.5 did not
    affect ferric or ferrous iron uptake, suggesting that if iron is
    entering via DMT1 in marine fish intestine this transporter works
    efficiently under circumneutral conditions.

    PMID: 16431145 [PubMed - as supplied by publisher]

    --------------------------------------------------------------------------------

    Who loves ya.
    Tom


    Jesus Was A Vegetarian!
    http://jesuswasavegetarian.7h.com


    Man Is A Herbivore!
    http://pages.ivillage.com/ironjustice/manisaherbivore


    DEAD PEOPLE WALKING
    http://pages.ivillage.com/ironjustice/deadpeoplewalking
     
  5. Kumar

    Kumar Guest

    "A New Perspective on Iron Deficiency

    Presentation Given by Roberta Crawford in June 2001 at NIH Workshop in
    Bethesda, MD


    A prevailing myth says that iron deficiency is the world's greatest
    nutritional problem.

    Let's define anemia: a deficiency of red cells or hemoglobin, or
    red cells that die too young or are discolored or possess an abnormal
    shape, or red cells that lack adequate iron.

    Now defining iron deficiency -- so-called "normal" iron levels vary
    from lab to lab. Most "normal" levels are set too high. Saturation:
    12 to 40-45% is reasonable at the present time. Ferritin: 5 to
    probably 50. As our years of study have shown, we have had to lower
    these levels several times to be safe.

    Think about it. If "normal" levels are set artificially high, and
    your levels fall below that "normal," you are "iron deficient."

    So how much iron does the human body really need? Iron is not
    excreted. The iron you absorb stays and accumulates in storage except
    that you can lose one milligram a day through hair, finger nails, skin
    cells and other detritus. That is the amount needed every day to
    replace the loss. One milligram. (Women in reproductive years, one
    and a half milligram). The RDAs or RDIs recommended by the Food and
    Nutrition Board is out of date and incorrect. The other way to lose
    iron, of course, is by blood loss.

    The normal levels of iron need to be lowered.

    Hemoglobin is not iron! Unfortunately physicians prescribe iron to
    anemic people who test with low hemoglobin. Yes, the patients are
    anemic, but the iron is collecting in storage instead of going into
    hemoglobin. These people are iron-loaded. They need iron removed
    despite the anemia. The anemia should be treated with B vitamins,
    especially B12, B6 and folic acid. Many patients with anemia are dying
    of iron overload, and some are hastened to their death by their
    physicians who give iron. Blood banks seem to believe that hemoglobin
    and iron are the same. They have prepared lists of high iron foods to
    give out to donors with low hemoglobin. They invariably tell these
    people: "Your iron is low." Dangerous misinformation.

    Physicians like to diagnose or rule out a disease called
    hemochromatosis. That causes confusion and many problems. There is no
    consensus. Doctors hesitate to treat without a diagnosis. Too bad
    that word was ever invented. Each patient is different with different
    symptoms and different iron levels.

    First: treatment does no harm whether there is excess iron or not.
    A cutoff is set on hematocrit to prevent severe anemia, and when the
    patient tests under that cutoff, blood is not taken that day. Giving
    blood is beneficial.

    Second: even a small amount of excess iron can damage heart and
    brain and other storage sites in the body and lead to heart attack or
    stroke. It is foolish to wait until iron levels confirm
    "hemochromatosis."

    There is exaggerated concern when hemoglobin falls temporarily,
    following surgery, for example. Blood transfusions are over-used. A
    study shows that surgery patients who do not receive transfusions
    survive better than those who do. [NEJM Feb 1999 340:409-17]

    Before taking iron you must test saturation and ferritin.
    (Ferritin indicates storage iron, which is not essential to maintain
    life). If both saturation and ferritin are extremely low, you must
    discover why. Low iron is a signal that iron is being used by cancer
    cells or is feeding bacteria, or usually it means there is chronic
    daily blood loss. The bleeding could be from an ulcer or tumor, etc.
    The source must be found.

    Iron is in just about everything. If you are not absorbing the one
    daily milligram, you are truly on a starvation diet, and low iron is
    the least of your worries.

    Let's look at iron with 21st Century eyes and be aware of excess
    iron's toxic ability to harm
    http://www.ironoverload.org/anemia.htm "
     
  6. Robert

    Robert Guest

    "Kumar" <[email protected]> wrote in message
    news:[email protected]
    > "A New Perspective on Iron Deficiency
    >
    > Presentation Given by Roberta Crawford in June 2001 at NIH Workshop in
    > Bethesda, MD
    >
    >
    > A prevailing myth says that iron deficiency is the world's greatest
    > nutritional problem.


    Iron deficiency anemia is a very common form of anemia.
    One becomes iron deficient before they develop complications of that
    deficiency.

    >
    > Let's define anemia: a deficiency of red cells or hemoglobin, or
    > red cells that die too young or are discolored or possess an abnormal
    > shape, or red cells that lack adequate iron.


    No. Anemia is defined by the hemoglobin level or the hematocrit level.
    One does not need to have abnormal shape or color to have anemia nor does it
    constitute anemia in their presence.

    >
    > Now defining iron deficiency -- so-called "normal" iron levels vary
    > from lab to lab.

    Because they use differing techniques and instruments and one should always
    use the reference range obtained from that particular lab that did the test.
    They must validate the instrument methodology in use with that patient
    population by actually running "normal" samples.
    Reference ranges do not establish what is "normal" or "abnormal".
    They only state what a population of non-diseased individuals are expected
    to yield. A normal person can have a value outside this reference range. Lab
    results do not diagnose disease it is the clinical evaluation with regards
    to the lab results that constitutes what is abnormal or disease. The
    clinical evaluation is what determines disease and not lab results.

    Most "normal" levels are set too high. Saturation:
    > 12 to 40-45% is reasonable at the present time. Ferritin: 5 to
    > probably 50. As our years of study have shown, we have had to lower
    > these levels several times to be safe.


    These are clinical evaluations and that is appropriate in evaluating the
    result. It is not the value that is being changed only the clinical
    interpretation.
    The reference or gold standard for adequate iron stores is the bone biopsy.
    Blood markers involved in iron study can be impacted by time of collection,
    late evening giving lower iron levels or disease not related to iron stores
    but to iron handling.
    >
    > Think about it. If "normal" levels are set artificially high, and
    > your levels fall below that "normal," you are "iron deficient."


    Again you are not using clinical judgement and only going by the number.
    Conversely if you lower the range then you will see iron deficient
    individuals or borderline being missed because there is generally a bell
    curve without clear separation between iron deficient people and those not
    deficient. You can lower your range to very low levels and miss even more.
    The intent of setting the range is important. Do you want to call somebody
    iron deficient with high certainty then yes lower the range and increase
    your positive predictive value.
    Do you want to catch everyone that might be iron deficient then leave them
    there and perform more diagnostic testing such as ferritin and TIBC %
    saturation. One does not go by the iron level alone. Low serum, low ferritin
    and low % saturation is convincing evidence of iron deficiency.
     
  7. Kumar

    Kumar Guest

    Thanks. I have posted an article on Ironoverlad association.
    Robert wrote:
    > "Kumar" <[email protected]> wrote in message
    > news:[email protected]
    > > "A New Perspective on Iron Deficiency
    > >
    > > Presentation Given by Roberta Crawford in June 2001 at NIH Workshop in
    > > Bethesda, MD
    > >
    > >
    > > A prevailing myth says that iron deficiency is the world's greatest
    > > nutritional problem.

    >
    > Iron deficiency anemia is a very common form of anemia.
    > One becomes iron deficient before they develop complications of that
    > deficiency.
    >
    > >
    > > Let's define anemia: a deficiency of red cells or hemoglobin, or
    > > red cells that die too young or are discolored or possess an abnormal
    > > shape, or red cells that lack adequate iron.

    >
    > No. Anemia is defined by the hemoglobin level or the hematocrit level.
    > One does not need to have abnormal shape or color to have anemia nor does it
    > constitute anemia in their presence.


    Do high or low hemoglobin not changes shape of red cells?
    > >
    > > Now defining iron deficiency -- so-called "normal" iron levels vary
    > > from lab to lab.

    > Because they use differing techniques and instruments and one should always
    > use the reference range obtained from that particular lab that did the test.
    > They must validate the instrument methodology in use with that patient
    > population by actually running "normal" samples.
    > Reference ranges do not establish what is "normal" or "abnormal".
    > They only state what a population of non-diseased individuals are expected
    > to yield. A normal person can have a value outside this reference range. Lab
    > results do not diagnose disease it is the clinical evaluation with regards
    > to the lab results that constitutes what is abnormal or disease. The
    > clinical evaluation is what determines disease and not lab results.
    >
    > Most "normal" levels are set too high. Saturation:
    > > 12 to 40-45% is reasonable at the present time. Ferritin: 5 to
    > > probably 50. As our years of study have shown, we have had to lower
    > > these levels several times to be safe.

    >
    > These are clinical evaluations and that is appropriate in evaluating the
    > result. It is not the value that is being changed only the clinical
    > interpretation.


    Can't normal range be differnt in different communitis, different
    areas, vegs and non-vegs>

    The reference or gold standard for adequate iron stores is the bone
    biopsy.
    > Blood markers involved in iron study can be impacted by time of collection,
    > late evening giving lower iron levels or disease not related to iron stores
    > but to iron handling.


    How late evening gives lower iron levels? Is it ue to used during day
    activities? But still how it can be higher in morning sample?

    > > Think about it. If "normal" levels are set artificially high, and
    > > your levels fall below that "normal," you are "iron deficient."

    >
    > Again you are not using clinical judgement and only going by the number.
    > Conversely if you lower the range then you will see iron deficient
    > individuals or borderline being missed because there is generally a bell
    > curve without clear separation between iron deficient people and those not
    > deficient. You can lower your range to very low levels and miss even more.
    > The intent of setting the range is important. Do you want to call somebody
    > iron deficient with high certainty then yes lower the range and increase
    > your positive predictive value.
    > Do you want to catch everyone that might be iron deficient then leave them
    > there and perform more diagnostic testing such as ferritin and TIBC %
    > saturation. One does not go by the iron level alone. Low serum, low ferritin
    > and low % saturation is convincing evidence of iron deficiency.


    Can't immune/body system trigger lower absorption or more loss of iron
    in case of getting chronic/latent/autoimmune diseases or cancer to
    handle or starve dormant agents?

    How can we check really defficient, overload and imbalanced iron(more
    at one part higher on other still blood level normal)? Does bood level
    will not give false interpretation in blood normal level?

    Many type of anemias are indicated and all are not iron based as on
    medlineplus;
    http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm
     
  8. >> Iron is in just about everything. If you are not absorbing the one
    daily milligram, you are truly on a starvation diet, and low iron is
    the least of your worries.<<

    This is the .. key .. phrase ..

    The above holds true ..

    If one is .. fed .. one is NEVER .. iron 'deficient' ..

    Anyone who tells you elsewise is a .. fool ..

    If one encounters one who is TRULY iron .. deficient .. there is MUCH
    more wrong ..

    Starvation , bleeding internally ..

    So anything 'Robert' might .. tell you .. it seems .. is bullsht ..

    He holds to the belief without the likes of him the world would have
    died off long ago ..

    "Everyone is iron deficient .. " ..

    Braindeadmoron ..

    Who loves ya.
    Tom


    Jesus Was A Vegetarian!
    http://jesuswasavegetarian.7h.com


    Man Is A Herbivore!
    http://pages.ivillage.com/ironjustice/manisaherbivore


    DEAD PEOPLE WALKING
    http://pages.ivillage.com/ironjustice/deadpeoplewalking
     
  9. Kumar

    Kumar Guest

    [email protected] wrote:
    > >> Iron is in just about everything. If you are not absorbing the one

    > daily milligram, you are truly on a starvation diet, and low iron is
    > the least of your worries.<<
    >
    > This is the .. key .. phrase ..
    >
    > The above holds true ..
    >
    > If one is .. fed .. one is NEVER .. iron 'deficient' ..
    >
    > Anyone who tells you elsewise is a .. fool ..
    >
    > If one encounters one who is TRULY iron .. deficient .. there is MUCH
    > more wrong ..
    >
    > Starvation , bleeding internally ..
    >
    > So anything 'Robert' might .. tell you .. it seems .. is bullsht ..
    >
    > He holds to the belief without the likes of him the world would have
    > died off long ago ..
    >
    > "Everyone is iron deficient .. " ..
    >
    > Braindeadmoron ..
    >

    No one has told. It is just a link of Ironoverload association.

    Irony: the use of words to express something other than and especially
    the opposite of the literal meaning.

    Can excess or low iron make a person irony? :D
     
  10. Kumar

    Kumar Guest

    "About 65% of the iron in the body is found in hemoglobin (in red blood
    cells) and about 4% in myoglobin (in skeletal muscle). About 30% of the
    iron in the body is stored (as ferritin or hemosiderin) in the liver,
    bone marrow, and spleen. A small percentage of the body's iron is in
    transport between various parts of the body or is a component of
    proteins in cells throughout the body.

    The body efficiently conserves iron so that only about 1 mg (men and
    post-menopausal women) or 1.8 mg (premenopausal adult women) is lost
    per day in the urine or menstrual blood. Since only about 10-15% of the
    iron we eat in our food is absorbed, even under optimum circumstances,
    the recommended daily allowance for iron is 10 mg (men and
    post-menopausal women) and 18 mg (premenopausal adult women). Pregnancy
    greatly increases the need for iron, and iron deficiency is most common
    in women of reproductive age.

    Higher-than-normal levels may indicate:

    hemochromatosis
    hemolysis
    hemolytic anemias
    hemosiderosis
    hepatic (liver) necrosis (tissue death)
    hepatitis
    vitamin B-12 deficiency, vitamin B-6 deficiency
    iron poisoning
    multiple blood transfusions

    Lower-than-normal levels may indicate:
    chronic gastrointestinal blood loss
    chronic heavy menstrual bleeding
    inadequate absorption of iron
    insufficient dietary iron
    pregnancy
    http://www.nlm.nih.gov/medlineplus/ency/article/003488.htm
    Iron overdose
    http://www.nlm.nih.gov/medlineplus/ency/article/002659.htm "

    Pls check under normal/average circumstances. Whether iron
    overdose/overload is highly roxic?
     
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