Don't give me no LIP / labile iron pool

Discussion in 'Food and nutrition' started by Doe, Feb 21, 2004.

  1. Doe

    Doe Guest

    Med Hypotheses. 2004 Mar;62(3):442-5. Related Articles, Links

    Serum markers of stored body iron are not appropriate markers of health effects of iron: a focus on
    serum ferritin.

    Lee DH, Jacobs DR Jr.

    Experimental studies have consistently shown that iron is a critical catalyst in generating oxygen
    free radicals via Fenton chemistry. Nevertheless, epidemiologic studies conflict on the association
    between stored body iron markers and disease outcomes, including coronary heart disease. We
    hypothesize that stored body iron markers common in epidemiologic studies, such as serum ferritin,
    transferrin saturation, iron, or iron-binding capacity, are inappropriate to investigate harmful
    health effects related to iron overload. Oxygen free radicals are produced only by free iron, but
    stored body iron markers reflect iron bound to ferritin or transferrin, which are produced to
    sequester catalytically active free iron. Moreover, increased serum ferritin may occur as a defense
    mechanism in response to oxidative stress; such increase might eventually minimize oxidative stress
    and consequent pathology due to free iron. Therefore, though highly correlated with stored body
    iron, a measure of bound iron will fail to identify any harmful effect, unless it is also a marker
    of free iron. It is generally believed that free iron rarely exists, except in iron-overload with
    100% transferrin saturation. However, some recent studies find non-transferrin bound iron (NTBI) or
    the intracellular labile iron pool
    (LIP) in the presence of triggers disturbing iron homeostasis, such as alcohol consumption. In
    contrast to the tight bond in ferritin or transferrin, free iron is more likely to dissociate
    from a looser bond. Therefore research on the relation of iron with disease outcomes should
    investigate NTBI or the intracellular LIP. Any positive influence of iron on coronary heart
    and other diseases might be observable only when a trigger is present. These factors may
    explain why there have been conflicting results between serum markers of stored body iron and
    disease outcomes in epidemiological studies.

    PMID: 14975519 [PubMed - in process]

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    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
     
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  2. markd

    markd Guest

    We luvs ya Tom. I love it when our friend Tom shoots himself in the foot with the fruits of his
    search engine activity. The contents of the current posting just about destroys in large part his
    whole thesis about iron storage and disease and disorders in humans. It says stored iron is no
    problem as it is by definition bound and is not a source of "rust", as Tom likes to say. It is only
    free iron that may be a problem and it appears only rarely, perhaps with an adverse physical
    trigger. The authors consider this reality as to why the reports in the literature are in great
    conflict about iron stores and problems. But of course we never see the conflicting abstracts, now
    do we, one wonders why? This one goes along nicely with another of his that said it is only iron in
    red meat that is related to some problems, while total iron intake and other meat sources show no
    such relationshipp. Which of course suggests right away it is red meat and not meat or total iron
    that is the source of theproblem in the first place.
     
  3. GMCarter

    GMCarter Guest

    On 22 Feb 2004 01:28:45 GMT, [email protected] wrote:

    >We luvs ya Tom. I love it when our friend Tom shoots himself in the foot with the fruits of his
    >search engine activity. The contents of the current posting just about destroys in large part his
    >whole thesis about iron storage and disease and disorders in humans.

    Ah--I don't buy your interpretation in the slightest. What it suggests is that the sensitivity and
    specificity of currently available blood tests may be inadequate, although they do note that
    "Therefore, though highly correlated with stored body iron, a measure of bound iron will fail to
    identify any harmful effect, unless it is also a marker of free iron." Thus, at least in the
    abstract, this does not utterly invalidate the use of markers like ferritin.

    dysfunction, arthralgia, cardiac symptoms, difficulty breathing to evaluate the relevance of these
    tests (see abstract below).

    Indeed, there are a variety of methods that can be used. A study of iron overload in African
    Americans further suggests a potentially heritable trade of iron retention that may result
    in overload.

    >It says stored iron is no problem as it is by definition bound and is not a source of "rust", as
    >Tom likes to say. It is only free iron that may be a problem and it appears only rarely, perhaps
    >with an adverse physical trigger.

    Ah--in general, yes. But I think the point is that it occurs in some chronic ailments. I do disagree
    with Tom's focus on iron in HCV disease--I think it is a problem that is significant for a subset of
    this population but not necessarily central to disease pathogenesis overall. By contrast, oxidative
    stress generally and glutathione depletion specifically may be more critical.

    >The authors consider this reality as to why the reports in the literature are in great conflict
    >about iron stores and problems. But of course we never see the conflicting abstracts, now do we,
    >one wonders why? This one goes along nicely with another of his that said it is only iron in red
    >meat that is related to some problems, while total iron intake and other meat sources show no such
    >relationshipp. Which of course suggests right away it is red meat and not meat or total iron that
    >is the source of theproblem in the first place.

    Excessive consumption of red meat is probably contraindicated for a significant proportion of the
    population. Another dimension to that debate, of course, is the environmental one. Consumption of
    meat requires a great deal of arable land and water to feed cattle that is in excess of the energy
    produced. Aside from the ethical consideration of the way animals are raised and slaughtered, the
    risk of diseases such as BSE and the increased risk of coronary and vascular diseases, we must
    recognize that the overpopulated planet on which we reside cannot sustain the type of consumption
    Americans typically engage in. An interesting table in the recent National Geographic underscores
    the differences between US consumption and that in China. Given the clear cutting of jungles and
    forests to raise these animals for a few seasons at most before the land reverts to desert, we are
    doing our species and life on the planet a bit of a disservice by indulging excessively or at all in
    the consumption of red meat.

    George M. Carter

    ***
    Presse Med. 2003 Nov 8;32(36):1716-23. Related Articles, Links

    [Hereditary haemochromatosis]

    [Article in French]

    Bismuth M, Aguilar-Martinez P, Michel H.

    Service d'hepato-gastro-enterologie, Hopital Saint Eloi, Montpellier. [email protected]

    EPIDEMIOLOGY ADN PHYSIOPATHOLOGY: Hereditary haemochromatosis is the most common genetic disease in
    France. Its frequency is on average 1 out of 300 French individuals. It is due to excessive dietary
    iron absorption, leading to accumulation of iron in the body. Mutations of the HFE1 gene are
    responsible for the majority of the case of haemochromatosis. FROM A CLINICAL POINT OF VIEW: The
    first clinical

    symptoms, dyspnoea on effort) can occur after the age of 30 years in men and 35 years in women
    (protected for longer by menstruation, pregnancy and delivery). In the absence of diagnosis, severe
    complications can develop during the 5th decade: nervous breakdown, arthropathy, heart failure,
    diabetes mellitus, cirrhosis with risk of progression towards carcinoma, responsible for handicaps
    and premature death. DIAGNOSTIC ELEMENTS: The diagnosis is evoked in the case of an increase in
    transferrine saturation (>45%), associated or not with excessive ferritin plasma levels. It is
    confirmed by the genetic test, showing homozygotes for the C282Y mutation or compound heterozygotes
    for the C282Y and H63D mutations on the HFE1 gene. RMI quantifies hepatic iron loading and generally
    avoids the need for a liver biopsy. The differential diagnosis must exclude secondary iron overload
    due to chronic transfusions in congenital or acquired blood diseases, a polymetabolic syndrome,
    chronic viral or alcoholic hepatic diseases and porphyria cutanea tarda. EFFICIENT TREATMENT: Today,
    haemochromatosis is still treated by phlebotomy. This consists in withdrawing 400 to 500ml of blood
    every week at the initial depletion stage and subsequently a maintenance therapy in order to
    maintain ferritin levels below 50 ng/ml. Paradoxically and through ignorance, hereditary
    haemochromatosis remains a serious disease, although its diagnosis is easy and the treatment simple
    and effective.

    ***
    Blood Cells Mol Dis. 2003 Nov-Dec;31(3):310-9. Related Articles, Links

    Genotypic and phenotypic heterogeneity of African Americans with primary iron overload.

    Barton JC, Acton RT, Rivers CA, Bertoli LF, Gelbart T, West C, Beutler
    E.

    Southern Iron Disorders Center, G-105, 20220 Brookwood Medical Center Drive, Birmingham, AL 35209,
    USA. [email protected]

    Primary iron overload may be relatively common in African Americans, but its cause is incompletely
    understood. Thus, we evaluated genotype and phenotype characteristics of unselected African
    American index patients with primary iron overload who reside in central Alabama. All had hepatic
    iron concentration > or =30 micromol/g dry wt or > or =2.0 g of iron mobilized by phlebotomy to
    achieve iron depletion. Genotype analyses were performed in African American control subjects from
    the same region. There were 23 patients (19 men, 4 women); mean age at diagnosis was 52 +/- 12
    years (1 SD) (range 32-69 years). Nine (39.1%) reported that they consumed > or =45 g of ethanol
    daily; five had chronic hepatitis C. Eight had some form of hemoglobinopathy or thalassemia. Mean
    serum transferrin saturation was 56 +/- 28% (range 15-100%). The geometric mean serum ferritin at
    diagnosis was 1076 ng/mL [95% confidence interval 297-3473 ng/mL]. Increased stainable liver iron
    was observed in hepatocytes only in 4 patients, in macrophages only in 8 patients, and in
    hepatocytes and macrophages in 8 patients. The mean quantity of iron mobilized by phlebotomy
    (corrected for iron absorbed during treatment) was 5.3 +/- 2.0 g (range 4.0-8.4 g). Iron removed by
    phlebotomy was greater in patients with hemoglobinopathy or thalassemia than in those without these
    forms of anemia (6.6 +/- 1.3 g vs 3.9 +/- 1.6 g, respectively; P = 0.0144). Daily consumption of >
    or =45 g of ethanol or chronic hepatitis C was not associated with an increased or decreased amount
    of phlebotomy-mobilized iron, on the average. The percentage of index patients positive for HFE
    C282Y was greater than that of controls (P = .0058). The respective percentages of phenotype
    positivity for HFE H63D, D6S105(8), and HLA-A*03 were similar in patients and controls. HFE S65C,
    I105T, and G93R were not detected in index or control subjects. Two of 13 patients were
    heterozygous for the ferroportin allele nt 744 G-->T (Q248H), although the phenotype frequency of
    this allele was similar in patients and 39 controls. Synonymous ferroportin alleles were also
    detected in some patients. The ceruloplasmin mutation nt 1099C-->T (exon 6; Arg367Cys) was detected
    in 1 of 2 patients tested. Abnormal alleles of beta-2 microglobulin, Nramp2, TFR2, hepcidin, or
    IRP2 alleles were not detected in either of the 2 patients so tested. We conclude that primary iron
    overload in African Americans is not the result of the mutation of a single gene. HFE C282Y,
    ferroportin 744 G-->T, and common forms of heritable anemia appear to account for increased iron
    absorption or retention in some patients.
     
  4. GMCarter

    GMCarter Guest

    On 23 Feb 2004 18:50:50 GMT, [email protected] wrote:

    >"Ah--I don't buy your interpretation in the slightest. What it suggests"
    >
    >It was not my interpretation, only my restatement of the abstract with regard to our friend's
    >thesis, the authors are the one's to address your observations. It, as stated, contradics the main
    >thrust of his these and the ironny, pun intended, was too much to pass. He plucks hits on iron in
    >biomed abstracts as support for his religious thesis, no one is questioning that iron can be toxic
    >at certain levels and situations, as any number of other substances. But, in this case my thesis is
    >supported he doesn't understand/or doesn't read carefully the contents but just slaps it in this
    >and other ngs if it has some biomed inmplication.

    I understand the distinction you are making. So, without trying to be TOO Pollyanna--you are both
    correct to a certain extent. That "extent" is defined by where the rubber hits the road: the
    individual. In some people, iron is lacking (e.g., menstruating women). In others, it is a problem
    (e.g., and in general only, adult men, post-menopausal women).

    And, too, with diseases--in iron-deficiency anemia, LACK of iron is the problem. In hemochromatosis,
    iron IS the problem. In other diseases, its role may be more variable, e.g., hepatitis C, where
    excess unbound iron may result in added oxidative stress in a disease whose progression is already
    intimately tied to inflammatory processes.

    George M. Carter
     
  5. Manky Badger

    Manky Badger Guest

    "GMCarter" <[email protected]> wrote in message
    news:[email protected]...

    > I understand the distinction you are making.

    > And, too, with diseases--in iron-deficiency anemia, LACK of iron is the problem.

    My mate Tommy assures me there ain't no such animal !!

    MB
     
  6. GMCarter

    GMCarter Guest

    On Tue, 24 Feb 2004 15:23:52 -0000, "Manky Badger"
    <[email protected]> wrote:

    >
    >"GMCarter" <[email protected]> wrote in message news:[email protected]...
    >
    >> I understand the distinction you are making.
    >
    >> And, too, with diseases--in iron-deficiency anemia, LACK of iron is the problem.
    >
    >My mate Tommy assures me there ain't no such animal !!

    Excellent. I trust Tommy has rigorous science and logic to back up his claims that he will share
    with us here!

    In the meantime, other sources persist in recognizing its existence.
    E.g., http://www.nlm.nih.gov/medlineplus/ency/article/000584.htm

    or perhaps: http://www.pitt.edu/~super1/lecture/lec0641/

    George M. Carter
     
  7. Manky Badger

    Manky Badger Guest

    "GMCarter" <[email protected]> wrote in message
    news:[email protected]...
    > On Tue, 24 Feb 2004 15:23:52 -0000, "Manky Badger" <[email protected]> wrote:
    >
    > >
    > >"GMCarter" <[email protected]> wrote in message news:[email protected]...
    > >
    > >> I understand the distinction you are making.
    > >
    > >> And, too, with diseases--in iron-deficiency anemia, LACK of iron is the problem.
    > >
    > >My mate Tommy assures me there ain't no such animal !!
    >
    > Excellent. I trust Tommy has rigorous science and logic to back up his claims that he will share
    > with us here!

    Why not ask him - good luck !!
     
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