The removal of Iron

    It is known that premenopausal women have a lower risk of heart attacks and cancer than do men of the same age.  The advantage is partially due to the monthly loss of iron in the menses.  This is confirmed by the fact that postmenopausal women lose this advantage, while men who donate blood as little as once a year have the same reduced risk as premenopausal women.

            Chelation has an affinity for iron as shown on the chart two pages back.  If you look on the chart, you will see that EDTA can remove two different forms of iron, both the metabolically active Fe2+ and the oxidative Fe3+ forms of iron, but that it preferentially bonds to the oxidative Fe3+ form as evidences by Fe3+ being to the left of Fe2+ on the chart.  This is an important distinction, as you will see, since Fe3+ is quite a problem in the body.   

Methemoglobinemia is the clinical state in which circulating hemoglobin is present with iron in the oxidized Fe3+ state instead of the usual Fe2+ state.  Fe3+ cannot carry oxygen.  Fe 3+ also moves the oxyhemoglobin dissociation curve to the left, thus what little oxygen is present on other hemoglobin molecules has a harder time being released into the tissues.  The lack of oxygen is obvious from the chocolate brown appearance (shown below) of methemoglobineminic blood.

 In health, a small amount of oxidized Fe3+ iron is formed by auto-oxidation of the circulating red blood cells.  Fe2+ is oxidized to Fe3+ at the rate of about 3% per day.

This iron is reduced back to Fe2+ by the enzyme NADH-cytochrome b5 reductase and reduced glutathione. 

             Perhaps the gradual decrease of tissue oxygen seen as we age (see chart below) is due to the downgrading of these antioxidant systems.  While enzyme NADH-cytochrome b5 reductase may be upregulated with niacin, this enzyme accounts for perhaps only 5% of the reduction of Fe3+ to Fe2+.  Glutathione reduces Fe3+ to Fe2+ non-enzymatically, but it is a difficult antioxidant to raise in the body.  Perhaps our best defense against Fe3+ for now is the use of EDTA. 

             Since local anesthetics cause the oxidation of Fe2+ to Fe3, and I.V. chelation is usually given with procaine (to numb the burning sensation caused by Di-sodium EDTA), we see another advantage of suppository chelation with Magnesium di-potassium EDTA, over I.V. chelation, in that it will not cause the conversion of Fe2+ to Fe3+ thus lowering oxygen carrying and delivery capacity since no anesthetics are required.

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