Iron catalyzed oxidative damage, in spite of normal ferritin and transferrin saturation levels and its possible role in Werner's syndrome, Parkinson's disease, cancer, gout, rheumatoid arthritis, etc.

Iron loading in hemochromatosis attains extremely high levels and is accompanied by many signs (ferritin >300 microg/l, hematocrit >50%, transferrin saturation >70%, etc.). Nevertheless, the disease is often overlooked by physicians, until several organs have been damaged permanently (heart, liver, brain, pancreas, kidneys, spleen, etc.). Therefore, severe oxidative damage catalyzed by Fe could occur, without the extremely high ferritin, hematocrit and transferrin saturation levels of hemochromatosis, and it is unlikely that it would ever be detected or even suspected. I postulate a mechanism, by which a cell can continue to express transferrin receptors, without producing ferritin, even when it is saturated with iron. Furthermore, I suggest that this silent iron loading, induced by cadmium and other metals, plays an important role in many degenerative diseases involving free radicals, DNA damage and peroxynitrite, all of which are intimately linked to iron.Moreover, since ferritin, transferrin saturation and hematocrit levels are not directly related to cellular iron levels, and since excess iron can wreak havoc in the cell, we can conclude that there is a need for a better way to evaluate intracellular iron levels and especially the intracellular free iron levels by a non-invasive technique.Finally, phlebotomy is suggested as the best way to reduce Fe and Mo stores, and chelation with succimer is recommended in order to eliminate Cd.