Cadmium exposure and iron status

Abstract: People are exposed to cadmium, a ubiquitous toxic metal, mainly via basic foods such as cereals and vegetables. Cadmium accumulates in the kidney, and renal tubular damage is considered the critical effect. Recently, association with osteoporosis at environmental exposure levels was indicated. Factors affecting accumulation of cadmium in humans are poorly investigated. The present work focuses on interactions between cadmium and iron. The hypothesis tested was that iron deficiency influences accumulated dose of cadmium in the body by increasing the intestinal cadmium absorption. Associations were studied between various indicators of cadmium exposure and body burden (i.e. cadmium concentrations in diet, feces, blood, urine and placenta) on the one hand, and iron status (from iron deficiency anemia to iron overload) on the other. In subjects with a wide range of dietary fiber intake, iron stores was the main determinant of blood cadmium. Depleted iron stores and a higher fiber intake (validated data) led, independently of each other, to increased concentrations of cadmium in blood and in validated 24-hour urine. No obvious protective effect of dietary fiber on cadmium uptake was observed. To further test the hypothesis, we chose pregnant women as a study group because of their increased iron demand. To fully characterize iron status during pregnancy, we evaluated the usefulness of the soluble transferrin receptor in serum (sTfR) as a marker of iron deficiency. The sTfR was shown to be a specific and sensitive index of iron deficiency in pregnancy with advantages over both serum ferritin and hemoglobin. Together with serum ferritin (sTfR: serum ferritin ratio; sTfR/Fer), early changes in iron status were revealed. About 50% of the women reached the point of exhausted iron stores in late gestation and 14% developed tissue iron deficiency. Even one year after delivery iron status had not regained the first trimester levels. Decreasing serum ferritin and increasing sTfR and sTfR/Fer were associated with increasing concentrations of cadmium in blood and urine. Blood cadmium increased longitudinally from early gestation to lactation both in women with low and in women with adequate iron stores. Increasing urinary cadmium was detected only in those with depleted iron stores or iron deficiency during pregnancy. There was an interaction between age and parity, leading to a more pronounced age dependent increase in urinary cadmium in multiparous women than in nulliparous ones. In order to test whether subjects with pathologically increased iron absorption due to hemochromatosis (HH) have a similar increase in blood cadmium as iron deficient subjects, we determined blood cadmium in HH subjects and controls. Blood cadmium was significantly higher in subjects with HH on maintenance phlebotomy treatment than in controls. There was a strong age-independent positive association between blood cadmium and the number of years of phlebotomy treatment. The findings indicate that the treatment rather than the disease increases cadmium uptake in subjects with HH. Taken together, the results provide strong evidence for increased uptake of cadmium, along with iron, due to depleted iron stores or to phlebotomy, resulting in increased cadmium accumulation. The findings indicate that the generally higher cadmium concentration in women compared to men is caused by a higher prevalence of depleted iron stores in women and/or by pregnancy.