Iron occurs in food in two forms: as heme iron in meat (Fe2+) and as the somewhat less utilizable non-heme iron (Fe3+) in all other foods. The bioavailability of (non-heme) iron from the diet can be enhanced by concomitant ingestion of vitamin C and/or vitamin A, whereas excessive intakes of other metal ions (e. g., zinc, copper and manganese) can strongly inhibit iron absorptionthrough the formation of complexes (40). Iron is absorbed mainly from the small intestine. After absorption iron is either bound in the form of ferritin (a protein that stores iron) or carried in the plasma to cells and tissues with the aid of a transport protein (transferrin). Around 80% of the iron in the body is present as a component of active biological compounds: most of it is needed to produce hemoglobin (41) – the oxygen transporter in the red blood cells (erythro-cytes) – and only a small part is used to synthesize myoglobin (which stores oxygen in muscle tissue) or for the mitochondrial respiratory chain and iron-dependent enzymes (42). About 20% of the iron reserves are found bound to protein (as ferritin) in the organs of storage, in particular liver, spleen, intestinal mucosa and bone marrow. The amount of stored iron regulates the absorption of non-heme iron, whilst the more readily absorbed heme iron is taken up regardless of nutritional status. Blood ferritin levels provide a reliable measure of nutritional iron status.
Because there are no regulated excretion mechanisms for iron, excessive intakes of iron in the diet cannot be compensated by increased excretion. Some studies conclude that substantially raised ferritin levels lead, in the long term, to an increase in the risk of atherosclerosis and heart attacks (43, 44). Many other trials come to very different conclusions, however (45-47). Based on the oxidative activity of iron and the possible negative influence of oxidative stress on the incidence of bowel cancer precursors, the hypothesis was formed that high intakes of iron could contribute to the risk for bowel cancer (48). However, no such effect has been observed by any study as yet (49). Isolated cases have been reported of children under 3 years who have accidentally consumed more than 900 mg iron in high-dose preparations and subsequently suffered gastrointestinal side effects (50).
After reviewing the available studies, the US Institute of Medicine decided to set a tolerable upper intake level for iron of 45 mg per day in total from all sources for adults (51). Above these doses gastrointestinal side effects (e.g., constipation) might be expected. The European Food Safety Authority described the data available as insufficient to define a UL (52).
The trace element selenium occurs in protein-rich animal-source foods (fish, meat, offal and eggs) and also in plant-source foods (e.g., pulses, nuts and fungi) in the form of selenium-containing amino acids (seleno-cysteine and selenomethionine). Inorganic selenium compounds play a role primarily in dietary supplements and medicines. Orally ingested selenium is absorbed via the small intestine. The rate of absorption depends on the type, quantity and source of the ingested selenium compounds and on interactions between them and other food ingredients (e.g., sulfur and heavy metals. The selenium status of the individual does not influence absorption (53). After absorption, selenium is transported in the bloodstream to the liver, where it accumulates in proteins while producing selenoproteins P (SeP). These are transported in the bloodstream to tissues. The highest concentrations are found in the liver, kidneys, heart, spleen, brain, gonads (especially testes), erythrocytes and thrombocytes. However, because of its greater overall weight, the skeletal musculature contains the largest proportion of selenium, with 40–50% of selenium reserves found here. Whereas selenium in cells such as erythrocytes, immune cells and thrombocytes functions as an essential component of many enzymes and proteins (e.g., the antioxidant glutathione peroxidases), outside the cells it is bound to plasma proteins (selenoprotein P, beta-globulin and albumin).
Selenomethionine from the diet can be unspecifically incorporated into proteins in place of the sulfur-containing amino acid methionine, whilst selenocysteine is available for incorporation into the peptide chain of selenium-dependent proteins and enzymes. Inorganic selenite and selenate are used as precursors for the synthesis of selenocysteine. Selenium is excreted primarily via the kidneys; excretion depends on both the selenium status of the individual and on oral intakes. In contrast to other trace elements, like iron, copper and zinc, whose balance is controlled mainly via absorption from the small intestine, selenium is regulated above all by excretion via the kidneys, and in the case of excessive selenium, through respiration (54).
Some observational and intervention studies provided evidence that increased intakes of selenium could help reduce the risk of developing some forms of cancer (55-57) and type 2 diabetes (58). More recent clinical studies investigated these possible associations in greater depth (including in combination with other micro-nutrients): In the SELECT study daily consumption of 200 micrograms of selenomethionine (around 4 times the recommended amount) alone and in combination with vitamin E led to no reduction in the risk for prostate cancer (59). The SU.VI.MAX study revealed that targeted consumption of selenium in combination with vitamins C and E as well as beta-carotene and zinc had no influence on the incidence of chronic diseases such as cancer, diabetes or cardiovascular disease as compared with placebo (60). In this instance, participants with normal blood levels of prostate-specific antigen (one parameter in the diagnosis of prostate carcinoma) appeared to experience a significant reduction for the risk of prostate cancer, while subjects with raised antigen values demonstrated a slight increase in risk (61). This latter could not be observed in the SELECT study (59, 62). Some of the study results relating to a possible association between selenium intakes and the risk for type 2 diabetes are contradictory. Whereas some trials indicated a preventive effect (58, 63), some indicated rather the opposite (64).
Based on the available studies the US Institute of Medicine decided to set the tolerable upper intake levels for selenium in adults at 400 micrograms per day in total from all sources (65). The European Commission’s Scientific Committee on Food defined a UL for adults of 300 micrograms per day in total (66).