Trace Minerals

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28.10— Trace Minerals
Iron Is Efficiently Reutilized
Iron metabolism is unique in that it operates largely as a closed system, with iron stores being efficiently reutilized by the body. Iron losses are minimal (<1 mg day–1), but iron absorption is also minimal under the best of conditions. Iron usually occurs in foods in the ferric form bound to protein or organic acids. Before absorption can occur, the iron must be split from these carriers (a process that is facilitated by the acid secretions of the stomach) and reduced to the ferrous form (a process that is enhanced by ascorbic acid). Only 10% of the iron in an average mixed diet is usually absorbed, but the efficiency of absorption can be increased to 30% by severe iron deficiency. Iron absorption and metabolism have been discussed in Chapter 24 and are summarized in Figure 28.15.
Figure 28.15 Overview of iron metabolism. This figure reviews some of the features of iron metabolism discussed previously in Chapter 24. The red arrows indicate that most of the body's iron is efficiently reutilized by the pathway shown. Hb, hemoglobin; MyoHb, myoglobin; Cyt, cytochromes; and NHI, nonheme iron.
Iron plays a number of important roles in the body. As a component of hemoglobin and myoglobin, it is required for O2 and CO2 transport. As a component of cytochromes and nonheme iron proteins, it is required for oxidative phosphorylation. As a component of the essential lysosomal enzyme myeloperoxidase, it is required for proper phagocytosis and killing of bacteria by neutrophils. The best­known symptom of iron deficiency is a microcytic hypochromic anemia. Iron deficiency is also associated with decreased immunocompetence.
Assuming a 10–15% efficiency of absorption, the Food and Nutrition Board has set a recommended dietary allowance of 10 mg day–1 for normal adult males and 15 mg day–1 for menstruating females. For pregnant females this allowance is raised to 30 mg day–1. While 10 mg of iron can easily be obtained from a normal diet, 15 mg is marginal at best and 30 mg can almost never be obtained. The best dietary sources are meats, dried legumes, dried fruits, and enriched cereal products.
Iron­deficiency anemia is considered the most prevalent nutritional disorder in the United States. Young children and pregnant females need enough iron for a continuing increase in blood volume. Menstruating females lose iron through blood loss and lactating females through production of lactoferrin. Thus iron deficiency anemia is primarily a problem for these population groups. This is reflected in dietary surveys, which indicate that 95% or more of children and menstruating females are not obtaining adequate iron in their diet. It is also reflected in biochemical measurements of a 10–25% incidence of iron deficiency anemia in this same group. Iron­
deficiency anemia is also occasionally a problem with the elderly due to poor dietary intake and increased frequency of achlorhydria.
Because of the widespread nature of iron­deficiency anemia, government programs of nutritional intervention such as the WIC program have emphasized iron­rich foods. There has also been discussion of more extensive iron fortification of foods. There is concern among some nutritionists that iron deficiency has been overemphasized. Some recent studies suggest that excess iron intake may increase the risk of cardiovascular disease. Thus iron supplementation and the consumption of iron­fortified foods may be inappropriate for adult men and postmenopausal women. Excess iron can also lead to a rare condition called hemochromatosis in which iron deposits are found in abnormally high levels in many tissues. This can lead to liver, pancreatic, and cardiac dysfunction as well as pigmentation of the skin. This condition is usually only seen in hemolytic anemias and liver disease.
Iodine Is Incorporated into Thyroid Hormones
Dietary iodine is efficiently absorbed and transported to the thyroid gland, where it is stored and used for synthesis of the thyroid hormones triiodothyro­
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nine and thyroxine. These hormones function in regulating the basal metabolic rate of adults and the growth and development of children. Saltwater fish are the best natural food sources of iodine and in earlier years population groups living in inland areas suffered from the endemic deficiency disease goiter. The most characteristic symptom of goiter is the enlargement of the thyroid gland to the point where a large nodule is visible on the neck. Since iodine has been routinely added to table salt, goiter has become relatively rare. However, in some inland areas, mild forms of goiter may still be seen in up to 5% of the population.
Zinc Is a Cofactor for Many Enzymes
Zinc absorption appears to be proportional to metallothionein levels in intestinal mucosa cells. The exact function of metallothionein in zinc transport is uncertain, but it may serve as a buffer for zinc ions as the metal transverses the intestinal cells. Over 300 zinc metalloenzymes have been described to date, including a number of regulatory proteins and both RNA and DNA polymerases. Zinc deficiencies in children are usually marked by poor growth and impairment of sexual development. In both children and adults zinc deficiencies result in poor wound healing. Zinc is also present in gustin, a salivary polypeptide that appears to be necessary for normal development of taste buds. Thus zinc deficiencies also lead to decreased taste acuity.
The few dietary surveys that have been carried out in this country have indicated that zinc intake may be marginal for many individuals. However, few symptoms of zinc deficiency other than decreased taste acuity can be demonstrated in those individuals. Severe zinc deficiency is seen primarily in alcoholics (especially if they have cirrhosis), patients with chronic renal disease or severe malabsorption diseases, and occasionally in people after long­term parenteral nutrition (TPN). The most characteristic early symptom of zinc­deficient patients on TPN is dermatitis. Zinc is occasionally used therapeutically to promote wound healing and may be of some use in treating gastric ulcers.
Copper Is Also a Cofactor for Important Enzymes
Copper absorption may also be dependent on the protein metallothionein, since excess intake of either copper or zinc interferes with the absorption of the other. Copper is present in a number of important metalloenzymes, including cytochrome c oxidase, dopamine b ­hydroxylase, superoxide dismutase, lysyl oxidase, and 9­
desaturase. 9­Desaturase is responsible for converting stearic acid (a C18 saturated fatty acid) to oleic acid (a C18 monounsaturated fatty acid). This may be responsible for the fact that dietary stearic acid does not have the cholesterol­raising property of the other saturated fatty acids. Lysyl oxidase is necessary for the conversion of certain lysine residues in collagen and elastin to allysine, which is needed for cross­linking. Some of the symptoms of copper deficiency include hypercholesterolemia, demineralization of bones, leukopenia, anemia, fragility of large arteries, and demyelination of neural tissue. Anemia appears to be due to a defect in iron metabolism. The copper­containing enzyme ferroxidase is necessary for conversion of iron from the Fe2+ state (in which form it is absorbed) to the Fe3+ state (in which form it can bind to the plasma protein transferrin). The bone demineralization and blood vessel fragility can be traced directly to defects in collagen and elastin formation. The hypercholesterolemia may be related to increases in the ratio of saturated to monounsaturated fatty acids of the C18 series due to reduced activity of the C18, 9­desaturase.
Copper balance studies carried out with human volunteers seem to indicate a minimum requirement of 1.0–2.6 mg day–1. The RDA has been set at 1.5–3 mg day–1. Most dietary surveys find the average American diet provides only 1 mg at <2000 cal day–1. This remains a puzzling problem. Few symptoms of