Essential metal deficiencies

Given the broad spectrum of important functions that essential metals perform in biological systems, it should not be surprising that essential metal deficiency can cause significant problems. Deficiencies can arise if the supply of essential metals are lacking in the diet, as a result of impaired regulation or as result of exposure to nonessential toxic metals. 

The most common essential metal deficiency in the United States is that of iron. Iron-deficiency anemia is the result of inadequate iron availability, leading to decreased hemoglobin production. Clinically, this is recognized by smaller red blood cells with lower hemoglobin content than normal red blood cells. Other nutritional... 

A classic example of essential metal deficiency resulting from nonessential metal exposure is Itai itai disease. Cadmium pollution in the Jinzu River basin in Japan resulted in severe nephrotoxicity in approximately 184 people. Renal tubule damage caused excessive loss of electrolytes and small proteins from the urine. In severe cases, urinary Ca loss was so severe that bone Ca was mobilized, resulting in osteomalacia. Renal tubular defects persisted for life and induced hypophosphatemia, hyperuricemia, and hyperchloremia, which are characteristic biochemical features of Itai-itai disease (see Section 21.6.1). 

It is only rarely that excess of one essential metal ion can compensate for deficiency of another. More usually, the effects of a deficiency are exacerbated. Quite generally, excessive intake of essential metal ions is harmful to the organism. This is illustrated by considering the uptake of iron, needed for the synthesis of cytochromes, haemoglobin and a number of enzymes including catalase. 

Excessive levels of essential metal ions can be undesirable and chelation therapy may be needed for adequate control to be achieved. The treatment of patients suffering from Wilson s disease (hepatolenticular degeneration in which there is intracellular deposition of copper in the liver and brain, accompanied by a deficiency of the copper-containing protein, caeruloplasmin) is an example45. ... 

Cadmium shows a very high bioconcentration factor (BCF), mainly because of its extremely slow elimination, although the absorption is rather low. The metal is not biomethylated and does not exist in any highly bioavailable organic forms. Its uptake is coupled to calcium and iron transporting mechanisms in which cadmium is mistaken for the essential metal and consequently transported. The uptake of cadmium is thus enhanced in situations of iron deficiency. 

Thirdly, the expected average life-span of a baby at birth has almost doubled over the last couple of centuries. This means that the cumulative effects of such non-essential metals become an increasing challenge to an elderly person. Furthermore, such elderly patients may well be deficient in essential or beneficial trace elements, thus magnifying the threat from extraneous metals present as contaminants. 

Anemia results from insufficient oxygen supply, often because of a decrease in hemoglobin (Hb) blood levels. Approximately 65 to 70 percent of total body iron resides in Hb. In the U.S., many foods, especially those derived from flour, are enriched in iron. In third-world countries, however, scarcity of dietary iron is a major contributor to anemia. This information illustrates one important fact about disease that results from metal deficiency, namely, the need for an adequate supply of essential metals in food. A related aspect, one of greater interest for bioinorganic chemistry, is the requirement that metals be adequately absorbed by cells, appropriately stored, and ultimately inserted into the proper environment to carry out the requisite biological function. For iron, these tasks. 

Essential metals and medical consequences resulting from their deficiency. ... 

It may be noted that many toxic metals are also essential for the body, at trace levels. Their absence from the diet can produce various deficiency syndromes and adverse health effects. Such essential metals include selenium, copper, cobalt, zinc, and iron. On the other hand, excessive intake can produce serious adverse reactions. Also, a number of metals, such as aluminum, bismuth, lithium, gold, platinum, and thallium, have been used in medicine. Despite their beneficial effects, excessive intake of these metals and their salts can cause serious poisoning. 

Zinc is another essential metal, a cofactor to many metalloenzymes. Its deficiency can induce effects on liver, nervons system, eye, skin and testis. Excessive intake of this metal, however, may prodnce adverse effects. The toxicity of the metal from ingestion is relatively low as it is readily excreted. Chronic exposure to the fume, however, may lead to metal fume fever, which could probably be attributed to the bivalent zinc ion, Zn +. Althongh the metal in its zero-valent state exhibits little inhalation toxicity, in its oxidation state or as oxide it can present a serions health hazard. Inhalation of Zn2+ or metal oxide fnme can prodnce a sweet metallic taste, congh, chills, fever, dry throat, nansea, vomiting, blnrred vision, ache, weakness, and other symptoms. The nontoxic fnme of the metal is snsceptible to oxidize in the air in the presence of moistnre and in contact with many other snbstances in air. The metal powder or its dnst is a skin irritant. 

Attempts to induce Cr deficiency in experimental animals have also led to controversial results [(6) and references cited therein]. Recently, Anderson and co-workers (475, 476) formulated the conditions for inducing Cr deficiency in rats (1) careful removal of Cr sources from food and environment (e.g., stainless steel cages cannot be used) and (2) sucrose- or fat-based diet. These conditions led to abnormal insulin levels, characteristic of the first stage of type II diabetes, that could be prevented by addition of CrCls (5 ppm) to drinking water. In these experiments, Cr(III) apparently acts as an insulin potentiator under the conditions of dietary stress, which corresponds to the beneficial rather than essential metal ion category (470, 477). 

Heavy metals, in traces, are essential for all forms of life. They are taken up by the living cell as cations, and their uptake is strictly regulated because most (or all) of them are toxic in excess. A remarkable specificity has been found seldom can an excess of one essential metal prevent the damage caused by a deficiency of another. In fact, such an excess often increases the injurious effect of the deficiency. 

The question whether Cr(III) might be toxic is complicated by the fact that it is considered an essential metal. Biologically active Cr(III) facilitates the action of insulin. Chromium deficiency results in impaired glucose tolerance, which can be corrected by the administration of chromium (Anderson et al. 1983 Anderson 1986). Hypoglycemia and its associated symptoms can also be corrected by administration of chromium (Anderson et al. 1987). These effects of chromium supplementation are often associated with improvements in lipid levels, with a net decrease in total lipids and cholesterol and an increase in the ratio of HDL cholesterol to LDL cholesterol (Riales and Albrink 1981 Mossop 1983 Evans 1989 Wang et al. 1989). 

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