The Trace Elements

KENNETH J. MONTY AND WILLIAM D. McELROY.

ALL living things contain a variety of minerals. Some occur in such small amounts that early chemical analyses could barely detect them. They therefore became known as the trace minerals, metals, or elements.

For only a few of them have nutritional requirements or biological functions been demonstrated. It is likely that many of the others occur in living things only by accident, having been acquired in the food or water, or absorbed through the skin, or even inhaled.

At the present stage of our biological knowledge, however, we cannot ignore the possibility that some of the trace elements we now think of as nonessential do have as yet unrecognized functions in the body's processes.

People found out about the need for trace elements when they saw that some deficiency diseases in livestock, and sometimes in human beings, could be treated by large doses of a specific mineral.

An example is iodine, which was used in a somewhat hit-or-miss way to treat goiter as long ago as 1820. A study of the distribution of iodine in soils and water later led to the belief that goiter often is a nutritional disease, especially in places where the natural supply of iodine is low. Scientists in 1895 proved that iodine is a normal component of the thyroid gland and is depleted in cases of endemic goiter. Today we recognize iodine as a component of the hormones produced by the thyroid gland.

Another example is cobalt. Investigators in 1935 discovered that this element prevented certain wasting diseases of sheep and cattle in localities in Australia and New Zealand. Subsequent studies demonstrated that a deficiency of cobalt was responsible for similar diseases in Florida, parts of England and Scotland, and Kenya. As with iodine, the function of cobalt remained obscure for some time after the need for it in animal nutrition was recognized.

Scientists in later years have brought about artificial deficiencies in animals in order to study further their requirements of trace elements. They carefully purify or combine various diets that omit the trace element they are studying in order to see whether it is essential for health. Feeding such unbalanced diets to small laboratory animals demonstrated the essentiality of copper, manganese, and zinc in animal nutrition.

We now know that trace elements required for the growth of animals include copper, iodine, iron, magnesium, manganese, and zinc. Cobalt is essential for the growth of ruminants.

Selenium can prevent certain degenerative conditions of the liver in animals and birds.

Also important to animals are molybdenum and fluorine. Molybdenum is a component of certain enzymes, but a deficiency of molybdenum usually does not depress growth.

One exception has been noted. Researchers at the Missouri Agricultural Experiment Station demonstrated that molybdenum is necessary for micro-organisms of the rumen of sheep to carry out their function of degrading cellulose to a form in which the sheep can utilize it. Molybdenum also may be required for best growth of chicks.

Fluorine has never been reported to influence the growth of animals, but it is beneficial in the diet because it helps prevent dental caries. In a sense, it may be considered as essential to the formation of perfect teeth.

ONE OF THE GREAT PROBLEMS today is to set standards for fixing the need for trace elements or any constituent of diet.

The old attitude was that a constituent is essential if slow growth or none or death results from failure to include it in the diet. It has been apparent for some years that that definition is not good enough.

An example is vitamin E. Too little of it leads to sterility in many mammals but often has no effect upon other physiological processes, such as growth. Yet vitamin E is essential.

Other examples lead us to question whether we can take inadequacy of growth as a sole criterion of essentiality. Deficiencies of fluorine and molybdenum are not necessarily incompatible With the continuation of life or the maintenance of normal growth, although both have beneficial biological functions.

It seems wise, then, to introduce into nutrition the concept of functional nutrients. A diet must supply a proper balance of essential nutrients and functional nutrients to insure overall physiological perfection.

THE ESTABLISHMENT of minimal dietary requirements for the trace elements is a difficult problem, for many factors may affect their absorption and utilization. Besides the effects trace elements may have on each other is the fact that other nutrients may modify the degree of absorption, utilization, and excretion of the trace elements, usually by entering into chemical complexes (chelates) with the trace elements and thereby modifying their solubility properties.

We must consider also the degree of physical activity and various other minor physiological stress conditions. Scientists therefore have been unable to assign exact requirements, even to small laboratory animals. Because human beings consume large amounts of food, it is technically difficult and expensive to prepare suitable test and experimental diets.

Human requirements for trace elements have been estimated from studies of normal intake and excretion. The recommended daily requirements we list here probably greatly exceed the minimum daily requirements, but they certainly are adequate to supply the body's needs under normal circumstances.

Data from several sources indicate the following daily allowances: Copper, 2 milligrams;

Iodine, 0.1 to 0.2 milligram;

Iron, 1 milligram per kilogram of body weight for infants and children (up to about 9 years), 10-12 milligrams for adults, 15-20 milligrams for pregnant women;

Manganese, 0.3 milligram per kilogram of body weight;

Zinc, 0.3 milligram per kilogram of body weight.

(A kilogram is approximately 2.2 pounds. There are approximately 30,000 milligrams in an ounce. Thus an 11-pound-5 kilograms baby requires about 1.5 ten-thousandths of an ounce-5 milligrams of iron a day.)

If molybdenum is in fact essential for humans, its daily requirement is considerably less than 0.3 milligram per kilogram of body weight.

The optimum level of fluorine for drinking water is 0.0001-0.00015 percent.

Cobalt apparently is required only as part of vitamin B₁₂.

No information is available as to a possible requirement for selenium in human beings.

TRACE ELEMENTS carry out a variety of functions in a variety of ways in the animal body. Several are parts of complex molecules that are indispensable to body processes.

Cobalt, for example, is a component of vitamin B₁₂, the extrinsic factor, in pernicious anemia. As far as we know, cobalt is indispensable to the activity of vitamin B₁₂, which functions in the production of hemoglobin, in the phase of intermediary metabolism known as one-carbon transfer (the transfer of methyl groups) and in the preparation of amino acids for assembly into protein chains.

Iodine, like cobalt, seems to have its sole function as part of a complex organic molecule. Iodine is an essential part of the thyroid hormone, and as such is of great importance in regulating the rates at which many body functions are carried out.

A third trace element may fall into this category of function. Evidence has been obtained at the National Institutes of Health that the active form of selenium in the animal body is an organic molecule that has not been identified. This molecule may function in oxidative reactions in metabolism.

SOME TRACE ELEMENTS carry out their specific duties as parts of protein molecules.

For. example, the transport of oxygen in the blood stream of most animals is the function of a group of metal-containing proteins.

The iron-containing protein, hemoglobin, is the chief respiratory protein in mammals and many other animals. Different iron-containing proteins, the erythrocruorins, perform this function in some invertebrates. Oxygen transport is assigned to copper-containing proteins (hemocyanins) in many of the common shellfish (crabs, lobsters, and snails) and in squids and octopuses.

In all of these respiratory pigments, the metal is attached quite rigidly to the protein molecule, often through some subsidiary organic molecule (called a prosthetic group). Thus the iron in hemoglobin is attached primarily to a porphyrin molecule, which in turn is attached to the protein, globin.

The iron-containing respiratory pigments are red or brown. Those containing copper are blue. Myoglobin, an iron protein similar in many ways to hemoglobin, serves as a storage site for oxygen in muscle tissue. Related oxygen-storage proteins occur in many animals. Oxygen is carried as a complex with the metal in all of the respiratory proteins.

ENZYMES, a group of proteins that direct and hasten catalyze chemical reactions in living things, sometimes contain trace elements as integral parts of their structures.

Iron is involved in many such proteins that catalyze a variety of oxidative reactions. As with hemoglobin, the iron is attached to the protein through a porphyrin molecule.

Among the iron-containing enzymes are catalase, which decomposes hydrogen peroxide; the peroxidases, which catalyze the oxidation by hydrogen peroxide of a variety of molecules; and the cytochrome enzymes, which are essential to the trapping of energy during the oxidation of carbohydrate and fat by oxygen.

Molybdenum is a part of at least two animal enzymes, xanthine oxidase and aldehyde oxidase. How it is attached to the protein is not fully understood.

Another example of the inclusion of a trace element in a protein molecule is chlorophyll, the green pigment in plants. Magnesium is attached to the protein of chlorophyll through a porphyrin molecule similar to those involved in many of the iron-containing proteins.