Isabel H. Tipton

Essential trace metals in man: manganese. A study in homeostasis.

MANGANESE, a transitional metal with atomic number 25, has been considered essential for the normal physiological function of mammals and birds for 30 years. In spite of incontrovertible but indirect evidence of a requirement for dietary manganese, however, deficiency in man has not been recognized. There is considerable interest in the physiological and biochemical role of manganese by nutritionists, enzymologists and pathologists. The subject has been excellently reviewed on two occasions by COTZIAS

Trace metals in man: Strontium and barium☆

[l, 21. There are gaps, however, in some of the basic data and, at the risk ofbeing repetitious, we have surveyed the field from biogeochemical and analytical viewpoints, as we have other trace elements, in order to answer certain questions pertinent to manganese metabolism in man. These are: (1) What are the environmental sources of manganese? (2) How good is the human homeostatic mechanism for the metal? (3) Does manganese deficiency exist in man, even if slight? (4) Do diseases caused by accumulation of manganese occur in man? (5) What is the actual daily intake of manganese by normal human beings? (6) What living organisms have homeostatic mechanisms for manganese? This report is the tenth of a series on trace elements in human beings [3-111 and represents the first on an essential one. Although there are much older data in the literature, we have attempted to present newer material not available elsewhere as well as to repeat many analyses done by others in order to arrive at our own viewpoint.

Essential trace metals in man: copper.

IN 1808, Sir Humphrey Davy added two

TRACE ELEMENTS IN HUMAN TISSUE. PART III. SUBJECTS FROM AFRICA, THE NEAR AND FAR EAST AND EUROPE

elements to an expanding list. One he named strontium, after Strontian, a town in Scotland, and the other barium, after the Greek word barys (heavy) [l]. Both occur in relatively high concentrations on the earth’s crust, at 400 and 450 ppm, respectively, and both are constituents of sea water, at 8.1 ppm for strontium and 0.03 ppm for barium [2]. Therefore, living things have grown and evolved in the presence of these two alkaline earths, and have incorporated them in their tissues. Aside from natural occurrences, man has exposed himself to increasing concentrations of barium. Barite (barium sulfate) is used as a lubricating agent in drilling oil wells, 564,000 tons being consumed in the United States in 1968. Barium compounds are employed in making glass, ceramics, television picture tubes, as a pigment in paint (lithopone), in brick and tile refractories, for paper coating, steel hardening, vinyl stabilizers, lubricating oil additives, permanent magnets, railroad flares, fireworks and sugar refining. About 208,000 tons of barium compounds were sold in the United States in 1968. Some 2,172,OOO tons of barium were consumed in the world in that year [3,4]. Uses of strontium are fewer, there being only 12,500 tons produced in the free world in 1968 [3]. Major uses were as getters to remove traces of gas from vacuum tubes and as colors for tracer bullets, signal rockets, flares and fireworks. Strontium compounds also have a place in ceramics, medicines, greases, plastics, purifying zinc, permanent magnets and iron castings [3]. Although the actual amounts of exposures of the population were small, the greatest health hazard to the population at large came from atmospheric testing of atomic bombs, O”Sr being a fission product.

Abnormal trace metals in man—Vanadium

COPPER, atomic number 29, has played a dominant role in civilization since the Stone Age. Attractive to the eye, malleable and ductile, found native and in many minerals, copper was probably the first metal worked by ancient man some 7000 to 8000 years ago. The earliest known artifacts of hammered copper were found in Anatolia, Syria, Iraq and Iran; they date from the 6th and 5th millennia, B.C. Annealing and toolmaking were developed during the next 500 years, altering the course of human history. After 4000 B.C., melting and casting of copper became common practices in the Near East& Smelting was developed about 3000 B.C., followed in 500 years by the invention of bronze, exploited probably near Byblos (Lebanon), which stimulated an extensive civilization lasting a thousand years. The new art of metallurgy apparently spread over most of the world, although bronze was little used in the Western Hemisphere and not at all in Africa for many centuries [ll. Brass was not developed until Roman times [2]. In the modern age, Western civilization has become even more dependent upon copper. Copper’s electrical conductivity is second only to that of silver. Its abundance has provided the means for the enormous advances based on electricity during the past 80 years. Food has been cooked in copper vessels since the metal was first worked, for copper is the best of all metals as a conductor of heat. One of the Laws of Moses concerned the cleanliness of copper vessels5 which are still used over much of the known world for cooking food. In India, pots and pans of copper are periodically tinned to prevent contact of food with the metal.

Chromium deficiency as a factor in atherosclerosis

Abstract Central values and an estimate of variation about the central values are given for twenty-four trace elements and the ash per cent of dry weight of samples of ten different tissues of 162 adult subjects from outside continental United States. When groups of adult males from different geographical locations were compared, “essential” elements showed little geographical variation but those elements for which no role is known showed significant geographical difference.

Trace Elements in Human Tissue Part I. Methods

VANADIUM was discovered in 1801 by DEL RIO who called it erythronium. Later he decided that it was a form of chromium. Not until 1831 was it finally identified by SEFSTR~M who namea it after Vanaciis, the race of Freia, the Norse goddess of beauty [l]. Such beauty as it may have is chemical, lying in its excellent catalytic properties and physical, in the color of its compounds, but not particularly in the green tongues it causes in exposed workers [2]. During the age of metallotherapy (perhaps now due for a renaissance) compounds of vanadium were given therapeutically for a diverse variety of disorders; as antiseptic, spirochetocide, anti-tuberculous and anti-anemic agents; to boost resistance to infection and as tonics to improve appetite, nutrition and general health [I]. Obviously vanadium was not very toxic, for the doses employed were often large, 150 mg of the sodium tartrate intramuscularly and l-8 mg of the metavanadate by mouth [3]. Its use was largely given up two decades or more ago. To the BERTRANDS, p&e et jils, is largely owed interest in the possible biological activities of vanadium. Since 1903 some 18 of their publications have appeared, one on work done under the severe conditions of the German Occupation of Paris [4]. Partly because of their continuing investigations, vanadium as a trace metal has occupied a position of theoretical importance to plant and animal life for over half a century. Further interest was aroused when its activity on two currently popular substances was demonstrated. CURRAN [5] showed that vanadium suppressed the hepatic synthesis of cholesterol and offered evidence that it might inhibit experimental atherosclerosis [6]. PERRY et al. [7] found enhancement of activity of monoamine oxidase, an enzyme which long ago was shown to be acutely anti-hypertensive in rats and dogs [81 and which inactivated angiotensin [8-101. The purpose of this report, the sixth of a series, is to examine vanadium from its biogeochemical aspects in order to decide whether or not it behaves as an essential trace metal in man. To do this, it was necessary to evaluate distributions, mammalian exposures, biological activities and clinical experiments, and to estimate exchanges and balances. Some of our findings were surprising.

Essential trace metals in man: molybdenum

IT IS becoming increasingly clearthat severe atherosclerosis in man isusuallyassociated with abnormalities of glucose metabolism, a low tolerance to glucose being often found [l-4]. For many years the association of diabetes mellitus and atherosclerosis has been known; today, atherosclerosis is the largest single cause of death in diabetic subjects. The association of glucose and lipid metabolism is well known [5, 61, and in atherosclerosis, disorders of both are found in disease of the coronary arteries [7, 81 and in older atherosclerotic subjects without obvious localized arterial obstruction [9]. The common factor appears to be a high level of circulating insulin [l]. Chromium is a trace metal essential for glucose and lipid metabolism [lo], being necessary for the action of insulin [ll]. Experimental chromium deficiency leads, in rats [ 121 and squirrel monkeys [ 131, to diminished glucose tolerance, and eventually to a state mimicking mild to moderate diabetes mellitus in its physiological aspects [14]. In rats, chromium deficiency also has led to relatively elevated serum cholesterol levels [15] and to the deposition of aortic plaques [16]. Furthermore, the feeding of chromium to rats appeared to prevent both the formation of aortic plaques and the rise of serum cholesterol with age [17], human phenomena more or less common in industrial societies but unusual in more primitive ones [18]. Therefore, a syndrome similar to moderate human atherosclerosis has been reproduced in rats by chronic chromium deficiency. According to emission spectrographic analyses, chromium deficiency existed in a sizeable fraction of human tissues from United States subjects [19], but was rarely found in foreign tissues [20, 211. Samples from areas of the world where atherosclerosis is mild or virtually absent have shown more chromium than did those where the disease was endemic [22].

Essential trace metals in man: Cobalt

The concentrations of trace elements in normal tissues and the distribution of these elements throughout the body were determined by emission spectroscopy. The methods of collection and preparation of samples, of spectrographic analysis, and of statistical treatment of data are described.

Essential trace metals in man: Zinc. Relation to environmental cadmium

A survey of human exposures to molybdenum, a trace metal essential for almost all forms of life, was made by analyzing human tissues of 381 subjects from around the world by emission spectroscopy, and foods and beverages by a colorimetric method. Molybdenum was present in all human livers, kidneys and adrenals examined. Total body content of United States subjects was less than 9 mg and most organs and tissues contained little. Unlike other essential trace metals, mean concentrations of molybdenum in liver and kidney were relatively low in the newborn, rising to a peak in the second decade of life and declining slightly thereafter. Mean hepatic and renal concentrations of United States and foreign subjects were similar, but the latter had more molybdenum and it occurred more frequently in other organs and tissues. Only a few correlations of molybdenum with other trace metals in tissues were significant. The daily intake of molybdenum in standard diets was about 350 μg. Fish and animal meats supplied variable amounts; legumes, whole grains and their products supplied the majority. Plant foods high in purines were usually high in molybdenum, whereas most vegetables had little or none. Molybdenum in wheat was depleted in refining to white flour; that in sugar was concentrated in molasses and syrups. Rats fed a diet low in molybdenum had higher serum uric acid levels than those given added molybdenum. There is evidence that dental caries may be prevented by a high intake of molybdenum. It is possible that renal xanthine calculi may result from low intakes and that molybdenum may somehow be involved in disturbances of uric acid metabolism.